{"_id": "WikiPedia_Hematology$$$corpus_1", "text": "Jan Blatn\u00fd  (born 24 March 1970) [ 1 ]  is a  Czech   physician ,  teacher [ 2 ]  and  politician . On 29 October 2020 he was named as  Minister of Health of the Czech Republic  by Prime Minister  Andrej Babi\u0161  following the resignation of  Roman Prymula . On 7 April 2021 he was replaced by  Petr Arenberger ."}
{"_id": "WikiPedia_Hematology$$$corpus_2", "text": "This biographical article related to medicine in the Czech Republic is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_3", "text": "This article about the  COVID-19 pandemic  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4", "text": "Robin Wayne Carrell  (born 5 April 1936) is a New Zealand-born haematologist."}
{"_id": "WikiPedia_Hematology$$$corpus_5", "text": "Born in 1936, [ 1 ]  Carrell was educated at  Christchurch Boys' High School  from 1949 to 1953. [ 2 ]  He graduated  MB ChB  from the  University of Otago  in 1959, [ 3 ]  and  BSc(Hons)  in chemistry and biochemistry from the  University of Canterbury  and  Lincoln College  in 1965. [ 1 ] [ 4 ]  He completed his PhD at the  University of Cambridge  in 1967 and in 1968 he was appointed head of clinical biochemistry at  Christchurch Hospital , [ 5 ]  the department later becoming part of the  University of Otago Christchurch School of Medicine . As a spin-off from his research he co-founded biotechnology company Canterbury Scientific in 1985. [ 6 ]  He returned to Cambridge the following year as professor of haematology, retiring in 2003, but as professor emeritus he has continued his research at Cambridge. [ 5 ]  He retired from the board of directors of Canterbury Scientific in 2012. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6", "text": "In 1986 he won the  Hector Medal , at the time the highest award in New Zealand science. [ 8 ]  He was elected a  Fellow of the Royal Society of New Zealand  in 1980, [ 9 ]  a Fellow of  Trinity College, Cambridge  in 1987, [ 10 ]  and a  Fellow of the Royal Society  in 2002. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7", "text": "This biographical article about a New Zealand academic is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_8", "text": "Kathryn Elizabeth Crosier   ONZM  ( n\u00e9e \u00a0 Barber ) is a New Zealand academic, a clinical  haematologist , and is an emeritus professor at the  University of Auckland , specialising in  molecular medicine . In 2005, she was appointed an  Officer of the New Zealand Order of Merit  for services to medicine."}
{"_id": "WikiPedia_Hematology$$$corpus_9", "text": "Crosier completed a medical degree at the  University of Otago  followed by a  PhD  titled  The regulation of human haemopoiesis by cytokines  at the University of Auckland in 1988. [ 1 ]  Crosier then joined the faculty of the University of Auckland, rising to full professor as Professor of Molecular Medicine and Pathology. Crosier is a clinical haematologist, and her husband Philip Crosier is also an emeritus professor of the university. [ 2 ] [ 3 ]  Crosier is a  Fellow of the Royal Australasian College of Physicians  and a Fellow of the  Royal College of Pathologists of Australasia . [ 2 ]  Crosier was appointed Associate Deputy Vice-Chancellor (Research) for  PBRF  at the university in 2010. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_10", "text": "Crosier served as a member of the  New Zealand Blood Service , being appointed in 2003 for a three year term, and subsequently reappointed in 2006 for a second term. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_11", "text": "Crosier's research interests include  medical genetics ,  leukaemia  and  stem cell  development. Crosier was part of a team that announced a breakthrough in understanding of the formation of  lymphatic vessels  in 2019. [ 7 ] [ 8 ]  The research, funded by the  Health Research Council , the  Marsden fund  and the Auckland Medical Research Foundation, involved a collaboration between researchers at Auckland, the  University of M\u00fcnster  and the  University of Queensland . Researchers used fluorescent  zebra fish  to show that lymphatic vessels can develop through different routes, rather than from blood vessels as previously thought. [ 7 ]  The findings have relevance to the development of treatments for  lymphedoema , a common condition resulting from some cancer treatments. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_12", "text": "One of Crosier's notable doctoral students is rheumatologist  Fiona McQueen . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_13", "text": "In the  2005 New Year Honours , Crosier was appointed an  Officer of the New Zealand Order of Merit , for services to medicine. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_14", "text": "She is married to  Phil Crosier , an emeritus professor of molecular medicine and pathology at the University of Auckland. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_15", "text": "Bj\u00f6rn Dahlb\u00e4ck  (born 1949) is a Swedish physician, medical researcher, and professor of clinical chemistry, specializing in  hematology  and the molecular mechanisms of blood coagulation. [ 1 ]  He determined that  activated protein C (APC) resistance  is the most common inherited risk factor of  venous thrombosis ."}
{"_id": "WikiPedia_Hematology$$$corpus_16", "text": "Dahlb\u00e4ck graduated with an M.D. from  Lund University  and then completed his medical internship and residency at  Malm\u00f6 's University Hospital, [ 2 ]  which is now merged into  Sk\u00e5ne University Hospital . In 1981 he received from Lund University his doctorate with dissertation  The activation of prothrombin on the platelet surface [ 3 ]  under the supervision of  Johan Stenflo . Dahlb\u00e4ck was a postdoc at  La Jolla 's  Scripps Research , where his supervisor was  Hans J. M\u00fcller-Eberhard , and later was a visiting scholar at  Oklahoma Medical Research Foundation  (OMRF). In 1989 at Lund University, Dahlb\u00e4ck was appointed a full professor of clinical chemistry, specializing in hematology and cardiac and cardiovascular systems. [ 2 ] [ 1 ]  He is also the director of the blood coagulation unit at Malm\u00f6 General Hospital. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_17", "text": "His research was important in showing that  APC resistance  is caused by a harmful mutation in the  F5  gene corresponding to the protein  Factor V ; the specific mutation was subsequently identified by several groups of researchers and is now called  Factor V Leiden . [ 2 ]  In 2013, Dahlb\u00e4ck and colleagues identified the  F5  gene mutation that causes the phenotype called \"east Texas bleeding disorder\". [ 5 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_18", "text": "He has received several honors and awards, [ 2 ]  including in 1996 the  Louis-Jeantet Prize for Medicine [ 4 ]  and in 2019  H. M. The King's Medal  ( H.M. Konungens Medalj ) of the 12th size from the  Royal Court of Sweden . [ 6 ]  He is a member of the  Royal Swedish Academy of Sciences . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_19", "text": "In 2000,  Academic Press  published  Hematology: Landmark Papers of the Twentieth Century  , which included the 1994 paper  Resistance to activated protein C as a basis for venous thrombosis  by Peter J. Svensson and Bj\u00f6rn Dahlb\u00e4ck. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_20", "text": "Brian G.M. Durie  is a Scottish  hematologist  known  for his research and efforts regarding  multiple myeloma  and blood disorders, especially  his development of the multiple myeloma staging system.  He is the chairman of the board and Scientific Director for the Myeloma Foundation and a specialist in multiple myeloma and related disorders at the Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute .."}
{"_id": "WikiPedia_Hematology$$$corpus_21", "text": "Durie was born December 1942 in  Gullane , Scotland. [ 1 ]  and graduated in 1960 from North Berwick High School. [ 1 ]  He attended the  University of Edinburgh Medical School  and graduated in 1966. After Medical and Surgical House Officer positions at the  University of Edinburgh  Royal Infirmary in 1967, [ 1 ]  he moved to the United States to complete his medical residency and subspecialty training. His training at  Mayo Clinic  in Minnesota was completed in 1972 [ 1 ]  and led to Specialty Board Certification in Internal Medicine (ABIM) in 1972 followed by his Certification in Hematology (ABIM) in 1974 [ 1 ]  and Oncology (ABIM) in 1975. [ 1 ]  Durie obtained his Medical licensure in Minnesota in 1972, [ 1 ]  Arizona in 1974 [ 1 ]  and California in 1993 [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_22", "text": "Upon completing subspecialty training, Durie joined the Medical Faculty of the  University of Arizona College of Medicine - Tucson    in 1972 where he progressed to Full Professor status in the Section of Hematology/Oncology in 1981. [ 1 ]  He served as Head of the Hematology Section and Director of the Myeloma Program. [ 2 ]  In 1989, he became a professor and Head of the Department of Clinical and Laboratory Hematology at the  University of London  where he also established a myeloma program. [ 2 ]  In 1992, he returned to the United States in the Division of Hematology/Oncology at  Cedars-Sinai Medical Center  in Los Angeles. [ 3 ]  Upon   return to the United States, he  assume Directorship of the Hematological Research and Myeloma Programs for Aptium Oncology Inc. (subsequently  AMyC Myeloma Consortium) [ 4 ]  also based at Cedars-Sinai Medical Center in the Comprehensive Cancer Center Division. He currently remains as a myeloma specialist physician [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_23", "text": "Durie's key research articles have focused on classifying and staging myeloma. Durie's first faculty position at the University of Arizona was with  Sydney Salmon with the assignment to develop a clinical staging system for multiple myeloma. [ 5 ]  This was based upon a new system for directly measuring the number of myeloma cells within the body, an  approach which led to the publication of a seminal paper on myeloma staging in the journal  Cancer  in 1975, [ 6 ]  which has been cited more than 3000 times by other scientists. This publication continues to be referenced as the standard way to clinically stage multiple myeloma, named the Durie-Salmon Staging System. Durie has co-authored two updates to the staging system."}
{"_id": "WikiPedia_Hematology$$$corpus_24", "text": "Salmon and Durie  authored a paper that concluded that the pretreatment labeling index provides helpful prognostic information in addition to tumor mass staging, which was patented. [ 7 ]  Furthermore, Durie showed it was possible to stratify myeloma patients based on combinations of serum beta 2 microglobulin with both albumin and age, producing significant separation of patients into low-, intermediate-, and high-risk categories. [ 8 ]  His research concluded that serum beta 2 microglobulin is the most powerful prognostic factor currently available for multiple myeloma. [ 8 ]  In 2006, Durie and team created an international uniform response criteria for multiple myeloma, which became very substantial for use by doctors and other researchers. [ 9 ]  Durie co-authored an update to the response criteria in 2016 [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_25", "text": "In 1990, Durie co-created a non-profit foundation, the  International Myeloma Foundation . Formed in conjunction with Brian Novis and Susie Lavitt. [ 11 ]  Durie has continued to serve as  chairman of the board and Scientific Director. The foundation has established myeloma patient support groups in the US and globally, created th p International Myeloma Working Group ] [ 12 ]  with 250 myeloma experts to conduct collaborative research and guideline development, and established the Black Swan Research Initiative to conduct treatment trials. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_26", "text": "Durie is a Leukemia Society of America Scholar and a U.S. Hematologic Research Foundation Annual Awardee. Hr received the 2006 Robert A. Kyle Lifetime Achievement Award, which honors a physician in myeloma research. In 2009, he received the Waldenstr\u00f6m's Award in recognition of his contributions to that field. He was awarded an Honorary Doctorate of Medicine from the  Vrije Universiteit Brussel    in 2019."}
{"_id": "WikiPedia_Hematology$$$corpus_27", "text": "1991\t5th Annual Hematological Research Award [ 2 ] \n2002\tNuclear Medicine First Prize Award [ 2 ]   \n2006\tRobert A. Kyle Lifetime Achievement Award [ 14 ]   \n2009\tWaldenstr\u00f6m Award for Myeloma Research [ 15 ]   \n2014\tMayo Distinguished Alumni Award [ 16 ] [ 17 ]   \n2019\tHonorary Doctorate of Medicine: Free University of Brussels [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_28", "text": "Durie has   written over 600 research papers, sixteen book chapters, and five books. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_29", "text": "Robert (Robin) Sanno F\u00e5hr\u00e6us  (15 October 1888 \u2013 18 September 1968) was a  Swedish  medical researcher noted for his contributions to  hemorheology . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_30", "text": "F\u00e5hr\u00e6us was the son of art historian  Klas F\u00e5hraeus  and actress  Olga Bj\u00f6rkegren . [ 2 ]  He commenced studies at  Karolinska Institute  in 1908, where he received his medical license in 1922. Before that, in 1921, he had completed his research doctorate with the title  The suspension-stability of the blood . He became associate professor of experimental  pathology  at the Karolinska Institute in 1922. He was professor of pathology at  Uppsala University  from 1928 to 1947, and professor of general pathology and pathological anatomy in Uppsala from 1947 to 1955, after his previous chair had been split in two. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_31", "text": "F\u00e5hr\u00e6us became a member of the  Royal Swedish Academy of Sciences  in 1935. [ 1 ]  In 1966, the  International Society of Hemorheology  awarded him their first Poiseuille medal, the Society's highest award. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_32", "text": "While studying at the Karolinska Institute he conducted research on  eclampsia  and observed that blood samples from pregnant women easily could be distinguished from other blood samples because the  red blood cells  descended more quickly in the test tubes, leaving a thick layer of  blood plasma  on top. [ 2 ]  This phenomenon is the  erythrocyte sedimentation rate , which can be used as a diagnostic tool."}
{"_id": "WikiPedia_Hematology$$$corpus_33", "text": "After F\u00e5hr\u00e6us had received his position at the Karolinska Institute in 1922, he sought contact with professor  Theodor Svedberg  in Uppsala and suggested that the recently built  ultracentrifuge  should be used to determine the  molecular mass  of  hemoglobin . Svedberg and F\u00e5hr\u00e6us published the result in 1926, the same year Svedberg received the  Nobel Prize in Chemistry . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_34", "text": "In Uppsala from 1928, F\u00e5hr\u00e6us started to study the flow of blood in thin blood vessels, which led to the discovery of two effects named after him. In 1929 he described the  F\u00e5hr\u00e6us effect , a decrease in the average concentration of red blood cells when blood flows in a tube of smaller diameter. In 1931 he and co-worker Torsten Lindqvist described the  F\u00e5hr\u00e6us\u2013Lindqvist effect , the change of the  viscosity  of blood with the diameter of the tube it travels through."}
{"_id": "WikiPedia_Hematology$$$corpus_35", "text": "Floy Agnes  \" Aggie \" ( Naranjo Stroud )  Lee  was a biologist who worked on the  Manhattan Project  at  Los Alamos  as a hematology technician."}
{"_id": "WikiPedia_Hematology$$$corpus_36", "text": "Floy Agnes Lee was born July 23, 1922, at the  Albuquerque Indian School  and was the fourth of five siblings. [ 1 ] [ 2 ]  Her mother was a German-American teacher from Indiana who had traveled in the US teaching at different Indian schools including the Winnebago Indian schools in Wisconsin, in Santa Fe, and at the Albuquerque Indian School. Her father was a member of the  Santa Clara Pueblo ."}
{"_id": "WikiPedia_Hematology$$$corpus_37", "text": "Lee grew up at the Albuquerque Indian School, but was sent to St. Mary's Catholic School for her education. She then went on to graduate from  Albuquerque High School . In 1945, she graduated from the  University of New Mexico  (UNM) with a degree in biology. While there, she worked for a professor putting different solutions into each plant to see how they grew. This job made her more interested in doing research. [ 2 ]  During her college years she also learned to fly planes and worked at a grocery store to pay for flying lessons. She was one flight short of qualifying to become a member of the  Women\u2019s Airforce Service Pilots  before the program was disbanded in 1944. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_38", "text": "In 1945, Lee was asked by professor Edward Castetter, head of UNM's biology department, to do research for him. While she was compiling and recording information on what the Indigenous people of New Mexico ate before colonization, Castetter asked her to postpone a trip that she had planned to see her mother's relatives in order to finish the research. While Lee was continuing this research, Castetter got a call from Los Alamos. They told him that they were looking for a biology student or a graduate to work in the hematology laboratory. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_39", "text": "Lee accepted this position at the hematology lab at Los Alamos in 1945. She collected and examined blood samples from Manhattan Project scientists, including  Louis Hempelmann , as well as  Louis Slotin  and  Alvin Graves  after  the criticality accident  that exposed Slotin to a fatal dose of radiation. Lee said that she learned how to take blood, read blood cell counts, and identify blood types on the job, but that she excelled at these tasks once taught. She was sent to different sites of the Manhattan Project where she would draw blood from individuals. While working in the hematology lab at Los Alamos, Lee was assigned specific scientists to monitor, including  Enrico Fermi ."}
{"_id": "WikiPedia_Hematology$$$corpus_40", "text": "Lee and Fermi became friends during this time. In Lee's oral history, conducted by the  Atomic Heritage Foundation , she elaborated on her relationship with Fermi: \"We got to talking about what I liked to do and what he liked to, and we got on the subject of tennis. Now, I did not know that this was Enrico Fermi. I only knew him as a number, because they wouldn\u2019t give names out. So we would play tennis. This was before the bomb was dropped, and then afterwards also. He was a short man, and he had a funny little hat.\" [ 2 ]  After the  atomic bombs  were detonated over Hiroshima and Nagasaki, Lee was told that she had been playing tennis with a Nobel Prize-winner for months. She was shocked. She said that her response was: \"'Oh, I can't believe that.' Because I was beating him in tennis every time. So when we went out to play tennis later, I didn't beat him. I tried not to. We became very, very good friends.\" [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_41", "text": "After the war ended, Fermi encouraged Lee to continue her studies at the  University of Chicago . [ 2 ]  She moved to Chicago, began her doctorate in biology, and worked at  Argonne National Laboratory . She continued to study, work at the lab and raise her child after her husband passed away from cancer. After 14 years, she received her PhD. She later worked at the  Jet Propulsion Lab  in California and returned to work at  Los Alamos National Laboratory  before she retired. Over the course of her long career, she conducted research on the impact of radiation on chromosomes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_42", "text": "Lee died in 2018 at the age of 95. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_43", "text": "Munib Jalal Shahid  ( Arabic :  \u0645\u0646\u064a\u0628 \u062c\u0644\u0627\u0644 \u0634\u0647\u064a\u062f ,  romanized :\u00a0 Mun\u012bb Jal\u0101l Shah\u012bd ; 1908\u20131973) was Chairman of Hematology and Oncology at the Faculty of Medicine of the  American University of Beirut . [ 1 ] [ 2 ]   He built the hematology laboratory at the Faculty of Medicine, a development that increased research output significantly. [ 3 ]   The Dr. Munib Shahid Award is presented annually at the American University of Beirut to the fourth year medical student demonstrating the best performance in internal medicine and a mature character. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_44", "text": "Munib Shahid was born in 1908 in  Acre, Palestine  to a prominent  Bah\u00e1\u02bc\u00ed lineage . He was the great-grandson of  Bah\u00e1\u02bcu'll\u00e1h , the founder-prophet of the  Bah\u00e1\u02bc\u00ed Faith . His parents were Jalal, an  Afn\u00e1n , and R\u00fa\u1e25\u00e1, a daughter of  \u02bbAbdu'l-Bah\u00e1 . His paternal grandfather was Muhammad-Hasan, titled \" King of the Martyrs \". In 1944, he married  Serene Husseini  according to the Muslim rites. She was related to the  Grand Mufti of Jerusalem , an enemy of the Bah\u00e1\u02bc\u00eds.  Shoghi Effendi , Munib's cousin and then head of the Bah\u00e1\u02bc\u00ed Faith, labeled this marriage a \"treacherous act\" and excommunicated Munib Shahid as a  Covenant-breaker . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_45", "text": "Munib and Serene Husseini continued to live in Beirut, where he pursued his academic career, and she promoted cottage industries among  Palestinian refugees .  Serene Shahid wrote a critically acclaimed autobiography of her childhood, titled,  Jerusalem Memories. [ 7 ]   The couple had three daughters, including  Leila Shahid . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_46", "text": "Among Shahid's publications were: [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_47", "text": "Ruth Lilian Spearing   CNZM  is a New Zealand  haematologist , and researches blood cancer. In 2023 Spearing was appointed a Companion of the  New Zealand Order of Merit  for services to haematology."}
{"_id": "WikiPedia_Hematology$$$corpus_48", "text": "Spearing attended the  University of Otago . [ 1 ]  She has worked as a consultant haematologist at  Christchurch Hospital  since 1989, and is the clinical director of haematology at  Canterbury District Health Board . [ 2 ]  From 2003 until 2017 Spearing served as Chair of the Canterbury Hospitals\u2019 Medical Staff Association. [ 2 ]  Spearing was also Canterbury Clinical Lead for the Adolescent and Young Adult Cancer Service. [ 2 ]  Spearing was also a board member of the  New Zealand Medical Association , and a trustee of the Chronic Lymphocytic Leukaemia Advocates New Zealand. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_49", "text": "Spearing led the New Zealand involvement in international collaborative trials with the UK's  Medical Research Council  and the Australasian Leukaemia and Lymphoma Group. [ 2 ]  These trials have investigated treatments for a range of blood cancers including  myeloma ,  chronic lymphocytic leukaemia ,  acute lymphocytic  and  myeloid leukaemia , and have resulted in increased survival rates from 13% for acute myeloid leukaemia in the 1980s to 65 per cent. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_50", "text": "In 2008 Spearing established the Ruth Spearing Cancer Research Trust, to support haematology research in the South Island. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_51", "text": "In 2024 Spearing led calls for  Pharmac  chief executive Sarah Fitt to step down after an  Official Information Act  request revealed internal communications showing disdain for patients and their advocates. [ 5 ]  Spearing has been critical of Pharmac's approach to funding new drugs, especially drugs for blood cancers, pointing out that New Zealand funds far fewer blood cancer drugs than other countries. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_52", "text": "In the  2023 King's Birthday and Coronation Honours  Spearing was appointed a Companion of the New Zealand Order of Merit for services to haematology. [ 2 ] [ 8 ]  Spearing is a Life Member of ALLG, the Australasian Leukaemia and Lymphoma Group. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_53", "text": "Swee Lay Thein  is a Malaysian haematologist and  physician-scientist  who is Senior Investigator at the  National Institutes of Health . She works on the  pathophysiology  of  haemoglobin  disorders including  sickle cell disease  and  thalassemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_54", "text": "Thein was born in  Kuala Lumpur ,  Malaysia . [ 1 ]  She studied medicine in both Malaysia and the  United Kingdom . [ 2 ]  She graduated from the  University of Malaya  in 1976. [ 3 ]  She specialised in  hematology  at the  Royal Postgraduate Medical School  and the  Royal Free Hospital . She moved to  Oxford , where she worked at the  Medical Research Council  (MRC) Molecular Hematology Unit in the  Weatherall Institute of Molecular Medicine  and the  John Radcliffe Hospital . She held various positions at Oxford, including a MRC Clinical Training position, a  Wellcome Trust  senior fellowship and an honorary consultancy. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_55", "text": "In 2000 Thein joined  King's College London  as a Professor of Molecular Haematology. She was made Clinical Director of the Red Blood Cell clinic at  King's College Hospital . Her work considers the  pathophysiology  of haemoglobin disorders; which include  sickle cell disease  and  thalassemia . The only cures for sickle cell disease and thalassemia are  bone marrow  transplants, but these are not always available. Whilst both conditions can present with a variety of clinical severities, a remediating factor is the ability to produce  foetal haemoglobin  (HbF). Foetal haemoglobin is the haemoglobin that transports oxygen during  foetal  life and in infants until they are six months old. [ 4 ]  She has studied the mechanisms responsible for the formation of foetal haemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_56", "text": "Thein demonstrated that HbF levels are mainly controlled by genetics, and that majority of the genetic variance is accounted for by factors outside the  globin  locus. [ 1 ]  Thein used  linkage analysis  to identify two of the  quantitative trait loci  (QTL) for this HbF variability. These loci are involved with the control  haematopoiesis  and the production of HbF. The loci are located on the chromosomes 6q and 2p which are located within the  BCL11A  gene. Whilst it was known that BCL11A was involved with cancer, Thein was the first to show that BCL11A was associated with red blood cell disorders. [ 5 ]  The 6q QTL contains  single-nucleotide polymorphisms  distributed across three  linkage disequilibrium  blocks, in an intergenic region between  MYB  and  HBS1L . [ 1 ]  Thain showed that this interval contains regulatory sequences. She has investigated how QTL regulates the expression of MYB and HBS1L. [ 1 ]  These two QTLs (6q and 2p), and a single-nucleotide polymorphism on the  HBB  cluster account for around half of the variability in HbF levels. [ 1 ]  She established that these two variants had spread from Africa into almost all human populations. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_57", "text": "By delineating the genetics of foetal haemoglobin control in adults, she hopes to explain the trait variance in adults as well as identifying the loci and sequences of variants. She believes that by identifying the HbF QTLs she will be able to improve patient management through the development of novel therapies, more sophisticated genetic counselling and better predictions of disease severity. These therapies may include approaches to activate the BCL11A gene. [ 5 ]  By trying to find the relationships between genotypes and phenotypes, Thein has helped with  DNA  diagnostics in the  haemoglobinopathies . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_58", "text": "Sickle cell disease occurs because rigid strands form inside  red blood cells , destroying their structure and resulting in the formation of sickled cell shapes. Thein is working on therapeutic agents that can work against this polymerisation, stopping the cells changing shape. [ 5 ]  Thein has served as Chair of the  European Hematology Association  working group on red blood cells. [ 7 ]  She has been involved with the teaching of their programs on haematology. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_59", "text": "She moved to the  National Institutes of Health  as Senior Investigator and Chief of the new NIH Sickle Cell Branch in 2015. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_60", "text": "Thein is an editor for  Blood ,  Annals of Haematology ,  Hemoglobin , and the  American Journal of Hematology . [ 5 ]  She is feature editor of the  Sickle Blood Hub , an online space for the journal  Blood . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_61", "text": "Wilhelm T\u00fcrk  (2 April 1871 \u2013 20 May 1916) was an Austrian haematologist and professor of medicine at the  University of Vienna .  He coined the term \"lymphatic reaction\" and the T\u00fcrk cell is named for him. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_62", "text": "This biographical article related to medicine is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_63", "text": "Peter Valent  (born 9 October 1962 in  Vienna ,  Austria ) is an Austrian  hematologist  and  stem cell  researcher. Since 1990 he leads a research group at the  Medical University of Vienna . From 2002 he coordinates the  European Competence Network on Mastocytosis  and since 2008 he is Scientific Director of the  Ludwig Boltzmann Institute for Hematology and Oncology  of the  Ludwig Boltzmann Society  in Austria. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_64", "text": "Valent studied medicine at the  Medical University of Vienna  and graduated in 1987. He is a specialist in  internal medicine  and  hematology  and was promoted to Assistant Professor for  Experimental Hematology  in 1992 and Associate Professor for Internal Medicine in 1995. Valent visited several universities in Germany as Guest Scientist, including the Institute of Pathology of the  University of T\u00fcbingen , the University of Schleswig-Holstein (Campus L\u00fcbeck) and the  LMU Munich . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_65", "text": "Between 1989 and 1999 Valent examined the phenotype and growth characteristics of human mast cells. [ 3 ]  He found that mast cells form a unique lineage in the hematopoietic cell system. [ 4 ] [ 5 ]  In subsequent studies, neoplastic mast cells were characterized. [ 6 ] [ 7 ]  The resulting data contributed essentially to the development of diagnostic criteria and the  WHO  classification of  mastocytosis . [ 8 ]  In 2000, Valent organized a Working Conference on Mastocytosis to implement this classification together with an international consensus group. [ 9 ]  Since 2002 Valent coordinates the  European Competence Network on Mastocytosis  that expanded rapidly and provides a useful basis for the development and conduct of studies and activities in the field of mastocytosis. [ 10 ]  In the forthcoming years, the diagnostic WHO criteria of mastocytosis were validated, adjusted and extended. [ 11 ]  To discuss these developments, Valent and his team organized additional conferences in Vienna, including a  Working Conference on Standards and Standardization of Diagnostic Criteria and Therapies in Mastocytosis [ 12 ]  and one on the  Global Classification of Mast Cell Disorders and Mast Cell Activation Syndromes  (2010). [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_66", "text": "One additional focus in Valent\u00b4s research is the neoplastic stem cell, also termed cancer stem cell in the context of cancer and leukemic stem cell in leukemia contexts. Valent investigates the phenotype of these cells in various hematologic neoplasms and develops concepts predicting the step-wise development of these cells from normal stem cells. The major aim in his research is to identify molecular targets in these cells and to develop more effective (curative) therapies by eliminating these cells in various blood cell disorders, including  Acute Myeloid Leukemia ,  Chronic Myeloid Leukemia , [ 14 ]   Systemic Mastocytosis [ 15 ]  and  Myelodysplastic Syndromes . [ 16 ]  These studies are primarily conducted in the  Ludwig Boltzmann Institute for Hematology and Oncology  at the Medical University of Vienna. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_67", "text": "Valent is a member of numerous scientific organizations and has published over 850 publications since 1988, including more than 500 original papers, over 200 review articles and numerous book contributions. He also published numerous textbook chapters. In 2001, 2008 and 2016 he drew book chapters on mastocytosis as the author of the WHO. Peter Valent is one of the most frequently cited scientists from German-speaking countries in the field of immunology from 2011 to 2015. In Austria he is one of the top 5 scientists in the field of medicine (as of June 2022 -  https://research.com  /scientists-rankings/medicine/at). In total, his work has been cited more than 35,000 times by March 2019 and his h-index is 103 (as of April 2022). Peter Valent is currently ranked #777 among the world's top scientists in Biology and Biochemistry as of April 2022, and #913 among the world's top scientists in Medicine as of June 2022 -  https://research.com/scientists-  rankings/medicine)."}
{"_id": "WikiPedia_Hematology$$$corpus_68", "text": "Valent received several national and international awards, including the  Karl Landsteiner -Award  of the  Austrian Society for Allergy and Immunology , the  Paracelsus Award  of the  Austrian Society for Internal Medicine , the  Wilhelm T\u00fcrk Award  of the  Austrian Society for Hematology and Oncology , the  Theodor-Billroth Medal  of the  Austrian Medical Association , the  Mac Forster Award  of the  European Society for Clinical Investigation  and the  Middle European Award for Interdisciplinary Cancer Research . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_69", "text": "Hematology  ( spelled   haematology  in  British English ) is the branch of  medicine  concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to  blood . [ 1 ] [ 2 ]  It involves treating diseases that affect the production of blood and its components, such as  blood cells ,  hemoglobin ,  blood proteins ,  bone marrow ,  platelets ,  blood vessels ,  spleen , and the mechanism of  coagulation . Such diseases might include  hemophilia ,  sickle cell anemia , blood clots ( thrombus ), other bleeding disorders, and blood  cancers  such as  leukemia ,  multiple myeloma , and  lymphoma . [ 3 ]  The laboratory analysis of blood is frequently performed by a  medical technologist  or  medical laboratory scientist ."}
{"_id": "WikiPedia_Hematology$$$corpus_70", "text": "Physicians specialized in hematology are known as  hematologists  or  haematologists . [ 2 ]  Their routine work mainly includes the care and treatment of patients with hematological diseases, although some may also work at the hematology laboratory viewing  blood films  and  bone marrow  slides under the  microscope , interpreting various hematological test results and  blood clotting test  results. In some institutions, hematologists also manage the hematology laboratory. [ 3 ]  Physicians who work in hematology laboratories, and most commonly manage them, are pathologists specialized in the diagnosis of hematological diseases, referred to as  hematopathologists  or  haematopathologists . Hematologists and hematopathologists generally work in conjunction to formulate a diagnosis and deliver the most appropriate therapy if needed. Hematology is a distinct subspecialty of internal medicine, separate from but overlapping with the subspecialty of medical  oncology . Hematologists may specialize further or have special interests, for example, in:"}
{"_id": "WikiPedia_Hematology$$$corpus_71", "text": "Starting hematologists (in the US) complete a four-year medical degree followed by three or four more years in residency or internship programs. After completion, they further expand their knowledge by spending two or three more years learning how to experiment, diagnose, and treat blood disorders. [ 7 ]  Some exposure to  hematopathology  is typically included in their fellowship training. Job openings for hematologists require training in a recognized fellowship program to learn to diagnose and treat numerous blood-related benign conditions and  blood cancers . Hematologists typically work across specialties  to care for patients with complex illnesses, such as  sickle cell disease , who require complex, multidisciplinary care, and to provide consultation on cases of  disseminated intravascular coagulation ,  thrombosis  and other conditions that can occur in hospitalized patients. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_72", "text": "1q21.1  copy number variations  (CNVs) [ 1 ]  are rare aberrations of human  chromosome 1 ."}
{"_id": "WikiPedia_Hematology$$$corpus_73", "text": "In a common situation a human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 CNVs one chromosome of the pair is not complete because a part of the sequence of the chromosome is missing, or overcomplete, because some parts of the sequence are duplicated. The result is that one chromosome is of normal length and the other one is too long or too short. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_74", "text": "The structure of 1q21.1 is complex. The area has a size of approximately 6 Mega base  (Mb) (from 141.5 Mb to 147.9 Mb). Within 1q21.1 there are two areas where the CNVs can be found: the proximal area or TAR area (144.1 to 144.5) and the distal area (144.7 to 145.9). A 1q21.1 CNV will commonly be found in one of these areas, but an overlap with the other area or parts that are outside these areas are possible. 1q21.1 has multiple repetitions of the same structure: Only 25% of the structure is not duplicated. There are several gaps in the sequence. There is no further information available about the DNA-sequence in those areas up till now. The gaps represent approximately 700 Kilobase. New genes are expected in the gaps. The area of 1q21.1 is one of the most difficult parts of the human genome to map. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_75", "text": "CNVs occur due to  non-allelic homologous recombination  mediated by  low copy repeats  (sequentially similar regions), commonly found in 1q21.1. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_76", "text": "Four separate forms of 1q21.1 CNVs are mentioned in literature. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_77", "text": "The CNVs lead to a very variable  phenotype  and the manifestations in individuals are quite variable. Some people who have a CNV can function in a normal way, while others have symptoms of mental retardation and various physical anomalies. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_78", "text": "Meiosis  is the process of dividing cells in humans. In meiosis, the chromosome pairs splits and a representative of each pair goes to one daughter cell. In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after being randomized. Which information of the parent cell ends up in the daughter cell is purely decided by chance. Besides this random process, there is a second random process. In this second random process the DNA will be scrambled in a way that pieces are omitted ( deletion ), added ( duplication ), moved from one place to another ( translocation ) and inverted ( inversion ). This is a common process, which leads to about 0,4% variation in the DNA. It explains why even identical twins are not genetically 100% identical. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_79", "text": "Problem of the second random process is that genetic mistakes can occur. Especially due to the deletion and duplication process, the chromosomes that come together in a new cell may be shorter or longer. The result of this spontaneous change in the structure of DNA is a so-called  copy number variation . Due to the CNV chromosomes of different sizes can be combined in a new cell. If this occurs around conception, the result will be a first cell of a human with a genetic variation. This can be either positive or negative. In positive cases this new human will be capable of a special skill that is assessed positively, for example, in sports or science. In negative cases, you have to deal with a syndrome or a severe disability, as in this case the 1q21.1 CNVs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_80", "text": "Based on the meiotic process, the syndrome may occur in two ways."}
{"_id": "WikiPedia_Hematology$$$corpus_81", "text": "Due to this genetic misprint the embryo may experience problems in the development during the first months of pregnancy. Approximately 20 to 40 days after fertilization, something goes wrong in the construction of the body parts and brain, which leads to a chain reaction."}
{"_id": "WikiPedia_Hematology$$$corpus_82", "text": "Because of the repetitions in 1q21.1, there is a larger chance on an unequal crossing-over during  meiosis ."}
{"_id": "WikiPedia_Hematology$$$corpus_83", "text": "Genes related to the proximal area are  HFE2 ,  TXNIP ,  POLR3GL ,  LIX1L ,  RBM8A ,  PEX11B ,  ITGA10 ,  ANKRD35 ,  PIAS3 ,  NUDT17 ,  POLR3C ,  RNF115 ,  CD160 ,  PDZK1 , and  GPR89A \nGenes related to the distal area are  PDE4DIP ,  HYDIN2 ,  PRKAB2 ,  PDIA3P ,  FMO5 ,  CHD1L ,  BCL9 ,  ACP6 ,  GJA5 ,  GJA8 ,  NBPF10 ,  GPR89B ,  GPR89C ,  PDZK1P1  and  NBPF11 ."}
{"_id": "WikiPedia_Hematology$$$corpus_84", "text": "1q21.1 deletion syndrome  is a rare aberration of  chromosome 1 . A human cell has one pair of identical chromosomes on  chromosome 1 . With the 1q21.1 deletion syndrome, one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. One chromosome has the normal length and the other is too short."}
{"_id": "WikiPedia_Hematology$$$corpus_85", "text": "In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the deletion is situated."}
{"_id": "WikiPedia_Hematology$$$corpus_86", "text": "The syndrome is a form of the  1q21.1 copy number variations , and it is a deletion in the distal area of the 1q21.1 part. The  CNV  leads to a very variable  phenotype , and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of intellectual impairment and various physical anomalies. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_87", "text": "1q21.1 microdeletion is a very rare chromosomal condition. Only 46 individuals with this deletion have been reported in medical literature as of August 2011. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_88", "text": "Approximately 75% of all children with a 1q21.1 microdeletion exhibit  delayed development , notably in  motor skills  such as sitting, standing, and walking. [ 1 ]  Individuals may have generalized mild  learning difficulties ;  about\u00a030% of those diagnosed with 1q21.1 deletion syndrome are affected. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_89", "text": "Dysmorphic craniofacial  traits are common, however,\u00a0they are highly varied and thus difficult to identify.  Microcephaly  has been reported in 39% of those with the 1q21.1 deletion. [ 4 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_90", "text": "It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have completely different effects on members of the same family. [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_91", "text": "Genitourinary  abnormalities include  vesicoureteral reflux ,  hydronephrosis ,  inguinal hernia ,  cryptorchidism , and  genital malformations .\u00a0There have been two reported cases of  Mayer-Rokitansky-Kuster-Hauser syndrome  alongside 1q21.1 deletion syndrome. [ 6 ] [ 4 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_92", "text": "The majority of affected people have normal  neurologic  physical examinations, however  hypotonia  and  tremors  are quite common.  Seizures \u00a0affect roughly 16% of children and typically begin during infancy. [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_93", "text": "Possible psychiatric and behavioral abnormalities include  autism spectrum disorder ,  attention deficit hyperactivity disorder , and  mood disorders . Furthermore, distal 1q21.1 microdeletions have been found in 0.2%-0.6% of those with  schizophrenia . [ 4 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_94", "text": "A common deletion is between 1.0-1.9Mb. Mefford states that the standard for a deletion is 1.35Mb. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_95", "text": "1q21.1 deletion is  autosomal dominant , with 18%-50% of deletions developing  de novo \u00a0and 50%-82%  inherited  from a parent. [ 4 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_96", "text": "The majority of affected\u00a0individuals\u00a0are missing a 1.35 million  DNA   base pair sequence , also written as 1.35  megabases  (Mb), in the q21.1 region of  chromosome 1 , though the exact size of the deleted region differs. This deletion affects one of each cell's two copies of  chromosome 1 . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_97", "text": "The symptoms caused by a 1q21.1 microdeletion are most likely due to the loss of many  genes  in this region. Researchers are attempting to determine which missing genes may contribute to 1q21.1 deletions' specific characteristics. Because some people with a 1q21.1 microdeletion have no clear associated traits, it is hypothesized that additional  genetic  and  environmental factors  influence the development of symptoms. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_98", "text": "Due to this genetic misprint, the  embryo  may experience problems in the development during the first months of pregnancy. Approximately 20 to 40 days after  fertilization , something goes wrong in the construction of the body parts and brain, which leads to a chain reaction. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_99", "text": "The recurring distal 1.35-Mb  heterozygous  deletion within the position of 145\u2013146.35 Mb in the reference  genome  confirms the diagnosis of 1q21.1 deletion. The  copy number  of sequences can be determined using  chromosome microarrays  or targeted deletion analysis by  fluorescence in situ hybridization . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_100", "text": "22q11.2 microdeletion  shares several characteristics with 1q21.1 microdeletion including  developmental delays ,  learning disabilities ,  intellectual disability , and  behavioral deviations . Those with recurrent 1q21.1 microdeletion, on the other hand, do not have the distinctive facial traits seen in the  22q11.2  microdeletion syndrome. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_101", "text": "Several examinations should be performed to determine the level of  disability  and the needs of a person with the 1q21.1 deletion. Because of the vast range of symptoms,  ophthalmologic ,  cardiac ,  developmental ,  neurological , and  psychiatric  evaluations may be helpful in identifying the manifestations of 1q21.1 deletion. Different developmental abnormalities of the  skull  and  genitourinary system  can be identified with  brain imaging  and  renal ultrasounds . Consultations with a  medical geneticist  or  genetic counselor  can aid in determining the cause of 1q21.1 deletion. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_102", "text": "Because of the variability in 1q21.1 deletion, management is dependent on specific symptoms.  Occupational  and  physical therapy , as well as special learning programs, may be used to manage symptoms. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_103", "text": "Nonallelic homologous recombination  (NAHR), mediated by  low copy repeats  (LCRs), is a well-known mechanism of  copy number alterations  in an array of  genomic diseases . Individually, these conditions are uncommon, yet collectively, they impact a significant portion of the population. 1q21.1 deletions are estimated to occur in about 0.015% of the population. However, these  CNVs  are incompletely  penetrant , therefore it is likely that the actual prevalence in the general population is greater than the current\u00a0predictions. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_104", "text": "Statistical research showed that schizophrenia is more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with  1q21.1 duplication syndrome . Further research confirmed that the odds on a relation between schizophrenia and deletions at 1q21.1,  3q29 , 15q13.3, 22q11.21 en Neurexin 1 (NRXN1) and duplications at 16p11.2 are at 7.5% or higher. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_105", "text": "Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_106", "text": "Research is done on 10\u201312 genes on 1q21.1 that produce  DUF1220 -locations. DUF1220 is an unknown  protein , which is active in the  neurons  of the  brain  near the  neocortex . Based on research on  apes  and other  mammals , it is assumed that DUF1220 is related to cognitive development (man: 212 locations; chimpanzee: 37 locations; monkey: 30 locations; mouse: 1 location). It appears that the DUF1220-locations on 1q21.1 are in areas that are related to the size and the development of the brain. The aspect of the size and development of the brain is related to autism ( macrocephaly ) and schizophrenia ( microcephaly ). It has been proposed that a deletion or duplication of a gene that produces DUF1220-areas might cause growth and development disorders in the brain [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_107", "text": "Another relation between  macrocephaly  with duplications and  microcephaly  with deletions has been seen in research on the HYDIN Paralog or HYDIN2. This part of 1q21.1 is involved in the development of the brain. It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2. [ 14 ] \nResearch on the genes  CHD1L  and  PRKAB2  within  lymphoblast  cells [ 15 ]  lead to the conclusion that anomalies appear with the 1q21.1-deletion syndrome:"}
{"_id": "WikiPedia_Hematology$$$corpus_108", "text": "GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5  tetralogy of Fallot  is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_109", "text": "The  partial thromboplastin time  ( PTT ), also known as the  activated partial thromboplastin time  ( aPTT  or  APTT ), is a  blood test  that characterizes  coagulation  of the  blood . A historical name for this measure is the  Kaolin-cephalin clotting time  ( KCCT ), [ 1 ]  reflecting  kaolin  and  cephalin  as materials historically used in the test. Apart from detecting abnormalities in blood clotting, [ 2 ]  partial thromboplastin time is also used to monitor the treatment effect of  heparin , a widely prescribed  drug that reduces blood's tendency to clot ."}
{"_id": "WikiPedia_Hematology$$$corpus_110", "text": "The PTT measures the overall speed at which blood clots form by means of two consecutive series of biochemical reactions known as the  intrinsic  pathway  and  common pathway  of  coagulation . The PTT indirectly measures action of the following  coagulation factors :  I (fibrinogen) ,  II (prothrombin) ,  V (proaccelerin) ,  VIII (anti-hemophilic factor) ,  X (Stuart\u2013Prower factor) ,  XI (plasma thromboplastin antecedent) , and  XII (Hageman factor) . The PTT is often used in conjunction with another measure of how quickly blood clotting takes place called the  prothrombin time  (PT). The PT measures the speed of clotting by means of the  extrinsic  pathway  and  common pathway ."}
{"_id": "WikiPedia_Hematology$$$corpus_111", "text": "Activated partial thromboplastin time (APTT) is typically analyzed by a medical technologist or laboratory technician, either manually or using an automated instrument at 37\u00b0C, which approximates normal human body temperature.  Prothrombin time  utilizes complete  thromboplastin , a combination of  tissue factor  and  phospholipids . In contrast, APTT employs partial thromboplastin, containing only phospholipids and no tissue factor\u2014hence the term \"partial thromboplastin time.\" An activator is used in the APTT test to initiate the intrinsic pathway of blood coagulation. Common activators include kaolin, silica, celite, and ellagic acid. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_112", "text": "The typical  reference range  is between 25  seconds  and 33 s (depending on laboratory). Longer times of up to 50 s do apply to infants. Shortening of the PTT is considered to have little clinical relevance, but some research indicates that it might increase risk of  thromboembolism . [ 4 ]  Normal PTT requires the presence of the following coagulation factors: I, II, V, VIII, IX, X, XI and XII. Notably, deficiencies in factors VII or XIII will not be detected with the PTT test. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_113", "text": "Prolonged aPTT may indicate: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_114", "text": "To distinguish the above causes,  mixing tests  are performed, in which the patient's plasma is mixed (initially at a 50:50 dilution) with normal plasma. If the abnormality does not disappear, the sample is said to contain an \"inhibitor\" (either heparin, antiphospholipid antibodies or coagulation factor specific inhibitors), while if it does disappear a factor deficiency is more likely. Deficiencies of  factors VIII ,  IX ,  XI  and  XII  and rarely  von Willebrand factor  (if causing a low factor VIII level) may lead to a prolonged aPTT correcting on mixing studies."}
{"_id": "WikiPedia_Hematology$$$corpus_115", "text": "The aPTT is usually normal in  pregnancy  but tends to slightly decrease in late pregnancy. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_116", "text": "The aPTT-based  activated protein C  (APC) resistance test is used in the diagnosis of  APC resistance  (APCR). [ 7 ]  It involves a modified aPTT test performed in the presence and absence of APC. [ 7 ] [ 8 ]  The ratio of these aPTT values is calculated and is called the APC sensitivity ratio (APCsr) or simply APC ratio (APCr). [ 7 ] [ 8 ]  This ratio is inversely related to the degree of APC resistance. [ 9 ]  The aPTT-based APC resistance test was developed in 1993. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_117", "text": "The partial thromboplastin time was first described in 1953 by researchers at the  University of North Carolina at Chapel Hill . [ 10 ]  The initial exogenous phospholipid used in PTT testing was  Cephalin . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_118", "text": "Agglutination  is the clumping of particles.  The word  agglutination  comes from the  Latin   agglutinare  (glueing to)."}
{"_id": "WikiPedia_Hematology$$$corpus_119", "text": "Agglutination is a reaction in which particles (as red blood cells or bacteria) suspended in a liquid collect into clumps usually as a response to a specific antibody."}
{"_id": "WikiPedia_Hematology$$$corpus_120", "text": "This occurs in biology in two main examples:"}
{"_id": "WikiPedia_Hematology$$$corpus_121", "text": "Hemagglutination  is the process by which  red blood cells  agglutinate, meaning clump or clog. The agglutin involved in hemagglutination is called  hemagglutinin .  In  cross-matching ,  donor  red blood cells and the recipient's serum or plasma are incubated together.  If agglutination occurs, this indicates that the donor and recipient blood types are  incompatible ."}
{"_id": "WikiPedia_Hematology$$$corpus_122", "text": "When a person produces  antibodies  against their own red blood cells, as in  cold agglutinin disease  and other  autoimmune  conditions, the cells may agglutinate spontaneously. [ 1 ]  This is called  autoagglutination  and it can interfere with laboratory tests such as  blood typing  and the  complete blood count . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_123", "text": "Leukoagglutination occurs when the particles involved are  white blood cells ."}
{"_id": "WikiPedia_Hematology$$$corpus_124", "text": "An example is the PH-L form of  phytohaemagglutinin ."}
{"_id": "WikiPedia_Hematology$$$corpus_125", "text": "Agglutination is commonly used as a method of identifying specific bacterial antigens and the identity of such bacteria, and therefore is an important technique in diagnosis."}
{"_id": "WikiPedia_Hematology$$$corpus_126", "text": "Two bacteriologists, Herbert Edward Durham (-1945) and  Max von Gruber  (1853\u20131927), discovered specific agglutination in 1896. The clumping became known as Gruber-Durham reaction. Gruber introduced the term agglutinin (from the Latin) for any substance that caused agglutination of cells."}
{"_id": "WikiPedia_Hematology$$$corpus_127", "text": "French physician Fernand Widal (1862\u20131929) put Gruber and Durham's discovery to practical use later in 1896, using the reaction as the basis for a test for  typhoid fever . Widal found that blood serum from a typhoid carrier caused a culture of typhoid bacteria to clump, whereas serum from a typhoid-free person did not. This  Widal test  was the first example of serum diagnosis."}
{"_id": "WikiPedia_Hematology$$$corpus_128", "text": "Austrian physician  Karl Landsteiner  found another important practical application of the agglutination reaction in 1900. Landsteiner's agglutination tests and his discovery of ABO blood groups was the start of the science of  blood transfusion  and  serology  which has made transfusion possible and safer."}
{"_id": "WikiPedia_Hematology$$$corpus_129", "text": "Antigen-antibody interaction,  or  antigen-antibody reaction , is a specific chemical interaction between  antibodies  produced by  B cells  of the  white blood cells  and  antigens  during  immune reaction . The antigens and antibodies combine by a process called agglutination. It is the fundamental reaction in the body by which the body is protected from complex foreign molecules, such as pathogens and their chemical toxins. In the blood, the antigens are specifically and with high affinity bound by antibodies to form an antigen-antibody complex. The immune complex is then transported to cellular systems where it can be destroyed or deactivated."}
{"_id": "WikiPedia_Hematology$$$corpus_130", "text": "The first correct description of the antigen-antibody reaction was given by Richard J. Goldberg at the  University of Wisconsin  in 1952. [ 1 ] [ 2 ]  It came to be known as \"Goldberg's theory\" (of antigen-antibody reaction). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_131", "text": "There are several types of antibodies and antigens, and each antibody is capable of binding only to a specific antigen. The specificity of the binding is due to specific chemical constitution of each antibody. The  antigenic determinant  or epitope is recognized by the  paratope  of the antibody, situated at the variable region of the polypeptide chain. The variable region in turn has hyper-variable regions which are unique  amino acid sequences  in each antibody. Antigens are bound to antibodies through weak and noncovalent interactions such as  electrostatic interactions ,  hydrogen bonds ,  Van der Waals forces , and  hydrophobic interactions . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_132", "text": "The principles of specificity and cross-reactivity of the antigen-antibody interaction are useful in clinical laboratory for diagnostic purposes. One basic application is determination of ABO blood group. It is also used as a molecular technique for infection with different pathogens, such as HIV, microbes, and  helminth  parasites."}
{"_id": "WikiPedia_Hematology$$$corpus_133", "text": "Immunity developed as an individual is exposed to antigens is called adaptive or acquired immunity, in contrast to immunity developed at birth, which is innate immunity. Acquired immunity depends upon the interaction between antigens and a group of proteins called antibodies produced by B cells of the blood. There are many antibodies and each is specific for a particular type of antigen. Thus immune response in acquired immunity is due to the precise binding of antigens to antibody. Only very small area of the antigens and antibody molecules actually interact through complementary binding sites, called epitopes in antigens and paratopes in antibody. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_134", "text": "In an antibody, the  Fab (fragment, antigen-binding) region  is formed from the amino-terminal end of both the light and heavy chains of the  immunoglobulin  polypeptide. This region, called the variable (V) domain, is composed of amino acid sequences that define each type of antibody and their binding affinity to an antigen. The combined sequence of variable light chain (V L ) and variable heavy chain (V H ) creates three hypervariable regions (HV1, HV2, and HV3). In V L  these are roughly from residues 28 to 35, from 49 to 59, and from 92 to 103, respectively. HV3 is the most variable part. Thus these regions may be part of a paratope, the part of an antibody that recognizes and binds to an antigen. The rest of the V region between the hypervariable regions are called framework regions. Each V domain has four framework domains, namely  FR1, FR2, FR3, and FR4. [ 4 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_135", "text": "Antibodies bind antigens through weak chemical interactions, and bonding is essentially  non-covalent .  Electrostatic interactions ,  hydrogen bonds ,  van der Waals forces , and  hydrophobic interactions  are all known to be involved depending on the interaction sites. [ 7 ] [ 8 ]  Non-covalent bonds between antibody and antigen can also be mediated by interfacial water molecules. Such indirect bonds can contribute to the phenomenon of cross-reactivity, i.e. the recognition of different but related antigens by a single antibody. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_136", "text": "Antigen and antibody interact through a high affinity binding much like lock and key. [ 10 ]  A dynamic equilibrium exists for the binding. For example, the reaction is a reversible one, and can be expressed as: [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_137", "text": "where [Ab] is the  antibody  concentration and [Ag] is the  antigen  concentration, either in free ([Ab],[Ag]) or bound ([AbAg]) state."}
{"_id": "WikiPedia_Hematology$$$corpus_138", "text": "The equilibrium association constant  K a  can therefore be represented as:"}
{"_id": "WikiPedia_Hematology$$$corpus_139", "text": "where  k on  and  k off  are the association and dissociation rate constants, respectively."}
{"_id": "WikiPedia_Hematology$$$corpus_140", "text": "Reciprocally, the equilibibrium dissociation constant  K d  will be:"}
{"_id": "WikiPedia_Hematology$$$corpus_141", "text": "The antibody-antigen binding kinetic can be described by the rate equation of a  second-order reversible reaction . However, these equations are applicable only to a single epitope binding, i.e. one antigen on one antibody. Since the antibody necessarily has two paratopes, and in many circumstances complex binding occurs, the multiple binding equilibrium can be summed up as:"}
{"_id": "WikiPedia_Hematology$$$corpus_142", "text": "where, at equilibrium, c is the concentration of free ligand, r represents the ratio of the concentration of bound ligand to total antibody concentration and n is the maximum number of binding sites per antibody molecule (the antibody valence). [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_143", "text": "The overall strength of the binding of an antibody to an antigen is termed its  avidity  for that antigen. Since antibodies are bivalent or polyvalent, this is the sum of the strengths of individual antibody-antigen interactions. The strength of an individual interaction between a single binding site on an antibody and its target epitope is termed the affinity of that interaction. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_144", "text": "Avidity and affinity can be judged by the  dissociation constant  for the interactions they describe. The lower the dissociation constant, the higher the avidity or affinity, and the stronger the interaction. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_145", "text": "Normally antibodies can detect and differentiate molecules from outside of the body and those produced inside the body as a result of cellular activities. Self molecules as ignored by the immune system. However, in certain conditions, the antibodies recognise self molecules as antigens and triggers unexpected immune responses. This results in different  autoimmune diseases  depending on the type of antigens and antibodies involved. Such conditions are always harmful and sometimes deadly. The exact nature of antibody-antigen interaction in autoimmune disease is not yet understood. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_146", "text": "Antigen-antibody interaction is used in laboratory techniques for serological test of blood compatibility and various pathogenic infections. The most basic is  ABO blood group  determination, which is useful for  blood transfusion . [ 19 ]  Sophisticated applications include  ELISA , [ 20 ]   enzyme-linked immunospot ( Elispot ),  immunofluorescence , and  immunoelectrophoresis . [ 21 ] [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_147", "text": "Soluble antigens combine with soluble antibodies in presence of an electrolyte at suitable temperature and pH to form insoluble visible complex. This is called a  precipitation reaction . It is used for qualitative and quantitative determination of both antigen and antibody. It involves the reaction of soluble  antigen with soluble  antibodies to form large interlocking aggravated called lattice. [ 24 ]  It occurs in two distinct stages. Firstly, the antigen and antibody rapidly form antigen-antibody complexes within few seconds and this is followed by a slower reaction in which the antibody-antigen complexes forms lattices that precipitate from the solution. [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_148", "text": "A special ring test is useful for diagnosis of anthrax and determination of adulteration in food. [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_149", "text": "It acts on antigen-antibody reaction in which the antibodies cross-link particulate antigens resulting in the visible clumping of the particle. There are two types, namely active and passive  agglutination . [ 29 ]  They are used in blood tests for diagnosis of  enteric fever . [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_150", "text": "Apheresis  ( \u1f00\u03c6\u03b1\u03af\u03c1\u03b5\u03c3\u03b9\u03c2  ( aphairesis , \"a taking away\")) is a  medical technology  in which the  blood  of a person is passed through an apparatus that separates out one particular  constituent  and returns the remainder to the circulation.  It is thus an  extracorporeal  therapy."}
{"_id": "WikiPedia_Hematology$$$corpus_151", "text": "One of the uses of apheresis is for collecting  hematopoetic stem cells . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_152", "text": "Depending on the substance that is being removed, different processes are employed in apheresis. If separation by  density  is required,  centrifugation  is the most common method. Other methods involve absorption onto beads coated with an absorbent material [ 2 ]  and filtration. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_153", "text": "The centrifugation method can be divided into two basic categories: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_154", "text": "Continuous flow centrifugation (CFC) historically required two  venipunctures  as \"continuous\" means the blood is collected, spun, and returned simultaneously. Newer systems can use a single venipuncture by pooling blood in a vessel and cycling through drawing and returning blood though the needle while the centrifuge continuously processes blood remaining in the vessel. [ 5 ]  The main advantage of this system is the low extracorporeal volume (calculated by volume of the apheresis chamber, the donor's  hematocrit , and total blood volume of the donor) used in the procedure, which may be advantageous in the elderly and for children. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_155", "text": "Intermittent flow centrifugation (IFC) works in cycles, taking blood, spinning/processing it and then giving back the unused parts to the donor in a  bolus . The main advantage is a single venipuncture site. It does require a larger extracorporeal volume, and takes significantly longer to perform the procedure via IFC. As such, it is less likely to be used for therapeutic reasons, and is often seen in Donation Center settings. [ 6 ]  To stop the blood from  coagulating ,  anticoagulant  is automatically mixed with the blood as it is pumped from the body into the apheresis machine. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_156", "text": "The centrifugation process itself has four variables that can be controlled to selectively remove desired components. The first is spin speed and bowl diameter, the second is \"sit time\" in centrifuge, the third is solutes added, and the fourth is not as easily controllable: plasma volume and cellular content of the donor. The result in most cases is the classic sedimented blood sample with the  RBCs  at the bottom, the  buffy coat  of platelets and  WBCs  ( lymphocytes ,  granulocytes ,  monocytes ) in the middle and the plasma on top. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_157", "text": "There are numerous types of apheresis."}
{"_id": "WikiPedia_Hematology$$$corpus_158", "text": "Blood taken from a healthy donor can be separated into its component parts during  blood donation , where the needed component is collected and the unharvested components are returned to the donor.  Fluid replacement  is usually not needed in this type of collection.  In many countries, apheresis donors can donate platelets more often than those donating whole blood. There are several categories of component collections:"}
{"_id": "WikiPedia_Hematology$$$corpus_159", "text": "Two apheresis kit recalls were:"}
{"_id": "WikiPedia_Hematology$$$corpus_160", "text": "People who do not use a drug that may prevent blood donation, who do not have the risk of the carrier of a disease, and who have suitable vascular structure may be apheresis donors. For apheresis platelet donation the donor's pre platelet count should be above 150 x 10^9/L. For apheresis plasma donation, the donor's total protein level should be greater than 60 g/L. For double red cell apheresis, donors of either gender require a minimum hemoglobin level of 14.0 g/dl. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_161", "text": "Apheresis uses plastics and tubing, which come into contact with the blood. The plastics are made of  PVC  in addition to additives such as a  plasticizer , often  DEHP . DEHP leaches from the plastic into the blood, and people have begun to study the possible effects of this leached DEHP on donors as well as transfusion recipients. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_162", "text": "The various apheresis techniques may be used whenever the removed constituent is causing severe symptoms of disease. Generally, apheresis has to be performed fairly often, and is an invasive process. It is therefore only employed if other means to control a particular disease have failed, or the symptoms are of such a nature that waiting for medication to become effective would cause suffering or risk of complications.  For autoimmune diseases in which apheresis is effective, it is used not as a standalone treatment, but rather in conjunction with therapies that reduce production of autoantibodies."}
{"_id": "WikiPedia_Hematology$$$corpus_163", "text": "In 2023, [ 22 ]  the  American Society for Apheresis  published the 9th Special Edition of  evidence based guidelines  for the practice of Apheresis Medicine.  These guidelines are based upon a systematic review of available scientific literature.  Clinical utility for a given disease is denoted by assignment of an  ASFA Category  (I \u2013 IV).  The quality and strength of evidence are denoted by standard  GRADE  recommendations. ASFA Categories are defined as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_164", "text": "Only diseases (or mentioned special conditions thereof) with ASFA category I or II are displayed in  bold , with category I being  underlined  in addition."}
{"_id": "WikiPedia_Hematology$$$corpus_165", "text": "When an apheresis system is used for therapy, the system is removing relatively small amounts of fluid (not more than 10.5 mL/kg body weight). That fluid must be replaced to keep correct intravascular volume. The fluid replaced is different at different institutions. If a  crystalloid  like  normal saline  (NS) is used, the infusion amount should be triple what is removed as the 3:1 ratio of normal saline for plasma is needed to keep up  oncotic pressure . Some institutions use  human serum albumin , but it is costly and can be difficult to find. Routine use of  fresh frozen plasma  (FFP) is not generally appropriate because of the dangers including citrate toxicity (from the anticoagulant),  ABO incompatibility ,  infection , and allergic reactions.  However, FFP should be used in cases of  thrombotic thrombocytopenic purpura  or patients at high risk of bleeding."}
{"_id": "WikiPedia_Hematology$$$corpus_166", "text": "{{ }}"}
{"_id": "WikiPedia_Hematology$$$corpus_167", "text": "Arterial blood  is the oxygenated blood in the  circulatory system  found in the  pulmonary vein , the left chambers of the  heart , and in the  arteries . [ 1 ]  It is bright red in color, while  venous blood  is dark red in color (but looks purple through the translucent skin). It is the  contralateral  term to  venous blood . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_168", "text": "Framed in the  cardiac cycle , often historically accredited to the  Wiggers diagram , arterial blood has just passed through the lungs and is ready to boost  oxygen  to sustain the peripheral organs. The essential difference between venous and arterial blood is the curve of the oxygen saturation of  haemoglobin . The difference in the oxygen content of the blood between the arterial blood and the venous blood is known as the  arteriovenous oxygen difference . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_169", "text": "The  Ashby technique  is a method for determining the volume and life span of red blood cells in humans, first published by  Dr. Winifred Ashby  in 1919. [ 1 ]  The technique involves injection of compatible donor red blood cells of a different  blood group  into a recipient, followed by blood testing periodically afterwards. Differential  agglutination  of the red cells is then used to determine the number of remaining donor cells, allowing the survival rate to be determined. It does not involve  radioisotope  technology, and was the first technique to successfully establish the correct red blood cell life span. In particular,  Type O blood  is first transfused into  Type A or B  subjects. In subsequent blood samples, the patient's own A and B blood cells are removed by agglutination with either anti-A or anti-B  serum . The number of remaining nonagglutinated Type O cells as a function of time defines the survival rate of blood cells. [ 2 ]  This technique was used extensively during World War II and shortly after but has more recently been replaced by techniques that label one's own blood, due to the dangers of using donor blood. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_170", "text": "This  medical  diagnostic article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_171", "text": "In  hematology ,  atypical localization of immature precursors  ( ALIP ) refers to finding of atypically localized precursors ( myeloblasts  and  promyelocytes ) on  bone marrow biopsy . In healthy humans, precursors are rare and are found localized near the endosteum, and consist of 1\u20132 cells. In some cases of  myelodysplastic syndromes  (MDS), immature precursors might be located in the intertrabecular region and occasionally aggregate as clusters of 3\u20135 cells. The presence of ALIPs is associated with worse prognosis of MDS. [ 1 ]  Recently, in bone marrow sections of patients with  acute myeloid leukemia  cells similar to ALIPs were defined as ALIP-like clusters. The presence of ALIP-like clusters in AML patients within remission was reported to be associated with  early relapse of the disease. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_172", "text": "This article related to  pathology  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_173", "text": "An  azurophilic granule  is a cellular object readily  stainable  with a  Romanowsky stain .  In  white blood cells  and  hyperchromatin , staining imparts a  burgundy  or merlot coloration.  Neutrophils  in particular are known for containing azurophils loaded with a wide variety of anti-microbial  defensins  that fuse with  phagocytic   vacuoles .  Azurophils may contain  myeloperoxidase ,  phospholipase A2 ,  acid hydrolases ,  elastase , defensins, neutral  serine proteases ,  bactericidal permeability-increasing protein , [ 1 ]   lysozyme ,  cathepsin G ,  proteinase 3 , and  proteoglycans . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_174", "text": "Azurophil granules are also known as \"primary granules\". [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_175", "text": "Furthermore, the term \"azurophils\" may refer to a unique type of cells, identified only in  reptiles .  These cells are similar in size to so-called  heterophils  with abundant  cytoplasm  that is finely to coarsely granular and may sometimes contain vacuoles.  Granules may impart a purplish hue to the cytoplasm, particularly to the outer region.  Occasionally, azurophils are observed with vacuolated cytoplasm. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_176", "text": "This  hematology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_177", "text": "4U0Q ,  3B5H ,  3I84 ,  3I85 ,  3QQN ,  3QR2"}
{"_id": "WikiPedia_Hematology$$$corpus_178", "text": "682"}
{"_id": "WikiPedia_Hematology$$$corpus_179", "text": "12215"}
{"_id": "WikiPedia_Hematology$$$corpus_180", "text": "ENSG00000172270"}
{"_id": "WikiPedia_Hematology$$$corpus_181", "text": "ENSMUSG00000023175"}
{"_id": "WikiPedia_Hematology$$$corpus_182", "text": "P35613"}
{"_id": "WikiPedia_Hematology$$$corpus_183", "text": "P18572"}
{"_id": "WikiPedia_Hematology$$$corpus_184", "text": "NM_001728 NM_198589 NM_198590 NM_198591 NM_001322243"}
{"_id": "WikiPedia_Hematology$$$corpus_185", "text": "NM_001077184 NM_009768"}
{"_id": "WikiPedia_Hematology$$$corpus_186", "text": "NP_001309172 NP_001719 NP_940991 NP_940992 NP_940993"}
{"_id": "WikiPedia_Hematology$$$corpus_187", "text": "NP_001070652 NP_033898"}
{"_id": "WikiPedia_Hematology$$$corpus_188", "text": "Basigin  ( BSG ) also known as  extracellular matrix metalloproteinase inducer  ( EMMPRIN ) or  cluster of differentiation 147  ( CD147 ) is a  protein  that in humans is encoded by the  BSG   gene . [ 5 ] [ 6 ] [ 7 ]  This protein is a determinant for the Ok  blood group system . There are three known antigens in the Ok system; the most common being Ok a  (also called OK1), OK2 and OK3. Basigin has been shown to be an essential receptor on red blood cells for the human malaria parasite,  Plasmodium falciparum . [ 8 ]  The common isoform of basigin (basigin-2) has two immunoglobulin domains, and the extended form basigin-1 has three. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_189", "text": "Basigin is a member of the  immunoglobulin superfamily , with a structure related to the putative primordial form of the family. As members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic phenomena, differentiation, and development, basigin is thought also to play a role in intercellular recognition (Miyauchi et al., 1991; Kanekura et al., 1991). [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_190", "text": "It has a variety of functions. In addition to its metalloproteinase-inducing ability, basigin also regulates several distinct functions, such as  spermatogenesis , expression of the  monocarboxylate transporter  and the responsiveness of  lymphocytes . [ 6 ] \nBasigin is a type I  integral membrane receptor  that has many  ligands , including the  cyclophilin  (CyP) proteins Cyp-A and CyP-B and certain  integrins . [ 12 ] [ 13 ] [ 14 ]  Basigin also serves as a receptor for S100A9 and platelet glycoprotein VI, and basigin-1 acts as a receptor for the rod-derived cone viability factor. [ 9 ]  It is expressed by many cell types, including  epithelial cells ,  endothelial cells , neural progenitor cells [ 15 ]  and  leukocytes . The human basigin protein contains 269 amino acids that form two heavily  glycosylated   C2 type immunoglobulin-like domains  at the N-terminal extracellular portion. A second form of basigin has also been characterized that contains one additional immunoglobulin-like domain in its extracellular portion. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_191", "text": "Basigin has been shown to  interact  with  Ubiquitin C . [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_192", "text": "Basigin has been shown to form a complex with  monocarboxylate transporters  in the retina of mice. Basigin appears to be required for proper placement of MCTs in the membrane.  In the Basigin  null mouse , the failure of MCTs to integrate with the membrane may be directly linked to a failure of nutrient transfer in the retinal pigmented epithelium (the lactates transported by MCTs 1, 3, and 4 are essential nutrients for the developing RPE), resulting in loss of sight in the null animal. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_193", "text": "Basigin interacts with the fourth  C-type lectin [ circular reference ]  domain in the receptor  Endo180 [ 18 ]  to form a molecular  epithelial-mesenchymal transition [ citation needed ]  suppressor complex that if disrupted results in the induction of invasive prostate epithelial cell behavior associated with poor prostate cancer survival. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_194", "text": "It have been shown that  Atorvastatin  suppresses CD147 and  MMP-3  expression. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_195", "text": "It has recently (November 2011) been found that basigin is a receptor that is essential to erythrocyte invasion by most strains of  Plasmodium falciparum , the most virulent species of the  plasmodium  parasites that cause human  malaria .  It is hoped that by developing antibodies to the parasite ligand for Basigin,  Rh5 , a better vaccine for malaria might be found. [ 8 ]  Basigin is bound by the PfRh5 protein on the surface of the malaria parasite. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_196", "text": "Meplazumab , an anti-CD147 antibody, was tested in patients with SARS-CoV-2 pneumonia. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_197", "text": "Some of these claims have been challenged by another group of scientists who found no evidence of a direct role for basigin in either binding the viral spike protein or promoting lung cell infection. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_198", "text": "More recent studies suggests CD147 as SARS-CoV-2 entry receptor of  platelets  and  megakaryocytes , leading to hyperactivation and thrombosis, that differs from common cold coronavirus  CoV-OC43 . Incubation of megakaryocyte cells with SARS-CoV-2 resulted in a significant increase in the proinflammatory transcripts  LGALS3BP  and  S100A9 . Notably, CD147 antibody-mediated blocking significantly reduced the expression of  S100A9 , and  S100A8  on megakaryocytes following incubation with SARS-CoV-2. These data indicate that megakaryocytes and platelets actively take up SARS-CoV-2 virions, likely via an  ACE-2 -independent mechanism. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_199", "text": "Another study states that platelets challenged with SARS-CoV-2 undergo activation, dependent on the CD147 receptor. [ 25 ]  Yet SARS-CoV-2 does not replicate in human platelets, but initiates cell death. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_200", "text": "Yet another study describes high-interaction coupling of N-RBD of SARS-CoV-2 and CD147 as the main way of infecting  lymphocytes  allegedly leading to  Acquired Immune Deficiency Syndrome . [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_201", "text": "Bence Jones protein  is a monoclonal  globulin   protein  or  immunoglobulin light chain  found in the  urine , with a molecular weight of 22\u201324  kDa . [ 1 ]    Detection of Bence Jones protein may be suggestive of  multiple myeloma , [ 2 ]  or  Waldenstr\u00f6m's macroglobulinemia . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_202", "text": "Bence Jones proteins are particularly diagnostic of multiple myeloma in the context of target organ manifestations such as  kidney failure , lytic (or \"punched out\") bone lesions,  anemia , or large numbers of  plasma cells  in the  bone marrow .  Bence Jones proteins are present in 2/3 of multiple myeloma cases. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_203", "text": "The proteins are  immunoglobulin light chains  ( paraproteins ) and are produced by  neoplastic  plasma cells. They can be kappa (most of the time) or lambda. [ 3 ]  The light chains can be immunoglobulin fragments or single homogeneous immunoglobulins. They are found in urine as a result of decreased kidney filtration capabilities due to  kidney failure , sometimes induced by  hypercalcemia  from the calcium released as the bones are destroyed, dehydration due to polyuria, amyloidosis or from the light chains themselves. [ citation needed ]  The light chains were historically detected by heating a  urine  specimen (which causes the protein to precipitate) and nowadays by  electrophoresis  of concentrated urine. [ 4 ]   More recently,  serum free light chain assays  have been utilised in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma [ 5 ] [ 6 ] [ 7 ]  and  amyloid light chain amyloidosis (AL amyloidosis) . [ 7 ] [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_204", "text": "The Bence Jones protein was described by the English physician  Henry Bence Jones  in 1847 and published in 1848. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_205", "text": "\u03b2-Thromboglobulin  ( \u03b2-TG ), or  beta-thromboglobulin , is a  chemokine   protein  secreted by  platelets . [ 1 ] [ 2 ]  It is a type of  chemokine (C-X-C motif) ligand 7 . [ 3 ]  Along with  platelet factor 4  (PF4), \u03b2-TG is one of the best-characterized platelet-specific proteins. [ 4 ]  \u03b2-TG and PF4 are stored in  platelet alpha granules  and are released during  platelet activation . [ 1 ] [ 4 ] [ 5 ]  As a result, they are useful markers of platelet activation. [ 1 ] [ 4 ]  \u03b2-TG also has multiple  biological activities , for instance being involved in maturation of  megakaryocytes . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_206", "text": "\u03b2-TG is a  chemoattractant , strongly for  fibroblasts  and weakly for  neutrophils . It is a stimulator of  mitogenesis ,  extracellular matrix  synthesis,  glucose metabolism , and  plasminogen activator  synthesis in human fibroblasts. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_207", "text": "\u03b2-TG also affects  megakaryocyte  maturation, and thus helps in regulating  platelet  production. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_208", "text": "Levels of \u03b2-TG is used to index platelet activation. It is measured by  ELISA  in  blood plasma  or urine, and often in conjunction with PF4. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_209", "text": "\u03b2-TG levels may increase with age. [ 7 ]  It is elevated in  diabetes mellitus . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_210", "text": "\u03b2-TG levels have been found to be increased by treatment with the  synthetic   estrogen   ethinylestradiol , though were not significantly increased by the  natural  estrogen  estradiol valerate . [ 9 ] [ 10 ] [ 11 ] [ 12 ]  Levels of \u03b2-TG have also been found to be increased or unchanged during normal  pregnancy . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_211", "text": "This  biochemistry  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_212", "text": "Bilirubin glucuronide  is a water-soluble  reaction intermediate  over the process of  conjugation  of indirect  bilirubin . [ 1 ]  Bilirubin  glucuronide  itself belongs to the category of conjugated bilirubin along with  bilirubin di-glucuronide . [ 2 ]  However, only the latter one is primarily excreted into the bile in the normal setting. [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_213", "text": "Upon  macrophages  spot and  phagocytize  the effete  Red Blood Corpuscles  containing  hemoglobin , [ 6 ]  unconjugated bilirubin is discharged from macrophages into the blood plasma. [ 7 ] [ 8 ]  Most often, the free and water-insoluble unconjugated bilirubin which has an internal hydrodren [ clarification needed ]  bonding [ 9 ]  will bind to  albumin  and, to a much lesser extent, high density  lipoprotein  in order to decrease its  hydrophobicity  and to limit the probability of unnecessary contact with other tissues [ 1 ] [ 9 ]  and keep bilirubin in the vascular space from traversing to extravascular space including  brain , and from ending up increasing  glomerular filtration . [ 9 ]  Nevertheless, there is still a little portion of indirect bilirubins stays free-of-bound. [ 9 ]  Free unconjugated bilirubin can poison the  cerebrum . [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_214", "text": "Finally, albumin leads the indirect bilirubin to the  liver . [ 1 ] [ 9 ]  In the  liver sinusoid , albumin disassociates with the indirect bilirubin and returns to the circulation while the  hepatocyte  transfers the indirect bilirubin to  ligandin  and  glucuronide  conjugates the indirect bilirubin in the  endoplasmic reticulum  by disrupting unconjugated bilirubin's internal  hydrogen bonding , which is the thing that makes indirect bilirubin having the property of eternal half-elimination life and insoluble in water, [ 20 ] [ 9 ] [ 1 ] [ 21 ] [ 22 ]  and by attaching two molecules of  glucuronic acid  to it in a two step process. [ 23 ]  The reaction is  a transfer of two glucuronic acid groups  including  UDP glucuronic acid  sequentially to the  propionic acid  groups of the bilirubin, primarily catalyzed by  UGT1A1 . [ 23 ] [ 24 ] [ 5 ]  In greater detail about this reaction, a glucuronosyl moiety is conjugated to one of the  propionic acid  side chains, located on the C8 and C12 carbons of the two central  pyrrole rings  of bilirubin. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_215", "text": "When the first step is completely done, the  substrate  bilirubin glucuronide (also known as mono- glucuronide [ 26 ] ) is born at this stage and is water-soluble and readily excreted in  bile . [ 24 ] [ 9 ]  Thereafter, so long as the second step of attachment of the other glucuronic acid to it succeeds (officially called \"re- glucuronidated \" [ 26 ] ), the substrate bilirubin glucuronide will turn into bilirubin  di -glucuronide (8,12-diglucuronide [ 26 ] ) and be excreted into  bile canaliculi  by way of  C-MOAT [ note 1 ]   [ 27 ] [ 28 ] [ 29 ] [ 30 ]  and  MRP2 [ 5 ] [ 31 ]  as normal human bile along with a little amount of unconjugated bilirubin as much as only 1 to 4 percent of total  pigments  in normal bile. [ 9 ] [ 32 ]  That means up to 96%-99% of bilirubin in the bile are conjugated. [ 9 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_216", "text": "Normally, there is just a little conjugated bilirubin escapes into the general circulation. [ 1 ]  Nonetheless, in the setting of severe  liver disease , a significantly greater number of conjugated bilirubin will leak into circulation and then dissolve into the  blood [ note 2 ]  and thereby filtered by the  kidney , and only a part of the leaked conjugated bilirubin will be re-absorbed in the  renal tubules , the remainder will be present in the  urine  making it dark-colored. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_217", "text": "The clinical significance of bilirubin glucuronide is involved in many conditions. Drugs that inhibit the activities of the components involved in bilirubin metabolism can give rise to accumulation of bilirubin in the blood. [ 5 ]  In comparison, conjugation of some drugs is also usually impaired if the liver cannot normally  metabolize  indirect bilirubin. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_218", "text": "When  excretion of bilirubin glucuronide by the kidney  is detected in the  urine  through urine examination, meaning that a conspicuous amount of conjugated bilirubin is present and circulating in the blood. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_219", "text": "In  Dubin\u2013Johnson syndrome , impaired biliary excretion of bilirubin glucuronide is due to a mutation in the canalicular  multiple drug-resistance protein 2 (MRP2) . A darkly pigmented liver is due to polymerized  epinephrine   metabolites , not bilirubin. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_220", "text": "If it is the liver that cannot effectively transfer the indirect bilirubin into bilirubin glucuronide and further into bilirubin di-glucuronide, the consequence will be  hyperbilirubinemia  or  intrahepatic (or hepatocellular) jaundice . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_221", "text": "Moreover, the  unconjugated hyperbilirubinemia  arises in case the components of liver transfer the indirect bilirubin into bilirubin glucuronide in the rate  slower  than they should be. [ 3 ]  This condition is associated with either decreased uptake of bilirubin into  hepatocytes  ( Rotor syndrome [ 34 ] ) or defective intracellular protein binding. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_222", "text": "In similar fashion, the  conjugated hyperbilirubinemia  emerges in case the components of the liver have difficulty turning bilirubin glucuronide into bilirubin di-glucuronide. [ 3 ]  Note that  biliary duct blockage  can also lead to  conjugated hyperbilirubinemia  but the pathophysiology is that backflow of bilirubin di-glucuronide with little indirect bilirubin and bilirubin glucuronide from bile duct through liver into blood plasma. [ 3 ] [ 35 ]  These conditions are associated with either defective intracellular protein binding (for the second time) or disturbed secretion into the  bile canaliculi  ( Dubin\u2013Johnson syndrome [ 34 ] ). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_223", "text": "Liver failure  and  hepatitis  are the most etiological in liver-genesis  hyperbilirubinemia . [ 3 ]  In case of hyperbilirubinemia due to  intrahepatic  or  extrahepatic   bile ducts  blockage, e.g.  gallstone , the name is given as  Post-hepatic (or obstructive)  jaundice . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_224", "text": "Bilirubin concentration is not a sensitive early indicator of  liver diseases  as the liver may have reserved its capacity in removal of bilirubin to save energy and unreserved the previously reserved capacity when encountering a sudden rise of unconjugated bilirubin. [ 36 ]  In short, there is still a chance for an ill liver to get rid of excessive unconjugated bilirubin in the blood plasma, displaying a total bilirubin level that is within normal reference range. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_225", "text": "In  Crigler Najjar disease , there is an inherited deficiency of  glucuronyl transferase  resulting in high concentrations of unconjugated bilirubin appear in the plasma. [ 3 ]  Furthermore, those affected may develop  kernicterus  (deposits of pigment in the brain) that can cause  nerve degeneration . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_226", "text": "In  Gilbert's syndrome ,  glucuronyl transferase  activity is reduced by approximately 70%, leading to mild accumulation of unconjugated bilirubin in the plasma. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_227", "text": "At birth, infants don't develop enough ability to conjugate bilirubin. [ 37 ]  Up to 8% to 11% neonates will develop  hyperbilirubinemia  in the first week of their lives. [ 37 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_228", "text": "In  jaundice  owing to  hemolysis  (prehepatic, or  hemolytic , jaundice), the  pathophysiology  is that overproduction of bilirubin from the extravascular or intravascular hemolysis overwhelms the capacity of the liver to excrete it. [ 3 ]  The bilirubin present in the plasma is largely unconjugated in this setting as they haven't been taken up and conjugated by the liver. [ 3 ]  In this case, total serum bilirubin increases while the ratio of direct bilirubin to indirect bilirubin remains 96 to 4 as up to 96%-99% of bilirubin in the bile are conjugated mentioned above. [ 9 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_229", "text": "Although there were some studies that showed an  inverse correlation  between  serum  bilirubin level and prevalences of  ischemic   coronary artery disease , [ 38 ]   cancer  mortality, [ 39 ]  or  colorectal cancer [ 40 ]  in general population, the potential benefits of the chemopreventive function of bilirubin and their causative relations haven't been proved. [ 40 ] [ 9 ] [ 10 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ excessive citations ]"}
{"_id": "WikiPedia_Hematology$$$corpus_230", "text": "Blood  is a  body fluid  in the  circulatory system  of  humans  and other  vertebrates  that delivers necessary substances such as  nutrients  and  oxygen  to the  cells , and transports  metabolic waste products  away from those same cells. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_231", "text": "Blood is composed of blood cells suspended in  blood plasma . Plasma, which constitutes 55% of blood fluid, is mostly  water  (92% by volume), [ 2 ]  and contains  proteins ,  glucose , mineral  ions , and  hormones . The blood cells are mainly  red blood cells  (erythrocytes),  white blood cells  (leukocytes), and (in mammals)  platelets  (thrombocytes). [ 3 ]  The most abundant cells are red blood cells. [ 4 ]  These contain  hemoglobin , which facilitates oxygen transport by reversibly binding to it, increasing its solubility. [ 5 ]   Jawed vertebrates  have an  adaptive immune system , based largely on white blood cells. White blood cells help to resist infections and parasites. Platelets are important in the  clotting  of blood."}
{"_id": "WikiPedia_Hematology$$$corpus_232", "text": "Blood is circulated around the body through  blood vessels  by the pumping action of the  heart . In animals with  lungs ,  arterial  blood carries oxygen from inhaled air to the tissues of the body, and  venous  blood carries carbon dioxide, a waste product of  metabolism  produced by cells, from the tissues to the lungs to be exhaled. Blood is bright red when its hemoglobin is oxygenated and dark red when it is  deoxygenated . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_233", "text": "Medical terms related to blood often begin with  hemo- ,  hemato- ,  haemo-  or  haemato-  from the Greek word  \u03b1\u1f37\u03bc\u03b1  ( haima ) for \"blood\". In terms of  anatomy  and  histology , blood is considered a specialized form of  connective tissue , [ 8 ]  given its origin in the bones and the presence of potential molecular fibers in the form of  fibrinogen . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_234", "text": "Blood performs many important functions within the body, including:"}
{"_id": "WikiPedia_Hematology$$$corpus_235", "text": "Blood accounts for 7% of the human body weight, [ 9 ] [ 10 ]  with an average density around 1060\u00a0kg/m 3 , very close to pure water's density of 1000\u00a0kg/m 3 . [ 11 ]  The average adult has a  blood volume  of roughly 5  litres  (11\u00a0US\u00a0pt) or 1.3 gallons, [ 10 ]  which is composed of plasma and  formed elements . The formed elements are the two types of blood cell or  corpuscle  \u2013 the  red blood cells , (erythrocytes) and  white blood cells  (leukocytes), and the cell fragments called  platelets [ 12 ]  that are involved in clotting. By volume, the red blood cells constitute about 45% of whole blood, the plasma about 54.3%, and white cells about 0.7%."}
{"_id": "WikiPedia_Hematology$$$corpus_236", "text": "Whole blood (plasma and cells) exhibits  non-Newtonian   fluid dynamics . [ specify ]"}
{"_id": "WikiPedia_Hematology$$$corpus_237", "text": "One microliter of blood contains:"}
{"_id": "WikiPedia_Hematology$$$corpus_238", "text": "45 \u00b1 7 (38\u201352%) for males \n42 \u00b1 5 (37\u201347%) for females"}
{"_id": "WikiPedia_Hematology$$$corpus_239", "text": "Oxygenated: 98\u201399% \nDeoxygenated: 75%"}
{"_id": "WikiPedia_Hematology$$$corpus_240", "text": "About 55% of blood is  blood plasma , a fluid that is the blood's liquid medium, which by itself is straw-yellow in color. The blood plasma volume totals of 2.7\u20133.0 liters (2.8\u20133.2 quarts) in an average human. It is essentially an  aqueous  solution containing 92% water, 8% blood plasma  proteins , and trace amounts of other materials. Plasma circulates dissolved nutrients, such as  glucose ,  amino acids , and  fatty acids  (dissolved in the blood or bound to plasma proteins), and removes waste products, such as  carbon dioxide ,  urea , and  lactic acid ."}
{"_id": "WikiPedia_Hematology$$$corpus_241", "text": "Other important  components  include:"}
{"_id": "WikiPedia_Hematology$$$corpus_242", "text": "The term  serum  refers to plasma from which the clotting proteins have been removed. Most of the proteins remaining are albumin and  immunoglobulins ."}
{"_id": "WikiPedia_Hematology$$$corpus_243", "text": "Blood pH  is regulated to stay within the narrow range of 7.35 to 7.45, making it slightly  basic  (compensation). [ 17 ] [ 18 ]  Extra-cellular fluid in blood that has a pH below 7.35 is too  acidic , whereas blood pH above 7.45 is too basic. [ 16 ]  A pH below 6.9 or above 7.8 is usually lethal. [ 16 ]  Blood pH,  partial pressure of oxygen (pO 2 ) ,  partial pressure of carbon dioxide (pCO 2 ) , and  bicarbonate  (HCO 3 \u2212 ) are carefully regulated by a number of  homeostatic mechanisms , which exert their influence principally through the  respiratory system  and the  urinary system  to control the  acid\u2013base balance  and respiration, which is called compensation. [ 16 ]  An  arterial blood gas test  measures these. Plasma also circulates  hormones  transmitting their messages to various tissues. The list of normal  reference ranges  for various blood electrolytes is extensive."}
{"_id": "WikiPedia_Hematology$$$corpus_244", "text": "Human blood is typical of that of mammals, although the precise details concerning cell numbers, size,  protein structure , and so on, vary somewhat between species. In non-mammalian vertebrates, however, there are some key differences: [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_245", "text": "Blood is circulated around the body through  blood vessels  by the pumping action of the  heart . In humans, blood is pumped from the strong  left ventricle  of the heart through  arteries  to peripheral  tissues  and returns to the right  atrium of the heart  through  veins . It then enters the right  ventricle  and is pumped through the  pulmonary artery  to the  lungs  and returns to the left atrium through the  pulmonary veins . Blood then enters the left ventricle to be circulated again. Arterial blood carries oxygen from inhaled air to all of the cells of the body, and  venous blood  carries carbon dioxide, a waste product of  metabolism  by  cells , to the lungs to be exhaled. However, one exception includes pulmonary arteries, which contain the most deoxygenated blood in the body, while the pulmonary veins contain oxygenated blood."}
{"_id": "WikiPedia_Hematology$$$corpus_246", "text": "Additional return flow may be generated by the movement of  skeletal muscles , which can compress veins and push blood through the valves in veins toward the  right atrium ."}
{"_id": "WikiPedia_Hematology$$$corpus_247", "text": "The blood circulation was famously described by  William Harvey  in 1628. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_248", "text": "In vertebrates, the various cells of blood are made in the  bone marrow  in a process called  hematopoiesis , which includes  erythropoiesis , the production of red blood cells; and  myelopoiesis , the production of white blood cells and platelets. During childhood, almost every human bone produces red blood cells; as adults, red blood cell production is limited to the larger bones: the bodies of the vertebrae, the breastbone (sternum), the ribcage, the pelvic bones, and the bones of the upper arms and legs. In addition, during childhood, the  thymus  gland, found in the  mediastinum , is an important source of  T lymphocytes . [ 21 ] \nThe proteinaceous component of blood (including clotting proteins) is produced predominantly by the  liver , while hormones are produced by the  endocrine glands  and the watery fraction is regulated by the  hypothalamus  and maintained by the  kidney ."}
{"_id": "WikiPedia_Hematology$$$corpus_249", "text": "Healthy  erythrocytes  have a plasma life of about 120 days before they are degraded by the  spleen , and the  Kupffer cells  in the liver. The liver also clears some proteins, lipids, and amino acids. The kidney actively secretes waste products into the  urine ."}
{"_id": "WikiPedia_Hematology$$$corpus_250", "text": "About 98.5% [ 22 ]  of the  oxygen  in a sample of arterial blood in a healthy human breathing air at sea-level pressure is chemically combined with the  hemoglobin . About 1.5% is physically dissolved in the other blood liquids and not connected to hemoglobin. The hemoglobin molecule is the primary transporter of oxygen in  mammals  and many other species. Hemoglobin has an oxygen binding capacity between 1.36 and 1.40 ml O 2  per gram hemoglobin, [ 23 ]  which increases the total  blood oxygen capacity  seventyfold, [ 24 ]  compared to if oxygen solely were carried by its solubility of 0.03\u00a0ml O 2  per liter blood per mm\u00a0Hg partial pressure of oxygen (about 100\u00a0mm\u00a0Hg in arteries). [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_251", "text": "With the exception of pulmonary and  umbilical arteries  and their corresponding veins, arteries carry  oxygenated blood  away from the heart and deliver it to the body via  arterioles  and  capillaries , where the oxygen is consumed; afterwards,  venules  and veins carry  deoxygenated blood  back to the heart."}
{"_id": "WikiPedia_Hematology$$$corpus_252", "text": "Under normal conditions in adult humans at rest, hemoglobin in blood leaving the lungs is about 98\u201399%  saturated with oxygen , achieving an oxygen delivery between 950 and 1150 ml/min [ 25 ]  to the body. In a healthy adult at rest, oxygen consumption is approximately 200\u2013250 ml/min, [ 25 ]  and deoxygenated blood returning to the lungs is still roughly 75% [ 26 ] [ 27 ]  (70 to 78%) [ 25 ]  saturated. Increased oxygen consumption during sustained exercise reduces the oxygen saturation of venous blood, which can reach less than 15% in a trained athlete; although breathing rate and blood flow increase to compensate, oxygen saturation in arterial blood can drop to 95% or less under these conditions. [ 28 ]  Oxygen saturation this low is considered dangerous in an individual at rest (for instance, during surgery under anesthesia). Sustained hypoxia (oxygenation less than 90%), is dangerous to health, and severe hypoxia (saturations less than 30%) may be rapidly fatal. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_253", "text": "A  fetus , receiving oxygen via the  placenta , is exposed to much lower oxygen pressures (about 21% of the level found in an adult's lungs), so fetuses produce another form of hemoglobin with a much higher affinity for oxygen ( hemoglobin F ) to function under these conditions. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_254", "text": "CO 2  is carried in blood in three different ways. (The exact percentages vary depending whether it is arterial or venous blood). Most of it (about 70%) is converted to bicarbonate ions  HCO \u2212 3  by the enzyme  carbonic anhydrase  in the red blood cells by the reaction  CO 2  + H 2 O  \u2192  H 2 CO 3   \u2192  H +  + HCO \u2212 3 ; about 7% is dissolved in the plasma; and about 23% is bound to hemoglobin as  carbamino  compounds. [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_255", "text": "Hemoglobin, the main oxygen-carrying molecule in red blood cells, carries both oxygen and carbon dioxide. However, the CO 2  bound to hemoglobin does not bind to the same site as oxygen. Instead, it combines with the N-terminal groups on the four globin chains. However, because of  allosteric  effects on the hemoglobin molecule, the binding of CO 2  decreases the amount of oxygen that is bound for a given partial pressure of oxygen. The decreased binding to carbon dioxide in the blood due to increased oxygen levels is known as the  Haldane effect , and is important in the transport of carbon dioxide from the tissues to the lungs. A rise in the partial pressure of CO 2  or a lower pH will cause offloading of oxygen from hemoglobin, which is known as the  Bohr effect ."}
{"_id": "WikiPedia_Hematology$$$corpus_256", "text": "Some oxyhemoglobin loses oxygen and becomes deoxyhemoglobin. Deoxyhemoglobin binds most of the hydrogen ions as it has a much greater affinity for more hydrogen than does oxyhemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_257", "text": "In mammals, blood is in equilibrium with  lymph , which is continuously formed in tissues from blood by capillary ultrafiltration. Lymph is collected by a system of small lymphatic vessels and directed to the  thoracic duct , which drains into the left  subclavian vein , where lymph rejoins the systemic blood circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_258", "text": "Blood circulation transports heat throughout the body, and adjustments to this flow are an important part of  thermoregulation . Increasing blood flow to the surface (e.g., during warm weather or strenuous exercise) causes warmer skin, resulting in faster heat loss. In contrast, when the external temperature is low, blood flow to the extremities and surface of the skin is reduced and to prevent heat loss and is circulated to the important organs of the body, preferentially."}
{"_id": "WikiPedia_Hematology$$$corpus_259", "text": "Rate of blood flow varies greatly between different organs. Liver has the most abundant blood supply with an approximate flow of 1350 ml/min. Kidney and brain are the second and the third most supplied organs, with 1100 ml/min and ~700 ml/min, respectively. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_260", "text": "Relative rates of blood flow per 100 g of tissue are different, with kidney, adrenal gland and thyroid being the first, second and third most supplied tissues, respectively. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_261", "text": "The restriction of blood flow can also be used in specialized tissues to cause engorgement, resulting in an  erection  of that tissue; examples are the  erectile tissue  in the  penis  and  clitoris ."}
{"_id": "WikiPedia_Hematology$$$corpus_262", "text": "Another example of a hydraulic function is the  jumping spider , in which blood forced into the legs under pressure causes them to straighten for a powerful jump, without the need for bulky muscular legs. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_263", "text": "Hemoglobin is the principal determinant of the color of blood ( hemochrome ). Each molecule has four heme groups, and their interaction with various molecules alters the exact color. Arterial blood and capillary blood are bright red, as oxygen imparts a strong red color to the heme group. Deoxygenated blood is a darker shade of red; this is present in veins, and can be seen during  blood donation  and when venous blood samples are taken. This is because the spectrum of light absorbed by hemoglobin differs between the oxygenated and deoxygenated states. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_264", "text": "Blood in  carbon monoxide poisoning  is bright red, because  carbon monoxide  causes the formation of  carboxyhemoglobin . In  cyanide  poisoning, the body cannot use oxygen, so the venous blood remains oxygenated, increasing the redness. There are some conditions affecting the heme groups present in hemoglobin that can make the skin appear blue\u00a0\u2013 a symptom called  cyanosis . If the heme is oxidized,  methemoglobin , which is more brownish and cannot transport oxygen, is formed. In the rare condition  sulfhemoglobinemia , arterial hemoglobin is partially oxygenated, and appears dark red with a bluish hue."}
{"_id": "WikiPedia_Hematology$$$corpus_265", "text": "Veins close to the surface of the skin appear blue for a variety of reasons. However, the factors that contribute to this alteration of  color perception  are related to the light-scattering properties of the skin and the processing of visual input by the  visual cortex , rather than the actual color of the venous blood. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_266", "text": "Skinks  in the genus  Prasinohaema  have green blood due to a buildup of the waste product  biliverdin . [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_267", "text": "Substances other than oxygen can bind to hemoglobin; in some cases, this can cause irreversible damage to the body. Carbon monoxide, for example, is extremely dangerous when carried to the blood via the lungs by inhalation, because carbon monoxide irreversibly binds to hemoglobin to form carboxyhemoglobin, so that less hemoglobin is free to bind oxygen, and fewer oxygen molecules can be transported throughout the blood. This can cause suffocation insidiously. A fire burning in an enclosed room with poor ventilation presents a very dangerous hazard, since it can create a build-up of carbon monoxide in the air. Some carbon monoxide binds to hemoglobin when smoking tobacco. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_268", "text": "Blood for transfusion is obtained from human donors by  blood donation  and stored in a  blood bank . There are many different  blood types  in humans, the  ABO blood group system , and the  Rhesus blood group system  being the most important. Transfusion of blood of an incompatible blood group may cause severe, often fatal, complications, so  crossmatching  is done to ensure that a compatible blood product is transfused."}
{"_id": "WikiPedia_Hematology$$$corpus_269", "text": "Other blood products administered  intravenously  are platelets, blood plasma, cryoprecipitate, and specific coagulation factor concentrates."}
{"_id": "WikiPedia_Hematology$$$corpus_270", "text": "Many forms of medication (from  antibiotics  to  chemotherapy ) are administered intravenously, as they are not readily or adequately absorbed by the digestive tract."}
{"_id": "WikiPedia_Hematology$$$corpus_271", "text": "After severe acute blood loss, liquid preparations, generically known as plasma expanders, can be given intravenously, either solutions of salts (NaCl, KCl, CaCl 2  etc.) at physiological concentrations, or colloidal solutions, such as dextrans,  human serum albumin , or fresh frozen plasma. In these emergency situations, a plasma expander is a more effective life-saving procedure than a blood transfusion, because the metabolism of transfused red blood cells does not restart immediately after a transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_272", "text": "In modern  evidence-based medicine , bloodletting is used in management of a few rare diseases, including  hemochromatosis  and  polycythemia . However,  bloodletting  and  leeching  were common unvalidated interventions used until the 19th century, as many diseases were incorrectly thought to be due to an excess of blood, according to  Hippocratic  medicine."}
{"_id": "WikiPedia_Hematology$$$corpus_273", "text": "English  blood  ( Old English   blod ) derives from  Germanic  and has cognates with a similar range of meanings in all other Germanic languages (e.g. German  Blut , Swedish  blod , Gothic  bl\u014d\u00fe ). There is no accepted  Indo-European  etymology. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_274", "text": "Robin F\u00e5hr\u00e6us  (a Swedish physician who devised the  erythrocyte sedimentation rate ) suggested that the Ancient Greek system of  humorism , wherein the body was thought to contain four distinct bodily fluids (associated with different temperaments), were based upon the observation of blood clotting in a transparent container. When blood is drawn in a glass container and left undisturbed for about an hour, four different layers can be seen. A dark clot forms at the bottom (the \"black bile\"). Above the clot is a layer of red blood cells (the \"blood\"). Above this is a whitish layer of white blood cells (the \"phlegm\"). The top layer is clear yellow serum (the \"yellow bile\"). [ 42 ] [ failed verification ]"}
{"_id": "WikiPedia_Hematology$$$corpus_275", "text": "In general, Greek thinkers believed that blood was made from food. Plato and Aristotle are two important sources of evidence for this view, but it dates back to Homer's  Iliad . [ 43 ]  Plato thinks that fire in our bellies transform food into blood. [ 44 ]  Plato believes that the movements of air in the body as we exhale and inhale carry the fire as it transforms our food into blood. [ 45 ]  Aristotle believed that food is concocted into blood in the heart and transformed into our body's matter. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_276", "text": "The ABO blood group system was discovered in the year 1900 by  Karl Landsteiner .  Jan Jansk\u00fd  is credited with the first classification of blood into the four types (A, B, AB, and O) in 1907, which remains in use today. In 1907 the first  blood transfusion  was performed that used the ABO system to predict compatibility. [ 47 ]  The first non-direct transfusion was performed on 27 March 1914. The Rhesus factor was discovered in 1937."}
{"_id": "WikiPedia_Hematology$$$corpus_277", "text": "Due to its importance to life, blood is associated with a large number of beliefs. One of the most basic is the use of blood as a symbol for family relationships through birth/parentage; to be \"related by blood\" is to be related by ancestry or descendence, rather than marriage. This bears closely to  bloodlines , and sayings such as \" blood is thicker than water \" and \" bad blood \", as well as \" Blood brother \"."}
{"_id": "WikiPedia_Hematology$$$corpus_278", "text": "Blood is given particular emphasis in the  Islamic ,  Jewish , and  Christian  religions, because  Leviticus  17:11 says \"the life of a creature is in the blood.\" This phrase is part of the Levitical law forbidding the drinking of blood or eating meat with the blood still intact instead of being poured off."}
{"_id": "WikiPedia_Hematology$$$corpus_279", "text": "Mythic references to blood can sometimes be connected to the life-giving nature of blood, seen in such events as childbirth, as contrasted with the blood of injury or death."}
{"_id": "WikiPedia_Hematology$$$corpus_280", "text": "In many  indigenous Australian Aboriginal peoples'  traditions,  ochre  (particularly red) and blood, both high in iron content and considered  Maban , are applied to the bodies of dancers for ritual. As Lawlor states:"}
{"_id": "WikiPedia_Hematology$$$corpus_281", "text": "In many Aboriginal rituals and ceremonies, red ochre is rubbed all over the naked bodies of the dancers. In secret, sacred male ceremonies, blood extracted from the veins of the participant's arms is exchanged and rubbed on their bodies. Red ochre is used in similar ways in less-secret ceremonies. Blood is also used to fasten the feathers of birds onto people's bodies. Bird feathers contain a protein that is highly magnetically sensitive. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_282", "text": "Lawlor comments that blood employed in this fashion is held by these peoples to attune the dancers to the invisible energetic realm of the  Dreamtime . Lawlor then connects these invisible energetic realms and  magnetic fields , because iron is  magnetic ."}
{"_id": "WikiPedia_Hematology$$$corpus_283", "text": "Among the  Germanic tribes , blood was used during their sacrifices; the  Bl\u00f3ts . The blood was considered to have the power of its originator, and, after the butchering, the blood was sprinkled on the walls, on the statues of the gods, and on the participants themselves. This act of sprinkling blood was called  bl\u00f3edsian  in  Old English , and the terminology was borrowed by the  Roman Catholic Church  becoming  to bless  and  blessing . The  Hittite  word for blood,  ishar  was a cognate to words for \"oath\" and \"bond\", see  Ishara .\nThe  Ancient Greeks  believed that the blood of the gods,  ichor , was a substance that was poisonous to mortals."}
{"_id": "WikiPedia_Hematology$$$corpus_284", "text": "As a relic of Germanic Law, the  cruentation , an ordeal where the corpse of the victim was supposed to start bleeding in the presence of the murderer, was used until the early 17th century. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_285", "text": "In  Genesis  9:4, God prohibited  Noah  and his sons from eating blood (see  Noahide Law ). This command continued to be observed by the  Eastern Orthodox Church ."}
{"_id": "WikiPedia_Hematology$$$corpus_286", "text": "It is also found in the Bible that when the Angel of Death came around to the Hebrew house that the first-born child would not die if the angel saw lamb's blood wiped across the doorway."}
{"_id": "WikiPedia_Hematology$$$corpus_287", "text": "At the  Council of Jerusalem , the  apostles  prohibited certain Christians from consuming blood\u00a0\u2013 this is documented in Acts 15:20 and 29. This chapter specifies a reason (especially in verses 19\u201321): It was to avoid offending Jews who had become Christians, because the Mosaic Law Code prohibited the practice."}
{"_id": "WikiPedia_Hematology$$$corpus_288", "text": "Christ's blood is the means for the  atonement  of sins. Also, \"... the blood of Jesus Christ his [God] Son cleanseth us from all sin.\" (1 John 1:7), \"... Unto him [God] that loved us, and washed us from our sins in his own blood.\" (Revelation 1:5), and \"And they overcame him (Satan) by the blood of the Lamb [Jesus the Christ], and by the word of their testimony ...\" (Revelation 12:11)."}
{"_id": "WikiPedia_Hematology$$$corpus_289", "text": "Some Christian churches, including Roman Catholicism,  Eastern Orthodoxy ,  Oriental Orthodoxy , and the  Assyrian Church of the East  teach that, when consecrated, the  Eucharistic  wine  actually becomes  the  blood of Jesus  for worshippers to drink. Thus in the consecrated wine, Jesus becomes spiritually and physically present. This teaching is rooted in  the Last Supper , as written in the four gospels of the Bible, in which Jesus stated to his  disciples  that the bread that they ate was his body, and the wine was his blood.  \"This cup is the new testament in my blood, which is shed for you.\" ( Luke 22:20 ) ."}
{"_id": "WikiPedia_Hematology$$$corpus_290", "text": "Most forms of Protestantism, especially those of a  Methodist  or  Presbyterian  lineage, teach that the wine is no more than a symbol of the blood of Christ, who is spiritually but not physically present.  Lutheran  theology teaches that the body and blood is  present together \"in, with, and under\"  the bread and wine of the Eucharistic feast."}
{"_id": "WikiPedia_Hematology$$$corpus_291", "text": "In  Judaism , animal blood may not be consumed even in the smallest quantity (Leviticus 3:17 and elsewhere); this is reflected in Jewish  dietary  laws ( Kashrut ). Blood is purged from meat by rinsing and soaking in water (to loosen clots),  salting  and then rinsing with water again several times. [ 50 ]  Eggs must also be checked and any blood spots removed before consumption. [ 51 ]  Although blood from fish is biblically kosher, it is rabbinically forbidden to consume fish blood to avoid the appearance of breaking the Biblical prohibition. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_292", "text": "Another ritual involving blood involves the covering of the blood of  fowl  and  game  after slaughtering (Leviticus 17:13); the reason given by the  Torah  is: \"Because the life of the animal is [in] its blood\" (ibid 17:14). In relation to human beings,  Kabbalah  expounds on this verse that the  animal soul  of a person is in the blood, and that physical desires stem from it."}
{"_id": "WikiPedia_Hematology$$$corpus_293", "text": "Likewise, the mystical reason for salting temple sacrifices and slaughtered meat is to remove the blood of animal-like passions from the person. By removing the animal's blood, the animal energies and life-force contained in the blood are removed, making the meat fit for human consumption. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_294", "text": "Consumption of food containing blood is forbidden by  Islamic dietary laws . This is derived from the statement in the  Qur'an , sura  Al-Ma'ida  (5:3): \"Forbidden to you (for food) are: dead meat, blood, the flesh of swine, and that on which has been invoked the name of other than Allah.\""}
{"_id": "WikiPedia_Hematology$$$corpus_295", "text": "Blood is considered unclean, hence there are specific methods to obtain physical and ritual status of cleanliness once bleeding has occurred. Specific rules and prohibitions apply to  menstruation , postnatal bleeding and irregular vaginal bleeding. When an animal has been slaughtered, the animal's neck is cut in a way to ensure that the spine is not severed, hence the brain may send commands to the heart to pump blood to it for oxygen. In this way, blood is removed from the body, and the meat is generally now safe to cook and eat. In modern times, blood transfusions are generally not considered against the rules."}
{"_id": "WikiPedia_Hematology$$$corpus_296", "text": "Based on their interpretation of scriptures such as Acts 15:28, 29 (\"Keep abstaining...from blood.\"), many  Jehovah's Witnesses  neither consume blood nor accept transfusions of whole blood or its major components: red blood cells, white blood cells, platelets (thrombocytes), and plasma. Members may personally decide whether they will accept medical procedures that involve their own blood or substances that are further fractionated from the four major components. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_297", "text": "Vampires  are mythical creatures that drink blood directly for sustenance, usually with a preference for human blood. Cultures all over the world have myths of this kind; for example the ' Nosferatu ' legend, a human who achieves  damnation  and immortality by drinking the blood of others, originates from Eastern European folklore.  Ticks ,  leeches , female  mosquitoes ,  vampire bats , and an assortment of other natural creatures do consume the blood of other animals, but only bats are associated with vampires. This has no relation to vampire bats, which are  New World  creatures discovered well after the origins of the European myths."}
{"_id": "WikiPedia_Hematology$$$corpus_298", "text": "In invertebrates, a body fluid analogous to blood called hemolymph is found, the main difference being that hemolymph is not contained in a closed circulatory system. Hemolymph may function to carry oxygen, although hemoglobin is not necessarily used.  Crustaceans  and  mollusks  use  hemocyanin  instead of hemoglobin. [ 55 ]  In most insects, their hemolymph does not contain oxygen-carrying molecules because their bodies are small enough for their  tracheal system  to suffice for supplying oxygen."}
{"_id": "WikiPedia_Hematology$$$corpus_299", "text": "Blood residue  can help  forensic  investigators identify weapons, reconstruct a criminal action, and link suspects to the crime. Through  bloodstain pattern analysis , forensic information can also be gained from the spatial distribution of bloodstains."}
{"_id": "WikiPedia_Hematology$$$corpus_300", "text": "Blood residue analysis is also a technique used in  archeology ."}
{"_id": "WikiPedia_Hematology$$$corpus_301", "text": "Blood is one of the body fluids that has been used in art. [ 56 ]  In particular, the performances of  Viennese Actionist   Hermann Nitsch ,  Istvan Kantor ,  Franko B ,  Lennie Lee ,  Ron Athey ,  Yang Zhichao ,  Lucas Abela  and  Kira O'Reilly , along with the photography of  Andres Serrano , have incorporated blood as a prominent visual element.  Marc Quinn  has made sculptures using frozen blood, including a cast of his own head made using his own blood."}
{"_id": "WikiPedia_Hematology$$$corpus_302", "text": "The term  blood  is used in  genealogical circles  to refer to one's  ancestry ,  origins , and  ethnic background  as in the word  bloodline . Other terms where blood is used in a family history sense are  blue-blood ,  royal blood ,  mixed-blood  and  blood relative ."}
{"_id": "WikiPedia_Hematology$$$corpus_303", "text": "A  blood donation  occurs when a person voluntarily has  blood  drawn and used for  transfusions  and/or made into  biopharmaceutical medications  by a process called  fractionation  (separation of  whole blood  components). A donation may be of  whole blood , or of specific components directly ( apheresis ).  Blood banks  often participate in the collection process as well as the procedures that follow it."}
{"_id": "WikiPedia_Hematology$$$corpus_304", "text": "Today in the  developed world , most  blood donors  are unpaid volunteers who donate blood for a community supply. In some countries, established supplies are limited and donors usually give blood when family or friends need a transfusion (directed donation).  Many donors donate for several reasons, such as a form of charity, general awareness regarding the demand for blood, increased confidence in oneself, helping a personal friend or relative, and  social pressure .  Despite the many reasons that people donate, not enough potential donors actively donate.  However, this is reversed during disasters when blood donations increase, often creating an excess supply that will have to be later discarded.  In countries that allow paid donation some people are paid, and in some cases there are incentives other than money such as  paid time off  from work. People can also have blood drawn for their own future use ( autologous donation ). Donating is relatively safe, but some donors have bruising where the needle is inserted or may feel faint."}
{"_id": "WikiPedia_Hematology$$$corpus_305", "text": "Potential donors are evaluated for anything that might make their blood unsafe to use. The screening includes testing for diseases that can be transmitted by a blood transfusion, including  HIV  and  viral hepatitis . The donor must also answer questions about  medical history  and take a short  physical examination  to make sure the donation is not hazardous to their health. How often a donor can donate varies from days to months based on what component they donate and the laws of the country where the donation takes place. For example, in the United States, donors must wait 56 days (eight weeks) between  whole-blood donations  but only seven days between  platelet apheresis  donations and twice per seven-day period in  plasmapheresis . [ 1 ] :\u200aHow often can I donate blood?"}
{"_id": "WikiPedia_Hematology$$$corpus_306", "text": "The amount of blood drawn and the methods vary. The collection can be done manually or with automated equipment that takes only specific components of the blood. Most of the components of blood used for transfusions have a short  shelf life , and maintaining a constant supply is a persistent problem. This has led to some increased interest in  autotransfusion , whereby a patient's blood is salvaged during surgery for continuous  reinfusion \u2014or alternatively, is self-donated prior to when it will be needed. Generally, the notion of donation does not refer to giving to one's self, though in this context it has become somewhat acceptably idiomatic."}
{"_id": "WikiPedia_Hematology$$$corpus_307", "text": "Charles Richard Drew  (1904\u20131950) was an American  surgeon  and  medical researcher . His research was in the field of  blood transfusions , developing improved techniques for blood storage, and applied his expert knowledge to developing large-scale  blood banks  early in  World War II . This allowed medics to save thousands of lives of the  Allied  forces. As the most prominent  African American  in the field, Drew protested against the practice of  racial segregation  in the donation of blood, as it lacked scientific foundation, and resigned his position with the  American Red Cross , which maintained the policy until 1950. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_308", "text": "Blood donations are divided into groups based on who will receive the collected blood. [ 2 ]  An  allogeneic  (also called  homologous ) donation is when a donor gives blood for storage at a  blood bank  for  transfusion  to an unknown recipient. A  directed  donation is when a person, often a family member, donates blood for transfusion to a specific individual. [ 3 ]  Directed donations are relatively rare when an established supply exists. [ 4 ]  A  replacement donor  donation is a hybrid of the two and is common in developing countries. [ 5 ]  In this case, a friend or family member of the recipient donates blood to replace the stored blood used in a transfusion, ensuring a consistent supply. When a person has blood stored that will be transfused back to the donor at a later date, usually after surgery, that is called an  autologous donation . [ 6 ]  Blood that is used to make medications can be made from allogeneic donations or from donations exclusively used for manufacturing. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_309", "text": "Sometimes there are specific reasons for preferring one form or the other.  Allogeneic donations have a lower risk of some complications than blood from a family member. [ 8 ]   Neonatal alloimmune thrombocytopenia  may require a transfusion from the mother's own platelets. [ 8 ]   Autologous (self) donations may be preferred for someone with a rare blood type for a planned surgery. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_310", "text": "Blood is sometimes collected using similar methods for  therapeutic phlebotomy , similar to the ancient practice of  bloodletting , which is used to treat conditions such as  hereditary hemochromatosis  or  polycythemia vera . This blood is sometimes treated as a blood donation, but may be immediately discarded if it cannot be used for transfusion or further manufacturing. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_311", "text": "The actual process varies according to the laws of the country, and recommendations to donors vary according to the collecting organization. [ 10 ] [ 11 ] [ 12 ]  The  World Health Organization  gives recommendations for blood donation policies, [ 13 ]  but in developing countries many of these are not followed. For example, the recommended testing requires laboratory facilities, trained staff, and specialized reagents, all of which may not be available or too expensive in developing countries. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_312", "text": "A  blood drive  or a  blood donor session  is an event in which donors come to donate allogeneic blood. These can occur at a blood bank, but they are often set up at a location in the community, such as a shopping center, workplace, school, or house of worship. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_313", "text": "Donors are typically required to give  consent  for the process, and meet a certain criteria such as weight and hemoglobin levels, and this requirement means  minors  cannot donate without permission from a parent or guardian. [ 16 ]  In some countries, answers are associated with the donor's blood, but not name, to provide anonymity; in others, such as the United States, names are kept to create lists of ineligible donors. [ 17 ]  If a potential donor does not meet these criteria, they are 'deferred'. This term is used because many donors who are ineligible may be allowed to donate later. Blood banks in the United States may be required to label the blood if it is from a therapeutic donor, so some do not accept donations from donors with any blood disease. [ 18 ]  Others, such as the  Australian Red Cross Blood Service , accept blood from donors with  hemochromatosis . It is a genetic disorder that does not affect the safety of the blood. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_314", "text": "The donor's race or ethnic background is sometimes important since certain  blood types , especially rare ones, are more common in certain ethnic groups. [ 20 ]  Historically, in the United States donors were segregated or excluded on race, religion, or ethnicity, but this is no longer a standard practice. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_315", "text": "Donors are screened for health risks that could make the donation unsafe for the recipient. Some of these restrictions are controversial, such as  restricting donations from men who have sex with men  (MSM) because of the risk of transmitting  HIV . [ 23 ]  In 2011, the UK (excluding Northern Ireland) reduced its blanket ban on MSM donors to a narrower restriction which only prevents MSM from donating blood if they have had sex with other men within the past year. [ 24 ]  A similar change was made in the US in late 2015 by the  Food and Drug Administration  (FDA). [ 25 ]  In 2017, the UK and US further reduced their restrictions to three months. [ 26 ]  In 2023, the FDA announced new policies easing restrictions on gay and bisexual men donating blood. [ 27 ]  These updated guidelines stipulate that men in monogamous relationships with other men, or who have not recently had sex, can donate. [ 27 ]  Individuals who report having sex with people who are HIV positive or have had sex with a new partner who has engaged in anal sex are still barred from blood donation. [ 27 ]   Autologous  donors are not always screened for recipient safety problems since the donor is the only person who will receive the blood. [ 28 ]  Since the donated blood may be given to pregnant women or women of child-bearing age, donors taking  teratogenic  (birth defect-causing) medications are deferred. These medications include  acitretin ,  etretinate ,  isotretinoin ,  finasteride , and  dutasteride . [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_316", "text": "Donors are examined for signs and symptoms of diseases that can be transmitted in a blood transfusion, such as  HIV ,  malaria , and  viral hepatitis . Screening may include questions about risk factors for various diseases, such as travel to countries at risk for malaria or  variant Creutzfeldt\u2013Jakob disease  (vCJD). These questions vary from country to country. For example, while blood centers in  Qu\u00e9bec  and the rest of  Canada ,  Poland , and many other places defer donors who lived in the United Kingdom for risk of vCJD, [ 30 ] [ 31 ]  donors in the United Kingdom are only restricted for vCJD risk if they have had a blood transfusion in the United Kingdom. [ 32 ]  Australia removed its UK-donor deferral in July 2022. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_317", "text": "Directed donations from family members (e.g., a father donating blood to his child) carry extra risks for the recipient. [ 8 ]   Any blood transfusion carries some risk of a  transfusion reaction , but between genetically related family members, there are additional risks. [ 8 ]   The donated blood must be irradiated to prevent a potentially deadly  graft-versus-host disease , which is more likely between genetically related people. [ 8 ]   Not all healthcare facilities have the equipment to do this on site. [ 8 ]   Alloimmunization  is a particular risk for directed  granulocyte donations . [ 8 ]   It is a common misconception that directed donations are safer for the recipient; however, family members and close friends, especially parents who have not previously donated blood, frequently feel pressured into lying about disqualifying risk factors (e.g., drug use or prior sexual relationships) and their eligibility, which can result in a higher risk of infection with  bloodborne pathogens . [ 8 ]   Additionally, in the less common case of a person with leukemia or other bone marrow disease, a familial blood transfusion can trigger the production of  alloantibodies  against  HLA  proteins, which can cause a  bone marrow transplant  from that donor to fail in the future. [ 8 ]   (Closely related family members are usually the best match for a bone marrow transplant. [ 8 ] )  A directed donation from an unrelated friend, however, would not have the same risk."}
{"_id": "WikiPedia_Hematology$$$corpus_318", "text": "The donor is also examined and asked specific questions about their medical history to make sure that donating blood is not hazardous to their health. The donor's  hematocrit  or  hemoglobin  level is tested to make sure that the loss of blood will not make them  anemic , and this check is the most common reason that a donor is ineligible. [ 34 ]  Accepted hemoglobin levels for blood donations, by the American Red Cross, is 12.5g/dL (for females) and 13.0g/dL (for males) to 20.0g/dL, anyone with a higher or lower hemoglobin level cannot donate. [ 35 ]   Pulse ,  blood pressure , and  body temperature  are also evaluated. Elderly donors are sometimes also deferred on age alone because of health concerns. [ 36 ]  In addition to age, weight and height are important factors when considering the eligibility for donors. For example, the American Red Cross requires a donor to be 110 pounds (50\u00a0kg) or more for whole blood and platelet donation and at least 130 pounds (59\u00a0kg) (males) and at least 150 pounds (68\u00a0kg) (females) for power red donations (double red  erythrocytapheresis ). [ 37 ]  The safety of donating blood during pregnancy has not been studied thoroughly, and pregnant women are usually deferred until six weeks after the pregnancy. [ 38 ]  Donors with aortic stenosis have traditionally been deferred out of concern that the acute volume depletion (475 mL) of blood donation might compromise cardiac output. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_319", "text": "The donor's  blood type  must be determined if the blood will be used for transfusions. The collecting agency usually identifies whether the blood is type  A, B, AB, or O  and the donor's  Rh (D) type  and will screen for  antibodies  to less common antigens. More testing, including a  crossmatch , is usually done before a transfusion. Type O negative is often cited as the \"universal donor\" [ 40 ]  but this only refers to  red cell  and whole blood transfusions. For  plasma  and platelet transfusions the system is reversed: AB positive is the universal platelet donor type while both AB positive and AB negative are universal plasma donor types. [ 41 ] [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_320", "text": "Most blood is tested for diseases, including some  STDs . [ 43 ]  The tests used are  high-sensitivity screening tests  and no actual diagnosis is made. Some of the test results are later found to be false positives using more  specific testing . [ 44 ]   False negatives  are rare, but donors are discouraged from using blood donation for the purpose of anonymous STD  screening  because a false negative could mean a contaminated unit. The blood is usually discarded if these tests are positive, but there are some exceptions, such as  autologous donations . The donor is generally notified of the test result. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_321", "text": "Donated blood is tested by many methods, but the core tests recommended by the World Health Organization are these four: [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_322", "text": "The WHO reported in 2006 that 56 out of 124 countries surveyed did not use these basic tests on all blood donations. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_323", "text": "A variety of other tests for  transfusion transmitted infections  are often used based on local requirements. Additional testing is expensive, and in some cases the tests are not implemented because of the cost. [ 47 ]  These additional tests include other infectious diseases such as  West Nile fever [ 48 ]  and  babesiosis . [ 49 ]  Sometimes multiple tests are used for a single disease to cover the limitations of each test. For example, the  HIV antibody test  will not detect a recently infected donor, so some blood banks use a  p24 antigen  or  HIV nucleic acid  test in addition to the basic antibody test to detect infected donors.  Cytomegalovirus  is a special case in donor testing in that many donors will test positive for it. [ 50 ]  The virus is not a hazard to a healthy recipient, but it can harm infants [ 51 ]  and other recipients with weak immune systems. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_324", "text": "Blood testing in the US takes at least 48 hours. [ 52 ]  Because of the time required for testing, directed donations are not practical in emergencies. [ 8 ] [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_325", "text": "There are two main methods of obtaining blood from a donor. The most frequent is to simply take the blood from a vein as  whole blood . This blood is typically separated into parts, usually  red blood cells  and  plasma , since most recipients (other than trauma patients) need only a specific component for transfusions. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_326", "text": "The amount of blood donated in one session \u2013 generally called a 'unit' \u2013 is defined by the WHO as 450 millilitres. [ 54 ]  Some countries like Canada follow this standard, [ 55 ]  but others have set their own rules, and sometimes there is variation even among different agencies within a country. For example, whole blood donations in the United States are in the 460\u2013500 ml range, [ 56 ] [ 57 ]  while those in the EU must be in the 400-500 ml range. [ 58 ]  Other countries have smaller units \u2013 India uses 350 ml, [ 59 ]  Singapore 350 or 450 ml, [ 60 ]  and Japan 200 or 400 ml. [ 61 ]  Historically, donors in the  People's Republic of China  would donate only 200 ml, though larger 300 and 400 ml donations have become more common, particularly in northern China and for heavier donors. [ 62 ]  In any case, an additional 5-10 ml of blood may be collected separately for testing."}
{"_id": "WikiPedia_Hematology$$$corpus_327", "text": "The other method is to draw blood from the donor, separate it using a  centrifuge  or a filter, store the desired part, and return the rest to the donor. This process is called  apheresis , and it is often done with a machine specifically designed for this purpose. This process is especially common for  plasma ,  platelets , and  red blood cells . [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_328", "text": "For direct transfusions a vein can be used but the blood may be taken from an  artery  instead. [ 64 ]  In this case, the blood is not stored, but is pumped directly from the donor into the recipient. This was an early method for blood transfusion and is rarely used in modern practice. [ 65 ]   It was phased out during  World War II  because of problems with  logistics , and doctors returning from treating wounded soldiers set up banks for stored blood when they returned to civilian life. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_329", "text": "The blood is drawn from a large arm  vein close to the skin , usually the  median cubital vein  on the inside of the elbow. The skin over the blood vessel is cleaned with an  antiseptic  such as  iodine  or  chlorhexidine [ 67 ]  to prevent skin bacteria from contaminating the collected blood [ 67 ]  and also to prevent infections where the needle pierced the donor's skin. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_330", "text": "A large [ 69 ]   needle  (16 to 17  gauge ) is used to minimize  shearing  forces that may physically  damage  red blood cells as they flow through the needle. [ 70 ]  A  tourniquet  is sometimes wrapped around the upper arm to increase the  pressure of the blood in the arm veins  and speed up the process. The donor may also be prompted to hold an object and squeeze it repeatedly to  increase the blood flow  through the vein. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_331", "text": "The most common method is collecting the blood from the donor's vein into a container. The amount of blood drawn varies from 200 millilitres to 550 millilitres depending on the country, but 450 millilitres is typical. [ 54 ]  The blood is usually stored in a flexible plastic bag that also contains  sodium citrate ,  phosphate ,  dextrose , and  adenine . This combination keeps the blood from clotting and preserves it during storage up to 42 days. [ 71 ] [ 72 ] [ 73 ]  Other chemicals are sometimes added during  processing ."}
{"_id": "WikiPedia_Hematology$$$corpus_332", "text": "The plasma from whole blood can be used to make  plasma for transfusions  or it can also be processed into other medications using a process called  fractionation . This was a development of the  dried plasma  used to treat the wounded during World War II and variants on the process are still used to make a variety of other medications. [ 74 ] [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_333", "text": "Apheresis is a blood donation method where the blood is passed through an apparatus that separates out one particular constituent and returns the remainder to the donor. Usually the component returned is the red blood cells, the portion of the blood that takes the longest to replace. Using this method an individual can donate  plasma  or  platelets  much more frequently than they can safely donate whole blood. [ 76 ]  These can be combined, with a donor giving both plasma and platelets in the same donation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_334", "text": "Platelets  can also be separated from whole blood, but they must be pooled from multiple donations. From three to ten units of whole blood are required for a  therapeutic dose . [ 77 ]  Plateletpheresis provides at least one full dose from each donation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_335", "text": "During a platelet donation, the blood is drawn from the patient and the platelets are separated from the other blood components. The remainder of the blood, red blood cells, plasma, and white blood cells are returned to the patient. This process is completed several times for a period of up to two hours to collect a single donation. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_336", "text": "Plasmapheresis  is frequently used to collect  source plasma  that is used for manufacturing into medications much like the plasma from whole blood. Plasma collected at the same time as plateletpheresis is sometimes called  concurrent plasma ."}
{"_id": "WikiPedia_Hematology$$$corpus_337", "text": "Apheresis is also used to collect more red blood cells than usual in a single donation (commonly known as \" double reds \") and to  collect white blood cells  for transfusion. [ 79 ] [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_338", "text": "Donors are usually kept at the donation site for 10\u201315 minutes after donating since most adverse reactions take place during or immediately after the donation. [ 81 ]  Blood centers typically provide light refreshments, such as orange juice and cookies, or a lunch allowance to help the donor recover. [ 82 ]  The needle site is covered with a  bandage  and the donor is directed to keep the bandage on for several hours. [ 56 ]  In hot climates, donors are advised to avoid  dehydration  (strenuous exercise and games, alcohol) until a few hours after donation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_339", "text": "Donated plasma is replaced after 2\u20133 days. [ 83 ]  Red blood cells are replaced by bone marrow into the circulatory system at a slower rate, on average 36 days in healthy adult males. In one study, the range was 20 to 59 days for recovery. [ 84 ]  These replacement rates are the basis of how frequently a donor can donate blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_340", "text": "Plasmapheresis  and  plateletpheresis  donors can donate much more frequently because they do not lose significant amounts of red cells. The exact rate of how often a donor can donate differs from country to country. For example, plasmapheresis donors in the United States are allowed to donate large volumes twice a week and could nominally donate 83 litres (about 22 gallons) in a year, whereas the same donor in Japan may only donate every other week and could only donate about 16 litres (about 4 gallons) in a year. [ 85 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_341", "text": "Iron supplementation  decreases the rates of donor deferral due to low hemoglobin, both at the first donation visit and at subsequent donations. Iron-supplemented donors have higher hemoglobin and iron stores. On the other hand, iron supplementation frequently causes  diarrhea ,  constipation  and  epigastric  abdominal discomfort. The long-term effects of iron supplementation without measurement of iron stores are unknown. [ 86 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_342", "text": "Donors are screened for health problems that would put them at risk for serious complications from donating. First-time donors, teenagers, and women are at a higher risk of a reaction. [ 81 ] [ 87 ] \nOne study showed that 2% of donors had an adverse reaction to donation. [ 88 ]  Most of these reactions are minor. A study of 194,000 donations found only one donor with long-term complications. [ 89 ]  In the United States, a blood bank is required to report any death that might possibly be linked to a blood donation. An analysis of all reports from October 2008 to September 2009 evaluated six events and found that five of the deaths were clearly unrelated to donation, and in the remaining case they found no evidence that the donation was the cause of death. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_343", "text": "Hypovolemic  reactions can occur because of a rapid change in  blood pressure .  Fainting  is generally the worst problem encountered. [ 91 ]  Falls due to loss of consciousness may result in injuries in rare cases. [ 92 ]  The risk for developing dizziness with fainting is increased in female and young donors.  [ 93 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_344", "text": "The process has similar risks to other forms of  phlebotomy .  Bruising  of the arm from the needle insertion is the most common concern. One study found that less than 1% of donors had this problem. [ 94 ]  A number of less common complications of blood donation are known to occur. These include arterial puncture, delayed bleeding, nerve irritation, nerve injury, tendon injury, thrombophlebitis, and allergic reactions. [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_345", "text": "Donors sometimes have adverse reactions to the  sodium citrate  used in  apheresis  collection procedures to keep the blood from clotting. Since the anticoagulant is returned to the donor along with blood components that are not being collected, it can bind the  calcium  in the donor's blood and cause  hypocalcemia . [ 96 ]  These reactions tend to cause tingling in the lips, but may cause convulsions, seizure, hypertension, or more serious problems. [ 97 ]  Donors are sometimes given calcium supplements during the donation to prevent these side effects. [ 98 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_346", "text": "In apheresis procedures, the  red blood cells  are returned. If this is done manually and the donor receives the blood from a different donor, a  transfusion reaction  can take place. Manual apheresis is extremely rare in the developed world because of this risk and automated procedures are as safe as whole blood donations. [ 99 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_347", "text": "The final risk to blood donors is from equipment that has not been properly  sterilized . [ 100 ]  In most cases, the equipment that comes in direct contact with blood is discarded after use. [ 101 ]  Re-used equipment was a significant problem in  China  in the 1990s, and up to 250,000 blood plasma donors may have been exposed to HIV from shared equipment. [ 102 ] [ 103 ] [ 104 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_348", "text": "The collected blood is usually stored in a blood bank as separate components, and some of these have short shelf lives. There are no storage methods to keep platelets for extended periods of time, though some were being studied as of 2008. [ 105 ]  The longest shelf life used for platelets is seven days. [ 106 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_349", "text": "Red blood cells (RBC), the most frequently used component, have a shelf life of 35\u201342 days at refrigerated temperatures. [ 107 ] [ 108 ]  For (relatively rare) long-term storage applications, this can be extended by freezing the blood with a mixture of  glycerol , but this process is expensive and requires an extremely cold freezer for storage. [ 50 ]  Plasma can be stored frozen for an extended period of time and is typically given an expiration date of one year and maintaining a supply is less of a problem. [ 109 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_350", "text": "The American Red Cross states that in the United States, someone needs blood every two seconds, and someone needs platelets every thirty seconds. [ 110 ]   There is not a consistent demand for each blood type.  One type of blood being in stock does not guarantee that another type is.  Blood banks may have some units in stock but lack others, ultimately causing the patients that need units for specific blood types to have delayed or canceled procedures. [ 111 ]   Additionally, every year there is an increase of around 5-7% for transfusions without an increase of donors to balance it as well as a growing population of elderly people that will need more transfusions in the future without a predicted increase in donations [ 112 ]  to reflect those growing numbers. This was supported in 1998 where blood donations to the Red Cross increased to 8%, totaling 500,000 units but hospitals' need for donations increased by 11%. [ 113 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_351", "text": "Blood donations tend to always be high in demand with numerous accounts repeatedly stating periodic shortages over the decades. [ 114 ]   However, this trend is disrupted during national disasters.  The trend demonstrates that people are donating the most during catastrophes when, arguably, donations are not as needed compared to periods without disasters. [ 114 ]   From 1988 to 2013, it has been reported that during every national disaster, there was a surplus of donations; a surplus that consisted of over 100 units. [ 115 ]   One of the most notable examples of this pattern was the September 11th attacks. A study observed that compared to the four weeks before September 11, there was an estimated increase of 18,700 donations from first-time donors for the first week after the attack: 4,000 was the average of donations from first-time donors before the attack which increased to about 22,700 donations; while repeat donors increased their donations by 10,000 per week:  initially, donations were estimated to be around 16,400 which increased to 26,400 donations after September 11. [ 116 ]   Therefore, in the first week after the attack on 9/11, there was an overall estimated 28,700 increase in donations compared to the average weekly donations made four weeks prior to the attack.  Increases in donations were observed in all blood donation centers, beginning on the day of the attack. [ 116 ]  While blood donations were above average after the first few weeks following 9/11, the number of donations fell from an estimated 49,000 donations in the first week to 26,000\u201328,000 donations between the second and fourth weeks after 9/11. [ 116 ] [ 114 ]  Despite the substantial increase of donors, the rate that first-time donors would become repeat donors were the same before and after the attack. [ 116 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_352", "text": "The limited storage time means that it is difficult to have a stockpile of blood to prepare for a disaster. The subject was discussed at length after the  September 11 attacks  in the United States, and the consensus was that collecting during a disaster was impractical and that efforts should be focused on maintaining an adequate supply at all times. [ 117 ]  Blood centers in the U.S. often have difficulty maintaining even a three-day supply for routine transfusion demands. [ 118 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_353", "text": "The  World Health Organization  (WHO) recognizes World Blood Donor Day on 14 June each year to promote blood donation. This is the birthday of  Karl Landsteiner , the scientist who discovered the  ABO blood group system . [ 119 ]  The theme of the 2012 World Blood Donor Day campaign, \"Every blood donor is a hero\" focuses on the idea that everyone can become a hero by giving blood. Based on data reported by 180 countries between 2011 and 2013, the WHO estimated that approximately 112.5 million units of blood were being collected annually. [ 120 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_354", "text": "In the United States it is estimated that 111 million citizens are eligible blood donors, [ 121 ]  or 37% of the population. [ 122 ]  However less than 10% of the 37% eligible blood donors donate annually. [ 122 ]  In the UK the  NHS  reports blood donation levels at \"only 4%\" [ 123 ]  while in Canada the rate is 3.5%. [ 124 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_355", "text": "Multiple studies have shown that the main reason people donate is due to prosocial motivators (e.g., altruism, selflessness, charity), general awareness regarding the demand for blood, increased confidence in oneself, helping a personal friend/relative, and social pressure. [ 125 ] [ 126 ]  On the other hand, lack of blood donations can occur due to fear, lack of faith in the medical professionals, inconvenience, and the lack of consideration for donating, [ 127 ]  or perceived racial discrimination. [ 126 ]  Pathologist Leo McCarthy states that blood shortages routinely occur in the United States between July 4 and Labor day and between Christmas and New Year. [ 112 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_356", "text": "In patients prone to  iron overload , blood donation prevents the accumulation of toxic quantities. [ 128 ]  Donating blood may reduce the risk of heart disease for men, but the link has not been firmly established and may be from  selection bias  because donors are screened for health problems. [ 129 ] [ 130 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_357", "text": "Research published in 2012 demonstrated that in patients with  metabolic syndrome , repeated blood donation is effective in reducing  blood pressure ,  blood glucose ,  HbA1c , low-density lipoprotein/high-density lipoprotein ratio, and  heart rate . [ 131 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_358", "text": "A study published in JAMA Network Open tracked  PFAS  levels in a clinical trial and showed that regular blood or plasma donations resulted in a significant reduction in PFAS levels for the participants. [ 132 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_359", "text": "The World Health Organization set a goal in 1997 for all blood donations to come from unpaid volunteer donors, but as of 2006, only 49 of 124 countries surveyed had established this as a standard. [ 14 ]  Some countries, such as  Tanzania , have made great strides in moving towards this standard, with 20 percent of donors in 2005 being unpaid volunteers and 80 percent in 2007, but 68 of 124 countries surveyed by WHO had made little or no progress. [ 5 ]  Most  plasmapheresis  donors in the  United States  are still paid for their donations. [ 133 ]  Donors are now paid between $25 and $50 per donation. [ 134 ]  In some countries, for example  Brazil  and the  United Kingdom , it is illegal to receive any compensation, monetary or otherwise, for the donation of blood or other human tissues. [ 135 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_360", "text": "Regular donors are often given some sort of non-monetary recognition. Time off from work is a common benefit. [ 136 ]  For example, in  Italy , blood donors receive the donation day as a paid holiday from work. [ 137 ]  In 2023, Poland introduced legislation that secured two days off work for employed persons when they donate - the donation day and the subsequent next day. [ 138 ]  Blood centers will also sometimes add incentives such as assurances that donors would have priority during shortages, free T-shirts, first aid kits, windshield scrapers, pens, and similar trinkets. There are also incentives for the people who recruit potential donors, such as prize drawings for donors and rewards for organizers of successful drives. [ 139 ]  Recognition of dedicated donors is common. For example, the  Singapore Red Cross Society  presents awards for voluntary donors who have made a certain number of donations under the Blood Donor Recruitment Programme starting with a \"bronze award\" for 25 donations. [ 140 ]  In Ireland the  Irish Blood Transfusion Service  awards a silver pin or pendant for 10 donations, a gold pin or pendant for 20 donations, a gold lapel pin for 50 donations while those reaching 100 donations attend a dinner ceremony where they are presented with a small porcelain statue depicting the logo of the IBTS (a pelican). [ 141 ]  The government of  Malaysia  also offers free outpatient and hospitalization benefits for blood donors, for example, 4 months of free outpatient treatment and hospitalization benefits after every donation. [ 142 ]  In Poland, after donating a specific amount of blood (18 litres for men and 15 for women), a person is gifted with the title of \"Distinguished Honorary Blood Donor\" as well as a medal. In addition, a popular privilege in larger Polish cities is the right to free use of public transport, but the conditions for obtaining a privilege may vary depending on the city. Also in Poland,  Pozna\u0144 's theatre  Teatr Nowy  offers theatregoers standing discounts on theatre tickets. [ 143 ]  During the  COVID-19 pandemic , many US blood centers advertised free COVID-19 antibody testing as an incentive to donate; however, these antibody tests were also useful for blood centers in determining which donors could be flagged for convalescent plasma donations. [ 144 ] [ 145 ] [ 146 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_361", "text": "Most allogeneic blood donors donate as an act of charity and do not expect to receive any direct benefit from the donation. [ 147 ]  The sociologist  Richard Titmuss , in his 1970 book  The Gift Relationship: From Human Blood to Social Policy , compared the merits of the commercial and non-commercial blood donation systems of the US and the UK, coming down in favor of the latter. The book became a bestseller in the US, resulting in legislation to regulate the private market in blood. [ 148 ]  The book is still referenced in modern debates about turning blood into a commodity. [ 149 ]  The book was republished in 1997 and the same ideas and principles are applied to analogous donation programs, such as  organ donation  and  sperm donation . [ 150 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_362", "text": "In low-resource countries, directed donation from family members and friends is common, because there is no other realistic option. [ 8 ]   The practice causes ethical challenges, because the donor may feel coerced or may be receiving undisclosed payments. [ 8 ]   Additionally, relying on a social network means that people with large networks of healthy adults have a better chance of receiving life-saving treatment than people without the same social privileges. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_363", "text": "Blood gas tension  refers to the  partial pressure  of  gases  in  blood . [ 1 ]  There are several significant purposes for measuring gas tension. [ 2 ]  The most common gas tensions measured are  oxygen  tension (P x O 2 ),  carbon dioxide  tension (P x CO 2 ) and  carbon monoxide  tension (P x CO). [ 3 ]  The subscript  x  in each symbol represents the source of the gas being measured: \" a \" meaning  arterial , \" A \" being  alveolar , \" v \" being  venous , and \" c \" being  capillary . [ 3 ]   Blood gas tests  (such as  arterial blood gas  tests) measure these partial pressures."}
{"_id": "WikiPedia_Hematology$$$corpus_364", "text": "P a O 2  \u2013 Partial pressure of oxygen at sea level (160\u00a0 mmHg  in the atmosphere, 21% of standard atmospheric pressure of 760\u00a0mmHg) in  arterial blood  is between 75\u00a0mmHg and 100\u00a0mmHg. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_365", "text": "P v O 2  \u2013 Oxygen tension in  venous blood  at sea level is between 30\u00a0mmHg and 40\u00a0mmHg. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_366", "text": "Carbon dioxide is a by-product of food metabolism and in high amounts has toxic effects including:  dyspnea ,  acidosis  and  altered consciousness . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_367", "text": "P a CO 2  \u2013 Partial pressure of carbon dioxide at sea level in arterial blood is between 35 mmHg and 45 mmHg. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_368", "text": "P v CO 2  \u2013 Partial pressure of carbon dioxide at sea level in venous blood is between 40 mmHg and 50 mmHg. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_369", "text": "P a CO  \u2013 Partial pressure of CO at sea level in arterial blood is approximately 0.02. It can be slightly higher in smokers and people living in dense urban areas."}
{"_id": "WikiPedia_Hematology$$$corpus_370", "text": "The partial pressure of gas in blood is significant because it is directly related to   gas exchange , as the driving force of   diffusion  across the   blood gas barrier  and thus blood  oxygenation . [ 10 ]   When used alongside the  pH  balance of the blood, the P a CO 2  and  HCO \u2212 3  (and  lactate ) suggest to the health care practitioner which interventions, if any, should be made. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_371", "text": "The constant, 1.36, is the amount of oxygen (ml at 1 atmosphere) bound per gram of  hemoglobin . The exact value of this constant varies from 1.34 to 1.39, depending on the reference and the way it is derived. S a O 2  refers to the percent of arterial hemoglobin that is saturated with oxygen. The constant 0.0031 represents the amount of oxygen dissolved in plasma per mm Hg of partial pressure. The dissolved-oxygen term is generally small relative to the term for hemoglobin-bound oxygen, but becomes significant at very high P a O 2  (as in a  hyperbaric chamber ) or in severe  anemia . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_372", "text": "This is an estimation and does not account for differences in temperature, pH and concentrations of 2,3 DPG. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_373", "text": "Blood plasma  is a light  amber -colored liquid component of  blood  in which  blood cells  are absent, but which contains  proteins  and other constituents of  whole blood  in  suspension . It makes up about 55% of the body's total blood volume. [ 1 ]  It is the  intravascular part  of  extracellular fluid  (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains important dissolved proteins (6\u20138%; e.g.,  serum albumins ,  globulins , and  fibrinogen ), [ 2 ]   glucose ,  clotting factors ,  electrolytes  ( Na + ,  Ca 2+ ,  Mg 2+ ,  HCO 3 \u2212 ,  Cl \u2212 , etc.),  hormones ,  carbon dioxide  (plasma being the main medium for excretory product transportation), and  oxygen . [ 3 ]  It plays a vital role in an intravascular  osmotic  effect that keeps electrolyte concentration balanced and protects the body from  infection  and other blood-related disorders. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_374", "text": "Blood plasma can be separated from whole blood through  blood fractionation , by adding an  anticoagulant  to a tube filled with blood, which is spun in a  centrifuge  until the blood cells fall to the bottom of the tube. The blood plasma is then poured or drawn off. [ 5 ]  For  point-of-care testing  applications, plasma can be extracted from whole blood via filtration [ 6 ]  or via  agglutination [ 7 ]  to allow for rapid testing of specific biomarkers. Blood plasma has a density of approximately 1,025\u00a0kg/m 3  (1.025\u00a0g/ml). [ 8 ]   Blood serum  is blood plasma without clotting factors. [ 5 ]   Plasmapheresis  is a medical therapy that involves blood plasma extraction, treatment, and reintegration."}
{"_id": "WikiPedia_Hematology$$$corpus_375", "text": "Fresh frozen plasma  is on the  WHO Model List of Essential Medicines , the most important medications needed in a basic  health system . [ 9 ]  It is of critical importance in the treatment of many types of trauma which result in blood loss, and is therefore kept stocked universally in all medical facilities capable of treating trauma (e.g.,  trauma centers , hospitals, and ambulances) or that pose a risk of patient blood loss such as surgical suite facilities.  [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_376", "text": "Blood plasma volume may be expanded by or drained to  extravascular fluid  when there are changes in  Starling forces  across capillary walls. For example, when  blood pressure  drops in  circulatory shock , Starling forces drive fluid into the  interstitium , causing  third spacing . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_377", "text": "Standing still for a prolonged period will cause an increase in  transcapillary hydrostatic pressure . As a result, approximately 12% of blood plasma volume will cross into the  extravascular compartment . This  plasma shift  causes an increase in  hematocrit ,  serum total protein ,  blood viscosity  and, as a result of increased concentration of  coagulation factors , it causes  orthostatic hypercoagulability . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_378", "text": "Serum albumins are the most common plasma proteins, and they are responsible for maintaining the osmotic pressure of the blood. Without  albumins , the consistency of blood would be closer to that of water. The increased viscosity of blood prevents fluid from entering the bloodstream from outside the capillaries. Albumins are produced in the liver, assuming the absence of a hepatocellular deficiency. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_379", "text": "The second most common type of protein in the blood plasma are globulins. Important globulins include immunoglobins which are important for the immune system and transport hormones and other compounds around the body. There are three main types of globulins. Alpha-1 and Alpha-2 globulins are formed in the liver and play an important role in mineral transport and the inhibition of blood coagulation. [ 14 ]  An example of beta globulin found in blood plasma includes low-density lipoproteins (LDL) which are responsible for transporting fat to the cells for steroid and membrane synthesis. [ 15 ]   Gamma globulin, better known as immunoglobulins, are produced by plasma B cells, and provides the human body with a defense system against invading pathogens and other immune diseases. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_380", "text": "Fibrinogen proteins make up most of the remaining proteins in the blood. Fibrinogens are responsible for clotting blood to help prevent blood loss. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_381", "text": "Plasma is normally yellow due to  bilirubin ,  carotenoids ,  hemoglobin , and  transferrin . [ 18 ]  In abnormal cases, plasma can have varying shades of orange, green, or brown. The green color can be due to  ceruloplasmin  or  sulfhemoglobin . The latter may form due to medicines that are able to form  sulfonamides  once ingested. [ 19 ]  A dark brown or reddish color can appear due to  hemolysis , in which  methemoglobin  is released from broken blood cells. [ 20 ]  Plasma is normally relatively transparent, but sometimes it can be opaque. Opaqueness is typically due to elevated content of lipids like  cholesterol  and  triglycerides . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_382", "text": "Plasma and serum are both derived from full blood, but serum is obtained by removing blood cells, fibrin clots, and other coagulation factors while plasma is obtained by only removing blood cells. [ 22 ]  Blood plasma and  blood serum  are often used in  blood tests . Tests can be done on plasma, serum or both. [ 23 ]  In addition, some tests have to be done with  whole blood , such as the determination of the amount of  blood cells  in blood via  flow cytometry . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_383", "text": "Plasma preparation is quick, as it is not  coagulated . Serum sample preparation requires about 30 minutes of waiting time before it can be  centrifuged  and then analyzed. [ 23 ]  However, coagulation can be hastened down to a few minutes by adding  thrombin  or similar agents to the serum sample. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_384", "text": "Compared to serum, 15\u201320% larger volume of plasma can be obtained from a blood sample of certain size. Serum lacks some  proteins  that partake in coagulation and increase the sample volume. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_385", "text": "Serum preparation can cause measurement errors by increasing or decreasing the concentration of the  analyte  that is meant to be measured. For example, during coagulation, blood cells consume  blood glucose  and  platelets  increase the sample content of compounds like  potassium ,  phosphates  and  aspartate transaminase  by secreting them. Glucose or these other compounds may be the analytes. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_386", "text": "Plasma preparation requires the addition of  anticoagulants , which can cause expected and unexpected measurement errors. For example, anticoagulant salts can add extra cations like  NH 4 + ,  Li + ,  Na +  and  K +  to the sample, [ 23 ]  or impurities like  lead  and  aluminum . [ 26 ]   Chelator  anticoagulants like  EDTA  and  citrate  salts work by binding  calcium  (see  carboxyglutamic acid ), but they may also bind other ions. Even if such ions are not the analytes, chelators can interfere with  enzyme activity  measurements. For example, EDTA binds  zinc  ions, which  alkaline phosphatases  need as  cofactors . Thus, phosphatase activity cannot be measured if EDTA is used. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_387", "text": "An unknown volume of anticoagulants can be added to a plasma sample by accident, which may ruin the sample as the analyte concentration is changed by an unknown amount. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_388", "text": "No anticoagulants are added to serum samples, which decreases the preparation cost of the samples relative to plasma samples. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_389", "text": "Plasma samples can form tiny clots if the added anticoagulant is not properly mixed with the sample. Non-uniform samples can cause measurement errors. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_390", "text": "Plasma was already well known when described by William Harvey in  de Motu Cordis  in 1628, but knowledge of it probably dates as far back as Vesalius (1514\u20131564). The discovery of fibrinogen by William Henson,  c. \u20091770 , [ 27 ]  made it easier to study plasma, as ordinarily, upon coming in contact with a foreign surface \u2013 something other than the vascular endothelium \u2013 clotting factors become activated and clotting proceeds rapidly, trapping RBCs etc. in the plasma and preventing separation of plasma from the blood. Adding citrate and other anticoagulants is a relatively recent advance. Upon the formation of a clot, the remaining clear fluid (if any) is blood serum, which is essentially plasma without the clotting factors [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_391", "text": "The use of blood plasma as a substitute for whole blood and for transfusion purposes was proposed in March 1918, in the correspondence columns of the British Medical Journal, by Gordon R. Ward. \"Dried plasmas\" in powder or strips of material format were developed and first used in  World War II . Prior to the United States' involvement in the war, liquid plasma and  whole blood  were used. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_392", "text": "Dr. Jos\u00e9 Antonio Grifols Lucas, a scientist from Vilanova i la Geltr\u00fa, Spain, [ 30 ]  founded Laboratorios Grifols in 1940. [ 31 ]  Dr. Grifols pioneered a first-of-its-kind technique called  plasmapheresis , [ 31 ]  where a donor's red blood cells would be returned to the donor's body almost immediately after the separation of the blood plasma. This technique is still in practice today, almost 80 years later. In 1945, Dr. Grifols opened the world's first plasma donation center. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_393", "text": "The \"Blood for Britain\" program during the early 1940s was quite successful (and popular in the United States) based on  Charles Drew 's contribution. A large project began in August 1940 to collect blood in New York City hospitals for the export of plasma to Britain. Drew was appointed medical supervisor of the \" Plasma for Britain \" project. His notable contribution at this time was to transform the  test tube  methods of many blood researchers into the first successful mass production techniques. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_394", "text": "Nevertheless, the decision was made to develop a dried plasma package for the armed forces as it would reduce breakage and make the transportation, packaging, and storage much simpler. [ 33 ]  The resulting dried plasma package came in two tin cans containing 400 cc bottles. One bottle contained enough  distilled water  to reconstitute the dried plasma contained within the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. The Blood for Britain program operated successfully for five months, with total collections of almost 15,000 people donating blood, and with over 5,500 vials of blood plasma. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_395", "text": "Following the Supplying Blood Plasma to England project, Drew was named director of the  Red Cross   blood bank  and assistant director of the  National Research Council , in charge of blood collection for the  United States Army  and  Navy . Drew argued against the armed forces directive that blood/plasma was to be separated by the  race  of the  donor . Drew insisted that there was no racial difference in human blood and that the policy would lead to needless deaths as soldiers and sailors were required to wait for \"same race\" blood. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_396", "text": "By the end of the war the  American Red Cross  had provided enough blood for over six million plasma packages. Most of the surplus plasma was returned to the United States for civilian use.  Serum albumin  replaced dried plasma for combat use during the  Korean War . [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_397", "text": "Plasma as a  blood product  prepared from  blood donations  is used in  blood transfusions , typically as  fresh frozen plasma  (FFP) or Plasma Frozen within 24 hours after phlebotomy (PF24). When donating whole blood or  packed red blood cell  (PRBC) transfusions,  O-  is the most desirable and is considered a \"universal donor,\" since it has neither A nor B  antigens  and can be safely transfused to most recipients. Type AB+ is the \"universal recipient\" type for PRBC donations. However, for plasma the situation is somewhat reversed. Blood donation centers will sometimes collect only plasma from AB donors through  apheresis , as their plasma does not contain the antibodies that may cross react with recipient antigens. As such, AB is often considered the \"universal donor\" for plasma. Special programs exist just to cater to the male AB plasma donor, because of concerns about  transfusion related acute lung injury  (TRALI) and female donors who may have higher leukocyte antibodies. [ 36 ]  However, some studies show an increased risk of TRALI despite increased leukocyte antibodies in women who have been pregnant. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_398", "text": "Following fears of  variant Creutzfeldt-Jakob disease  ( vCJD ) being spread through the blood supply, the British government began to phase out blood plasma from U.K. donors and by the end of 1999 had imported all blood products made with plasma from the United States. [ 38 ]  In 2002, the British government purchased Life Resources Incorporated, an American blood supply company, to import plasma. [ 39 ]  The company became Plasma Resources UK (PRUK) which owned  Bio Products Laboratory . In 2013, the British government sold an 80% stake in PRUK to American hedge fund  Bain Capital , in a deal estimated to be worth \u00a3200 million. The sale was met with criticism in the UK. [ 40 ]  In 2009, the U.K. stopped importing plasma from the United States, as it was no longer a viable option due to regulatory and jurisdictional challenges. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_399", "text": "At present (2024), blood donated in the United Kingdom is used by UK Blood Services for the manufacture of plasma blood components (Fresh Frozen Plasma (FFP) and cryoprecipitate). However, plasma from UK donors is still not used for the commercial manufacture of fractionated plasma medicines. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_400", "text": "Simulated body fluid  (SBF) is a solution having a similar ion concentration to that of human blood plasma. SBF is normally used for the surface modification of metallic implants, and more recently in  gene delivery  application. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_401", "text": "Blood transfusion  is the process of transferring  blood products  into a person's  circulation   intravenously . [ 1 ]  Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used  whole blood , but modern medical practice commonly uses only components of the blood, such as  red blood cells ,  plasma ,  platelets , and other  clotting factors .  White blood cells  are transfused only in very rare circumstances, since  granulocyte transfusion  has limited applications.   Whole blood  has come back into use in the  trauma  setting. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_402", "text": "Red blood cells (RBC) contain  hemoglobin  and supply the  cells  of the body with  oxygen . White blood cells are not commonly used during transfusions, but they are part of the immune system and also fight infections. Plasma is the \"yellowish\" liquid part of blood, which acts as a buffer and contains proteins and other important substances needed for the body's overall health. Platelets are involved in blood clotting, preventing the body from bleeding. Before these components were known, doctors believed that blood was homogeneous. Because of this scientific misunderstanding, many patients died because of incompatible blood transferred to them."}
{"_id": "WikiPedia_Hematology$$$corpus_403", "text": "Historically,  red blood cell transfusion  was considered when the  hemoglobin  level fell below 100g/L or  hematocrit  fell below 30%. [ 3 ] [ 4 ]  Because each unit of blood given carries risks, a trigger level lower than that, at 70 to 80g/L, is now usually used, as it has been shown to have better patient outcomes. [ 5 ] [ 6 ] [ 7 ]  The administration of a single unit of blood is the standard for hospitalized people who are not bleeding, with this treatment followed with re-assessment and consideration of symptoms and hemoglobin concentration. [ 5 ]  Patients with poor  oxygen saturation  may need more blood. [ 5 ]  The advisory caution to use blood transfusion only with more severe  anemia  is in part due to evidence that outcomes are worsened if larger amounts are given. [ 8 ]  One may consider transfusion for people with symptoms of  cardiovascular disease  such as chest pain or shortness of breath. [ 4 ]  In cases where patients have low levels of hemoglobin due to iron deficiency, but are cardiovascularly stable, oral or  parenteral iron  is a preferred option based on both efficacy and safety. [ 9 ]  Other blood products are given where appropriate, e.g.,  fresh frozen plasma  to treat clotting deficiencies and  platelets  to treat or prevent bleeding in thrombocytopenic patients."}
{"_id": "WikiPedia_Hematology$$$corpus_404", "text": "Before a blood transfusion is given, there are many steps taken to ensure quality of the blood products, compatibility, and safety to the recipient. In 2012, a national blood policy was in place in 70% of countries and 69% of countries had specific legislation that covers the safety and quality of blood transfusion. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_405", "text": "The source of blood to be transfused can either be the potential recipient ( autologous  transfusion), or someone else ( allogeneic  or homologous transfusion). The latter is much more common than the former. Using another's blood must first start with donation of blood. Blood is most commonly donated as  whole blood  obtained intravenously and mixed with an  anticoagulant . In first-world countries, donations are usually anonymous to the recipient, but products in a  blood bank  are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. [ 11 ]  This enables management and investigation of any suspected transfusion related disease transmission or  transfusion reaction . Developing countries rely heavily on replacement and remunerated donors rather than voluntary nonremunerated donors due to concerns regarding donation- and transfusion-transmitted infection as well as local and cultural beliefs. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_406", "text": "It is unclear whether applying alcohol swab alone or alcohol swab followed by antiseptic is able to reduce contamination of donor's blood. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_407", "text": "Studies show that the main motivators to blood donation tend to be prosocial (e.g., altruism, selflessness, charity), while the main deterrents include fear, distrust, [ 14 ] [ 15 ]  or perceived racial discrimination in historic contexts. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_408", "text": "Donated blood is usually subjected to processing after it is collected, to make it suitable for use in specific patient populations. Collected blood is then separated into blood components by centrifugation:  red blood cells ,  plasma , and  platelets .  Plasma can be further processed to manufacture  albumin   protein , clotting factor concentrates,  cryoprecipitate ,  fibrinogen  concentrate, and  immunoglobulins  ( antibodies ). Red cells, plasma and platelets can also be donated individually via a more complex process called  apheresis ."}
{"_id": "WikiPedia_Hematology$$$corpus_409", "text": "Before a recipient receives a transfusion, compatibility testing between donor and recipient blood must be done. The first step before a transfusion is given is to type and screen the recipient's blood. Typing of recipient's blood determines the ABO and Rh status. The sample is then screened for any alloantibodies that may react with donor blood. [ 29 ]  It takes about 45 minutes to complete (depending on the method used). The blood bank scientist also checks for special requirements of the patient (e.g. need for washed, irradiated or CMV negative blood) and the history of the patient to see if they have previously identified antibodies and any other serological anomalies."}
{"_id": "WikiPedia_Hematology$$$corpus_410", "text": "A positive screen warrants an antibody panel/investigation to determine if it is clinically significant. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for antigens that correspond to commonly encountered and clinically significant alloantibodies. Donor cells may have homozygous (e.g. K+k+), heterozygous (K+k-) expression or no expression of various antigens (K\u2212k\u2212). The phenotypes of all the donor cells being tested are shown in a chart. The patient's serum is tested against the various donor cells using an indirect  Coombs test . Based on the reactions of the patient's serum against the donor cells, a pattern will emerge to confirm the presence of one or more antibodies. Not all antibodies are clinically significant (i.e. cause transfusion reactions, HDN, etc.). Once the patient has developed a clinically significant antibody it is vital that the patient receive antigen-negative red blood cells to prevent future transfusion reactions. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_411", "text": "If there is no antibody present, an immediate spin  crossmatch  may be performed where the recipient serum and donor rbc are incubated. In the immediate spin method, two drops of patient serum are tested against a drop of 3\u20135% suspension of donor cells in a test tube and spun in a serofuge. Agglutination or hemolysis (i.e., positive Coombs test) in the test tube is a positive reaction.  If the crossmatch is positive, then further investigation is needed.  Patients with no history of red cell antibodies may qualify for computer-assisted crossmatch, which does not involve combining patient serum with donor cells."}
{"_id": "WikiPedia_Hematology$$$corpus_412", "text": "If an antibody is suspected, potential donor units must first be screened for the corresponding antigen by phenotyping them. Antigen negative units are then tested against the patient plasma using an antiglobulin/indirect crossmatch technique at 37 degrees Celsius to enhance reactivity and make the test easier to read."}
{"_id": "WikiPedia_Hematology$$$corpus_413", "text": "In urgent cases where crossmatching cannot be completed, and the risk of dropping hemoglobin outweighs the risk of transfusing uncrossmatched blood, O-negative blood is used, followed by crossmatch as soon as possible. O-negative is also used for children and women of childbearing age. It is preferable for the laboratory to obtain a pre-transfusion sample in these cases so a type and screen can be performed to determine the actual blood group of the patient and to check for alloantibodies."}
{"_id": "WikiPedia_Hematology$$$corpus_414", "text": "This chart shows possible matches in blood transfusion between donor and receiver using ABO and Rh system. The symbol   indicates compatibility."}
{"_id": "WikiPedia_Hematology$$$corpus_415", "text": "In the same way that the safety of pharmaceutical products is overseen by  pharmacovigilance , the safety of blood and blood products is overseen by haemovigilance. This is defined by the World Health Organization (WHO) as a system \"...to identify and prevent occurrence or recurrence of transfusion related unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of the transfusion chain from donor to recipient.\" The system should include monitoring, identification, reporting, investigation and analysis of adverse events, near-misses, and reactions related to transfusion and manufacturing. [ 31 ]  In the UK this data is collected by an independent organisation called SHOT (Serious Hazards Of Transfusion). [ 32 ]  Haemovigilance systems have been established in many countries with the objective of ensuring the safety of blood for transfusion, but their organisational set-up and operating principles can vary. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_416", "text": "Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is controversy on potential quality degradation during storage. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_417", "text": "The use of greater amount of red blood cells has been suggested to increase the risk of infections, not only transfusion-transmitted infections, but also due to a phenomenon known as transfusion-related immunomodulation (TRIM). TRIM may be caused by macrophages and their byproducts. [ 42 ]  In those who were given red blood cells only with significant anemia (\"restrictive\" strategy), serious infection rates were 10.6% while in those who were given red blood at milder levels of anemia (\"liberal\" strategy), serious infection rates were 12.7%. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_418", "text": "On rare occasions, blood products are contaminated with bacteria. This can result in a life-threatening infection known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2020 [update] , at about 1 in 2,500 platelet transfusions, and 1 in 2,000,000 red blood cell transfusions. [ 44 ]  Blood product contamination, while rare, is still more common than actual infection. The reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. Contamination is also more common with longer duration of storage, especially if that means more than 5 days. Sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and containers. Contaminating organisms vary greatly, and include skin flora, gut flora, and environmental organisms. There are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination. A definite diagnosis of transfusion-transmitted bacterial infection includes the identification of a positive culture in the recipient (without an alternative diagnosis) as well as the identification of the same organism in the donor blood."}
{"_id": "WikiPedia_Hematology$$$corpus_419", "text": "Since the advent of HIV testing of donor blood in the mid/later 1980s, ex. 1985's  ELISA , the  transmission of HIV during transfusion  has dropped dramatically. Prior testing of donor blood only included testing for antibodies to HIV. However, because of latent infection (the \"window period\" in which an individual is infectious, but has not had time to develop antibodies) many cases of HIV seropositive blood were missed. The development of a nucleic acid test for the HIV-1 RNA has dramatically lowered the rate of donor blood seropositivity to about 1 in 3 million units. As transmittance of HIV does not necessarily mean HIV infection, the latter could still occur at an even lower rate."}
{"_id": "WikiPedia_Hematology$$$corpus_420", "text": "The transmission of hepatitis C via transfusion currently stands at a rate of about 1 in 2 million units. As with HIV, this low rate has been attributed to the ability to screen for both antibodies as well as viral RNA nucleic acid testing in donor blood."}
{"_id": "WikiPedia_Hematology$$$corpus_421", "text": "Other rare transmissible infections include  hepatitis B ,  syphilis ,  Chagas disease ,  cytomegalovirus  infections (in immunocompromised recipients),  HTLV , and  Babesia ."}
{"_id": "WikiPedia_Hematology$$$corpus_422", "text": "Transfusion inefficacy or insufficient efficacy of a given unit(s) of blood product, while not itself a \"complication\"  per se , can nonetheless indirectly lead to complications \u2013 in addition to causing a transfusion to fully or partly fail to achieve its clinical purpose. This can be especially significant for certain patient groups such as critical-care or neonatals."}
{"_id": "WikiPedia_Hematology$$$corpus_423", "text": "For red blood cells (RBC), by far the most commonly transfused product, poor transfusion efficacy can result from units damaged by the so-called storage lesion \u2014 a range of biochemical and biomechanical changes that occur during storage. With red cells, this can decrease viability and ability for tissue oxygenation. [ 46 ]  Although some of the biochemical changes are reversible after the blood is transfused, [ 47 ]  the biomechanical changes are less so, [ 48 ]  and rejuvenation products are not yet able to adequately reverse this phenomenon. [ 49 ]  There has been controversy about whether a given product unit's age is a factor in transfusion efficacy, specifically about whether \"older\" blood directly or indirectly increases risks of complications. [ 50 ] [ 51 ]  Studies have not been consistent on answering this question, [ 52 ]  with some showing that older blood is indeed less effective but with others showing no such difference; [ 53 ] [ 54 ]  these developments are being closely followed by hospital  blood bankers  \u2014 who are the physicians, typically pathologists, who collect and manage inventories of transfusable blood units."}
{"_id": "WikiPedia_Hematology$$$corpus_424", "text": "Certain regulatory measures are in place to minimize RBC storage lesion \u2014 including a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold (currently 1% in the US, 0.8% in Europe), and a minimum level of post-transfusion RBC survival  in vivo  (currently 75% after 24 hours). [ 55 ]  However, all of these criteria are applied in a universal manner that does not account for differences among units of product. [ 56 ]  For example, testing for the post-transfusion RBC survival  in vivo  is done on a sample of healthy volunteers, and then compliance is presumed for all RBC units based on universal (GMP) processing standards (RBC survival by itself does not guarantee efficacy, but it is a necessary prerequisite for cell function, and hence serves as a regulatory proxy). Opinions vary as to the \"best\" way to determine transfusion efficacy in a patient  in vivo . [ 57 ]  In general, there are not yet any  in vitro  tests to assess quality or predict efficacy for specific units of RBC blood product prior to their transfusion, though there is exploration of potentially relevant tests based on RBC membrane properties such as  erythrocyte deformability [ 58 ]  and  erythrocyte fragility  (mechanical). [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_425", "text": "Physicians have adopted a so-called \"restrictive protocol\" \u2014 whereby transfusion is held to a minimum \u2014 in part because of the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions. [ 60 ] [ 61 ] [ 62 ]  However, the restrictive protocol is not an option with some especially vulnerable patients who may require the best possible efforts to rapidly restore tissue oxygenation."}
{"_id": "WikiPedia_Hematology$$$corpus_426", "text": "Although transfusions of platelets are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_427", "text": "Globally around 85 million units of red blood cells are transfused in a given year. [ 4 ]  The global demand is much higher and there is an unmet need for safe blood for transfusion in many low- and middle-income countries. [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_428", "text": "In the United States, blood transfusions were performed nearly 3 million times during hospitalizations in 2011, making it the most common procedure performed. The rate of hospitalizations with a blood transfusion nearly doubled from 1997, from a rate of 40 stays to 95 stays per 10,000 population. It was the most common procedure performed for patients 45 years of age and older in 2011, and among the top five most common for patients between the ages of 1 and 44 years. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_429", "text": "According to the  New York Times : \"Changes in medicine have eliminated the need for millions of blood transfusions, which is good news for patients getting procedures like coronary bypasses and other procedures that once required a lot of blood.\" And, \"Blood bank revenue is falling, and the decline may reach $1.5 billion a year this year [2014] from a high of $5 billion in 2008.\" In 2014, the Red Cross was predicting job losses as high as 12,000 within the next three to five years, roughly a quarter of the total in the industry. [ 77 ]  As of 2019, the trend of declining transfusions appeared to be stabilizing, with 10,852,000 RBC units transfused in the United States. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_430", "text": "Beginning with  William Harvey 's experiments on the circulation of blood, recorded research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts by physicians to transfuse animal blood into humans gave variable, often fatal, results. [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_431", "text": "Pope Innocent VIII  is sometimes said to have been given \"the world's first blood transfusion\" by his  Italian-Jewish  physician Giacomo di San Genesio, who had him drink (by mouth) the blood of three 10-year-old boys. The boys consequently died, as did the Pope himself. However, the evidence for this story is unreliable and considered a possible  anti-Jewish blood libel . [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_432", "text": "Working at the  Royal Society  in the 1660s, the physician  Richard Lower  began examining the effects of changes in blood volume on circulatory function and developed methods for cross-circulatory study in animals, obviating clotting by closed arteriovenous connections. The new instruments he was able to devise enabled him to perform the first reliably documented successful transfusion of blood in front of his distinguished colleagues from the Royal Society. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_433", "text": "According to Lower's account, \"...towards the end of February 1665 [I] selected one dog of medium size, opened its jugular vein, and drew off blood, until its strength was nearly gone. Then, to make up for the great loss of this dog by the blood of a second, I introduced blood from the cervical artery of a fairly large mastiff, which had been fastened alongside the first, until this latter animal showed ... it was overfilled ... by the inflowing blood.\" After he \"sewed up the jugular veins\", the animal recovered \"with no sign of discomfort or of displeasure\"."}
{"_id": "WikiPedia_Hematology$$$corpus_434", "text": "Lower had performed the first blood transfusion between animals. He was then \"requested by the Honorable  [Robert] Boyle  ... to acquaint the  Royal Society  with the procedure for the whole experiment\", which he did in December 1665 in the Society's  Philosophical Transactions . [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_435", "text": "The first blood transfusion from animal to human was administered by Dr.  Jean-Baptiste Denys , eminent physician to  King Louis\u00a0XIV  of France, on June\u00a015, 1667. [ 82 ]  He transfused the blood of a  sheep  into a 15-year-old boy, who survived the transfusion. [ 83 ]  Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to the small amount of blood that was actually transfused into these people. This allowed them to withstand the  allergic reaction ."}
{"_id": "WikiPedia_Hematology$$$corpus_436", "text": "Denys's third patient to undergo a blood transfusion was Swedish Baron  Gustaf Bonde . He received two transfusions. After the second transfusion Bonde died. [ 84 ]  In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood.  On the third account Mauroy died. [ 85 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_437", "text": "Six months later in London, Lower performed the first human transfusion of animal blood in Britain, where he \"superintended the introduction in [a patient's] arm at various times of some ounces of sheep's blood at a meeting of the Royal Society, and without any inconvenience to him.\" The recipient was Arthur Coga, \"the subject of a harmless form of insanity.\" Sheep's blood was used because of speculation about the value of blood exchange between species; it had been suggested that blood from a gentle lamb might quiet the tempestuous spirit of an agitated person and that the shy might be made outgoing by blood from more sociable creatures. Coga received 20 shillings (equivalent to \u00a3217 in 2023) to participate in the experiment. [ 86 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_438", "text": "Lower went on to pioneer new devices for the precise control of blood flow and the transfusion of blood; his designs were substantially the same as modern  syringes  and  catheters . [ 81 ]  Shortly after, Lower moved to London, where his growing practice soon led him to abandon research. [ 87 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_439", "text": "These early experiments with animal blood provoked a heated controversy in Britain and France. [ 84 ]  Finally, in 1668, the Royal Society and the French government both banned the procedure. The  Vatican  condemned these experiments in 1670. Blood transfusions fell into obscurity for the next 150 years. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_440", "text": "The science of blood transfusion dates to the first decade of the 20th century, with the discovery of distinct  blood types  leading to the practice of mixing some blood from the donor and the receiver before the transfusion (an early form of  cross-matching ). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_441", "text": "In the early 19th century, British  obstetrician  Dr.  James Blundell  made efforts to treat  hemorrhage  by transfusion of human blood using a syringe. In 1818, after experiments with animals, he performed the first successful transfusion of human blood to treat  postpartum hemorrhage . Blundell used the patient's husband as a donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented a number of instruments for the transfusion of blood. [ 88 ]  He made a substantial amount of money from this endeavour, roughly $2 million ($50 million  real dollars ). [ 89 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_442", "text": "In 1840, at  St George's Hospital Medical School  in London,  Samuel Armstrong Lane , aided by Blundell, performed the first successful whole blood transfusion to treat  haemophilia . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_443", "text": "However, early transfusions were risky and many resulted in the death of the patient. By the late 19th century, blood transfusion was regarded as a risky and dubious procedure, and was largely shunned by the medical establishment."}
{"_id": "WikiPedia_Hematology$$$corpus_444", "text": "Work to emulate James Blundell continued in Edinburgh. In 1845 the  Edinburgh Journal  described the successful transfusion of blood to a woman with severe uterine bleeding. Subsequent transfusions were successful with patients of  Professor James Young Simpson , after whom the  Simpson Memorial Maternity Pavilion  in Edinburgh was named. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_445", "text": "Various isolated reports of successful transfusions emerged towards the end of the 19th century. [ 91 ]  The largest series of early successful transfusions took place at the  Edinburgh Royal Infirmary  between 1885 and 1892. Edinburgh later became the home of the first blood donation and blood transfusion services. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_446", "text": "Only in 1901, when the Austrian  Karl Landsteiner  discovered three human  blood groups  (O, A, and B), did blood transfusion achieve a scientific basis and become safer. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_447", "text": "Landsteiner discovered that adverse effects arise from mixing blood from two incompatible individuals. He found that mixing incompatible types triggers an immune response and the red blood-cells clump. The immunological reaction occurs when the receiver of a blood transfusion has antibodies against the donor blood-cells. The  destruction of red blood cells  releases free  hemoglobin  into the bloodstream, which can have fatal consequences. Landsteiner's work made it possible to determine blood group and allowed blood transfusions to take place much more safely. For his discovery he won the Nobel Prize in Physiology and Medicine in 1930;  many other blood groups  have been discovered since. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_448", "text": "George Washington Crile  is credited with performing the first surgery using a direct blood transfusion in 1906 at St. Alexis Hospital in Cleveland while a professor of surgery at  Case Western Reserve University . [ 92 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_449", "text": "Jan Jansk\u00fd  also discovered the human blood groups; in 1907 he classified blood into four groups: I, II, III, IV. [ 93 ]  His nomenclature is still used in Russia and in states of the former USSR, in which blood types O, A, B, and AB are respectively designated I, II, III, and IV."}
{"_id": "WikiPedia_Hematology$$$corpus_450", "text": "Dr. William Lorenzo Moss's (1876\u20131957) Moss-blood typing technique of 1910 was widely used until  World War II . [ 94 ] [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_451", "text": "William Stewart Halsted , M.D. (1852\u20131922), an American surgeon,  performed one of the first blood transfusions in the United States. He had been called to see his sister after she had given birth. He found her moribund from blood loss, and in a bold move withdrew his own blood, transfused his blood into his sister, and then operated on her to save her life. [ 96 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_452", "text": "While the first transfusions had to be made directly from donor to receiver before  coagulation , it was discovered that by adding  anticoagulant  and  refrigerating  the blood it was possible to store it for some days, thus opening the way for the development of  blood banks .  John Braxton Hicks  was the first to experiment with chemical methods to prevent the coagulation of blood at  St Mary's Hospital, London  in the late-19th century. His attempts, using  phosphate of soda , however, proved unsuccessful."}
{"_id": "WikiPedia_Hematology$$$corpus_453", "text": "The  Belgian  doctor  Albert Hustin  performed the first non-direct transfusion on March\u00a027, 1914, though this involved a diluted solution of blood. The  Argentine  doctor  Luis Agote  used a much less diluted solution in November of the same year. Both used  sodium citrate  as an anticoagulant. [ 97 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_454", "text": "The  First World War  (1914\u20131918) acted as a catalyst for the rapid development of blood banks and transfusion techniques.  Francis Peyton Rous  and Joseph R. Turner at the  Rockefeller University  (then The Rockefeller Institute for Medical Research) made the first important discoveries that blood typing was necessary to avoid blood clumping (coagulation) and blood samples could be preserved using chemical treatment. [ 98 ] [ 99 ]  Their first report in March 1915 showed that gelatine, agar, blood serum extracts, starch and beef albumin proved to be useless preservatives. [ 100 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_455", "text": "However, building on the same experiment, they discovered that a mixture  sodium citrate  and glucose ( dextrose ) solution was a perfect preservative; as they reported in February issue of the  Journal of Experimental Medicine ,  the preserved bloods were just like fresh bloods and that they \"function excellently when reintroduced into the body.\" [ 101 ]  Blood could be preserved for up to four weeks. An accompanying experiment using citrate-saccharose (sucrose) mixture was also a success which could maintain blood cells for two weeks. [ 102 ]  This use of citrate and sugars, sometimes known as Rous-Turner solution, was the foundation for the development of blood banks and improvement of transfusion method. [ 103 ] [ 104 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_456", "text": "Another discovery of Rous and Turner was the most critical step in the safety of blood transfusion. Rous was well aware that Landsteiner's concept of blood types had not yet find practical value, as he remarked: \"The fate of Landsteiner's effort to call attention to the practical bearing of the group differences in human bloods provides an exquisite instance of knowledge marking time on technique. Transfusion was still not done because (until at least 1915), the risk of clotting was too great.\" [ 105 ]  In June 1915, they made a crucial report in the  Journal of the American Medical Association  that agglutination could be avoided if the blood samples of the donor and recipient were tested before. Which they called a rapid and simple method for testing blood compatibility, sodium citrate was used to dilute the blood samples, and after mixing the recipient's and donor's blood in 9:1 and 1:1 parts, blood would either clump or remain watery after 15 minutes. According to their advice, blood without clumping \"should always be chosen if possible.\" [ 106 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_457", "text": "Canadian doctor and Lieutenant  Lawrence Bruce Robertson  became instrumental in persuading the  Royal Army Medical Corps  to adopt the use of blood transfusion at the  Casualty Clearing Stations  for the wounded. In October 1915, Robertson performed his first wartime transfusion with a syringe to a patient who had multiple shrapnel wounds. He followed this up with four subsequent transfusions in the following months, and his success was reported to Sir  Walter Morley Fletcher , director of the  Medical Research Committee . [ 107 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_458", "text": "Robertson published his findings in the  British Medical Journal  in 1916 and, with the help of a few like-minded individuals (including the eminent physician  Edward William Archibald ), was able to persuade the British authorities of the merits of blood transfusion. Robertson went on to establish the first blood-transfusion apparatus at a Casualty Clearing Station on the  Western Front  in the spring of 1917. [ 107 ] [ 108 ]  Robertson did not test crossmatching so that one died of hemolysis in his 1916 transfusion, and three in 1917. [ 109 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_459", "text": "Oswald Hope Robertson , a medical researcher and  U.S.\u00a0Army  officer, was attached to the  RAMC  in 1917, where he became instrumental in establishing the first blood banks in preparation for the anticipated  Third Battle of Ypres . [ 110 ]  He used  sodium citrate  as the anticoagulant; blood was extracted from punctures in the  vein  and was stored in bottles at British and American Casualty Clearing Stations along the Front. Robertson also experimented with preserving separated  red blood cells  in iced bottles. [ 108 ]   Geoffrey Keynes , a British surgeon, developed a portable machine that could store blood to enable transfusions to be carried out more easily."}
{"_id": "WikiPedia_Hematology$$$corpus_460", "text": "The secretary of the  British Red Cross ,  Percy Lane Oliver , established the world's first blood-donor service in 1921. In that year, Oliver was contacted by  King's College Hospital , where they were in urgent need of a blood donor.\n [ 111 ]  After providing a donor, Oliver set about organizing a system for the voluntary registration of blood donors at clinics around London, with Sir  Geoffrey Keynes  appointed as a medical adviser. Volunteers were subjected to a series of physical tests to establish their  blood group . The  London Blood Transfusion Service  was free of charge and expanded rapidly in its first few years of operation. By 1925 it was providing services for almost 500 patients; it was incorporated into the structure of the British Red Cross in 1926. Similar systems developed in other cities, including  Sheffield ,  Manchester  and  Norwich , and the service's work began to attract international attention. France, Germany, Austria, Belgium, Australia and Japan established similar services. [ 112 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_461", "text": "Alexander Bogdanov  founded an academic institution devoted to the science of blood transfusion in  Moscow  in 1925. Bogdanov was motivated, at least in part, by a search for  eternal youth , and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of  whole blood . Bogdanov died in 1928 as a result of one of his experiments, when the blood of a student with  malaria  and  tuberculosis  was given to him in a transfusion. [ 113 ]  Following Bogdanov's lead, Vladimir Shamov and  Sergei Yudin  in the  USSR  pioneered the  transfusion of cadaveric blood  from recently deceased donors. Yudin performed such a transfusion successfully for the first time on March 23, 1930, and reported his first seven  clinical  transfusions with cadaveric blood at the Fourth Congress of  Ukrainian  Surgeons at Kharkiv in September. However, this method was never used widely, even in the Soviet Union. Nevertheless, the Soviet Union was the first to establish a network of facilities to collect and store blood for use in transfusions at hospitals."}
{"_id": "WikiPedia_Hematology$$$corpus_462", "text": "Frederic Dur\u00e1n-Jord\u00e0  established one of the earliest blood banks during the  Spanish Civil War  in 1936. Duran joined the Transfusion Service at the  Barcelona Hospital  at the start of the conflict, but the hospital was soon overwhelmed by the demand for blood and the paucity of available donors. With support from the Department of Health of the  Spanish Republican Army , Duran established a blood bank for the use of wounded soldiers and civilians. The 300\u2013400\u00a0mL of extracted blood was mixed with 10% citrate solution in a modified Duran Erlenmeyer flask. The blood was stored in a sterile glass enclosed under pressure at 2\u00a0\u00b0C. During 30 months of work, the Transfusion Service of Barcelona registered almost 30,000 donors, and processed 9,000 liters of blood. [ 114 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_463", "text": "In 1937  Bernard Fantus , director of therapeutics at the  Cook County Hospital  in  Chicago , established the first hospital blood-bank in the  United States . In setting up a hospital laboratory that preserved, refrigerated and stored donor blood, Fantus originated the term \"blood bank\". Within a few years, hospital and community blood-banks were established across the United States. [ 115 ]   Until the middle of World War II, the newly established US blood banks rejected African-American donors.  During the war, Black people were allowed to donate blood, but the donated blood was labeled as being suitable only for transfusion into another person from the same race. [ 116 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_464", "text": "Frederic Dur\u00e1n-Jord\u00e0 fled to Britain in 1938 and worked with Dr  Janet Vaughan  at the  Royal Postgraduate Medical School  at Hammersmith Hospital to establish a system of national blood banks in London. [ 117 ]  With the outbreak of  war  appearing imminent in 1938, the  War Office  created the Army Blood Supply Depot (ABSD) in Bristol, headed by  Lionel Whitby  and in control of four large blood-depots around the country. British policy through the war was to supply military personnel with blood from centralized depots, in contrast to the approach taken by the Americans and Germans where troops at the front were bled to provide required blood. The British method proved more successful in adequately meeting all requirements, and over 700,000 donors were bled over the course of the war. This system evolved into the  National Blood Transfusion Service  established in 1946, the first national service to be implemented.\n [ 118 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_465", "text": "Stories tell of  Nazis  in Eastern Europe during World War II using captive children as repeated involuntary blood-donors. [ 119 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_466", "text": "A blood-collection program was initiated [ by whom? ]  in the US in 1940 and  Edwin Cohn  pioneered the process of  blood fractionation . He worked out the techniques for isolating the  serum albumin  fraction of  blood plasma , which is essential for maintaining the  osmotic pressure  in the  blood vessels , preventing their collapse."}
{"_id": "WikiPedia_Hematology$$$corpus_467", "text": "Gordon R. Ward, writing in the correspondence columns of the  British Medical Journal , proposed the use of  blood plasma  as a substitute for whole blood and for transfusion purposes as early as 1918. At the onset of  World War II , liquid plasma was used in Britain. A large project, known as \"Blood for Britain\", began in August 1940 to collect blood in  New York City  hospitals for the export of plasma to  Britain . A  freeze-dried  plasma package was developed by the Surgeons General of the Army and Navy, working with the  National Research Council , [ 120 ]  which reduced breakage and made transportation, packaging, and storage much simpler. [ 121 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_468", "text": "The resulting dried plasma package came in two tin cans containing 400 mL bottles. One bottle contained enough  distilled water  to reconstitute the dried plasma contained within the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. [ 122 ]  Dr.  Charles R. Drew  was appointed medical supervisor, and he was able to transform the  test-tube  methods into the first successful technique for mass production."}
{"_id": "WikiPedia_Hematology$$$corpus_469", "text": "Another important breakthrough came in 1937\u201340 when  Karl Landsteiner  (1868\u20131943), Alex Wiener, Philip Levine, and R.E. Stetson discovered the  Rhesus blood group system , which was found to be the cause of the majority of  transfusion reactions  up to that time. Three years later, the introduction by  J.F. Loutit  and Patrick L. Mollison of  acid\u2013citrate\u2013dextrose  (ACD) solution, which reduced the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer-term storage."}
{"_id": "WikiPedia_Hematology$$$corpus_470", "text": "Carl Walter and W.P. Murphy Jr. introduced the  plastic bag  for blood collection in 1950. Replacing breakable  glass  bottles with durable plastic bags made from  PVC  allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood."}
{"_id": "WikiPedia_Hematology$$$corpus_471", "text": "In the field of  cancer surgery , the replacement of massive blood-loss became a major problem. The cardiac-arrest rate was high. In 1963 C. Paul Boyan and William S. Howland discovered that the temperature of the blood and the rate of infusion greatly affected survival rates, and introduced blood warming to surgery. [ 123 ] [ 124 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_472", "text": "Further extending the shelf-life of stored blood up to 42 days was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks. [ 125 ] [ 126 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_473", "text": "As of 2006 [update]  about 15 million units of blood products were transfused per year in the United States. [ 127 ]  By 2013 the number had declined to about 11 million units, because of the shift towards  laparoscopic surgery  and other surgical advances and studies that have shown that many transfusions were unnecessary. For example, the standard of care reduced the amount of blood transfused in one case from 750 to 200\u00a0mL. [ 77 ]   In 2019, 10,852,000 RBC units, 2,243,000 platelet units, and 2,285,000 plasma units were transfused in the United States. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_474", "text": "To ensure the safety of blood transfusion to pediatric patients, hospitals are taking additional precautions to avoid infection and prefer to use pediatric blood units that are guaranteed \"safe\" from  Cytomegalovirus . Some guidelines have recommended the provision of CMV-negative blood components and not simply leukoreduced components for newborns or low birthweight infants in whom the immune system is not fully developed, [ 128 ]  but practice varies. [ 129 ]  These requirements place additional restrictions on blood donors who can donate for neonatal use, which may be impractical given the rarity of CMV seronegative donors and the preference for fresh units."}
{"_id": "WikiPedia_Hematology$$$corpus_475", "text": "Neonatal transfusions typically fall into one of two categories:"}
{"_id": "WikiPedia_Hematology$$$corpus_476", "text": "A  massive transfusion protocol  is used when significant blood loss is present such as in  major trauma , when more than ten units of blood are needed. Packed red blood cells, fresh frozen plasma, and platelets are generally administered. [ 131 ]  Typical ratios of  fresh frozen plasma ,  platelets  and  packed red blood cells  are between 1:1:1 and 1:1:2. [ 132 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_477", "text": "In some locations, blood has begun to be administered  pre-hospital  in an effort to reduce preventable deaths from significant blood loss. Earlier analyses suggested that in the US, up to 31,000 patients per year bleed to death that otherwise could have survived if pre-hospital transfusions were widely available. [ 133 ]  For example, when a mother experiences severe blood loss during pregnancy, [ 134 ]  ambulances are able to arrive with blood stored in portable, FDA listed blood refrigerators, similar to those found in blood banks. Once the infusion is given on scene, the patient and the ambulance have more time to get to a hospital for surgery and additional infusions if needed. This could be critical in rural areas or sprawling cities where patients can be far from a major hospital and the local emergency medical team may need to use blood infusions to keep that patient alive during transport.  Larger studies pointed to improvements in 24-hour mortality with pre-hospital plasma and RBC transfusions, but no difference in 30-day or long-term mortality. [ 135 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_478", "text": "Because  blood type  O negative is compatible with anyone, it is often overused and in short supply. [ 136 ]  According to the   Association for the Advancement of Blood and Biotherapies , the use of this blood should be restricted to persons with O negative blood, as nothing else is compatible with them, and women who might be pregnant and for whom it would be impossible to do blood group testing before giving them emergency treatment. [ 136 ]  Whenever possible, the AABB recommends that O negative blood be conserved by using blood type testing to identify a less scarce alternative. [ 136 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_479", "text": "Jehovah's Witnesses may object to blood transfusions  because of their belief that blood is sacred. [ 137 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_480", "text": "Sometimes people refuse blood transfusions because of fears about the safety of the blood supply. [ 116 ]   Generally speaking, the rules of  informed consent  allow mentally  competent  adults to refuse blood transfusions even when their objections are based on  misinformation  or  prejudice  and even when their refusal may result in serious and permanent harm, including death. [ 116 ]   For example, since  COVID-19 vaccines  became available, some people in the US have refused blood transfusions because the donor might have been vaccinated, and they fear that this would cause secondhand harm to them. [ 116 ]   This choice is based on false beliefs, but a mentally competent adult's choices are normally respected. [ 138 ]   However, if doctor's opinions are that parents and guardians are making harmful choices about children, they can be overruled (in some jurisdictions) using legal arguments based on the  harm principle ; in this case if doctors believe that refusing the blood transfusion would put the child at risk of serious injury or death. [ 138 ]   Blood banks do not collect information that is irrelevant to the transfusion process, including the donors' race, ethnicity, sexual orientation, COVID-19 vaccination status, etc., so selecting blood units based on the individual's personal objections is not practical. [ 116 ] [ 138 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_481", "text": "Although there are clinical situations where transfusion with red blood cells is the only clinically appropriate option, clinicians look at whether alternatives are feasible. This can be due to several reasons, such as patient safety, economic burden or scarcity of blood. Guidelines recommend blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia. [ 139 ] [ 140 ]  In stable patients with iron deficiency anemia, oral or  parenteral iron  is recommended."}
{"_id": "WikiPedia_Hematology$$$corpus_482", "text": "Thus far, there are no FDA-approved  oxygen-carrying   blood substitutes , which is the typical objective of a blood (RBC) transfusion. Non-blood  volume expanders  are available for cases where only volume restoration is required, but a substance with oxygen-carrying capacity would help doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of  Jehovah's Witnesses  and others who have religious objections to receiving transfused blood."}
{"_id": "WikiPedia_Hematology$$$corpus_483", "text": "The research in this area is ongoing. A number of blood substitutes have been explored, but thus far they all have serious limitations. [ 141 ] [ 142 ]  Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in  emergency medicine  and in pre-hospital  EMS  care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results.  Hemopure , a hemoglobin-based therapy, is approved for use in  South Africa  and has been used in the United States on a case-by-case basis through the emergency Investigational New Drug (IND) process. [ 143 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_484", "text": "Veterinarians  also administer transfusions to other animals. Various  species  require different levels of testing to ensure a compatible match. For example,  cats  have 3 known blood types, [ 144 ]   cattle  have 11, [ 144 ]   dogs  have at least 13, [ 145 ]   pigs  have 16, [ 146 ]  and  horses  over 30. [ 144 ]  However, in many species (especially horses and dogs), cross matching is not required before the  first  transfusion, as antibodies against non-self cell surface antigens are not expressed constitutively \u2014 i.e. the animal has to be sensitized before it will mount an immune response against the transfused blood. [ 147 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_485", "text": "The rare and experimental practice of inter-species blood transfusions ( xenotransfusion ) is a form of  xenograft ."}
{"_id": "WikiPedia_Hematology$$$corpus_486", "text": "A  blood type  (also known as a  blood group ) is  a classification of  blood , based on the presence and absence of  antibodies  and  inherited   antigenic  substances on the surface of  red blood cells  (RBCs). These antigens may be  proteins ,  carbohydrates ,  glycoproteins , or  glycolipids , depending on the blood group system. Some of these antigens are also present on the surface of other types of  cells  of various  tissues . Several of these red blood cell surface antigens can stem from one  allele  (or an alternative version of a gene) and collectively form a blood group system. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_487", "text": "Blood types are inherited and represent contributions from both parents of an individual. As of 31\u00a0December\u00a02023, [update]  a total of 45 [ 2 ]   human blood group systems  are recognized by the  International Society of Blood Transfusion  (ISBT). [ 3 ]  The two most important blood group systems are  ABO  and  Rh ; they determine someone's blood type (A, B, AB, and O, with + or \u2212 denoting  RhD  status) for suitability in  blood transfusion ."}
{"_id": "WikiPedia_Hematology$$$corpus_488", "text": "A complete blood type would describe each of the 45 blood groups, and an individual's blood type is one of many possible combinations of blood-group antigens. [ 3 ]  Almost always, an individual has the same blood group for life, but very rarely an individual's blood type changes through addition or suppression of an antigen in  infection ,  malignancy , or  autoimmune disease . [ 4 ] [ 5 ] [ 6 ] [ 7 ]  Another more common cause of blood type change is a  bone marrow transplant . Bone-marrow transplants are performed for many  leukemias  and  lymphomas , among other diseases. If a person receives bone marrow from someone of a different ABO type (e.g., a type O patient receives a type A bone marrow), the patient's blood type should eventually become the donor's type, as the patient's  hematopoietic stem cells  (HSCs) are destroyed, either by ablation of the bone marrow or by the donor's T-cells. Once all the patient's original red blood cells have died, they will have been fully replaced by new cells derived from the donor HSCs. Provided the donor had a different ABO type, the new cells' surface antigens will be different from those on the surface of the patient's original red blood cells. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_489", "text": "Some blood types are associated with inheritance of other diseases; for example, the  Kell antigen  is sometimes associated with  McLeod syndrome . [ 9 ] For another example,  Von Willebrand disease  may be more severe or apparent in people with blood type O.  Certain blood types may affect susceptibility to infections.  For example, people with blood type O may be less susceptible to pro-thrombotic events induced by  COVID-19  or  long covid . [ 10 ] [ 11 ]  Another example being the resistance to specific  malaria  species seen in individuals lacking the  Duffy antigen . [ 12 ]  The Duffy antigen, presumably as a result of  natural selection , is less common in population groups from areas having a high incidence of malaria. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_490", "text": "The ABO blood group system involves two antigens and two antibodies found in human blood. The two antigens are antigen A and antigen B. The two antibodies are antibody A and antibody B. The antigens are present on the red blood cells and the antibodies in the  serum . Regarding the antigen property of the blood all human beings can be classified into four groups, those with antigen A (group A), those with antigen B (group B), those with both antigen A and B (group AB) and those with neither antigen (group O). The antibodies present together with the antigens are found as follows: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_491", "text": "There is an  agglutination  reaction between similar antigen and antibody (for example, antigen A agglutinates the antibody A and antigen B agglutinates the antibody B). Thus, transfusion can be considered safe as long as the serum of the recipient does not contain antibodies for the blood cell antigens of the donor. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_492", "text": "The ABO system is the most important blood-group system in human-blood transfusion. The associated anti-A and anti-B antibodies are usually  immunoglobulin M , abbreviated  IgM , antibodies. It has been hypothesized that ABO IgM  antibodies  are produced in the first years of life by sensitization to environmental substances such as food,  bacteria , and  viruses , although blood group compatibility rules are applied to newborn and infants as a matter of practice. [ 14 ]  The original terminology used by  Karl Landsteiner  in 1901 for the classification was A/B/C; in later publications \"C\" became \"O\". [ 15 ]  Type O is often called  0  ( zero , or  null ) in other languages. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_493", "text": "The Rh system (Rh meaning  Rhesus ) is the second most significant blood-group system in human-blood transfusion with currently 50 antigens. The most significant Rh antigen is the D antigen, because it is the most likely to provoke an immune system response of the five main Rh antigens. It is common for D-negative individuals not to have any anti-D IgG or IgM antibodies, because anti-D antibodies are not usually produced by sensitization against environmental substances. However, D-negative individuals can produce  IgG  anti-D antibodies following a sensitizing event: possibly a fetomaternal transfusion of blood from a fetus in pregnancy or occasionally a blood transfusion with D positive  RBCs . [ 17 ]   Rh disease  can develop in these cases. [ 18 ]  Rh negative blood types are much less common in Asian populations (0.3%) than they are in European populations (15%). [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_494", "text": "The presence or absence of the Rh(D) antigen is signified by the + or \u2212 sign, so that, for example, the A\u2212 group is ABO type A and does not have the Rh (D) antigen. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_495", "text": "As with many other genetic traits, the distribution of ABO and Rh blood groups varies significantly between populations. [ citation needed ] [ 21 ]  While theories are still debated in the scientific community as to why blood types vary geographically and why they emerged in the first place, evidence suggests that the evolution of blood types may be driven by genetic selection for those types whose antigens confer resistance to particular diseases in certain regions \u2013 such as the prevalence of blood type O in malaria-endemic countries where individuals of blood type O exhibit the highest rates of survival. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_496", "text": "As of 31\u00a0December\u00a02022, [update]  42 blood-group systems have been identified by the International Society for Blood Transfusion in addition to the ABO and Rh systems. [ 3 ]  Thus, in addition to the ABO antigens and Rh antigens, many other antigens are expressed on the RBC surface membrane. For example, an individual can be AB, D positive, and at the same time M and N positive ( MNS system ), K positive ( Kell system ), Le a  or Le b  negative ( Lewis system ), and so on, being positive or negative for each blood group system antigen. Many of the blood group systems were named after the patients in whom the corresponding antibodies were initially encountered. Blood group systems other than ABO and Rh pose a potential, yet relatively low, risk of complications upon mixing of blood from different people. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_497", "text": "Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems: [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_498", "text": "Transfusion medicine is a specialized branch of  hematology  that is concerned with the study of blood groups, along with the work of a  blood bank  to provide a  transfusion  service for blood and other blood products. Across the world, blood products must be prescribed by a medical doctor (licensed  physician  or  surgeon ) in a similar way as medicines. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_499", "text": "Much of the routine work of a  blood bank  involves testing blood from both donors and recipients to ensure that every individual recipient is given blood that is compatible and as safe as possible. If a unit of incompatible blood is  transfused  between a  donor  and recipient, a severe  acute hemolytic reaction  with  hemolysis  (RBC destruction),  kidney failure  and  shock  is likely to occur, and death is a possibility. [ 27 ]  Antibodies can be highly active and can attack RBCs and bind components of the  complement system  to cause massive hemolysis of the transfused blood. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_500", "text": "Patients should ideally receive their own blood or type-specific blood products to minimize the chance of a  transfusion reaction . It is also possible to use the patient's own blood for transfusion. This is called  autotransfusion , which is always compatible with the patient. The procedure of washing a patient's own red blood cells goes as follows: The patient's lost blood is collected and washed with a saline solution. The washing procedure yields concentrated washed red blood cells. The last step is reinfusing the packed red blood cells into the patient. There are multiple ways to wash red blood cells. The two main ways are centrifugation and filtration methods. This procedure can be performed with microfiltration devices like the Hemoclear filter. Risks can be further reduced by  cross-matching  blood, but this may be skipped when blood is required for an emergency. Cross-matching involves mixing a sample of the recipient's serum with a sample of the donor's red blood cells and checking if the mixture  agglutinates , or forms clumps. If agglutination is not obvious by direct vision, blood bank technologist usually check for  agglutination  with a  microscope . If agglutination occurs, that particular donor's blood cannot be transfused to that particular recipient.  In a blood bank it is vital that all blood specimens are correctly identified, so labelling has been standardized using a  barcode  system known as  ISBT 128 ."}
{"_id": "WikiPedia_Hematology$$$corpus_501", "text": "The blood group may be included on  identification tags  or on  tattoos  worn by military personnel, in case they should need an emergency blood transfusion. Frontline German  Waffen-SS had blood group tattoos  during  World War II ."}
{"_id": "WikiPedia_Hematology$$$corpus_502", "text": "Rare blood types can cause supply problems for  blood banks  and hospitals. For example,  Duffy -negative blood occurs much more frequently in people of African origin, [ 29 ]  and the rarity of this blood type in the rest of the population can result in a shortage of Duffy-negative blood for these patients.  Similarly, for RhD negative people there is a risk associated with travelling to parts of the world where supplies of RhD negative blood are rare, particularly  East Asia , where blood services may endeavor to encourage Westerners to donate blood. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_503", "text": "A  pregnant  woman may carry a  fetus  with a blood type which is different from her own. Typically, this is an issue if a Rh- mother has a child with a Rh+ father, and the fetus ends up being Rh+ like the father. [ 31 ]  In those cases, the mother can make  IgG  blood group antibodies. This can happen if some of the fetus' blood cells pass into the mother's blood circulation (e.g. a small fetomaternal  hemorrhage  at the time of childbirth or obstetric intervention), or sometimes after a therapeutic  blood transfusion .  This can cause  Rh disease  or other forms of  hemolytic disease of the newborn  (HDN) in the current pregnancy and/or subsequent pregnancies.  Sometimes this is lethal for the fetus; in these cases it is called  hydrops fetalis . [ 32 ]  If a pregnant woman is known to have anti-D antibodies, the Rh blood type of a  fetus  can be tested by analysis of fetal DNA in maternal plasma to assess the risk to the fetus of Rh disease. [ 33 ]  One of the major advances of twentieth century medicine was to prevent this disease by stopping the formation of Anti-D antibodies by D negative mothers with an injectable medication called  Rho(D) immune globulin . [ 34 ] [ 35 ]  Antibodies associated with some blood groups can cause severe HDN, others can only cause mild HDN and others are not known to cause HDN. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_504", "text": "To provide maximum benefit from each blood donation and to extend shelf-life,  blood banks   fractionate  some whole blood into several products. The most common of these products are packed RBCs,  plasma ,  platelets ,  cryoprecipitate , and  fresh frozen plasma  (FFP).  FFP is quick-frozen to retain the labile  clotting factors   V  and  VIII , which are usually administered to patients who have a potentially fatal clotting problem caused by a condition such as advanced  liver  disease, overdose of  anticoagulant , or  disseminated intravascular coagulation  (DIC). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_505", "text": "Units of packed red cells are made by removing as much of the plasma as possible from whole blood units."}
{"_id": "WikiPedia_Hematology$$$corpus_506", "text": "Clotting factors  synthesized by modern  recombinant  methods are now in routine clinical use for  hemophilia , as the risks of infection transmission that occur with pooled blood products are avoided."}
{"_id": "WikiPedia_Hematology$$$corpus_507", "text": "Table note \n1. Assumes absence of atypical antibodies that would cause an incompatibility between donor and recipient blood, as is usual for blood selected by cross matching."}
{"_id": "WikiPedia_Hematology$$$corpus_508", "text": "An Rh D-negative patient who does not have any anti-D antibodies (never being previously sensitized to D-positive RBCs) can receive a transfusion of D-positive blood once, but this would cause sensitization to the D antigen, and a female patient would become at risk for  hemolytic disease of the newborn .  If a D-negative patient has developed anti-D antibodies, a subsequent exposure to D-positive blood would lead to a potentially dangerous transfusion reaction. Rh D-positive blood should never be given to D-negative women of child-bearing age or to patients with D antibodies, so blood banks must conserve Rh-negative blood for these patients. In extreme circumstances, such as for a major bleed when stocks of D-negative blood units are very low at the blood bank, D-positive blood might be given to D-negative females above child-bearing age or to Rh-negative males, providing that they did not have anti-D antibodies, to conserve D-negative blood stock in the blood bank. The converse is not true; Rh D-positive patients do not react to D negative blood."}
{"_id": "WikiPedia_Hematology$$$corpus_509", "text": "This same matching is done for other antigens of the Rh system as C, c, E and e and for other blood group systems with a known risk for immunization such as the Kell system in particular for females of child-bearing age or patients with known need for many transfusions."}
{"_id": "WikiPedia_Hematology$$$corpus_510", "text": "Blood plasma  compatibility is the inverse of red blood cell compatibility. [ 39 ]  Type AB plasma carries neither anti-A nor anti-B antibodies and can be transfused to individuals of any blood group; but type AB patients can only receive type AB plasma. Type O carries both antibodies, so individuals of blood group O can receive plasma from any blood group, but type O plasma can be used only by type O recipients."}
{"_id": "WikiPedia_Hematology$$$corpus_511", "text": "Table note \n1. Assuming absence of strong atypical antibodies in donor plasma"}
{"_id": "WikiPedia_Hematology$$$corpus_512", "text": "Rh D antibodies are uncommon, so generally neither D negative nor D positive blood contain anti-D antibodies.  If a potential donor is found to have anti-D antibodies or any strong atypical blood group antibody by antibody screening in the blood bank, they would not be accepted as a donor (or in some blood banks the blood would be drawn but the product would need to be appropriately labeled); therefore, donor blood plasma issued by a blood bank can be selected to be free of D antibodies and free of other atypical antibodies, and such donor plasma issued from a blood bank would be suitable for a recipient who may be D positive or D negative, as long as blood plasma and the recipient are ABO compatible. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_513", "text": "In transfusions of packed red blood cells, individuals with type O Rh D negative blood are often called universal donors. Those with type AB Rh D positive blood are called universal recipients. However, these terms are only generally true with respect to possible reactions of the recipient's anti-A and anti-B antibodies to transfused red blood cells, and also possible sensitization to Rh D antigens. One exception is individuals with  hh antigen system  (also known as the Bombay phenotype) who can only receive blood safely from other hh donors, because they form antibodies against the H antigen present on all red blood cells. [ 41 ] [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_514", "text": "Blood donors with exceptionally strong anti-A, anti-B or any atypical blood group antibody may be excluded from blood donation. In general, while the plasma fraction of a blood transfusion may carry donor antibodies not found in the recipient, a significant reaction is unlikely because of dilution."}
{"_id": "WikiPedia_Hematology$$$corpus_515", "text": "Additionally, red blood cell surface antigens other than A, B and Rh D, might cause adverse reactions and sensitization, if they can bind to the corresponding antibodies to generate an immune response.  Transfusions are further complicated because  platelets  and  white blood cells  (WBCs) have their own systems of surface antigens, and sensitization to platelet or WBC antigens can occur as a result of transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_516", "text": "For transfusions of  plasma , this situation is reversed.  Type O plasma, containing both anti-A and anti-B antibodies, can only be given to O recipients.  The antibodies will attack the antigens on any other blood type.  Conversely, AB plasma can be given to patients of any ABO blood group, because it does not contain any anti-A or anti-B antibodies."}
{"_id": "WikiPedia_Hematology$$$corpus_517", "text": "Typically, blood type tests are performed through addition of a blood sample to a solution containing antibodies corresponding to each antigen. The presence of an antigen on the surface of the blood cells is indicated by  agglutination ."}
{"_id": "WikiPedia_Hematology$$$corpus_518", "text": "In addition to the current practice of serologic testing of blood types, the progress in molecular diagnostics allows the increasing use of blood group genotyping. In contrast to serologic tests reporting a direct blood type phenotype, genotyping allows the prediction of a phenotype based on the knowledge of the molecular basis of the currently known antigens. This allows a more detailed determination of the blood type and therefore a better match for transfusion, which can be crucial in particular for patients with needs for many transfusions to prevent allo-immunization. [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_519", "text": "Blood types were first discovered by an Austrian physician,  Karl Landsteiner , working at the Pathological-Anatomical Institute of the University of Vienna (now  Medical University of Vienna ). In 1900, he found that blood sera from different persons would clump together (agglutinate) when mixed in test tubes, and not only that, some human blood also agglutinated with animal blood. [ 45 ]  He wrote a two-sentence footnote:"}
{"_id": "WikiPedia_Hematology$$$corpus_520", "text": "The serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. It remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_521", "text": "This was the first evidence that blood variation exists in humans. The next year, in 1901, he made a definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human bloods into three groups, namely group A, group B, and group C. He defined that group A blood agglutinates with group B, but never with its own type. Similarly, group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B. [ 47 ]  This was the discovery of blood groups for which Landsteiner was awarded the Nobel Prize in Physiology or Medicine in 1930. (C was later renamed to O after the German  Ohne , meaning without, or zero, or null. [ 48 ] ) Another group (later named AB) was discovered a year later by Landsteiner's students Adriano Sturli and Alfred von Decastello without designating the name (simply referring it to as \"no particular type\"). [ 49 ] [ 50 ]  Thus, after Landsteiner, three blood types were initially recognised, namely A, B, and C. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_522", "text": "Czech serologist  Jan Jansk\u00fd  was the first to recognise and designate four blood types in 1907 that he published in a local journal, [ 51 ]  using the Roman numerical I, II, III, and IV (corresponding to modern O, A, B, and AB respectively). [ 52 ]  Unknown to Jansk\u00fd, American physician  William L. Moss  introduced an almost identical classification in 1910, [ 53 ]  but with Moss's I and IV corresponding to Jansk\u00fd's IV and I. [ 54 ]  Thus the existence of two systems immediately created confusion and potential danger in medical practice. Moss's system was adopted in Britain, France, and the US, while Jansk\u00fd's was preferred in most other European countries and some parts of the US. It was reported that \"The practically universal use of the Moss classification at that time was completely and purposely cast aside. Therefore in place of bringing order out of chaos, chaos was increased in the larger cities.\" [ 55 ]  To resolve the confusion, the  American Association of Immunologists , the  Society of American Bacteriologists , and the Association of Pathologists and Bacteriologists made a joint recommendation in 1921 that the Jansky classification be adopted based on priority. [ 56 ]  But it was not followed particularly where Moss's system had been used. [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_523", "text": "In 1927, Landsteiner, who had moved to the  Rockefeller Institute for Medical Research  in New York, and as a member of a committee of the  National Research Council  concerned with blood grouping suggested to substitute Jansk\u00fd's and Moss's systems with the letters O, A, B, and AB, first instroduced by Polish physician  Ludwik Hirszfeld  and German physician  Emil von Dungern . [ 58 ]  There was another confusion on the use of O which was introduced in 1910. [ 59 ]  It was never clear whether it was meant for the figure 0, German  null  for zero or the upper case letter O for  ohne , meaning without; Landsteiner chose the latter. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_524", "text": "In 1928 the Permanent Commission on Biological Standardization adopted Landsteiner's proposal and stated:"}
{"_id": "WikiPedia_Hematology$$$corpus_525", "text": "The Commission learns with satisfaction that, on the initiative of the Health Organization of the League of Nations, the nomenclature proposed by von Dungern and Hirszfeld for the classification of blood groups has been generally accepted, and recommends that this nomenclature shall be adopted for international use as follows: 0 A B AB. To facilitate the change from the nomenclature hitherto employed the following is suggested:"}
{"_id": "WikiPedia_Hematology$$$corpus_526", "text": "This classification became widely accepted and after the early 1950s it was universally followed. [ 62 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_527", "text": "Hirszfeld and Dungern discovered the inheritance of blood types as  Mendelian genetics  in 1910 and the existence of sub-types of A in 1911. [ 59 ] [ 63 ]  In 1927, Landsteiner, with  Philip Levine , discovered the  MN blood group system , [ 64 ]  and the  P system . [ 65 ]  Development of the  Coombs test  in 1945, [ 66 ]  the advent of  transfusion medicine , and the understanding of  ABO hemolytic disease of the newborn  led to discovery of more blood groups. As of October\u00a02024 [update] , the International Society of Blood Transfusion (ISBT) recognizes 47 blood groups. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_528", "text": "A popular  pseudoscientific  belief in Eastern Asian countries (especially in  Japan  and  South Korea [ 67 ] ) known as \u8840\u6db2\u578b  ketsuekigata / hyeoraekhyeong  is that a person's ABO blood type is predictive of their  personality ,  character , and  compatibility with others . [ 68 ]  Researchers have established no scientific basis exists for blood type personality categorization, and studies have found no \"significant relationship between personality and blood type, rendering the theory 'obsolete' and concluding that no basis exists to assume that personality is anything more than randomly associated with blood type.\" [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_529", "text": "Redirect to:"}
{"_id": "WikiPedia_Hematology$$$corpus_530", "text": "Bone marrow examination  refers to the  pathologic  analysis of samples of  bone marrow  obtained by  bone marrow biopsy  (often called  trephine  biopsy) and  bone marrow aspiration . Bone marrow examination is used in the diagnosis of a number of conditions, including  leukemia ,  multiple myeloma ,  lymphoma ,  anemia , and  pancytopenia .  The bone marrow produces the cellular elements of the  blood , including  platelets ,  red blood cells  and  white blood cells . While much information can be gleaned by testing the blood itself (drawn from a vein by  phlebotomy ), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on  hematopoiesis ; this is the role of bone marrow aspiration and biopsy."}
{"_id": "WikiPedia_Hematology$$$corpus_531", "text": "Bone marrow samples can be obtained by aspiration and trephine biopsy.  Sometimes, a bone marrow examination will include both an aspirate and a biopsy.  The aspirate yields semi-liquid bone marrow, which can be examined by a  pathologist  under a  light microscope  and analyzed by  flow cytometry ,  chromosome analysis , or  polymerase chain reaction  (PCR). Frequently, a trephine biopsy is also obtained, which yields a narrow, cylindrically shaped solid piece of bone marrow, 2\u00a0mm wide and 2\u00a0cm long (80 \u03bcL), which is examined microscopically (sometimes with the aid of  immunohistochemistry ) for cellularity and infiltrative processes. An aspiration, using a 20 mL syringe, yields approximately 300 \u03bcL of bone marrow. [ 1 ]  A volume greater than 300 \u03bcL is not recommended, since it may dilute the sample with peripheral blood. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_532", "text": "Aspiration does not always represent all cells since some such as  lymphoma  stick to the  trabecula , and would thus be missed by a simple aspiration. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_533", "text": "Bone marrow aspiration and trephine biopsy are usually performed on the back of the hipbone, or posterior  iliac crest .  An  aspirate  can also be obtained from the  sternum  (breastbone).  For the sternal aspirate, the patient lies on their back, with a pillow under the shoulder to raise the chest. A  trephine biopsy  should never be performed on the sternum, due to the risk of injury to  blood vessels ,  lungs  or the  heart .  Bone marrow aspiration may also be performed on the tibial (shinbone) site in children up to 2 years of age while spinous process aspiration is frequently done in a lumbar puncture position and on the L3-L4 vertebrae. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_534", "text": "Anesthesia is used to reduce surface pain at the spot where the needle is inserted.  Pain may result from the procedure's insult to the marrow, which cannot be anesthetized, as well as short periods of pain from the anesthetic process itself.  The experience is not uniform; different patients report different levels of pain, and some do not report any pain at certain expected points. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_535", "text": "A bone marrow biopsy may be done in a health care provider's office or in a hospital.  Informed consent  for the procedure is typically required. The patient is asked to lie on their abdomen ( prone position ) or on their side (lateral  decubitus  position). The skin is cleansed, and a  local anesthetic  such as  lidocaine  or  procaine  is injected to numb the area. Patients may also be pretreated with  analgesics  and/or  anti-anxiety medications , although this is not a routine practice."}
{"_id": "WikiPedia_Hematology$$$corpus_536", "text": "Typically, the aspirate is performed first. An aspirate needle is inserted through the skin using manual pressure and force until it hits the  bone . Then, with a twisting motion of clinician's hand and wrist, the needle is advanced through the  bony cortex  (the hard outer layer of the bone) and into the marrow cavity. Once the needle is in the marrow cavity, a syringe is attached and used to aspirate (\"suck out\") liquid bone marrow. A twisting motion is performed during the aspiration to avoid excess content of blood in the sample, which might be the case if an excessively large sample from one single point is taken. Subsequently, the biopsy is performed if indicated.  A different, larger  trephine  needle is inserted and anchored in the bony cortex. The needle is then advanced with a twisting motion and rotated to obtain a solid piece of bone marrow. This piece is then removed along with the needle. The entire procedure, once preparation is complete, typically takes 10\u201315 minutes."}
{"_id": "WikiPedia_Hematology$$$corpus_537", "text": "If several samples are taken, the needle is removed between the samples to avoid blood coagulation."}
{"_id": "WikiPedia_Hematology$$$corpus_538", "text": "After the procedure is complete, the patient is typically asked to lie flat for 5\u201310 minutes to provide pressure over the procedure site. After that, assuming no bleeding is observed, the patient can get up and go about their normal activities.  Paracetamol  (aka acetaminophen) or other simple analgesics can be used to ease soreness, which is common for 2\u20133 days after the procedure. Any worsening pain, redness, fever, bleeding or swelling may suggest a complication. Patients are also advised to avoid washing the procedure site for at least 24 hours after the procedure is completed."}
{"_id": "WikiPedia_Hematology$$$corpus_539", "text": "There are few  contraindications  to bone marrow examination. It is important to note that thrombocytopenia or bleeding disorders are  not  contraindications as long as the procedure is performed by a skilled clinician. [ 3 ]  Bone marrow aspiration and biopsy can be safely performed even in the setting of extreme  thrombocytopenia  (low  platelet  count). If there is a skin or soft tissue infection over the hip, a different site should be chosen for bone marrow examination. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_540", "text": "While mild soreness lasting 12\u201324 hours is common after a bone marrow examination, serious  complications  are extremely rare. In a large review, an estimated 55,000 bone marrow examinations were performed, with 26  serious adverse events  (0.05%), including one fatality. [ 4 ]  The same author collected data on over 19,000 bone marrow examinations performed in the  United Kingdom  in 2003, and found 16  adverse events  (0.08% of total procedures), the most common of which was bleeding. In this report, complications, while rare, were serious in individual cases. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_541", "text": "Bone marrow failure  occurs in individuals who produce an insufficient amount of  red blood cells ,  white blood cells  or  platelets .  Red blood cells  transport oxygen to be distributed throughout the body's tissue.  White blood cells  fight off infections that enter the body. Bone marrow progenitor cells known as  megakaryocytes  produce  platelets , which trigger  clotting , and thus help stop the blood flow when a wound occurs. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_542", "text": "The two most common signs and symptoms of bone marrow failure are bleeding and bruising. Blood may be seen throughout the gums, nose or the skin, and bleeding tends to last longer than normal. Children have a greater chance of seeing blood in their urine or stools, which results in digestive problems with an unpleasant scent. Individuals with this condition may also encounter tooth loss or tooth decay. Chronic fatigue, shortness of breath, and recurrent infections can also be symptoms of bone marrow failure. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_543", "text": "Bone marrow failure in both children and adults can be either inherited or acquired. Inherited bone marrow failure is often the cause in young children, while older children and adults may acquire the disease later in life. [ 3 ]   Acquired bone marrow failure may be due to  aplastic anemia [ 4 ]  or  myelodysplastic syndrome ."}
{"_id": "WikiPedia_Hematology$$$corpus_544", "text": "Inherited marrow failure syndromes include:"}
{"_id": "WikiPedia_Hematology$$$corpus_545", "text": "Fanconi anemia  is an inherited blood disorder due to abnormal breakages in DNA genes. It is linked to hyperpigmentation, which is the darkening of an area of skin or nails caused by increased melanin, though in about 30% of FA patients no physical abnormalities are found. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_546", "text": "Dyskeratosis congenita  often affects multiple parts of the body. Individuals with this disorder usually show changes in skin pigmentations, unusual fingernail growth, and mucosa leukoplakia; the inner part of the mouth is encased with white patches. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_547", "text": "Inherited bone marrow failure syndromes represent a kind of premature aging of the bone marrow. In patients with these syndromes, as in elderly patients, mutations associated with  clonal hematopoiesis  may arise as an adaptive response to a progressively deteriorating hematopoietic niche, i.e., a depleting pool of  Hematopoietic stem cells . The mutated stem cells then acquire a self-renewal advantage. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_548", "text": "Aplastic anemia  is an acquired autoimmune disease in which  T cells  attack and destroy bone marrow precursor cells. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_549", "text": "Myelodysplastic syndrome  (MDS) is a form of blood cancer in which the bone marrow no longer produces enough healthy, normal blood cells. [ 9 ]  MDS are a frequently unrecognized and rare group of bone marrow failure disorders, yet the incidence rate has rose from 143 reported cases in 1973 to approximately 15,000 cases in the United States each year.  MDS is likely under-diagnosed, with the believed actual incidence rate estimated at 35,000 to 55,000 new cases annually. [ 10 ]  One in three people with MDS progress to acute myeloid leukemia. [ 9 ]  For lower risk patients, those who do not undergo a bone marrow transplant have an average survival rate of up to six years. [ 9 ]  However, high-risk patients have a survival rate of approximately five months. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_550", "text": "Cytopenias may be noted in the peripheral blood.  Bone marrow examination is required to assess erythroid, myeloid and  megakaryocytic precursors, identify genetic abnormalities, and rule out other entities such as leukemia. [ 11 ]   B-cell lymphopenia has been observed in some patients with MECOM deficiency but is not a definitive indicator. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_551", "text": "For those with severe bone marrow failure, the cumulative incidence of resulting stem cell transplantation or death was greater than 70% by individuals 60 years of age. [ 13 ]  The incidence of bone marrow failure is triphasic: one peak at two to five years during childhood (due to inherited causes), and two peaks in adulthood, between 20 and 25 years old and after 60 years old (from acquired causes). [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_552", "text": "One in ten individuals with bone marrow failure have unsuspected Fanconi anemia (FA). [ 14 ]  FA is the most common inherited bone marrow failure with an incidence of one to five episodes per million individuals. [ 14 ]  The carrier frequency for FA is 1 in 200 to 300, however this differs by ethnicity. [ 14 ]  In Europe and North America, the incidence of acquired aplastic anemia is rare with two episodes per million people each year, yet in Asia rises with 3.9 to 7.4 episodes per million people each year. [ 15 ]  While acquired aplastic anemia with an unknown cause is rare, it is commonly permanent and life-threatening as half of those with this condition die within the first six months. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_553", "text": "The prevalence of bone marrow failure is over three times higher in Japan and East Asia than in the United States and Europe. [ 10 ]  When one's body fails to produce blood cell lines, the morbidity and mortality rate increases. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_554", "text": "Supportive care with  blood transfusions  including  platelets  should be provided for symptoms of anemia and bleeding. Inherited bone marrow failure syndromes may require  hematopoietic stem cell transplantation .  Depending on severity,  aplastic anemia  may be treated with T-cell suppression in the form of  cyclosporine  and  anti-thymocyte globulin , or may require  hematopoietic stem cell transplantation ."}
{"_id": "WikiPedia_Hematology$$$corpus_555", "text": "Bone marrow suppression  also known as  myelotoxicity  or  myelosuppression , is the decrease in production of cells responsible for providing immunity ( leukocytes ), carrying oxygen ( erythrocytes ), and/or those responsible for normal blood clotting ( thrombocytes ). [ 1 ]   Bone marrow  suppression is a serious  side effect  of  chemotherapy  and certain drugs affecting the  immune system  such as  azathioprine . [ 2 ]  The risk is especially high in cytotoxic chemotherapy for  leukemia . In the case of  non-small-cell lung cancer , myelosuppression predisposition was shown to be modulated by  enhancer  mutations. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_556", "text": "Nonsteroidal anti-inflammatory drugs  (NSAIDs), in some rare instances, may also cause bone marrow suppression. The decrease in blood cell counts does not occur right at the start of chemotherapy because the drugs do not destroy the cells already in the bloodstream (these are not dividing rapidly). Instead, the drugs affect new blood cells that are being made by the bone marrow. [ 4 ]  When myelosuppression is severe, it is called myeloablation. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_557", "text": "Many other drugs including common antibiotics may cause bone marrow suppression. Unlike chemotherapy the effects may not be due to direct destruction of stem cells but the results may be equally serious. The treatment may mirror that of chemotherapy-induced myelosuppression or may be to change to an alternate drug or to temporarily suspend treatment."}
{"_id": "WikiPedia_Hematology$$$corpus_558", "text": "Because the bone marrow is the manufacturing center of blood cells, the suppression of bone marrow activity causes a deficiency of blood cells. This condition can rapidly lead to life-threatening  infection , as the body cannot produce  leukocytes  in response to invading  bacteria  and  viruses , as well as leading to  anaemia  due to a lack of  red blood cells  and spontaneous severe bleeding due to deficiency of  platelets ."}
{"_id": "WikiPedia_Hematology$$$corpus_559", "text": "Parvovirus B19  inhibits  erythropoiesis  by lytically infecting RBC precursors in the bone marrow and is associated with a number of different diseases ranging from benign to severe. In  immunocompromised  patients, B19 infection may persist for months, leading to chronic  anemia  with B19 viremia due to chronic marrow suppression. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_560", "text": "Bone marrow suppression due to  azathioprine  can be treated by changing to another medication such as  mycophenolate mofetil  (for organ transplants) or other disease-modifying drugs in  rheumatoid arthritis  or  Crohn's disease ."}
{"_id": "WikiPedia_Hematology$$$corpus_561", "text": "Bone marrow suppression due to anti-cancer chemotherapy is much harder to treat and often involves hospital admission, strict infection control, and aggressive use of intravenous  antibiotics  at the first sign of infection. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_562", "text": "G-CSF  is used clinically (see  Neutropenia ) but tests in mice suggest it may lead to bone loss. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_563", "text": "GM-CSF  has been compared to G-CSF as a treatment of chemotherapy-induced myelosuppression/ Neutropenia . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_564", "text": "Trilaciclib (COSELA) , a  CDK4/6 inhibitor , is administered before  chemotherapy  in  small cell lung cancer  to control chemotherapy-induced myelosuppression.  [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_565", "text": "In developing new chemotherapeutics, the efficacy of the drug against the disease is often balanced against the likely level of myelotoxicity the drug will cause. In-vitro colony forming cell (CFC) assays using normal human bone marrow grown in appropriate semi-solid media such as ColonyGEL have been shown to be useful in predicting the level of clinical myelotoxicity a certain compound might cause if administered to humans. [ 12 ]  These predictive in-vitro assays reveal effects the administered compounds have on the bone marrow progenitor cells that produce the various mature cells in the blood and can be used to test the effects of single drugs or the effects of drugs administered in combination with others."}
{"_id": "WikiPedia_Hematology$$$corpus_566", "text": "A  bruise , also known as a  contusion , is a type of  hematoma  of  tissue , [ 3 ]  the most common cause being  capillaries  damaged by  trauma , causing localized bleeding that  extravasates  into the surrounding  interstitial  tissues. Most bruises occur close enough to the epidermis such that the bleeding causes a visible discoloration. The bruise then remains visible until the blood is either absorbed by tissues or cleared by  immune system  action. Bruises which do not  blanch  under pressure can involve capillaries at the level of skin,  subcutaneous tissue , muscle, or bone. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_567", "text": "Bruises are not to be confused with other similar-looking  lesions . Such lesions include  petechia  (less than 3\u00a0mm (0.12\u00a0in), resulting from numerous and diverse etiologies such as adverse reactions from medications such as warfarin, straining, asphyxiation,  platelet  disorders and diseases such as  cytomegalovirus ); [ 6 ]  and  purpura  (3\u201310\u00a0mm (0.12\u20130.39\u00a0in)), classified as palpable purpura or non-palpable purpura and indicating various pathologic conditions such as  thrombocytopenia . [ 7 ]  Additionally, although many  terminology  schemas treat an  ecchymosis  (plural, ecchymoses) (over 1\u00a0cm (0.39\u00a0in)) as synonymous with a bruise, [ 1 ]  in some other schemas, an ecchymosis is differentiated by its remoteness from the source and cause of bleeding, with blood dissecting through tissue planes and settling in an area remote from the site of trauma or even nontraumatic pathology, such as in  periorbital  ecchymosis (\" raccoon eyes \"), arising from a  basilar skull fracture  or from a  neuroblastoma . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_568", "text": "As a type of hematoma, a bruise is always caused by internal bleeding into the interstitial tissues which does not break through the skin, usually initiated by  blunt trauma , which causes damage through  physical compression  and  deceleration  forces. Trauma sufficient to cause bruising can occur from a wide variety of situations including accidents, falls, and surgeries. Disease states such as insufficient or malfunctioning  platelets , other  coagulation  deficiencies, or vascular disorders, such as venous blockage associated with severe  allergies [ 9 ]  can lead to the formation of purpura which is not to be confused with trauma-related bruising/contusion. [ 10 ]  If the trauma is sufficient to break the skin and allow blood to escape the interstitial tissues, the injury is not a bruise but bleeding, a different variety of hemorrhage. Such injuries may be accompanied by bruising elsewhere. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_569", "text": "Bruises often induce pain immediately after the trauma that results in their formation, but small bruises are not normally dangerous alone. Sometimes bruises can be serious, leading to other more life-threatening forms of hematoma, such as when associated with serious injuries, including  fractures  and more severe  internal bleeding .  The likelihood and severity of bruising depends on many factors, including type and healthiness of affected tissues. Minor bruises may be easily recognized in people with light skin color by characteristic blue or purple appearance (idiomatically described as \"black and blue\") in the days following the injury."}
{"_id": "WikiPedia_Hematology$$$corpus_570", "text": "Hematomas can be subdivided by size. By definition, ecchymoses are 1 centimetres in size or larger, and are therefore larger than  petechiae  (less than 3 millimetres in diameter) [ 12 ]  or  purpura  (3 to 10 millimetres in diameter). [ 13 ]  Ecchymoses also have a more diffuse border than other purpura. [ 14 ]  A broader definition of ecchymosis is the escape of blood into the tissues from ruptured blood vessels. [ 15 ] [ 16 ]  The term also applies to the subcutaneous discoloration resulting from seepage of blood within the injured tissue."}
{"_id": "WikiPedia_Hematology$$$corpus_571", "text": "Bruise colors vary from red, blue, or almost black, depending on the severity of broken capillaries or blood vessels within the bruise site. Broken  venules  or  arterioles  often result in a deep blue or dark red bruise, respectively. Darker colored bruises may result from a more severe bleeding from both blood vessels. Older bruises may appear yellow, green or brown. [ 11 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_572", "text": "There are many causes of subcutaneous hematomas including ecchymoses.  Coagulopathies  such as  hemophilia A  may cause ecchymosis formation in children. [ 18 ]  The medication  betamethasone  can have the adverse effect of causing ecchymosis. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_573", "text": "The presence of bruises may be seen in patients with  platelet  or  coagulation  disorders, or those who are being treated with an  anticoagulant . Unexplained bruising may be a warning sign of  child abuse ,  domestic abuse , or serious medical problems such as  leukemia  or  meningoccocal  infection. Unexplained bruising can also indicate internal bleeding or certain types of cancer. Long-term glucocorticoid therapy can cause easy bruising. Bruising present around the  navel  (belly button) with severe abdominal pain suggests acute  pancreatitis . Connective tissue disorders such as  Ehlers\u2013Danlos syndrome  may cause relatively easy or spontaneous bruising depending on the severity. Spontaneous bruising or bruising with minimal trauma in the absence of other explanations and together with other minor or major criteria suggestive of vascular Ehlers\u2013Danlos Syndrome (vEDS) suggests  genetic testing  for the condition. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_574", "text": "During an  autopsy , bruises accompanying  abrasions  indicate the abrasions occurred while the individual was alive, as opposed to damage incurred post mortem."}
{"_id": "WikiPedia_Hematology$$$corpus_575", "text": "Bruise shapes may correspond directly to the instrument of injury or be modified by additional factors. Bruises often become more prominent as time lapses, resulting in additional size and swelling, and may grow to a large size over the course of the hours after the injury that caused the bruise was inflicted."}
{"_id": "WikiPedia_Hematology$$$corpus_576", "text": "Bruises can be scored on a scale from 0\u20135 to categorize the severity and danger of the injury."}
{"_id": "WikiPedia_Hematology$$$corpus_577", "text": "The harm score is determined by the extent and severity of the injuries to the organs and tissues causing the bruising, in turn depending on multiple factors.  For example, a  contracted  muscle will bruise more severely, as will tissues crushed against underlying bone.   Capillaries  vary in strength, stiffness and toughness, which can also vary by age and medical conditions."}
{"_id": "WikiPedia_Hematology$$$corpus_578", "text": "Low levels of damaging forces produce small bruises and generally cause the individual to feel minor pain straight away. Repeated impacts worsen bruises, increasing the harm level. Normally, light bruises heal nearly completely within two weeks, although duration is affected by variation in severity and individual healing processes; [ 22 ]  generally, more severe or deeper bruises take somewhat longer."}
{"_id": "WikiPedia_Hematology$$$corpus_579", "text": "Severe bruising (harm score 2\u20133) may be dangerous or cause serious complications.  Further bleeding and excess fluid may accumulate causing a hard, fluctuating lump or swelling hematoma.  This has the potential to cause  compartment syndrome  in which the swelling cuts off blood flow to the tissues.  The trauma that induced the bruise may also have caused other severe and potentially fatal harm to internal  organs .  For example, impacts to the head can cause  traumatic brain injury : bleeding, bruising and massive swelling of the brain with the potential to cause  concussion ,  coma  and death.  Treatment for brain bruising may involve emergency surgery to relieve the pressure on the brain."}
{"_id": "WikiPedia_Hematology$$$corpus_580", "text": "Damage that causes bruising can also cause bones to be  broken ,  tendons  or muscles to be  strained ,  ligaments  to be  sprained , or other tissue to be damaged.  The symptoms and signs of these injuries may initially appear to be those of simple bruising. Abdominal bruising or severe injuries that cause difficulty in moving a limb or the feeling of liquid under the skin may indicate life-threatening injury and require the attention of a physician."}
{"_id": "WikiPedia_Hematology$$$corpus_581", "text": "Increased distress to tissue causes  capillaries  to break under the skin, allowing blood to escape and build up. As time progresses, blood seeps into the surrounding tissues, causing the bruise to darken and spread.  Nerve  endings within the affected tissue detect the increased pressure, which, depending on severity and location, may be perceived as pain or pressure or be  asymptomatic . The damaged capillary  endothelium  releases  endothelin , a  hormone  that causes  narrowing of the blood vessel  to minimize bleeding. As the endothelium is destroyed, the underlying  von Willebrand factor  is exposed and initiates  coagulation , which creates a temporary  clot  to plug the wound and eventually leads to restoration of normal tissue."}
{"_id": "WikiPedia_Hematology$$$corpus_582", "text": "During this time, larger bruises may change color due to the breakdown of  hemoglobin  from within escaped  red blood cells  in the extracellular space. The striking colors of a bruise are caused by the  phagocytosis  and sequential degradation of hemoglobin to  biliverdin  to  bilirubin  to  hemosiderin , with hemoglobin itself producing a red-blue color, biliverdin producing a green color, bilirubin producing a yellow color, and hemosiderin producing a golden-brown color. [ 11 ]  As these products are cleared from the area, the bruise disappears. Often the underlying tissue damage has been repaired long before this process is complete."}
{"_id": "WikiPedia_Hematology$$$corpus_583", "text": "Treatment for light bruises is minimal and may include  RICE  ( rest ,  ice ,  compression , and  elevation ),  painkillers  (particularly  NSAIDs ) and, later in recovery, light stretching exercises. Particularly, immediate application of ice while elevating the area may reduce or completely prevent swelling by restricting blood flow to the area and preventing internal bleeding. Rest and preventing re-injury is essential for rapid recovery."}
{"_id": "WikiPedia_Hematology$$$corpus_584", "text": "Very gently massaging the area and applying heat may encourage blood flow and relieve pain according to the  Gate control theory  of pain, although causing additional pain may indicate the massage is exacerbating the injury. [ 23 ]  As for most injuries, these techniques should not be applied until at least three days following the initial damage to ensure all internal bleeding has stopped, because although increasing blood flow will allow more healing factors into the area and encourage drainage, if the injury is still bleeding this will allow more blood to seep out of the wound and cause the bruise to become worse."}
{"_id": "WikiPedia_Hematology$$$corpus_585", "text": "Folk medicine , including ancient medicine of Egyptians, Greeks, Celts, Turks, Slavs, Maya, Aztecs and Chinese, has used bruising as a treatment for some health problems. The methods vary widely and include cupping, scraping, and slapping.  Fire cupping  uses suction which causes bruising in patients. Scraping ( gua sha ) uses a small hand device with a rounded edge to gently scrape the scalp or the skin. Another ancient device that creates mild bruising is a  strigil , used by Greeks and Romans in the bath. Archaeologically there is no precedent for scraping tools before Greek archaeological evidence, not Chinese or Egyptian. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_586", "text": "The word  ecchymosis  ( / \u02cc \u025b k \u026a \u02c8 m o\u028a s \u026a s / ; plural  ecchymoses ,  / \u02cc \u025b k \u026a \u02c8 m o\u028a s i\u02d0 s / ), comes to English from  Neo-Latin , based on  Greek   \u1f10\u03ba\u03c7\u03cd\u03bc\u03c9\u03c3\u03b9\u03c2 ,  ekchym\u014dsis , from  \u1f10\u03ba\u03c7\u03c5\u03bc\u03bf\u1fe6\u03c3\u03b8\u03b1\u03b9 ,  ekchymousthai , 'to extravasate blood', from  \u1f10\u03ba- ,  ek-  (elided to  \u1f10- ,  e- ) and  \u03c7\u03c5\u03bc\u03cc\u03c2 ,  chymos , 'juice'. [ 25 ]  Compare  enchyma , \"tissue infused with organic juice\"; elaboration from chyme, the formative juice of tissues."}
{"_id": "WikiPedia_Hematology$$$corpus_587", "text": "\u03b1-Naphthyl butyrate esterase , also referred to as  naphthyl butyrate esterase  or  butyrate esterase , is a  histological stain  specific for  white blood cells  of the  monocytic  proliferation line. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_588", "text": "Cauterization  (or  cauterisation , or  cautery ) is a medical practice or technique of  burning  a part of a body to remove or close off a part of it. It destroys some tissue in an attempt to mitigate  bleeding  and damage, remove an undesired growth, or minimize other potential medical harm, such as  infections  when  antibiotics  are unavailable. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_589", "text": "The practice was once widespread for treatment of wounds. Its utility before the advent of antibiotics was said to be effective at more than one level:"}
{"_id": "WikiPedia_Hematology$$$corpus_590", "text": "Cautery was historically believed to prevent infection, but current research shows that cautery actually increases the risk for infection by causing more tissue damage and providing a more hospitable environment for bacterial growth. [ 2 ]   Actual cautery  refers to the metal device, generally heated to a dull red glow, that a physician applies to produce  blisters , to stop  bleeding  of a  blood vessel , and for other similar purposes. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_591", "text": "The main forms of cauterization used today are  electrocautery  and  chemical cautery \u2014both are, for example, prevalent in cosmetic removal of  warts  and stopping  nosebleeds . Cautery can also mean the  branding of a human ."}
{"_id": "WikiPedia_Hematology$$$corpus_592", "text": "Cauterize is a  Middle English  word borrowed from the Old French  cauteriser , from Late Latin  cauterizare  \"to burn or brand with a hot iron\", from Ancient Greek  \u03ba\u03b1\u03c5\u03c4\u03b7\u03c1\u03b9\u03ac\u03b6\u03b5\u03b9\u03bd  ( kauteriazein ), from  \u03ba\u03b1\u03c5\u03c4\u03ae\u03c1  ( kauter ), \"burning or branding iron\", and  \u03ba\u03b1\u03af\u03b5\u03b9\u03bd  ( kaiein ) \"to burn\" (of caustic). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_593", "text": "Cauterization has been used to stop heavy bleeding since antiquity. The process was described in the  Edwin Smith Papyrus [ 5 ]  and  Hippocratic Corpus . [ 6 ]  It was primarily used to control hemorrhages, especially those resulting from surgery, in  ancient Greece .  Archigenes  recommended cauterization in the event of hemorrhaging wounds, and  Leonides of Alexandria  described excising breast tumors and cauterizing the resulting wound in order to control bleeding. [ 7 ]  The Chinese  Su wen  recommends cauterization as a treatment for various ailments, including dog bites. [ 8 ]   Indigenous peoples of the Americas ,  ancient Arabs , and Persians also used the technique. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_594", "text": "Tools used in the ancient cauterization process ranged from heated lances to cauterizing knives. The piece of metal was heated over fire and applied to the wound. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_595", "text": "Cauterization continued to be used as a common treatment in medieval times. The  Babylonian Talmud  (redacted in 500 AD), alluding to the practice, states: \"...and the effect of the hot iron comes and removes the traces of the stroke.\" [ 11 ]  While mainly employed to stop blood loss, it was also used in cases of tooth extraction and as a treatment for mental illness. In the  Muslim world , scholars  Al-Zahrawi  and  Avicenna  wrote about techniques and instruments used for cauterization. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_596", "text": "As late as the 20th-century,  Bedouins  of the  Negev  in Israel had it as their practice to take the root of the Shaggy sparrow-wort ( Thymelaea hirsuta ), cut splinters lengthwise in the root, burn the splinter in fire, and then apply the red-hot tip of a splinter to the forehead of a person who was ill with ringworm ( Dermatophytosis ). [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_597", "text": "The technique of  ligature  of the arteries as an alternative to cauterization was later improved and used more effectively by  Ambroise Par\u00e9 ."}
{"_id": "WikiPedia_Hematology$$$corpus_598", "text": "Electrocauterization is the process of destroying tissue (or cutting through soft tissue) using  heat conduction  from a metal probe heated by electric current. The procedure stops bleeding from small vessels (larger vessels being  ligated ). Electrocautery applies high frequency alternating current by a  unipolar  or  bipolar  method. It can be a continuous  waveform  to cut tissue, or intermittent to coagulate tissue."}
{"_id": "WikiPedia_Hematology$$$corpus_599", "text": "The electrically produced heat in this process inherently can do numerous things to the tissue, depending on the waveform and power level, including cauterize, coagulate, cut, and dry (desiccate). Thus electrocautery, electrocoagulation, electrodesiccation, and electrocurettage are closely related and can co-occur in the same procedure when desired.  Electrodesiccation and curettage  is a common procedure."}
{"_id": "WikiPedia_Hematology$$$corpus_600", "text": "In unipolar cauterization, the physician contacts the tissue with a single small electrode. The circuit's exit point is a large surface area, such as the buttocks, to prevent electrical burns. The amount of heat generated depends on the size of contact area, power setting or frequency of current, duration of application, and waveform. A constant waveform generates more heat than intermittent. The frequency used in cutting the tissue is higher than in coagulation mode."}
{"_id": "WikiPedia_Hematology$$$corpus_601", "text": "Bipolar electrocautery passes the current between two tips of a forceps-like tool. It has the advantage of not disturbing other electrical body rhythms (such as the heart) and also coagulates tissue by pressure. Lateral thermal injury is greater in unipolar than bipolar devices. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_602", "text": "Electrocauterization is preferable to chemical cauterization, because chemicals can leach into neighbouring tissue and cauterize outside of intended boundaries. [ 15 ]  Concern has also been raised regarding toxicity of the  surgical smoke  electrocautery produces. This contains chemicals that, through inhalation, may harm patients or medical staff. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_603", "text": "Ultrasonic  coagulation and ablation systems are also available."}
{"_id": "WikiPedia_Hematology$$$corpus_604", "text": "Many chemical reactions can destroy tissue, and some are used routinely in medicine, most commonly to remove small skin lesions such as  warts  or necrotized tissue, or for  hemostasis . [ 17 ]  Because chemicals can leach into areas not intended for cauterization, laser and electrical methods are preferable where practical. [ 18 ]  Some cauterizing agents are:"}
{"_id": "WikiPedia_Hematology$$$corpus_605", "text": "Frequent  nosebleeds  are most likely caused by an exposed blood vessel in the nose, usually one in  Kiesselbach's plexus ."}
{"_id": "WikiPedia_Hematology$$$corpus_606", "text": "Even if the nose is not bleeding at the time, a physician may cauterize it to prevent future bleeding. Cauterization methods include burning the affected area with acid, hot metal, or lasers. Such a procedure is naturally quite painful. Sometimes, a physician uses  liquid nitrogen  as a less painful alternative, though it is less effective. A physician may apply  cocaine  in the few countries that allow it for medical use. Cocaine is the only  local anesthetic  that also produces  vasoconstriction , [ 23 ]  making it ideal for controlling nosebleeds."}
{"_id": "WikiPedia_Hematology$$$corpus_607", "text": "More modern treatment applies  silver nitrate  after a local anesthetic. The procedure is generally painless, but after the anesthetic wears off, there may be pain for several days, and the nose may run for up to a week after this treatment."}
{"_id": "WikiPedia_Hematology$$$corpus_608", "text": "Nasal cauterization can cause  empty nose syndrome . [ 24 ] [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_609", "text": "Cauterization has been used for the  circumcision  of infants in the  United States  and  Canada . The  College of Physicians and Surgeons of Manitoba  advises against its use in neonatal circumcision. [ 27 ]  This method of circumcision resulted in several infants having their  penises  severely burned. [ 28 ] [ 29 ] [ 30 ] [ 31 ] [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_610", "text": "Chromatography  is a physical method of separation that distributes the components you want to separate between two phases, one stationary (stationary phase), the other (the mobile phase) moving in a definite direction. Cold ethanol precipitation, developed by Cohn in 1946, manipulates pH, ionic strength, ethanol concentration and temperature to precipitate different protein fractions from plasma. Chromatographic techniques utilise ion exchange, gel filtration and affinity resins to separate proteins. Since the 1980s it has emerged as an effective method of purifying blood components for therapeutic use."}
{"_id": "WikiPedia_Hematology$$$corpus_611", "text": "Blood plasma  is the liquid component of blood, which contains dissolved proteins, nutrients, ions, and other soluble components. In whole blood,  red blood cells ,  white blood cells , and  platelets  are suspended within the plasma. The goal of  plasma purification and processing  is to extract specific materials that are present in blood, and use them for restoration and repair.  There are several components that make up blood plasma, one of which is the protein  albumin . Albumin is a highly water-soluble protein with considerable structural stability. It serves as a transportation device for materials such as hormones, enzymes, fatty acids, metal ions, and medicinal products.  It is also used for therapeutic purposes, being essential in restoration and maintenance of circulating blood volume in imperative situations such as severe trauma or surgery.  With little room for error, extremely pure samples that are lacking impurities needs to be at hand in good amount. Human blood plasma is important for the body so the nutrients etc. can be stored."}
{"_id": "WikiPedia_Hematology$$$corpus_612", "text": "Traditionally, the  Cohn process  incorporating cold ethanol fractionation has been used for albumin purification.  However,  chromatographic methods  for separation started being adopted in the early 1980s.  Developments were ongoing in the time period between when Cohn fractionation started being used, in 1946, and when chromatography started being used, in 1983.  In 1962, the Kistler & Nistchmann process was created which was a spinoff of the Cohn process. Chromatographic processes began to take shape in 1983. In the 1990s, the Zenalb and the CSL Albumex processes were created which incorporated chromatography with a few variations."}
{"_id": "WikiPedia_Hematology$$$corpus_613", "text": "The general approach to using chromatography for plasma fractionation for albumin is: recovery of supernatant I, delipidation,  anion exchange chromatography , cation exchange chromatography, and gel filtration chromatography."}
{"_id": "WikiPedia_Hematology$$$corpus_614", "text": "The recovered purified material is formulated with combinations of sodium octanoate and sodium N-acetyl tryptophanate and then subjected to viral inactivation procedures, including pasteurisation at 60\u00a0\u00b0C."}
{"_id": "WikiPedia_Hematology$$$corpus_615", "text": "This is a more efficient alternative than the Cohn process for four main reasons:\n1) smooth automation and a relatively inexpensive plant was needed,\n2) easier to sterilize equipment and maintain a good manufacturing environment,\n3) chromatographic processes are less damaging to the albumin protein, and\n4) a more successful albumin end result can be achieved."}
{"_id": "WikiPedia_Hematology$$$corpus_616", "text": "Compared with the Cohn process, the albumin purity went up from about 95% to 98% using chromatography, and the yield increased from about 65% to 85%.  Small percentage increases make a difference in regard to  sensitive measurements like purity. There is one big drawback in using chromatography, which has to do with the economics of the process. Although the method was efficient from the processing aspect, acquiring the necessary equipment is a big task.  Large machinery is necessary, and for a long time the lack of equipment availability was not conducive to its widespread use.  The components are more readily available now but it is still a work in progress and will possibly be ready in the future to help the world."}
{"_id": "WikiPedia_Hematology$$$corpus_617", "text": "Integrating traditional and modern methods is a useful way to process albumin."}
{"_id": "WikiPedia_Hematology$$$corpus_618", "text": "There are three main steps that combine Cohn fractionation with chromatography: 1) factors I, II, and III are removed via cold ethanol fractionation, 2)  Sepharose  fast flow ion exchange and sepharose fast flow chromatography procedures are run, and 3) gel filtration is run. The result is albumin with 9% lower aluminum levels with a processing time that is almost twice as fast."}
{"_id": "WikiPedia_Hematology$$$corpus_619", "text": "Although it was hard to make chromatographic processing methods widely adopted, global expansion is a work in progress.  Various blood components must be readily available at various medical treatment centers around the world.  The Institute of Transfusion Medicine in  Skopje ,  North Macedonia  is a plasma fractionation center in the Balkans. Their modernized albumin purification process consists of five steps:"}
{"_id": "WikiPedia_Hematology$$$corpus_620", "text": "The end result is a highly pure and safe batch of albumin that is 100% non- pyrogenic , sterile, and free of active  HIV virus . The product purity is greater than 98% and the protein content is about 50 g/L."}
{"_id": "WikiPedia_Hematology$$$corpus_621", "text": "Other plasma processing methods exist, but generally do not provide the resolution or purity of chromatographic methods. \n Two-phase liquid extraction  may be performed using  polyethylene glycol  (PEG)-phosphate  Aqueous two-phase systems , with a PEG-rich top layer and a phosphate-rich bottom layer. Although this method is somewhat useful for protein recovery, it does not work as well for the recovery of other blood components. \nMembrane fractionation has the advantage of minimal protein loss yet high removal of pathological plasma components.  This method incorporates processes such as thermofiltration and applying pulsate flow. The latest two-stage membrane system utilizes a high flow recirculation circuit that is effective for removal of  LDL  cholesterol.  It may prove useful for patients that have clogged arteries and other cardiovascular problems involving cholesterol. \nBatch adsorption, e.g. onto ion exchange media, is only useful when dealing with smaller samples of plasma, typically 200 mL or less. Batch adsorption recovers the product in a larger volume of elution buffer than does column chromatography or frontal chromatography, and the resulting more dilute product requires concentration, typically on a membrane system, which can lead to loss of product by irreversible adsorption to the membrane."}
{"_id": "WikiPedia_Hematology$$$corpus_622", "text": "Clonal hematopoiesis of indeterminate potential , or  CHIP , is a common aging-related phenomenon in which  hematopoietic stem cells (HSCs)  or other early blood  cell progenitors  contribute to the formation of a genetically distinct subpopulation of  blood cells . [ 1 ] [ 2 ] [ 3 ]  As the name suggests, this subpopulation in the blood is characterized by a shared unique  mutation  in the cells'  DNA ; it is thought that this subpopulation is \"clonally\" derived from a single founding cell and is therefore made of genetic \"clones\" of the founder. [ 4 ] [ 5 ] [ 6 ] [ 7 ]  The establishment of a clonal population may occur when a stem or progenitor cell acquires one or more somatic mutations that give it a competitive advantage in  hematopoiesis  over the stem/progenitor cells without these mutations. [ 1 ] [ 3 ]  Alternatively, clonal hematopoiesis may arise without a driving mutation, through mechanisms such as  neutral drift  in the stem cell population. [ 8 ]  Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic diseases. [ 1 ] [ 9 ] [ 10 ]  The clonal population may vary in size depending on the person, where it can be less than 2% of the blood or, at the other end, can sometimes grow close to 100%. [ 4 ] [ 9 ]  The incidence of clonal hematopoiesis has been found to rise dramatically with age. Recent studies have demonstrated that less than 1% of the population under age 40 but approximately 10-20% of the population over age 70 has observable clonal hematopoiesis. [ 4 ] [ 5 ] [ 6 ]  Having clonal hematopoiesis has been linked to a more than 10-fold increased risk of developing a blood cancer, though the overall likelihood is still low. [ 4 ] [ 5 ]  Clonal hematopoiesis does not typically give rise to noticeable symptoms, but does lead to increased risk of  cardiovascular disease . [ 1 ] [ 5 ] [ 11 ]  Patients with solid tumors or lymphoma and clonal hematopoiesis have been shown to have an inferior outcome. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_623", "text": "The first major evidence for the existence of prevalent clonal hematopoiesis in healthy people was put forth in the 1990s. Using the  HUMARA assay , scientists found that there was nonrandom  X-inactivation  of the  X chromosome  in the blood of some healthy women. [ 13 ] [ 14 ]  This means that a greater than expected proportion of the blood had the silencing of one specific X chromosome in the chromosome pair. Just as the observation of the same DNA mutation in a subset of cells suggests a single founding source, this X-inactivation skew suggests that a greater than expected number of cells are being generated from the same precursor. Importantly, these findings described an increase in this nonrandom skewing with increasing age, hinting that unobserved mutations acquired with age could be driving a  clonal expansion . In a similar vein, other studies using the HUMARA technology had found that hematologic malignancies are clonal diseases even when there is no apparent chromosomal abnormality, [ 15 ] [ 16 ]  and that there are pre-leukemic clonal populations which precede  acute myeloid leukemia (AML) . [ 17 ]  As the HUMARA assay is based on the  epigenetic  state of cells, the underlying genetic determinants of the clonal expansion remained to be uncovered."}
{"_id": "WikiPedia_Hematology$$$corpus_624", "text": "This set of evidence led to the suggestion in 2005 that driving mutations in leukemia are acquired in a step-wise manner. [ 18 ]  This model has received support from studies showing subpopulations of blood cells harboring initiating but not late somatic mutations in patients with  chronic lymphocytic leukemia (CLL) , [ 19 ] [ 20 ]   hairy cell leukemia (HCL) , [ 21 ]  and AML. [ 22 ] [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_625", "text": "The combination of these two ideas, that clonal hematopoiesis might be common in the elderly population and that AML evolves from pre-leukemic populations, led to the hypothesis that malignancy-associated mutations could also contribute to asymptomatic clonal hematopoiesis in healthy individuals. [ 1 ]  This view gained mechanistic support in 2012 when it was found a number of the women who showed evidence for clonal hematopoiesis through X-inactivation skew also had mutations in the hematologic-malignancy-associated gene  TET2 . [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_626", "text": "In 2014, several independent studies confirmed the presence of malignancy-associated mutations in the blood of individuals who have no clinical signs of hematologic malignancy. [ 4 ] [ 5 ] [ 6 ]  In combination, these studies have demonstrated the widespread incidence of clonal hematopoiesis in the healthy adult population and have stimulated further efforts to broaden our understanding of clonal hematopoiesis in health and disease.  The term \"clonal hematopoiesis of indeterminate potential\" (CHIP) was proposed later that year to describe persons who do not have a malignancy meeting World Health Organization diagnostic criteria, yet have somatic mutations in hematopoietic stem and progenitor cells involving genes that have been associated with hematological malignancy, and these mutations are present in blood cells with a variant allele frequency of at least 2%. [ 3 ]   The 2% threshold was chosen in part because of technical limitations (i.e., analytic sensitivity of clinically available sequencing assays) but also because very small clones are of unclear clinical significance."}
{"_id": "WikiPedia_Hematology$$$corpus_627", "text": "The advent of next-generation DNA sequencing has allowed for the targeted identification of somatic mutations involved in clonal hematopoiesis at the population level. The studies undertaken as of 2017 are largely consistent in their main findings. One common finding has been that observable clonal hematopoiesis is virtually absent from the under-40 population, with a sharp uptick in frequency past 60 years of age. [ 4 ] [ 5 ] [ 6 ]  Indeed, the evidence from these studies suggests that between 10% and 20% of the population over age 70 have clonal hematopoiesis. In the U.S. alone, this means that, at the low end, some 2,975,000 seniors over 70 years of age are living with this condition. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_628", "text": "The other main common finding is that there are many different mutations involved in clonal hematopoiesis. Many of these fall into the categories of epigenetic regulators ( DNMT3a ,  TET2 , and  ASXL1 ), signaling proteins ( JAK2 ),  spliceosome  components ( SF3B1  and  SRSF2 ), or members of the DNA damage response ( TP53  and  PPM1D ). [ 4 ] [ 5 ] [ 6 ]  Many people identified as having clonal hematopoiesis have a mutation in a single gene, though a significant number have mutations in two or more genes. [ 4 ] [ 5 ] [ 6 ]  The number and variety of observed mutations suggests that these mutations may contribute to clonal hematopoiesis by several distinct mechanisms, discussed in more detail below.  While  DNMT3A  is the most prevalent driver mutation,  TET2  and splicing gene mutations are more prevalent in those over 75 years old. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_629", "text": "There is also limited evidence suggesting clonal hematopoiesis may be ubiquitous in healthy adults, albeit at extremely low levels (less than 0.1% of peripheral blood cells). A study employing the ultra-sensitive  digital droplet PCR  method found that 95% of studied individuals (19 out of 20) between the ages of 50 and 70 had at least low-level clonal hematopoiesis. [ 28 ]  This finding does not necessarily conflict with earlier reports that clonal hematopoiesis is not ubiquitous in this age bracket, as these previous studies' experimental designs compels the use of a higher threshold to identify legitimate clonal hematopoiesis. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_630", "text": "Ongoing studies are examining what genetic and epidemiological factors may influence the acquisition of mutations in clonal hematopoiesis.  Once mutated, the HSCs with a relative fitness advantage give rise to clones capable of expansion, in a type of Darwinian selection. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_631", "text": "Clonal hematopoiesis is thought to originate with the hematopoietic stem cells that make blood. An adult human has approximately 10,000 to 20,000 HSCs. [ 29 ]  The fact that these cells are maintained for life and each HSC may acquire about one mutation in a protein-coding  exon  each decade [ 30 ]  means that an elderly individual will have a certain amount of genetic mosaicism, or a variety of cells with different unique mutations, within their HSC population. However, this does not lead to clonal hematopoiesis in all cases. It is only when the genetic mutation confers a selective advantage on its host or there is another favorable stem cell dynamic that there is a clonal expansion."}
{"_id": "WikiPedia_Hematology$$$corpus_632", "text": "There are several general mechanisms by which a mutation could provide such an advantage and it is likely that the mutations found in clonal hematopoiesis act through different pathways. First, a mutation could provide a growth advantage, causing HSCs to divide more rapidly and contribute a larger proportion of the mature blood cells. This may be the case for mutations in genes related to signaling, such as that which causes the activating V617F substitution in the JAK2 signaling protein. Mutations in the DNA damage response genes would appear more likely to act via a second mechanism: allowing for HSC survival and proliferation under normally lethal cytotoxic stress. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_633", "text": "Other mechanisms are more likely to be associated with the disruption of epigenetic regulators, which comprises 80% of observed mutations in clonal hematopoiesis. A third potential mechanism of action is that the mutation makes the HSC-derived progenitor cells less able to differentiate into mature blood cells. This would allow these cells to continue to divide even after they would have normally stopped, since progenitor cells may divide whereas normal mature blood cells cannot. A fourth possibility is that the mutation makes the progenitor cells and cells derived from them more like stem cells in their ability to keep dividing. The previous two possibilities are very similar in terms of physiologic outcome and mainly differ on what is happening at the DNA level: whether differentiation genes are suppressed or a stem cell program is upregulated. A final possibility is that a gradient of epigenetic states is created in the HSC and progenitor cells and the cells with the most favorable epigenetics are able to grow out faster than unmutated cells. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_634", "text": "An expansion of blood cells from a single source does not necessarily require a mutation to act as the driving force. A large proportion of the population who exhibit clonal hematopoiesis have no identifiable mutations in known candidate driver genes. [ 4 ] [ 8 ]  One possible explanation is that among a naturally-occurring spectrum of inheritable epigenetic states, there are those which augment the self-renewal or proliferation of a stem cell and its progeny. [ 8 ]  Another explanation is that a process of \"neutral drift\" [ 31 ]  causes the predominance of a clonal stem cell population over time. In this scenario, all stem cells have an equal proliferative potential but some of them die out in a stochastic manner leading some of the remaining cells to proliferate to replace them. [ 8 ] [ 32 ]  This can be equated to a game of chance where all players start with the same odds of winning. As the game is played, winners and losers will arise despite the equal starting positions. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_635", "text": "Clonal hematopoiesis by itself is not considered to be a hematologic cancer; nevertheless, evidence is mounting that this condition may adversely affect human health. It has been proposed to label the group of individuals who have clonal hematopoiesis defined by a mutation in a malignancy-associated gene but without evidence of disease (such as  cytopenia ,  dysplasia  or immature \"blast\" cells in the bone marrow) as having  Clonal Hematopoiesis of Indeterminate Potential (CHIP) . [ 1 ] [ 3 ] [ 33 ]  A clonal involvement (sometimes referred to simply as the size of a \"clone\") of 2% of the blood has been tentatively proposed as a cutoff, though there is discussion that a lower floor that is more inclusive could also be appropriate. [ 1 ] [ 3 ] [ 28 ] [ 34 ]  This cutoff may ultimately depend on whether clones must reach a certain size before influencing health. The level at which a clone begins to have a potential clinical impact is an open question, though there is already data to suggest larger clones have a larger effect on health. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_636", "text": "The presence of clonal hematopoiesis/CHIP has been shown to increase blood cancer risk and is correlated with an increased risk of mortality overall. [ 4 ] [ 5 ] [ 8 ]  This is true both of clonal hematopoiesis with known candidate drivers as well as in cases without such drivers. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_637", "text": "One area of health that CHIP has been definitively shown to influence is the risk of progression to blood cancer. In a given year, a tiny fraction of the general population will develop a hematologic cancer such as  myelodysplastic syndrome (MDS)  or AML; it is estimated that just 3 to 4 people per 100,000 will get MDS in a given year, [ 35 ]  and 4 people per 100,000 will develop AML. [ 36 ]  With CHIP, the risk of acquiring a hematologic malignancy like MDS or AML is increased more than 10-fold. [ 4 ] [ 5 ]  Despite this increased risk, people with CHIP are still at low overall risk for developing a blood cancer, with only about 0.5-1.0% transformation per year. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_638", "text": "The risk of transformation to myeloid malignancy depends on the specific mutation and the size of the clone. Single  DNMT3A  mutations have the lowest risk of progression, while splicing factor genes,  JAK2 ,  TP53 ,  IDH1 ,  IDH2 ,  FLT3 , and  RUNX1  have the highest risk. The clonal hematopoiesis risk score (CHRS) can be used to estimate the risk of progression to myeloid malignancy. CHRS predicts high, intermediate, or low risk based on the presence or absence of mutations in high-risk genes, the clone size, number of different mutations, findings of  macrocytosis  (MCV \u2265100 fL),  anisocytosis  (RDW \u2265 15%), cytopenias ( anemia ,  neutropenia , or  thrombocytopenia ) and age \u2265 65 years. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_639", "text": "A second area of health that may be affected by CHIP is the risk for  heart attack  and  stroke . A strong association between CHIP and heart attack/ischemic stroke has been identified in one human genetic dataset, where CHIP was a stronger predictor of heart attack/stroke than if a patient was a smoker, had hypertension, had high cholesterol, or was overweight. In this study, which shows correlation but not causation, people with CHIP were 2.3 times more likely to have a heart attack, or 4.4 times as likely if the variant allele frequency (VAF, a measure of clone size) [ 38 ]  in their blood was greater than 0.10, than matched controls without CHIP. [ 5 ]  It has also been found that there is an increased risk of cardiovascular mortality in patients who exhibit CHIP and receive self-derived stem cell transplantation. [ 10 ]  In addition to heart attack and stroke, human studies further suggest an association of CHIP with  heart failure  and cardiac  arrhythmias . [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_640", "text": "The idea of CHIP having a causal role in human heart attacks/strokes has been given support by a 2017 study that showed impairment of the  Tet2  CHIP gene in mice causally led to accelerated atherosclerosis, [ 41 ]  and this finding in mice has been independently validated. [ 11 ]  The possibility of somatic mutations in the blood contributing not only to cancer risk but also to heart attack and stroke has generated much discussion in top-level scientific publications [ 42 ] [ 43 ]  and a large multi-cohort study published in 2017 appears to confirm the causal link between CHIP and cardiovascular disease in humans. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_641", "text": "In addition to its effects on those who would otherwise be considered healthy, CHIP may have implications in certain disease contexts. It has been shown that patients with CHIP who receive  autologous stem cell transplantation (ASCT)  as part of their treatment for  lymphoma  have worse outcomes than patients without CHIP. The poorer prognosis for these patients is due to both an increase in subsequent therapy-related myeloid neoplasms and increased risk for cardiovascular mortality. [ 10 ]   Clonal expansion may be related to  inflammaging , the low-level systemic inflammation implicated in age-related chronic illnesses. [ 44 ]  Aging and persistent inflammation both exhaust normal  hematopoietic stem cells  by requiring increased proliferation to replenish immune cells. [ 45 ]  CHIP has been documented in people with HIV infection [ 46 ]  and autoimmune disease. [ 47 ]   Interferons ,  Interleukin-6 ,  TNF-alpha  and the  TGF-beta  pathway are all thought to play a role in  inflammaging  as it relates to hematologic malignancies. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_642", "text": "Inherited  bone marrow failure  syndromes carry a risk of myeloid malignancy, particularly when there are germ line mutations in  CEBPA ,  DDX41 ,  GATA2 ,  RUNX1 , or SAMD9/9L.  Examples include ribosomopathies such as  Schwachman-Diamond syndrome , in which mutations in  EIF6  may lead to aberrant  p53  activation;  Severe Congenital Neutropenia , in which  CSF3R  mutation may lead to myeloid hyperproliferation; telomeropathies such as  dyskeratosis congenita  with acquired mutations in the  TERT  promoter, and  Fanconi anemia . [ 49 ]  Inherited  DNMT3A  mutations cause Tatton-Brown-Rahman syndrome, characterized by larger body habitus and intellectual disability. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_643", "text": "Inherited  bone marrow failure  syndromes represent a kind of premature aging of the bone marrow.  In patients with these syndromes and in elderly patients, mutations associated with Clonal Hematopoiesis may arise as an adaptive response to a progressively deteriorating hematopoietic niche, i.e., a depleting pool of  Hematopoietic stem cells .  The mutated stem cells then acquire a self-renewal advantage. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_644", "text": "There are currently no therapies for slowing or targeting CHIP mutations. Together with the fact that progression from CHIP to outright hematologic malignancy remains infrequent, medical experts have argued against preemptive screening for CHIP but suggest routine follow-up for incidental CHIP findings. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_645", "text": "Clonal hematopoiesis is sometimes compared to the unrelated blood disorders of  monoclonal gammopathy of undetermined significance (MGUS)  and  monoclonal B-cell lymphocytosis (MBL)  to which it bears similarities in its apparent priming for more advanced hematologic disease combined with a lack of symptoms and overall low risk of progression. [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_646", "text": "The acquisition of additional mutations can cause CHIP to transform into the related blood disorders  MDS  and  AML . [ 3 ] [ 33 ]  Clonal Cytopenias of Undetermined Significance (CCUS) is defined [ 51 ]  as:"}
{"_id": "WikiPedia_Hematology$$$corpus_647", "text": "CCUS has a much higher risk of progression to MDS/AML than CHIP.  The most frequent CCUS mutations are in epigenetic regulators ( DNMT3A ,  TET2 , and  ASXL1 ), RNA splicing factors ( SF3B1 , SRSF2),  TP53 , and  PPM1D . [ 48 ]  It is likely that a mutational progression occurs, such that splicing factors are mutated early in the development of MDS, while mutations in signaling pathways ( FLT3 ,  PTPN11 , and  RAS ) and transcription factors ( CEBPA  and  RUNX1 ) occur as a late event. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_648", "text": "Cold sensitive antibodies  ( CSA ) are  antibodies  sensitive to cold temperature. Some cold sensitive antibodies are pathological and can lead to  blood disorder . These pathological cold sensitive antibodies include  cold agglutinins ,  Donath\u2013Landsteiner antibodies , and  cryoglobulins  which are the culprits of  cold agglutinin disease ,  paroxysmal cold hemoglobinuria  in the process of  Donath\u2013Landsteiner hemolytic anemia , and  vasculitis , respectively."}
{"_id": "WikiPedia_Hematology$$$corpus_649", "text": "Cold agglutinins are  antibodies , typically  immunoglobulin M  ( IgM ), that are acquainted with and then binding the antigens on red blood cells, typically  antigens \"I\" or \"i\"  on the RBC surface, [ 1 ]  in the environment in which the temperatures are lower than normal core body temperature and, thus, ends up leading to  agglutinations of the red blood cells and hemolysis reaction occurring outside the vessels  (extra-vessels), resulting in anemia without  hemoglobinuria  in ordinary cases. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_650", "text": "Cold agglutinins can cause two pathological conditions, that are, primary cold agglutinin disease (CAD) [ 3 ]  and secondary cold agglutinin syndrome (CAS), [ 2 ]  both of which are sole two  subtypes of  cold agglutinin disease ."}
{"_id": "WikiPedia_Hematology$$$corpus_651", "text": "Primary cold agglutinin disease is idiopathic, meaning the phenomenons of agglutinations of the red blood cells and hemolysis reaction occurring outside the vessels are absent from any underlying cause. [ 3 ]  Nevertheless, what is known is, those with idiopathic cold agglutinin disease are susceptible to having or developing mild  clonal bone marrow disorder . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_652", "text": "Secondary cold agglutinin syndrome refers to cold agglutinin disease that is identified to be caused by  viral infection ,  autoimmune disorder ,  lymphoid malignancy , or any other underlying disease. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_653", "text": "Cold agglutinins (CA) are autoantibodies that agglutinate RBCs with a temperature optimum of 3-4\u00a0\u00b0C but may also act in a warmer environment, depending on the  thermal amplitude  of the CA. If the thermal amplitude exceeds 28\u201330\u00a0\u00b0C, the CA will be pathogenic. Low- affinity  CA also occurs in many healthy individuals; these nonpathogenic CA are  polyclonal , have low thermal amplitude, and are present in low  titers , not higher than 256 and usually lower than 64. More than 90% of pathogenic CA are of the IgM class and these IgM macromolecules can be  pentameric  or  hexameric . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_654", "text": "Donath\u2013Landsteiner antibodies share similarities with cold agglutinin disease in recognition and connection of the antigens on the red blood cells' surface in the presence of relatively lower temperatures compared to core body temperature. Yet, the place where the hemolysis taking place differentiates between  D-L  antibodies and cold agglutinin. [ 6 ] [ 7 ] [ 8 ]  D-L antibodies rather fix  complement system  which result in  hemolysis in vessels  (intra-vessels).  Blood vessels  are pathways carrying living-required elements to reach everywhere inside the body through circulation. This explains why the clinical manifestations of hemolysis caused by D-L antibodies are in line with representations of  hemoglobinemia  and  hemoglobinuria . D-L antibodies, typically  IgG , are characterized by targeting against red blood cells' on-surface  antigens called \"P\" . [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_655", "text": "The  pathophysiology  of  Donath\u2013Landsteiner hemolytic anemia  has been entitled as  paroxysmal cold hemoglobinuria . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_656", "text": "Cryoglobulins are abnormal antibodies that only dissolve/disappear at temperature higher than 37\u00a0\u00b0C (99\u00a0\u00b0F) and form solid or gel-like immune complexes in presence of the environment under 37\u00a0\u00b0C (99\u00a0\u00b0F), [ 11 ] [ 12 ]  which can block blood vessels and cause a variety of health problems [ 12 ]  including inflammation and organ damage. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_657", "text": "Many people affected by cryoglobulins will not experience any unusual signs or symptoms. When present, symptoms vary but may include  breathing problems ;  fatigue ;  glomerulonephritis ;  joint pain  or  muscle pain ;  purpura ;  Raynaud's phenomenon ;  skin death ; and/or  skin ulcers . In some cases, the exact underlying cause is unknown; however, cryoglobulinemia can be associated with a variety of conditions including certain types of infection; chronic inflammatory diseases (such as autoimmune disease); and/or cancers of the blood or immune system. Treatment varies based on the severity of the condition, the symptoms present in each person and the underlying cause. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_658", "text": "At least 90% of cases having cryoglobulins in body,  hepatitis C  is to blame, [ 11 ] [ 13 ]  reflecting the importance of preclusion of hepatitis C. [ 11 ] [ 13 ]  The presence of cryoglobulins in body satisfies the criterion of the diagnosis of  cryoglobulinemia , a disease that  inflame the blood vessels  and organs like kidney, nerves, joints, lungs and skin. [ 11 ]  Normally, no cryoglobulins should be found in the body. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_659", "text": "Cryoglobulins more than often do not interact with red blood cells, unless it combines the features of cold agglutinin with cryoglobulins, although the chance is deemed rare.  Therefore, cryoglobulins don't produce hemolysis effect, however its serious  complications  such as  systemic inflammatory  or neoplastic disorders can in turn lead to anemia. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_660", "text": "Although there is some overlap of symptoms, cryoglobulinemia and cold agglutinin disease differ in the process by which blood vessels become blocked. [ 12 ]  In cryoglobulinemia, antibodies accumulate and block blood vessels. [ 12 ] [ 15 ]  In cold agglutinin disease, antibodies (different from those in cryoglobulinemia) attack and kill red blood cells, which then accumulate and  block blood vessels . [ 12 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_661", "text": "Common features among the three conditions above include:"}
{"_id": "WikiPedia_Hematology$$$corpus_662", "text": "Complement activation  plays a definitive but limited role in warm-antibody AIHA (w-AIHA), whereas primary cold agglutinin disease (CAD), secondary cold agglutinin syndrome (CAS), and paroxysmal cold hemoglobinuria (PCH) are entirely complement-dependent disorders. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_663", "text": "Hemolysis induced by cold agglutinin disease taking place  outside  the vessels while which of Donath\u2013Landsteiner antibodies is taking place  inside  the vessels. [ 10 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_664", "text": "Complement component 4  ( C4 ), in humans, is a protein involved in the intricate  complement system , originating from the  human leukocyte antigen  (HLA) system. It serves a number of critical functions in immunity, tolerance, and autoimmunity with the other numerous components. Furthermore, it is a crucial factor in connecting the recognition pathways of the overall system instigated by antibody-antigen (Ab-Ag) complexes to the other effector proteins of the innate immune response. For example, the severity of a dysfunctional  complement system  can lead to fatal diseases and infections. Complex variations of it can also lead to  schizophrenia . [ 1 ]  The C4 protein was thought to derive from a simple two-locus allelic model, which however has been replaced by a much more sophisticated multimodular  RCCX  gene complex model which contain long and short forms of the  C4A  or  C4B  genes usually in tandem  RCCX  cassettes with copy number variation, that somewhat parallels variation in the levels of their respective proteins within a population along with  CYP21  in some cases depending on the number of cassettes and whether it contains the functional gene instead of pseudogenes or fragments. [ 2 ]  Originally defined in the context of the Chido/Rodgers blood group system, the C4A-C4B genetic model is under investigation for its possible role in  schizophrenia  risk and development."}
{"_id": "WikiPedia_Hematology$$$corpus_665", "text": "One of the earlier genetic studies on the C4 protein identified two different groups, found within a human serum, called the Chido/Rogers (Ch/Rg) blood groups. O\u2019Neill et al. have demonstrated that two different C4 loci express the different Ch/Rg antigens on the membranes of erythrocytes. [ 3 ]  More specifically, the two proteins, Ch and Rg, function together as a medium for interaction between the Ab-Ag complex and other complement components. [ 4 ]  Moreover, the two loci are linked to the HLA, or the human analog of the  major histocompatibility complex  (MHC) on the short arm of chromosome 6, whereas previously they were believed to have been expressed by two codominant alleles at a single locus. [ 3 ] [ 5 ]  In gel electrophoresis studies, O\u2019Neill et al. have identified two genetic variants: F, signifying the presence (F+) or absence (f0/ f0) of four fast moving bands, and S, signifying the presence (S+) or absence (s0/ s0) of four slow moving bands. [ 3 ]  The homogeneity or heterogeneity of the two loci, with the addition of these null (f0, s0) genes, allow for duplication/non-duplication of the C4 loci. [ 6 ]  Therefore, having separate loci for C4, C4F and C4S (later identified as C4A or C4B, respectively), possibly account for producing multiple allelic forms, leading to the great size and  copy number variation . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_666", "text": "Two important contributors, Carroll and Porter, in their study of cloning the human C4 gene showed that all six of their clones contained the same C4 gene. [ 7 ]  The C4 protein consists of 3 subunits (\u03b1, \u03b2, and \u03b3) having molecular weights (MWs) of ~95,000, 78,000, and 31,000, respectively and they are all joined by interchain disulfide bridges. [ 7 ] [ 8 ] [ 9 ] [ 10 ]  In a study by Roos et al., the \u03b1-chains between the C4A and C4B were found to be slightly different (MW of ~96,000 and 94,000, respectively), proving that there is actually a structural difference between the two variants. [ 9 ]  Moreover, they implicated that a lack of C4 activity could be attributed to the structural differences between the \u03b1-chains. [ 9 ]  Nevertheless, Carroll and Porter demonstrated that there is a 1,500-bp region that acts as an  intron  in the genomic sequence, which they believed to be the known C4d region, a byproduct of C4 activity. [ 7 ]  Carroll et al. later published work that characterized the structure and organization of the C4 genes, which are situated in the HLA class III region and linked with C2 and factor B on the chromosome. [ 11 ]  Through experiments involving restriction mapping, nucleotide sequence analysis, and hybridization with C4A and C4B, they found that the genes are actually fairly similar though they have their differences. [ 11 ]  For example, single nucleotide polymorphisms were detected, which allowed them to be class differences between C4A and C4B. [ 11 ]  Furthermore, class and allelic differences would affect the performance of the C4 proteins with the immune complex. [ 11 ]  Finally, by overlapping cDNA cloned fragments, they were able to determine that the C4 loci, an estimated 16 kilobase (kb) long, are spaced by 10 kb and aligned 30 kb from the factor B locus. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_667", "text": "In the same year, studies relatedly identified a 98 kb region of the chromosome the four class III genes (that express C4A, C4B, C2, and factor B) are closely linked, which does not allow for cross-overs to occur. [ 10 ]  Using protein variants visualized by electrophoresis, the four structural genes were located between HLA-B and HLA-D. [ 10 ]  More specifically, they verified the proposed molecular map in which the gene order went from  factor B , C4B, C4A, and C2 with C2 nearest to HLA-B. [ 10 ]  In another study, Law et al. then continued to delve deeper, this time comparing the properties of both the C4A and C4B, both of which are substantial players in the human immunity system. [ 12 ]  Through methods that include incubation, different pH levels, and treatment with methylamine, they had biochemically illustrated the different reactivities of the C4 genes. [ 12 ]  More specifically, the C4B has shown to react much more efficiently and effectively despite the 7 kb difference between C4A and C4B. In whole serum, C4B alleles performed at a rate several fold greater during hemolytic activity, in direct comparison with C4A alleles. [ 12 ]  Biochemically, they also found that C4A reacted more steadily with an antibody\u2019s amino acid side chains and antigens that are amino groups, while C4B reacted better with carbohydrate hydroxyl groups. [ 12 ]  Thus, upon analysis of the varying reactivities, they proposed that the exceptional polymorphism of C4 genes may bring about some biological advantages (i.e. complement activation with a more extensive range of Ab-Ag complexes formed upon infections). [ 12 ]  Though at this point in time, the genomic and derived amino acid sequence of either C4A or C4B had yet to be determined. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_668", "text": "The early studies vastly expanded the knowledge of the C4 complex, laying down the foundations that paved the way to discovering the gene and protein structures. C. Yu successfully determined the complete sequence of the human complement component C4A gene. [ 4 ]  In the findings, the whole genome was found to have of 41 exons, with a total of 1744 residues (despite avoiding the sequence of a large Intron 9). [ 4 ]  The C4 protein is synthesized into a single chain precursor, which then undergoes proteolytic cleavage into three chains (in order of how they are chained, \u03b2-\u03b1-\u03b3). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_669", "text": "The \u03b2-chain consists of 656 residues, coded by exons 1-16. [ 4 ]  The most prominent aspect of the \u03b2-chain is the presence of a large intron, ranging from six to seven kilobases in size. [ 4 ]  It is present in the first locus (coding for C4A) for all C4 genes and in the second locus (coding for C4B) only in a few C4 genes. [ 4 ]  The \u03b1-chain consists of residues 661-1428, encoding exons 16-33. [ 4 ]  Within this chain, two cleavage sites marked by exons 23 and 30 produces the C4d fragment (where the thioester, Ch/Rg antigens, and isotypic residues are located); moreover, most of the polymorphic sites cluster in this region. [ 4 ]  The \u03b3-chain consists of 291 residues, encoding exons 33-41. [ 4 ]  Unfortunately, no specific function has been attributed to the \u03b3-chain. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_670", "text": "The study completed by Vaishnaw et al. sought to identify the key region and factors related to the efforts of gene expression of the C4 gene. [ 13 ]  Their research concluded with the fact that the Sp1 binding site (positioned at -59 to -49) plays an important role in accurately starting basal transcription of C4. [ 13 ]  Utilization of electromobility shift assays and DNase I footprint analyses demonstrated specific DNA-protein correlations of the C4 promoter at the nuclear factor 1, two E box (-98 to -93 and -78 to -73), and Sp1 binding domains. [ 13 ]  These findings were later added to in another extensive study, that found a third E box site. [ 14 ]  In addition, the same findings postulated that two physical entities within the gene sequence could have a role in the expression levels of human C4A and C4B, which include the both presence of the endogenous retrovirus that can have positive or negative regulatory influences affecting C4 transcription and the varying genetic environment (dependent on which genetic modular component is present) past position -1524. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_671", "text": "To provide more context, in the latter study, the previously noted bimodular structure (C4A-C4B) has been updated to a quadrimodular structure of one to four discrete segments, containing one or more RP-C4-CYP21-TNX ( RCCX ) modules. [ 2 ]  The size of either C4A or C4B gene can be 21 kb (long, L) or 14.6 kb (short, S). Also, the long C4 gene uniquely contains a retrovirus HERV-K(C4) in its intron 9 that imposes  transcription  of an extra 6.36 kb, hence the \u201clonger\u201d string of gene. [ 2 ] [ 14 ]  Thus, C4 genes have a complex pattern of variation in gene size, copy number, and polymorphisms. [ 2 ] [ 14 ]  Examples of these mono-, bi-, tri-, and quadri-modular structures include: L or S (monomodular with one long or short C4 gene), LL or LS or SS (bimodular with a combination of homozygous or heterozygous L or S genes), LLL or LLS or LSS (trimodular RCCX with three L or S C4 genes), LLLL (quadrimodular structure with four L or S C4 genes). [ 14 ]  Not all the structural groups have the same percentage of appearance, possibly even further differences within separate ethnic groups. For example, the Caucasian population studied showed 69% bimodular configuration (C4A-C4B, C4A-C4A, or C4B-C4B) and 31% trimodular configuration (equally split between LLL as C4A-C4A-C4B or LSS as C4A-C4B-C4B). [ 14 ]  Regarding C4 protein sequence polymorphism, a total of 24 polymorphic residues were found. Among them, the \u03b2-chain expressed of five, as the \u03b1-chain and \u03b3-chain produced 18 and one, respectively. These polymorphisms can be further categorized into groups: 1) four isotypic residues at specific positions, 2) Ch/Rg antigenic determinants at specific positions, 3) C5 binding sites, 4) private allelic residues. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_672", "text": "Additionally, the same study identified the expression of human complement C4 transcripts in multiple tissues. The results of a Northern blot analysis, using a C4d probe and RD probe as positive control, showed that the liver contains the majority of transcripts throughout the body. [ 14 ]  Even so, moderate quantities were expressed in adrenal cortices/medulla, thyroid, and kidney. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_673", "text": "As noted, C4 (mixture of C4A and C4B) participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is \"triggered spontaneously,\" while the classical and lectin pathways are elicited in response to the recognition of particular microbes. [ 16 ]  All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a  lytic pathway  and formation of a  macromolecular assembly  of multiple proteins, termed the membrane-attack complex (MAC), which serves as a pore in the membrane of the targeted pathogen, leading to invading cell disruption and eventual lysis. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_674", "text": "In the  classical pathway,  the complement component\u2014hereafter abbreviated by the \"C\" preceding the protein number\u2014 termed  C1s,  a  serine protease , is activated by upstream steps of the pathway, resulting in its cleavage of the native, parent ~200  kilodalton  (kDa) C4 protein\u2014composed of three chains. [ 16 ] :\u200a288\u200a  The C4 is cleaved by the protease into two parts, a peptide C4a (small at ~9 kDa, and  anaphylotoxic ), and the higher molecular weight protein C4b, at about 190 kDa. [ 17 ]  The cleavage of the C4 results in C4b bearing a  thioester  functional group [-S-C(O)-]: work in the 1980s on C3, and then on C4, indicated the presence, within the parent C3 and C4 structures, of a unique protein modification, a 15-atom (15-membered)  thionolactone  ring serving to connect the thiol side chain of the amino acid cysteine (Cys) in a -Cys-Gly-Glu-Glx- sequence with a side chain  acyl group  of what began as a  glutamine  side chain (Glx, here) that resided three amino acid residues downstream (where the remaining atoms of the 15 were  backbone  and side chain atoms); [ 17 ] [ 18 ]  upon cleavage, this unique  thionolactone  ring structure becomes exposed at the surface of the new C4b protein. [ 16 ] [ 17 ] [ 18 ]  Because of proximity to the microbial surface, some portion of the released C4b proteins, with this reactive thionolactone, react with  nucleophilic  amino acid side chains and other groups on the foreign microbe's cell surface, resulting in  covalent  attachment of the slightly modified C4b protein to the cell surface, via the original Glx residue of C4. [ 16 ] [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_675", "text": "C4b has further functions. It interacts with protein C2; the same protease invoked earlier, C1s, then cleaves C2 into two parts, termed C2a and C2b, with C2b being released, and C2a remaining in association with C4b; the C4b-C2a complex of the two proteins then exhibits a further system-associated protease activity toward protein C3 (cleaving it), with subsequent release of both proteins, C4b and C2a, from their complex (whereupon C4b can bind another protein C2, and conduct these steps again). [ 16 ]  Because C4b is regenerated, and a cycle is created, the C4b-C2a complex with protease activity has been termed the  C3 convertase. [ 16 ]  Protein 4b can be further cleaved into 4c and 4d. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_676", "text": "Although other diseases (i.e.  systemic lupus erythematosus ) have been implicated, the C4 gene is also being investigated for the role it may play in schizophrenia risk and development. In the Wu et al. study, they utilized the real-time polymerase chain reaction (rt-PCR) as an assay to determine the copy number variance (CNV) or genetic diversity of C4. [ 20 ]  Accordingly, with these results, future prognoses, flares, and remissions will become more feasible to determine. The results basically show copy number variants as a mechanism to effect genetic diversity. As discussed before, the different phenotypes allowed for by the varying genetic variety of complement C4 include a wide range of plasma or serum C4 proteins among two isotypes\u2014C4A and C4B\u2014with multiple protein allotypes that can have unique physiological functions. [ 20 ]  CNVs are sources of inherent genetic diversity and are engaged in gene-environment interaction. [ 20 ]  CNVs (and associated polymorphisms) play a role in filling in the gap towards understanding the genetic basis of quantitative traits and the different susceptibilities to autoimmune and neurobiological diseases. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_677", "text": "Substantial data from all over the world has been collected and analyzed to determine that schizophrenia, indeed, has a strong genetic relationship with a region in the MHC locus on chromosome arm 6. [ 21 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_678", "text": "Data and information collected internationally can shed light onto the mysteries of  schizophrenia . Sekar et al. analyzed  single nucleotide polymorphisms  (SNP) of 40 cohorts in 22 countries, in total adding up to nearly 29,000 cases. [ 1 ]  They found out two features: 1) A great number of SNPs reaching only 2Mb across the end, 2) peak of association centered at C4, predicting that C4A expression levels is most strongly correlated with schizophrenia. [ 1 ]  In addition, they have discovered a mechanism by which schizophrenia could arise from the genetic predisposition of the human complement C4. [ 1 ]  As shown in Figure 1, four common  structural variations  discovered in  genome-wide association studies  (GWAS) studies have pointed to the high turnout of schizophrenia. [ 1 ]  Possibly, the higher levels of expression of C4 protein due to pattern of variants of the C4 gene, allows for the unwanted increase in  synaptic pruning  (an effect produced by the effector proteins of the  complement system  in which the C4 partakes)."}
{"_id": "WikiPedia_Hematology$$$corpus_679", "text": "Congenital rubella syndrome  (CRS) occurs when a human  fetus  is infected with the  rubella virus  (German measles) via maternal-fetal transmission and develops  birth defects . [ 1 ]  The most common congenital defects affect the ophthalmologic, cardiac, auditory, and neurologic systems. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_680", "text": "Rubella infection in pregnancy can result in various outcomes ranging from asymptomatic infection to  congenital defects  to  miscarriage  and fetal death. [ 3 ] [ 4 ]  If infection occurs 0\u201311 weeks after conception, the infant has a 90% risk of being affected. [ 1 ]  If the infection occurs 12\u201320 weeks after conception, the risk is 20%. Infants are not generally affected if rubella is contracted during the third trimester. [ 3 ]  Diagnosis of congenital rubella syndrome is made through a series of clinical and laboratory findings and management is based on the infant's clinical presentation. Maintaining  rubella  outbreak control via vaccination is essential in preventing congenital rubella infection and congenital rubella syndrome. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_681", "text": "Congenital rubella syndrome was discovered in 1941 by Australian  Norman McAlister Gregg . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_682", "text": "The classic triad for congenital rubella syndrome is: [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_683", "text": "Other manifestations of CRS may include:"}
{"_id": "WikiPedia_Hematology$$$corpus_684", "text": "Children who have been exposed to rubella in the womb should also be watched closely as they age for any indication of:"}
{"_id": "WikiPedia_Hematology$$$corpus_685", "text": "Diagnosis of congenital rubella syndrome is made based on clinical findings and laboratory criteria. [ 3 ]  Laboratory criteria includes at least one of the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_686", "text": "Clinical definition is characterized by findings in the following categories:"}
{"_id": "WikiPedia_Hematology$$$corpus_687", "text": "A patient is classified into the following cases depending on their clinical and laboratory findings: [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_688", "text": "Vaccinating the majority of the population is effective at preventing congenital rubella syndrome. [ 25 ]  With the introduction of the rubella vaccine in 1969, the number of cases of rubella in the United States has decreased 99%, from 57,686 cases in 1969 to 271 cases in 1999. [ 3 ]  For women who plan to become pregnant, the  MMR (measles mumps, rubella) vaccination  is highly recommended, at least 28 days prior to conception. [ 17 ]  The vaccine should not be given to women who are already pregnant as it contains live viral particles. [ 17 ]  Other preventative actions can include the screening and vaccinations of high-risk personnel, such as medical and child care professions. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_689", "text": "Infants with birth defects suspected to be caused by congenital rubella infection should be investigated thoroughly. Confirmed cases should be reported to the local or state health department to assess control of the virus and isolation of the infant should be maintained. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_690", "text": "Infants with known rubella exposure during pregnancy or those with a confirmed or suspected infection should receive close follow-up and supportive care. There are no medications or antivirals that will shorten the clinical course of the virus. [ 4 ]  Only those with  immunity  to rubella should have contact with infected infants, as they can shed viral particles in their respiratory secretions though 1 year of age (unless they test with repeated negative viral cultures at age 3 months). [ 3 ]  Many infants can be born with multiple birth defects that require multidisciplinary management and interventions based on clinical manifestations. Often these infants will require extended period or life-long follow up with medical specialists. Early diagnosis of congenital rubella syndrome is important for planning future medical care and educational placement. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_691", "text": "Many infants with CRS may be born with  sensorineural deafness  and thus should undergo a newborn hearing evaluation. Hearing loss may not be apparent at birth and thus requires close auditory follow up. Infants with confirmed hearing impairment may require hearing aids and may benefit from an early intervention program. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_692", "text": "Eye abnormalities including cataracts, infantile glaucoma and retinopathy are common in infants born with CRS. [ 27 ]  Infants should undergo eye examinations after birth and during early childhood. Those with congenital eye defects require care from a pediatric ophthalmologist for specialized care and follow up. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_693", "text": "Congenital cardiac anomalies including  pulmonary artery stenosis  and  patent ductus arteriosus  can be seen in infants with CRS. Infants should undergo cardiac evaluation soon after birth and those with confirmed cardiac lesions will require specialized care with a pediatric cardiologist for any interventions and follow-up care. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_694", "text": "Critical green inclusions , also known as  green neutrophilic inclusions  and informally,  death crystals  or  crystals of death , [ 1 ] [ 2 ]  are amorphous blue-green  cytoplasmic inclusions  found in  neutrophils  and occasionally in  monocytes . They appear brightly coloured and refractile when stained with  Wright-Giemsa stain . These inclusions are most commonly found in critically ill patients, particularly those with  liver disease , and their presence on the  peripheral blood smear  is associated with a high short-term mortality rate. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_695", "text": "Critical green inclusions are a rare finding, and when found they are suggestive of a poor prognosis, hence the colloquial term  death crystals . A 2018 review found that 56% of patients died shortly after the inclusions were first identified (usually within two weeks). [ 5 ]  However, critical green inclusions are of limited utility for predicting mortality because they are usually found in severely ill patients whose poor prognosis is already evident for other reasons by the time the crystals are detected. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_696", "text": "The inclusions were once hypothesized to be bile products  phagocytized  during fulminant hepatic injury, due to the high incidence of critical green inclusions observed in cases of acute hypoxic and ischaemic  hepatitis . [ 7 ]  However, recent studies have highlighted that the inclusions stain positive for  Oil Red O  as opposed to bile stains, suggesting high lipid content. [ 8 ]  Additionally, some cases with critical green inclusions were not associated with notable hepatic injury. Currently, it is suggested that critical green inclusions are more likely to be phagocytized products of lysosomal degradation related to tissue injury. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_697", "text": "The composition of the inclusions is not well understood, but  transmission electron microscopy  has shown that they are rich in lipids and possibly related to  lipofuscin . Microscopic examination of liver tissue in patients with critical green inclusions has demonstrated prominent deposition of lipofuscin, suggesting that the white blood cell inclusions represent  phagocytosis  of this substance following severe injury to the liver. [ 3 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_698", "text": "Crizanlizumab , sold under the brand name  Adakveo  among others, is a  monoclonal antibody  medication that binds to  P-selectin . [ 3 ]  It is a medication used to reduce the frequency of  vaso-occlusive crisis  in people aged 16 years and older who have  sickle cell anemia . [ 3 ] [ 4 ] [ 6 ]  It is given by injection into a vein. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_699", "text": "The most common side effects include joint pain, nausea, back pain, fever and abdominal (belly) pain. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_700", "text": "Crizanlizumab was approved for medical use in the United States in November 2019. [ 6 ] [ 7 ] [ 8 ]  The EU's EMA withdrew authorization in May 2023 based on no significant effects from a phase 3 trial. [ 9 ]  The U.S.  Food and Drug Administration  (FDA) considers it to be a  first-in-class medication . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_701", "text": "Crizanlizumab is  indicated  for the prevention of recurrent vaso occlusive crises in sickle cell disease patients aged 16 years and older. [ 4 ]  It can be given as an add on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_702", "text": "Vaso-occlusive crisis is a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells (red cells are usually round and flexible, but sometimes many red cells in a person with sickle cell anemia will become rigid and crescent-shaped due to  polymerization  of hemoglobin). [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_703", "text": "P-selectin  molecules are present on the surface of activated platelets and vascular  endothelial cells  and have been linked to sickle cell vaso-occlusive crises. [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_704", "text": "The US  Food and Drug Administration  (FDA) approved crizanlizumab based on evidence from one clinical trial (Trial 1/NCT01895361) of 132 participants with sickle cell diseases who had a history of vaso-occlusive crisis. [ 8 ]  The trial was conducted at 60 sites in the United States, Brazil and Jamaica. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_705", "text": "The FDA granted the application for crizanlizumab  priority review ,  breakthrough therapy  designation, and  orphan drug  designation. [ 6 ]  The FDA granted approval of Adakveo to  Novartis . [ 6 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_706", "text": "The European Medicines Agency's human medicines committee (CHMP) has recommended the withdrawal of Adakveo (crizanlizumab), a medicine for preventing vaso-occlusive crises in patients with sickle cell disease, due to the lack of sufficient benefits outweighing the risks. [ 15 ]  The STAND phase III study showed that Adakveo does not effectively reduce the number of painful crises requiring healthcare visits or treatment at home compared to a placebo, and it exhibits a higher rate of severe side effects. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_707", "text": "Immune activation :  Dostarlimab \n Other:   Ibalizumab"}
{"_id": "WikiPedia_Hematology$$$corpus_708", "text": "This  drug  article relating to the  blood  and  blood forming organs  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_709", "text": "Cross-matching  or  crossmatching  is a test performed before a  blood transfusion  as part of  blood compatibility testing . Normally, this involves adding the recipient's  blood plasma  to a sample of the donor's  red blood cells . If the blood is incompatible, the  antibodies  in the recipient's plasma will bind to  antigens  on the donor red blood cells. This  antibody-antigen reaction  can be detected through visible  clumping  or  destruction  of the red blood cells, or by reaction with  anti-human globulin . Along with  blood typing  of the donor and recipient and  screening for unexpected blood group antibodies , cross-matching is one of a series of steps in pre-transfusion testing. In some circumstances, an  electronic cross-match  can be performed by comparing records of the recipient's  ABO  and  Rh blood type  against that of the donor sample. [ 1 ] :\u200a600\u22123\u200a  In emergencies, blood may be issued before cross-matching is complete. [ 2 ] :\u200a263\u200a  Cross-matching is also used to determine compatibility between a donor and recipient in solid  organ transplantation  including heart/lung transplation. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_710", "text": "Immediate-spin cross-matching (ISCM) is an abbreviated form of cross-matching that is faster, but less  sensitive ; its primary use is to detect a mismatch between ABO blood types. It is an immediate test that involves combining the patient's serum and donor's red blood cells at room temperature, then  centrifuging  the sample and observing for agglutination or hemolysis. A lack of agglutination or hemolysis indicates a negative test reaction, or compatible match. [ 1 ] :\u200a603\u200a  ISCM is not appropriate in all circumstances; if the recipient's antibody screen is positive, or if they have had a positive antibody screen in the past, a full crossmatch is performed instead. [ 2 ] :\u200a261"}
{"_id": "WikiPedia_Hematology$$$corpus_711", "text": "The AHG crossmatch is done by incubating the recipient serum/plasma with the donor's red blood cells and adding anti-human globulin. It is essentially an indirect  Coomb's test . It is also called \"full cross-matching\", \"IAT cross-matching\" and \"Coomb's cross-matching\". [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_712", "text": "Electronic cross-matching is a computer-assisted analysis using data, from the  donor  unit (where a donor's blood is tested prior to donation) and testing done on blood samples from the intended recipient. This includes  ABO / Rh  typing of the unit and of the recipient, and an antibody screen of the recipient. Electronic cross-matching can only be used if a patient has a negative antibody screen, which means that they do not have any active  red blood cell  atypical  antibodies , or they are below the detectable level of current testing methods. If all of the data entered is compatible, the computer will print a compatibility label stating that the unit is safe to transfuse."}
{"_id": "WikiPedia_Hematology$$$corpus_713", "text": "As the complete cross-matching process takes approximately 1 hour, it is not always used in emergencies."}
{"_id": "WikiPedia_Hematology$$$corpus_714", "text": "In the case of an emergency, a type-specific blood to which the recipient has no antibodies, can be requested. It is thought that this lifesaving measure is of more benefit than any risk of an antibody-mediated  transfusion reaction . This type of blood has less risk of a serious transfusion reaction because it is both ABO compatible and Rhesus (Rh)-compatible."}
{"_id": "WikiPedia_Hematology$$$corpus_715", "text": "Universal donor blood, which is both type O and Rh negative, can be given if the recipient's blood group is not known, as may happen in an emergency. It is the policy of some institutions to reserve the releasing of O\u2212 blood only for female patients of childbearing age. This serves two purposes. First, it preserves the lower stock of O\u2212 blood and secondly, this eliminates the risk of O\u2212 negative mothers forming anti-D (Rh) antibodies from exposure to O+ blood. Anti-D (Rh) can cross the placenta during pregnancy and attack an unborn child's RBCs if they are D (Rh) positive causing  haemolytic disease of the newborn ."}
{"_id": "WikiPedia_Hematology$$$corpus_716", "text": "In an emergency, blood grouping can be done easily and quickly in 2 or 3 minutes in the laboratory on glass slides with appropriate reagents, by trained technical staff. This method depends on the presence or absence of  agglutination  (clumping of red blood cells), which can usually be visualized directly. Presence of agglutination indicates incompatibility. Occasionally a light  microscope  may be needed. If laboratory services are not available, the bedside card method of blood grouping may be used, where a drop of the intended recipients blood is added to dried reagents on a prepared card. This method may not be as reliable as laboratory methods, which are preferable."}
{"_id": "WikiPedia_Hematology$$$corpus_717", "text": "Dabie bandavirus , also called  SFTS virus , is a  tick-borne  virus in the genus  Bandavirus  in the family  Phenuiviridae , order  Bunyavirales . [ 2 ]  The clinical condition it caused is known as  severe fever with thrombocytopenia syndrome  (SFTS). [ 2 ]  SFTS is an emerging infectious disease that was first described in northeast and central China 2009 and now has also been discovered in Japan, South Korea, Vietnam and Taiwan in 2015. SFTS has a fatality rate of 12% and as high as over 30% in some areas. The major clinical symptoms of SFTS are fever, vomiting, diarrhea, multiple organ failure, thrombocytopenia (low platelet count), leukopenia (low white blood cell count) and elevated liver enzyme levels. Another outbreak occurred in East China in the early half of 2020."}
{"_id": "WikiPedia_Hematology$$$corpus_718", "text": "In 2009, Xue-jie Yu and colleagues isolated the SFTS virus (SFTSV) from SFTS patients\u2019 blood. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_719", "text": "The sequence of the genome was published in 2011. [ 2 ]  There are three segments\u2014large (L), medium (M) and small (S). Five proteins have been identified\u2014an  RNA dependent RNA polymerase  (RdRp), a glycoprotein N (Gn), a glycoprotein C (Gc), a nuclear protein (NP) and a non structural protein (NSs). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_720", "text": "The L segment encodes the RNA polymerase with 2084 amino acid residues. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_721", "text": "The M segment encodes one  open reading frame  encoding 1073 amino acid precursors of glycoproteins (Gn and Gc). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_722", "text": "The S segment has 1746 nucleotides of ambisense RNA encoding two proteins, the N and NSs proteins. These lie in opposite orientations and are separated by a 54 nucleotide intergenic region. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_723", "text": "The virus originated 50\u2013150 years ago and has undergone a recent population expansion. [ 4 ] \nFive genotypes (A\u2013E) have been identified. [ 5 ]  Strains from  China  could be grouped into all five genotypes while isolates from  South Korea  lay in three (types A, D and E) and those from  Japan  only in one (type E). The virus appears to have originated in the  Dabie Mountains  in central China between 1918 and 1995. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_724", "text": "Among bunyaviruses, it appears to be more closely related to the  Uukuniemi virus  serogroup than to the Sandfly fever group. [ 2 ]  It is a member of the Bhanja virus serocomplex. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_725", "text": "SFTSV is a tick-borne virus; it is not clear whether it can be transmitted by other blood-sucking arthropods. [ 7 ]  It can infect many mammalian hosts, including  cats ,  mice ,  hedgehogs ,  weasels ,  brushtail possums  and  yaks . Humans appear to be accidental hosts, and play no essential role in the life cycle of SFTSV. SFTSV has been detected from the ixodid  tick ,  Haemaphysalis longicornis ,  Ixodes nipponensis ,  Amblyomma testudinarium [ 8 ]  and  Rhipicephalus microplus . [ 9 ]  In addition to tick bite, SFTSV can be transmitted from person to person through contact with blood or mucus of an infected person. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_726", "text": "This virus has been found in the Chinese provinces of  Anhui ,  Henan ,  Hubei ,  Jiangsu ,  Liaoning  and  Shandong . SFTS occurs in rural areas, from March to November, and a majority of cases are found from April to July. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_727", "text": "The virus has also been found in South Korea, Japan, Vietnam and Taiwan. [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_728", "text": "Danicopan , sold under the brand name  Voydeya , is a medication used for the treatment of  paroxysmal nocturnal hemoglobinuria . [ 6 ] [ 7 ]  It is a  complement  inhibitor which reversibly binds to factor D to prevent alternative pathway-mediated  hemolysis  and deposition of  complement C3  proteins on red blood cells. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_729", "text": "The most common side effects include fever, headache, increased levels of liver enzymes (a sign of possible liver problems) and pain in the extremities (arms and legs). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_730", "text": "Danicopan was approved for medical use in Japan in January 2024, [ 9 ]  in the United States in March 2024, [ 6 ] [ 10 ]  and in the European Union in April 2024. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_731", "text": "Danicopan is  indicated  as add-on therapy to  ravulizumab  or  eculizumab  for the treatment of extravascular hemolysis in adults with paroxysmal nocturnal hemoglobinuria. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_732", "text": "Danicopan was approved for medical use in Japan, [ 11 ]  the United States, [ 6 ]  and the European Union in 2024. [ 7 ]  The FDA granted the application  breakthrough therapy  designation. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_733", "text": "In February 2024, the  Committee for Medicinal Products for Human Use  of the EMA adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Voydeya, intended as add-on therapy to ravulizumab or eculizumab for the treatment of residual hemolytic anemia in adults with paroxysmal nocturnal hemoglobinuria (PNH). [ 7 ] [ 13 ]  The applicant for this medicinal product is Alexion Europe. [ 7 ]  Danicopan was approved for medical use in the European Union in April 2024. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_734", "text": "In October 2024, the  National Institute for Health and Care Excellence (NICE)  adopted a recommendation for danicopan\u00a0as an add-on therapy for adults with the  paroxysmal nocturnal haemoglobinuria (PNH)  based results from the phase 3 ALPHA trial, which evaluated the efficacy and safety of the drug as an add-on to  ravulizumab  or  eculizumab  in patients with PNH who experienced clinically significant extravascular haemolysis. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_735", "text": "Danicopan is the  international nonproprietary name . [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_736", "text": "This  pharmacology -related article is a  stub . You can help Wikipedia by  expanding it ."}
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{"_id": "WikiPedia_Hematology$$$corpus_748", "text": "Complement decay-accelerating factor , also known as  CD55  or  DAF , is a  protein  that, in humans, is encoded by the  CD55   gene . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_749", "text": "DAF regulates the  complement system  on the  cell  surface. It recognizes C4b and C3b fragments that are created during activation of C4 ( classical  or  lectin  pathway) or C3 ( alternative  pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2a  C3-convertase , and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complement\ncascade, DAF indirectly blocks the formation of the  membrane attack complex . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_750", "text": "This  glycoprotein  is broadly distributed among  hematopoietic  and non-hematopoietic cells. It is a determinant for the Cromer blood group system."}
{"_id": "WikiPedia_Hematology$$$corpus_751", "text": "DAF is a 70  kDa   membrane protein  that attaches to the cell membrane via a  glycophosphatidylinositol  (GPI) anchor."}
{"_id": "WikiPedia_Hematology$$$corpus_752", "text": "DAF contains four  complement control protein  (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2, CCP3, CCP4 and three consecutive  lysine  residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of the  alternate complement pathway . CCP2 and CCP3 alone are involved in its inhibition of the  classical pathway . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_753", "text": "Because DAF is a  GPI -anchored protein, its expression is reduced in persons with mutations that reduce GPI levels such as those with  paroxysmal nocturnal hemoglobinuria  (PNH). In PNH disorder,  red blood cells  with very low levels of DAF and  CD59  undergo  complement -mediated hemolysis. Symptoms include low red blood cell count (anemia), fatigue, and episodes of dark colored urine and other complications. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_754", "text": "DAF is used as a receptor by some  coxsackieviruses  and other  enteroviruses . [ 9 ]  Recombinant soluble DAF- Fc  has been tested in mice as an anti-enterovirus therapy for heart damage; [ 10 ]  however, the human enterovirus that was tested binds much more strongly to human DAF than to  mouse  or  rat  DAF. Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF. [ 11 ]  and DAF-Fc has yet to be tested in humans."}
{"_id": "WikiPedia_Hematology$$$corpus_755", "text": "Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement mediated lysis. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_756", "text": "Deep vein thrombosis  ( DVT ) is a type of  venous thrombosis  involving the formation of a  blood clot  in a  deep vein , most commonly in the legs or pelvis. [ 9 ] [ a ]  A minority of DVTs occur in the arms. [ 11 ]  Symptoms can include pain, swelling, redness, and enlarged veins in the affected area, but some DVTs have no symptoms. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_757", "text": "The most common life-threatening concern with DVT is the potential for a clot to  embolize  (detach from the veins), travel as an  embolus  through the right side of the heart, and become lodged in a  pulmonary artery  that supplies blood to the  lungs . This is called a  pulmonary embolism  (PE). DVT and PE comprise the  cardiovascular disease  of  venous thromboembolism  (VTE). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_758", "text": "About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. [ 12 ]  The most frequent long-term DVT  complication  is  post-thrombotic syndrome , which can cause pain, swelling, a sensation of heaviness, itching, and in severe cases,  ulcers . [ 5 ]  Recurrent VTE occurs in about 30% of those in the ten years following an initial VTE. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_759", "text": "The mechanism behind DVT formation typically involves some combination of  decreased blood flow , increased  tendency to clot , changes to the  blood vessel wall , and inflammation. [ 13 ]  Risk factors include recent surgery, older age, active  cancer ,  obesity , infection, inflammatory diseases,  antiphospholipid syndrome , personal history and  family history  of VTE, trauma, injuries, lack of movement,  hormonal birth control ,  pregnancy , and the  period following birth . VTE has a strong genetic component, accounting for approximately 50 to 60% of the variability in VTE rates. [ 4 ]  Genetic factors include non-O  blood type , deficiencies of  antithrombin ,  protein C , and  protein S  and the mutations of  factor V Leiden  and  prothrombin G20210A . In total, dozens of genetic risk factors have been identified. [ 4 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_760", "text": "People suspected of having DVT can be assessed using a  prediction rule  such as the  Wells score . A  D-dimer  test can also be used to assist with excluding the diagnosis or to signal a need for further testing. [ 5 ]  Diagnosis is most commonly confirmed by  ultrasound  of the suspected veins. [ 5 ]  VTE becomes much more common with age. The condition is rare in children, but occurs in almost 1% of those \u2265 age 85 annually. [ 3 ]  Asian, Asian-American, Native American, and Hispanic individuals have a lower VTE risk than Whites or Blacks. [ 4 ] [ 15 ]  Populations in Asia have VTE rates at 15 to 20% of what is seen in Western countries. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_761", "text": "Using  blood thinners  is the standard treatment. Typical medications include  rivaroxaban ,  apixaban , and  warfarin . Beginning warfarin treatment requires an additional non-oral anticoagulant, often injections of  heparin . [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_762", "text": "Prevention of VTE for the general population includes avoiding obesity and maintaining an active lifestyle. Preventive efforts following low-risk surgery include early and frequent walking. Riskier surgeries generally prevent VTE with a blood thinner or  aspirin  combined with  intermittent pneumatic compression . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_763", "text": "Symptoms classically affect a leg and typically develop over hours or days, [ 20 ]  though they can develop suddenly or over a matter of weeks. [ 21 ]  The legs are primarily affected, with 4\u201310% of DVT occurring in the arms. [ 11 ]  Despite the signs and symptoms being highly variable, [ 5 ]  the typical symptoms are pain,  swelling , and redness. However, these symptoms might not manifest in the lower limbs of those unable to walk. [ 22 ]  In those who are able to walk, DVT can reduce one's ability to do so. [ 23 ]  The pain can be described as throbbing and can worsen with weight-bearing, prompting one to bear more weight with the unaffected leg. [ 21 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_764", "text": "Additional signs and symptoms include tenderness,  pitting edema  ( see image ), dilation of surface veins, warmth, discoloration, a \"pulling sensation\", and even  cyanosis  (a blue or purplish discoloration) with fever. [ 5 ] [ 20 ] [ 21 ]  DVT can also exist without causing any symptoms. [ 22 ]  Signs and symptoms help in determining the likelihood of DVT, but they are not used alone for diagnosis. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_765", "text": "At times, DVT can cause symptoms in both arms or both legs, as with bilateral DVT. [ 25 ]  Rarely, a clot in the  inferior vena cava  can cause both legs to swell. [ 26 ]   Superficial vein thrombosis , also known as  superficial thrombophlebitis , is the formation of a  blood clot (thrombus)  in a  vein close to the skin . It can co-occur with DVT and can be felt as a \"palpable cord\". [ 20 ]   Migratory thrombophlebitis (Trousseau's syndrome)  is a noted finding in those with  pancreatic cancer  and is associated with DVT. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_766", "text": "A  pulmonary embolism  (PE) occurs when a blood clot from a  deep vein  (a DVT) detaches from a vein ( embolizes ), travels through the right side of the heart, and becomes lodged as an  embolus  in a  pulmonary artery  that supplies deoxygenated blood to the lungs for oxygenation. [ 28 ]  Up to one-fourth of PE cases are thought to result in sudden death. [ 12 ]  When not fatal, PE can cause symptoms such as sudden onset  shortness of breath  or  chest pain , coughing up blood ( hemoptysis ), and fainting ( syncope ). [ 29 ] [ 30 ]  The chest pain can be  pleuritic  (worsened by deep breaths) [ 29 ]  and can vary based upon where the embolus is lodged in the lungs. An estimated 30\u201350% of those with PE have detectable DVT by  compression ultrasound . [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_767", "text": "A rare and massive DVT that causes significant obstruction and discoloration (including cyanosis) is  phlegmasia cerulea dolens . [ 31 ] [ 32 ]  It is life-threatening, limb-threatening, and carries a risk of venous  gangrene . [ 33 ]  Phlegmasia cerulea dolens can occur in the arm but more commonly affects the leg. [ 34 ] [ 35 ]  If found in the setting of acute  compartment syndrome , an urgent  fasciotomy  is warranted to protect the limb. [ 36 ]   Superior vena cava syndrome  is a rare complication of arm DVT. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_768", "text": "DVT is thought to be able to cause a  stroke  in the presence of a  heart defect . This is called a  paradoxical embolism  because the clot abnormally travels from the pulmonary circuit to the systemic circuit while inside the heart. The  defect  of a  patent foramen ovale  is thought to allow clots to travel through the  interatrial septum  from the  right atrium  into the left atrium. [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_769", "text": "In most suspected cases, DVT is ruled out after evaluation. [ 39 ]   Cellulitis  is a frequent mimic of DVT, with its  triad  of pain, swelling, and redness. [ 20 ]  Symptoms concerning for DVT are more often due to other causes, including cellulitis, ruptured  Baker's cyst ,  hematoma ,  lymphedema , and  chronic venous insufficiency . [ 1 ]  Other  differential diagnoses  include tumors, venous or arterial  aneurysms ,  connective tissue disorders , [ 40 ]   superficial vein thrombosis , muscle vein thrombosis, and  varicose veins . [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_770", "text": "DVT and PE are the two manifestations of the  cardiovascular disease   venous thromboembolism  (VTE). [ 2 ]  VTE can occur as DVT only, DVT with PE, or PE only. [ 3 ]  About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. [ 12 ]  VTE, along with superficial vein thrombosis, are common types of venous thrombosis. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_771", "text": "DVT is classified as  acute  when the clots are developing or have recently developed, whereas  chronic  DVT persists more than 28 days. [ 42 ]  Differences between these two types of DVT can be seen with ultrasound. [ 43 ]  An episode of VTE after an initial one is classified as recurrent. [ 44 ] [ 45 ]  Bilateral DVT refers to clots in both limbs while unilateral means only a single limb is affected. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_772", "text": "DVT in a leg above the knee is termed  proximal DVT  ( proximal ). DVT in a leg below the knee is termed  distal DVT  ( distal ), also called  calf DVT  when affecting the calf, [ 47 ] [ 48 ]  and has limited  clinical significance  compared to proximal DVT. [ 49 ]  Calf DVT makes up about half of DVTs. [ 50 ]   Iliofemoral DVT  is described as involving either the  iliac , or  common femoral vein ; [ 51 ]  elsewhere, it has been defined as involving at a minimum the  common iliac vein , which is near the top of the pelvis. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_773", "text": "DVT can be classified into provoked and unprovoked categories. [ 52 ]  For example, DVT that occurs in association with cancer or surgery can be classified as provoked. [ 52 ]  However, the  European Society of Cardiology  in 2019 urged for this dichotomy to be abandoned to encourage more personalized risk assessments for recurrent VTE. [ 53 ]  The distinction between these categories is not always clear. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_774", "text": "Traditionally, the three factors of  Virchow's triad \u2014 venous stasis ,  hypercoagulability , and changes in the  endothelial  blood vessel lining\u2014contribute to VTE and were used to explain its formation. [ 55 ]  More recently,  inflammation  has been identified as playing a clear causal role. [ 13 ]  Other related causes include activation of  immune system  components, the state of  microparticles  in the blood, the concentration of oxygen, and possible  platelet  activation. [ 56 ]  Various risk factors contribute to VTE, including genetic and environmental factors, though many with multiple risk factors never develop it. [ 57 ] [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_775", "text": "Acquired risk factors include the strong risk factor of older age, [ 5 ]  which alters blood composition to favor clotting. [ 59 ]  Previous VTE, particularly unprovoked VTE, is a strong risk factor. [ 60 ]  A leftover clot from a prior DVT increases the risk of a subsequent DVT. [ 61 ]  Major surgery and  trauma  increase risk because of  tissue factor  from outside the vascular system entering the blood. [ 62 ]  Minor injuries, [ 63 ]  lower limb amputation, [ 64 ]   hip fracture , and  long bone  fractures are also risks. [ 9 ]  In  orthopedic surgery , venous stasis can be temporarily provoked by a cessation of blood flow as part of the procedure. [ 56 ]  Inactivity and immobilization contribute to venous stasis, as with  orthopedic casts , [ 65 ]  paralysis, sitting, long-haul travel, bed rest, hospitalization, [ 62 ]   catatonia , [ 66 ]  and in survivors of acute  stroke . [ 67 ]  Conditions that involve compromised blood flow in the veins are  May\u2013Thurner syndrome , where a vein of the pelvis is compressed, and venous  thoracic outlet syndrome , which includes  Paget\u2013Schroetter syndrome , where compression occurs near the base of the neck. [ 68 ] [ 69 ] [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_776", "text": "Infections, including  sepsis ,  COVID-19 ,  HIV , and active  tuberculosis , increase risk. [ 71 ] [ 72 ] [ 73 ] [ 74 ] [ 75 ]  Chronic inflammatory diseases and some  autoimmune diseases , [ 76 ]  such as  inflammatory bowel disease , [ 77 ]   systemic sclerosis , [ 78 ]   Beh\u00e7et's syndrome , [ 79 ]  primary  antiphospholipid syndrome , [ 80 ]  and  systemic lupus erythematosus  (SLE) [ 81 ]  increase risk. SLE itself is frequently associated with secondary antiphospholipid syndrome. [ 82 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_777", "text": "Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor. [ 83 ]  Cancers of the blood, lung, pancreas, brain, stomach, and bowel are associated with high VTE risk. [ 84 ]  Solid tumors such as  adenocarcinomas  can contribute to both VTE and  disseminated intravascular coagulation . In severe cases, this can lead to simultaneous clotting and bleeding. [ 85 ]   Chemotherapy  treatment also increases risk. [ 86 ]  Obesity increases the potential of blood to clot,  as does pregnancy.  In the  postpartum ,  placental  tearing releases substances that favor clotting. Oral contraceptives [ b ]  and  hormonal replacement therapy  increase the risk through a variety of mechanisms, including altered blood coagulation protein levels and reduced  fibrinolysis . [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_778", "text": "Dozens of genetic risk factors have been identified, [ 14 ]  and they account for approximately 50 to 60% of the variability in VTE rates. [ 4 ]  As such,  family history  of VTE is a risk factor for a first VTE. [ 88 ]   Factor V Leiden , which makes  factor V  resistant to inactivation by  activated protein C , [ 88 ]  mildly increases VTE risk by about three times. [ 14 ] [ 88 ]  Deficiencies of three proteins that normally prevent blood from clotting\u2014 protein C ,  protein S , and  antithrombin \u2014contribute to VTE. These  deficiencies in antithrombin ,  protein C , and  protein S [ c ]  are rare but strong, or moderately strong, risk factors. [ 62 ] [ 56 ]  They increase risk by about 10 times. [ 89 ]   Having a non-O blood type roughly doubles VTE risk. [ 56 ]  Non-O blood type is common globally, making it an important risk factor. [ 90 ]  Individuals without O blood type have higher blood levels of  von Willebrand factor  and  factor VIII  than those with O blood type, increasing the likelihood of clotting. [ 90 ]  Those  homozygous  for the common  fibrinogen gamma gene  variant rs2066865 have about a 1.6 times higher risk of VTE. [ 91 ]  The genetic variant  prothrombin G20210A , which increases prothrombin levels, [ 62 ]  increases risk by about 2.5 times. [ 14 ]  Additionally, approximately 5% of people have been identified with a background genetic risk comparable to the factor V Leiden and prothrombin G20210A mutations. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_779", "text": "Blood alterations including  dysfibrinogenemia , [ 65 ]  low free protein S, [ 58 ]   activated protein C resistance , [ 58 ]   homocystinuria , [ 92 ]   hyperhomocysteinemia , [ 62 ]   high  fibrinogen  levels, [ 62 ]  high  factor IX  levels, [ 62 ]  and high  factor XI  levels [ 62 ]  are associated with increased risk. Other associated conditions include  heparin-induced thrombocytopenia ,  catastrophic antiphospholipid syndrome , [ 93 ]   paroxysmal nocturnal hemoglobinuria , [ 94 ]   nephrotic syndrome , [ 58 ]   chronic kidney disease , [ 95 ]   polycythemia vera ,  essential thrombocythemia , [ 96 ]  intravenous drug use, [ 97 ]  and smoking. [ d ]"}
{"_id": "WikiPedia_Hematology$$$corpus_780", "text": "Some risk factors influence the location of DVT within the body. In isolated distal DVT, the profile of risk factors appears distinct from proximal DVT. Transient factors, such as surgery and immobilization, appear to dominate, whereas  thrombophilias [ e ]  and age do not seem to increase risk. [ 101 ]  Common risk factors for having an upper extremity DVT include having an existing foreign body (such as a central venous catheter, a pacemaker, or a triple-lumen PICC line), cancer, and recent surgery. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_781", "text": "Blood has a natural tendency to clot when blood vessels are damaged ( hemostasis ) to minimize blood loss. [ 102 ]  Clotting is activated by the  coagulation cascade  and the clearing of clots that are no longer needed is accomplished by the process of  fibrinolysis . Reductions in fibrinolysis or increases in coagulation can increase the risk of DVT. [ 102 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_782", "text": "DVT often develops in the calf veins and \"grows\" in the direction of venous flow, towards the heart. [ 42 ] [ 103 ]  DVT most frequently affects veins in the leg or pelvis [ 9 ]  including the  popliteal vein  (behind the knee),  femoral vein  (of the thigh), and iliac veins of the pelvis. Extensive lower-extremity DVT can even reach into the  inferior vena cava  (in the abdomen). [ 104 ]  Upper extremity DVT most commonly affects the subclavian, axillary, and  jugular veins . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_783", "text": "The process of fibrinolysis, where DVT clots can be dissolved back into the blood, acts to temper the process of thrombus growth. [ 105 ]  This is the preferred process. Aside from the potentially deadly process of embolization, a clot can resolve through organization, which can damage the valves of veins, cause vein fibrosis, and result in non-compliant veins. [ 106 ] [ 107 ]  Organization of a thrombus into the vein can occur at the third stage of its  pathological  development, in which collagen becomes the characteristic component. The first pathological stage is marked by red blood cells, and the second is characterized by medium-textured fibrin. [ 107 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_784", "text": "In arterial thrombosis, blood vessel wall damage is required, as it initiates  coagulation , [ 108 ]  but clotting in the veins mostly occurs without any such mechanical damage. [ 62 ]  The beginning of venous thrombosis is thought to arise from \"activation of endothelial cells, platelets, and leukocytes, with initiation of inflammation and formation of microparticles that trigger the coagulation system\" via tissue factor. [ 77 ]  Vein wall inflammation is likely the inciting event. [ 77 ]  Importantly, the  activated endothelium  of veins interacts with circulating white blood cells (leukocytes). [ 55 ]  While leukocytes normally help prevent blood from clotting (as does normal endothelium), upon stimulation, leukocytes facilitate clotting. [ 109 ]  Neutrophils are recruited early in the process of venous thrombi formation. [ 55 ]  They release pro-coagulant granules [ 109 ]  and  neutrophil extracellular traps  (NETs) or their components, which play a role in venous thrombi formation. [ 55 ] [ 110 ]  NET components are pro-thrombotic through both the intrinsic and extrinsic coagulation pathways. [ 110 ]  NETs provide \"a scaffold for adhesion\" of platelets, red blood cells, and multiple factors that potentiate platelet activation. [ 111 ]  In addition to the pro-coagulant activities of neutrophils, multiple stimuli cause  monocytes  to release tissue factor. [ 109 ]  Monocytes are also recruited early in the process. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_785", "text": "Tissue factor, via the tissue factor\u2013 factor VIIa  complex, [ 112 ]  activates the extrinsic pathway of coagulation and leads to conversion of prothrombin to thrombin, followed by fibrin deposition. [ 86 ]  Fresh venous clots are  red blood cell  and  fibrin  rich. [ 42 ]  Platelets and  white blood cells  are also components. Platelets are not as prominent in venous clots as they are in arterial ones, but they can play a role. [ 56 ]  In cancer, tissue factor is produced by cancer cells. [ 84 ]  Cancer also produces unique substances that stimulate  factor Xa , cytokines that promote  endothelial dysfunction , and  plasminogen activator inhibitor-1 , which inhibits the breakdown of clots (fibrinolysis). [ 84 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_786", "text": "Often, DVT begins in the valves of veins. [ 105 ]  The blood flow pattern in the valves can cause low oxygen concentrations in the blood ( hypoxemia ) of a valve sinus. Hypoxemia, which is worsened by venous stasis, activates pathways\u2014ones that include  hypoxia-inducible factor-1  and  early-growth-response protein 1 . Hypoxemia also results in the production of  reactive oxygen species , which can activate these pathways, as well as  nuclear factor-\u03baB , which regulates hypoxia-inducible factor-1  transcription . [ 86 ]  Hypoxia-inducible factor-1 and early-growth-response protein 1 contribute to monocyte association with endothelial proteins, such as  P-selectin , prompting monocytes to release tissue factor-filled  microvesicles , which presumably begin clotting after binding to the endothelial surface. [ 86 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_787", "text": "D-dimers  are a  fibrin degradation product , a natural byproduct of fibrinolysis that is typically found in the blood. An elevated level [ f ]  can result from  plasmin  dissolving a clot\u2014or other conditions. [ 113 ]  Hospitalized patients often have elevated levels for multiple reasons. [ 39 ]   Anticoagulation , the standard treatment for DVT, prevents further clot growth and PE, but does not act directly on existing clots. [ 114 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_788", "text": "A  clinical probability assessment  using the  Wells score  (see column in the table below) to determine if a potential DVT is \"likely\" or \"unlikely\" is typically the first step of the diagnostic process. The score is used in suspected first lower extremity DVT (without any PE symptoms) in primary care and outpatient settings, including the  emergency department . [ 1 ] [ 5 ]  The numerical result (possible score \u22122 to 9) is most commonly grouped into either \"unlikely\" or \"likely\" categories. [ 1 ] [ 5 ]  A Wells score of two or more means DVT is considered \"likely\" (about a 28% chance), while those with a lower score are considered \"unlikely\" to have DVT (about a 6% chance). [ 39 ]  In those unlikely to have DVT, a diagnosis is excluded by a negative D-dimer blood test. [ 1 ]  In people with likely DVT,  ultrasound  is the standard  imaging  used to confirm or exclude a diagnosis. [ 5 ]  Imaging is also needed for hospital inpatients with suspected DVT and those initially categorized as unlikely to have DVT but who have a positive D-dimer test. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_789", "text": "While the Wells score is the predominant and most studied clinical prediction rule for DVT, [ 39 ] [ 115 ]  it does have drawbacks. The Wells score requires a subjective assessment regarding the likelihood of an alternate diagnosis and performs less well in the elderly and those with a prior DVT. The  Dutch Primary Care Rule  has also been validated for use. It contains only objective criteria but requires obtaining a D-dimer value. [ 116 ]  With this prediction rule, three points or less means a person is at low risk for DVT. A result of four or more points indicates an ultrasound is needed. [ 116 ]  Instead of using a prediction rule, experienced physicians can make a DVT  pre-test probability  assessment using clinical assessment and gestalt, but prediction rules are more reliable. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_790", "text": "Compression  ultrasonography for suspected deep vein thrombosis  is the standard diagnostic method, and it is highly sensitive for detecting an initial DVT. [ 118 ]  A  compression ultrasound  is considered positive when the vein walls of normally compressible veins do not collapse under gentle pressure. [ 39 ]  Clot visualization is sometimes possible, but is not required. [ 119 ]  Three compression ultrasound scanning techniques can be used, with two of the three methods requiring a second ultrasound some days later to rule out the diagnosis. [ 118 ]  Whole-leg ultrasound is the option that does not require a repeat ultrasound, [ 118 ]  but proximal compression ultrasound is frequently used because distal DVT is only rarely clinically significant. [ 117 ]  Ultrasound methods including  duplex  and  color flow Doppler  can be used to further characterize the clot [ 117 ]  and Doppler ultrasound is especially helpful in the non-compressible iliac veins. [ 119 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_791", "text": "CT scan venography , MRI venography, or a non-contrast MRI are also diagnostic possibilities. [ 120 ]  The  gold standard  for judging imaging methods is contrast  venography , which involves injecting a peripheral vein of the affected limb with a contrast agent and taking X-rays, to reveal whether the venous supply has been obstructed. Because of its cost, invasiveness, availability, and other limitations, this test is rarely performed. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_792", "text": "Treatment for DVT is warranted when the clots are either proximal, distal and symptomatic, or upper extremity and symptomatic. [ 2 ]  Providing anticoagulation, or blood-thinning medicine, is the typical treatment after patients are checked to make sure they are not subject to  bleeding . [ 2 ] [ i ]  However, treatment varies depending upon the location of DVT. For example, in cases of isolated distal DVT, ultrasound surveillance (a second ultrasound after 2 weeks to check for proximal clots), might be used instead of anticoagulation. [ 5 ] [ 124 ]  Although, those with isolated distal DVT at a high risk of VTE recurrence are typically anticoagulated as if they had proximal DVT. Those at a low risk for recurrence might receive a four- to six-week course of anticoagulation, lower doses, or no anticoagulation at all. [ 5 ]  In contrast, those with proximal DVT should receive at least 3 months of anticoagulation. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_793", "text": "Some anticoagulants can be taken by mouth, and these oral medicines include  warfarin  (a  vitamin K antagonist ),  rivaroxaban  (a  factor Xa inhibitor ),  apixaban  (a factor Xa inhibitor),  dabigatran  (a  direct thrombin inhibitor ), and  edoxaban  (a factor Xa inhibitor). [ 2 ]  Other anticoagulants cannot be taken by mouth. These  parenteral  (non-oral) medicines include  low-molecular-weight heparin ,  fondaparinux , and  unfractionated heparin . Some oral medicines are sufficient when taken alone, while others require the use of an additional parenteral blood thinner. Rivaroxaban and apixaban are the typical first-line medicines, and they are sufficient when taken orally. [ 19 ]  Rivaroxaban is taken once daily, and apixaban is taken twice daily. [ 5 ]   Warfarin, dabigatran, and edoxaban require the use of a parenteral anticoagulant to initiate oral anticoagulant therapy. [ 19 ] [ 125 ]   When warfarin is initiated for VTE treatment, a 5-day minimum of a parenteral anticoagulant [ j ]  together with warfarin is given, which is followed by warfarin-only therapy. [ 17 ] [ 18 ]  Warfarin is taken to maintain an  international normalized ratio  (INR) [ k ]  of 2.0\u20133.0, with 2.5 as the target. [ 128 ]  The benefit of taking warfarin declines as the duration of treatment extends, [ 129 ]  and the risk of bleeding increases with age. [ 130 ]  Periodic INR monitoring is not necessary when first-line direct oral anticoagulants are used. Overall, anticoagulation therapy is complex, and many circumstances can affect how these therapies are managed. [ 131 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_794", "text": "The duration of anticoagulation therapy (whether it will last 4 to 6 weeks, [ 5 ]  6 to 12 weeks, 3 to 6 months, [ 19 ]  or indefinitely) is a key factor in clinical  decision making . [ 52 ]  When proximal DVT is provoked by surgery or trauma a 3-month course of anticoagulation is standard. [ 19 ]  When a first VTE is proximal DVT that is either unprovoked or associated with transient non-surgical risk factor, low-dose anticoagulation beyond 3 to 6 months might be used. [ 19 ]  In those with an annual risk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation is a possibility. [ 132 ]  Those who finish warfarin treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs about 4% for normal results), and this result might be used in clinical decision making. [ 133 ]  Thrombophilia test results rarely play a role in the length of treatment. [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_795", "text": "Treatment for acute leg DVT is suggested to continue at home for uncomplicated DVT instead of hospitalization. Factors that favor hospitalization include severe symptoms or additional medical issues. [ 12 ]  Early walking is suggested over bedrest. [ 134 ]  Graduated compression stockings\u2014which apply higher pressure at the ankles and a lower pressure around the knees [ 126 ]  can be trialed for symptomatic management of acute DVT symptoms, but they are not recommended for reducing the risk of  post-thrombotic syndrome , [ 125 ]  as the potential benefit of using them for this goal \"may be uncertain\". [ 5 ]  Nor are compression stockings likely to reduce VTE recurrence. [ 135 ]  They are, however, recommended in those with isolated distal DVT. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_796", "text": "If someone decides to stop anticoagulation after an unprovoked VTE instead of being on lifelong anticoagulation, aspirin can be used to reduce the risk of recurrence, [ 136 ]  but it is only about 33% as effective as anticoagulation in preventing recurrent VTE. [ 52 ]   Statins  have also been investigated for their potential to reduce recurrent VTE rates, with some studies suggesting effectiveness. [ 137 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_797", "text": "An unprovoked VTE might signal the presence of an unknown cancer, as it is an underlying condition in up to 10% of unprovoked cases. [ 1 ]  A thorough clinical assessment is needed and should include a  physical examination , a review of  medical history , and universal  cancer screening  done in people of that age. [ 19 ] [ 138 ]  A review of prior imaging is considered worthwhile, as is \"reviewing baseline blood test results including  full blood count ,  renal  and  hepatic function ,  PT  and  APTT .\" [ 138 ]  It is not recommended practice to obtain  tumor markers  or a  CT of the abdomen and pelvis  in asymptomatic individuals. [ 1 ]   NICE  recommends that further investigations are unwarranted in those without relevant signs or symptoms. [ 138 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_798", "text": "Thrombolysis  is the injection of an enzyme into the veins to dissolve blood clots, and while this treatment has been proven effective against the life-threatening emergency clots of stroke and heart attacks, randomized controlled trials [ 139 ] [ 140 ] [ 141 ]  have not established a net benefit in those with acute proximal DVT. [ 5 ] [ 142 ]  Drawbacks of  catheter-directed thrombolysis  (the preferred method of administering the clot-busting enzyme [ 5 ] ) include a risk of bleeding, complexity, [ l ]  and the cost of the procedure. [ 125 ]  Although, while anticoagulation is the preferred treatment for DVT, [ 125 ]  thrombolysis is a treatment option for those with the severe DVT form of phlegmasia cerula dorens ( bottom left image ) and in some younger patients with DVT affecting the iliac and common femoral veins. [ 12 ]  Of note, a variety of  contraindications to thrombolysis  exist. [ 125 ]  In 2020, NICE kept their 2012 recommendations that catheter-directed thrombolysis should be considered in those with iliofemoral DVT who have \"symptoms lasting less than 14 days, good functional status, a life expectancy of 1 year or more, and a low risk of bleeding.\" [ 138 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_799", "text": "A mechanical thrombectomy device can remove DVT clots, particularly in acute iliofemoral DVT (DVT of the major veins in the pelvis), but there is limited data on its efficacy. It is usually combined with thrombolysis, and sometimes temporary IVC filters are placed to protect against PE during the procedure. [ 143 ]  Catheter-directed thrombolysis with thrombectomy [ 141 ]  against iliofemoral DVT has been associated with a reduction in the severity of post-thrombotic syndrome at an estimated cost-effectiveness ratio of about $138,000 [ m ]  per gained  QALY . [ 144 ] [ 145 ]  Phlegmasia cerulea dolens might be treated with catheter-directed thrombolysis and/or thrombectomy. [ 19 ] [ 143 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_800", "text": "In DVT in the arm, the first (topmost) rib can be surgically removed as part of the typical treatment when the DVT is due to  thoracic outlet syndrome  or  Paget\u2013Schroetter syndrome . This treatment involves initial anticoagulation followed by thrombolysis of the  subclavian vein  and staged  first rib resection  to relieve the thoracic outlet compression and prevent recurrent DVT. [ 146 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_801", "text": "The placement of an  inferior vena cava filter  (IVC filter) is possible when either the standard treatment for acute DVT, anticoagulation, is  absolutely contraindicated  (not possible), or if someone develops a PE despite being anticoagulated. [ 138 ]  However, a 2020 NICE review found \"little good evidence\" for their use. [ 138 ]  A 2018 study associated IVC filter placement with a 50% reduction in PE, a 70% increase in DVT, and an 18% increase in 30 day mortality when compared to no IVC placement. [ 1 ] [ 148 ]  Other studies including a systematic review and meta-analysis did not find a difference in mortality with IVC placement. [ 30 ]  If someone develops a PE despite being anticoagulated, care should be given to optimize anticoagulation treatment and address other related concerns before considering IVC filter placement. [ 138 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_802", "text": "Patients with a history of DVT might be managed by  primary care ,  general internal medicine ,  hematology ,  cardiology ,  vascular surgery , or  vascular medicine . [ 149 ]  Patients suspected of having an acute DVT are often referred to the emergency department for evaluation. [ 150 ]   Interventional radiology  is the specialty that typically places and retrieves IVC filters, [ 151 ]  and vascular surgery might do catheter directed thrombosis for some severe DVTs. [ 147 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_803", "text": "For the  prevention of blood clots  in the general population, incorporating leg exercises while sitting down for long periods, or having breaks from a sitting position and walking around, having an active lifestyle, and maintaining a healthy body weight are recommended. [ 6 ]  Walking increases blood flow through the leg veins. [ 152 ]  Excess body weight is modifiable unlike most risk factors, and interventions or lifestyle modifications that help someone who is overweight or obese  lose weight  reduce DVT risk. [ 88 ]  Avoiding both smoking and a  Western pattern diet  are thought to reduce risk. [ 153 ]  Statins have been investigated for  primary prevention  (prevention of a first VTE), and the  JUPITER trial , which used  rosuvastatin , has provided some tentative evidence of effectiveness. [ 14 ] [ 154 ]  Of the statins, rosuvastatin appears to be the only one with the potential to reduce VTE risk. [ 155 ]  If so, it appears to reduce risk by about 15%. [ 153 ]  However, the  number needed to treat  to prevent one initial VTE is about 2000, limiting its applicability. [ 156 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_804", "text": "Acutely ill hospitalized patients are suggested to receive a parenteral anticoagulant, although the potential net benefit is uncertain. [ 63 ]  Critically ill hospitalized patients are recommended to either receive unfractionated heparin or low-molecular weight heparin instead of foregoing these medicines. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_805", "text": "Major orthopedic surgery\u2014 total hip replacement ,  total knee replacement , or  hip fracture surgery \u2014has a high risk of causing VTE. [ 157 ]  If prophylaxis is not used after these surgeries, symptomatic VTE has about a 4% chance of developing within 35 days. [ 158 ]  Following major orthopedic surgery, a blood thinner or aspirin is typically paired with  intermittent pneumatic compression , which is the preferred mechanical prophylaxis over graduated compression stockings. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_806", "text": "Options for VTE prevention in people following non-orthopedic surgery include early walking, mechanical prophylaxis, and blood thinners (low-molecular-weight heparin and low-dose-unfractionated heparin) depending upon the risk of VTE, risk of major bleeding, and person's preferences. [ 159 ]  After low-risk surgeries, early and frequent walking is the best preventive measure. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_807", "text": "The risk of VTE is increased in pregnancy by about four to five times because of a more hypercoagulable state that protects against fatal  postpartum hemorrhage . [ 28 ]  Preventive measures for pregnancy-related VTE were suggested by the  American Society of Hematology  in 2018. [ 160 ]  Warfarin, a common vitamin K antagonist, can cause birth defects and is not used for prevention during pregnancy. [ 161 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_808", "text": "Travelling \"is an often cited yet relatively uncommon\" cause of VTE. [ 28 ]  Suggestions for at-risk [ n ]  long-haul travelers include calf exercises, frequent walking, and aisle seating in airplanes to ease walking. [ 162 ] [ 163 ]  Graduated compression stockings have sharply reduced the levels of asymptomatic DVT in airline passengers, but the effect on symptomatic DVT, PE, or mortality is unknown, as none of the individuals studied developed these outcomes. [ 164 ]  However, graduated compression stockings are not suggested for long-haul travelers (>4 hours) without risk factors for VTE. Likewise, neither aspirin nor anticoagulants are suggested in the general population undertaking long-haul travel. [ 63 ]  Those with significant VTE risk factors [ o ]  undertaking long-haul travel are suggested to use either graduated compression stockings or LMWH for VTE prevention. If neither of these two methods are feasible, then aspirin is suggested. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_809", "text": "DVT is most frequently a disease of older age that occurs in the context of nursing homes, hospitals, and active cancer. [ 3 ]  It is associated with a 30-day  mortality rate  of about 6%, with PE being the cause of most of these deaths. [ 1 ]  Proximal DVT is frequently associated with PE, unlike distal DVT, which is rarely if ever associated with PE. [ 39 ]  Around 56% of those with proximal DVT also have PE, although a chest CT is not needed simply because of the presence of DVT. [ 1 ]  If proximal DVT is left untreated, in the following 3 months approximately half of people will experience symptomatic PE. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_810", "text": "Another frequent complication of proximal DVT, and the most frequent chronic complication, is post-thrombotic syndrome, where individuals have chronic venous symptoms. [ 5 ]  Symptoms can include pain, itching, swelling,  paresthesia , a sensation of heaviness, and in severe cases,  leg ulcers . [ 5 ]  After proximal DVT, an estimated 20\u201350% of people develop the syndrome, with 5\u201310% experiencing severe symptoms. [ 165 ]  Post-thrombotic syndrome can also be a complication of distal DVT, though to a lesser extent than with proximal DVT. [ 166 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_811", "text": "In the 10 years following an initial VTE, about 30% of people will have a recurrence. [ 3 ]  VTE recurrence in those with prior DVT is more likely to recur as DVT than PE. [ 167 ]  Cancer [ 5 ]  and unprovoked DVT are strong risk factors for recurrence. [ 60 ]  After initial proximal unprovoked DVT with and without PE, 16\u201317% of people will have recurrent VTE in the 2 years after they complete their course of anticoagulants. VTE recurrence is less common in distal DVT than proximal DVT. [ 44 ] [ 45 ]  In upper extremity DVT, annual VTE recurrence is about 2\u20134%. [ 130 ]  After surgery, a provoked proximal DVT or PE has an annual recurrence rate of only 0.7%. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_812", "text": "About 1.5 out of 1000 adults a year have a first VTE in high-income countries. [ 168 ] [ 169 ]  The condition becomes much more common with age. [ 3 ]  VTE rarely occurs in children, but when it does, it predominantly affects hospitalized children. [ 170 ]  Children in North America and the Netherlands have VTE rates that range from 0.07 to 0.49 out of 10,000 children annually. [ 170 ]  Meanwhile, almost 1% of those aged 85 and above experience VTE each year. [ 3 ]  About 60% of all VTEs occur in those 70 years of age or older. [ 9 ]  Incidence is about 18% higher in males than in females, [ 4 ]  though there are ages when VTE is more prevalent in women. [ 15 ]  VTE occurs in association with hospitalization or nursing home residence about 60% of the time, active cancer about 20% of the time, and a central venous catheter or transvenous pacemaker about 9% of the time. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_813", "text": "During pregnancy and after childbirth, acute VTE occurs in about 1.2 of 1000 deliveries. Despite it being relatively rare, it is a leading cause of maternal morbidity and  mortality . [ 160 ]  After surgery with preventive treatment, VTE develops in about 10 of 1000 people after total or partial knee replacement, and in about 5 of 1000 after total or partial hip replacement. [ 171 ]  About 400,000 Americans develop an initial VTE each year, with 100,000 deaths or more attributable to PE. [ 169 ]   Asian, Asian-American, Native American, and Hispanic individuals have a lower VTE risk than Whites or Blacks. [ 4 ] [ 15 ]  Populations in Asia have VTE rates at 15 to 20% of what is seen in Western countries, with an increase in incidence seen over time. [ 16 ]  In North American and European populations, around 4\u20138% of people have a thrombophilia, [ 89 ]  most commonly factor V leiden and prothrombin G20210A. For populations in China, Japan, and Thailand, deficiences in protein S, protein C, and antithrombin predominate. [ 172 ]  Non-O blood type is present in around 50% of the general population and  varies with ethnicity , and it is present in about 70% of those with VTE. [ 90 ] [ 173 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_814", "text": "DVT occurs in the upper extremities in about 4\u201310% of cases, [ 11 ]  with an incidence of 0.4\u20131.0 people out of 10,000 a year. [ 5 ]  A minority of upper extremity DVTs are due to Paget\u2013Schroetter syndrome, also called effort thrombosis, which occurs in 1\u20132 people out of 100,000 a year, usually in athletic males around 30 years of age or in those who do significant amounts of overhead manual labor. [ 69 ] [ 147 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_815", "text": "Being on blood thinners because of DVT can be life-changing because it can prevent lifestyle activities such as contact or winter sports to prevent bleeding after potential injuries. [ 175 ]  Head injuries prompting brain bleeds are of particular concern. This has caused NASCAR driver  Brian Vickers  to forego participation in races. Professional basketball players including NBA players  Chris Bosh  and hall of famer  Hakeem Olajuwon  have dealt with recurrent blood clots, [ 176 ]  and Bosh's career was significantly hampered by DVT and PE. [ 177 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_816", "text": "Tennis star  Serena Williams  was hospitalized in 2011 for PE thought to have originated from DVT. [ 178 ]  Years later, in 2017, due to her knowledge of DVT and PE, Serena accurately  advocated  for herself to have a PE diagnosed and treated. During this encounter with VTE, she was hospitalized after a  C-section  surgery and was off of blood thinners. After feeling the sudden onset of a PE symptom, shortness of breath, she told her nurse and requested  a CT scan  and an IV heparin drip, all while gasping for air. She started to receive an ultrasound to look for DVT in the legs, prompting her to express dissatisfaction to the medical staff that they were not looking for clots where she had symptoms (her lungs), and they were not yet treating her presumed PE. After being diagnosed with PE and not DVT, and after receiving heparin by IV, the coughing from the PE caused her C-section surgical site to open and the heparin contributed to bleeding at the site. Serena later received an IVC filter while in the hospital. [ 174 ] [ 179 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_817", "text": "Other notable people have been affected by DVT. Former United States President  Richard Nixon  had recurrent DVT, [ 180 ]  and so has former Secretary of State  Hillary Clinton . She was first diagnosed while  First Lady  in 1998 and again in 2009. [ 181 ]   Dick Cheney  was diagnosed with an episode while  Vice President , [ 182 ]  and TV show host  Regis Philbin  had DVT after hip-replacement surgery. [ 183 ]  DVT has also contributed to the deaths of famous people. For example, DVT and PE played a role in rapper  Heavy D 's death at age 44. [ 184 ]  NBC journalist  David Bloom  died at age 39 while covering the Iraq War from a PE that was thought to have progressed from a missed DVT, [ 185 ]  and actor  Jimmy Stewart  had DVT that progressed to a PE when he was 89. [ 183 ] [ 186 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_818", "text": "The book  Sushruta Samhita , an  Ayurvedic  text published around 600\u2013900 BC, contains what has been cited as the first description of DVT. [ 187 ]  In 1271, DVT symptoms in the leg of a 20-year-old male were described in a French manuscript, which has been cited as the first case or the first Western reference to DVT. [ 187 ] [ 188 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_819", "text": "In 1856, German physician and pathologist  Rudolf Virchow  published his analysis after the insertion of foreign bodies into the jugular veins of dogs, which migrated to the pulmonary arteries. These foreign bodies caused pulmonary emboli, and Virchow was focused on explaining their consequences. [ 189 ]  He cited three factors, which are now understood as hypercoagulability, stasis, and endothelial injury. [ 190 ]  It was not until 1950 that this framework was cited as Virchow's triad, [ 189 ]  but the teaching of Virchow's triad has continued in light of its utility as a theoretical framework and as a recognition of the significant progress Virchow made in expanding the understanding of VTE. [ 189 ] [ 190 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_820", "text": "Methods to observe DVT by ultrasound were established in the 1960s. [ 120 ]  Diagnoses were commonly performed by  impedance plethysmography  in the 1970s and 1980s, [ 191 ]  but ultrasound, particularly after utility of probe compression was demonstrated in 1986, became the preferred diagnostic method. [ 187 ]  Yet, in the mid-1990s, contrast venography and impedance plethysmography were still described as common. [ 192 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_821", "text": "Multiple pharmacological therapies for DVT were introduced in the 20th century: oral anticoagulants in the 1940s,  subcutaneous injections  of LDUH in 1962 and subcutaneous injections of LMWH in 1982. [ 193 ]  1974 was when vascular inflammation and venous thrombosis were first proposed to be interrelated. [ 112 ]  For around 50 years, a months-long warfarin (Coumadin) regimen was the mainstay of pharmacological treatment. [ 194 ] [ 195 ]  To avoid the blood monitoring required with warfarin and the injections required by heparin and heparin-like medicines,  direct oral anticoagulants  (DOACs) were developed. [ 195 ]  In the late 2000s to early 2010s, DOACs\u2014including rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa)\u2014came to the market. [ 60 ]   The New York Times  described a \"furious battle\" among the three makers of these drugs \"for the prescription pads of doctors\". [ 194 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_822", "text": "VTE costs the US healthcare system about $7 to 10 billion dollars annually. [ 169 ]  Initial and average DVT costs for a hospitalized US patient is about $10,000 (2015 estimate). [ 196 ]   In Europe, the costs for an initial VTE hospitalization are significantly less, costing about  \u20ac 2000 to 4000 (2011 estimate). [ 197 ]  Post-thrombotic syndrome is a significant contributor to DVT follow-up costs. [ 198 ]  Outpatient treatment significantly reduces costs, and treatment costs for PE exceed those of DVT. [ 199 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_823", "text": "A 2019 study published in  Nature Genetics  reported more than doubling the known  genetic loci  associated with VTE. [ 14 ]  In their updated 2018 clinical practice guidelines, the  American Society of Hematology  identified 29 separate research priorities, most of which related to patients who are acutely or critically ill. [ 63 ]  Inhibition of  factor XI ,  P-selectin ,  E-selectin , and a reduction in formation of  neutrophil extracellular traps  are potential therapies that might treat VTE without increasing bleeding risk. [ 200 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_824", "text": "Cited literature"}
{"_id": "WikiPedia_Hematology$$$corpus_825", "text": "The haemostatic (blood clotting) system involves the interaction of proteins in the blood, the blood vessel wall and the flow of blood to control bleeding and  blood clotting .  Developmental  Haemostasis  is a term that represents the maturation of the haemostatic system from birth to adulthood. There are differences in the concentration, structure and activity of many proteins involved in blood clotting. [ 1 ] [ 2 ]  These changes play an important role in physiological development and are important in providing appropriate diagnosis and treatment of bleeding and clotting disorders (e.g.  thrombosis ). [ 3 ] [ 4 ]  The age-specific differences in the blood clotting system may contribute to the fact that children are less prone to developing thrombosis compared to adults. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_826", "text": "Studies have shown that there are structural differences in some of the major blood clotting proteins in newborns and children when compared to adults. [ 5 ] [ 6 ] [ 7 ]  These structural differences can lead to differences in the activity of haemostatic proteins within the blood clotting system, as well as other physiological systems (e.g. immune system)."}
{"_id": "WikiPedia_Hematology$$$corpus_827", "text": "Some examples of age-specific differences in the structure of blood clotting proteins are: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_828", "text": "Reference ranges  demonstrate the normal test values for a healthy population. Diseases and disorders are diagnosed when a test value is outside the reference range. Many laboratories compare paediatric results to adult reference ranges or to published paediatric reference ranges that may not be specific for the test used. [ 11 ]  This can lead to misdiagnosis or over-diagnosis of blood clotting disorders as many proteins exist at levels during stages of infancy that would be associated with disease in adults. This can lead to unnecessary stress for families and can have significant medical implications for the child (e.g. further testing).\nThe differences in the haemostatic proteins can lead to different interactions with  anticoagulant  drugs that are used to prevent and treat thrombosis in children. [ 12 ] [ 13 ]  More studies are required to determine the optimal treatment strategies and doses of anticoagulants in children. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_829", "text": "The role of developmental haemostasis in normal physiology is still not fully understood. It has been observed that the newborn haemostatic system is protective and contributes to a decreased risk of bleeding or thrombosis compared to adults. The differences may also be due to the role haemostatic proteins play within other physiological systems. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_830", "text": "Divicine  (2,6-diamino-4,5-dihydroxypyrimidine) is an oxidant and a base with alkaloidal properties found in  fava beans  and  Lathyrus sativus . It is an  aglycone  of  vicine . A common derivative is the diacetate form (2,6-diamino-1,6-dihydro-4,5-pyrimidinedione). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_831", "text": "Divicine is found in  fava beans  and in the legume  Lathyrus sativus , also known as khesari, which is a cheap and robust food source commonly grown in Asia and East Africa. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_832", "text": "In plants, reduced divicine is formed from the hydrolysis of the inactive \u03b2\u2013glucoside,  vicine . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_833", "text": "A simplified three-step process for artificial divicine synthesis:"}
{"_id": "WikiPedia_Hematology$$$corpus_834", "text": "Some chemical characteristics of divicine have been examined. It is known that it vigorously reduces  alkaline  solutions of 2,6-dichlorophenolindophenol, phosphomolybdate or phosphotungstate and produces an intense blue colour when reacting with an ammoniacal ferric chloride solution, which is used for the identification and proof of the presence of an enolic  hydroxyl  group."}
{"_id": "WikiPedia_Hematology$$$corpus_835", "text": "Divicine is very unstable if oxygen is present and the oxidation is most rapid at alkaline pH levels. The half-life of divicine, at room temperature and neutral pH, is around half an hour. Both compounds are almost immediately destroyed by boiling, and breakdown in regular conditions can be accelerated by the presence of heavy metal ions, especially Cu 2+ . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_836", "text": "Divicine has been deemed a  hemotoxic  component of  fava beans  and plays a role in the development of  favism , a disorder that involves a hemolytic response to the consumption of broad beans due to  glucose-6-phosphate dehydrogenase  (G6PD or G6PDH) deficiency.  This deficiency, an X-linked recessive hereditary disease, is the most common enzyme deficiency worldwide.  It is particularly common in those of African, Asian, Mediterranean, and Middle-Eastern descent.  Symptoms of  favism  include  hemolysis , prolonged  jaundice ,  kernicterus , and even  acute renal failure  in extreme cases. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_837", "text": "Divicine reacts with oxygen in red blood cells, which creates  reactive oxygen species  such as  hydrogen peroxide  and  superoxide anion . These molecules are strong oxidizers of  NADPH  and  glutathione . [ 6 ] \u00a0G6PD deficient individuals cannot regenerate NADPH quickly enough to prevent depletion of glutathione. This depletion results in the cells having no protection against oxidative stress caused by the aglycones. Oxidative stress leads to damage of haemoglobin and disulphide bond aggregates ( Heinz bodies ), which result in haemolytic anaemia, called favism. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_838", "text": "Divicine is also present in and at least partially responsible for the poisonous action of  Lathyrus sativus  - a legume commonly grown in drought- and famine-prone regions of Asia and East Africa as an \u2018insurance crop\u2019 for human consumption and livestock feed when other crops fail to grow, despite their known health hazards. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_839", "text": "In vitro studies in rats showed that a hemotoxic dose of divicine of 1.5 mM, when added to a suspension of red blood cells, resulted in a rapid decline in cellular glutathione, formation of  echinocytes  and damage to the membrane skeleton. This resulted in a decrease in  haematocrit . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_840", "text": "Duteplase  is a  plasminogen activator . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_841", "text": "Effective arterial blood volume  (EABV) refers to the adequacy of the arterial blood volume to \"fill\" the capacity of the  arterial vasculature . Normal EABV exists when the ratio of cardiac output to peripheral resistance maintains venous return and cardiac output at normal levels. EABV can be reduced, therefore, by factors which reduce actual arterial blood volume (hemorrhage, dehydration), increase arterial vascular capacitance (cirrhosis, sepsis) or reduce cardiac output (congestive heart failure). EABV can be reduced in the setting of low, normal, or high actual blood volume. Whenever EABV falls, the kidney is triggered to retain sodium and water. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_842", "text": "In cases of  edema , increases in  extracellular fluid  (ECF) is associated with a corresponding decrease in EABV.  The kidneys detect changes in EABV and through Na +  excretions, they attempt to restore EABV balance.  The kidney mechanisms used to restore EABV include, (1) increased  sympathetic  nerve activity; (2) decreased  Atriopeptin  (ANP) secretion from the atria; (3) increased  oncotic pressure  ( Starling forces ); (4) increased activity of the  Renin\u2013angiotensin\u2013aldosterone system . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_843", "text": "Elliptocytes , also known as  ovalocytes  or  cigar cells , are abnormally shaped red blood cells that appear oval or elongated, from slightly egg-shaped to rod or pencil forms. They have normal central pallor with the hemoglobin appearing concentrated at the ends of the elongated cells when viewed through a  light microscope . The ends of the cells are blunt and not sharp like  sickle cells . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_844", "text": "Elliptocytes are commonly associated with  hereditary elliptocytosis . However, they may also be seen in  iron deficiency anemia ,  sepsis ,  malaria  and other pathological states that decrease red blood cell turnover and or production. [ 2 ]  In the case of iron deficiency anemia,  microcytosis  and  hypochromia  would also be expected. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_845", "text": "Rare elliptocytes (less than 1%) on a  peripheral blood smear  are a normal finding. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_846", "text": "These abnormal red blood cells are seen in higher numbers in the  blood films  of patients with  blood disorders  such as: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_847", "text": "An  embolism  is the lodging of an  embolus , a blockage-causing piece of material, inside a  blood vessel . [ 1 ]  The embolus may be a blood clot ( thrombus ), a fat globule ( fat embolism ), a bubble of air or other gas ( gas embolism ),  amniotic fluid  ( amniotic fluid embolism ), or  foreign material ."}
{"_id": "WikiPedia_Hematology$$$corpus_848", "text": "An embolism can cause partial or total blockage of  blood flow  in the affected vessel. [ 2 ]  Such a blockage ( vascular occlusion ) may affect a part of the body distant from the origin of the embolus. An embolism in which the embolus is a piece of thrombus is called a  thromboembolism ."}
{"_id": "WikiPedia_Hematology$$$corpus_849", "text": "An embolism is usually a pathological event, caused by illness or injury. Sometimes it is created intentionally for a therapeutic reason, such as to  stop bleeding  or to kill a cancerous tumor by stopping its blood supply. Such therapy is called  embolization ."}
{"_id": "WikiPedia_Hematology$$$corpus_850", "text": "There are different types of embolism, some of which are listed below."}
{"_id": "WikiPedia_Hematology$$$corpus_851", "text": "Embolism can be classified based on where it enters the circulation, either in  arteries  or in  veins . Arterial embolism are those that follow and, if not dissolved on the way, lodge in a more distal part of the  systemic circulation . Sometimes, multiple classifications apply; for instance a  pulmonary embolism  is classified as an arterial embolism as well, [ 3 ]  because the clot follows the  pulmonary artery  carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins, e.g.  deep vein thrombosis . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_852", "text": "Arterial embolism  can cause occlusion in any part of the body. It is a major cause of  infarction  (tissue death from blockage of the blood supply). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_853", "text": "An embolus lodging in the brain from either the  heart  or a  carotid artery  will most likely be the cause of a  stroke  due to  ischemia . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_854", "text": "An arterial embolus might originate in the heart (from a thrombus in the  left atrium , following  atrial fibrillation  or be a septic embolus resulting from  endocarditis ). Emboli of  cardiac origin  are frequently encountered in clinical practice.  Thrombus formation within the atrium occurs mainly in patients with  mitral valve  disease, and especially in those with  mitral valve   stenosis  (narrowing), with  atrial fibrillation  (AF).  In the absence of AF, pure mitral regurgitation has a low incidence of  thromboembolism . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_855", "text": "The risk of emboli forming in AF depends on other risk factors such as age,  hypertension ,  diabetes , recent heart failure, or previous stroke.\nThrombus formation can also take place within the  ventricles , and it occurs in approximately 30% of anterior-wall  myocardial infarctions , compared with only 5% of inferior ones. Some other risk factors are poor ejection fraction (<35%), size of infarct, and the presence of AF. In the first three months after infarction, left-ventricle  aneurysms  have a 10% risk of emboli forming. Patients with  prosthetic  valves also carry a significant increase in risk of thromboembolism. Risk varies, based on the valve type (bioprosthetic or mechanical); the position (mitral or aortic); and the presence of other factors such as AF, left-ventricular dysfunction, and previous emboli [ citation needed ] ."}
{"_id": "WikiPedia_Hematology$$$corpus_856", "text": "Emboli often have more serious consequences when they occur in the so-called \"end circulation\": areas of the body that have no redundant blood supply, such as the brain and  heart . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_857", "text": "Assuming a normal circulation, an embolus formed in a systemic  vein  will always impact in the lungs, after passing through the right side of the heart. This will form a  pulmonary embolism  that will result in a blockage of the  main artery of the lung  and can be a complication of  deep-vein thrombosis . The most common sites of origin of pulmonary emboli are the  femoral  veins . The deep veins of the calf are the most common sites of actual thrombi. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_858", "text": "In paradoxical embolism, also known as crossed embolism, an embolus from the veins crosses to the arterial blood system. This is generally found only with heart problems such as septal defects  (holes in the cardiac septum) between the atria or ventricles. The most common such abnormality is  patent foramen ovale , occurring in about 25% of the adult population, but here the defect functions as a valve which is normally closed, because pressure is slightly higher in the left side of the heart. Sometimes, for example if a patient coughs just when an embolus is passing, it might cross to the arterial system. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_859", "text": "The direction of the embolus can be one of two types: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_860", "text": "In anterograde embolism, the movement of emboli is in the direction of blood flow. In retrograde embolism, the emboli move in opposition to the blood flow direction; this is usually significant only in blood vessels with low pressure (veins) or with emboli of high weight. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_861", "text": "The word  embolism  comes from the Greek \u1f10\u03bc\u03b2\u03bf\u03bb\u03b9\u03c3\u03bc\u03cc\u03c2, meaning \"interpressure\". [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_862", "text": "An  embolus  ( / \u02c8 \u025b m b \u0259 l \u0259 s / ; [ 1 ]   pl. :  emboli ; from the Greek \u1f14\u03bc\u03b2\u03bf\u03bb\u03bf\u03c2 \"wedge\", \"plug\") is an unattached mass that travels through the  bloodstream  and is capable of creating blockages. When an embolus occludes a blood vessel, it is called an  embolism  or embolic event. [ 2 ]  There are a number of different types of emboli, including  blood clots ,  cholesterol  plaque or crystals,  fat globules ,  gas bubbles , and  foreign bodies , which can result in different types of embolisms."}
{"_id": "WikiPedia_Hematology$$$corpus_863", "text": "The term is distinct from  embolism  and  thromboembolism , which may be consequences of an embolus, as discussed below. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_864", "text": "The term was coined in 1848 by  Rudolf Virchow  as part of his foundational research into  blood clots . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_865", "text": "The term embolus refers generally to any free-floating mass in the bloodstream. A related term is embolism, which describes the phenomenon of an embolus lodging in a vessel and creating a blockage. [ 2 ]  An embolism is technically a consequence of an embolus, but the terms are sometimes used interchangeably. [ 6 ]  Both emboli and embolisms are usually named according to their composite substance. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_866", "text": "In contrast to emboli, which can cause occlusion at sites distant from their points of origin, there are also non-traveling blockages that develop locally from vascular trauma and inflammation or other epithelial pathology, such as  atheromata  and  thrombi . If these local blockages dislodge into circulation, they become emboli and if not broken down during circulation, may cause embolism(s). [ 3 ]  For example, a  thromboembolism  is the result of a thrombus that has broken off the interior of a blood vessel and caused a vessel blockage elsewhere in the circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_867", "text": "Details of embolism classification are discussed below."}
{"_id": "WikiPedia_Hematology$$$corpus_868", "text": "The physical composition of the embolic material is the defining feature for classification, and this composition reflects the underlying pathophysiologic mechanism of the embolus' formation. Furthermore, different types of emboli result in different types of embolisms, each with distinct clinical characteristics."}
{"_id": "WikiPedia_Hematology$$$corpus_869", "text": "In  thromboembolism , the thrombus (blood clot) from a blood vessel is completely or partially detached from the site of thrombosis (clot). The blood flow will then carry the embolus (via blood vessels) to various parts of the body where it can block the lumen (vessel cavity) and cause vessel obstruction or occlusion. The free-moving thrombus is called an embolus. [ 7 ]  A thrombus is always attached to the vessel wall and is never freely moving in the blood circulation. This is also the key difference for pathologists to determine the cause of a blood clot, either by thrombosis or by post-mortem blood clot. Vessel obstruction will then lead to different pathological issues such as blood  stasis  and  ischemia . However, not only thromboembolism will cause the obstruction of blood flow in vessels, but also any kind of embolism is capable of causing the same problem."}
{"_id": "WikiPedia_Hematology$$$corpus_870", "text": "Fat embolism  usually occurs when endogenous (from sources within the organism) fat tissue escapes into the blood circulation. The usual cause of fat embolism is therefore the  fracture  of tubular bones (such as the  femur ), which will lead to the leakage of fat tissue within the bone marrow into ruptured vessels. There are also exogenous (from sources of external origin) causes such as intravenous injection of  emulsions ."}
{"_id": "WikiPedia_Hematology$$$corpus_871", "text": "An  air embolism , on the other hand, is usually always caused by exogenic factors. This can be the rupture of  alveoli , and inhaled air can be leaked into the blood vessels. Other more-common causes include the puncture of the  subclavian vein  by accident or during operation where there is negative pressure. Air is then sucked into the veins by the negative pressure caused by thoracic expansion during the inhalation phase of respiration. Air embolism can also happen during intravenous therapy, when air is leaked into the system (however this  iatrogenic  error in modern medicine is extremely rare)."}
{"_id": "WikiPedia_Hematology$$$corpus_872", "text": "Gas embolism  is a common concern for deep-sea divers because the gases in human blood (usually nitrogen and helium) can be easily dissolved at higher amounts during the descent into deep sea. However, when the diver ascends to the normal atmospheric pressure, the gases become insoluble, causing the formation of small bubbles in the blood. This is also known as  decompression sickness  or the bends. This phenomenon is explained by  Henry's Law  in physical chemistry."}
{"_id": "WikiPedia_Hematology$$$corpus_873", "text": "Embolism by  other materials  is rare.  Septic embolism  happens when a purulent tissue ( pus -containing tissue) is dislodged from its original focus.  Tissue embolism  is a near-equivalent to  cancer   metastasis , which happens when cancer tissue infiltrates blood vessels, and small fragments of them are released into the blood stream.  Foreign-body embolism  happens when exogenous\u2014and only exogenous\u2014materials such as  talc  enter the blood stream and cause occlusion or obstruction of blood circulation.   Bullet  embolism occurs in approximately 0.3% cases of  gunshot wounds . [ 8 ]   Amniotic-fluid embolism  is a rare complication of childbirth."}
{"_id": "WikiPedia_Hematology$$$corpus_874", "text": "Emboli are clinically significant for their capacity to cause embolisms, which are a major cause of morbidity and mortality. [ 9 ] [ 10 ]  By themselves, emboli are pathologic and therefore indicate some underlying dysfunction."}
{"_id": "WikiPedia_Hematology$$$corpus_875", "text": "It may be difficult in the clinical setting to differentiate a thrombotic event (i.e., a local clot at the site of symptoms) from an embolic event (i.e., local obstruction due to a free-floating mass that traveled through circulation from elsewhere in the body)."}
{"_id": "WikiPedia_Hematology$$$corpus_876", "text": "Septic emboli may also be a contributor to spreading infection through the bloodstream to other tissues. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_877", "text": "Rudolf Virchow , the German physician and \"father of pathology\", is generally credited with the first explanation of the relationship between thrombi, emboli, and embolisms. He coined the terms embolism (initially called \"Embolia\") and thrombosis while proposing a hypothesis for the pathophysiology of pulmonary thromboembolism. [ 5 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_878", "text": "In his work, he described the consequences of thrombosis and the factors leading thereto, a concept which today is known as  Virchow's Triad . However, there is some dispute regarding certain aspects of this attribution. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_879", "text": "Endothelial cell anergy  is a condition during the process of  angiogenesis , [ 2 ]  where  endothelial cells , the cells that line the inside of blood vessels, can no longer respond to  inflammatory cytokines . [ 3 ] [ 4 ]  These cytokines are necessary to induce the expression of  cell adhesion molecules  to allow  leukocyte  infiltration from the blood into the tissue at places of  inflammation , such as a tumor. This condition, which protects the tumor from the immune system, is the result of exposure to angiogenic growth factors."}
{"_id": "WikiPedia_Hematology$$$corpus_880", "text": "Next to endothelial cell anergy, there are more vascular mechanisms that contribute to escape from immunity, such as the expression of  immune checkpoint  molecules (e.g.  PD-L1 /2) and proteins that can deliver death signals in leukocytes ( Fas ligand  and  galectin-1 )."}
{"_id": "WikiPedia_Hematology$$$corpus_881", "text": "The formation of a leukocyte infiltrate at places of inflammation is dependent on the interaction of leukocytes in the blood with the vascular wall. This interaction and  leukocyte extravasation  is mediated by  cell adhesion molecules  on both leukocytes and  endothelium . The endothelial cells normally express low levels of adhesion molecules, but at places of inflammation these adhesion molecules become expressed due to the exposure to inflammatory cytokines, such as interleukin 1,  interferon gamma  and  tumor necrosis factor  alpha."}
{"_id": "WikiPedia_Hematology$$$corpus_882", "text": "Endothelial cell anergy was first described in 1996 when it was shown that endothelial cells in a tumor are not able to upregulate the expression of adhesion molecules, such as  intercellular adhesion molecule-1  (ICAM-1, CD54),  vascular cell adhesion molecule-1  (VCAM-1, CD106) and  E-selectin  (CD62E), as a result from exposure angiogenic stimulation by e.g.  vascular endothelial growth factor  (VEGF) or fibroblast growth factor (FGF). [ 3 ] [ 4 ]  The result of endothelial cell anergy in a tumor is that leukocytes will not be able to reach the tumor, resulting in hampering of the anti-tumor immune response. Next to induction of endothelial cell anergy, ongoing angiogenesis is immunosuppressive at multiple levels. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_883", "text": "Since this form of immune suppression is mediated by angiogenic stimulation, it was shown that anti-angiogenic therapy could revert endothelial cell anergy, allow leukocytes to infiltrate tumors and stimulate anti-tumor immunity. [ 6 ] [ 7 ]  Overcoming endothelial cell anergy underlies the current success of clinical treatment of cancer with a combination of anti-angiogenic therapy and immunotherapy, mainly  immune checkpoint blockade . [ 8 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_884", "text": "It has been suggested that endothelial cell anergy also occurs during embryonic stages to allow efficient development of the  embryo  under immune silent conditions and help protecting the embryo from the  maternal immune response . Tumors have hijacked this process to grow under the support of endothelial cell anergy mediated immune suppression. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_885", "text": "The concept of endothelial cell anergy was introduced by Griffioen and coworkers in 1996. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_886", "text": "Endovascular and hybrid trauma and bleeding management   is a new and rapidly evolving concept within medical healthcare and endovascular  resuscitation . It involves early multidisciplinary evaluation and management of hemodynamically unstable patients with traumatic injuries as well as being a bridge to definitive treatment. [ 1 ] [ 2 ] [ 3 ]  It has recently been shown that the EVTM concept may also be applied to non-traumatic hemodynamically unstable patients. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_887", "text": "The fundamental principles of  trauma care  are built around  advanced trauma life support  (ATLS) guidelines using the mnemonic  ABCDE  for early assessment of the patient and detection of airway and circulatory problems. This way, life-threatening conditions are identified and resuscitation may be initiated, despite the lack of definitive diagnosis. [ 5 ]  The EVTM concept of acute trauma care incorporates modern endovascular techniques and procedures as additional adjuncts to this well-established protocol. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  The new suggested algorithm of  A ABCDE has emerged for EVTM enabled providers. The additional \u201cA\u201d stands for  A ccess, indicating the importance of gaining early vascular access to the  femoral artery  (and  vein ), and is fundamental to this concept of trauma care. [ 6 ]  As with traditional trauma care, vascular access in the peripheral or central veins allows for blood sampling and administration of drugs or fluids. However, for EVTM enabled providers, early femoral arterial access provides the possibility to use potentially lifesaving endovascular diagnostic and therapeutic tools for temporary management and bridge to definitive endovascular or open surgical treatment, in addition to arterial blood sampling and invasive blood pressure monitoring. [ 1 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_888", "text": "One of the major elements of EVTM is the multidisciplinary team approach. By combining the expertise present allows for optimal treatment not just at the time of patient arrival but also in the pre-hospital setting and later in the operating suite. It is all about teamwork with a common goal, to save the patient. It allows for the hybrid use of open surgery and endovascular methods for hemorrhage control and definitive treatment. In a hemodynamically unstable bleeding patient, traditional treatment is  laparotomy  with abdominal packing, but an EVTM team might simultaneously gain vascular access and perform REBOA for proximal control or embolization as a part in definitive treatment. An EVTM multidisciplinary approach requires complete transparency, good communication and leadership. It is however also important to remember that just because you can, doesn't mean that you should use an EVTM approach. EVTM should always be considered but only used in the optimally selected patient at the right time if the expertise and equipment is present to do it safely. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_889", "text": "In the acute setting, the femoral artery is most often the easiest to identify and access thanks to its typically reasonable size. This is however obviously relative to individual anatomical differences and hemodynamic state of the patient. It is in general beneficial to gain early vascular access as the inguinal area is seldom occupied and, if possible, attempt to do this on the contralateral side to a major lower extremity injury. Access may be attempted by ultrasound-guided or blind puncture and surgical cut-down, where ultrasound-guided is the safest and most reasonable alternative for the less experienced. Vascular access is based on the  Seldinger technique . After puncturing the vessel with a needle and confirmation of arterial access a wire is advanced, the needle removed and a vascular sheath is introduced. The access is then ready to use. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_890", "text": "The use of endovascular modalities for bleeding control and treatment on hemodynamically unstable trauma patients is increasing. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for hemorrhage control, angioembolization and stent grafts are highly established tools used for both arterial and venous hemorrhage in both traumatic and non-traumatic patients. [ 4 ] [ 9 ] [ 10 ] [ 11 ]  To be able to provide an endovascular opportunity for resuscitation requires good organization and a well-established endovascular team. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_891", "text": "Acute care of a hemodynamically unstable trauma patient is never an ideal task. [ 12 ] [ 13 ]  The emphasis is on stopping blood extravasation and hemodynamic stabilisation without delay, despite if it is pre-hospital, in the emergency department or in a hybrid operating suite. REBOA, also called Aortic Balloon Occlusion (ABO), is a powerful endovascular tool that inflates an intra-aortic balloon occluding the lumen of the vessel and decreased or completely prevents blood flow to the more distal parts. If inflated in the aorta proximal to the identified source of bleeding it may help to diminish or stop blood extravasation, also potentially aiding to increase cardiac afterload. This should increase the central pressure and secure adequate myocardial and cerebral perfusion, hopefully rendering the patient, at least temporarily, more hemodynamically stable. REBOA is used as an endovascular tool for hemodynamic control and as a resuscitation adjunct that may prolong the life of the critical patient. REBOA is not only used from an endovascular resuscitation aspect, but may also to help by allowing more time for definitive treatment. [ 6 ] [ 9 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ excessive citations ]"}
{"_id": "WikiPedia_Hematology$$$corpus_892", "text": "Embolization  is a minimally invasive technique used in EVTM of selected hemodynamically unstable patients with both  traumatic  and non-traumatic injuries. It is the artificial creation of a thrombus by the introduction of various substances to intentionally occlude a vessel with the aim to stop or diminish blood extravasation and is a critical part of the modern management of arterial injuries. [ 6 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_893", "text": "Stent grafts , or endo-grafts, are a more permanent solution in the hemodynamically unstable patient and are an important part of the tool kit for EVTM. They are self-expanding artificial reconstructions of vessels with fabric coating deployed inside the original vessel and help to gain temporary control, stop the hemorrhage and repair the damaged vessel wall. They can be used and positioned, by an experienced surgeon, in every major vessel in the body. [ 6 ] [ 11 ] [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_894", "text": "The  Journal of Endovascular Resuscitation and Trauma Management  (JEVTM) is an open access platform for publishing  peer-reviewed research  regarding endovascular hybrid hemorrhage control. The first issue was published August 2017 with continued publications quarterly. The editorial board is made up by clinicians and scientists who are experts within the field. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_895", "text": "In  hematology ,  erythrocyte deformability  refers to the ability of  erythrocytes  (red blood cells, RBCs) to change shape under a given level of applied  stress  without  hemolysing  (rupturing). This is an important property because erythrocytes must change their shape extensively under the influence of mechanical forces in  fluid flow  or while passing through  microcirculation  (see  hemodynamics ). The extent and  geometry  of this shape change can be affected by the mechanical properties of the erythrocytes, the magnitude of the applied forces, and the orientation of erythrocytes with the applied forces.  Deformability  is an intrinsic cellular property of erythrocytes determined by geometric and material properties of the  cell membrane , [ 1 ]  although as with many measurable properties the ambient conditions may also be relevant factors in any given measurement. No other cells of  mammalian  organisms have deformability comparable with erythrocytes; furthermore, non-mammalian erythrocytes are not deformable to an extent comparable with mammalian erythrocytes. In human RBCs there are structural supports that aid resilience, which include the  cytoskeleton :  actin  and  spectrin  that are held together by  ankyrin ."}
{"_id": "WikiPedia_Hematology$$$corpus_896", "text": "Shape change of erythrocytes under applied forces (i.e., shear forces in blood flow) is reversible and the biconcave-discoid shape, which is normal for most mammals, is maintained after the removal of the deforming forces. In other words, erythrocytes behave like  elastic  bodies, while they also resist to shape change under deforming forces. This viscoelastic behavior of erythrocytes is determined by the following three properties: [ 2 ]  1) Geometry of erythrocytes; the biconcave-discoid shape provides an extra surface area for the cell, enabling shape change without increasing surface area. This type of shape change requires significantly smaller forces than those required for shape change with surface area expansion. 2) Cytoplasmic viscosity; reflecting the  cytoplasmic   hemoglobin  concentration of erythrocytes. 3) Visco-elastic properties of erythrocyte membrane, mainly determined by the special membrane skeletal network of erythrocytes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_897", "text": "Erythrocyte deformability is an important determinant of blood viscosity, hence blood flow resistance in the vascular system. [ 3 ]  It affects blood flow in large blood vessels, due to the increased frictional resistance between fluid laminae under laminar flow conditions. It also affects the microcirculatory blood flow significantly, where erythrocytes are forced to pass through blood vessels with diameters smaller than their size. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_898", "text": "Erythrocyte deformability is altered under various  pathophysiological  conditions.  Sickle-cell disease  is characterized by extensive impairment in erythrocyte deformability, being dependent on the  oxygen   partial pressure . Erythrocyte deformability has also been demonstrated to be impaired in  diabetes , peripheral  vascular  diseases,  sepsis  and a variety of other diseases.  The property offers broad utility in disease diagnosis [ 4 ]  (also see  Measurement , below)."}
{"_id": "WikiPedia_Hematology$$$corpus_899", "text": "Stored packed red blood cells (sometimes denoted \"pRBC\" or \"StRBC\") also experience changes in membrane properties like deformability during storage and related processing, as part of a broader phenomenon known as \"storage lesion.\" While the clinical implications are still being explored, deformability can be indicative of quality or preservation thereof for stored RBC product available for  blood transfusion . [ 5 ] [ 6 ] [ 7 ]   Perfusion (or perfusability) is a deformability-based metric that may offer a particularly physiologically-relevant representation of storage-induced deterioration of RBC occurring in  blood banks , and the associated impacts of storage conditions/systems. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_900", "text": "Erythocyte deformability is a measurable property, and various means for its measurement have been explored - with each having results and significance being highly particularized to the given approach employed. Accordingly, the term is somewhat loose in the sense that a given cell or sample of cells may be deemed significantly more \"deformable\" by one means/metric relative to another means/metric. Thus for meaningful \"apples-to-apples\" comparisons involving cell deformability, it is important to utilize the same qualitative approach. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_901", "text": "Ektacytometry  based on  laser diffraction analysis  is a commonly preferred (and a fairly direct) method for measuring deformability. [ 9 ]   Another direct metric is  optical tweezers , which targets individual cells.  Deformability can in effect be measured indirectly, such as by how much pressure and/or time it takes cells pass through pores of a filter (i.e.,  filterability  or filtration) [ 10 ]  or perfuse through capillaries ( perfusion ), [ 11 ]   in vitro  or  in vivo , having smaller diameters than the cells'.  Some deformability tests may be more physiologically-relevant than others for given applications. For example, perfusion is more sensitive to relatively small changes in deformability (compared to filterability), [ 12 ]  thus making it preferable for assessing RBC deformability in contexts where microcirculatory implications are of particular interest.  Moreover, some tests may track how deformability itself changes as conditions change and/or as deformation is repeated. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_902", "text": "Erythrocytes/RBC may also be tested for other (related) membrane properties, including  erythrocyte fragility  (osmotic or mechanical) and cell morphology.  Morphology can be measured by indexes which characterize shape changes of differences among cells.  Fragility testing involves subjecting a sample of cells to osmotic and/or mechanical stress(es), then ascertaining how much hemolysis results thereafter, and then characterizing susceptibility to or propensity for stress-induced hemolysis with an index or profile (which can be useful to assess cells' ability to withstand sustained or repeated stresses). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_903", "text": "Other related red blood cell properties can include adhesion and aggregation, which along with deformability are often classed as RBC \"flow properties.\""}
{"_id": "WikiPedia_Hematology$$$corpus_904", "text": "151176"}
{"_id": "WikiPedia_Hematology$$$corpus_905", "text": "227358"}
{"_id": "WikiPedia_Hematology$$$corpus_906", "text": "ENSG00000178752"}
{"_id": "WikiPedia_Hematology$$$corpus_907", "text": "ENSMUSG00000047443"}
{"_id": "WikiPedia_Hematology$$$corpus_908", "text": "Q4G0M1"}
{"_id": "WikiPedia_Hematology$$$corpus_909", "text": "Q6PGN1"}
{"_id": "WikiPedia_Hematology$$$corpus_910", "text": "NM_152521 NM_001291832"}
{"_id": "WikiPedia_Hematology$$$corpus_911", "text": "NM_173395"}
{"_id": "WikiPedia_Hematology$$$corpus_912", "text": "NP_001278761"}
{"_id": "WikiPedia_Hematology$$$corpus_913", "text": "NP_775571"}
{"_id": "WikiPedia_Hematology$$$corpus_914", "text": "Erythroferrone  is a protein hormone encoded in humans by the  ERFE  gene.  Erythroferrone is produced by  erythroblasts , inhibits the production of  hepcidin  in the liver, and so increases the amount of  iron  available for  hemoglobin  synthesis. [ 5 ] [ 6 ]  Skeletal muscle secreted ERFE has been shown to maintain systemic metabolic homeostasis. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_915", "text": "It was identified in 2014 in mice where the transcript was found in  bone marrow , encoded by the mouse  Fam132b  gene. [ 6 ]   The homologous gene in humans is  FAM132B  and the sequence is conserved in other species. The protein is synthesized by erythroblasts and secreted. [ 6 ]   This sequence had previously been found expressed in mouse skeletal muscle, called  myonectin  (CTRP15), and linked to lipid homeostasis. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_916", "text": "Seldin and his colleagues have written: \"Myonectin is expressed and secreted predominantly by skeletal muscle.... (Our) results suggest that myonectin is a nutrient-responsive metabolic regulator secreted by skeletal muscle in response to changes in cellular energy state resulting from glucose or fatty acid fluxes. Many metabolically relevant secreted proteins (e.g.  adiponectin ,  leptin ,  resistin , and  RBP ) and the signaling pathways they regulate in tissues are known to be dysregulated in the condition of obesity. The reduction in expression and circulating levels of myonectin in the obese state may represent yet another component of the complex metabolic circuitry dysregulated by excess caloric intake. Although exercise has long been known to have profound positive impacts on systemic insulin sensitivity and energy balance, the underlying mechanisms remain incompletely understood. That voluntary exercise dramatically increases the expression and circulating levels of myonectin to promote fatty acid uptake into cells may underlie one of the beneficial effects of physical exercise.\" [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_917", "text": "Myonectin was shown in 2015 to be identical to erythroferrone, a hormone produced in erythroblasts that is involved in iron metabolism. [ 5 ] > [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_918", "text": "Erythroferrone in humans is transcribed as a  precursor  of 354 amino acids, with a  signal peptide  of 28 amino acids.  The mouse gene encodes a 340 amino acid protein which is 71% identical. [ 6 ]   Homology is greater at the C-terminal where there is a  TNF-alpha -like domain. [ 10 ]  As a member of the C1q/TNF-Related Protein ( CTRP ) family, erythroferrone has a 4-domain structure with a unique N-terminus. The two larger domains are connected by a short, proline-rich, collagenous linker that is thought to promote protein multimerization. Erythroferrone is predicted to contain two PCSK3/ furin  recognition sites. The protein hormone weighs approximately 35-40  kDa . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_919", "text": "Erythroferrone is a hormone that regulates  iron metabolism  through its actions on hepcidin. [ 5 ]   As shown in mice and humans, it is produced in erythroblasts, which proliferate when new red cells are synthesized, such as after hemorrhage when more iron is needed (so-called stress  erythropoiesis ). [ 12 ]   This process is governed by the renal hormone,  erythropoietin . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_920", "text": "Its mechanism of action is to inhibit the expression of the liver hormone, hepcidin. [ 12 ]   This process is governed by the renal hormone,  erythropoietin . [ 6 ]   By suppressing hepcidin, ERFE increases the function of the cellular iron export channel,  ferroportin .  This then results in increased iron absorption from the  intestine  and mobilization of iron from stores, which can then be used in the synthesis of  hemoglobin  in new  red blood cells . [ 6 ]  Erythroferrone inhibits hepcidin synthesis by binding bone morphogenetic proteins and thereby inhibiting the bone morphogenetic protein pathway that controls hepcidin expression. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_921", "text": "Mice deficient in the gene encoding erythroferrone have transient maturational hemoglobin deficits and impaired hepcidin suppression in response to phlebotomy with a delayed recovery from  anemia . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_922", "text": "In its role as myonectin, it also promotes lipid uptake into adipocytes and hepatocytes. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_923", "text": "Synthesis of erythroferrone is stimulated by erythropoietin binding to its receptor and activating the  Jak2 / Stat5  signaling pathway. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_924", "text": "The clinical significance in humans is becoming clear. [ 15 ]   From parallels in the mouse studies, there may be diseases where its function could be relevant.  In a mouse model of  thalassemia , its expression is increased, resulting in  iron overload , which is also a feature of the human disease. [ 16 ]   A role in the recovery from the  anemia of inflammation  in mice has been shown [ 17 ]  and involvement in inherited anemias with ineffective erythropoiesis, anemia of chronic kidney diseases and iron-refractory iron-deficiency anemia has been suggested. [ 6 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_925", "text": "Erythroferrone levels in blood have been shown by immunoassay to be higher after blood loss or  erythropoetin  administration. Patients with  beta-thalassemia  have very high levels, and these decrease after  blood transfusion . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_926", "text": "Faggot cells  are cells normally found in the hypergranular form of  acute promyelocytic leukemia  (FAB - M3). These promyelocytes (not blast cells) have numerous  Auer rods  in the  cytoplasm  which gives the appearance of a  bundle of sticks , from which the cells are given their name. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_927", "text": "30061"}
{"_id": "WikiPedia_Hematology$$$corpus_928", "text": "53945"}
{"_id": "WikiPedia_Hematology$$$corpus_929", "text": "ENSG00000138449"}
{"_id": "WikiPedia_Hematology$$$corpus_930", "text": "ENSMUSG00000025993"}
{"_id": "WikiPedia_Hematology$$$corpus_931", "text": "Q9NP59"}
{"_id": "WikiPedia_Hematology$$$corpus_932", "text": "Q9JHI9"}
{"_id": "WikiPedia_Hematology$$$corpus_933", "text": "NM_014585"}
{"_id": "WikiPedia_Hematology$$$corpus_934", "text": "NM_016917"}
{"_id": "WikiPedia_Hematology$$$corpus_935", "text": "NP_055400"}
{"_id": "WikiPedia_Hematology$$$corpus_936", "text": "NP_058613"}
{"_id": "WikiPedia_Hematology$$$corpus_937", "text": "Ferroportin-1 , also known as  solute carrier family 40 member 1 (SLC40A1)  or  iron-regulated transporter 1 (IREG1) , is a  protein  that in humans is encoded by the  SLC40A1   gene . [ 5 ]  Ferroportin is a  transmembrane protein  that transports  iron  from the inside of a  cell  to the outside of the cell. Ferroportin is the only known iron exporter. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_938", "text": "After dietary iron is absorbed into the cells of the small intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream. Fpn also mediates the efflux of iron recycled from macrophages resident in the spleen and liver. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_939", "text": "Ferroportin is regulated by hepcidin, a hormone produced by the liver;  hepcidin  binds to Fpn and limits its iron-efflux activity, thereby reducing iron delivery to the blood plasma. [ 8 ]  Therefore, the interaction between Fpn and hepcidin controls systemic  iron homeostasis ."}
{"_id": "WikiPedia_Hematology$$$corpus_940", "text": "Members of the ferroportin family consist of 400-800  amino acid  residues, [ 9 ]  with a  highly conserved   histidine  at residue position 32 (H32), and exhibit 8-12 putative  transmembrane domains . Human Fpn consists of 571 amino acid residues. [ 9 ]  When H32 is mutated in mice, iron transport activity is impaired. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_941", "text": "Recent crystal structures generated from a bacterial  homologue  of ferroportin (from  Bdellovibrio bacteriovorus ) revealed that the Fpn structure resembles that of  major facilitator superfamily  (MFS) transporters. [ 11 ] [ 12 ]  The prospective substrate binding site is located at the interface between the  N-terminal  and  C-terminal  halves of the protein, and is alternately accessible from either side of the cell membrane, [ 12 ]  consistent with MFS transporters."}
{"_id": "WikiPedia_Hematology$$$corpus_942", "text": "Ferroportin-mediated iron efflux is  calcium -activated; studies of human Fpn expressed in  Xenopus laevis  oocytes demonstrated that calcium is a required  cofactor  for Fpn, but that Fpn does not transport calcium. [ 12 ]  Thus, Fpn does not function as an iron/calcium antiporter. The thermodynamic driving force for Fpn remains unknown."}
{"_id": "WikiPedia_Hematology$$$corpus_943", "text": "In addition to iron, human ferroportin has been shown to transport  cobalt ,  zinc , [ 13 ]  and  nickel . [ 12 ]  Ferroportin may also function as a  manganese  exporter. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_944", "text": "Ferroportin is found on the basolateral membranes of intestinal epithelia of mammals, including: [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_945", "text": "Ferroportin-1 plays an important role in  neural tube  closure and  forebrain  patterning. [ 17 ]  Mouse embryos lacking the  Slc40a1  gene are aborted before  gastrulation  occurs, suggesting that the Fpn1 protein encoded is necessary and essential for normal embryonic development. [ 15 ]  Fpn1 is expressed in the  syncytiotrophoblast  cells in the placenta and visceral  endoderm  of mice at E7.5. [ 5 ] [ 15 ]  Further, several retrospective studies have noted an increased incidence of  spina bifida  occurring after low maternal intake of iron during embryonic and fetal development. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_946", "text": "A study examining the consequences of several different mutations of the  Slc40a1  mouse gene suggested that several serious neural tube and patterning defects were produced as a result, including spina bifida,  exencephaly , and forebrain truncations, among others. [ 17 ]  Given the findings of studies to date, there appears to be significant evidence that intact iron transport mechanisms are critical to normal neural tube closure. Furthermore, other experiments have suggested that  Fpn1  product and activity is required along the entire anterior-posterior axis of the animal to ensure proper closure of the neural tube. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_947", "text": "It is known that ferroportin (SLC40A1) gene is expressed at a low level in infertile women. Its mRNA levels were discovered to be down-regulated in these women, specifically in  granulosa cells . What's more, low expression of ferroportin is also associated with infertility when some features like age and smoking habits are considered.\nIt is also important to mention that, not only is ferroportin down-regulated in granulosa cells, but also in cervical cells of infertile women, and that the association between infertility and low ferroportin levels in these cells can be seen, again, when mRNA ferroportin levels was adjusted by age and smoking status. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_948", "text": "Ferroportin is inhibited by hepcidin, which binds to ferroportin and internalizes it within the cell. [ 8 ]  This results in the retention of iron within  enterocytes ,  hepatocytes , and  macrophages  with a consequent reduction in iron levels within the blood serum. This is especially significant with enterocytes which, when shed at the end of their lifespan, results in significant iron loss. Hepcidin is synthesized in response to various cytokines, as described in the  Hepcidin  article, as well as in this article by Ganz. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_949", "text": "Ferroportin expression is also regulated by the  IRP  regulatory mechanism. If the iron concentration is too low, the IRP concentration increases, thus inhibiting the ferroportin translation and increasing intracellular iron and  ferritin  concentrations. The ferroportin translation is also down regulated post-transcriptionally by the micro RNA miR-485-3p, which is produced in response to iron deficiency. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_950", "text": "Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as  Hemochromatosis type 4   or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with  African iron overload . Ferroportin and hepcidin are critical proteins for the regulation of systemic iron homeostasis."}
{"_id": "WikiPedia_Hematology$$$corpus_951", "text": "Ferroportin is part of the  ferroportin (Fpn) family . Members of the family are found across eukaryotes in animals and plants as well as in  Proteobacteria , a group of bacteria. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_952", "text": "As of  this edit , this article uses content from  \"2.A.100 The Ferroportin (Fpn) Family\" , which is licensed in a way that permits reuse under the  Creative Commons Attribution-ShareAlike 3.0 Unported License , but not under the  GFDL . All relevant terms must be followed."}
{"_id": "WikiPedia_Hematology$$$corpus_953", "text": "Gestational (incidental) thrombocytopenia  is a condition that commonly affects pregnant women.  Thrombocytopenia  is defined as the drop in  platelet  count from the normal range of 150,000\u2013400,000/\u03bcL to a count lower than 150,000/\u03bcL. [ 1 ]  There is still ongoing research to determine the reason for the lowering of platelet count in women with a normal pregnancy. Some researchers speculate the cause to be dependent on dilution, decreased production of platelets, or an increased turnover event. [ 2 ]  Although women with normal pregnancy experience a low platelet count, women experiencing a continuous drop in platelet will be diagnosed with thrombocytopenia and women with levels greater than 70,000/\u03bcL will be diagnosed with gestational thrombocytopenia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_954", "text": "Thrombocytopenia affects approximately 7\u201310% of pregnant women and of the 7\u201310%, within that population; approximately 70\u201380% have gestational thrombocytopenia  [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_955", "text": "Gestational thrombocytopenia is a disorder similar to  immune thrombocytopenia  (ITP) and is difficult to differentiate between the two disorders. [ 2 ]  Therefore, a medical history is conducted to because a diagnostic test is unavailable. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_956", "text": "Although there are no alarming symptoms related to gestational thrombocytopenia, an individual with thrombocytopenia might show the following symptoms [ 4 ]  \u2013"}
{"_id": "WikiPedia_Hematology$$$corpus_957", "text": "It is evident that there is a decrease in platelet count during pregnancy; however, the cause of the decrease is unknown. [ 2 ]   However researchers theorize that the decrease in platelet count is due to the decreased production of platelets and/or increased destruction of platelets. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_958", "text": "Generally, there is a decrease in  platelet  count in pregnant women and it will be due to many reasons. [ 1 ]  The two main causes of thrombocytopenia are a decrease in the production of platelets in the  bone marrow  and an increase in the destruction of the platelets. [ 4 ]  Platelets, along with other components of the blood, are produced in the spongy tissue found in the bone, known as bone marrow. [ medical citation needed ]   Low platelet count maybe due to the decreased production of platelets in the bone marrow. A decreased production would be due to vitamin B12 deficiency, iron deficiency,  aplastic anemia , viral infections,  chemotherapy , alcohol consumption,  leukemia ,  myelodysplasia , and  cirrhosis . [ medical citation needed ]  During pregnancy, the fetus\u2019 waste products diffuse into the mother\u2019s sinuses (blood stream), and cause the mother's  spleen  to become overactive and enlarged. [ 5 ]  Normally, the spleen filters and removes the waste products and with the overload of unwanted substances in the bloodstream, the spleen will remove blood cells too quickly  [ 5 ]  or store the platelets. [ 4 ]   In both cases, the overactive spleen would cause a decrease in the circulation of the platelets. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_959", "text": "Gestational thrombocytopenia will become evident during the mid-second trimester through the third trimester of pregnancy and it is diagnosed based on exclusion. [ 2 ]  For example, women with a history of immune thrombocytopenia or thrombocytopenia, prior to pregnancy, will not be diagnosed with gestational thrombocytopenia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_960", "text": "Patients with low platelet counts, lower than 70,000/\u03bcL, will be difficult to diagnose because low platelet counts maybe due to gestational thrombocytopenia or immune thrombocytopenia. [ 6 ]   In such cases, a treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) will be instructed. [ 6 ]  If there is an improvement in the platelet levels, the patient will be diagnosed with immune thrombocytopenia, and if not the patient will be diagnosed with severe gestational thrombocytopenia [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_961", "text": "In order for the physician to  determine the underlying cause of the gestational thrombocytopenia, the following tests are conducted:"}
{"_id": "WikiPedia_Hematology$$$corpus_962", "text": "During routine prenatal checkups, the physician will conduct a complete blood count test to determine the components of blood. The complete blood count will provide further information about platelet levels."}
{"_id": "WikiPedia_Hematology$$$corpus_963", "text": "The physician may conduct an ultrasound around the spleen to determine if the spleen is enlarged. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_964", "text": "The physician may conduct a bone marrow aspiration or bone marrow biopsy, if there is a decreased production of platelets in the bone marrow. [ medical citation needed ]  A bone marrow aspiration and bone marrow biopsy may be conducted at the same time."}
{"_id": "WikiPedia_Hematology$$$corpus_965", "text": "There is no known information regarding the prevention of this disorder. [ citation needed ]  There is no known information regarding the group of women who are likely to be diagnosed with this disorder. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_966", "text": "Women, diagnosed with gestational thrombocytopenia, will have their complete blood test conducted during each pre-natal visit and monitored by the doctor. [ 6 ]  Having diagnosed gestational thrombocytopenia, women should continue their normal activities because the diagnosis does not change the management of pregnancy. [ 6 ]  Also, the diagnosis of gestational thrombocytopenia poses no harm or risk to the mother or the fetus. [ 7 ]  There are no diagnostic tests available for gestational thrombocytopenia; rather it is diagnosed based on exclusion. [ 6 ]   Women who have a history of immune thrombocytopenia or thrombocytopenia prior to becoming pregnant would not be diagnosed with gestational thrombocytopenia [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_967", "text": "Women who have platelet levels lower than 70,000 / \u03bcL, during pregnancy, maybe experiencing severe gestational thrombocytopenia or immune thrombocytopenia. [ 6 ]   In such cases, if the treatment of immune thrombocytopenia therapy (corticosteroids, or intravenous immunoglobulin) [ 2 ]   does not improve the platelet count, the patient will be diagnosed with severe gestational thrombocytopenia. [ 2 ]  Severe gestational thrombocytopenia may pose a risk for complications with the use of epidural or general anesthesia during delivery. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_968", "text": "Those who have no previous history of thrombocytopenia, besides the occurrence in previous pregnancies (gestational thrombocytopenia), the platelet levels will go back to a normal range 1\u20132 months after the delivery. [ 6 ]  Post delivery, approximately 1\u20133 months later, women with gestational thrombocytopenia should have a complete blood test conducted. [ 6 ]  Lastly, gestational thrombocytopenia is a disorder that may reoccur in future pregnancies  [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_969", "text": "A history of this disorder has not yet been established."}
{"_id": "WikiPedia_Hematology$$$corpus_970", "text": "The  Haldane effect  is a property of  hemoglobin  first described by  John Scott Haldane , within which oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin, increasing the removal of carbon dioxide. Consequently, oxygenated blood has a reduced affinity for carbon dioxide. Thus, the Haldane effect describes the ability of hemoglobin to carry increased amounts of carbon dioxide (CO 2 ) in the deoxygenated state as opposed to the oxygenated state. Vice versa, it is true that a high concentration of CO 2  facilitates dissociation of oxyhemoglobin, though this is the result of two distinct processes (Bohr effect and Margaria-Green effect) and should be distinguished from Haldane effect."}
{"_id": "WikiPedia_Hematology$$$corpus_971", "text": "Carbon dioxide travels through the  blood  in three different ways. One of these ways is by binding to  amino  groups, creating  carbamino  compounds. Amino groups are available for binding at the N-terminals and at side-chains of  arginine  and  lysine  residues in hemoglobin. When carbon dioxide binds to these residues  carbaminohemoglobin  is formed. [ 1 ]  This amount of  carbaminohemoglobin  formed is inversely proportional to the amount of oxygen attached to hemoglobin. Thus, at lower oxygen saturation, more  carbaminohemoglobin  is formed. These dynamics explain the relative difference in hemoglobin's affinity for carbon dioxide depending on oxygen levels known as the Haldane effect. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_972", "text": "Histidine  residues in hemoglobin can accept protons and act as  buffers . Deoxygenated hemoglobin is a better  proton acceptor  than the oxygenated form. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_973", "text": "In red blood cells, the enzyme  carbonic anhydrase  catalyzes the conversion of dissolved carbon dioxide to  carbonic acid , which rapidly dissociates to  bicarbonate  and a free  proton :"}
{"_id": "WikiPedia_Hematology$$$corpus_974", "text": "By  Le Chatelier's principle , anything that stabilizes the proton produced will cause the reaction to shift to the right, thus the enhanced affinity of deoxyhemoglobin for protons enhances synthesis of bicarbonate and accordingly increases capacity of deoxygenated blood for carbon dioxide. The majority of carbon dioxide in the blood is in the form of bicarbonate. Only a very small amount is actually dissolved as carbon dioxide, and the remaining amount of carbon dioxide is bound to hemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_975", "text": "In addition to enhancing removal of carbon dioxide from oxygen-consuming tissues, the Haldane effect promotes dissociation of  carbon dioxide  from hemoglobin in the presence of  oxygen . In the oxygen-rich capillaries of the lung, this property causes the displacement of carbon dioxide to plasma as low-oxygen blood enters the  alveolus  and is vital for  alveolar gas exchange ."}
{"_id": "WikiPedia_Hematology$$$corpus_976", "text": "The general equation for the Haldane Effect is:"}
{"_id": "WikiPedia_Hematology$$$corpus_977", "text": "However, this equation is confusing as it reflects primarily the  Bohr effect . The significance of this equation lies in realizing that oxygenation of Hb promotes dissociation of H +  from Hb, which shifts the bicarbonate buffer equilibrium towards CO 2  formation; therefore, CO 2  is released from RBCs. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_978", "text": "In patients with lung disease, lungs may not be able to increase  alveolar ventilation  in the face of increased amounts of dissolved CO 2 ."}
{"_id": "WikiPedia_Hematology$$$corpus_979", "text": "This partially explains the observation that some patients with  emphysema  might have an increase in P a CO 2  (partial pressure of arterial dissolved carbon dioxide) following administration of supplemental oxygen even if content of CO 2  stays equal. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_980", "text": "The  Harrington\u2013Hollingsworth experiment  was an  experiment  that established the  autoimmune  nature of the  blood disorder   immune thrombocytopenic purpura . [ 1 ] [ 2 ]  It was performed in 1950 by the academic staff of  Barnes-Jewish Hospital  in  St. Louis, Missouri . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_981", "text": "The experiment was undertaken in 1950 by William J. Harrington and  James W. Hollingsworth , who postulated that in patients with  idiopathic thrombocytopenic purpura  (ITP), it was a blood factor that caused the destruction of  platelets . [ 2 ]  To test this hypothesis, Harrington received 500 ml of blood from a patient with ITP. [ 2 ]  Within three hours, his platelets dropped to dangerously low levels and he experienced a  seizure . [ 2 ]  His platelet count remained extremely low for four days, finally returning to normal levels by the fifth day. [ 2 ]   Bone marrow biopsy  from Harrington's  sternum  demonstrated normal  megakaryocytes , the cells necessary for  platelet production . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_982", "text": "Subsequently the experiment was repeated on all suitable staff members at the Barnes-Jewish Hospital. All subjects developed low platelet counts within three hours, and all recovered after a period of several days. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_983", "text": "Schwartz notes that the Harrington\u2013Hollingsworth experiment was a turning point in the understanding of ITP's pathophysiology:"}
{"_id": "WikiPedia_Hematology$$$corpus_984", "text": "The Harrington\u2013Hollingsworth experiment changed the meaning of the \"I\" in ITP from idiopathic to immune, but \"immune\" in this case means \"autoimmune,\" because the antibodies bind to and cause the destruction of the patient's own platelets. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_985", "text": "The experiment was the first to demonstrate that infusion of an ITP patient's plasma into a normal patient caused a precipitous drop in platelet count. [ 2 ]  This suggested that low platelet counts ( thrombocytopenia ) in patients with ITP was caused by a circulating factor found in the blood. [ 2 ]  Many studies performed since then have demonstrated that this circulating factor is in fact a collection of  immunoglobulins . [ 3 ] [ 4 ] \nMany physician-scientists believe the findings had a major influence on the field of autoimmunity, which was not universally accepted at the time as a mechanism of human disease."}
{"_id": "WikiPedia_Hematology$$$corpus_986", "text": "Hemagglutination , or  haemagglutination , is a specific form of  agglutination  that involves  red blood cells  (RBCs). It has two common uses in the laboratory: blood typing and the  quantification of virus  dilutions in a  haemagglutination assay ."}
{"_id": "WikiPedia_Hematology$$$corpus_987", "text": "Blood type can be determined by using  antibodies  that bind to the  A or B blood group   antigens  in a sample of blood."}
{"_id": "WikiPedia_Hematology$$$corpus_988", "text": "For example, if antibodies that bind the A blood group are added and agglutination occurs, the blood is either type A or type AB. To determine between type A or type AB, antibodies that bind the B group are added and if agglutination does not occur, the blood is type A. If agglutination does not occur with either antibodies that bind to type A or type B antigens, then neither antigen is present on the blood cells, which means the blood is type\u00a0O. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_989", "text": "In blood grouping, the patient's serum is tested against RBCs of known blood groups and also the patient's RBCs are tested against known serum types. In this way the patient's blood group is confirmed from both RBCs and serum. A direct  Coombs test  is also done on the patient's blood sample in case there are any confounding antibodies."}
{"_id": "WikiPedia_Hematology$$$corpus_990", "text": "Many viruses attach to molecules present on the surface of RBCs. A consequence of this is that at certain concentrations, a viral suspension may bind together (agglutinate) the RBCs, thus preventing them from settling out of suspension. Since agglutination is not linked to infectivity, attenuated viruses can therefore be used in  assays  while an additional assay such as a  plaque assay  must be used to determine infectivity. By serially diluting a virus suspension into an assay tray (a series of wells of uniform volume) and adding a standard amount of blood cells, an estimation of the number of virus particles can be made. While less accurate than a  plaque assay , it is cheaper and quicker (taking just 30 minutes). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_991", "text": "This assay may be modified to include the addition of an antiserum. By using a standard amount of virus, a standard amount of blood cells, and serially diluting the  antiserum , one can identify the concentration of the antiserum (the greatest dilution which inhibits hemagglutination)."}
{"_id": "WikiPedia_Hematology$$$corpus_992", "text": "Hemagglutinins  (alternatively spelt  haemagglutinin , from the Greek  haima , 'blood' + Latin  gluten , 'glue') are homotrimeric  glycoproteins  present on the  protein capsids  of  viruses  in the  Paramyxoviridae  and  Orthomyxoviridae  families. [ 1 ] [ 2 ] [ 3 ]  Hemagglutinins are responsible for binding to  receptors ,  sialic acid residues , on host cell membranes to initiate virus docking and  infection . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_993", "text": "Specifically, they recognize  cell-surface   glycoconjugates  containing sialic acid on the surface of host  red blood cells  with a low affinity and use them to enter the  endosome  of host cells. [ 6 ]  Hemagglutinins tend to recognize \u03b1-2,6-linked sialic acids of the host cells in humans and \u03b1-2,3-linked sialic acids in avian species, although there is evidence that hemagglutinin specificity can vary. This correlates to the fact that  Influenza A  typically establishes infections in the upper respiratory tract in humans, where many of these \u03b1-2,6-linked sialic acids are present. [ 7 ]  There are various subtypes of hemagglutinins, in which H1, H2, and H3 are known to have human susceptibility. [ 8 ]  It is the variation in hemagglutinin (and  neuraminidase ) subtypes that require health organizations (ex.  WHO ) to constantly update and surveil the known circulating flu viruses in human and animal populations (ex.  H5N1 )."}
{"_id": "WikiPedia_Hematology$$$corpus_994", "text": "In the endosome, hemagglutinins undergo conformational changes due to a  pH  drop to of 5\u20136.5 enabling viral attachment through a fusion  peptide . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_995", "text": "Virologist  George K. Hirst  discovered agglutination and hemagglutinins in 1941. [ 10 ]   Alfred Gottschalk  proved in 1957 that hemagglutinins bind a  virus  to a host cell by attaching to  sialic acids  on  carbohydrate  side chains of  cell-membrane   glycoproteins  and  glycolipids . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_996", "text": "The name \"hemagglutinin\" comes from the  protein 's ability to cause red blood cells (erythrocytes) to clump together (\" agglutinate \")  in vitro . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_997", "text": "Hemagglutinins are small proteins that extend from the surface of the virus membrane as spikes that are 135 Angstroms (\u00c5) in length and 30-50 \u00c5 in diameter. [ 19 ]  Each spike is composed of three identical  monomer  subunits, making the protein a  homotrimer . These monomers are formed of two  glycopeptides , HA1 and HA2, and linked by two  disulphide   polypeptides , including membrane-distal HA1 and the smaller membrane-proximal HA2.  X-ray crystallography ,  NMR spectroscopy , and  cryo-electron microscopy  were used to solve the protein's structure, the majority of which is  \u03b1-helical . [ 20 ]  In addition to the homotrimeric core structure, hemagglutinins have four subdomains: the membrane-distal receptor binding R subdomain, the vestigial domain E, that functions as a receptor-destroying  esterase , the fusion domain F, and the membrane anchor subdomain M. The membrane anchor subdomain forms elastic protein chains linking the hemagglutinin to the  ectodomain . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_998", "text": "On the viral capsids of influenza types  A  and  B , hemagglutinin is initially inactive. Only when cleaved by host proteins, does each monomer polypeptide of the homotrimer transforms into a dimer \u2013 composed of HA1 and HA2 subunits attached by disulfide bridges. [ 22 ]  The HA1 subunit is responsible for docking the viral capsid onto the host cell by binding to sialic acid residues present on the surface of host respiratory cells. This binding triggers  endocytosis . [ 5 ]  The pH in the endosomal compartment then decreases from proton influx, and this causes a conformational change in HA that forces the HA2 subunit to \u201cflip outward.\u201d The HA2 subunit is responsible for membrane fusion. It binds to the endosomal membrane, pulling the viral capsid membrane and the endosomal membrane tightly together, eventually forming a pore through which the viral genome can enter into the host cell cytoplasm. [ 3 ]  From here, the virus can use host machinery to proliferate."}
{"_id": "WikiPedia_Hematology$$$corpus_999", "text": "Hematidrosis , also called  hematohidrosis ,  haematidrosis ,  hemidrosis  and  blood sweat , is a very rare condition in which a human  sweats   blood . [ 1 ]  The term is from  Ancient Greek   ha\u00eema / ha\u00edmatos  ( \u03b1\u1f37\u03bc\u03b1 / \u03b1\u1f35\u03bc\u03b1\u03c4\u03bf\u03c2 ), meaning blood, and  h\u012bdr\u1e53s  ( \u1f31\u03b4\u03c1\u03ce\u03c2 ), meaning sweat."}
{"_id": "WikiPedia_Hematology$$$corpus_1000", "text": "Blood usually oozes from the forehead, nails,  umbilicus , and other skin surfaces. In addition, oozing from  mucocutaneous  surfaces causing  nosebleeds , blood-stained tears, and vicarious menstruation are common. [ 2 ]  The episodes may be preceded by intense  headache  and abdominal pain and are usually self-limiting. In some conditions, the secreted fluid is more dilute and appears to be blood-tinged, while others may have darker, bright red secretions resembling blood. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1001", "text": "While the extent of blood loss generally is minimal, hematidrosis also results in the skin becoming extremely tender and fragile."}
{"_id": "WikiPedia_Hematology$$$corpus_1002", "text": "Hematidrosis is a condition in which  capillary  blood vessels that feed the  sweat glands  rupture, causing them to exude blood, occurring under conditions of extreme physical or emotional  stress . [ 4 ]  Severe mental  anxiety  activates the  sympathetic nervous system  to invoke the  fight-or-flight response  to such a degree as to cause hemorrhage of the vessels supplying the sweat glands. [ 5 ]  It has been suggested that acute fear and extreme stress can cause hematidrosis. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1003", "text": "Investigations such as  platelet  count, platelet aggregation test,  coagulation  profile, and  skin biopsy  reveal no abnormalities, and direct light microscopy of fluid demonstrates presence of normal  red blood cells . Investigations also fail to show any  vasculitis  or skin appendages (i.e.  sweat glands ,  sebaceous glands  and  hair follicles ) abnormalities. [ 3 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1004", "text": "A 2015 case study investigated hematidrosis with a patient who has  epilepsy . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1005", "text": "Effects on the body include weakness and mild-to-moderate dehydration from the severe anxiety and both blood and sweat loss. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1006", "text": "The condition is very rare, but there are reports in the medical literature of successful treatment with  beta blockers  ( propranolol  10\u00a0mg), [ 10 ] [ 11 ]  with significant reduction in the frequency of spontaneous blood oozing. The successful use of beta blockers supports the theory that the condition is induced by stress and anxiety. However, this etiology is not yet fully established, as the high prevalence of stress and anxiety in the modern era has not changed the incidence of this extremely rare disease, suggesting that other co-abnormalities also play a key role. [ 7 ]   Atropine  sulfate  transdermal patches  have also been used successfully. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1007", "text": "Favorable results with psychiatric counselling to reduce stress highlight the relationship between psychogenic causes and hematohidrosis. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1008", "text": "Dermatological research notes the presence of hematidrosis in people awaiting execution. [ 5 ]  It has also been proposed as a possible explanation for Jesus'  agony in the garden  of  Gethsemane  ( Luke 22:44 ), [ 12 ]  and for claims associated with  stigmata . [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1009", "text": "Leonardo da Vinci  described a soldier who sweated blood before battle. The phenomenon has also been observed in individuals in fear for their lives; a case occurred during the  London Blitz , and a case of fear of a storm while sailing, etc. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1010", "text": "Hematology analyzers  ( also spelled   haematology analysers  in  British English ) are used to count and identify blood cells at high speed with accuracy. [ 1 ] [ 2 ] [ 3 ]  During the 1950s, laboratory technicians counted each individual blood cell underneath a  microscope . Tedious and inconsistent, this was replaced with the first, very basic hematology analyzer, engineered by  Wallace H. Coulter . The  early hematology analyzers  relied on Coulter's principle (see  Coulter counter ). However, they have evolved to encompass numerous techniques. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1011", "text": "Hematology analyzers are used to conduct a  complete blood count  (CBC), which is usually the first test requested by physicians to determine a patient's general health status. [ 5 ]  A complete blood count includes  red blood cell  (RBC),  white blood cell  (WBC),  hemoglobin , and  platelet  counts, as well as  hematocrit  levels. Other analyses include:  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1012", "text": "A 3-part differential cell counter uses Coulter's principle to find the size and volume of the cell. The sample is lysed and dissolved into an electrolyte solution in a container, which also holds a smaller container. The smaller container has two pumps running to and from its solution, one creating a vacuum and the other replacing the lost solution. The smaller container has a small hole (an orifice) near the bottom of the container. Coulter's principle is applied through the use of two electrodes. One electrode (the internal electrode) is within the smaller container, and the other (the external electrode) is outside of the smaller container but within the electrolyte/sample solution. As the vacuum draws the sample cells through the orifice, the cell momentarily causes electrical resistance to the current as it passes through the orifice. This resistance is recorded, measured, amplified, and processed which can then be interpreted by the computer into a histogram. The 3-part analyzer is able to differentiate between three types of white blood cells (WBCs):  neutrophils ,  lymphocytes , and  monocytes . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1013", "text": "This type of hematology analyzer utilizes both Coulter's principle and flow cytometry to determine the  granularity , diameter, and inner complexity of the cells. Using hydrodynamic focusing, the cells are sent through an aperture one cell at a time. During this, a laser is directed at them, and the scattered light is measured at multiple angles. The absorbance is also recorded. The cell can be identified based on the intensity of the scattered light and the level of absorbance. [ 8 ]  A 5-part cell counter can differentiate all WBC types (neutrophils, lymphocytes,  basophils ,  eosinophils , and monocytes). 5-part analyzers are more expensive than 3-part analyzers, but provide more in-depth information about the sample. Specific jobs, such as  allergy  testing, require 5-part differential analysis. However, most medical tasks can be completed with the 3-part analyzer. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1014", "text": "The hematology analyzer is broken down into five key components: [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1015", "text": "These are the major companies that are known to make quality Hematology Analyzers for hospitals and laboratories:  [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1016", "text": "Hematopoietic stem-cell transplantation  ( HSCT ) is the  transplantation  of  multipotent hematopoietic stem cells , usually derived from  bone marrow ,  peripheral blood , or  umbilical cord blood , in order to replicate inside a patient and produce additional normal blood cells. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ]  HSCT may be  autologous  (the patient's own stem cells are used),   syngeneic  (stem cells from an  identical twin ), or  allogeneic  (stem cells from a donor). [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1017", "text": "It is most often performed for patients with certain  cancers  of the  blood  or bone marrow, such as  multiple myeloma ,  leukemia , some types of  lymphoma  and  immune deficiencies . [ 5 ]  In these cases, the recipient's immune system is usually suppressed with  radiation  or  chemotherapy  before the transplantation. Infection and  graft-versus-host disease  are major complications of allogeneic HSCT. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1018", "text": "HSCT remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As survival following the procedure has increased, its use has expanded beyond cancer to  autoimmune diseases [ 7 ] [ 8 ]  and hereditary  skeletal dysplasias , notably  malignant infantile osteopetrosis [ 9 ] [ 10 ]  and  mucopolysaccharidosis . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1019", "text": "Indications for stem-cell transplantation are:"}
{"_id": "WikiPedia_Hematology$$$corpus_1020", "text": "Many recipients of HSCTs are  multiple myeloma [ 15 ]  or  leukemia  patients [ 16 ]  who would not benefit from prolonged treatment with, or are already resistant to,  chemotherapy . Candidates for HSCTs include  pediatric  cases where the patient has an inborn defect such as  severe combined immunodeficiency  or  congenital neutropenia  with defective stem cells, and also children or adults with  aplastic anemia [ 17 ]  who have lost their stem cells after birth. Other conditions [ 18 ]  treated with stem cell transplants include  sickle cell disease ,  myelodysplastic syndrome ,  neuroblastoma ,  lymphoma ,  Ewing's sarcoma ,  desmoplastic small round cell tumor ,  chronic granulomatous disease ,  Hodgkin's disease  and  Wiskott\u2013Aldrich syndrome . Non-myeloablative, so-called  mini transplant (microtransplantation)  procedures, have been developed requiring smaller doses of preparative chemotherapy and  radiation therapy , allowing HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1021", "text": "In 2006, 50,417 first HSCTs were recorded worldwide, according to a global survey of 1,327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation.  Of these, 28,901 (57%) were autologous and 21,516 (43%) were allogeneic (11,928 from family donors and 9,588 from unrelated donors).  The main indications for transplant were lymphoproliferative disorders (55%) and leukemias (34%), and many took place in either Europe (48%) or the Americas (36%). [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1022", "text": "The Worldwide Network for Blood and Marrow Transplantation reported the millionth transplant to have been undertaken in December 2012. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1023", "text": "In 2014, according to the  World Marrow Donor Association , stem-cell products provided for unrelated transplantation worldwide had increased to 20,604 (4,149 bone-marrow donations, 12,506 peripheral blood stem-cell donations, and 3,949 cord-blood units). [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1024", "text": "Autologous HSCT requires the extraction ( apheresis ) of hematopoietic stem cells (HSCs) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose  chemotherapy  with or without  radiotherapy  with the intention of eradicating the patient's malignant cell population at the cost of partial or complete  bone marrow  ablation (destruction of patient's bone marrow's ability to grow new blood cells).  The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood-cell production. [ 2 ]  Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment, since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection is very rare (and graft-versus-host disease impossible) due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as  lymphoma . [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1025", "text": "For other cancers such as  acute myeloid leukemia , though, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, so the allogeneic treatment may be preferred for those conditions. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1026", "text": "Researchers have conducted small studies using nonmyeloablative HSCT as a possible treatment for  type I (insulin dependent) diabetes  in children and adults. Results have been promising, but as of 2019 [update] , speculating whether these experiments will lead to effective treatments for diabetes is premature. [ 25 ] [ 26 ] [ 27 ]  Autologous HSCT is an effective treatment against aggressive Multiple Sclerosis. [ 28 ]  The type of autologous HSCT used as a Multiple Sclerosis treatment is considered safe and the serious adverse events rare. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1027", "text": "Allogeneic HSCT involves two people \u2013 the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue ( human leukocyte antigen , HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more  loci  of the HLA gene, and a perfect match at these loci is preferred. Even if a good match exists at these critical  alleles , the recipient will require  immunosuppressive  medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA-matched sibling), syngeneic (a  monozygotic  or identical twin of the patient \u2013 necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA-matched stem cells), unrelated (donor who is not related and found to have very close degree of HLA matching), or, as in the case of Haploidentical Transplantation, a half-matched relative such as a parent, child, or sibling. Unrelated donors may be found through a registry of bone-marrow donors, such as the  National Marrow Donor Program  (NMDP) in the U.S.  A \" savior sibling \" may be intentionally selected by  preimplantation genetic diagnosis  to match a child both regarding HLA type and being free of any obvious inheritable disorder. Allogeneic transplants are also performed using umbilical  cord blood  as the source of stem cells. In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved. [ 30 ] [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1028", "text": "A compatible donor is found by doing additional HLA testing from the blood of potential donors. The HLA genes fall in two categories (types I and II). In general, mismatches of the type-I genes (i.e.  HLA-A ,  HLA-B , or  HLA-C ) increase the risk of graft rejection.  A mismatch of an HLA type II gene (i.e.  HLA-DR  or   HLA-DQB1 ) increases the risk of graft-versus-host disease.  In addition, a genetic mismatch as small as a single  DNA   base pair  is significant, so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient.  Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1029", "text": "Race  and  ethnicity  are known to play a major role in donor recruitment drives, as members of the same ethnic group are more likely to have matching genes, including the genes for HLA. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1030", "text": "As of 2013 [update] , at least two commercialized allogeneic cell therapies have been developed,  Prochymal  and  Cartistem . [ 34 ]   Omidubicel  was approved for medical use in the United States in April 2023. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1031", "text": "To limit the risks of transplanted stem-cell  rejection  or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same HLA-typing as the recipient. About 25 to 30% of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called \"perfect matches\" may have mismatched minor alleles that contribute to graft-versus-host disease. With recent advances in  T-cell -depleting therapies such as post-transplant  cyclophosphamide ,  haploidentical  (half-matched) transplants have permitted successful transplantation of many patients who would otherwise have lacked a donor. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1032", "text": "In the case of a bone-marrow transplant, the HSCs are removed from a large bone of the donor, typically the  pelvis , through a large  needle  that reaches the center of the bone. The technique is referred to as a bone-marrow harvest and is performed under  local  or  general anesthesia . [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1033", "text": "Peripheral blood stem cells [ 38 ]  are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as  apheresis . The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes  white blood cells . The  red blood cells  are returned to the donor. The peripheral stem cell yield is boosted with daily  subcutaneous injections  of  granulocyte-colony stimulating factor , serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1034", "text": "Extracting stem cells from  amniotic fluid  is possible and may have applications for  autologous  and  heterologous  use. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1035", "text": "Unlike other organs, bone-marrow cells can be frozen ( cryopreserved ) for prolonged periods without damaging too many cells. This is a necessity with autologous HSCs because the cells must be harvested from the recipient months in advance of the transplant treatment. In the case of  allogeneic transplants , fresh HSCs are preferred to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a  cord blood bank  because it is only obtainable at the time of  childbirth . To cryopreserve HSCs, a preservative,  dimethyl sulfoxide , must be added, and the cells must be cooled very slowly in a controlled-rate freezer to prevent  osmotic  cellular injury during ice-crystal formation. HSCs may be stored for years in a cryofreezer, which typically uses  liquid nitrogen . [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1036", "text": "The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSCs and to suppress immune reactions. The bone marrow can be ablated (destroyed) with dose-levels that cause minimal injury to other tissues. In allogeneic transplants, a combination of  cyclophosphamide  with  total body irradiation  is conventionally employed. This treatment also has an  immunosuppressive  effect that prevents rejection of the HSCs by the recipient's  immune system . The post-transplant prognosis often includes acute and chronic graft-versus-host disease that may be life-threatening. In certain leukemias, though, this can coincide with protection against cancer relapse owing to the  graft-versus-tumor effect . [ 42 ]  Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease."}
{"_id": "WikiPedia_Hematology$$$corpus_1037", "text": "A newer treatment approach, nonmyeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone-marrow cells of the recipient. [ 43 ] :\u200a320\u2013321\u200a  Instead, nonmyeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse. [ 44 ] [ 45 ]  Also significantly, while requiring high doses of  immunosuppressive agents  in the early stages of treatment, these doses are less than for conventional transplants. [ 46 ]  This leads to a state of mixed  chimerism  early after transplant where both recipient and donor HSC coexist in the bone marrow space. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1038", "text": "Decreasing doses of immunosuppressive therapy then allow donor  T-cells  to eradicate the remaining recipient HSCs and to induce the graft-versus-tumor effect. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate marker for the emergence of the desirable graft versus tumor effect, and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of immunosuppressive agents. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1039", "text": "Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality, so allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. The optimal conditioning strategy for each disease and recipient has not been fully established, but RIC can be used in elderly patients unfit for myeloablative regimens, for whom a higher risk of cancer relapse may be acceptable. [ 43 ] [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1040", "text": "After several weeks of growth in the bone marrow, expansion of HSCs and their progeny is sufficient to normalize the blood cell counts and reinitiate the immune system. The offspring of donor-derived HSCs have been documented to populate many different organs of the recipient, including the  heart ,  liver , and  muscle , and these cells had been suggested to have the abilities of regenerating injured tissue in these organs.  However, recent research has shown that such lineage infidelity does not occur as a normal phenomenon. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1041", "text": "Chimerism  monitoring is a method to monitor the balance between the patient's own stem cells and the new stem cells from a donor. In cases where the patient's own stem cells are increasing in number after treatment, the treatment may potentially not have worked as intended. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1042", "text": "HSCT is associated with a high treatment-related  mortality  in the recipient, which limits its use to conditions that are themselves life-threatening. (The one-year survival rate has been estimated to be roughly 60%, although this figure includes deaths from the underlying disease, as well as from the transplant procedure.) [ 51 ]  Major complications include  veno-occlusive disease ,  mucositis , infections ( sepsis ), graft-versus-host disease, and the development of new  malignancies . [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1043", "text": "Bone-marrow transplantation usually requires that the recipient's own bone marrow be destroyed (myeloablation). Prior to the administration of new cells (engraftment), patients may go for several weeks without appreciable numbers of white blood cells to help fight  infection . This puts a patient at high risk of infections, sepsis, and  septic shock , despite  prophylactic   antibiotics . However,  antiviral   medications , such as  acyclovir  and  valacyclovir , are quite effective in prevention of HSCT-related outbreak of  herpetic  infection in  seropositive  patients. [ 53 ]  The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of  opportunistic infection . Immunosuppressive drugs are given for a minimum of six months after a transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as  measles  or  polio . So, transplant patients must be retreated with childhood  vaccines  once they are off immunosuppressive medications. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1044", "text": "Severe liver injury can result from hepatic veno-occlusive disease (VOD), newly termed sinusoidal obstruction syndrome (SOS). [ 55 ]  Elevated levels of  bilirubin ,  hepatomegaly , and fluid retention are clinical hallmarks of this condition. The appreciation of the generalized cellular injury and obstruction in  hepatic vein  sinuses is now greater. Severe cases of SOS are associated with a high mortality rate.  Anticoagulants  or  defibrotide  may be effective in reducing the severity of VOD but may also increase bleeding complications.  Ursodiol  has been shown to help prevent VOD, presumably by facilitating the flow of  bile ."}
{"_id": "WikiPedia_Hematology$$$corpus_1045", "text": "The injury of the mucosal lining of the mouth and throat is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening, but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1046", "text": "The mucosal lining of the bladder is affected in about 5% of children undergoing HSCT. This causes  hematuria  (blood in urine), frequent urination, abdominal pain and  thrombocytopenia . [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1047", "text": "Graft-versus-host disease (GvHD) is an inflammatory disease that is unique to allogeneic transplantation. It is an attack by the \"new\" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is named graft-versus-host disease because the transplanted cells must accept the body rather than the body accepting the new cells. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1048", "text": "Acute GvHD typically occurs in the first three months after transplantation and may involve the  skin ,  intestine , or  liver . High-dose  corticosteroids , such as  prednisone , are a standard treatment, but this immunosuppressive treatment often leads to deadly infections. Chronic GvHD may also develop after allogeneic transplant. It is the major source of late treatment-related complications, although it less often results in death. In addition to inflammation, chronic GvHD may lead to the development of  fibrosis , or scar tissue, similar to  scleroderma ; it may cause functional disability and require prolonged immunosuppressive therapy. GvHD is usually mediated by T cells, which react to foreign peptides presented on the  major histocompatibility complex  of the host. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1049", "text": "Further research is needed to determine whether mesenchymal stromal cells can be use for prophylaxis and treatment of GvHD. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1050", "text": "Graft-versus-tumor effect (GVT), or \"graft versus leukemia\" effect, is the beneficial aspect of the GvHD phenomenon. For example, HSCT patients with either acute, or in particular chronic, GvHD after an allogeneic transplant tend to have a lower risk of cancer relapse. [ 61 ] [ 42 ]  This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants, compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants that do not employ the highest immunosuppressive regimens."}
{"_id": "WikiPedia_Hematology$$$corpus_1051", "text": "Graft versus tumor is mainly beneficial in diseases with slow progress, e.g. chronic leukemia, low-grade lymphoma, and in some cases multiple myeloma, but is less effective in rapidly growing acute leukemias. [ 62 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1052", "text": "If cancer relapses after HSCT, another transplant can be performed, infusing the patient with a greater quantity of donor white blood cells ( donor lymphocyte infusion ). [ 62 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1053", "text": "Patients after HSCT are at a higher risk for  oral   carcinoma . Post-HSCT  oral cancer  may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1054", "text": "A meta-analysis showed that the risk of secondary cancers such as  bone cancer ,  head and neck cancers , and  melanoma , with standardized incidence ratios of 10.04 (3.48\u201316.61), 6.35 (4.76\u20137.93), and 3.52 (2.65\u20134.39), respectively, was significantly increased after HSCT. So, diagnostic tests for these cancers should be included in the screening program of these patients for the prevention and early detection of these cancers. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1055", "text": "Prognosis  in HSCT varies widely dependent upon disease type, stage, stem-cell source, HLA-matched status (for allogeneic HSCT), and conditioning regimen. A transplant offers a chance for cure or long-term remission if the inherent complications of graft versus host disease, immunosuppressive treatments and the spectrum of opportunistic infections can be survived. [ 30 ] [ 31 ]  In recent years, survival rates have been gradually improving across almost all populations and subpopulations receiving transplants. [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1056", "text": "Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror  et al ., [ 66 ]  using the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). The HCT-CI was derived and validated by investigators at the  Fred Hutchinson Cancer Research Center  in the U.S. The HCT-CI modifies and adds to a well-validated comorbidity index, the  Charlson Comorbidity Index  (CCI) (Charlson,  et al .) [ 67 ]  The CCI was previously applied to patients undergoing allogeneic HCT, but appears to provide less survival prediction and discrimination than the HCT-CI scoring system."}
{"_id": "WikiPedia_Hematology$$$corpus_1057", "text": "Patients who were successfully treated with HSCT and total body irradiation in childhood were found to have increased fat mass percentage, leading to significantly decreased exercise capacity in adulthood. This suggests patients who underwent successful treatment with HSCT have an increased predisposition to cardiovascular disease later in life. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1058", "text": "The risks of a complication depend on patient characteristics, health care providers, and the apheresis procedure, and the colony-stimulating factor used ( G-CSF ). G-CSF drugs include  filgrastim  (Neupogen, Neulasta), and  lenograstim  (Graslopin)."}
{"_id": "WikiPedia_Hematology$$$corpus_1059", "text": "Filgrastim is typically dosed in the 10 microgram/kg level for 4\u20135 days during the harvesting of stem cells. The documented adverse effects of filgrastim include  splenic rupture ,  acute respiratory distress syndrome , alveolar hemorrhage, and allergic reactions (usually experienced in first 30 minutes). [ 69 ] [ 70 ] [ 71 ]  In addition, platelet and hemoglobin levels dip postprocedurally, not returning to normal until after a month. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1060", "text": "The question of whether geriatrics (patients over 65) react the same as patients under 65 has not been sufficiently examined.  Coagulation issues and inflammation of atherosclerotic plaques are known to occur as a result of G-CSF injection. G-CSF has also been described to induce genetic changes in  agranulocytes  of normal donors. [ 70 ]  There is no statistically significant evidence either for or against the hypothesis that myelodysplasia (MDS) or acute myeloid leukaemia (AML) can be induced by G-CSF in susceptible individuals. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1061", "text": "Blood is drawn from a peripheral vein in a majority of patients, but a central line to the jugular, subclavian, and femoral veins may be used. Adverse reactions during apheresis were experienced in 20% of women and 8% of men, these adverse events primarily consisted of numbness/tingling, multiple line attempts, and nausea. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1062", "text": "A study involving 2,408 donors (aged 18\u201360 years) indicated that  bone pain  (primarily back and hips) as a result of filgrastim treatment is observed in 80% of donors. [ 71 ]  Donation is not recommended for those with a history of back pain. [ 71 ]  Other symptoms observed in more than 40 percent of donors include muscle pain, headache, fatigue, and difficulty sleeping. [ 71 ]  These symptoms all returned to baseline 1 month after donation in the majority of patients. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1063", "text": "In one meta-study that incorporated data from 377 donors, 44% of patients reported having adverse side effects after peripheral blood HSCT. [ 72 ]  Side effects included pain prior to the collection procedure as a result of G-CSF injections, and postprocedural generalized skeletal pain, fatigue, and reduced energy. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1064", "text": "A study that surveyed 2,408 donors found that serious adverse events (requiring prolonged hospitalization) occurred in 15 donors (at a rate of 0.6%), although none of these events was fatal. [ 71 ]  Donors were not observed to have higher than normal rates of cancer with up to 4\u20138 years of follow-up. [ 71 ] \nOne study based on a survey of medical teams covered about 24,000 peripheral blood HSCT cases between 1993 and 2005, and found a serious cardiovascular adverse reaction rate of about one in 1,500. [ 70 ]  This study reported a cardiovascular-related fatality risk within the first 30 days of HSCT of about two in 10,000. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1065", "text": "In 1939, a woman with aplastic anaemia received the first human bone marrow transfusion. This patient received regular blood transfusions, and an attempt was made to increase her leukocyte and platelet counts by intravenous bone marrow injection without unexpected reaction. [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1066", "text": "Stem-cell transplantation was pioneered using bone marrow-derived stem cells by a team at the  Fred Hutchinson Cancer Research Center  from the 1950s through the 1970s led by  E. Donnall Thomas , whose work was later recognized with a  Nobel Prize in Physiology or Medicine . Thomas' work showed that bone-marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening graft-versus-host disease. [ 74 ]  Collaborating with  Eloise Giblett , a professor at the  University of Washington , he discovered genetic markers that could confirm donor matches."}
{"_id": "WikiPedia_Hematology$$$corpus_1067", "text": "The first physician to perform a successful human bone-marrow transplant on a disease other than cancer was  Robert A. Good  at the  University of Minnesota  in 1968. [ 75 ] \nIn 1975, John Kersey, also of the University of Minnesota, performed the first successful bone-marrow transplant to cure lymphoma. His patient, a 16-year-old-boy, is today the longest-living lymphoma transplant survivor. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1068", "text": "At the end of 2012, 20.2 million people had registered their willingness to be a bone-marrow donor with one of the 67 registries from 49 countries participating in  Bone Marrow Donors Worldwide . Around 17.9 million of these registered donors had been ABDR typed, allowing easy matching.  A further 561,000 cord blood units had been received by one of 46 cord blood banks from 30 countries participating.  The highest total number of bone-marrow donors registered were those from the U.S. (8.0 million), and the highest number per capita were those from Cyprus (15.4% of the population). [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1069", "text": "Within the U.S., racial minority groups are the least likely to be registered, so are the least likely to find a potentially life-saving match.  In 1990, only six African Americans were able to find a bone-marrow match, and all six had common European genetic signatures. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1070", "text": "Africans are more genetically diverse than people of European descent, which means that more registrations are needed to find a match. Bone marrow and cord blood banks exist in  South Africa , and a new program is beginning in  Nigeria . [ 78 ]  Many people belonging to different races are requested to donate as a shortage of donors exists in African, mixed race, Latino, aboriginal, and many other communities."}
{"_id": "WikiPedia_Hematology$$$corpus_1071", "text": "Two registries in the U.S. recruit unrelated allogeneic donors: NMDP or Be the Match, and the  Gift of Life Marrow Registry ."}
{"_id": "WikiPedia_Hematology$$$corpus_1072", "text": "In 2007, a team of doctors in Berlin, Germany, including  Gero H\u00fctter , performed a stem-cell transplant for  leukemia  patient  Timothy Ray Brown , who was also  HIV -positive. [ 79 ]  From 60 matching donors, they selected a  [CCR5]-\u039432 homozygous  individual with two  genetic copies  of a rare variant of a  cell surface receptor . This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1,000 people of European ancestry have this inherited  mutation , but it is rarer in other populations. [ 80 ] [ 81 ]  The transplant was repeated a year later after a leukemia relapse. Over three years after the initial transplant, and despite discontinuing  antiretroviral therapy , researchers cannot detect HIV in the transplant recipient's blood or in various biopsies of his tissues. [ 82 ]  Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV, but scientists emphasise that this is an unusual case. [ 83 ]  Potentially fatal transplant complications (the \"Berlin patient\" developed graft-versus-host disease and  leukoencephalopathy ) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found. [ 84 ] [ 85 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1073", "text": "In 2012,  Daniel Kuritzkes  reported results of two stem-cell transplants in patients with HIV.  They did not, however, use donors with the \u039432 deletion. After their transplant procedures, both were put on antiretroviral therapies, during which neither showed traces of HIV in their blood plasma and purified  CD4 +  T cells  using a sensitive culture method (less than 3 copies/ml). The virus was once again detected in both patients some time after the discontinuation of therapy. [ 86 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1074", "text": "In 2019, a British man became the second to be cleared of HIV after receiving a bone-marrow transplant from a virus-resistant (\u039432) donor. This patient is being called \"the London patient\" (a reference to the famous Berlin patient). [ 87 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1075", "text": "Since McAllister's 1997 report on a patient with  multiple sclerosis  (MS) who received a bone-marrow transplant for chronic myelogenous leukemia (CML), [ 88 ]  over 600 reports have been published describing HSCTs performed primarily for MS. [ 89 ]  These have been shown to \"reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients\" who have aggressive, highly active MS, \"in the absence of chronic treatment with disease-modifying agents\". [ 89 ]  A randomized clinical trial including 110 patients showed that HSCT significantly prolonged time to disease progression compared to disease-modifying therapy. [ 90 ]  Long-term outcome in patients with severe disease has showed that complete disease remission after HSCT is possible. [ 91 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1076", "text": "HSCT can also be used for treating selected, severe cases of other autoimmune neurological diseases such as  neuromyelitis optica ,  chronic inflammatory demyelinating polyneuropathy , and  myasthenia gravis . [ 92 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1077", "text": "Peripheral blood stem cell transplantation  ( PBSCT ), also called \"Peripheral stem cell support\", [ 1 ]  is a method of replacing  blood-forming   stem cells . Stem cells can be destroyed through cancer treatments such as chemotherapy or radiation, as well as any blood-related diseases, such as  leukemia ,  lymphoma ,  neuroblastoma  and  multiple myeloma . [ 2 ]  PBSCT is now a much more common procedure than its  bone marrow harvest  equivalent due to the ease and less invasive nature of the procedure. [ 3 ] [ 4 ]  Studies suggest that PBSCT has a better outcome in terms of the number of  hematopoietic stem cell  ( CD34+ cells ) yield. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1078", "text": "Immature  hematopoietic stem cells  in the circulating  blood  that are similar to those in the  bone marrow  are collected by  apheresis  from a donor (PBSC collection). The product is then administered  intravenously  to the patient after treatment. The administered  hematopoietic stem cells  then migrate to the recipient's bone marrow, through a process known as  stem cell homing , where the transplanted cells override the previous  bone marrow . This allows the  bone marrow  to recover, proliferate and continue producing healthy  blood cells . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1079", "text": "The transplantation may be  autologous  (an individual's own blood cells),  allogeneic  (blood cells donated by someone else with matching  HLA ), or  syngeneic  (blood cells donated by an  identical twin ). The apheresis procedure typically lasts for 4\u20136 hours, depending on the  blood volume  of the donor. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1080", "text": "Granulocyte colony stimulating factor  (GCSF) are naturally occurring  glycoproteins  that stimulate white blood cell proliferation.  Filgrastim  is a synthetic form of GCSF produced in  E.coli . [ 7 ]  PBSC donors are given a course of GCSF prior to PBSC collection. The increase in white blood cell proliferation as a result of the Filgrastim ensures a better results from the donation. The course is usually given over a 4-day period prior to PBSC collection. [ 8 ]  The most common side effects of Filgrastim are bone, joint, back, arm, leg, mouth, throat, and muscle pain. [ 9 ]  Additionally, headache, nausea, vomiting, dizziness, fatigue, rash, loss of appetite, and difficulty falling or staying asleep are common. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1081", "text": "Since  allogeneic  PBSCT involves transformation of blood between different individuals, this naturally carries more complications than  autologous  PBSCT. [ 10 ] \nFor example, calculations must be made to ensure consistency in the amount of total blood volume between the donor and recipient. If the total blood volume of the donor is less than that of the recipient (such as when a child is donating to an adult), multiple PBSCT sessions may be required for adequate collection. Performing such a collection in a single setting could result in risks such as  hypovolemia , which could lead to  cardiac arrest  and death. Health care providers must exercise careful precaution when considering donor-recipient matching in  allogeneic  PBSCT. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1082", "text": "An early example of a successful peripheral stem cell transplant was carried out in the wake of the  1999 Tokaimura nuclear accident . Hisashi Ouchi, who received the highest dose of  radiation  was treated with PBSCT in an attempt to restore his destroyed immune system. Cells from the patient's sister's bone marrow were administered, and in the following weeks successfully began dividing and differentiating into  white blood cells . However, several weeks later, the cells were found to have been mutated by the radiation still present within the patient's body, and were observed carrying out  autoimmune responses . [ 12 ]  Later studies on the incident and subsequent use of PBSCT found that the transplant had also induced  neoendothelialization  of the aortic  endothelium . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1083", "text": "This article incorporates  public domain material  from  Dictionary of Cancer Terms .  U.S. National Cancer Institute ."}
{"_id": "WikiPedia_Hematology$$$corpus_1084", "text": "Hematoporphyrin  ( Photodyn ,  Sensibion ) is a  porphyrin  prepared from  hemin .  It is a derivative of  protoporphyrin IX , where the two vinyl groups have been hydrated (converted to alcohols). It is a deeply colored solid that is usually encountered as a solution.  Its  chemical structure  was determined in 1900. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1085", "text": "It is used as a photosensitizer in  photodynamic therapy .  Acetylation of hematoporphyrin followed by hydrolysis of the product of that reaction affords a mixture called  hematoporphyrin derivative  (HPD), which is also used in photodynamic therapy. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1086", "text": "Hematoporphyrin has also been used as an  antidepressant  and  antipsychotic  since the 1920s. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1087", "text": "This  drug  article relating to the  nervous system  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1088", "text": "A  hemoglobinometer  or  haemoglobinometer  ( British English ) is a medical device used to measure  hemoglobin   concentration  in  blood . [ 4 ]  It can operate by  spectrophotometric measurement  of hemoglobin concentration. Portable hemoglobinometers provide easy and convenient measurement of hematological variables, especially in areas where  clinic laboratories  are unavailable. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1089", "text": "As per guidelines of  National AIDS Control Organisation  (NACO) for accurate results & mass screening, [ citation needed ]  analysis using hemoglobinometer is a recommended method used for  absorbance  measurement of whole blood at Hb/HbO2/ Isobestic point , [ citation needed ]  based on  microcuvette  technology such as HemoCue 301 [ 6 ]  and Mokshit-Chanda-AM005A. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1090", "text": "Hemolysis  or  haemolysis  ( / h i\u02d0 \u02c8 m \u0252 l \u026a s \u026a s / ), [ 1 ]  also known by  several other names , is the rupturing ( lysis ) of  red blood cells  (erythrocytes) and the release of their contents ( cytoplasm ) into surrounding fluid (e.g.  blood plasma ). Hemolysis may occur  in vivo  or  in vitro ."}
{"_id": "WikiPedia_Hematology$$$corpus_1091", "text": "One cause of hemolysis is the action of  hemolysins , toxins that are produced by certain  pathogenic bacteria  or  fungi . Another cause is intense physical exercise. [ 2 ]   Hemolysins  damage the red blood cell's  cytoplasmic membrane , causing lysis and eventually cell death. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1092", "text": "From hemo- + -lysis, from  Ancient Greek   \u03b1\u1f37\u03bc\u03b1  ( ha\u00eema , 'blood') +  \u03bb\u03cd\u03c3\u03b9\u03c2   l\u00fasis , 'loosening')."}
{"_id": "WikiPedia_Hematology$$$corpus_1093", "text": "Hemolysis inside the body can be caused by a large number of medical conditions, including some parasites ( e.g. ,  Plasmodium ), some autoimmune disorders ( e.g. , autoimmune haemolytic anaemia, drug-induced  hemolytic anemia ,  atypical hemolytic uremic syndrome  (aHUS) [ 4 ] ), [ 5 ]  some genetic disorders ( e.g. ,  Sickle-cell disease  or  G6PD deficiency ), or blood with too low a solute concentration ( hypotonic  to cells). [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1094", "text": "Hemolysis can lead to  hemoglobinemia  due to  hemoglobin  released into the  blood plasma , which plays a significant role in the  pathogenesis  of  sepsis [ 7 ]  and can lead to increased risk of infection due to its inhibitory effects on the  innate immune system . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1095", "text": "Because the feeding process of the  Plasmodium  parasites damages red blood cells,  malaria  is sometimes called \"parasitic hemolysis\" in medical literature. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1096", "text": "Hemolytic disease of the newborn is an autoimmune disease resulting from the mother's antibodies crossing the placenta to the fetus. This most often occurs when the mother has previously been exposed to blood antigens present on the fetus but foreign to her, through either a blood transfusion or a previous pregnancy. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1097", "text": "Because  in vivo  hemolysis destroys red blood cells, in uncontrolled, chronic or severe cases it can lead to  hemolytic anemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_1098", "text": "A hemolytic crisis, or hyperhemolytic crisis, is characterized by an accelerated rate of red blood cell destruction leading to  anemia ,  jaundice , and  reticulocytosis . [ 9 ]  Hemolytic crises are a major concern with  sickle-cell disease  and  G6PD deficiency ."}
{"_id": "WikiPedia_Hematology$$$corpus_1099", "text": "Paxillus involutus  ingestion can cause hemolysis."}
{"_id": "WikiPedia_Hematology$$$corpus_1100", "text": "Spaceflight can cause hemolysis. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1101", "text": "Hemolysis may result from intrinsic defects in the red blood cell itself: [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1102", "text": "Extrinsic hemolysis is caused by the red blood cell's environment: [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1103", "text": "Intravascular hemolysis  describes hemolysis that happens mainly inside the  vasculature . [ 16 ]  As a result, the contents of the red blood cell are released into the general circulation, leading to  hemoglobinemia [ 17 ]  and increasing the risk of ensuing  hyperbilirubinemia . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1104", "text": "Intravascular hemolysis may occur when red blood cells are targeted by  autoantibodies , leading to  complement  fixation, or by damage by parasites such as  Babesia . [ 19 ]  Additionally, thrombotic microangiopathy (TMA) can result in hemolysis of red blood cells. [ 20 ]  TMA is frequently observed in  aHUS  patients where clots form in the small vessels of the kidney resulting in damaged red blood cells as they attempt to pass through the restricted vessels. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1105", "text": "Extravascular hemolysis  refers to hemolysis taking place in the  liver ,  spleen ,  bone marrow , and  lymph nodes . [ 16 ]  In this case little hemoglobin escapes into  blood plasma . [ 18 ]  The  macrophages  of the  reticuloendothelial system  in these organs  engulf and destroy  structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation. [ 22 ] [ 23 ]  Typically, the spleen destroys mildly abnormal red blood cells or those coated with  IgG-type antibodies , [ 24 ] [ 25 ]  while severely abnormal red blood cells or those coated with  IgM-type antibodies  are destroyed in the circulation or in the liver. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1106", "text": "If extravascular hemolysis is extensive,  hemosiderin  can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in  hemosiderosis . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1107", "text": "In vitro  hemolysis can be caused by improper technique during collection of blood specimens, by the effects of mechanical processing of blood, or by bacterial action in cultured blood specimens."}
{"_id": "WikiPedia_Hematology$$$corpus_1108", "text": "Most causes of  in vitro  hemolysis are related to specimen collection. Difficult collections, unsecure line connections, contamination, and incorrect needle size, as well as improper tube mixing and incorrectly filled tubes are all frequent causes of hemolysis. [ 27 ]  Excessive suction can cause the red blood cells to be smashed on their way through the  hypodermic needle  owing to turbulence and physical forces. Such hemolysis is more likely to occur when a patient's veins are difficult to find or when they collapse when blood is removed by a syringe or a modern vacuum tube. Experience and proper technique are key for any  phlebotomist , nurse or doctor to prevent hemolysis."}
{"_id": "WikiPedia_Hematology$$$corpus_1109", "text": "In vitro  hemolysis during specimen collection can cause inaccurate laboratory test results by contaminating the surrounding plasma with the contents of hemolyzed red blood cells. For example, the concentration of  potassium  inside red blood cells is much higher than in the plasma and so an elevated potassium level is usually found in biochemistry tests of hemolyzed blood."}
{"_id": "WikiPedia_Hematology$$$corpus_1110", "text": "After the blood collection process,  in vitro  hemolysis can still occur in a sample due to external factors, such as prolonged storage, incorrect storage conditions and excessive physical forces by dropping or vigorously mixing the tube."}
{"_id": "WikiPedia_Hematology$$$corpus_1111", "text": "In some surgical procedures (especially some heart operations) where substantial blood loss is expected, machinery is used for  intraoperative blood salvage . A centrifuge process takes blood from the patient, washes the red blood cells with  normal saline , and returns them to the patient's blood circulation. Hemolysis may occur if the centrifuge rotates too quickly (generally greater than 500 rpm)\u2014essentially this is hemolysis occurring outside of the body. Increased hemolysis occurs with massive amounts of sudden blood loss, because the process of returning a patient's cells must be done at a correspondingly higher speed to prevent  hypotension ,  pH  imbalance, and a number of other hemodynamic and blood level factors.  Modeling of fluid flows to predict the likelihood of red cell membrane rupture in response to stress is an active area of research. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1112", "text": "Visualizing the physical appearance of hemolysis in cultured blood samples may be used as a tool to determine the species of various  Gram-positive bacteria  infections ( e.g. ,  Streptococcus )."}
{"_id": "WikiPedia_Hematology$$$corpus_1113", "text": "Hemolysis is sometimes called  hematolysis ,  erythrolysis , or  erythrocytolysis . The words  hemolysis  ( / h i\u02d0 \u02c8 m \u0252 l \u026a s \u026a s / ) [ 1 ]  and  hematolysis  ( / \u02cc h i\u02d0 m \u0259 \u02c8 t \u0252 l \u026a s \u026a s / ) [ 29 ]  both use  combining forms  conveying the idea of \" lysis  of blood\" ( hemo-  or  hemato-  +  -lysis ). The words  erythrolysis  ( / \u02cc \u025br \u0259 \u02c8 \u03b8 r \u0252 l \u026a s \u026a s / ) [ 30 ]  and  erythrocytolysis  ( / \u0259 \u02cc r \u026a \u03b8 r o\u028a s a\u026a \u02c8 t \u0252 l \u026a s \u026a s / ) [ 31 ]  both use combining forms conveying the idea of \" lysis  of erythrocytes\" ( erythro-  \u00b1  cyto-  +  -lysis )."}
{"_id": "WikiPedia_Hematology$$$corpus_1114", "text": "Red blood cells (erythrocytes) have a short lifespan (approximately 120 days), and old ( senescent ) cells are constantly removed and replaced with new ones via  erythropoiesis . This breakdown/replacement process is called erythrocyte turnover. In this sense, erythrolysis or hemolysis is a normal process that happens continually. However, these terms are usually used to indicate that the lysis is  pathological ."}
{"_id": "WikiPedia_Hematology$$$corpus_1115", "text": "Pulmonary hypertension has been gaining recognition as a complication of chronic hereditary and acquired hemolysis. [ 32 ] [ 33 ] [ 34 ]  Free hemoglobin released during hemolysis inactivates the  vasodilator  nitric oxide (NO). [ 32 ]  Hemolysis also releases  arginase  that depletes  L-arginine , the substrate needed for NO synthesis. [ 32 ] [ 34 ]  This reduces NO-dependent vasodilation [ 32 ]  and induces  platelet  activation,  thrombin  generation,  procoagulant  factors and  tissue factor  activation, [ 32 ]  contributing to the formation of  thrombosis . [ 32 ]  This can lead to  esophageal spasm  and  dysphagia ,  abdominal pain ,  erectile dysfunction ,  systemic hypertension ,  decreased organ perfusion , promotion of  inflammation  and  coagulation , and  thrombosis . [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1116", "text": "Chronic hemolysis may also lead to  endothelial dysfunction , heightened  endothelin -1-mediated responses and  vasculopathy . [ 32 ] [ 36 ]   The release of  heme  leads to the production of  bilirubin  and depletion of plasma proteins, such as  albumin ,  haptoglobin , and  hemopexin , which may lead to  jaundice . [ 37 ] [ 38 ]  It may also lead to increased levels of the heme breakdown product  stercobilin  in the stool. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1117", "text": "Splenectomy  of those with hemolytic disorders appears to increase risk of developing  pulmonary thrombosis . [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1118", "text": "Complications may also arise from the increased workload for the kidney as it secretes  erythropoietin  to stimulate the  bone marrow  to produce more  reticulocytes  (red blood cell precursors) to compensate for the loss of red blood cells due to hemolysis. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1119", "text": "Hemorheology ,  also spelled   haemorheology  ( haemo  from  Greek  \u2018\u03b1\u1f37\u03bc\u03b1,  haima  ' blood '; and  rheology , from Greek \u1fe5\u03ad\u03c9  rh\u00e9\u014d , ' flow ' and -\u03bbo\u03b3\u03af\u03b1,  -logia  'study of'), or  blood rheology , is the study of flow properties of blood and its elements of  plasma  and  cells . Proper tissue  perfusion  can occur only when blood's  rheological  properties are within certain levels. Alterations of these properties play significant roles in disease processes. [ 1 ]  Blood  viscosity  is determined by plasma viscosity,  hematocrit  (volume fraction of red blood cell, which constitute 99.9% of the cellular elements) and mechanical properties of  red blood cells . Red blood cells have unique mechanical behavior, which can be discussed under the terms  erythrocyte deformability  and  erythrocyte aggregation . [ 2 ]  Because of that, blood behaves as a  non-Newtonian fluid . As such, the viscosity of blood varies with  shear rate . Blood becomes less viscous at high shear rates like those experienced with increased flow such as during exercise or in peak- systole . Therefore, blood is a  shear-thinning  fluid. Contrarily, blood viscosity increases when shear rate goes down with increased vessel diameters or with low flow, such as downstream from an obstruction or in  diastole .  Blood viscosity also increases with increases in red cell aggregability."}
{"_id": "WikiPedia_Hematology$$$corpus_1120", "text": "Blood viscosity is a measure of the resistance of blood to flow. It can also be described as the thickness and stickiness of blood. This  biophysical  property makes it a critical determinant of friction against the  vessel  walls, the rate of  venous return , the work required for the  heart  to pump blood, and how much  oxygen  is transported to tissues and organs. These functions of the  cardiovascular system  are directly related to  vascular resistance ,  preload ,  afterload , and  perfusion , respectively. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1121", "text": "The primary determinants of blood viscosity are  hematocrit ,  red blood cell deformability ,  red blood cell aggregation , and  plasma  viscosity. Plasma's viscosity is determined by water-content and  macromolecular  components, so these factors that affect blood viscosity are the  plasma protein  concentration and types of  proteins  in the plasma. [ 3 ]  Nevertheless, hematocrit has the strongest impact on whole blood viscosity. One unit increase in hematocrit can cause up to a 4% increase in blood viscosity. [ 2 ]  This relationship becomes increasingly sensitive as hematocrit increases. When the hematocrit rises to 60 or 70%, which it often does in  polycythemia , [ 4 ]  the blood viscosity can become as great as 10 times that of water, and its flow through blood vessels is greatly retarded because of increased resistance to flow. [ 5 ]  This will lead to decreased  oxygen delivery . [ 6 ]  Other factors influencing blood viscosity include  temperature , where an increase in temperature results in a decrease in viscosity. This is particularly important in  hypothermia , where an increase in blood viscosity will cause problems with blood circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_1122", "text": "Many conventional cardiovascular risk factors have been independently linked to whole blood viscosity."}
{"_id": "WikiPedia_Hematology$$$corpus_1123", "text": "Anemia  can reduce blood viscosity, which may lead to  heart failure . [ 7 ] \nFurthermore, elevation of plasma viscosity correlates to the progression of  coronary  and  peripheral artery diseases . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1124", "text": "In  pascal - seconds  (Pa\u00b7s), the  viscosity   \n \n \n \n \u03bc \n \n \n {\\displaystyle \\mu } \n \n  of blood at 37\u00a0\u00b0C is normally 3\u2009\u00d7\u200910 \u22123  to 4\u2009\u00d7\u200910 \u22123 , [ 8 ]  respectively 3 - 4 centi poise  (cP) in the  centimetre gram second system of units ."}
{"_id": "WikiPedia_Hematology$$$corpus_1125", "text": "\u03bc \n = \n ( \n 3 \n \u223c \n 4 \n ) \n \u22c5 \n \n 10 \n \n \u2212 \n 3 \n \n \n \n P \n a \n \u22c5 \n s \n \n \n {\\displaystyle \\mu =(3\\sim 4)\\cdot 10^{-3}\\,Pa\\cdot s}"}
{"_id": "WikiPedia_Hematology$$$corpus_1126", "text": "\u03bd \n = \n \n \n \u03bc \n \u03c1 \n \n \n = \n \n \n \n ( \n 3 \n \u223c \n 4 \n ) \n \u22c5 \n \n 10 \n \n \u2212 \n 3 \n \n \n P \n a \n \u22c5 \n s \n \n \n 1.06 \n \u22c5 \n \n 10 \n \n 3 \n \n \n \n \n \n k \n g \n \n \n m \n \n 3 \n \n \n \n \n \n \n \n = \n ( \n 2.8 \n \u223c \n 3.8 \n ) \n \u22c5 \n \n 10 \n \n \u2212 \n 6 \n \n \n \n \n \n \n m \n \n 2 \n \n \n s \n \n \n \n \n {\\displaystyle \\nu ={\\frac {\\mu }{\\rho }}={\\frac {(3\\sim 4)\\cdot 10^{-3}Pa\\cdot s}{1.06\\cdot 10^{3}{\\frac {kg}{m^{3}}}}}=(2.8\\sim 3.8)\\cdot 10^{-6}\\,{\\frac {m^{2}}{s}}} \n \n ,"}
{"_id": "WikiPedia_Hematology$$$corpus_1127", "text": "where  \n \n \n \n \u03c1 \n \n \n {\\displaystyle \\rho } \n \n  is the density. Blood viscosity can be measured by viscometers capable of measurements at various shear rates, such as a rotational  viscometer . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1128", "text": "Blood is a  viscoelastic  fluid, meaning that it possesses both viscous and fluid characteristics. The viscous component arises primarily through the  viscosity  of blood plasma, while the  elastic  component arises from deformation of the  red blood cells . As the heart contracts,  mechanical energy  is transferred from the heart to the blood; a small part of the energy is dissipated by the viscosity of the  suspension , another part is stored as elastic energy in the red blood cells, and the remaining energy is used to drive blood circulation and is thus converted to  kinetic energy . Viscoelastic fluids make up a larger class of fluids called  non-Newtonian fluids ."}
{"_id": "WikiPedia_Hematology$$$corpus_1129", "text": "The red blood cells occupy about half of the volume of blood and possess elastic properties.  This elastic property is the largest contributing factor to the viscoelastic behavior of blood. The large volume percentage of red blood cells at a normal  hematocrit  level leaves little room for cell motion and deformation without interacting with a neighboring cell.  Calculations have shown that the maximum volume percentage of red blood cells without deformation is 58% which is in the range of normally occurring levels. [ 10 ]  Due to the limited space between red blood cells, it is obvious that in order for blood to flow, significant cell to cell interaction will play a key role.  This interaction and tendency for cells to aggregate is a major contributor to the viscoelastic behavior of blood. Red blood cell deformation and aggregation is also coupled with flow-induced changes in the arrangement and orientation as a third major factor in its viscoelastic behavior. [ 11 ] [ 12 ]  Other factors contributing to the viscoelastic properties of blood is the plasma viscosity, plasma composition, temperature, and the rate of flow or shear rate. Together, these factors make human blood  viscoelastic , non- Newtonian , and  thixotropic . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1130", "text": "When the red cells are at rest or at very small shear rates, they tend to aggregate and stack together in an energetically favorable manner. The attraction is attributed to charged groups on the surface of cells and to the presence of fibrinogen and globulins. [ 14 ]  This aggregated configuration is an arrangement of cells with the least amount of deformation. With very low shear rates, the viscoelastic property of blood is dominated by the aggregation and cell deformability is relatively insignificant. As the shear rate increases the size of the aggregates begins to decrease. With a further increase in shear rate, the cells will rearrange and orient to provide channels for the plasma to pass through and for the cells to slide. In this low to medium shear rate range, the cells wiggle with respect to the neighboring cells allowing flow. The influence of aggregation properties on the viscoelasticity diminish and the influence of red cell deformability begins to increase.  As shear rates become large, red blood cells will stretch or deform and align with the flow. Cell layers are formed, separated by plasma, and flow is now attributed to layers of cells sliding on layers of plasma. The cell layer allows for easier flow of blood and as such there is a reduced viscosity and reduced elasticity. The viscoelasticity of the blood is dominated by the deformability of the red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_1131", "text": "Maxwell Model concerns Maxwell fluids or  Maxwell material . The material in Maxwell Model is a  fluid  which means it respects continuity properties for conservative equations\u00a0:  Fluids are a subset of the phases of matter and include liquids, gases, plasmas and, to some extent, plastic solids. Maxwell model is made to estimate local conservative values of viscoelasticity by a global measure in the integral volume of the model to be transposed to different flow situations. Blood is a complex material where different cells like red blood cells are discontinuous in plasma. Their size and shape are irregular too because they are not perfect spheres. Complicating moreover blood volume shape, red cells are not identically distributed in a blood sample volume because they migrate with velocity gradients in direction to the highest speed areas calling the famous representation of the  F\u00e5hr\u00e6us\u2013Lindqvist effect , aggregate or separate in sheath or plug flows described by Thurston. [ 15 ]  Typically, the Maxwell Model described below is uniformly considering the material (uniform blue color) as a perfect distributed particles fluid everywhere in the volume (in blue) but Thurston reveals that packs of red cells, plugs, are more present in the high speed region, if  y  is the height direction in the Maxwell model figure, ( y ~H) and there is a free cells layer in the lower speed area ( y ~0) what means the plasma fluid phase that deforms under Maxwell Model is strained following inner linings that completely escape from the analytical model by Maxwell. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1132", "text": "In theory, a fluid in a Maxwell Model behaves exactly similarly in any other flow geometry like pipes, rotating cells or in rest state. But in practice, blood properties vary with the geometry and blood has shown being an inadequate material to be studied as a fluid in common sense. So Maxwell Model gives trends that have to be completed in real situation followed by Thurston model  [ 15 ]  in a vessel regarding distribution of cells in sheath and plug flows. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1133", "text": "If a small cubical volume of blood is considered, with forces being acted upon it by the heart pumping and shear forces from boundaries.  The change in shape of the cube will have 2 components:"}
{"_id": "WikiPedia_Hematology$$$corpus_1134", "text": "When the force is removed, the cube would recover partially.  The elastic deformation is reversed but the slippage is not.  This explains why the elastic portion is only noticeable in unsteady flow.  In steady flow, the slippage will continue to increase and the measurements of non time varying force will neglect the contributions of the elasticity."}
{"_id": "WikiPedia_Hematology$$$corpus_1135", "text": "Figure 1 can be used to calculate the following parameters necessary for the evaluation of blood when a force is exerted."}
{"_id": "WikiPedia_Hematology$$$corpus_1136", "text": "A sinusoidal time varying flow is used to simulate the pulsation of a heart. A viscoelastic material subjected to a time varying flow will result in a phase variation between  \n \n \n \n \u03c4 \n \n \n {\\displaystyle \\tau } \n \n  and  \n \n \n \n \u03b3 \n \n \n {\\displaystyle \\gamma } \n \n  represented by  \n \n \n \n \u03d5 \n \n \n {\\displaystyle \\phi } \n \n . If  \n \n \n \n \u03d5 \n = \n 0 \n \n \n {\\displaystyle \\phi =0} \n \n , the material is a purely elastic because the stress and strain are in phase, so that the response of one caused by the other is immediate. If  \n \n \n \n \u03d5 \n \n \n {\\displaystyle \\phi } \n \n  = 90\u00b0, the material is a purely viscous because strain lags behind stress by 90 degrees. A viscoelastic material will be somewhere in between 0 and 90 degrees."}
{"_id": "WikiPedia_Hematology$$$corpus_1137", "text": "The sinusoidal time variation is proportional to  \n \n \n \n \n e \n \n i \n \u03c9 \n t \n \n \n \n \n {\\displaystyle e^{i\\omega t}} \n \n . Therefore, the size and phase relation between the stress, strain, and shear rate are described using this relationship and a radian frequency,  \n \n \n \n \u03c9 \n = \n 2 \n \u03c0 \n f \n \n \n {\\displaystyle \\omega =2\\pi f} \n \n  were  \n \n \n \n f \n \n \n {\\displaystyle f} \n \n  is the frequency in  Hertz ."}
{"_id": "WikiPedia_Hematology$$$corpus_1138", "text": "The components of the complex shear stress can be written as:"}
{"_id": "WikiPedia_Hematology$$$corpus_1139", "text": "Where  \n \n \n \n \n \u03c4 \n \u2032 \n \n \n \n {\\displaystyle \\tau '} \n \n  is the viscous stress and  \n \n \n \n \n \u03c4 \n \u2033 \n \n \n \n {\\displaystyle \\tau ''} \n \n  is the elastic stress.\nThe complex coefficient of viscosity  \n \n \n \n \n \u03b7 \n \n \u2217 \n \n \n \n \n {\\displaystyle \\eta ^{*}} \n \n  can be found by taking the ratio of the complex shear stress and the complex shear rate: [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1140", "text": "Similarly, the complex dynamic modulus G can be obtained by taking the ratio of the complex  shear stress  to the complex shear strain."}
{"_id": "WikiPedia_Hematology$$$corpus_1141", "text": "Relating the equations to common viscoelastic terms we get the storage modulus, G', and the loss modulus, G\"."}
{"_id": "WikiPedia_Hematology$$$corpus_1142", "text": "A viscoelastic  Maxwell material  model is commonly used to represent the viscoelastic properties of  blood .  It uses purely viscous damper and a purely elastic spring connected in series. Analysis of this model gives the complex viscosity in terms of the dashpot constant and the spring constant."}
{"_id": "WikiPedia_Hematology$$$corpus_1143", "text": "One of the most frequently used constitutive models for the  viscoelasticity  of blood is the Oldroyd-B model. There are several variations of the Oldroyd-B non-Newtonian model characterizing shear thinning behavior due to red blood cell aggregation and dispersion at low shear rate. Here we consider a three-dimensional Oldroyd-B model coupled with the momentum equation and the total stress tensor. [ 17 ]   A non Newtonian flow is used which insures that the viscosity of blood  \n \n \n \n \u03bc \n ( \n h \n , \n d \n ) \n \n \n {\\displaystyle \\mu (h,d)} \n \n  is a function of vessel diameter d and hematocrit h. In the Oldroyd-B model, the relation between the shear stress tensor B and the orientation stress tensor A is given by:"}
{"_id": "WikiPedia_Hematology$$$corpus_1144", "text": "S \n + \n \u03b3 \n \n [ \n \n \n \n \n D \n S \n \n \n D \n t \n \n \n \n \u2212 \n \u0394 \n V \n \u22c5 \n S \n \u2212 \n S \n \u22c5 \n \n \n ( \n \u0394 \n V \n ) \n \n \n T \n \n \n \n ] \n \n = \n \u03bc \n ( \n h \n , \n d \n ) \n \n [ \n \n B \n + \n \u03b3 \n \n ( \n \n \n \n \n D \n B \n \n \n D \n t \n \n \n \n \u2212 \n \u0394 \n V \n \u22c5 \n B \n \u2212 \n B \n \u22c5 \n \n \n ( \n \u0394 \n V \n ) \n \n \n T \n \n \n \n ) \n \n \n ] \n \n \u2212 \n g \n A \n + \n \n C \n \n 1 \n \n \n \n ( \n \n g \n A \n \u2212 \n \n \n \n \n C \n \n 2 \n \n \n I \n \n \n \u03bc \n ( \n h \n , \n d \n \n ) \n \n 2 \n \n \n \n \n \n \n ) \n \n \n \n {\\displaystyle S+\\gamma \\left[{\\frac {DS}{Dt}}-\\Delta V\\cdot S-S\\cdot {(\\Delta V)}^{T}\\right]=\\mu (h,d)\\left[B+\\gamma \\left({\\frac {DB}{Dt}}-\\Delta V\\cdot B-B\\cdot {(\\Delta V)}^{T}\\right)\\right]-gA+C_{1}\\left(gA-{\\frac {C_{2}I}{\\mu (h,d)^{2}}}\\right)}"}
{"_id": "WikiPedia_Hematology$$$corpus_1145", "text": "where D/Dt is the material derivative, V is the velocity of the fluid, C1, C2, g,  \n \n \n \n \u03b3 \n \n \n {\\displaystyle \\gamma } \n \n  are constants. S and B are defined as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_1146", "text": "Red blood cells are subjected to intense mechanical stimulation from both blood flow and vessel walls, and their rheological properties are important to their effectiveness in performing their biological functions in the microcirculation. [ 18 ]  Red blood cells by themselves have been shown to exhibit viscoelastic properties. There are several methods used to explore the mechanical properties of red blood cells such as:"}
{"_id": "WikiPedia_Hematology$$$corpus_1147", "text": "These methods worked  to characterize the deformability of the red blood cell in terms of the shear, bending, area expansion moduli, and relaxation times. [ 20 ]  However, they were not able to explore the viscoelastic properties. Other techniques have been implemented such as photoacoustic measurements. This technique uses a single-pulse laser beam to generate a photoacoustic signal in tissues and the decay time for the signal is measured. According to the theory of linear viscoelasticity, the decay time is equal to the viscosity-elasticity ratio and therefore the viscoelasticity characteristics of the red blood cells could be obtained. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1148", "text": "Another experimental technique used to evaluate viscoelasticity consisted of using Ferromagnetism beads bonded to a cells surface. Forces are then applied to the magnetic bead using optical magnetic twisting cytometry which allowed researchers to explore the time dependent responses of red blood cells. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1149", "text": "T \n \n s \n \n \n ( \n t \n ) \n \n \n {\\displaystyle T_{s}(t)} \n \n  is the mechanical torque per unit bead volume (units of stress) and is given by:"}
{"_id": "WikiPedia_Hematology$$$corpus_1150", "text": "where H is the applied magnetic twisting field,  \n \n \n \n \n \u03b8 \n \n \n \n {\\displaystyle {\\theta }} \n \n  is the angle of the bead\u2019s magnetic moment relative to the original magnetization direction, and c is the bead constant which is found by experiments conducted by placing the bead in a fluid of known viscosity and applying a twisting field."}
{"_id": "WikiPedia_Hematology$$$corpus_1151", "text": "Complex  Dynamic modulus  G can be used to represent the relations between the oscillating stress and strain:"}
{"_id": "WikiPedia_Hematology$$$corpus_1152", "text": "where  \n \n \n \n \n G \n \u2032 \n \n \n \n {\\displaystyle G'} \n \n  is the  storage modulus  and  \n \n \n \n \n G \n \u2033 \n \n \n \n {\\displaystyle G''} \n \n  is the  loss modulus :"}
{"_id": "WikiPedia_Hematology$$$corpus_1153", "text": "where  \n \n \n \n \n \u03c3 \n \n 0 \n \n \n \n \n {\\displaystyle \\sigma _{0}} \n \n  and  \n \n \n \n \n \u03b5 \n \n 0 \n \n \n \n \n {\\displaystyle \\varepsilon _{0}} \n \n  are the amplitudes of stress and strain and  \n \n \n \n \u03d5 \n \n \n {\\displaystyle \\phi } \n \n  is the phase shift between them."}
{"_id": "WikiPedia_Hematology$$$corpus_1154", "text": "From the above relations, the components of the complex modulus are determined from a loop that is created by comparing the change in torque with the change in time which forms a loop when represented graphically.  The limits of  \n \n \n \n \n T \n \n s \n \n \n ( \n t \n ) \n \n \n {\\displaystyle T_{s}(t)} \n \n  - d(t) loop and the area, A, bounded by the  \n \n \n \n \n T \n \n s \n \n \n ( \n t \n ) \n \n \n {\\displaystyle T_{s}(t)} \n \n  - d(t) loop, which represents the energy dissipation per cycle, are used in the calculations. The phase angle  \n \n \n \n \u03d5 \n \n \n {\\displaystyle \\phi } \n \n , storage modulus G', and loss modulus G  then become:"}
{"_id": "WikiPedia_Hematology$$$corpus_1155", "text": "where d is the displacement."}
{"_id": "WikiPedia_Hematology$$$corpus_1156", "text": "The hysteresis shown in figure 3 represents the viscoelasticity present in red blood cells.  It is unclear if this is related to membrane molecular fluctuations or metabolic activity controlled by intracellular concentrations of  ATP . Further research is needed to fully explore these interaction and to shed light on the underlying viscoelastic deformation characteristics of the red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_1157", "text": "When looking at viscoelastic behavior of blood  in vivo , it is necessary to also consider the effects of  arteries ,  capillaries , and  veins . The viscosity of blood has a primary influence on flow in the larger arteries, while the elasticity, which resides in the elastic deformability of red blood cells, has primary influence in the arterioles and the capillaries. [ 23 ]  Understanding wave propagation in arterial walls, local hemodynamics, and wall shear stress gradient is important in understanding the mechanisms of cardiovascular function. Arterial walls are anisotropic and heterogeneous, composed of layers with different bio-mechanical characteristics which makes understanding the mechanical influences that arteries contribute to blood flow very difficult. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1158", "text": "From a medical standpoint, the importance of studying the viscoelastic properties of blood becomes evident. With the development of cardiovascular prosthetic devices such as heart valves and blood pumps, the understanding of pulsating blood flow in complex geometries is required. A few specific examples are the effects of viscoelasticity of blood and its implications for the testing of a pulsatile Blood Pumps. [ 25 ]  Strong correlations between blood viscoelasticity and regional and global cerebral blood flow during cardiopulmonary bypass have been documented. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1159", "text": "This has also led the way for developing a blood analog in order to study and test prosthetic devices.  The classic analog of glycerin and water provides a good representation of viscosity and inertial effects but lacks the elastic properties of real blood. One such blood analog is an aqueous solution of Xanthan gum and glycerin developed to match both the viscous and elastic components of the complex viscosity of blood. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1160", "text": "Normal red blood cells are deformable but many conditions, such as  sickle cell disease , reduce their elasticity which makes them less deformable. Red blood cells with reduced deformability have increasing impedance to flow, leading to an increase in red blood cell aggregation and reduction in oxygen saturation which can lead to further complications. The presence of cells with diminished deformability, as is the case in sickle cell disease, tends to inhibit the formation of plasma layers and by measuring the viscoelasticity, the degree of inhibition can be quantified. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1161", "text": "In early theoretical work, blood was treated as a non-Newtonian viscous fluid. Initial studies had evaluated blood during steady flow and later, using oscillating flow. [ 29 ]  Professor George B. Thurston, of the University of Texas, first presented the idea of blood being viscoelastic in 1972.  The previous studies that looked at blood in steady flow showed negligible elastic properties because the elastic regime is stored in the blood during flow initiation and so its presence is hidden when a flow reaches steady state.  The early studies used the properties found in steady flow to derive properties for unsteady flow situations. [ 30 ] [ 31 ]   Advancements in medical procedures and devices required a better understanding of the mechanical properties of blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1162", "text": "The relationships between shear stress and shear rate for blood must be determined experimentally and expressed by  constitutive equations .  Given the complex macro-rheological behavior of blood, it is not surprising that a single equation fails to completely describe the effects of various rheological variables (e.g.,  hematocrit , shear rate).  Thus, several approaches to defining these equations exist, with some the result of curve-fitting experimental data and others based on a particular rheological model."}
{"_id": "WikiPedia_Hematology$$$corpus_1163", "text": "The finding that, for blood flowing steadily in tubes with diameters of less than 300 micrometres, the average hematocrit of the blood in the tube is less than the hematocrit of the blood in the reservoir feeding the tube is known as the F\u00e5hr\u00e6us effect.  This effect is generated in the concentration entrance length of the tube, in which erythrocytes move towards the central region of the tube as they flow downstream.  This entrance length is estimated to be about the distance that the blood travels in a quarter of a second for blood where red blood cell aggregation is negligible and the vessel diameter is greater than about 20 micrometres. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1164", "text": "As the characteristic dimension of a flow channel approaches the size of the particles in a suspension; one should expect that the simple continuum model of the suspension will fail to be applicable.  Often, this limit of the applicability of the continuum model begins to manifest itself at characteristic channel dimensions that are about 30 times the particle diameter: in the case of blood with a characteristic RBC dimension of 8 \u03bcm, an apparent failure occurs at about 300 micrometres.  This was demonstrated by F\u00e5hraeus and Lindqvist, who found that the apparent viscosity of blood was a function of tube diameter for diameters of 300 micrometres and less when they flowed constant-hematocrit blood from a well-stirred reservoir through a tube. The finding that for small tubes with diameters below about 300 micrometres and for faster flow rates which do not allow appreciable erythrocyte aggregation, the effective viscosity of the blood depends on tube diameter is known as the F\u00e5hr\u00e6us\u2013Lindqvist effect. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1165", "text": "Hemosiderin  or  haemosiderin  is an  iron -storage complex that is composed of partially digested ferritin and  lysosomes . The breakdown of  heme  gives rise to  biliverdin  and iron. [ 1 ] [ 2 ]  The body then traps the released iron and stores it as hemosiderin in tissues. [ 3 ]  Hemosiderin is also generated from the abnormal metabolic pathway of  ferritin . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1166", "text": "It is only found within cells (as opposed to circulating in blood) and appears to be a complex of  ferritin , denatured ferritin and other material. [ 4 ] [ 5 ]  The iron within deposits of hemosiderin is very poorly available to supply iron when needed.  Hemosiderin can be identified histologically with  Perls' Prussian blue  stain ; iron in hemosiderin turns blue to black when exposed to potassium ferrocyanide. [ 6 ]  In normal animals, hemosiderin deposits are small and commonly inapparent without special stains. Excessive accumulation of hemosiderin is usually detected within cells of the  mononuclear phagocyte system  (MPS) or occasionally within  epithelial cells  of the liver and kidney."}
{"_id": "WikiPedia_Hematology$$$corpus_1167", "text": "Several disease processes result in deposition of larger amounts of hemosiderin in tissues; although these deposits often cause no symptoms, they can lead to  organ damage ."}
{"_id": "WikiPedia_Hematology$$$corpus_1168", "text": "Hemosiderin is most commonly found in  macrophages  and is especially abundant in situations following  hemorrhage , suggesting that its formation may be related to  phagocytosis  of  red blood cells  and  hemoglobin . Hemosiderin can accumulate in different  organs  in various  diseases ."}
{"_id": "WikiPedia_Hematology$$$corpus_1169", "text": "Iron is required by many of the  chemical reactions  (i.e., oxidation-reduction reactions) in the body but is  toxic  when not properly contained. Thus, many methods of iron storage have developed."}
{"_id": "WikiPedia_Hematology$$$corpus_1170", "text": "Hemosiderin often forms after bleeding (haemorrhage). [ 7 ]  When blood leaves a ruptured blood vessel, the  red blood cell  dies, and the hemoglobin of the cell is released into the extracellular space. Phagocytic cells (of the  mononuclear phagocyte system ) called macrophages engulf (phagocytose) the hemoglobin to degrade it, producing hemosiderin and  biliverdin . Excessive systemic accumulations of hemosiderin may occur in macrophages in the liver, lungs, spleen, kidneys, lymph nodes, and bone marrow. These accumulations may be caused by excessive red blood cell destruction (haemolysis), excessive iron uptake/hyperferraemia, or decreased iron utilization (e.g., anaemia of copper toxicity) uptake hypoferraemia (which often leads to iron deficiency anemia)."}
{"_id": "WikiPedia_Hematology$$$corpus_1171", "text": "Cellular iron is found as either ferritin or hemosiderin. It is identified in cells by the Perls or Prussian blue reaction, in which ionic iron reacts with acid ferrocyanide to impart a blue color.<Wintrobe's Clinical Hematology>"}
{"_id": "WikiPedia_Hematology$$$corpus_1172", "text": "Hemosiderin may deposit in diseases associated with iron overload. [ 8 ]  These diseases are typically diseases in which chronic blood loss requires frequent  blood transfusions , such as  sickle cell anemia  and  thalassemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_1173", "text": "In  biology ,  hemostasis   or   haemostasis  is a process to prevent and stop  bleeding , meaning to keep  blood  within a damaged  blood vessel  (the opposite of hemostasis is  hemorrhage ). It is the first stage of  wound healing .  Hemostasis involves three major steps:"}
{"_id": "WikiPedia_Hematology$$$corpus_1174", "text": "Coagulation, the changing of blood from a liquid to a  gel  which forms the fibrin clots, is essential to hemostasis. Intact blood vessels moderate blood's tendency to form  clots . The  endothelial  cells of intact vessels prevent blood clotting with a heparin-like molecule and  thrombomodulin , and prevent platelet aggregation with  nitric oxide  and  prostacyclin . When endothelium of a blood vessel is damaged, the endothelial cells stop secretion of coagulation and aggregation inhibitors and instead secrete  von Willebrand factor , which initiates the maintenance of hemostasis after injury. These processes seal the injury or hole until tissues are healed."}
{"_id": "WikiPedia_Hematology$$$corpus_1175", "text": "The word  hemostasis  ( / \u02cc h i\u02d0 m o\u028a \u02c8 s t e\u026a s \u026a s / , [ 1 ] [ 2 ]   sometimes   / \u02cc h i\u02d0 \u02c8 m \u0252 s t \u0259 s \u026a s / ) uses the  combining forms   hemo-  and  -stasis ,  Neo-Latin  from  Ancient Greek   \u03b1\u1f31\u03bc\u03bf-   haimo-  (similar to  \u03b1\u1f37\u03bc\u03b1   ha\u00eema ), meaning \"blood\", and  \u03c3\u03c4\u03ac\u03c3\u03b9\u03c2   st\u00e1sis , meaning \" stasis \", yielding \"motionlessness or stopping of blood\"."}
{"_id": "WikiPedia_Hematology$$$corpus_1176", "text": "Hemostasis occurs when blood is present outside of the body or blood vessels. It is the innate response for the body to stop bleeding and loss of blood. During hemostasis three steps occur in a rapid sequence. Vascular spasm is the first response as the blood vessels constrict to allow less blood to be lost. In the second step, platelet plug formation,  platelets  stick together to form a temporary seal to cover the break in the vessel wall. The third and last step is called coagulation or blood clotting. Coagulation reinforces the platelet plug with fibrin threads that act as a \"molecular glue\". [ 3 ]  Platelets are a large factor in the hemostatic process. They allow for the creation of the \"platelet plug\" that forms almost directly after a blood vessel has been ruptured. Within seconds of a blood vessel's epithelial wall being disrupted, platelets begin to adhere to the sub- endothelium  surface. It takes approximately sixty seconds until the first fibrin strands begin to intersperse among the wound. After several minutes the platelet plug is completely formed by fibrin. [ 4 ]  Hemostasis is maintained in the body via three mechanisms:"}
{"_id": "WikiPedia_Hematology$$$corpus_1177", "text": "Hemostasis can be achieved in various other ways if the body cannot do it naturally (or needs help) during surgery or medical treatment. When the body is under shock and stress, hemostasis is harder to achieve. Though natural hemostasis is most desired, having other means of achieving this is vital for survival in many emergency settings. Without the ability to stimulate hemostasis the risk of  hemorrhaging   is great. During surgical procedures, the types of hemostasis listed below can be used to control bleeding while avoiding and reducing the risk of tissue destruction. Hemostasis can be achieved by  chemical agent  as well as mechanical or physical agents. Which hemostasis type used is determined based on the situation. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1178", "text": "Developmental Haemostasis  refers to the differences in the haemostatic system between children and adults."}
{"_id": "WikiPedia_Hematology$$$corpus_1179", "text": "Debates by physicians and medical practitioners still continue to arise on the subject of hemostasis and how to handle situations with large injuries. If an individual acquires a large injury resulting in extreme blood loss, then a  hemostatic agent  alone would not be very effective. Medical professionals continue to debate on what the best ways are to assist a patient in a chronic state; however, it is universally accepted that hemostatic agents are the primary tool for smaller bleeding injuries. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1180", "text": "Some main types of hemostasis used in emergency medicine include:"}
{"_id": "WikiPedia_Hematology$$$corpus_1181", "text": "The body's hemostasis system requires careful regulation in order to work properly. If the blood does not clot sufficiently, it may be due to bleeding disorders such as  hemophilia  or  immune thrombocytopenia ; this requires careful investigation. Over-active clotting can also cause problems;  thrombosis , where blood clots form abnormally, can potentially cause  embolisms , where blood clots break off and subsequently become lodged in a vein or artery. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1182", "text": "Hemostasis disorders can develop for many different reasons. They may be  congenital , due to a deficiency or defect in an individual's platelets or clotting factors. A number of disorders can be acquired as well, such as in  HELLP syndrome , which is due to pregnancy, or  Hemolytic-uremic syndrome  (HUS), which is due to  E. coli  toxins."}
{"_id": "WikiPedia_Hematology$$$corpus_1183", "text": "The process of preventing blood loss from a vessel or organ of the body is referred to as hemostasis. The term comes from the  Ancient Greek  roots \"heme\" meaning blood, and \"stasis\" meaning halting; Put together means the \"halting of the blood\". [ 3 ] \nThe origin of hemostasis dates back as far as ancient Greece; first referenced to being used in the  Battle of Troy . It started with the realization that excessive bleeding inevitably equaled death. Vegetable and mineral styptics were used on large wounds by the Greeks and Romans until the takeover of Egypt around 332BC by Greece. At this time many more advances in the general medical field were developed through the study of Egyptian  mummification  practice, which led to greater knowledge of the hemostatic process. It was during this time that many of the veins and arteries running throughout the human body were found and the directions in which they traveled. Doctors of this time realized if these were plugged, blood could not continue to flow out of the body. Nevertheless, it took until the invention of the printing press during the fifteenth century for medical notes and ideas to travel westward, allowing for the idea and practice of hemostasis to be expanded. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1184", "text": "There is currently a great deal of research being conducted on hemostasis. The most current research is based on genetic factors of hemostasis and how it can be altered to reduce the cause of  genetic disorders  that alter the natural process hemostasis. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1185", "text": "Von Willebrand disease  is associated with a defect in the ability of the body to create the platelet plug and the fibrin mesh that ultimately stops the bleeding. New research is concluding that the von Willebrand disease is much more common in adolescence. This disease negatively hinders the natural process of Hemostasis causing excessive bleeding to be a concern in patients with this disease. There are complex treatments that can be done including a combination of therapies,  estrogen - progesterone  preparations,  desmopressin , and Von Willebrand factor concentrates. Current research is trying to find better ways to deal with this disease; however, much more research is needed in order to find out the effectiveness of the current treatments and if there are more operative ways to treat this disease. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1186", "text": "Haemotoxins ,  hemotoxins  or  hematotoxins  are  toxins   that destroy  red blood cells , disrupt  blood   clotting , and/or cause  organ  degeneration and generalized  tissue  damage. The term  haemotoxin  is to some degree a  misnomer  since toxins that damage the blood also damage other tissues. Injury from a haemotoxic agent is often very painful and can cause permanent damage and in severe cases death. Loss of an affected limb is possible even with prompt treatment."}
{"_id": "WikiPedia_Hematology$$$corpus_1187", "text": "Haemotoxins are frequently employed by  venomous  animals, including snakes ( vipers  and  pit vipers ) and spiders ( brown recluse ). Animal venoms contain  enzymes  and other  proteins  that are haemotoxic or  neurotoxic  or occasionally both (as in the  Mojave rattlesnake , the  Japanese mamushi , [ 1 ]  and similar species). In addition to killing the prey, part of the function of a haemotoxic venom for some animals is to aid digestion. The venom breaks down protein in the region of the bite, making prey easier to digest."}
{"_id": "WikiPedia_Hematology$$$corpus_1188", "text": "The process by which a haemotoxin causes death is much slower than that of a  neurotoxin .  Snakes which envenomate a prey animal may have to track the prey as it flees.  Typically, a  mammalian  prey will stop fleeing not because of death, but due to shock caused by the venomous bite. Symptoms are dependent upon species, size, location of bite and the amount of venom injected. In humans, symptoms include nausea, disorientation, and headache; these may be delayed for several hours."}
{"_id": "WikiPedia_Hematology$$$corpus_1189", "text": "Haemotoxins are used in  diagnostic  studies of the  coagulation  system.  Lupus anticoagulant  is detected by changes in the  dilute Russell's viper venom time , which is a  laboratory  assay based on\u2014as its name indicates\u2014venom of the  Russell's viper ."}
{"_id": "WikiPedia_Hematology$$$corpus_1190", "text": "Histolysis  is the decay and dissolution of organic tissues or of blood. It is sometimes referred to as  histodialysis . [ 1 ]  In cells, histolysis may be caused by  uracil-DNA  degradation. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1191", "text": "Origin: New Latin, from  Greek   \u2018\u03b9\u03c3\u03c4\u03bf\u03c2  (histos) tissue +  \u03bb\u03c5\u03c3\u03b9\u03c2  (lusis) dissolution from  \u03bb\u03c5\u03b5\u03b9\u03bd  to loosen, dissolve."}
{"_id": "WikiPedia_Hematology$$$corpus_1192", "text": "Histolysis is associated with  metamorphosis  as well as other morphological changes. The loss of organs or blood begins with  cell death , which can be caused by a number of factors. In frogs, the histolysis of the tail associated with metamorphosis is also associated with a lowering of the  pH  of the blood. [ 3 ] \nIncreases in histolysis has been found to correspond with the pupal phase of insect metamorphosis, wherein larval organs break down before the  histogenesis  of the adult tissues occur. The histolysis is associated with an increase in the production of  ATP  and a decrease in metabolism.  [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1193", "text": "Thomas Hodgkin   RMS  (17 August 1798 \u2013 5 April 1866) was a British  physician , considered one of the most prominent  pathologists  of his time and a pioneer in  preventive medicine . He is now best known for the first account of  Hodgkin's disease , a form of  lymphoma  and  blood disease , in 1832. [ 1 ]  Hodgkin's work marked the beginning of times when a pathologist was actively involved in the clinical process. He was a contemporary of  Thomas Addison   and  Richard Bright  at  Guy's Hospital  in London."}
{"_id": "WikiPedia_Hematology$$$corpus_1194", "text": "Thomas Hodgkin was born to a  Quaker  family in  Pentonville ,  St. James Parish, Middlesex , the son of  John Hodgkin . [ 2 ]  He received private education with his brother  John Hodgkin , and in 1816 took a position as private secretary to  William Allen . [ 3 ]  His aim was to learn the trade of  apothecary , one of the routes into medicine, and Allen, despite prominence in that business, did not make it possible. They parted, and Hodgkin went to an apothecary cousin, John Glaisyer, in  Brighton  instead. [ 4 ]  He inherited property from his great-uncle of the same name, meaning that from age 21 he had a degree of financial independence. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1195", "text": "In September 1819 Hodgkin was admitted to  St. Thomas' and Guy's Medical School . He \"walked the wards\" for a year on the rounds of physicians and surgeons, and attended lectures, in particular those by  Astley Cooper . [ 6 ]  He then studied at the  University of Edinburgh , where the lecturers who impressed him included  Andrew Duncan, the younger , and  Robert Jameson  in natural history. His first published paper, on the  spleen , came from Duncan's course, and drew on the veterinary writings of his friend  Bracy Clark . [ 7 ]  During his time as a student, he became a member of the  Royal Medical Society . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1196", "text": "In 1821, Hodgkin went to France, where he learned to work with the  stethoscope , a recent invention of  Ren\u00e9 Laennec . He also took account of the exacting statistical and clinical approach of  Pierre Charles Alexandre Louis . [ 8 ]  He associated there with British expatriates including  Robert Knox  and  Helen Maria Williams . [ 9 ]  In 1823, he qualified for his M.D. at the  University of Edinburgh Medical School  with a thesis on the physiological mechanisms of absorption in animals. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1197", "text": "In Paris Hodgkin met  Benjamin Thorpe , a banker for Rothschild's at the time, who was suffering from  tuberculosis . Hodgkin became his physician for a while, and Thorpe was cured. [ 11 ]  This contact led to another appointment as physician to Abraham Montefiore, married to Henriette, daughter of  Mayer Amschel Rothschild . Once graduated at Edinburgh, Hodgkin joined the couple for travel in Italy. Abraham was seriously ill with tuberculosis (he died in 1824) and the position proved unsatisfactory for both sides, with Hodgkin dismissed. But the relationship he built up with  Moses Montefiore , Abraham's brother, proved a lifelong friendship. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1198", "text": "Staying in Paris for an extended period from September 1824 to June 1825, Hodgkin made significant medical contacts. The Edwards brothers,  William-Fr\u00e9d\u00e9ric Edwards  and  Henri Milne Edwards , were both physiologists with distinctive theories, and Hodgkin looked over their work in the next few years.  Achille-Louis Foville  was a neurologist, around whom Hodgkin tried unsuccessfully, from 1838, to set up a southern version of the  York Retreat . [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1199", "text": "Hodgkin found a position at Guy's, first as a volunteer clerk in 1825, and then in 1826 as the curator of the museum there, also carrying out autopsies. He built up his reputation on the work his posts brought him in morbid anatomy ( anatomical pathology  as it is now called). [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1200", "text": "Hodgkin's hospital career came to an end, however, in 1837, when he clashed with the autocratic  Benjamin Harrison . Harrison disliked Hodgkin's progressive views, and support for the new  University College, London , and had been personally offended by them in one instance (see below). [ 3 ]  There were two confrontational interviews in which Harrison went over pretexts for not giving Hodgkin a promotion (to Assistant Physician); Hodgkin had also been ill not long before. His friends pushed the issue to an acrimonious vote of the governors, which was in fact hopeless. The position went to the rival candidate  Benjamin Guy Babington , and Hodgkin moved reluctantly into private practice, after a period of convalescence. [ 16 ]  In 1840 he attended the  World Anti-Slavery Convention  in London representing the  Aborigines Protection Society . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1201", "text": "Hodgkin had a further period of involvement with hospital medicine, when in 1842 he was asked to take charge of teaching at  St. Thomas' Hospital . After joint management of Guy's and St. Thomas' had ended in 1825, St. Thomas' had found itself eclipsed as a medical school by its former partner. Hodgkin was brought in, and found new lecturers in  Marshall Hall  and  George Gregory ; he lectured himself, and with Charles Barker the four embarked on a lecture series. He also drew on his experience at Guy's to improve the museum and start a Clinical Society for reporting of cases. The outcome, however, was unsatisfactory for him. Hall was much preferred as lecturer, and Gregory, lecturing on  skin diseases , gained a reputation for clarity, and wrote a textbook. But Hodgkin was not asked to continue lecturing for another year, ending the relationship. [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1202", "text": "In around 1847, Hodgkin became guardian to an Aboriginal Australian youth,  Warrulan , who had been brought to England in 1845 by  Edward John Eyre , [ 20 ]  arranging for him to be educated at the Quaker  Sibford School . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1203", "text": "Hodgkin married in 1850 Sarah Frances Scaife, a widow; they had no children. [ 2 ]  When Lady Montefiore died in 1862, Hodgkin promised her to travel with her husband on future journeys. [ 22 ]  He accompanied  Moses Montefiore  to Palestine in 1866. There he contracted  dysentery  and died on 4 April 1866. He was buried in  Jaffa ."}
{"_id": "WikiPedia_Hematology$$$corpus_1204", "text": "Hodgkin like many other Quakers was concerned both with the  abolition of slavery  and the reduction of the impact of western colonization on indigenous peoples around the world. He stood aside from the  Anti-Slavery Society  of the 1820s and 1830s, however; the society took a different line on emancipation and colonization in Africa. It refused in the early 1830s to publish his views. [ 23 ]  Hodgkin began to take multiple initiatives of his own."}
{"_id": "WikiPedia_Hematology$$$corpus_1205", "text": "Hodgkin had an interest in both the  physical anthropology  and the cultural aspects of what would now be  ethnology , before the academic disciplines existed. In his role as keeper of the Museum at Guy's, he collected specimens from peoples from around the world. [ 24 ]  In 1827, in a letter supporting the missionary  Hannah Kilham  who was working with West African languages, he published for the first time long-held ideas on \" civilisation \"; [ 25 ]  a Civilization Society in London had been a Hodgkin family initiative some years earlier. [ 26 ]  In helping to found the  Aborigines Protection Society , he argued that languages constituted philological evidence of man's origins, and should therefore be preserved where threatened; [ 27 ]  he had written a paper on the topic, and proposed a questionnaire, for the  Philological Society  in 1835. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1206", "text": "For Hodgkin, language was a  racial trait . [ 29 ]  In Paris around the end of 1838, he prevailed upon W. F. Edwards to form a French society with the same aims as the Aborigines Protection Society; and in 1839 the  Soci\u00e9t\u00e9 Ethnologique de Paris  was set up in accordance with Edwards's own ideas. [ 30 ]  This development was reflected in 1843 when the  Ethnological Society of London  was set up, diverging from the Aborigines Protection Society by its scientific and linguistic interests, and disconnecting from missionary work. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1207", "text": "Hodgkin was a supporter of  Liberia  in the early days of its foundation; and he compared it favourably to  Sierra Leone . [ 32 ]  In supporting  Elliott Cresson  and the  American Colonization Society , he put himself outside the mainstream of Quaker and abolitionist thinking. When the American  abolitionist ,  William Lloyd Garrison , toured in England in 1833, Hodgkin tried at first to mediate between Garrison and Cresson. The formation, however, of the  British African Colonization Society  by Cresson had Hodgkin's support, and he found himself isolated from natural allies who were Quakers or physicians. There were personal attacks on Hodgkin from the Garrison camp. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1208", "text": "Hodgkin became involved in campaigning concerning the  Boothia Peninsula  and the  Hudson's Bay Company  around 1836\u201337, through his friend  Richard King . King had been on the expedition of Captain  George Back  in the north of Canada of 1833\u201335, and had written an 1836 book, his  Narrative , on it; he advocated a further expedition in the same area in 1836\u201337, a cause Hodgkin took up. Sensitive commercial interests were involved, as the Hudson's Bay Company's license was due for renewal in 1841. [ 34 ]  The  Narrative  contained a piece Hodgkin had written on the indifference of the company to the indigenous peoples of western Canada. [ 35 ]  Hodgkin then took up the behaviour of the company with Benjamin Harrison, Treasurer of Guy's, disastrously mixing his professional life with his activism: Harrison was concerned in the management of the company as deputy chairman, and was related by marriage to  John Henry Pelly , the chairman, who had crossed swords with King at parliamentary hearings. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1209", "text": "Hodgkin's concerns over the indigenous peoples in the Hudson's Bay Company territory in western Canada continued. They were pursued both by correspondence with  Sir George Simpson , and in the pages of the  Intelligencer  of the Aborigines Protection Society. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1210", "text": "Hodgkin collaborated with  Joseph Jackson Lister , who in 1830 enunciated design principles for the  achromatic  microscope. [ 38 ]  By that time Hodgkin and Lister had already published research on tissue samples, based on observations made with Lister's innovative microscope, in particular on the \"globule hypothesis\" of the time which was held in particular by Henri Milne Edwards. [ 39 ]  They denied the existence of globules in tissue;  Ernst Heinrich Weber  in 1830 contradicted them, and the debate continued for a decade. [ 40 ]  For a while microscopy suffered in its reputation, but by 1840  histology  was a recognised discipline, and in time the view of Hodgkin and Lister that \"globules\" were optical artefacts became accepted. [ 41 ]  The 1827 paper they published has been called \"the foundation of modern histology\". [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1211", "text": "Hodgkin described the disease that bears his name ( Hodgkin lymphoma ) in 1832, in a paper titled  On Some Morbid Appearances of the Absorbent Glands and Spleen . [ 43 ]  He received 33 years later the  eponym  through the recognition of British physician  Samuel Wilks , who rediscovered the disease. It is a malignancy that produces enlargement of  lymphoid tissue ,  spleen , and  liver , with invasion of other tissues. A more benign form is called  Hodgkin's paragranuloma , while a more invasive form is called  Hodgkin's sarcoma . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1212", "text": "Hodgkin published as a book his  Lectures on Morbid Anatomy  in 1836 and 1840. His major contribution to the teaching of pathology, however, was made in 1829, with his two volumed work entitled  The Morbid Anatomy of Serous and Mucous Membranes , which became a classic in modern pathology. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1213", "text": "Hodgkin was one of the earliest defenders of preventive medicine, having published  On the Means of Promoting and Preserving Health  in book form in 1841. Among other early observations were the first description of acute  appendicitis , of the biconcave format of  red blood cells  and the striation of  muscle  fibers."}
{"_id": "WikiPedia_Hematology$$$corpus_1214", "text": "Hodgkin also translated with Thomas Fisher, from the French of William-Fr\u00e9d\u00e9ric Edwards,  On the Influence of Physical Agents on Life  (London, 1832; Philadelphia 1838). [ 44 ] [ 45 ]  Edwards was a  vitalist  in physiology, who studied the effect of physical forces on processes in living organisms. [ 46 ]  The work as it appeared in English was much more than a translation, since it contained an appendix of over 200 pages containing two dozen papers, a compendium of medicine and science tangentially related to themes in Edwards, but related to his general approach. It included early work by Hodgkin and collaboration with Lister, as well as something on electricity and meteorology. [ 47 ]  He also published  The Means of Promoting and Preserving Health  (London, 1840), of which a second edition appeared in 1841, and an  Address on Medical Reform  (1847). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1215", "text": "Other works by Hodgkin were  Biographical Sketches : of  James Cowles Prichard  (1849); and of William Stroud (1789\u20131858), a medical collaborator. He also wrote abolitionist pamphlets and on the British African Colonization Societies (1833\u20131834). [ 2 ] [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1216", "text": "There is a  blue plaque  on his house in  Bedford Square , London.  The Friends' School, Hobart  named one of the four school houses after him. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1217", "text": "The  King's College London   School of Medicine's  Hodgkin Building is named in honour of Hodgkin. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1218", "text": "Homing  is the phenomenon whereby  cells  migrate to the organ of their origin. By homing, transplanted  hematopoietic  cells are able to travel to and engraft (establish residence) in the  bone marrow . Various  chemokines [ 1 ]  and  receptors [ 2 ]   are involved in the homing of  hematopoietic stem cells . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1219", "text": "The  hook effect  refers to the  prozone phenomenon , also known as  antibody excess , or the  postzone phenomenon , also known as  antigen excess .  It is an  immunologic  phenomenon whereby the effectiveness of  antibodies  to form  immune complexes  can be impaired when concentrations of an antibody or an antigen are very high. The formation of immune complexes stops increasing with greater concentrations and then decreases at extremely high concentrations, producing a  hook  shape on a  graph  of measurements. An important practical relevance of the phenomenon is as a type of interference that plagues certain  immunoassays  and  nephelometric assays , resulting in  false negatives  or inaccurately low results. Other common forms of interference include antibody interference,  cross-reactivity  and signal interference. The phenomenon is caused by very high concentrations of a particular  analyte  or  antibody  and is most prevalent in one-step (sandwich)  immunoassays . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1220", "text": "In an  agglutination  test, a person's  serum  (which contains  antibodies ) is added to a  test tube , which contains a particular  antigen . If the antibodies interact with the antigen to form  immune complexes , called agglutination, then the test is interpreted as positive. However, if too many antibodies that can bind to the antigen are present, then the antigenic sites are coated by antibodies, and few or no antibodies directed toward the pathogen are able to bind more than one antigenic particle. [ 4 ]  Since the antibodies do not bridge between antigens, no agglutination occurs. Because no agglutination occurs, the test is interpreted as negative. In this case, the result is a false negative. The range of relatively high antibody concentrations within which no reaction occurs is called the  prozone . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1221", "text": "The effect can also occur because of antigen excess, when both the capture and detection antibodies become saturated by the high analyte concentration. In this case, no sandwich can be formed by the capturing antibody, the antigen and the detection antibody. In this case, free antigen is in competition with captured antigen for detection antibody binding. [ 6 ]  Sequential addition of antigen and antibody, paired with stringent washing, can prevent the effect, as can increasing the relative concentration of antibody to antigen, thereby mediating the effect. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1222", "text": "Examples include high levels of  syphilis  antibodies in  HIV  patients or high levels of cryptococcal antigen leading to false negative tests in undiluted samples. [ 7 ] [ 8 ]  This phenomenon is also seen in serological tests for Brucellosis. [ citation needed ]  It may be seen in precipitation reactions. The antibody that fails to react is known as the  blocking antibody  and prevents the precipitating antibody from binding to the antigens. Thus the proper precipitation reaction does not take place. However, when the serum is diluted, the blocking antibody is as well and its concentration decreases enough for the proper precipitation reaction to occur. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1223", "text": "Lewis Thomas  described in his memoir a physiologic experiment of 1941 in which he observed the prozone effect  in vivo : immunity in rabbits to  meningococcus , which was robust, unexpectedly decreased when  immunization  was used to induce a heightened antibody response. [ 10 ]  In other words, getting the rabbits' bodies to produce more antibodies against this bacterium had the counterproductive effect of decreasing their immunity to it. From the viewpoint of an overly simplistic notion of the antibody/antigen relationship, this seems  paradoxical , although it is clearly logical from a viewpoint duly informed by present-day molecular biology. Thomas was interested in pursuing this physiologic research further, and remained so for decades afterward, but his career took him in other directions and he was not aware of anyone having pursued it by the time of his memoir. [ 10 ]  One kind of relevance that he hypothesized for this in vivo  blocking antibody  concept was as a driver of human susceptibility to certain infectious diseases. [ 10 ]  In the decades since, the concept has also been found to have clinical relevance in  allergen immunotherapy , where blocking antibodies can interfere with other antibodies involved in hypersensitivity and thus improve allergy treatment. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1224", "text": "Human iron metabolism  is the set of chemical reactions that maintain  human homeostasis  of  iron  at the systemic and cellular level.  Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically important part of many aspects of human health and disease.  Hematologists  have been especially interested in systemic iron  metabolism , because iron is essential for  red blood cells , where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of  iron overload , such as  hereditary hemochromatosis , and  iron deficiency , such as  iron-deficiency anemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_1225", "text": "Iron is an essential bioelement for most forms of life, from  bacteria  to  mammals . Its importance lies in its ability to mediate electron transfer. In the ferrous state (Fe 2+ ), iron acts as an  electron donor , while in the ferric state (Fe 3+ ) it acts as an  acceptor . Thus, iron plays a vital role in the  catalysis  of enzymatic reactions that involve electron transfer (reduction and oxidation,  redox ). Proteins can contain iron as part of different  cofactors , such as  iron\u2013sulfur clusters  (Fe-S) and  heme  groups, both of which are assembled in  mitochondria ."}
{"_id": "WikiPedia_Hematology$$$corpus_1226", "text": "Human cells require iron in order to obtain energy as  ATP  from a multi-step process known as cellular respiration, more specifically from  oxidative phosphorylation  at the mitochondrial  cristae . Iron is present in the iron\u2013sulfur cluster and heme groups of the  electron transport chain  proteins that generate a  proton gradient  that allows  ATP synthase  to synthesize ATP ( chemiosmosis )."}
{"_id": "WikiPedia_Hematology$$$corpus_1227", "text": "Heme groups are part of  hemoglobin , a protein found in red blood cells that serves to transport oxygen from the  lungs  to other tissues. Heme groups are also present in  myoglobin  to store and diffuse oxygen in muscle cells."}
{"_id": "WikiPedia_Hematology$$$corpus_1228", "text": "The human body needs iron for oxygen transport. Oxygen (O 2 ) is required for the functioning and survival of nearly all cell types. Oxygen is transported from the lungs to the rest of the body bound to the  heme  group of  hemoglobin  in red blood cells. In muscles cells, iron binds oxygen to  myoglobin , which regulates its release."}
{"_id": "WikiPedia_Hematology$$$corpus_1229", "text": "Iron is also potentially toxic. Its ability to donate and accept electrons means that it can catalyze the conversion of  hydrogen peroxide  into  free radicals . Free radicals can cause damage to a wide variety of cellular structures, and ultimately kill the cell. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1230", "text": "Iron bound to proteins or  cofactors  such as  heme  is safe. Also,  there are virtually no truly free iron ions in the cell, since they readily form complexes with organic molecules. However, some of the intracellular iron is bound to low-affinity complexes, and is termed labile iron or \"free\" iron. Iron in such complexes can cause damage as described above. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1231", "text": "To prevent that kind of damage, all life forms that use iron bind the iron atoms to  proteins . This binding allows cells to benefit from iron while also limiting its ability to do harm. [ 1 ] [ 3 ]  Typical intracellular labile iron concentrations in bacteria are 10-20 micromolar, [ 4 ]  though they can be 10-fold higher in anaerobic environment, [ 5 ]  where free radicals and  reactive oxygen species  are scarcer. In mammalian cells, intracellular labile iron concentrations are typically smaller than 1 micromolar, less than 5 percent of total cellular iron. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1232", "text": "In response to a systemic bacterial infection, the immune system initiates a process known as \" iron withholding \". If bacteria are to survive, then they must obtain iron from their environment. Disease-causing bacteria do this in many ways, including releasing iron-binding molecules called  siderophores  and then reabsorbing them to recover iron, or scavenging iron from hemoglobin and  transferrin . The harder the bacteria have to work to get iron, the greater a  metabolic price  they must pay. That means that iron-deprived bacteria reproduce more slowly. So, control of iron levels appears to be an important defense against many bacterial infections. Certain bacteria species have developed strategies to circumvent that defense,  TB  causing bacteria can reside within  macrophages , which present an iron rich environment and  Borrelia burgdorferi  uses  manganese  in place of iron. People with increased amounts of iron, as, for example, in hemochromatosis, are more susceptible to some bacterial infections. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1233", "text": "Although this mechanism is an elegant response to short-term bacterial infection, it can cause problems when it goes on so long that the body is deprived of needed iron for red cell production. Inflammatory  cytokines  stimulate the liver to produce the iron metabolism regulator protein  hepcidin , that reduces available iron. If hepcidin levels increase because of non-bacterial sources of inflammation, like viral infection, cancer, auto-immune diseases or other chronic diseases, then the  anemia of chronic disease  may result. In this case, iron withholding actually impairs health by preventing the manufacture of enough hemoglobin-containing red blood cells. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1234", "text": "Most well-nourished people in industrialized countries have 4 to 5\u00a0grams of iron in their bodies (~38\u00a0mg iron/kg body weight for women and ~50\u00a0mg iron/kg body for men). [ 7 ]  Of this, about  2.5\u00a0g  is contained in the hemoglobin needed to carry oxygen through the blood (around 0.5\u00a0mg of iron per mL of blood), [ 8 ]  and most of the rest (approximately 2\u00a0grams in adult men, and somewhat less in women of childbearing age) is contained in  ferritin  complexes that are present in all cells, but most common in bone marrow,  liver , and  spleen . The liver stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in industrialized countries tend to be lower in children and women of child-bearing age than in men and in the elderly. Women who must use their stores to compensate for iron lost through  menstruation ,  pregnancy  or  lactation  have lower non-hemoglobin body stores, which may consist of  500\u00a0mg , or even less."}
{"_id": "WikiPedia_Hematology$$$corpus_1235", "text": "Of the body's total iron content, about  400\u00a0mg  is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin) or performing energy-producing redox reactions ( cytochromes ). A relatively small amount (3\u20134\u00a0mg) circulates through the  plasma , bound to transferrin. [ 9 ]  Because of its toxicity, free soluble iron is kept in low concentration in the body."}
{"_id": "WikiPedia_Hematology$$$corpus_1236", "text": "Iron deficiency  first affects the storage of iron in the body, and depletion of these stores is thought to be relatively asymptomatic, although some vague and  non-specific symptoms  have been associated with it. Since iron is primarily required for hemoglobin,  iron deficiency anemia  is the primary clinical manifestation of iron deficiency. Iron-deficient people will suffer or die from organ damage well before their cells run out of the iron needed for intracellular processes like electron transport."}
{"_id": "WikiPedia_Hematology$$$corpus_1237", "text": "Macrophages  of the  reticuloendothelial system  store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells. Iron is also stored as a pigment called  hemosiderin , which is an ill-defined deposit of protein and iron, created by macrophages where excess iron is present, either locally or systemically, e.g., among people with iron overload due to frequent blood cell destruction and the necessary transfusions their condition calls for. If systemic iron overload is corrected, over time the hemosiderin is slowly resorbed by the macrophages."}
{"_id": "WikiPedia_Hematology$$$corpus_1238", "text": "Human iron homeostasis is regulated at two different levels. Systemic iron levels are balanced by the controlled absorption of dietary iron by  enterocytes , the cells that line the interior of the  intestines , and the uncontrolled loss of iron from epithelial sloughing, sweat, injuries and blood loss. In addition, systemic iron is continuously recycled. Cellular iron levels are controlled differently by different cell types due to the expression of particular iron regulatory and transport proteins."}
{"_id": "WikiPedia_Hematology$$$corpus_1239", "text": "The absorption of dietary iron is a variable and dynamic process. The amount of iron absorbed compared to the amount ingested is typically low, but may range from 5% to as much as 35% depending on circumstances and type of iron. The efficiency with which iron is absorbed varies depending on the source. Generally, the best-absorbed forms of iron come from animal products. Absorption of dietary iron in iron salt form (as in most supplements) varies somewhat according to the body's need for iron, and is usually between 10% and 20% of iron intake. Absorption of iron from animal products, and some plant products, is in the form of heme iron, and is more efficient, allowing absorption of from 15% to 35% of intake. Heme iron in animals is from blood and heme-containing proteins in meat and mitochondria, whereas in plants, heme iron is present in mitochondria in all cells that use oxygen for respiration."}
{"_id": "WikiPedia_Hematology$$$corpus_1240", "text": "Like most mineral nutrients, the majority of the iron absorbed from digested food or supplements is absorbed in the  duodenum  by  enterocytes  of the duodenal lining. These cells have special molecules that allow them to move iron into the body. To be absorbed, dietary iron can be absorbed as part of a protein such as heme protein or iron must be in its ferrous Fe 2+  form. A ferric reductase enzyme on the enterocytes'  brush border , duodenal cytochrome B ( Dcytb ), reduces ferric Fe 3+  to Fe 2+ . [ 10 ]  A protein called divalent metal transporter 1 ( DMT1 ), which can transport several  divalent  metals across the plasma membrane, then transports iron across the enterocyte's  cell membrane  into the cell. If the iron is bound to heme, it is instead transported across the apical membrane by  heme carrier protein 1  (HCP1). [ 11 ]  Heme is then  catabolized  by microsomal  heme oxygenase  into  biliverdin , releasing Fe 2+ . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1241", "text": "These intestinal lining cells can then either store the iron as  ferritin , which is accomplished by Fe 2+  binding to apoferritin (in which case the iron will leave the body when the cell dies and is sloughed off into  feces ), or the cell can release it into the body via the only known iron exporter in mammals,  ferroportin .  Hephaestin , a  ferroxidase  that can oxidize Fe 2+  to Fe 3+  and is found mainly in the small intestine, helps ferroportin transfer iron across the basolateral end of the intestine cells. Upon release into the bloodstream, Fe 3+  binds transferrin and circulates to tissues. In contrast, ferroportin is post-translationally repressed by  hepcidin , a 25-amino acid peptide hormone. The body regulates iron levels by regulating each of these steps. For instance, enterocytes synthesize more Dcytb, DMT1 and ferroportin in response to iron deficiency anemia. [ 13 ]  Iron absorption from diet is enhanced in the presence of vitamin C and diminished by excess calcium, zinc, or manganese. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1242", "text": "The human body's rate of iron absorption appears to respond to a variety of interdependent factors, including total iron stores, the extent to which the bone marrow is producing new red blood cells, the concentration of hemoglobin in the blood, and the oxygen content of the blood. The body also absorbs less iron during times of  inflammation , in order to deprive bacteria of iron. Recent discoveries demonstrate that hepcidin regulation of ferroportin is responsible for the syndrome of anemia of chronic disease."}
{"_id": "WikiPedia_Hematology$$$corpus_1243", "text": "Most of the iron in the body is hoarded and recycled by the reticuloendothelial system, which breaks down aged red blood cells. In contrast to iron uptake and recycling, there is no physiologic regulatory mechanism for  excreting  iron. People lose a small but steady amount by gastrointestinal blood loss, sweating and by shedding cells of the skin and the  mucosal  lining of the  gastrointestinal tract . The total amount of loss for healthy people in the developed world amounts to an estimated average of  1\u00a0mg  a day for men, and 1.5\u20132\u00a0mg a day for women with regular menstrual periods. [ 15 ]  People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more. [ 1 ]  Those who cannot regulate absorption well enough get disorders of iron overload. In these diseases, the toxicity of iron starts overwhelming the body's ability to bind and store it. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1244", "text": "Most cell types take up iron primarily through  receptor-mediated endocytosis  via  transferrin receptor 1  (TFR1),  transferrin receptor 2  (TFR2) and  GAPDH . TFR1 has a 30-fold higher affinity for transferrin-bound iron than TFR2 and thus is the main player in this process. [ 17 ] [ 18 ]  The higher order multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also acts as a transferrin receptor. [ 19 ] [ 20 ]  Transferrin-bound ferric iron is recognized by these transferrin receptors, triggering a conformational change that causes endocytosis. Iron then enters the cytoplasm from the endosome via importer DMT1 after being reduced to its ferrous state by a STEAP family reductase. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1245", "text": "Alternatively, iron can enter the cell directly via plasma membrane divalent cation importers such as DMT1 and ZIP14 (Zrt-Irt-like protein 14). [ 22 ]  Again, iron enters the cytoplasm in the ferrous state after being reduced in the extracellular space by a reductase such as STEAP2, STEAP3 (in red blood cells), Dcytb (in enterocytes) and SDR2. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1246", "text": "Iron can also enter cells via  CD44  in complexes bound to  hyaluronic acid  during  epithelial\u2013mesenchymal transition  (EMT). In this process,  epithelial cells  transform into  mesenchymal cells  with detachment from the  basement membrane , to which they\u2019re normally anchored, paving the way for the newly differentiated motile mesenchymal cells to begin migration away from the epithelial layer. [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1247", "text": "While EMT plays a crucial role in physiological processes like  implantation , where it enables the  embryo  to invade the  endometrium  to facilitate  placental  attachment, its dysregulation can also fuel the  malignant  spread of  tumors  empowering them to invade surrounding tissues and establish distant colonies ( metastasis ). [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1248", "text": "Malignant cells often exhibit a heightened demand for iron, fueling their transition towards a more invasive mesenchymal state. This iron is necessary for the expression of mesenchymal genes, like those encoding  transforming growth factor beta  (TGF-\u03b2), crucial for EMT. Notably, iron\u2019s unique ability to catalyze  protein  and  DNA   demethylation  plays a vital role in this gene expression process. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1249", "text": "Conventional iron uptake pathways, such as those using the transferrin receptor 1 (TfR1), often prove insufficient to meet these elevated iron demands in cancer cells. As a result, various  cytokines  and  growth factors  trigger the upregulation of CD44, a surface molecule capable of internalizing iron bound to the hyaluronan complex. This alternative pathway, relying on CD44-mediated endocytosis, becomes the dominant iron uptake mechanism compared to the traditional TfR1-dependent route. [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1250", "text": "In the cytoplasm, ferrous iron is found in a soluble, chelatable state which constitutes the labile iron pool (~0.001 mM). [ 25 ]  In this pool, iron is thought to be bound to low-mass compounds such as peptides, carboxylates and phosphates, although some might be in a free, hydrated form ( aqua ions ). [ 25 ]  Alternatively, iron ions might be bound to specialized proteins known as  metallochaperones . [ 26 ]  Specifically, poly-r(C)-binding proteins  PCBP1  and  PCBP2  appear to mediate transfer of free iron to ferritin (for storage) and  non-heme iron enzymes  (for use in catalysis). [ 22 ] [ 27 ]  The labile iron pool is potentially toxic due to iron's ability to generate reactive oxygen species. Iron from this pool can be taken up by mitochondria via  mitoferrin  to synthesize Fe-S clusters and heme groups. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1251", "text": "Iron can be stored in ferritin as ferric iron due to the  ferroxidase  activity of the ferritin heavy chain. [ 28 ]  Dysfunctional ferritin may accumulate as  hemosiderin , which can be problematic in cases of iron overload. [ 29 ]  The ferritin storage iron pool is much larger than the labile iron pool, ranging in concentration from 0.7 mM to 3.6 mM. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1252", "text": "Iron export occurs in a variety of cell types, including  neurons , red blood cells, hepatocytes, macrophages and enterocytes. The latter two are especially important since systemic iron levels depend upon them. There is only one known iron exporter,  ferroportin . [ 30 ]  It transports ferrous iron out of the cell, generally aided by  ceruloplasmin  and/or  hephaestin  (mostly in enterocytes), which oxidize iron to its ferric state so it can bind ferritin in the extracellular medium. [ 21 ]   Hepcidin  causes the internalization of ferroportin, decreasing iron export. Besides, hepcidin seems to downregulate both TFR1 and DMT1 through an unknown mechanism. [ 31 ]  Another player assisting ferroportin in effecting cellular iron export is GAPDH. [ 32 ]  A specific post translationally modified isoform of GAPDH is recruited to the surface of iron loaded cells where it recruits apo-transferrin in close proximity to ferroportin so as to rapidly chelate the iron extruded. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1253", "text": "The expression of hepcidin, which only occurs in certain cell types such as  hepatocytes , is tightly controlled at the transcriptional level and it represents the link between cellular and systemic iron homeostasis due to hepcidin's role as \"gatekeeper\" of iron release from enterocytes into the rest of the body. [ 21 ]   Erythroblasts  produce  erythroferrone , a hormone which inhibits hepcidin and so increases the availability of iron needed for hemoglobin synthesis. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1254", "text": "Although some control exists at the transcriptional level, the regulation of cellular iron levels is ultimately controlled at the translational level by  iron-responsive element-binding proteins  IRP1 and especially IRP2. [ 36 ]  When iron levels are low, these proteins are able to bind to  iron-responsive elements  (IREs). IREs are stem loop structures in the untranslated regions (UTRs) of mRNA. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1255", "text": "Both ferritin and ferroportin contain an IRE in their 5' UTRs, so that under iron deficiency their translation is repressed by IRP2, preventing the unnecessary synthesis of storage protein and the detrimental export of iron. In contrast, TFR1 and some DMT1 variants contain 3' UTR IREs, which bind IRP2 under iron deficiency, stabilizing the mRNA, which guarantees the synthesis of iron importers. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1256", "text": "Functional or actual iron deficiency can result from a variety of causes. These causes can be grouped into several categories:"}
{"_id": "WikiPedia_Hematology$$$corpus_1257", "text": "The body is able to substantially reduce the amount of iron it absorbs across the mucosa. It does not seem to be able to entirely shut down the iron transport process. Also, in situations where excess iron damages the intestinal lining itself (for instance, when children eat a large quantity of iron tablets produced for adult consumption), even more iron can enter the bloodstream and cause a potentially deadly syndrome of iron overload. Large amounts of free iron in the circulation will cause damage to critical cells in the liver, the  heart  and other metabolically active organs."}
{"_id": "WikiPedia_Hematology$$$corpus_1258", "text": "Iron toxicity results when the amount of circulating iron exceeds the amount of transferrin available to bind it, but the body is able to vigorously regulate its iron uptake. Thus, iron toxicity from ingestion is usually the result of extraordinary circumstances like iron tablet over-consumption [1] [ 42 ]  rather than variations in  diet . The type of acute toxicity from iron ingestion causes severe mucosal damage in the gastrointestinal tract, among other problems."}
{"_id": "WikiPedia_Hematology$$$corpus_1259", "text": "Excess iron has been linked to higher rates of disease and mortality. For example, breast cancer patients with low  ferroportin  expression (leading to higher concentrations of intracellular iron) survive for a shorter period of time on average, while high ferroportin expression predicts 90% 10-year survival in breast cancer patients. [ 43 ]  Similarly, genetic variations in iron transporter genes known to increase serum iron levels also reduce  lifespan  and the average number of years spent in good health. [ 44 ]  It has been suggested that mutations that increase iron absorption, such as the ones responsible for hemochromatosis (see below), were selected for during  Neolithic  times as they provided a  selective advantage  against iron-deficiency anemia. [ 45 ]  The increase in systemic iron levels becomes pathological in old age, which supports the notion that  antagonistic pleiotropy  or \"hyperfunction\" drives human aging. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1260", "text": "Chronic iron toxicity is usually the result of more chronic iron overload syndromes associated with genetic diseases, repeated transfusions or other causes. In such cases the iron stores of an adult may reach 50\u00a0grams (10 times normal total body iron) or more. The most common diseases of iron overload are  hereditary hemochromatosis  (HH), caused by mutations in the  HFE  gene, and the more severe disease  juvenile hemochromatosis  (JH), caused by mutations in either  hemojuvelin  ( HJV ) [ 46 ]  or hepcidin ( HAMP ). The exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So, while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes."}
{"_id": "WikiPedia_Hematology$$$corpus_1261", "text": "Hydremia  (or  Hydraemia ) is a  blood disorder  characterized by excessive fluid volume with or without reduction of  blood plasma  volume. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1262", "text": "This article about a disease of the blood or immune system is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1263", "text": "Hypervascularity  is an increased number or  concentration  of  blood vessels ."}
{"_id": "WikiPedia_Hematology$$$corpus_1264", "text": "In  Graves disease , the thyroid gland is hypervascular, which can help in differentiating the condition from  thyroiditis . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1265", "text": "90% of  thyroid papillary carcinoma  cases are hypervascular. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1266", "text": "This  cardiovascular system  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1267", "text": "Immunohematology  is a branch of  hematology  and  transfusion medicine  which studies  antigen - antibody  reactions and analogous phenomena as they relate to the pathogenesis and clinical manifestations of  blood disorders .  A person employed in this field is referred to as an immunohematologist or colloquially as a blood banker. Their day-to-day duties include  blood typing ,  cross-matching  and  antibody  identification. [ 1 ] [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1268", "text": "Immunohematology and Transfusion Medicine is a medical post graduate specialty in many countries. The specialist Immunohematology and Transfusion Physician provides expert opinion for difficult transfusions, massive transfusions, incompatibility work up, therapeutic  plasmapheresis ,  cellular therapy , irradiated blood therapy, leukoreduced and washed blood products, stem cell procedures, platelet rich plasma therapies,  HLA  and cord blood banking. Other research avenues are in the field of stem cell researches, regenerative medicine and cellular therapy. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1269", "text": "Immunohematology is one of the specialized branches of medical science. It deals with the concepts and clinical 2 techniques related to modern transfusion therapy. Efforts to save human lives by transfusing blood have been recorded for several centuries. The era of blood transfusion, however, really began when William Harvey described the circulation of blood in 1616."}
{"_id": "WikiPedia_Hematology$$$corpus_1270", "text": "This  immunology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1271", "text": "Immunophenotyping  is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose.  This can be done on tissue section (fresh or fixed tissue),  cell suspension , etc.  An example is the detection of  tumor markers , such as in the  diagnosis  of  leukemia . It involves the labelling of  white blood cells  with  antibodies  directed against surface  proteins  on their membrane. By choosing appropriate antibodies, the differentiation of  leukemic  cells can be accurately determined. The labelled cells are processed in a  flow cytometer , a laser-based instrument capable of analyzing thousands of cells per second. The whole procedure can be performed on cells from the  blood ,  bone marrow  or  spinal fluid  in a matter of a few hours. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1272", "text": "Immunophenotyping is a very common flow cytometry test in which fluorophore-conjugated antibodies are used as probes for staining target cells with high avidity and affinity. This technique allows rapid and easy phenotyping of each cell in a heterogeneous sample according to the presence or absence of a protein combination.  [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1273", "text": "The  International Prognostic Index  ( IPI ) is a clinical tool developed by  oncologists  to aid in predicting the  prognosis  of patients with aggressive  non-Hodgkin's lymphoma .  Previous to IPI's development, the primary consideration in assessing prognosis was the  Ann Arbor stage  alone, but this was increasingly found to be an inadequate means of predicting survival outcomes, and so other factors were studied. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1274", "text": "In 1984, the first prognostic indicator for advanced non-Hodkin's lymphoma was developed. An information theory guided, computer search and evaluation procedure  entropy minimax  was employed to discover the largest sub-groupings for which survival is as extreme as possible [ 1 ]  In the clinical trials analyzed retrospectively and containing a large fraction of patients not matching the 'good' - of 'good' (Karnofsky status >80 and 'A\" Symptoms and SGOT <36 U/L), 'poor' (Karnofsky status <70 or Night sweats) and 'intermediate' (All Remaining) prognosis patterns identified, a significant difference was found between the survival of patients with and those without a complete response to therapy.  The authors concluded that trials using a patient mix weighted toward good prognosis will not find such a difference."}
{"_id": "WikiPedia_Hematology$$$corpus_1275", "text": "In 1993, a retrospective analysis was performed on 2031 patients with aggressive non-Hodgkin's lymphoma, of all ages, treated with a  doxorubicin -based chemotherapy regimen such as  CHOP  between 1982 and 1987. [ 2 ]  Several patient characteristics were analyzed to determine whether they were associated with differences in survival, and the factors that emerged as significant were, in addition to the Ann Arbor stage: age, elevated serum  lactate dehydrogenase  (LDH),  performance status , and number of extranodal sites of disease."}
{"_id": "WikiPedia_Hematology$$$corpus_1276", "text": "One point is assigned for each of the following risk factors: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1277", "text": "The sum of the points allotted correlates with the following risk groups:"}
{"_id": "WikiPedia_Hematology$$$corpus_1278", "text": "A simplified index can be used when comparing patients within an age group (i.e. 60 or younger, or over 60) and includes only 3 of the above factors: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1279", "text": "Although the IPI has shown itself to be a useful clinical tool, widely used by oncologists and a mainstay of risk stratification in clinical trials for lymphoma, it should be kept in mind that it was developed prior to the use of  rituximab , which is now included with anthracycline-based combination chemotherapy as of the standard of care in  B-cell  lymphomas (the majority of non-Hodgkin's lymphomas). Rituximab has significantly improved the outcomes of lymphoma patients; and its effect on the prognostic value of the IPI is uncertain.  Future development of a more rigorous prognostic index may thus be useful."}
{"_id": "WikiPedia_Hematology$$$corpus_1280", "text": "Given the success of the IPI for intermediate grade lymphomas, an effort was undertaken to develop a similar prognostic index for the most common low-grade lymphoma,  follicular lymphoma . The prognostic factors that emerged from this were: age, stage, number of lymph node areas involved, serum  hemoglobin  level, and serum LDH. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1281", "text": "One point is assigned for each of the following adverse prognostic factors: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1282", "text": "An effort was more recently undertaken to identify a similar prognostic index predictive of outcome in advanced mantle cell lymphoma. There were four factors found to have independent prognostic relevance: age, performance status, LDH, and white blood cell count (WBC). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1283", "text": "The point values are assigned as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_1284", "text": "The sum of the allotted points correlates with the following risk groups:"}
{"_id": "WikiPedia_Hematology$$$corpus_1285", "text": "Intravascular hemolysis  describes  hemolysis  that happens mainly inside the  vasculature . [ 1 ]  As a result, the contents of the red blood cell are released into the general circulation, leading to  hemoglobinemia [ 2 ]  and increasing the risk of ensuing  hyperbilirubinemia . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1286", "text": "Intravascular hemolysis is the state when the red blood cell ruptures as a result of the complex of complement autoantibodies attached (fixed) on the surfaces of RBCs attack and rupture RBCs' membranes, or a parasite such as  Babesia  exits the cell that ruptures the RBC's membrane as it goes. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1287", "text": "Upon RBC's rupture, components of which are released and circulating in the blood plasma. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1288", "text": "These components comprise hemoglobin and others. [ 3 ]  At this stage, the hemoglobin is called  free hemoglobin . [ 3 ]  Free hemoglobin (also called  naked hemoglobin ) is the un-bound hemoglobin that is not enclosed in the red blood cell. The naked hemoglobin is devoid of its anti-oxidant sentries that are normally available within the RBC. [ 5 ]  Free hemoglobin is thus vulnerable to be oxidized. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1289", "text": "When the serum concentration of free hemoglobin is within the physiologic range of  haptoglobin , the potential deleterious effects of free hemoglobin are prevented because haptoglobin will bind to \"free hemoglobin\" forming a complex of \"free hemoglobin-haptoglobin\" evidenced by reduced amount of haptoglobin. [ 6 ]  However, during hyper-hemolytic conditions or with chronic hemolysis, haptoglobin is depleted so the remaining free hemoglobin readily distribute to tissues where it might be exposed to oxidative conditions, [ 2 ]  thus some of the ferrous heme (FeII), the oxygen-binding component of hemoglobin, of the free hemoglobin are oxidized and becoming  met-hemoglobin  (ferric hemoglobin). [ 2 ]  In such conditions, heme along with globin chains can be released from further oxidization of met-hemoglobin (ferric Hb). [ 2 ]  In which, the free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. At this time,  hemopexin , another plasma glycoprotein come to bind with heme with its privilege of high heme affinity, forming a complex of heme-hemopexin, which is non-toxic, and travel together to a receptor on hepatocytes and macrophages within the spleen, liver and bone marrow. [ 7 ] [ 2 ]  (Note that the \"free hemoglobin-haptoglobin\" complex is taken up by hepatocytes and, to the lesser extent, macrophages. [ 2 ] ) Thereafter, these complexes will undergo the metabolic mechanisms like extravascular hemolysis. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1290", "text": "Nevertheless, if the binding capacities of haptoglobin and hemopexin are saturated [ note 1 ] , the remaining \"free hemoglobin\" in the plasma will be oxidized to met-hemoglobin eventually, and then further disassociates into free heme and others. [ 3 ]  At this stage, the \"free heme\" will bind to albumin, forming  met-hemalbumin . [ 3 ] [ 8 ]  As to the remaining unbound (met)hemoglobin is filtered into the primary urine and re-absorbed via  proximal tubules  of the kidney. [ 3 ]  In proximal tubules, the iron is extracted and stored as  hemosiderin . [ 3 ]  (Long-term hemoglobinuria is associated with substantial deposition of hemosiderin in proximal tubule (excessive accumulation of hemosiderin in proximal tubule),  Fanconi syndrome  (damaged renal re-absorption capability of small molecules which give rises to hyper- aminoaciduria ,  glycosuria ,  hyperphosphaturia , and  bicarbonate  and  dehydration ), and  chronic kidney failure . [ 6 ] )"}
{"_id": "WikiPedia_Hematology$$$corpus_1291", "text": "In the end, if the plasma concentration of the \"free met-hemoglobin\" and/or \"free hemoglobin\" is still too high for proximal tubule to absorb back into the body, then  hemoglobinuria  occurs, [ 3 ]  indicating an extensive intravascular hemolysis. [ 3 ]  These remaining free hemoglobin entities also begin to consume  nitric oxide , which is critical regulators of vascular homeostasis and basal and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial adhesion molecule expression, and platelet activation and aggregation. [ 6 ]  The reduction of nitric oxide deeply disturbs the body's mechanism to maintain the stability of the hemodynamics. [ 6 ]  Additionally, free hemoglobin manifests direct cytotoxic, inflammatory, and pro-oxidant effects that in turn negatively impact endothelial function. [ 6 ]  At the meantime, free heme exerts its multiple pro-inflammatory and pro-oxidant effects to the tissues it goes through. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1292", "text": "It is important to note that although hemosiderins are also included in the urine in the setting of intravascular hemolytic hemoglobinuria, [ 3 ]  it will be detected only several days after the onset of the extensive intravascular hemolysis and will remain detectable several days after termination of intravascular hemolysis. [ 3 ]  The phenomenon tells that the detection of hemosiderin in urine is indicative of either ongoing or recent intravascular hemolysis characterized by excessive hemoglobin and/or met-hemoglobin filtered through the  renal glomerulus  as well as the loss of  hemosiderin-laden necrotic tubular cells . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1293", "text": "2PMV ,  3KQ4"}
{"_id": "WikiPedia_Hematology$$$corpus_1294", "text": "2694"}
{"_id": "WikiPedia_Hematology$$$corpus_1295", "text": "14603"}
{"_id": "WikiPedia_Hematology$$$corpus_1296", "text": "ENSG00000134812"}
{"_id": "WikiPedia_Hematology$$$corpus_1297", "text": "ENSMUSG00000024682"}
{"_id": "WikiPedia_Hematology$$$corpus_1298", "text": "P27352"}
{"_id": "WikiPedia_Hematology$$$corpus_1299", "text": "P52787"}
{"_id": "WikiPedia_Hematology$$$corpus_1300", "text": "NM_005142"}
{"_id": "WikiPedia_Hematology$$$corpus_1301", "text": "NM_008118"}
{"_id": "WikiPedia_Hematology$$$corpus_1302", "text": "NP_005133"}
{"_id": "WikiPedia_Hematology$$$corpus_1303", "text": "NP_032144"}
{"_id": "WikiPedia_Hematology$$$corpus_1304", "text": "Intrinsic factor  ( IF ),  cobalamin binding intrinsic factor , [ 5 ]  also known as  gastric intrinsic factor  ( GIF ), is a  glycoprotein  produced by the  parietal cells  (in humans) or chief cells (in rodents) of the  stomach . It is necessary for the absorption of  vitamin B 12  later on in the distal  ileum  of the  small intestine . [ 6 ]  In humans, the gastric intrinsic factor  protein  is encoded by the  CBLIF   gene . [ 5 ]   Haptocorrin  ( transcobalamin I ) is another glycoprotein secreted by the  salivary glands  which binds to  vitamin B 12 . Vitamin B 12  is acid-sensitive and in binding to haptocorrin it can safely pass through the acidic stomach to the duodenum. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1305", "text": "In the less acidic environment of the  small intestine , pancreatic enzymes digest the glycoprotein carrier and vitamin B 12  can then bind to intrinsic factor. [ 7 ]  This new complex is then absorbed by the epithelial cells ( enterocytes ) of the  ileum . [ 7 ]  Inside the cells, vitamin B 12  dissociates once again and binds to another protein,  transcobalamin II ; the new complex can then exit the epithelial cells to be carried to the liver. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1306", "text": "Intrinsic factor is secreted by  parietal cells  within the stomach, and so is present in the gastric juice as well as in the  gastric mucous membrane . [ 9 ]  The optimum pH for its action is approximately 7. [ 10 ]  Its concentration does not correlate with the amount of  HCl  or  pepsin  in the gastric juice, e.g., intrinsic factor may be present even when pepsin is largely absent. [ 11 ]  The site of formation of the intrinsic factor varies in different species. In pigs it is obtained from the  pylorus  and beginning of the  duodenum ; [ 12 ]   in human beings it is present in the  fundus  and body of the  stomach . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1307", "text": "The limited amount of normal human gastric intrinsic factor limits normal efficient absorption of B 12  to about 2\u00a0\u03bcg per meal, a nominally adequate intake of B 12 . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1308", "text": "In  pernicious anemia , which is usually an  autoimmune disease ,  autoantibodies  directed against intrinsic factor or parietal cells themselves lead to an intrinsic factor deficiency,  malabsorption  of vitamin B 12 , and subsequent  megaloblastic anemia . [ 15 ]   Atrophic gastritis  can also cause intrinsic factor deficiency and anemia through damage to the parietal cells of the stomach wall. [ 16 ]   Pancreatic exocrine insufficiency  can interfere with normal dissociation of vitamin B 12  from its binding proteins in the small intestine, preventing its absorption via the intrinsic factor complex. [ 17 ]  Other risk factors contributing to pernicious anemia are anything that damages or removes a portion of the stomach's parietal cells, including  bariatric surgery , gastric tumors, gastric ulcers, and excessive consumption of alcohol. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1309", "text": "Mutations in the  GIF  gene are responsible for a rare inheritable disease called  intrinsic factor deficiency [ 18 ]  which results in malabsorption of vitamin B 12 . [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1310", "text": "In most countries,  intramuscular injections  of vitamin B 12  are used to treat  pernicious anemia . [ 20 ]  Orally administered vitamin B 12  is absorbed without intrinsic factor, but at levels of less than one percent than if intrinsic factor is present. [ 21 ]   Despite the low amounts absorbed, oral vitamin B 12  therapy is effective at reducing symptoms of pernicious anemia. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1311", "text": "Vitamin B 12  can also be given  sublingually , but there is no evidence that this route of administration is superior to the oral route, [ 23 ]  and only Canada and Sweden routinely prescribe this route of administration. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1312", "text": "Because vitamin B 12  absorption is a multistep process that involves the stomach, pancreas and small intestine, and is mediated by two carriers:  Haptocorrin  and intrinsic factor, and because  Haptocorrin  ( transcobalamin I ) binds to vitamin B 12 , and  Vitamin B 12  is acid-sensitive, when vitamin B 12  binds to  Haptocorrin  it can safely pass through the acidic stomach to the duodenum, given time in the mouth. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1313", "text": "Iptacopan , sold under the brand name  Fabhalta , is a  medication  used for the treatment of  paroxysmal nocturnal hemoglobinuria (PNH) . [ 3 ]  It is a  complement factor B  inhibitor that was developed by  Novartis . [ 3 ]  It is taken  by mouth . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1314", "text": "Iptacopan was approved by the US  Food and Drug Administration  (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023. [ 5 ] [ 6 ]  The FDA considers it to be a  first-in-class medication . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1315", "text": "Iptacopan is  indicated  for the treatment of adults with paroxysmal nocturnal hemoglobinuria. [ 3 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1316", "text": "Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1317", "text": "In  PNH ,  intravascular hemolysis  (IVH) is mediated by the downstream membrane attack complex (MAC), while  extravascular hemolysis  (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1318", "text": "The FDA label for iptacopan contains a  black box warning  for the risk of serious and life-threatening infections caused by encapsulated bacteria, including  Streptococcus pneumoniae ,  Neisseria meningitidis , and  Haemophilus influenzae  type B. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1319", "text": "In March 2024, the  Committee for Medicinal Products for Human Use  (CHMP) of the  European Medicines Agency  (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fabhalta, intended for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). [ 4 ] [ 10 ]  The applicant for this medicinal product is Novartis Europharm Limited. [ 4 ]  Iptacopan was approved for medical use in the European Union in May 2024. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1320", "text": "In August 2024, the US FDA granted accelerated approval to Fabhalta (iptacopan) for reducing proteinuria in adults with primary IgA nephropathy (IgAN). [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1321", "text": "In a clinical study with twelve participants, iptacopan as a single drug led to the normalization of hemolytic markers in most patients, and no serious adverse events occurred during the 12-week study. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1322", "text": "Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related  macular degeneration  and some types of  glomerulopathies . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1323", "text": "Ischemic preconditioning  (IPC) is an experimental technique [ 1 ]  for producing resistance to the loss of  blood  supply, and thus  oxygen , to  tissues  of many types. In the heart, IPC is an intrinsic process whereby repeated short episodes of  ischaemia  protect the  myocardium  against a subsequent ischaemic insult. It was first identified in 1986 by Murry  et al.  This group exposed anesthetised open-chest dogs to four periods of 5 minute  coronary artery occlusions  followed by a 5-minute period of  reperfusion  before the onset of a 40-minute sustained occlusion of the coronary artery. The control animals had no such period of \u201cischaemic preconditioning\u201d and had much larger  infarct  sizes compared with the dogs that did. [ 2 ]  The exact molecular pathways behind this phenomenon have yet to be fully understood."}
{"_id": "WikiPedia_Hematology$$$corpus_1324", "text": "If the blood supply to an  organ  or a tissue is impaired for a short time (usually less than five minutes) then restored so that blood flow is resumed, and the process repeated two or more times, the cells downstream of the tissue or organ are robustly protected from a final  ischemic  insult when the blood supply is cut off entirely and permanently. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1325", "text": "The protective effect which is imparted by IPC has two windows of protection. The first lasts between 4\u20136 hours [ 3 ]  and has been named classical or early preconditioning. The second window begins at 24 hours and lasts up to 72 hours after the ischaemia and  reperfusion  stimulus. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1326", "text": "In an experimental setting if the  left anterior descending   coronary artery  of the animal is ligated the downstream cardiac cellular mass is infarcted and will be injured and then die. If on the other hand the tissue is subjected to IPC the downstream cellular mass will sustain only minimal to modest damage. IPC protects the tissue by initiating a cascade of biochemical events that allows for an up-regulation of the energetics of the tissue. The locus of this phenomenon is the intracellular organelle, the  mitochondrion . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1327", "text": "Investigations of various exogenous circulating ligands such as the delta active  opiates  and  opioids  simulate the phenomenon of IPC thus protecting the downstream tissues without the IPC intermittent ligating procedure."}
{"_id": "WikiPedia_Hematology$$$corpus_1328", "text": "Methods to either mimic or elicit IPC have been attempted in clinical practice in the area of coronary heart disease in an attempt to limit the injury caused to the heart via ischemia and reperfusion injury. [ 5 ]  Such injury would occur when a patient has an acute myocardial infarct followed by reperfusion by either  percutaneous coronary intervention  or  thrombolysis ."}
{"_id": "WikiPedia_Hematology$$$corpus_1329", "text": "Early preconditioning is thought to be stimulated by local action of  adenosine , opiates, and  bradykinin , which are all  endogenously  released by ischemic cells. The presence of each substance is not required but the protection is more potent if they are. They activate  G-protein  coupled pathways, which carries a protective signal to an end-effector. There have been many suggestions to what this might be, including the  sarcolemmal   ATP-sensitive potassium channel , the mitochondrial ATP-sensitive potassium channel, the  mitochondrial permeability transition pore ,  reactive oxygen species  generation,  chloride channels , the  inward rectifier potassium ion channel , and  connexon  43 related channels. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1330", "text": "It has also been shown that the protective effect of IPC is suppressed by pathological conditions such as  hypercholesterolemia ,  hyperglycemia ,  hypertension ,  cardiac hypertrophy , and  hyperhomocysteinemia .  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1331", "text": "The only group of humans who are chronically exposed to an opioid with delta activity are  methadone -maintained patients treated for chronic pain or  opioid addiction . These patients have a coronary risk profile greater than the general population:"}
{"_id": "WikiPedia_Hematology$$$corpus_1332", "text": "Preliminary and as yet unpublished surveys of the methadone-treated population point to a high degree of protection from myocardial ischemic events. The one published study, [ citation needed ]  an autopsy series from the  Office of Chief Medical Examiner of the City of New York  demonstrated significantly less evidence for coronary occlusive disease. Simulation of IPC with methadone could not be evaluated in this  post mortem  investigation."}
{"_id": "WikiPedia_Hematology$$$corpus_1333", "text": "Rather than blocking a  coronary artery , similar results have been seen by blocking the  brachial artery  using a blood pressure cuff prior to surgery. [ 6 ]  Some research also suggests that ischemic conditioning is also beneficial following a stroke, [ 7 ] [ 8 ]  chronic cerebral hypoperfusion, [ 9 ]  or heart attack. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1334", "text": "Jan Jansk\u00fd  ( Czech pronunciation:   [\u02c8jan   \u02c8janski\u02d0] ; 3 April 1873 \u2013 8 September 1921) was a Czech  serologist ,  neurologist  and  psychiatrist . He is credited with the classification of  blood  into four  types  (I, II, III, IV). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1335", "text": "Jansk\u00fd was born on 3 April 1873 in  Sm\u00edchov  (now part of  Prague ). He studied  medicine  at  Charles University  in Prague. From 1899, he worked in the  Psychiatric Clinic in Prague . In 1914, he was named  professor . During  World War I , Jansk\u00fd served two years as a doctor at the front until a heart attack disabled him. After the war he worked as a  neuropsychiatrist  in a military Hospital ( Vojensk\u00e1 nemocnice ). He had angina pectoralis and died of  ischaemic heart disease  in  Doln\u00ed Mokropsy  on 8 September 1921, at the age of 48."}
{"_id": "WikiPedia_Hematology$$$corpus_1336", "text": "Jansk\u00fd was also a proponent of voluntary  blood donations ."}
{"_id": "WikiPedia_Hematology$$$corpus_1337", "text": "Through his psychiatric research, Jansk\u00fd tried to find a correlation between mental diseases and  blood diseases . He found no such correlation existed and published a study,  Hematologick\u00e1 studie u psychotik\u016f  (1907,  Hematological study of psychotics ), in which he classified blood into four groups, I, II, III, and IV. (At the time, Jansk\u00fd was unaware of the work of  Karl Landsteiner , whose discovery of the A, B, and O blood types earned him the  Nobel Prize in Physiology or Medicine  in 1930.) At the time Jansk\u00fd's discovery passed almost unnoticed. In 1921 an American medical commission acknowledged Jansk\u00fd's classification. A similar classification was described by  William Lorenzo Moss , except the I and IV of Moss were the opposite to that of Jansk\u00fd's, leading to confusion in  blood transfusion  until the use of A, B and O became standard."}
{"_id": "WikiPedia_Hematology$$$corpus_1338", "text": "Jordans' anomaly  (also known as  Jordan anomaly  and  Jordans bodies ) is a familial abnormality of  white blood cell   morphology . Individuals with this condition exhibit persistent  vacuolation  of  granulocytes  and  monocytes  in the  peripheral blood  and  bone marrow . Jordans' anomaly is associated with  neutral lipid storage diseases . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1339", "text": "Jordans' anomaly is a characteristic finding in Chanarin-Dorfman syndrome and other neutral lipid storage diseases. [ 2 ] [ 4 ]  The anomaly is associated with mutations in the  PNPLA2  gene, which produces the enzyme  adipose triglyceride lipase  (ATGL), and the  ABHD5  gene, which encodes a cofactor of ATGL. These mutations lead to defective  triglyceride  breakdown and accumulation of lipid droplets in cells throughout the body. [ 3 ] [ 5 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1340", "text": "The vacuoles of Jordans' anomaly contain neutral lipids that stain positive with  Sudan staining  techniques. [ 2 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1341", "text": "The anomaly was first described in 1953, by Dr. G. H. Jordans, who identified abnormal  vacuolation  in the white blood cells of two brothers with  congenital muscular dystrophy . Using  special staining , Jordans demonstrated that the vacuoles contained  lipids . [ 1 ] [ 6 ]  In 1966, two further cases of persistent lipid vacuoles were reported in sisters presenting with  ichthyosis . [ 7 ]  The  Chanarin-Dorfman syndrome , comprising Jordans' anomaly, ichthyosis and lipid storage abnormalities, was defined in the 1970s, definitively connecting Jordans' anomaly to lipid storage disease. [ 8 ] [ 4 ]  Jordans' anomaly was linked to  genetic mutations  affecting  triglyceride  metabolism in 2006. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1342", "text": "KAHRP  (knob-associated histidine-rich protein) is a  protein  expressed by  Plasmodium falciparum  infecting  erythrocytes . KAHRP is a major component of knobs, feature found on Plasmodium falciparum infected erythrocytes."}
{"_id": "WikiPedia_Hematology$$$corpus_1343", "text": "It has been suggested that KAHRP may play a role in trafficking or docking  PfEMP1 , major malarial cytoadherence protein to the  erythrocyte membrane ; [ 1 ]  however, these findings were disputed by recent  NMR  and  fluorescence anisotropy  studies showing no interaction between  PfEMP1  and KAHRP. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1344", "text": "Instead, KAHRP was shown to interact with  Ankyrin , more precisely the D3 subunit of the Membrane-binding domain of Ankyrin type 1. [ 3 ]  This interaction was suggested via  SPR ,  ELISA , and  Pulldown  studies, however, it has not been confirmed by NMR,  ITC ,  crystallography , or fluorescence anisotropy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1345", "text": "This  protein -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1346", "text": "The  Keidel vacuum tube  was a type of  blood  collecting device, first manufactured by Hynson, Wescott and Dunning in around 1922. [ 1 ]  This vacuum was one of the first evacuated systems, predating the more well known  Vacutainer . [ 1 ]  Its primary use was to test for  syphilis  and  typhoid fever . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1347", "text": "Essentially, the Keidel vacuum consists of a sealed  ampule  with or without a  culture medium .  Connected to the ampule was a short rubber tube with a needle at the end, using a small glass tube as a cap.  The insertion of the needle into the  vein  crushes the ampule, thus creating a vacuum and forcing blood into the container.  Typically, a prominent vein in the forearm such as the  median cubital vein  would suffice, although the Keidel vacuum can take blood for any prominent peripheral vein.  This concept did not become popular until during  World War II , when quick and efficient first aid care was necessary in the battle field.  As a result, the vacutainer became the forefront device used for blood collection. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1348", "text": "Leucogenenol  is a blood cell stimulating  secondary metabolite  isolated from the mold  Penicillium gilmanii .  Its chemical structure was reported; [ 1 ]  however, later studies determined that the original structure is incorrect and the true chemical structure of leucogenenol remains unknown. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1349", "text": "This article about an  organic compound  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1350", "text": "Leukapheresis  ( / \u02cc l u \u02c8 k \u028c f \u025c\u02d0r i\u02d0 s \u026a s /   \u24d8 ) is a laboratory procedure in which  white blood cells  are separated from a sample of blood. It is a specific type of  apheresis , the more general term for separating out one particular constituent of blood and returning the remainder to the circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_1351", "text": "Leukapheresis may be performed to decrease a very high white blood cell count, to obtain blood cells from a patient ( autologous ) or donor ( allogeneic ) for later transplant into the patient, or to obtain cells for research purposes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1352", "text": "In the case of hematological malignancies such as chronic  leukemias , white blood cell counts may be high enough to cause  leukostasis  and \"sludging\" in the capillaries (acute leukemias have a more variable white cell count whereas chronic cases typically have higher white cell counts). This can affect retinal vasculature leading to vision changes, pulmonary vasculature leading to shortness of breath from decreased efficiency in oxygen exchange, as well as other organ systems such as the brain which would become clinically apparent with neurological deterioration of a patient from cerebrovascular compromise. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1353", "text": "Leukapheresis may be performed to obtain the patient's own blood cells for a later transplant. White blood cells may be removed to protect them from damage before high-dose chemotherapy, then transfused back into the patient, in the treatment of advanced breast cancer. [ 1 ]  Another novel use of cells obtained through leukapheresis is to stimulate a patient\u2019s immune system to target prostate cancer cells. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1354", "text": "Alternatively, only  granulocytes ,  macrophages  and  monocytes  may be removed, leaving the  lymphocyte  count largely unchanged. This is used as a treatment for  autoimmune diseases  such as  ulcerative colitis [ 3 ]  and  rheumatoid arthritis , [ 4 ]  where these cells play an active part in the inflammation process."}
{"_id": "WikiPedia_Hematology$$$corpus_1355", "text": "Leukapheresis, typically for granulocytes, is a rarely performed  blood donation  process.  The product is collected by automated  apheresis  and is used for systemic infections in patients with  neutropenia . [ 5 ]   The donor is typically a blood relative who has received stimulating medications (a directed donation), and the product is irradiated to prevent  GVHD .  The product generally has a 24-hour shelf life from collection and is often transfused before  infectious disease  testing is completed.  It is a therapy of last resort, and its use is controversial and rare."}
{"_id": "WikiPedia_Hematology$$$corpus_1356", "text": "Leukapheresis is used in evolving  CAR-T   cell therapy  to obtain leukocytes from a cancer patient or donor which can be modified and given to the patient as a therapeutic dose."}
{"_id": "WikiPedia_Hematology$$$corpus_1357", "text": "The word  leukapheresis  ( / \u02cc l u\u02d0 k \u0259 f \u0259 \u02c8 r i\u02d0 s \u026a s / ) uses  combining forms  of  leuk-  +  apheresis , although it quite plausibly could be parsed as  leuko-  +  pheresis , as both of those forms are accepted alternate forms ( leuk-/leuko-; apheresis/pheresis ). The latter parsing explains why people often spell the word with an  -o-  as  *leukopheresis ; nonetheless, no professionally curated dictionaries as of 2016 enter that spelling, and it is traditionally treated as a misspelling by medical  style guides  that mention it. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1358", "text": "Leukocyte adhesion deficiency  ( LAD ) is a rare  autosomal   recessive  disorder characterized by  immunodeficiency  resulting in recurrent  infections . [ 1 ]  LAD is currently divided into three subtypes:  LAD1 ,  LAD2 , and the recently described  LAD3 , also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a  Glanzmann thrombasthenia -like bleeding tendency. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1359", "text": "LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent  bacterial   infections , defects in  neutrophil  adhesion, and a delay in  umbilical cord  sloughing. The adhesion defects result in poor  leukocyte   chemotaxis , particularly neutrophil, inability to form pus and  neutrophilia . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1360", "text": "Individuals with LAD suffer from bacterial infections beginning in the  neonatal  period. Infections such as  omphalitis ,  pneumonia ,  gingivitis , and  peritonitis  are common and often life-threatening due to the infant's inability to properly destroy the invading  pathogens . These individuals do not form  abscesses  because  granulocytes  cannot migrate to the sites of  infection ."}
{"_id": "WikiPedia_Hematology$$$corpus_1361", "text": "Types of leukocyte adhesion deficiency include LAD1, LAD2, and LAD3. LAD1 is the most common. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1362", "text": "Patients with LAD1 have an  inherited   molecular defect  that causes a deficiency of the \u03b2-2  integrin  subunit, [ 5 ]  also called  CD18 , which is encoded by the ITGB2 gene found on  chromosome 21 . This subunit is involved in the formation of the \u03b2-2 integrins ( LFA-1 ,  integrin alphaXbeta2 /CR4/p150,95, and  Mac-1/CR3 ) by dimerization with different CD11 subunits. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1363", "text": "Mutations in the ITGB2 gene lead to absent, reduced, or aberrant  CD18   protein expression , causing a lack of expression in the leukocyte membrane of the \u03b2-2 integrins. The main function of these proteins is to allow  neutrophils  to make their way out of the blood stream and into the infected tissues by adhering to different  ligands  expressed by the  endothelium , e.g.  ICAM-1 . In LAD-I patients, neutrophils cannot  extravasate  and fight against bacteria in tissues. The bacteria can then proliferate, leading to  symptomatic  infection, which can spread unimpeded and cause serious injury to important  tissues . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1364", "text": "Typically,  diagnosis  involves several preliminary tests of  immune  function, including basic evaluation of the  humoral immune system  and the  cell-mediated immune system . A  WBC   differential  will reveal extremely elevated levels of neutrophils (on the order of 6\u201310x normal) because they are unable to leave the  blood vessels .\nIn the case of LAD-I, specific diagnosis is done by  flow cytometry . This technique will reveal absent or reduced  CD18  expression in the leukocyte membrane. Recently, prenatal diagnosis systems has been established, allowing an early detection of the disease.\nLAD-II diagnosis includes the study of different glycosylated forms of the  transferrin  protein. In LAD-III, as  platelet  function is also affected, this could be used to differentiate it from the other types. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1365", "text": "Although patients can receive intensive antibiotherapy and even  granulocyte transfusions  from healthy donors, the only current curative therapy is the  hematopoietic stem cell transplant . [ 8 ]  However, progress has been made in  gene therapy , an active area of research. Both  foamyviral  and  lentiviral vectors  expressing the human  ITGB2  gene under the control of different promoters have been developed and have been tested so far in preclinical LAD-I models (such as CD18-deficient mice and canine leukocyte adhesion deficiency-affected dogs). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1366", "text": "A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), the survival rate was 75%. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1367", "text": "LAD is a rare disease, with an estimated prevalence of one in 100,000 births, with no described racial or ethnic predilection. The most common type is LAD1."}
{"_id": "WikiPedia_Hematology$$$corpus_1368", "text": "In  immunology ,  leukocyte extravasation  (also commonly known as   leukocyte adhesion cascade  or  diapedesis  \u2013 the passage of cells through the intact vessel wall) is the movement of  leukocytes  (white blood cells) out of the  circulatory system  ( extravasation ) and towards the site of tissue damage or  infection . This process forms part of the  innate immune response , involving the recruitment of non-specific leukocytes.  Monocytes  also use this process in the absence of infection or tissue damage during their development into  macrophages ."}
{"_id": "WikiPedia_Hematology$$$corpus_1369", "text": "Leukocyte extravasation occurs mainly in post-capillary  venules , where  haemodynamic   shear forces  are minimised. This process can be understood in several steps: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1370", "text": "It has been demonstrated that leukocyte recruitment is halted whenever any of these steps is suppressed."}
{"_id": "WikiPedia_Hematology$$$corpus_1371", "text": "White blood cells (leukocytes) perform most of their functions in tissues. Functions include phagocytosis of foreign particles, production of antibodies, secretion of inflammatory response triggers (histamine and heparin), and neutralization of histamine. In general, leukocytes are involved in the defense of an organism and protect it from disease by promoting or inhibiting inflammatory responses.\nLeukocytes use the blood as a transport medium to reach the tissues of the body. Here is a brief summary of each of the four steps currently thought to be involved in leukocyte extravasation:"}
{"_id": "WikiPedia_Hematology$$$corpus_1372", "text": "Upon recognition of and activation by  pathogens , resident macrophages in the affected tissue release  cytokines  such as  IL-1 ,  TNF\u03b1  and  chemokines . IL-1, TNF\u03b1 and C5a [ 1 ]  cause the  endothelial cells  of blood vessels near the site of infection to express  cellular adhesion molecules , including  selectins . Circulating leukocytes are localised towards the site of injury or infection due to the presence of chemokines. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1373", "text": "Like velcro, carbohydrate ligands on the circulating leukocytes bind to selectin molecules on the inner wall of the vessel, with marginal  affinity . This causes the leukocytes to slow down and begin rolling along the inner surface of the vessel wall. During this rolling motion, transitory bonds are formed and broken between selectins and their  ligands ."}
{"_id": "WikiPedia_Hematology$$$corpus_1374", "text": "For example, the carbohydrate ligand for P-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), is expressed by different types of leukocytes (white blood cells). The binding of PSGL-1 on the leukocyte to P-selectin on the endothelial cell allows for the leukocyte to roll along the endothelial surface. This interaction can be tuned by the glycosylation pattern of PSGL-1, such that certain glycovariants of PSGL-1 will have unique affinities for different selectins, allowing in some cases for cells to migrate to specific sites within the body (e.g. the skin). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1375", "text": "At the same time, chemokines released by macrophages activate the rolling leukocytes and cause surface  integrin  molecules to switch from the default low-affinity state to a high-affinity state. This is assisted through  juxtacrine  activation of integrins by chemokines and soluble factors released by endothelial cells. In the activated state, integrins bind tightly to complementary receptors expressed on endothelial cells, with high affinity. This causes the immobilization of the leukocytes, which varies in vessels that contain different shear forces of the ongoing blood flow. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1376", "text": "The  cytoskeletons  of the leukocytes are reorganized in such a way that the leukocytes are spread out over the endothelial cells.  In this form, leukocytes extend  pseudopodia  and pass through gaps between endothelial cells. This passage of cells through the intact vessel wall is called  diapedesis . [ 3 ]  These gaps can form through interactions of the leukocytes with the endothelium, but also autonomously through endothelial mechanics. [ 4 ]  Transmigration of the leukocyte occurs as  PECAM  proteins, found on the leukocyte and endothelial cell surfaces, interact and effectively pull the cell through the endothelium. Once through the endothelium, the leukocyte must penetrate the  basement membrane . The mechanism for penetration is disputed, but may involve proteolytic digestion of the membrane, mechanical force, or both. [ 5 ]  The entire process of blood vessel escape is known as  diapedesis . Once in the  interstitial fluid , leukocytes migrate along a  chemotactic  gradient towards the site of injury or infection."}
{"_id": "WikiPedia_Hematology$$$corpus_1377", "text": "The phases of the leukocyte extravasation depicted in the schema are: approach, capture, rolling, activation, binding, strengthening of the binding and spreading, intravascular creeping, paracellular migration or transcellular migration."}
{"_id": "WikiPedia_Hematology$$$corpus_1378", "text": "Selectins are expressed shortly after cytokine activation of endothelial cells by tissue macrophages. Activated endothelial cells initially express P-selectin molecules, but within two hours after activation E-selectin expression is favoured. Endothelial selectins bind  carbohydrates  on leukocyte transmembrane  glycoproteins , including  sialyl-Lewis X ."}
{"_id": "WikiPedia_Hematology$$$corpus_1379", "text": "Suppressed expression of some selectins results in a slower immune response. If L-selectin is not produced, the immune response may be ten times slower, as P-selectins (which can also be produced by leukocytes) bind to each other. P-selectins can bind each other with high affinity, but occur less frequently because the receptor-site density is lower than with the smaller E-selectin molecules. This increases the initial leukocyte rolling speed, prolonging the slow rolling phase."}
{"_id": "WikiPedia_Hematology$$$corpus_1380", "text": "Integrins involved in cellular adhesion are primarily expressed on leukocytes. \u03b22 integrins on rolling leukocytes bind  endothelial   cellular adhesion  molecules, arresting cell movement."}
{"_id": "WikiPedia_Hematology$$$corpus_1381", "text": "Cellular activation via extracellular chemokines causes pre-formed \u03b22 integrins to be released from cellular stores. Integrin molecules migrate to the cell surface and congregate in high- avidity  patches. Intracellular integrin domains associate with the leukocyte cytoskeleton, via mediation with cytosolic factors such as  talin ,  \u03b1-actinin  and  vinculin . This association causes a conformational shift in the integrin's  tertiary structure , allowing ligand access to the binding site.  Divalent cations  (e.g.  Mg 2+ ) are also required for integrin-ligand binding."}
{"_id": "WikiPedia_Hematology$$$corpus_1382", "text": "Integrin ligands ICAM-1 and VCAM-1 are activated by inflammatory cytokines, while ICAM-2 is constitutively expressed by some endothelial cells but downregulated by inflammatory cytokines. ICAM-1 and ICAM-2 share two  homologous   N-terminal   domains ; both can bind LFA-1."}
{"_id": "WikiPedia_Hematology$$$corpus_1383", "text": "During chemotaxis, cell movement is facilitated by the binding of \u03b21 integrins to components of the  extracellular matrix : VLA-3, VLA-4 and VLA-5 to  fibronectin  and VLA-2 and VLA-3 to  collagen  and other extracellular matrix components."}
{"_id": "WikiPedia_Hematology$$$corpus_1384", "text": "Extravasation is regulated by the background cytokine environment produced by the  inflammatory response , and is independent of specific cellular  antigens . Cytokines released in the initial immune response induce  vasodilation  and lower the electrical charge along the vessel's surface. Blood flow is slowed, facilitating intermolecular binding."}
{"_id": "WikiPedia_Hematology$$$corpus_1385", "text": "In 1976, SEM images showed that there were homing receptors on microvilli-like tips on leukocytes that would allow white blood cells to get out of the blood vessel and get into tissue. [ 7 ]  Since the 1990s the identity of ligands involved in leukocyte extravasation have been studied heavily. This topic was finally able to be studied thoroughly under physiological shear stress conditions using a typical flow chamber. [ 8 ]    Since the first experiments, a strange phenomenon was observed. Binding interactions between the white blood cells and the vessel walls were observed to become stronger under higher force. Selectins (E-selectin, L-selectin, and P-selectin) were found to be involved in this phenomenon.\nThe shear threshold requirement seems counterintuitive because increasing shear elevates the force applied to adhesive bonds and it would seem that this should increase the dislodging ability. Nevertheless, cells roll more slowly and more regularly until an optimal shear is reached where rolling velocity is minimal. This paradoxical phenomenon has not been satisfactorily explained despite the widespread interest."}
{"_id": "WikiPedia_Hematology$$$corpus_1386", "text": "One initially dismissed hypothesis that has been gaining interest is the catch bond hypothesis, where the increased force on the cell slows off-rates and lengthen the bond lifetimes and stabilizing the rolling step of leukocyte extravasation. [ 9 ] \nFlow-enhanced cell adhesion is still an unexplained phenomenon that could result from a transport-dependent increase in on-rates or a force-dependent decrease in off-rates of adhesive bonds. L-selectin requires a particular minimum of shear to sustain leukocyte rolling on P-selectin glycoprotein ligand-1 (PSGL-1) and other vascular ligands. It has been hypothesized that low forces decrease L-selectin\u2013PSGL-1 off-rates (catch bonds), whereas higher forces increase off-rates (slip bonds).\nExperiments have found that a force-dependent decrease in off-rates dictated flow-enhanced rolling of L-selectin\u2013bearing microspheres or neutrophils on PSGL-1.  [5]  Catch bonds enable increasing force to convert short bond lifetimes into long bond lifetimes, which decrease rolling velocities and increase the regularity of rolling steps as shear rose from the threshold to an optimal value. As shear increases, transitions to slip bonds shorten their bond lifetimes and increase rolling velocities and decrease rolling regularity.\nIt is hypothesized that force-dependent alterations of bond lifetimes govern L-selectin\u2013dependent cell adhesion below and above the shear optimum. These findings establish a biological function for catch bonds as a mechanism for flow-enhanced cell adhesion. [ 10 ]   While leukocytes seem to undergo a catch bond behavior with increasing flow leading to the tethering and rolling steps in leukocyte extravasation, firm adhesion is achieved through another mechanism, integrin activation."}
{"_id": "WikiPedia_Hematology$$$corpus_1387", "text": "Other biological examples of a catch bond mechanism is seen in bacteria that tightly cling to urinary tract walls in response to high fluid velocities and large shear forces exerted on the cells and bacteria with adhesive tips of fimbria. [ 9 ] [ 11 ]   Schematic mechanisms of how increased shear force is proposed to cause stronger binding interactions between bacteria and target cells show that the catch bond acts very similar to a Chinese finger trap. For a catch-bond, the force on the cell pulls the adhesive tip of a fimbria to close tighter on its target cell. As the strength of the forces increases, the stronger the bond between the fimbria and the cell-receptor on the surface of the target cell. [ 11 ]  For a cryptic-bond, the force causes the fimbria to swivel toward the target cell and have more binding sites able to attach to the target cell ligands, mainly sugar molecules. This creates a stronger bonding interaction between the bacteria and the target cell."}
{"_id": "WikiPedia_Hematology$$$corpus_1388", "text": "Parallel plate flow chambers are among the most popular flow chambers used to study the leukocyte-endothelial interaction in vitro. They have been used for investigation since the later 1980s. [ 12 ]  Although flow chambers have been an important tool to study leukocyte rolling, there are several limitations when it comes to  studying the physiological in vivo conditions, as they lack correspondence with in vivo geometry, including scale/aspect ratio (microvasculature vs large vessel models), flow conditions (e.g. converging vs diverging flows at bifurcations), and require large reagent volumes (~ ml) due to their large size (height > 250\u00a0\u03bcm and width > 1mm). [ 13 ] \nWith the advent of microfluidic-based devices, these limitations have been overcome. A new in vitro model, called SynVivo Synthetic microvascular network (SMN) was produced by the CFD Research Corporation (CFDRC) and developed using the polydimethylsiloxane (PDMS) based soft-lithography process. The SMN can recreate the complex in vivo vasculature, including geometrical features, flow conditions, and reagent volumes, thereby providing a biologically realistic environment for studying the extravasation cellular behavior, but also for drug delivery and drug discovery.  [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1389", "text": "Leukocyte adhesion deficiency (LAD) is a genetic disease associated with a defect in the leukocyte extravasation process, caused by a defective integrin \u03b22 chain (found in LFA-1 and Mac-1). This impairs the ability of the leukocytes to stop and undergo diapedesis. People with LAD suffer from recurrent bacterial infections and impaired wound healing.  Neutrophilia  is a hallmark of LAD."}
{"_id": "WikiPedia_Hematology$$$corpus_1390", "text": "In widespread diseases such as sepsis, leukocyte extravasation enters an uncontrolled stage, where white blood neutrophils begin destroying host tissues at unprecedented rates, claiming the lives of about 200,000 people in the United States alone. [ 16 ]  Neutrophil dysfunction is usually preceded by an infection of some sort, which triggers pathogen-associated molecular patterns (PAMP). As leukocyte extravasation intensifies, more tissues are damaged by neutrophils, which release oxygen radicals and proteases. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1391", "text": "Recent studies with SynVivo Synthetic microvascular network (SMN) made it possible to study anti-inflammatory therapeutics to treat pathologies caused by neutrophil dysfunction. The SMN enables the thorough analysis of each stage of leukocyte extravasation, thereby providing a methodology to quantify the effect of the drug in impeding leukocyte extravasation. Some of the recent findings demonstrate the effect of hydrodynamics on neutrophil-endothelial interactions. In other words, adhesion of neutrophils is heavily impacted by shear forces as well as molecular interactions. Moreover, as shear rate decreases (e.g., in post-capillary venules), immobilization of the leukocytes becomes easier and thus, more prevalent. The opposite is also true; vessels in which shear forces are high render the immobilization of the leukocytes more difficult. This has high implications in various diseases, where disruptions in blood flow gravely impact immune system response by impeding or expediting the immobilization of the leukocytes. Having this knowledge allows for better studies of the effect of drugs on  leukocyte extravasation. [ 13 ] [ 16 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1392", "text": "Leukocyte-promoting factor , more commonly known as  leukopoietin , is a category of substances produced by  neutrophils  when they encounter a foreign  antigen . Leukopoietin stimulates the bone marrow to increase the rate of  leukopoiesis  in order to replace the neutrophils that will inevitably be lost when they begin to  phagocytose  the foreign antigens. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1393", "text": "Leukocyte-promoting factors include  colony stimulating factors  (CSFs) (produced by  monocytes  and  T lymphocytes ),  interleukins   (produced by monocytes,  macrophages , and  endothelial cells ),  prostaglandins , and  lactoferrin . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1394", "text": "Lymphoma  is a group of  blood and lymph tumors  that develop from  lymphocytes  (a type of  white blood cell ). [ 7 ]  The name typically refers to just the  cancerous  versions rather than all such tumours. [ 7 ]  Signs and symptoms may include  enlarged lymph nodes ,  fever , drenching  sweats , unintended weight loss,  itching , and constantly  feeling tired . [ 1 ] [ 2 ]  The enlarged lymph nodes are usually painless. [ 1 ]  The sweats are most common at night. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1395", "text": "Many subtypes of lymphomas are known. [ 8 ]  The two main categories of lymphomas are the  non-Hodgkin lymphoma  (NHL) (90% of cases) [ 9 ] [ 10 ]  and  Hodgkin lymphoma  (HL) (10%). [ 9 ]   Lymphomas,  leukemias  and myelomas are a part of the broader group of  tumors of the hematopoietic and lymphoid tissues . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1396", "text": "Risk factors for Hodgkin lymphoma include infection with  Epstein\u2013Barr virus  and a history of the disease in the family. [ 1 ]  Risk factors for common types of non-Hodgkin lymphomas include  autoimmune diseases ,  HIV/AIDS , infection with  human T-lymphotropic virus ,  immunosuppressant medications , and some  pesticides . [ 2 ] [ 12 ]  Eating large amounts of red meat and  tobacco smoking  may also increase the risk. [ 3 ] [ 13 ] [ 14 ]  Diagnosis, if enlarged lymph nodes are present, is usually by  lymph node biopsy . [ 1 ] [ 2 ]  Blood, urine, and  bone marrow testing  may also be useful in the diagnosis. [ 2 ]   Medical imaging  may then be done to determine if and where the cancer has spread. [ 1 ] [ 2 ]  Lymphoma most often spreads to the lungs, liver, and brain. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1397", "text": "Treatment may involve one or more of the following:  chemotherapy ,  radiation therapy ,  proton therapy ,  targeted therapy , and surgery. [ 1 ] [ 2 ]  In some non-Hodgkin lymphomas, an increased amount of protein produced by the lymphoma cells causes the blood to become so thick that  plasmapheresis  is performed to remove the protein. [ 2 ]   Watchful waiting  may be appropriate for certain types. [ 2 ]  The outcome depends on the subtype, with some being curable and treatment prolonging survival in most. [ 9 ]  The  five-year survival rate  in the United States for all Hodgkin lymphoma subtypes is 85%, [ 4 ]  while that for non-Hodgkin lymphomas is 69%. [ 15 ]  Worldwide, lymphomas developed in 566,000 people in 2012 and caused 305,000 deaths. [ 16 ]  They make up 3\u20134% of all cancers, making them as a group the seventh-most-common form. [ 16 ] [ 17 ]  In children, they are the third-most-common cancer. [ 18 ]  They occur more often in the  developed world  than in the  developing world . [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1398", "text": "Lymphoma may present with certain nonspecific symptoms; if the symptoms are persistent, an evaluation to determine their cause, including possible lymphoma, should be undertaken."}
{"_id": "WikiPedia_Hematology$$$corpus_1399", "text": "Lymphoma is definitively diagnosed by a  lymph-node biopsy , meaning a partial or total excision of a  lymph node  examined under the microscope. [ 22 ]  This examination reveals  histopathological  features that may indicate lymphoma. After lymphoma is diagnosed, a variety of tests may be carried out to look for specific features characteristic of different types of lymphoma. These include:"}
{"_id": "WikiPedia_Hematology$$$corpus_1400", "text": "According to the World Health Organization (WHO), lymphoma classification should reflect in which lymphocyte population the neoplasm arises. [ 23 ]  Thus, neoplasms that arise from precursor lymphoid cells are distinguished from those that arise from mature lymphoid cells. [ 23 ]  Most mature lymphoid neoplasms comprise the non-Hodgkin lymphomas. [ 23 ]  Historically, mature histiocytic and dendritic cell (HDC) neoplasms have been considered mature lymphoid neoplasms, since these often involve lymphoid tissue. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1401", "text": "Lymphoma can also spread to the  central nervous system , often around the brain in the  meninges , known as lymphomatous meningitis (LM). [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1402", "text": "Hodgkin lymphoma accounts for about 15% of lymphomas. [ 25 ]  It differs from other forms of lymphomas in its  prognosis  and several  pathological  characteristics. A division into Hodgkin and non-Hodgkin lymphomas is used in several of the older classification systems. A Hodgkin lymphoma is marked by the presence of a type of cell called the  Reed\u2013Sternberg cell . [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1403", "text": "Non-Hodgkin lymphomas , which are defined as being all lymphomas except Hodgkin lymphoma, are more common than Hodgkin lymphoma. A wide variety of lymphomas are in this class, and the causes, the types of cells involved, and the prognoses vary by type. The number of cases per year of non-Hodgkin lymphoma increases with age. It is further divided into several subtypes. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1404", "text": "Epstein\u2013Barr virus-associated lymphoproliferative diseases  are a group of benign,  premalignant , and malignant diseases of  lymphoid cells  (i.e.,  B cells ,  T cells ,  NK cells , and  histiocytic-dendritic cells ) in which one or more of these cell types is infected with the  Epstein\u2013Barr virus  (EBV). The virus may be responsible for the development and/or progression of these diseases. In addition to  EBV-positive Hodgkin lymphomas , the World Health Organization (2016) includes the following lymphomas, when associated with EBV infection, in this group of diseases:  Burkitt lymphoma ;  large B cell lymphoma, not otherwise specified ;  diffuse large B cell lymphoma associated with chronic inflammation ;  fibrin-associated diffuse large B cell lymphoma ;  primary effusion lymphoma ;  plasmablastic lymphoma ;  extranodal NK/T cell lymphoma, nasal type ;  peripheral T cell lymphoma, not otherwise specified ;  angioimmunoblastic T-cell lymphoma ;  follicular T cell lymphoma ; and  systemic T cell lymphoma of childhood . [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1405", "text": "The WHO classification, published in 2001 and updated in 2008, 2017, and 2022, [ 30 ]  is based upon the foundations laid within the \"revised European\u2013American lymphoma classification\" (REAL). This system groups lymphomas by cell type (i.e., the normal cell type that most resembles the tumor) and defining  phenotypic ,  molecular , or  cytogenetic  characteristics. The five groups are shown in the table. Hodgkin lymphoma is considered separately within the WHO and preceding classifications, although it is recognized as being a tumor, albeit markedly abnormal, of lymphocytes of mature B cell lineage. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1406", "text": "Of the many forms of lymphoma, some are categorized as indolent (e.g.  small lymphocytic lymphoma ), compatible with a long life even without treatment, whereas other forms are aggressive (e.g.  Burkitt's lymphoma ), causing rapid deterioration and death. However, most of the aggressive lymphomas respond well to treatment and are curable. The  prognosis , therefore, depends on the correct diagnosis and classification of the disease, which is established after examination of a biopsy by a  pathologist  (usually a  hematopathologist ). [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1407", "text": "Several previous classifications have been used, including Rappaport 1956, Lennert/Kiel 1974, BNLI, Working formulation (1982), and REAL (1994)."}
{"_id": "WikiPedia_Hematology$$$corpus_1408", "text": "The  Working Formulation  of 1982 was a classification of  non-Hodgkin lymphoma . It excluded the Hodgkin lymphomas and divided the remaining lymphomas into four grades (low, intermediate, high, and miscellaneous) related to prognosis, with some further subdivisions based on the size and shape of affected cells. This purely histological classification included no information about  cell surface markers  or genetics and made no distinction between  T-cell lymphomas  and  B-cell lymphomas . It was widely accepted at the time of its publication but by 2004 was obsolete. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1409", "text": "In 1994, the Revised European-American Lymphoma (REAL) classification applied immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except Hodgkin lymphoma. [ 41 ]  For coding purposes, the  ICD-O  (codes 9590\u20139999) [ 42 ]  and  ICD-10  (codes C81-C96) [ 43 ]  are available."}
{"_id": "WikiPedia_Hematology$$$corpus_1410", "text": "After a diagnosis and before treatment, cancer is  staged . This refers to determining if the cancer has spread, and if so, whether locally or to distant sites. Staging is reported as a grade between I (confined) and IV (spread). The stage of a lymphoma helps predict a patient's prognosis and is used to help select the appropriate therapy. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1411", "text": "The  Ann Arbor staging system  is routinely used for staging of both HL and NHL. In this staging system, stage I represents localized disease contained within a lymph node group, II represents the presence of lymphoma in two or more lymph nodes groups, III represents spread of the lymphoma to lymph nodes groups on both sides of the  diaphragm , and IV indicates spread to tissue outside the lymphatic system. Different suffixes imply the involvement of different organs, for example, S for the spleen and H for the liver. Extra-lymphatic involvement is expressed with the letter E. In addition, the presence of B symptoms (one or more of the following: unintentional loss of 10% body weight in the last 6 months, night sweats, or persistent fever of 38\u00a0\u00b0C or more) or their absence is expressed with B or A, respectively. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1412", "text": "CT scan  or  PET scan  imaging modalities are used to stage cancer. PET scanning is advised for  fluorodeoxyglucose -avid lymphomas, such as Hodgkin lymphoma, as a staging tool that can even replace bone marrow biopsy. For other lymphomas, CT scanning is recommended for staging. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1413", "text": "Age and poor  performance status  are other established poor prognostic factors. [ 46 ]   This means that people who are elderly or too sick to take care of themselves are more likely to be killed by lymphoma than others."}
{"_id": "WikiPedia_Hematology$$$corpus_1414", "text": "Certain lymphomas ( extranodal NK/T-cell lymphoma, nasal type  and  type II enteropathy-associated T-cell lymphoma ) can be mimicked by two benign diseases that involve the excessive proliferation of nonmalignant NK cells in the GI tract,  natural killer cell enteropathy , a disease wherein NK cell infiltrative lesions occur in the intestine, colon, stomach, or esophagus, and  lymphomatoid gastropathy , a disease wherein these cells' infiltrative lesions are limited to the stomach. These diseases do not progress to cancer, may regress spontaneously and do not respond to, and do not require, chemotherapy or other lymphoma treatments. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1415", "text": "Prognoses and treatments are different for HL and between all the different forms of NHL, [ 48 ]  and also depend on the  grade  of tumour, referring to how quickly a cancer replicates. Paradoxically, high-grade lymphomas are more readily treated and have better prognoses: [ 49 ]   Burkitt lymphoma , for example, is a high-grade tumour known to double within days, and is highly responsive to treatment."}
{"_id": "WikiPedia_Hematology$$$corpus_1416", "text": "Many low-grade lymphomas remain  indolent  (growing slowly or not at all) for many years \u2013 sometimes, for the rest of the person's life. With an indolent lymphoma, such as follicular lymphoma,  watchful waiting  is often the initial course of action, because monitoring is less risky and less harmful than early treatment. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1417", "text": "If a low-grade lymphoma becomes symptomatic, radiotherapy or chemotherapy are the treatments of choice.  Although these treatments do not permanently cure the lymphoma, they can alleviate the symptoms, particularly painful  lymphadenopathy . People with these types of lymphoma can live near-normal lifespans, even though the disease is technically  incurable ."}
{"_id": "WikiPedia_Hematology$$$corpus_1418", "text": "Some centers advocate the use of single agent  rituximab  in the treatment of follicular lymphoma rather than the wait-and-watch approach.  Watchful waiting  is not a desirable strategy for everyone, as it leads to significant distress and  anxiety  in some people. It has been called \"watch and worry\". [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1419", "text": "Treatment of some other, more aggressive, forms of lymphoma  [ which? ]  can result in a cure in the majority of cases, but the prognosis for people with a poor response to therapy is worse. [ 52 ]  Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the  CHOP or R-CHOP  regimen. A number of people are cured with first-line chemotherapy. Most relapses occur within the first two years, and the relapse risk drops significantly thereafter. [ 53 ]  For people who relapse, high-dose chemotherapy followed by autologous stem cell transplantation is a proven approach. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1420", "text": "The treatment of side effects is also important as they can occur due to the chemotherapy or the  stem cell transplantation . It was evaluated whether mesenchymal stromal cells can be used for the treatment and prophylaxis of  graft-versus-host diseases . The evidence is very uncertain about the therapeutic effect of mesenchymal stromal cells to treat graft-versus-host diseases on the all-cause mortality and complete disappear of chronic acute graft-versus-host diseases. Mesenchymal stromal cells may result in little to no difference in the all-cause mortality, relapse of malignant disease and incidence of acute and chronic graft-versus-host diseases if they are used for prophylactic reason. [ 55 ]  Moreover, it was seen that  platelet transfusions  for people undergoing a chemotherapy or a stem cell transplantation for the prevention of bleeding events had different effects on the number of participants with a bleeding event, the number of days on which a bleeding occurred, the mortality secondary to bleeding and the number of platelet transfusions depending on the way they were used (therapeutic, depending on a threshold, different dose schedules or prophylactic). [ 56 ] [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1421", "text": "Four  chimeric antigen receptor T cell  therapies are FDA-approved for non-Hodgkin lymphoma, including  lisocabtagene maraleucel  (for relapsed or refractory large B-cell lymphoma with two failed systemic treatments),  axicabtagene ciloleucel ,  tisagenlecleucel  (for large B-cell lymphoma), and  brexucabtagene autoleucel  (for  mantle cell lymphoma ). These therapies come with certification and other restrictions. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1422", "text": "Hodgkin lymphoma typically is treated with radiotherapy alone, as long as it is localized. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1423", "text": "Advanced Hodgkin disease requires systemic chemotherapy, sometimes combined with radiotherapy. [ 60 ]  Chemotherapy used includes the  ABVD  regimen, which is commonly used in the United States. Other regimens used in the management of Hodgkin lymphoma include  BEACOPP  and  Stanford V . Considerable controversy exists regarding the use of ABVD or BEACOPP. Briefly, both regimens are effective, but BEACOPP is associated with more toxicity. Encouragingly, a significant number of people who relapse after ABVD can still be salvaged by stem cell transplant. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1424", "text": "Scientists evaluated whether  positron emission tomography  scans between the chemotherapy cycles can be used to make assumptions about the survival. The evidence is very uncertain about the effect of negative (= good prognosis) or positive (= bad prognosis) interim PET scan results on the progression-free survival. Negative interim PET scan results may result in an increase in progression-free survival compared if the adjusted result was measured. Negative interim PET scan results probably result in a large increase in the overall survival compared to those with a positive interim PET scan result. [ 62 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1425", "text": "Current research evaluated whether  Nivolumab  can be used for the treatment of a Hodgkin's lymphoma. The evidence is very uncertain about the effect of Nivolumab for patients with a Hodgkin's lymphoma on the overall survival, the quality of life, the survival without a progression, the response rate (=complete disappear) and grade 3 or 4 serious adverse events. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1426", "text": "Palliative care , a specialized medical care focused on the symptoms, pain, and stress of a serious illness, is recommended by multiple national cancer treatment guidelines as an accompaniment to curative treatments for people with lymphoma. [ 64 ] [ 65 ]  It is used to address both the direct symptoms of lymphoma and many unwanted side effects that arise from treatments. [ 66 ] [ 67 ]  Palliative care can be especially helpful for children who develop lymphoma, helping both children and their families deal with the physical and emotional symptoms of the disease. [ 66 ] [ 68 ] [ 69 ] [ 70 ]  For these reasons, palliative care is especially important for people requiring bone marrow transplants. [ 71 ] [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1427", "text": "Adding physical exercises to the standard treatment for adult patients with haematological malignancies like lymphomas may result in little to no difference in the mortality, the quality of life and the physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect on anxiety and serious adverse events. [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1428", "text": "Lymphoma is the most common form of  hematological malignancy , or \"blood cancer\", in the developed world."}
{"_id": "WikiPedia_Hematology$$$corpus_1429", "text": "Taken together, lymphomas represent 5.3% of all cancers (excluding simple basal cell and squamous cell skin cancers) in the United States and 55.6% of all blood cancers. [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1430", "text": "According to the  U.S. National Institutes of Health , lymphomas account for about 5%, and Hodgkin lymphoma in particular accounts for less than 1% of all cases of cancer in the United States. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1431", "text": "Because the whole lymphatic system is part of the body's immune system, people with a weakened immune system such as from HIV infection or from certain drugs or medication also have a higher number of cases of lymphoma. [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1432", "text": "Thomas Hodgkin  published the first description of lymphoma in 1832, specifically of the form named after him. [ 78 ]  Since then, many other forms of lymphoma have been described."}
{"_id": "WikiPedia_Hematology$$$corpus_1433", "text": "The term \"lymphoma\" is from Latin  lympha  (\"water\") and from Greek  -oma  (\"morbid growth, tumor\"). [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1434", "text": "The two types of lymphoma research are clinical or  translational research  and  basic research . Clinical/translational research focuses on studying the disease in a defined and generally immediately applicable way, such as testing a new drug in people. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for people, or appropriate care in remission or after cures. Hundreds of  clinical trials  are being planned or conducted at any given time. [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1435", "text": "Basic science research studies the disease process at a distance, such as seeing whether a suspected carcinogen can cause healthy cells to turn into lymphoma cells in the laboratory or how the DNA changes inside lymphoma cells as the disease progresses. The results from basic research studies are generally less immediately useful to people with the disease, [ 81 ]  but can improve scientists' understanding of lymphoma and form the foundation for future, more effective treatments."}
{"_id": "WikiPedia_Hematology$$$corpus_1436", "text": "hidden"}
{"_id": "WikiPedia_Hematology$$$corpus_1437", "text": "Dominique Meyer [ 1 ]  (born 5 October 1939, in G\u00e9rardmer (Vosges)) is a French M.D. biologist and member of the  French Academy of Sciences . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1438", "text": "Medical Doctor and researcher, she was both director of an  Inserm  research unit at Bic\u00eatre Hospital and head of the biological hematology department at Antoine B\u00e9cl\u00e8re Hospital. [ 3 ]  She has done extensive work at the  Scripps Research Institute  in  La Jolla ,  California  and was President of the International Society on Thrombosis and Hemostasis from 1992 to 1994. [ 4 ]  She was President of the Scientific Council of the Fondation pour la Recherche M\u00e9dicale, [ 5 ]  President of the Board of Directors of Inserm, [ 6 ]  Vice-president of the Board of Directors of the  Institut Curie , Member of the  Institut universitaire de France , [ 7 ]  Member of the  Ethics Committee  of the  CNRS , [ 8 ]  Member of the Conseil \u00c9conomique, Social et Environnemental (CESE) [ 9 ]  and Head of Scientific Information and Communication of the  Acad\u00e9mie des Sciences . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1439", "text": "Dominique Meyer is currently professor emeritus of Hematology at the University of Paris XI, member of the Scientific Council of the Parliamentary Office for the Assessment of Scientific and Technological Choices (OPECST) [ 10 ]  and member of the Institut de France, whose Central Administrative Commission she chaired in 2019. [ 11 ]  Her world-renowned work has been devoted to the study of hemostasis and more specifically to the analysis of one of the proteins involved, von Willebrand factor, [ 12 ] [ 13 ]  which is the central focus of her research on the molecular mechanisms that ensure a balance between bleeding and thrombosis."}
{"_id": "WikiPedia_Hematology$$$corpus_1440", "text": "- On her research: more than 350 original articles and about fifty general reviews, book chapters or didactic articles. [ 14 ]  More than 300 communications presented at scientific conferences."}
{"_id": "WikiPedia_Hematology$$$corpus_1441", "text": "Her main scientific publications are:"}
{"_id": "WikiPedia_Hematology$$$corpus_1442", "text": "Member of the Conseil de l'Ordre de la L\u00e9gion d'Honneur from 2010 to 2016."}
{"_id": "WikiPedia_Hematology$$$corpus_1443", "text": "Microtransplantation  ( MST ) is an advanced technology to treat malignant hematological diseases and tumors by infusing patients with  granulocyte colony-stimulating factor  (G-CSF) mobilized  human leukocyte antigen  (HLA)-mismatched allogeneic  peripheral blood stem cells  following a reduced-intensity chemotherapy or targeted therapy. The term \"microtransplantation\" comes from its mechanism of reaching donor cell microchimerism."}
{"_id": "WikiPedia_Hematology$$$corpus_1444", "text": "Chemotherapy is used by lower doses only to destroy cancer and partially suppress patient\u2019s immune system, which will be reinitiated by donor\u2019s stem cells soon after transplantation, and will play a role as recipient-versus-tumor (RVT) effect combining donor cells\u2019 graft-versus-tumor (GVT) effect. Donor\u2019s stem cells, which have been processed, will also accelerate functional recovery of recipient\u2019s hematopoietic stem cells, greatly reducing infections and transplant-related mortality. Practices of microtransplantation has shown none  graft-versus-host disease  (GVHD) till present, thus  immunosuppressive drugs  for relieving GVHD wouldn't be necessary. Possible mechanisms of the successful avoidance of GVHD include donor cell microchimerism, less-toxic cells processed prior to transplantation, and the preservation of host immune system that is capable of resisting the GVH alloresponse. Moreover, as HLA-mismatched stem cells are employed, donor availability is extremely extended. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1445", "text": "Indications for microtransplantation are as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_1446", "text": "Hematologic Malignancies Tumors"}
{"_id": "WikiPedia_Hematology$$$corpus_1447", "text": "The cells employed are allogeneic peripheral blood stem cells. Matched HLA between donor and recipient is not necessary. The stem cells are collected from donor\u2019s blood through a process known as apheresis after a certain period of daily subcutaneous injections of Granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation. Fresh cells are infused to recipient for the first time, and then stored in a controlled-rate freezer. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1448", "text": "Donor\u2019s Requirements:"}
{"_id": "WikiPedia_Hematology$$$corpus_1449", "text": "In a randomized controlled trial from 2004 to 2009, 58 AML patients aged 60\u201388 years were randomly assigned to receive chemotherapy (control group; n=28) or it plus HLA-mismatched G-CSF\u2013mobilized donor peripheral blood stem cell (G-PBSC) (G-PBSC group/ Microtransplantation; n = 30). The complete remission rate was significantly higher in the G-PBSC group than in the control group (80.0% vs 42.8%); The median recovery times of neutrophils and platelets were 11 days and 14.5 days, respectively, in the G-PBSC group and 16 days and 20 days, respectively, in the control group after chemotherapy; The 2-year probability of disease-free survival (DFS) was significantly higher in the G-PBSC group than in the control group (38.9% vs 10.0%). [ 1 ]  No graft-versus-host disease was observed in any patient. [ 2 ]  Persistent donor microchimerism was successfully detected in all of the 4 female patients. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1450", "text": "In another long-term research from 2004\u20132011, 101 patients with AML-CR1 (9 to 65 years old) received Microtransplantation regimen. The 6-year leukemia-free survival (LFS) and overall survival (OS) rates were 84.4% and 89.5%, respectively, in the low-risk group, which were similar to the rates in the intermediate-risk group (59.2% and 65.2%, respectively); The 6-year LFS and OS were 76.4% and 82.1%, respectively, in patients who received a high dose of donor CD3+ T cells, which were significantly higher than the LFS and OS in patients who received a lower dose of donor CD3+ T cells (49.5% and 55.3%, respectively). [ 4 ]  No GVHD was observed in any of the patients. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1451", "text": "The positive results have also been verified by healthcare centers in Italy, [ 6 ]  America, [ 7 ]  Spain, [ 8 ]  etc."}
{"_id": "WikiPedia_Hematology$$$corpus_1452", "text": "Led by Dr. Huisheng Ai and his medical team at MST International Clinic for Leukemia in the 307th Hospital of Chinese People\u2019s Liberation Army located in Beijing, multicenter collaborative study on Microtransplantation has started since 2013 in nine authoritative blood institutes from China, Duke University and Keck School of Medicine-University of Southern California in United States, University of Sydney in Australia and University of Montreal in Canada. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1453", "text": "To overcome the intolerable severe reactions of high-dose chemotherapy and GVHD, as well as the challenge to find HLA-matched donors for conventional hematopoietic stem cell transplantation, Dr  Huisheng Ai ,  Guo Mei , etc. developed a new regimen of reduced-intensity chemotherapy plus G-CSF mobilized HLA-mismatched allogeneic peripheral blood stem cell infusion, which was firstly employed for a 75-year-old patient in 2002 and later named as microtransplantation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1454", "text": "Mixed autoimmune hemolytic anemia  ( MAIHA ) is a type of  autoimmune hemolytic anemia  which combines the features of  cold sensitive antibody -induced diseases and  warm autoimmune hemolytic anemia . The work-up for diagnosis is complex and the condition can be over-diagnosed. [ 1 ] [ 2 ] [ better\u00a0source\u00a0needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1455", "text": "People diagnosed with warm autoimmune hemolytic anemia (WAIHA) caused by  immunoglobulin G  (IgG) [ 3 ]  may also have a high number of  immunoglobulin M  ( IgM ) antibodies. These antibodies are active at room temperature, but are believed to be harmless since they are not the main antibodies responsible for WAIHA. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1456", "text": "However, studies revealed the existence of a few cases of WAIHA that may also carry  cold agglutinin antibodies  that are active at the environment where the temperatures is generally equal to or warmer than 30\u00a0\u00b0C (86\u00a0\u00b0F). Such coexistence suggests a diagnosis of the mixed (warm- and cold-antibody) autoimmune hemolytic anemia abbreviated as  MAIHA . [ 4 ] [ better\u00a0source\u00a0needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1457", "text": "Mixed warm and cold AIHA runs a chronic course with severe intermittent exacerbations, such as serious anemia, and is treated by  blood transfusion . Successful therapeutic options for the treatment of hemolysis associated with mixed AIHA are limited but increasing. [ 5 ] [ non-primary source needed ] [ 6 ] [ better\u00a0source\u00a0needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1458", "text": "In the past, there were two obvious sources of error regarding the diagnosis of AIHA. First, patients with w-AIHA can produce low- titer , low-thermal amplitude CA of no clinical significance. Second, up to 20% of patients with CAD have IgG on the RBC surface in addition to C3d. [ 7 ] [ 1 ] [ 6 ] [ non-primary source needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1459", "text": "A  myeloma protein  is an abnormal  antibody  (immunoglobulin) or (more often) a fragment thereof, such as an  immunoglobulin light chain , that is produced in excess by an abnormal  monoclonal  proliferation of  plasma cells , typically in  multiple myeloma  or  Monoclonal gammopathy of undetermined significance . Other terms for such a protein are  monoclonal protein ,  M protein ,  M component ,  M spike ,  spike protein , or  paraprotein . This proliferation of the myeloma protein has several deleterious effects on the body, including impaired immune function, abnormally high  blood viscosity   (\"thickness\" of the blood), and  kidney damage ."}
{"_id": "WikiPedia_Hematology$$$corpus_1460", "text": "In 1940, senior  pathologist   Kurt Apitz  of the   Charit\u00e9 \u2013 Berlin University Medicine  hospital, introduced the concept and word  paraprotein . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1461", "text": "Myeloma is a  malignancy  of plasma cells.  Plasma cells produce immunoglobulins, which are commonly called antibodies.  There are thousands of different antibodies, each consisting of pairs of heavy and light chains.  Antibodies are typically grouped into five classes:  IgA, IgD, IgE, IgG, and IgM.  When someone has myeloma, a malignant clone, a rogue plasma cell, reproduces in an uncontrolled fashion, resulting in overproduction of the specific antibody the original cell was generated to produce.  Each type of antibody has a different number of light chain and heavy chain pairs.  As a result, there is a characteristic normal distribution of these antibodies in the blood by molecular weight."}
{"_id": "WikiPedia_Hematology$$$corpus_1462", "text": "When there is a malignant clone, there is usually overproduction of a single antibody, resulting in a \"spike\" on the normal distribution (sharp peak on the graph), which is called an M spike (or monoclonal spike).  People will sometimes develop a condition called MGUS ( Monoclonal gammopathy of undetermined significance ), where there is overproduction of one antibody but the condition is benign (non-cancerous).  An explanation of the difference between multiple myeloma and MGUS can be found in the International Myeloma Foundation's Patient Handbook. [ 2 ]  and Concise Review [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1463", "text": "Detection of paraproteins in the  urine  or  blood  is most often associated with MGUS, where they remain \"silent\", [ 4 ]  and  multiple myeloma . An excess in the blood is known as  paraproteinemia . Paraproteins form a narrow band, or 'spike' in  protein electrophoresis  as they are all exactly the same protein. Unlike normal immunoglobulin antibodies, paraproteins cannot fight infection."}
{"_id": "WikiPedia_Hematology$$$corpus_1464", "text": "Serum free light-chain measurement  can detect free light chains in the blood. Monoclonal free light chains in the serum or urine are called  Bence Jones proteins ."}
{"_id": "WikiPedia_Hematology$$$corpus_1465", "text": "Blood serum  paraprotein levels of more than 30 g/L is diagnostic of  smouldering myeloma , an intermediate in a spectrum of step-wise progressive diseases termed  plasma cell dyscrasias . Elevated paraprotein level (above 30 g/L) in conjunction with end organ damage (elevated calcium,  kidney failure , anemia, or bone lesions) or other biomarkers of malignancy, is diagnostic of  multiple myeloma , according to the diagnostic criteria of the  International Myeloma Working Group , [ 5 ]  which were updated in 2014. [ 6 ]  Detection of paraprotein in serum of less than 30 g/L is classified as  monoclonal gammopathy of undetermined significance  in cases where clonal plasma cells constitute less than 10% on bone marrow biopsy and there is no myeloma-related organ or tissue impairment. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1466", "text": "Neonates are defined as babies up to 28 days after birth. [ 1 ]  Most extremely preterm babies (less than 28 weeks) require at least one red cell transfusion; [ 2 ]  this is partly due to the amount of blood removed with blood samples compared to the baby's total blood volume (iatrogenic anemia) [ 3 ]  and partly due to  anemia of prematurity . Most transfusions are given as small volume top-up transfusions to increase the baby's  hemoglobin  above a certain pre-defined level, or because the baby is unwell due to the  anemia . [ 2 ]  Possible side-effects of anemia in babies can be poor growth,  lethargy  and episodes of  apnea . Exchange blood transfusion is used to treat a rapidly rising  bilirubin  that does not respond to treatment with  phototherapy  or  intravenous immunoglobulin . [ 4 ]  This is usually due to  hemolytic disease of the newborn , but may also be due to other causes, e.g.,  G6PD deficiency ."}
{"_id": "WikiPedia_Hematology$$$corpus_1467", "text": "Below are suggested transfusion thresholds for very preterm neonates (less than 32 weeks gestation) by the British Society of Haematology. [ 2 ]  These are based on systematic reviews of transfusion in very preterm babies. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1468", "text": "Hb g/L"}
{"_id": "WikiPedia_Hematology$$$corpus_1469", "text": "There is no evidence for red cell transfusion thresholds in preterm neonates between 32 and 37 weeks gestation, and the British Society of Haematology suggests using the same thresholds as very preterm neonates that require no respiratory support. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1470", "text": "A small volume transfusion is usually 10 to 20 ml/kg administered at a rate of 5 ml/kg/hour. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1471", "text": "A large volume transfusion is the estimated entire blood volume of the baby (80 ml/kg) and is usually given during cardiac surgery. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1472", "text": "A red cell exchange transfusion is usually given to treat severe  hyperbilirubinemia  or anemia in babies with  hemolytic disease of the newborn . It removes neonatal red cells coated with maternal antibody and reduces the level of bilirubin. A \u2018double volume exchange\u2019 (160\u2013200 ml/kg) removes around 90% of neonatal red cells and 50% of bilirubin. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1473", "text": "The specification of the blood product differs depending on whether it is to be used for a small volume, large volume or exchange transfusion. [ 1 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1474", "text": "There does not appear to be any benefit to giving fresher red blood cells (less than a week from donation) compared to standard red cells (usually two weeks after donation) for small volume transfusions. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1475", "text": "The  Serious Hazards of Transfusion  (SHOT) hemovigilance reporting scheme has shown that there are a disproportionate number of transfusion errors in babies. There are multiple reasons why this occurs. [ 9 ]  It can be due to confusion between samples from the mother and the baby, birth of more than one baby, babies who don\u2019t yet have a first name, or that no ID information has been attached to the baby (e.g. wristband). [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1476", "text": "Paedipacks are multiple aliquots made from one adult blood donation. By using paedipacks, the baby is exposed to blood from fewer blood donors. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1477", "text": "ABO  blood grouping and screening for antibodies in neonates differs from blood grouping in adults and older children. [ 8 ]  Any antibodies detected are the mother's antibodies rather than the baby's. [ 8 ]  Therefore, any donor blood given to the baby must be ABO and D compatible with both mother and baby; and antigen-negative for any clinically significant maternal antibodies. [ 2 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1478", "text": "Necrotising enterocolitis  may occur after a red cell transfusion in neonates, although there is an association between the two there is no evidence that the transfusion causes the disorder. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1479", "text": "The  oxygen\u2013hemoglobin dissociation curve , also called the  oxyhemoglobin dissociation curve  or  oxygen dissociation curve  ( ODC ), is a  curve  that plots the proportion of  hemoglobin  in its saturated (oxygen-laden) form on the vertical axis against the prevailing  oxygen tension  on the horizontal axis. This curve is an important tool for understanding how our blood carries and releases oxygen. Specifically, the oxyhemoglobin dissociation curve relates  oxygen saturation  (S O 2 ) and  partial pressure  of oxygen in the blood (P O 2 ), and is determined by what is called \"hemoglobin affinity for oxygen\"; that is, how readily hemoglobin acquires and releases oxygen molecules into the fluid that surrounds it."}
{"_id": "WikiPedia_Hematology$$$corpus_1480", "text": "Hemoglobin  (Hb) is the primary vehicle for transporting  oxygen  in the  blood . Each hemoglobin molecule has the capacity to carry four oxygen molecules. These molecules of oxygen bind to the globin chain of the  heme   prosthetic group . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1481", "text": "When hemoglobin has no bound oxygen, nor bound  carbon dioxide , it has the unbound conformation (shape). The binding of the first oxygen molecule induces change in the shape of the hemoglobin that increases its ability to bind to the other three oxygen molecules."}
{"_id": "WikiPedia_Hematology$$$corpus_1482", "text": "In the presence of dissolved carbon dioxide, the  pH  of the blood changes; this causes another change in the shape of hemoglobin, which increases its ability to bind carbon dioxide and decreases its ability to bind oxygen. With the loss of the first oxygen molecule, and the binding of the first carbon dioxide molecule, yet another change in shape occurs, which further decreases the ability to bind oxygen, and increases the ability to bind carbon dioxide. The oxygen bound to the hemoglobin is released into the blood's plasma and absorbed into the  tissues , and the carbon dioxide in the tissues is bound to the hemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_1483", "text": "In the  lungs  the reverse of this process takes place. With the loss of the first carbon dioxide molecule the shape again changes and makes it easier to release the other three carbon dioxides."}
{"_id": "WikiPedia_Hematology$$$corpus_1484", "text": "Oxygen is also carried dissolved in the blood's  plasma , but to a much lesser degree. Hemoglobin is contained in  red blood cells . Hemoglobin releases the bound oxygen when  carbonic acid  is present, as it is in the tissues. In the  capillaries , where  carbon dioxide  is produced, oxygen bound to the hemoglobin is released into the blood's plasma and absorbed into the tissues."}
{"_id": "WikiPedia_Hematology$$$corpus_1485", "text": "How much of that capacity is filled by oxygen at any time is called the  oxygen saturation . Expressed as a percentage, the oxygen saturation is the ratio of the amount of oxygen bound to the hemoglobin, to the oxygen-carrying capacity of the hemoglobin. The oxygen-carrying capacity of hemoglobin is determined by the type of hemoglobin present in the blood. The amount of oxygen bound to the hemoglobin at any time is related, in large part, to the  partial pressure  of oxygen to which the hemoglobin is exposed. In the lungs, at the  alveolar\u2013capillary interface , the partial pressure of oxygen is typically high, and therefore the oxygen binds readily to hemoglobin that is present. As the blood circulates to other body tissue in which the partial pressure of oxygen is less, the hemoglobin releases the oxygen into the tissue because the hemoglobin cannot maintain its full bound capacity of oxygen in the presence of lower oxygen partial pressures."}
{"_id": "WikiPedia_Hematology$$$corpus_1486", "text": "The curve is usually best described by a  sigmoid  plot, using a formula of the kind:"}
{"_id": "WikiPedia_Hematology$$$corpus_1487", "text": "A hemoglobin molecule can bind up to four oxygen molecules in a reversible method."}
{"_id": "WikiPedia_Hematology$$$corpus_1488", "text": "The shape of the curve results from the interaction of bound oxygen molecules with incoming molecules. The binding of the first molecule is difficult. However, this facilitates the binding of the second, third and fourth, this is due to the induced conformational change in the structure of the hemoglobin molecule induced by the binding of an oxygen molecule."}
{"_id": "WikiPedia_Hematology$$$corpus_1489", "text": "In its simplest form, the oxyhemoglobin dissociation curve describes the relation between the partial pressure of oxygen (x axis) and the oxygen saturation (y axis). Hemoglobin's affinity for oxygen increases as successive molecules of oxygen bind. More molecules bind as the oxygen partial pressure increases until the maximum amount that can be bound is reached. As this limit is approached, very little additional binding occurs and the curve levels out as the hemoglobin becomes saturated with oxygen. Hence the curve has a sigmoidal or S-shape. At pressures above about 60\u00a0mmHg, the standard dissociation curve is relatively flat, which means that the oxygen content of the blood does not change significantly even with large increases in the oxygen partial pressure. To get more oxygen to the tissue would require blood transfusions to increase the hemoglobin count (and hence the oxygen-carrying capacity), or supplemental oxygen that would increase the oxygen dissolved in plasma.\nAlthough binding of oxygen to hemoglobin continues to some extent for pressures about 50\u00a0mmHg, as oxygen partial pressures decrease in this steep area of the curve, the oxygen is unloaded to peripheral tissue readily as the hemoglobin's affinity diminishes.\nThe partial pressure of oxygen in the blood at which the hemoglobin is 50% saturated, typically about 26.6\u00a0mmHg (3.5\u00a0kPa) for a healthy person, is known as the  P 50 . The P 50  is a conventional measure of hemoglobin affinity for oxygen. In the presence of disease or other conditions that change the hemoglobin oxygen affinity and, consequently, shift the curve to the right or left, the P 50  changes accordingly. An increased P 50  indicates a rightward shift of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation. This indicates a decreased affinity. Conversely, a lower P 50  indicates a leftward shift and a higher affinity."}
{"_id": "WikiPedia_Hematology$$$corpus_1490", "text": "The 'plateau' portion of the oxyhemoglobin dissociation curve is the range that exists at the pulmonary capillaries (minimal reduction of oxygen transported until the p(O 2 ) falls 50\u00a0mmHg)."}
{"_id": "WikiPedia_Hematology$$$corpus_1491", "text": "The 'steep' portion of the oxyhemoglobin dissociation curve is the range that exists at the systemic capillaries (a small drop in systemic capillary p(O 2 ) can result in the release of large amounts of oxygen for the metabolically active cells)."}
{"_id": "WikiPedia_Hematology$$$corpus_1492", "text": "To see the relative affinities of each successive oxygen as you remove/add oxygen from/to the hemoglobin from the curve compare the relative increase/decrease in p(O 2 ) needed for the corresponding increase/decrease in s(O 2 )."}
{"_id": "WikiPedia_Hematology$$$corpus_1493", "text": "The strength with which oxygen binds to hemoglobin is affected by several factors. These factors shift or reshape the oxyhemoglobin dissociation curve. A  shift to right indicates that the hemoglobin under study has a decreased affinity for oxygen. This makes it more difficult for hemoglobin to bind to oxygen (requiring a higher partial pressure of oxygen to achieve the same oxygen saturation), but it makes it easier for the hemoglobin to release oxygen bound to it. \nThe effect of this shift of the curve increases the partial pressure of oxygen in the tissues when it is most needed, such as during exercise, or hemorrhagic shock."}
{"_id": "WikiPedia_Hematology$$$corpus_1494", "text": "In contrast, the curve is shifted to the left by the opposite of these conditions."}
{"_id": "WikiPedia_Hematology$$$corpus_1495", "text": "This shift indicates that the hemoglobin under study has an increased affinity for oxygen so that hemoglobin binds oxygen more easily, but unloads it more reluctantly.\nLeft shift of the curve is a sign of hemoglobin's increased affinity for oxygen (e.g. at the lungs)."}
{"_id": "WikiPedia_Hematology$$$corpus_1496", "text": "Similarly, right shift shows decreased affinity, as would appear with an increase in either body temperature, hydrogen ions,  2,3-bisphosphoglycerate  (2,3-BPG) concentration or carbon dioxide concentration."}
{"_id": "WikiPedia_Hematology$$$corpus_1497", "text": "Note:"}
{"_id": "WikiPedia_Hematology$$$corpus_1498", "text": "The causes of shift to right can be remembered using the  mnemonic , \" CADET , face Right!\" for  C O 2 ,  A cid, 2,3- D PG, [ Note 1 ]   E xercise and  T emperature. [ 2 ]  Factors that move the oxygen dissociation curve to the right are those physiological states where tissues need more oxygen. For example, during exercise, muscles have a higher metabolic rate, and consequently need more oxygen, produce more carbon dioxide and lactic acid, and their temperature rises."}
{"_id": "WikiPedia_Hematology$$$corpus_1499", "text": "A decrease in pH (increase in  \u200a H +  ion concentration) shifts the standard curve to the right, while an increase shifts it to the left. This occurs because at greater  \u200a H +  ion concentration, various amino acid residues, such as Histidine 146 exist predominantly in their protonated form allowing them to form ion pairs that stabilize deoxyhemoglobin in the T state. [ 3 ]  The T state has a lower affinity for oxygen than the R state, so with increased acidity, the hemoglobin binds less O 2  for a given P O2  (and more H + ). This is known as the  Bohr effect . [ 4 ]  A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the  root effect . This is seen in bony fish. The binding affinity of hemoglobin to O 2  is greatest under a relatively high pH."}
{"_id": "WikiPedia_Hematology$$$corpus_1500", "text": "Carbon dioxide  affects the curve in two ways. First, CO 2  accumulation causes  carbamino  compounds to be generated through chemical interactions, which bind to hemoglobin forming  carbaminohemoglobin . CO 2  is considered an  Allosteric regulation  as the inhibition happens not at the binding site of hemoglobin. [ 5 ]  Second, it influences  intracellular pH  due to formation of bicarbonate ion. Formation of carbaminohemoglobin stabilizes T state hemoglobin by formation of ion pairs. [ 3 ]  Only about 5\u201310% of the total CO 2  content of blood is transported as carbamino compounds, whereas (80\u201390%) is transported as bicarbonate ions and a small amount is dissolved in the plasma. The formation of a bicarbonate ion will release a proton into the plasma, decreasing pH (increased acidity), which also shifts the curve to the right as discussed above; low CO 2  levels in the blood stream results in a high pH, and thus provides more optimal binding conditions for hemoglobin and O 2 . This is a physiologically favored mechanism, since hemoglobin will drop off more oxygen as the concentration of carbon dioxide increases dramatically where tissue respiration is happening rapidly and oxygen is in need. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1501", "text": "2,3-Bisphosphoglycerate or 2,3-BPG (formerly named 2,3-diphosphoglycerate or 2,3-DPG) is an organophosphate formed in  red blood cells  during  glycolysis  and is the  conjugate base  of  2,3-bisphosphoglyceric acid . The production of 2,3-BPG is likely an important adaptive mechanism, because the production increases for several conditions in the presence of diminished peripheral tissue O 2  availability, such as  hypoxemia , chronic lung disease,  anemia , and  congestive heart failure , among others, which necessitate easier oxygen unloading in the peripheral tissue. High levels of 2,3-BPG shift the curve to the right (as in childhood), while low levels of 2,3-BPG cause a leftward shift, seen in states such as  septic shock , and  hypophosphataemia . [ 4 ]  In the absence of 2,3-BPG, hemoglobin's affinity for oxygen increases. 2,3-BPG acts as a  heteroallosteric effector  of hemoglobin, lowering hemoglobin's affinity for oxygen by binding preferentially to deoxyhemoglobin. An increased concentration of BPG in red blood cells favours formation of the T (taut or tense), low-affinity state of hemoglobin and so the oxygen-binding curve will shift to the right."}
{"_id": "WikiPedia_Hematology$$$corpus_1502", "text": "Increase in temperature shifts the oxygen dissociation curve to the right. When temperature is increased keeping the oxygen concentration constant, oxygen saturation decreases as the bond between oxygen and iron gets denatured. Additionally, with increased temperature, the partial pressure of oxygen increases as well. So, one will have a lesser amount of hemoglobin saturated for the same oxygen concentration but at a higher partial pressure of oxygen. Thus, any point in the curve will shift rightwards (due to increased partial pressure of oxygen) and downwards (due to weakened  \n \n \n \n \n Hb \n \n \u2212 \n \n \n O \n \n 2 \n \n \n \n \n \n \n \n \n {\\displaystyle {\\ce {Hb-O2}}} \n \n bond), hence, the rightward shift of the curve. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1503", "text": "Hemoglobin binds with  carbon monoxide  210 times more readily than with oxygen. [ 4 ]  Because of this higher affinity of hemoglobin for carbon monoxide than for oxygen, carbon monoxide is a highly successful competitor that will displace oxygen even at minuscule partial pressures. The reaction HbO 2  + CO \u2192 HbCO + O 2  almost irreversibly displaces the oxygen molecules forming  carboxyhemoglobin ; the binding of the carbon monoxide to the iron centre of hemoglobin is much stronger than that of oxygen, and the binding site remains blocked for the remainder of the life cycle of that affected red blood cell. [ 9 ]   With an increased level of carbon monoxide, a person can suffer from severe tissue  hypoxia  while maintaining a normal pO 2  because carboxyhemoglobin does not carry oxygen to the tissues."}
{"_id": "WikiPedia_Hematology$$$corpus_1504", "text": "Methemoglobinaemia  is a form of abnormal hemoglobin where the iron centre has been oxidised from the  ferrous +2   oxidation state  (the normal form, which on binding with oxygen changes to the ferric state) to the  ferric +3  state. This causes a leftward shift in the oxygen hemoglobin dissociation curve, as any residual heme with oxygenated ferrous iron (+2 state) is unable to unload its bound oxygen into tissues (because 3+ iron impairs hemoglobin's cooperativity), thereby increasing its affinity with oxygen. However, methemoglobin has increased affinity for  cyanide , and is therefore useful in the treatment of  cyanide poisoning . In cases of accidental ingestion, administration of a  nitrite  (such as  amyl nitrite ) can be used to deliberately oxidise hemoglobin and raise methemoglobin levels, restoring the functioning of  cytochrome oxidase . The nitrite also acts as a  vasodilator , promoting the cellular supply of oxygen, and the addition of an iron salt provides for competitive binding of the free cyanide as the biochemically inert  hexacyanoferrate(III)  ion, [Fe(CN) 6 ] 3\u2212 . An alternative approach involves administering  thiosulfate , thereby converting cyanide to  thiocyanate , SCN \u2212 , which is excreted  via  the kidneys.  Methemoglobin is also formed in small quantities when the dissociation of oxyhemoglobin results in the formation of methemoglobin and  superoxide , O 2 \u2212 , instead of the usual products. Superoxide is a  free radical  and causes biochemical damage, but is neutralised by the action of the enzyme  superoxide dismutase ."}
{"_id": "WikiPedia_Hematology$$$corpus_1505", "text": "Myo-inositol trispyrophosphate  (ITPP), also known as OXY111A, is an  inositol phosphate  that causes a rightward shift in the oxygen hemoglobin dissociation curve through  allosteric modulation  of hemoglobin within red blood cells.  It is an experimental drug intended to reduce tissue  hypoxia .  The effects appear to last roughly as long as the affected red blood cells remain in circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_1506", "text": "Fetal hemoglobin  (HbF) is structurally different from normal  adult hemoglobin  (HbA), giving HbF a higher affinity for oxygen than HbA.  HbF is composed of two alpha and two gamma chains whereas HbA is composed of two alpha and two beta chains.  The fetal dissociation curve is shifted to the left relative to the curve for the normal adult because of these structural differences:"}
{"_id": "WikiPedia_Hematology$$$corpus_1507", "text": "In adult hemoglobin, the binding of 2,3-bisphosphoglycerate (2,3-BPG) primarily occurs with the beta chains, preventing the binding of oxygen with haemoglobin. This binding is crucial for stabilizing the  deoxygenated state of hemoglobin, promoting the efficient release of oxygen to body tissues."}
{"_id": "WikiPedia_Hematology$$$corpus_1508", "text": "In fetal hemoglobin, which possesses a gamma chain instead of a beta chain, the interaction with 2,3-BPG differes because 2,3 - -BPG not binds with gamma chain as it has lower to no affinity with gamma chain.This distinction contributes to fetal hemoglobin having a higher affinity for oxygen."}
{"_id": "WikiPedia_Hematology$$$corpus_1509", "text": "Typically, fetal arterial oxygen pressures are lower than adult arterial oxygen pressures.  Hence higher affinity to bind oxygen is required at lower levels of partial pressure in the fetus to allow diffusion of oxygen across the  placenta .  At the placenta, there is a higher concentration of  2,3-BPG  formed, and 2,3-BPG binds readily to beta chains rather than to alpha chains. As a result, 2,3-BPG binds more strongly to adult hemoglobin, causing HbA to release more oxygen for uptake by the fetus, whose HbF is unaffected by the 2,3-BPG. [ 10 ]  HbF then delivers that bound oxygen to tissues that have even lower partial pressures where it can be released."}
{"_id": "WikiPedia_Hematology$$$corpus_1510", "text": "Red blood cell concentrates , also known as red cell concentrates or packed red blood cells, are  red blood cells  that have been separated for  blood transfusion . [ 1 ]  A red blood cell concentrate typically has a haematocrit of 0.50 \u2013 0.70 L/L and a volume between 250 and 320 mL. Transfusion of red blood cell concentrates is indicated to compensate for a deficit caused by critical bleeding or to correct anaemic conditions, in order to increase the oxygen-carrying capacity and avoid detrimental effects caused by oxygen debt. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1511", "text": "In adults, one unit brings up hemoglobin levels by about 10 g/L (1 g/dL). [ 3 ] [ 4 ]  Repeated transfusions may be required in people receiving  cancer chemotherapy  or who have  haemoglobin disorders .  Cross-matching  may be required before the blood is given. [ 1 ]  A red blood cell concentrate is given by  injection into a vein . [ 5 ]  The widespread use of red blood cell concentrates as part of blood component therapy began in the middle of the 20th century, when polyvinyl chloride (PVC) blood bags were introduced as storage containers. [ 6 ]  Transfusion is on the  World Health Organization's List of Essential Medicines . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1512", "text": "The widespread use of packed red blood cells began in the 1960s. [ 8 ]  It is on the  World Health Organization's List of Essential Medicines . [ 9 ] [ 10 ]  A number of other versions also exist including whole blood,  leukocyte reduced red blood cells , and  washed red blood cells . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1513", "text": "Red blood cells are used to restore oxygen-carrying capacity in people with  anaemia  due to trauma or other medical problems"}
{"_id": "WikiPedia_Hematology$$$corpus_1514", "text": "Whenever a red blood cell transfusion is being considered for a patient, it is good practice to consider not only the haemoglobin level, but also the overall clinical context, patient preferences, and whether there are alternative treatments. If a patient is stable and has a haematinic deficiency, they should be treated for the deficiency ( iron deficiency ,  B 12  deficiency , or  folate deficiency ) rather than being given a red blood cell transfusion. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1515", "text": "In adults, blood transfusion is typically recommended when hemoglobin levels are below 70 g/L (7 g/dL) in those who have stable vital signs, unless they have anemia due to a  haematinic  deficiency. Transfusing at a restrictive haemoglobin threshold of between 70 g/L to 80 g/L (7 to 8g/dL) decreased the proportion of people given a red blood cell transfusion by 41% across a broad range of clinical specialties, including those people who are critically ill. There is no evidence that a restrictive transfusion strategy are stronger associated with death or major adverse events (e.g. cardiac events,  myocardial infarction ,  stroke ,  pneumonia ,  thromboembolism , infection) compared with a liberal transfusion strategy. There is not enough information in some patient groups to say whether a restrictive or liberal transfusion threshold is better. [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1516", "text": "This refers to transfusing a  single unit  or bag of red blood cells to a person who is not bleeding and haemodynamically stable followed by an assessment to see if further transfusion is required. [ 15 ] [ 16 ]  The benefits of single unit transfusion include reduced exposure to blood products. Each unit transfused increases the associated risks of transfusion such as infection,  transfusion associated circulatory overload  and other side effects. [ 17 ] [ 18 ]  Transfusion of a single unit also encourages less wastage of red blood cells. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1517", "text": "In adults with  upper gastrointestinal bleeding  transfusing at a higher threshold caused harm (increased risk of death and bleeding). [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1518", "text": "A review established that in patients undergoing heart surgery a restrictive transfusion strategy of 70 to 80\u00a0g/L (7 to 8\u00a0g/dL) is safe and decreased red cell use by 24%. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1519", "text": "There is less evidence available for the optimal transfusion threshold for people with heart disease, including those who are having a heart attack. [ 22 ] [ 21 ] [ 23 ]  Guidelines recommend a higher threshold for people with  heart disease  of 80\u00a0g/L (8\u00a0g/dL) if they are not undergoing cardiac surgery. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1520", "text": "There is insufficient evidence to suggest how to manage anemia in people with blood cancers in terms of transfusion thresholds. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1521", "text": "People with  thalassaemia  who are transfusion dependent require a higher hemoglobin threshold to suppress their own red cell production. To do this their hemoglobin levels should not be allowed to drop below 90 to 105\u00a0g/L (9 to 10.5\u00a0g/dL). [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1522", "text": "There is insufficient evidence to recommend a particular hemoglobin threshold in people with  myelodysplasia  or  aplastic anemia , [ 28 ]  and guidelines recommend an individualized approach to transfusion. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1523", "text": "There is less evidence for specific transfusion thresholds in children compared to adults. [ 22 ] [ 24 ]  There has only been one randomized trial assessing different thresholds in children, and this showed no difference between a restrictive or liberal transfusion strategy. [ 29 ]  This trial used similar thresholds to the adult studies, and transfusing when the hemoglobin is less than 70\u00a0g/L is also recommended in children. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1524", "text": "Neonatal red cell transfusion , and when it is appropriate depends on: the gestational age of the baby; how long since the baby had been born; and also on whether the baby is well or ill. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1525", "text": "To avoid transfusion reactions, the donor and recipient blood are tested, typically ordered as a \"type and screen\" for the recipient. The \"type\" in this case is the  ABO  and  Rh  type, specifically the  phenotype , and the \"screen\" refers to testing for atypical antibodies that might cause transfusion problems. The typing and screening are also performed on donor blood. The blood groups represent  antigens  on the surface of the red blood cells which might react with  antibodies  in the recipient. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1526", "text": "The ABO blood group system has four basic phenotypes: O, A, B, and AB. In the former  Soviet Union  these were called I, II, III, and IV, respectively. There are two important antigens in the system: A and B. Red cells without A or B are called type O, and red cells with both are called AB. Except in unusual cases like infants or seriously  immunocompromised  individuals, all people will have antibodies to any ABO blood type that isn't present on their own red blood cells, and will have an immediate hemolytic reaction to a unit that is not compatible with their ABO type. In addition to the A and B antigens, there are rare variations which can further complicate transfusions, such as the  Bombay phenotype . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1527", "text": "The Rh blood group system consists of nearly around 50 different antigens, but the one of the greatest clinical interest is the \"D\" antigen, though it has  other names  and is commonly just called \"negative\" or \"positive\". Unlike the ABO antigens, a recipient will not usually react to the first incompatible transfusion because the  adaptive immune system  does not immediately recognize it. After an incompatible transfusion the recipient may develop an antibody to the antigen and will  react  to any further incompatible transfusions. This antibody is important because it is the most frequent cause of  hemolytic disease of the newborn . Incompatible red blood cells are sometimes given to recipients who will never become pregnant, such as males or postmenopausal women, as long as they do not have an antibody, since the greatest risk of Rh incompatible blood is to current or future pregnancies. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1528", "text": "For RBCs, type O negative blood is considered a \"universal donor\" as recipients with types A, B, or AB can almost always receive O negative blood safely. Type AB positive is considered a \"universal recipient\" because they can receive the other ABO/Rh types safely. These are not truly universal, as other red cell antigens can further complicate transfusions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1529", "text": "There are many other  human blood group systems  and most of them are only rarely associated with transfusion problems. A screening test is used to identify if the recipient has any antibodies to any of these other blood group systems. If the screening test is positive, a complex set of tests must follow to identify which antibody the recipient has by process of elimination. Finding suitable blood for transfusion when a recipient has multiple antibodies or antibodies to extremely common antigens can be very difficult and time-consuming. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1530", "text": "Because this testing can take time, doctors will sometimes order a unit of blood transfused before it can be completed if the recipient is in critical condition. Typically two to four units of O negative blood are used in these situations, since they are unlikely to cause a reaction. [ 32 ]  A potentially fatal reaction is possible if the recipient has pre-existing antibodies, and uncross matched blood is only used in dire circumstances. Since O negative blood is not common, other blood types may be used if the situation is desperate. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1531", "text": "Red blood cell concentrates are produced either from  whole blood  or by  apheresis . Production from whole blood is far more common than apheresis due to collection and production efficacy as well as economical purposes. When red blood cell concentrates are produced from whole blood, the whole blood is first separated through centrifugation (usually between 3000 to 5000 x  g ). The red blood cells are denser than plasma and the other present blood cells (platelets, white blood cells) and settle at the bottom of the blood bag. After centrifugation, the red blood cells are separated from the other components (the majority of the plasma, platelets and white blood cells) through the use of an extractor (also referred to as blood press)."}
{"_id": "WikiPedia_Hematology$$$corpus_1532", "text": "After extraction, an additive solution is usually added in a ratio of 1:1.5 to 1:2. The purpose of the additive solution is to maintain adequate viscosity, provide nutrients and ATP/GTP building blocks and reduce haemolysis generation throughout blood bank storage. Choice of additive solution has an impact on the red blood cell viability and, thereby, shelf life (expiry date) of the red blood cell concentrate. Usually, shelf life is limited to 4 to 6 weeks, provided that the red blood cell concentrates are stored in adequate conditions (2-6\u00a0\u00b0C). \u00a0Commercial additive solutions are typically based on saline. They usually contain glucose, adenine, mannitol and, sometimes, phosphate and guanosine. [ 33 ]  The additive solution has no, or very little, buffering capacity, but buffering is provided by the red blood cells themselves. Traditional additive solutions are hypotonic, although experiments with next-generation additive solutions suggest that an alkali pH in combination with low chloride concentrations may be able to prolong the red blood cell viability. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1533", "text": "Leucocyte depletion of blood components, including red blood cell concentrates, is increasingly becoming standard practise; in many of the high-income countries of the world, 100% of the red blood cell supply is already being leucocyte depleted. [ 35 ]  Leucocyte depletion, usually by a leucocyte filter included in the blood bag system, is an efficient yet relatively cheap way of reducing the risk of transfusion reactions. Leucocyte depletion is most commonly performed as an integrated processing step, as bedside filtration is considered a less efficient method. [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1534", "text": "Red blood cell concentrates are sometimes modified to address specific needs of patients who, for different reasons, are unable to tolerate standard red blood cell concentrates."}
{"_id": "WikiPedia_Hematology$$$corpus_1535", "text": "Even after leucocyte filtration, a residual number of leucocytes remain in the red blood cell concentrate (<1 x 10 6  per unit). [ 38 ]  These may be harmful for patients who have an impaired, reduced or not yet fully developed immune system, or if the blood donor and recipient are closely related. Therefore, such patients may be issued irradiated blood components, including irradiated red blood cells. [ 39 ] [ 40 ]  X-ray or gamma sources are usually used for irradiation. [ 40 ]  When blood components are irradiated, the DNA is destroyed in any remaining white blood cells (leucocytes), which stops the leucocytes from being able to proliferate further. Although efficient in reducing the risk of transfusion reactions including fatal transfusion-associated graft-versus-host disease (TA-GvHD), irradiation is damaging to the red blood cell membrane, which can be seen as increased levels of haemolysis during storage. As a consequence, irradiated red blood cell concentrates are usually given a reduced shelf life. Therefore, irradiation of red blood cell concentrates is commonly only performed on demand or for specific parts of the supply. [ 41 ] [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1536", "text": "Red blood cell concentrates still contain a small amount of plasma after standard processing (usually 10-15 mL). In order to reduce the risk of allergic reactions to plasma proteins, or to modify the red blood cell concentrates for patients who are sensitive to IgA or potassium ions (K + ), the red blood cell concentrates can be washed. [ 44 ] [ 45 ]  Washing typically consists of diluting the red blood cells in saline-based washing solution or red blood cell additive solutions and then washing away any remaining plasma and debris during one or several centrifugation cycles. The process can be performed manually, or with an automated cell washer or processor. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1537", "text": "To increase the availability of RBCs of rare blood types, red blood cells can be stored cryopreserved (frozen) instead of refrigerated. With a controlled, standardised freezing and thawing process, the red blood cells can be stored in frozen condition for up to 30 years. [ 38 ] [ 47 ]  Also for cryopreservation, cell processors are frequently used for both the pre-freezing glycerolisation procedure and for washing away the glycerol after thawing of the red blood cells. Using an automated device allows for standardised processing to ensure optimal protection from ice crystal formation, which otherwise could damage the red blood cells. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1538", "text": "There are two general approaches for RBC cryopreservation, referred to as the high- and the low-glycerol method. Glycerol serves as cryoprotectant in both. The high-glycerol method uses 40% weight/volume glycerol, a slow freezing rate (1\u20133\u00a0\u00b0C per minute) and allows storage of the frozen red blood cells in common mechanical \u221260\u201380\u00a0\u00b0C freezers. The low-glycerol method is based on 20% weight/volume glycerol and demands plunge freezing in (\u2212150\u00a0\u00b0C) liquid nitrogen. Because of the extreme storage temperature, the low-glycerol method is not compatible with the PVC tubes of blood bags. PVC tubes are essential for sterile docking; a technology which maintains a closed system after thawing and, thereby, allows a longer post-thawing shelf-life. Because of this, and also because the high-glycerol method seems to protect the red blood cells better and is associated with less haemolysis than the low-glycerol method, the high-glycerol method is often preferred. [ 49 ] [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1539", "text": "Pathogen reduction is a technology predominantly used to reduce the risk of transfusion-transmitted infectious diseases and bacterial contamination. The principle resembles the one of irradiation: by adding an agent which interferes with the replication process of DNA or RNA, any present pathogen, as well as any residual leucocytes, will not be able to replicate further. [ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1540", "text": "Systems for pathogen inactivation of red blood cells are still awaiting market authorisation. However, studies suggest that the red blood cell quality is not negatively impacted by this processing procedure, which indicates that pathogen inactivation may be a suitable future substitute for irradiation and potentially also washing of red blood cells. [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1541", "text": "Red blood cell rejuvenation is a method which aims to increase the levels of  2,3-diphosphoglycerate  (2,3-DPG) and  ATP  in stored red blood cell concentrates, as the levels of both 2,3-DPG and ATP decrease over time. The rejuvenation process includes incubation of the red blood cells with a rejuvenation solution and subsequent washing. [ 55 ]  ATP is an important driver of a number of metabolic functions of the red blood cell, and declined ATP levels have been linked to reduced post-transfusion  in vivo  survival of the red blood cells. High levels of 2,3-DPG facilitates oxygen unloading from the red blood cells in the capillaries. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1542", "text": "Red blood cell concentrates can be modified to be suitable for paediatric patients. These modifications include split of regular units into smaller units (usually 3 \u2013 6 parts), which facilitates limiting the number of involved donors at repeated transfusions. The modification can also be red blood cells for intrauterine transfusion where, in short, the additive solution is removed, which increases the haematocrit to between 0.70 \u2013 0.85. [ 38 ]  A red blood cell concentrate can also be tailored for exchange transfusions for neonates. During this process, the additive solution is removed and instead, plasma is added to resemble a \u201cwhole blood\u201d. Both at intrauterine and exchange transfusion, compatibility [ 1 ]  between the foetus/baby and the mother is of great importance."}
{"_id": "WikiPedia_Hematology$$$corpus_1543", "text": "Adverse events related to transfusion in general may include  allergic reactions  such as  anaphylaxis ,  infection ,  volume overload , and  lung injury . \u00a0With current screening methods, the risk of  viral infections  such as  hepatitis C  and  HIV/AIDS  are less than one in a million. [ 1 ]   With current testing methods in high-income countries the \u00a0prevalence of transfusion-transmissible infections in blood donations is very low (median: HIV 0.002%, hepatitis B 0.02%, hepatitis C 0.007% and syphilis 0.02% in 2024). However, in low-income countries the risk of a blood donation being positive for  HIV ,  hepatitis C  or  syphilis  is up to 1%, and the risk of it being  hepatitis B  positive was approximately 2.8% in 2024.\u00a0 The differences relate to variations in eligible blood donors, whether the donation is paid or voluntary, non-remunerated, and the effectiveness of the system of educating and selecting donors. [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1544", "text": "Adverse events related to transfusion of red blood cells are mainly linked to incompatibility issues or other transfusion reactions. Incompatible AB0 transfusion can be fatal. [ 58 ] \u00a0For patients with a previous transfusion reaction history, the risk of repeated adverse events can be mitigated by choosing the proper processing modification and/or red blood cell phenotype combination."}
{"_id": "WikiPedia_Hematology$$$corpus_1545", "text": "In the United Kingdom they cost about \u00a3120 per unit. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1546", "text": "The product is typically abbreviated  RBC ,  pRBC ,  PRBC , sometimes  StRBC , or even  LRBC  (the latter being to indicate those that have been leukoreduced, which is now true for the vast majority of RBC units). The name \"Red Blood Cells\" with initial capitals indicates a standardized blood product in the  United States . [ 60 ]  Without capitalization, it is simply generic without specifying whether or not the cells comprise a blood product, patient blood, etc. (with other generic terms for it being \"erythrocyte\" and \"red cell\"). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1547", "text": "Plasminogen activators  are  serine proteases  that catalyze the activation of  plasmin  via proteolytic cleavage of its  zymogen  form  plasminogen . Plasmin is an important factor in  fibrinolysis , the breakdown of  fibrin  polymers formed during blood clotting. There are two main plasminogen activators:  urokinase (uPA)  and  tissue plasminogen activator (tPA).  Tissue plasminogen activators are used to treat medical conditions related to blood clotting including embolic or thrombotic stroke, myocardial infarction, and pulmonary embolism. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1548", "text": "Plasminogen activators are inhibited by  plasminogen activator inhibitor-1 ,  plasminogen activator inhibitor-2 , and  protein C inhibitor ."}
{"_id": "WikiPedia_Hematology$$$corpus_1549", "text": "Produced mainly in the liver, plasminogen is the inactive zymogen form of plasmin, and circulates in plasma in a closed conformation that cannot be activated.  Binding clots or cell surfaces cause their conformation to change, allowing them to be activated by plasminogen activators. Plasminogen activators do so by cleaving the R561/V562 peptide bond, producing the active protein plasmin, which catalyzes the degradation of fibrin polymers that make up the structure of blood clots. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1550", "text": "The main inhibitor of tissue plasminogen activator and urokinase is plasminogen activator inhibitor-1 (PAI-1). [ 3 ]  Plasminogen activator inhibitor-1 is a serine protease, synthesized by endothelial cells, that specifically inhibits  tissue plasminogen activator  (tPA) and  urokinase  (uPA). Tissue plasminogen activator and urokinase are the activators of  plasminogen  and result in the breakdown of blood clots ( fibrinolysis ). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1551", "text": "PAI-1 levels have also been studied in patients and how they influence certain diseases. Elevated serum levels of PAI-1 have been found in obese individuals. [ 5 ]   Elevated levels of PAI-1 also seem to increase the risk of atherothrombotic events and may also promote vascular disease. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1552", "text": "Plasminogen activator inhibitor-2 (PAI-2) is a serine protease that inactivates tPA and uPA. PAI-2 is produced by the placenta and only found in high quantities in the blood during pregnancy. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1553", "text": "Factor XIa and XIIa are two main factors involved in the plasminogen activator. Factor XI (FXI) is a serine protase produced by the liver and circulates in its inactive form. [ 8 ]  Deficiency in factor XI is known to cause  hemophilia C . [ 9 ]   Factor XIIa is another plasma protein that is involved in the activation of zymogen factor is activated into factor XIa. [ 10 ]  This activation is important to the coagulation cascade."}
{"_id": "WikiPedia_Hematology$$$corpus_1554", "text": "Due to its contribution to fibrinolysis, tissue plasminogen activator is used medically to treat blood clot-related disorders including  thrombotic  or  embolic stroke ,  myocardial infarction , and  pulmonary embolism . It is manufactured using recombinant techniques and is sold as alteplase, reteplase, and tenecteplase.  Alteplase was the first of these versions to go on the market, and has the same structure as tPA.  Reteplase and tenecteplase both received FDA approval after alteplase, and have nonidentical structures to tPA. [ 1 ]  These recombinant forms of tPA have been shown to have a longer half-life in the blood and greater resistance to inhibition, resulting in  an increased capacity to treat thrombolytic diseases. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1555", "text": "Urokinase is similarly used in the medical field, specifically for the treatment of pulmonary embolism. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1556", "text": "1B2I ,  1BML ,  1BUI ,  1CEA ,  1CEB ,  1DDJ ,  1HPJ ,  1HPK ,  1I5K ,  1KI0 ,  1KRN ,  1L4D ,  1L4Z ,  1PK4 ,  1PKR ,  1PMK ,  1QRZ ,  1RJX ,  2DOH ,  2DOI ,  2KNF ,  2L0S ,  2PK4 ,  3UIR ,  4A5T ,  4CIK ,  4DCB ,  4DUR ,  4DUU ,  5HPG"}
{"_id": "WikiPedia_Hematology$$$corpus_1557", "text": "5340"}
{"_id": "WikiPedia_Hematology$$$corpus_1558", "text": "18815"}
{"_id": "WikiPedia_Hematology$$$corpus_1559", "text": "ENSG00000122194"}
{"_id": "WikiPedia_Hematology$$$corpus_1560", "text": "ENSMUSG00000059481"}
{"_id": "WikiPedia_Hematology$$$corpus_1561", "text": "P00747"}
{"_id": "WikiPedia_Hematology$$$corpus_1562", "text": "P20918"}
{"_id": "WikiPedia_Hematology$$$corpus_1563", "text": "NM_001168338 NM_000301"}
{"_id": "WikiPedia_Hematology$$$corpus_1564", "text": "NM_008877"}
{"_id": "WikiPedia_Hematology$$$corpus_1565", "text": "NP_000292 NP_001161810"}
{"_id": "WikiPedia_Hematology$$$corpus_1566", "text": "NP_032903"}
{"_id": "WikiPedia_Hematology$$$corpus_1567", "text": "Plasminogen activator inhibitor-1 not only functions as an inhibitor, but other roles of PAI-1 could suggest it could contribute to cancer. The other roles of PAI-1 include, cell de-adhesion, cell proliferation, apoptosis, and cell signaling. These roles could suggest that PAI-1 expression in the tumor microenvironment enhances tumor cell progression. Urokinase cleaves the zymogen plasminogen into serine protease plasmin. The elevated levels of uPA are an indicator of cancer which could be found in the carcinoma of the breast. Plasmin can activate matrix metalloproteases (MMP's) in the extracellular matrix (ECM). MMP activation contributes to tumor cell invasion and metastasis by degradation of ECM components. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1568", "text": "Platelet adhesiveness  is the adhesion of  platelets  to other structures. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1569", "text": "It can be contrasted with  platelet aggregation , [ citation needed ]  which refers to the processes or factors which lead to the adhesion of platelets to other platelets."}
{"_id": "WikiPedia_Hematology$$$corpus_1570", "text": "The  platelet plug,  also known as the  hemostatic plug  or  platelet thrombus , is an aggregation of  platelets  formed during early stages of  hemostasis  in response to one or more injuries to  blood vessel   walls . After platelets are recruited and begin to accumulate around the breakage, their \u201csticky\u201d nature allows them to adhere to each other. This forms a platelet plug, which prevents more blood from leaving the body as well as any outside contaminants from getting in. The plug provides a temporary blockage of the break in the vasculature. As such, platelet plug formation occurs after  vasoconstriction  of the blood vessels but before the creation of the fibrin mesh clot, which is the more permanent solution to the injury. The result of the platelet plug formation is the coagulation of blood. It can also be referred to as primary hemostasis."}
{"_id": "WikiPedia_Hematology$$$corpus_1571", "text": "For many years, the critical role that platelets (also known as thrombocytes) played in hemostasis and blood coagulation went unnoticed by scientists. Even though the existence of platelets as a cell fragment was initially discovered in 1882, it took scientists until the 1960s before they moved their interest from the interaction of platelets with blood coagulation to the interaction of platelets with themselves. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1572", "text": "The discovery of  adenosine diphosphate  (ADP) as the primary inducer of platelet aggregation was a major breakthrough in the field of hematology. [ 2 ]  It was followed by the discovery of the platelet release reaction, as well as the aggregating properties of  thrombin  and  collagen ."}
{"_id": "WikiPedia_Hematology$$$corpus_1573", "text": "The platelet plug formation is the second step of hemostasis. It occurs after vasoconstriction. During the process, platelets begin to accumulate, or aggregate, on the damaged vessel wall. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1574", "text": "Platelet plug formation occurs in three major steps:"}
{"_id": "WikiPedia_Hematology$$$corpus_1575", "text": "Under normal physiological conditions, blood flows through the body without any noticeable aggregation of platelets. This is because platelets are not initially programmed to accumulate by themselves because this could cause an undesirable thrombosis. However, during hemostasis, coagulation is desired. As such, the platelets in the plasma must be alerted to the need for a plug formation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1576", "text": "Any discontinuity detected in the vascular endothelium triggers an automatic response in the clotting system, which in turns stimulates thrombin production. [ 3 ]  Thrombin also causes platelet aggregation."}
{"_id": "WikiPedia_Hematology$$$corpus_1577", "text": "As such, more often than not, platelet adhesion and activation occur in overlapping steps, where one directly influences and contributes to the other."}
{"_id": "WikiPedia_Hematology$$$corpus_1578", "text": "Once platelets are activated, when they come across injured endothelium cells, the  von Willebrand factor (vWF)  and  fibrinogen  will act as anchors to allow platelets to adhere onto the vessel wall. [ 4 ]  These molecules are released from the platelet themselves as a result of degranulation, a physiological change in the platelet's shape due to the secretion of the contents of the dense granules and alpha granules. [ 4 ]  From the dense granules, serotonin and adenosine diphosphate are released. From the alpha granules come molecules such as the platelet-derived growth factor, fibrinogen, and the von Willebrand factor (vWF), a glycoprotein critical in platelet activation and adhesion. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1579", "text": "The ADP secreted from the dense granules then binds to receptors on the membrane of platelets. However, to allow for platelet adhesion to occur requires an additional molecule. Glycoprotein lb is a protein on the surface of the platelet membrane that binds to vWF. [ 3 ]  When vWF is bound to glycoprotein lb, it helps the platelet interact with other surfaces, like the inside of a damaged vessel wall. At high shear stress levels, the GP1b-von Willebrand Factor will initiate the platelet adhesion. [ 5 ]  This process will then be mediated by integrins, such as \u03b21 (\u03b12\u03b21, \u03b15\u03b21) and \u03b23 (\u03b1IIb\u03b23) integrins."}
{"_id": "WikiPedia_Hematology$$$corpus_1580", "text": "In addition, platelets are activated, they will also change shape in their cortical actin cytoskeleton. [ 6 ]  The platelets will transform from smooth, biconcave discs to fully spread cells. This dramatically increases their surface area and therefore allows for both increased blockage of the damaged cells as well as more space for adhesion to occur."}
{"_id": "WikiPedia_Hematology$$$corpus_1581", "text": "After platelets make contact with the focal point of the vascular injury, they begin to interact with each other to form a platelet aggregate. Platelet aggregation is mainly mediated by \u03b23 (\u03b1IIb\u03b23) integrin and its ligands, such as vWF and fibrinogen. [ 4 ]   While platelet membranes have binding sites for fibrinogen, they must be induced by thrombin. Thrombin triggers the binding of the adhesive platelets with vWF and fibrinogen. [ 4 ]  ADP can then catalyze the aggregation of platelets, allowing for fibrinogen to link two platelets together. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1582", "text": "As more platelets accumulate, they release more chemicals, which in turn attract even more platelets. This is a positive feedback loop that eventually results in the formation of the platelet thrombus."}
{"_id": "WikiPedia_Hematology$$$corpus_1583", "text": "A secondary hemostatic plug is formed after the temporary blockage is created. This process involves the conversion of fibrinogen, a soluble glycoprotein, into  fibrin , an insoluble glycoprotein, using the enzyme  thrombin . The fibrinogen forms fibrin to encase the platelet thrombus, thus creating a secondary hemostatic plug that is much more stable and securely attached to the vessel wall. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1584", "text": "Due to the shear force, a platelet thrombus attached to the blood vessel's walls can easily be swept away or disintegrated. As such, after the platelets have been anchored to the vessel wall, have been linked together, and have been enmeshed in fibrin, they must also be consolidated to ensure they can withstand such force. This is accomplished by  factor XIII , also known as fibrin stabilizing factor, an enzyme that crosslinks fibrin. Factor XIII is critical in the consolidation of a hemostatic plug. Those who are found to be deficient in the enzyme exhibit delayed bleeding after surgical procedures. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1585", "text": "While platelet activation and plug formation are necessary for the cessation of bleeding and vascular injuries, if platelet adhesion and aggregation occur in an unwarranted location, the result will instead be vascular obstruction and thrombosis. This is commonly observed in myocardial infarctions, in which platelet aggregation and adhesion result in a blocked coronary artery. [ 4 ]  As such, the same factors that cause platelets to coagulate during hemostasis can also contribute to unwanted thrombosis."}
{"_id": "WikiPedia_Hematology$$$corpus_1586", "text": "While the general mechanisms of hemostasis and platelet plug formation have already been discovered, there is still much to learn in terms of the chemicals contributing to the process. Only the key factors have been identified; there are still many molecules present during hemostasis that scientists do not understand the role they play. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1587", "text": "Fibrinogen and vWF are known critical factors in hemostasis. However, it has been discovered that even in mice who lack both of these components, hemostasis and thrombosis still occur. [ 4 ]  This seems to suggest that there are other contributing molecules still undiscovered that may also play an important role in platelet aggregation and adhesion."}
{"_id": "WikiPedia_Hematology$$$corpus_1588", "text": "Platelet-activating factor , also known as  PAF ,  PAF-acether  or  AGEPC  (acetyl-glyceryl-ether-phosphorylcholine), is a potent  phospholipid  activator and mediator of many  leukocyte  functions,  platelet  aggregation and degranulation,  inflammation , and  anaphylaxis . It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of  arachidonic acid  metabolism in phagocytes."}
{"_id": "WikiPedia_Hematology$$$corpus_1589", "text": "PAF is produced by a variety of cells, but especially those involved in host defense, such as  platelets ,  endothelial  cells,  neutrophils ,  monocytes , and  macrophages . PAF is continuously produced by these cells but in low quantities and production is controlled by the activity of  PAF acetylhydrolases . It is produced in larger quantities by inflammatory cells in response to specific stimuli. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1590", "text": "PAF was discovered by French immunologist  Jacques Benveniste  in the early 1970s. [ 2 ] [ 3 ]  PAF was the first  phospholipid  known to have messenger functions. Benveniste made significant contributions in the role and characteristics of PAF and its importance in inflammatory response and mediation. Using lab rats and mice, he found that ionophore  A23187  (a mobile ion carrier that allows the passage of Mn 2+ , Ca 2+  and Mg 2+  and has antibiotic properties against bacteria and fungi)  caused the release of PAF. These developments led to the finding that macrophages produce PAF and that macrophages play an important function in aggregation of platelets and liberation of their inflammatory and vasoactive substances. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1591", "text": "Further studies on PAF were conducted by Constantinos A. Demopoulos in 1979. [ 4 ]  Demopoulos found that PAF plays a crucial role in heart disease and strokes. His experiment\u2019s data found that  atherosclerosis  (the accumulation of lipid-rich lesions in the  endothelium  of the arteries) can be attributed to PAF and PAF-like lipids, and identified biologically active compounds in the  polar   lipid  fractions of  olive oil , honey,  milk  and  yoghurt ,  mackerel , and  wine  that have PAF-antagonistic properties and inhibit the development of atherosclerosis in animal models. [ 5 ]  During the course of his studies, he also determined the chemical structure of the compound."}
{"_id": "WikiPedia_Hematology$$$corpus_1592", "text": "PAF can be found in  protozoans ,  yeasts ,  plants ,  bacteria , and  mammals . PAF has regulatory role in protozoans. The regulatory role is thought to diverge from that point and be maintained as living organisms started to evolve. During evolution, functions of PAF in the cell have been changing and enlarging. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1593", "text": "PAF has been found in plants but its function has not yet been determined. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1594", "text": "PAF is used to transmit signals between neighboring cells and acts as a  hormone ,  cytokines , and other signaling molecules. The PAF signaling system can trigger inflammatory and  thrombotic  cascades, amplify these cascades when acting with other mediators, and mediate molecular and cellular interactions ( cross talk ) between inflammation and thrombosis. [ 6 ]   Unregulated PAF signaling can cause pathological inflammation and has been found to be a cause in  sepsis ,  shock , and traumatic injury. PAF can be used as a local signaling molecule and travel over very short distances or it can be circulated throughout the body and act via  endocrine ."}
{"_id": "WikiPedia_Hematology$$$corpus_1595", "text": "PAF initiates an inflammatory response in allergic reactions. [ 7 ]   This has been demonstrated in the skin of humans and in the paws and skin of lab rabbits and rodents. The inflammatory response is enhanced by the use of vasodilators, including prostaglandin E1 (PGE,) and PGE2 and inhibited by vasoconstrictors. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1596", "text": "PAF also induces apoptosis in a different way that is independent of the  PAF receptor . The pathway to apoptosis can be inhibited by negative feedback from PAF acetylhydrolase (PAF-AH), an enzyme that catabolizes platelet-activating factor."}
{"_id": "WikiPedia_Hematology$$$corpus_1597", "text": "It is an important mediator of  bronchoconstriction ."}
{"_id": "WikiPedia_Hematology$$$corpus_1598", "text": "It causes platelets to aggregate and blood vessels to dilate. Thus, it is important to the process of  hemostasis . At a concentration of 10 \u221212  mol/L, PAF causes life-threatening inflammation of the airways to induce  asthma  like symptoms."}
{"_id": "WikiPedia_Hematology$$$corpus_1599", "text": "Toxins  such as fragments of destroyed bacteria induce the synthesis of PAF, which causes a drop in  blood pressure  and reduced volume of blood pumped by the heart, which leads to  shock  and possibly death."}
{"_id": "WikiPedia_Hematology$$$corpus_1600", "text": "Several molecular species of platelet-activating factor that vary in the length of the O-alkyl side-chain have been identified."}
{"_id": "WikiPedia_Hematology$$$corpus_1601", "text": "Studies found that PAF could not be modified without losing its  biological activity . Thus, small changes in the structure of PAF could render its signaling abilities inert. [ 9 ]  Investigation led to the understanding that platelet and blood pressure response were dependent on the sn-2 propionyl analog. If the sn-1 was removed then PAF lacked any sort of biological activity. Finally, the sn-3 position of PAF was experimented with by removing methyl groups sequentially. As more and more methyl groups were removed, biological activity diminished until it was eventually inactive."}
{"_id": "WikiPedia_Hematology$$$corpus_1602", "text": "PAF is produced by stimulated basophils, monocytes, polymorphonuclear neutrophils, platelets, and endothelial cells primarily through lipid remodeling. A variety of stimuli can initiate the synthesis of PAF. These stimuli could be macrophages going through phagocytosis or endothelium cells uptake of thrombin."}
{"_id": "WikiPedia_Hematology$$$corpus_1603", "text": "There are two different pathways in which PAF can be synthesized:  de novo  pathway and remodeling. The remodeling pathway is activated by inflammatory agents and it is thought to be the primary source of PAF under pathological conditions. The  de novo  pathway is used to maintain PAF levels during normal cellular function."}
{"_id": "WikiPedia_Hematology$$$corpus_1604", "text": "The most common pathway taken to produce PAF is remodeling. The precursor to the remodeling pathway is a phospholipid, which is typically phosphatidylcholine (PC).  The fatty acid is removed from the sn-2 position of the three-carbon backbone of the phospholipid by phospholipase A2 (PLA2) to produce the intermediate lyso-PC (LPC). An acetyl group is then added by LPC acetyltransferase (LPCAT) to produce PAF."}
{"_id": "WikiPedia_Hematology$$$corpus_1605", "text": "Using the  de novo  pathway, PAF is produced from  1-O-alkyl-2-acetyl-sn-glycerol  (AAG). Fatty acids are joined on the sn-1 position with 1-O-hexadecyl being the best for PAF activity.  Phosphocholine  is then added to the sn-3 site on AAG creating PAF."}
{"_id": "WikiPedia_Hematology$$$corpus_1606", "text": "The concentration of PAF is controlled by the synthesis of the compound and by the actions of PAF acetylhydrolases (PAF-AH).  PAF-AH are a family of enzymes that have the ability to catabolize and degrade PAF and turn it into an inactive compound.  The enzymes within this family are  lipoprotein-associated phospholipase A2 , cytoplasmic  platelet-activating factor acetylhydrolase 2 , and  platelet-activating factor acetylhydrolase 1b ."}
{"_id": "WikiPedia_Hematology$$$corpus_1607", "text": "Cations are one form of regulation in the production of PAF. Calcium plays a large role in the inhibition of enzymes that produce PAF in the  denovo  pathway of PAF biosynthesis."}
{"_id": "WikiPedia_Hematology$$$corpus_1608", "text": "The regulation of PAF is still not completely understood. Enzymes that are associated with the production of PAF are controlled by metal  ions ,  thiol  compounds,  fatty acids ,  pH , compartmentalization, and phosphorylation and dephosphorylation. These controls on these PAF producing enzymes are believed to work in conjunction to control it, but the overall pathway and reasoning is not well understood."}
{"_id": "WikiPedia_Hematology$$$corpus_1609", "text": "PAF antagonists do not provoke an inflammatory response upon binding, but block or lessen the effect of PAF. Examples of PAF antagonists are: [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1610", "text": "High PAF levels are associated with a variety of medical conditions. Some of these conditions include:"}
{"_id": "WikiPedia_Hematology$$$corpus_1611", "text": "\u2022Allergic reactions \n\u2022Stroke \n\u2022Sepsis \n\u2022Myocardial infarction \n\u2022Colitis, inflammation of the large intestine \n\u2022Multiple sclerosis"}
{"_id": "WikiPedia_Hematology$$$corpus_1612", "text": "While the effects that PAF has on inflammatory response and cardiovascular conditions are well understood, PAF is still a subject for discussion. Over the past 23 years, papers written on PAF have almost doubled from approximately 7,500 in 1997 to 14,500 in 2020. PubMed (June 2020).  \"Platelet-activating factor search results and historical activity metrics\" . PubMed.  Research into PAF is ongoing."}
{"_id": "WikiPedia_Hematology$$$corpus_1613", "text": "The  Pratt Test  is a simple test to check for  deep vein thrombosis  in the  leg . [ 1 ] [ 2 ]   It involves having the patient lie supine with the leg bent at the  knee , grasping the calf with both  hands  and pressing on the  popliteal vein  in the proximal calf.  If the patient feels  pain , it is a sign that a deep vein thrombosis exists. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1614", "text": "This  medical sign  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1615", "text": "1AUT ,  1LQV ,  3F6U ,  3JTC ,  4DT7"}
{"_id": "WikiPedia_Hematology$$$corpus_1616", "text": "5624"}
{"_id": "WikiPedia_Hematology$$$corpus_1617", "text": "19123"}
{"_id": "WikiPedia_Hematology$$$corpus_1618", "text": "ENSG00000115718"}
{"_id": "WikiPedia_Hematology$$$corpus_1619", "text": "ENSMUSG00000024386"}
{"_id": "WikiPedia_Hematology$$$corpus_1620", "text": "P04070"}
{"_id": "WikiPedia_Hematology$$$corpus_1621", "text": "P33587"}
{"_id": "WikiPedia_Hematology$$$corpus_1622", "text": "NM_000312"}
{"_id": "WikiPedia_Hematology$$$corpus_1623", "text": "NM_001042767 NM_001042768 NM_008934 NM_001313938"}
{"_id": "WikiPedia_Hematology$$$corpus_1624", "text": "NP_001362535 NP_001362536 NP_001362537 NP_001362538 NP_001362539 NP_001362540 NP_001362542"}
{"_id": "WikiPedia_Hematology$$$corpus_1625", "text": "NP_001036232 NP_001036233 NP_001300867 NP_032960"}
{"_id": "WikiPedia_Hematology$$$corpus_1626", "text": "Protein\u00a0C , also known as  autoprothrombin IIA  and  blood coagulation factor XIV , [ 5 ] :\u200a6822\u200a [ 6 ]  is a  zymogen , that is, an inactive enzyme. The activated form plays an important role in regulating  anticoagulation ,  inflammation , and  cell death  and maintaining the  permeability  of blood vessel walls in humans and other animals.  Activated protein\u00a0C  ( APC ) performs these operations primarily by  proteolytically  inactivating proteins  Factor V a  and  Factor VIII a . APC is classified as a  serine protease  since it contains a  residue  of  serine  in its  active site . [ 7 ] :\u200a35\u200a  In humans, protein C is encoded by the  PROC   gene , which is found on  chromosome 2 . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1627", "text": "The zymogenic form of protein C is a  vitamin K -dependent  glycoprotein  that circulates in  blood plasma . Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a  disulfide bond . [ 8 ] :\u200a4673\u200a  The protein C zymogen is activated when it binds to  thrombin , another protein heavily involved in coagulation, and protein C's activation is greatly promoted by the presence of  thrombomodulin  and  endothelial protein\u00a0C receptors  (EPCRs). Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls of blood vessels), and it is these cells and  leukocytes  (white blood cells) that APC affects. [ 7 ] :\u200a34\u200a [ 9 ] :\u200a3162\u200a  Because of the crucial role that protein C plays as an  anticoagulant , those with deficiencies in protein C, or some kind of  resistance to APC , suffer from a significantly increased risk of forming dangerous blood clots ( thrombosis )."}
{"_id": "WikiPedia_Hematology$$$corpus_1628", "text": "Research into the clinical use of a  recombinant  form of human Activated Protein\u00a0C (rhAPC) known as  Drotrecogin alfa-activated , branded Xigris by  Eli Lilly and Company , has been surrounded by controversy. Eli Lilly ran an aggressive marketing campaign to promote its use for people with severe  sepsis  and septic shock and sponsored the 2004  Surviving Sepsis Campaign  Guidelines. [ 10 ]  However, a 2012  Cochrane review  found that its use cannot be recommended since it does not improve survival and increases bleeding risk. [ 11 ]  In October 2011, Xigris was withdrawn from the market by Eli Lilly due to a higher mortality in a trial among adults. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1629", "text": "Protein C's  anticoagulant  role in the human body was first noted by Seegers  et al.  in 1960, [ 13 ]  who gave protein C its original name,  autoprothrombin II-a . [ 5 ] :\u200a6822\u200a  Protein\u00a0C was first isolated by  Johan Stenflo  from  bovine   plasma  in 1976, and Stenflo determined it to be a  vitamin K-dependent protein . [ 14 ]  He named it protein  C  because it was the third protein (\"peak C\") that  eluted  from a  DEAE-Sepharose   ion-exchange chromotograph . Seegers was, at the time, searching for vitamin K-dependent coagulation factors undetected by  clotting assays , which measure global clotting function. Soon after this, Seegers recognised Stenflo's discovery was identical with his own. [ 5 ] :\u200a6822\u200a  Activated protein\u00a0C was discovered later that year, [ 15 ]  and in 1977 it was first recognised that APC inactivates Factor V a . [ 16 ] :\u200a2382\u200a [ 17 ]  In 1980, Vehar and Davie discovered that APC also inactivates Factor VIII a , [ 18 ]  and soon after,  Protein S  was recognised as a  cofactor  by Walker. [ 19 ]  In 1982, a family study by Griffin  et al . first associated  protein\u00a0C deficiency  with symptoms of  venous thrombosis . [ 20 ]  Homozygous protein\u00a0C deficiency and the consequent serious health effects were described in 1984 by several scientists. [ 21 ] :\u200a1214\u200a  cDNA cloning of protein\u00a0C was first performed in 1984 by Beckmann  et al.  which produced a map of the gene responsible for producing protein\u00a0C in the liver. [ 22 ]  In 1987 a seminal experiment was performed (Taylor  et al. ) whereby it was demonstrated that activated protein\u00a0C prevented  coagulopathy  and death in baboons  infused  with lethal concentrations of  E. coli . [ 16 ] :\u200a2382\u200a [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1630", "text": "In 1993, a heritable resistance to APC was detected by  Dahlb\u00e4ck   et al.  and associated with familial  thrombophilia . [ 24 ]   In 1994, the relatively common genetic mutation that produces  Factor V Leiden  was noted (Bertina  et al. ). [ 25 ]  Two years later, Gla-domainless APC was imaged at a resolution of 2.8\u00a0 \u00c5ngstr\u00f6ms . [\u03b1] [ 5 ]   Beginning with the PROWESS  clinical trial  of 2001, [ 26 ]  it was recognised that many of the symptoms of  sepsis  may be ameliorated by infusion of APC, and mortality rates of septic patients may be significantly decreased. [ 9 ] :\u200a3161,\u200a6\u200a  Near the end of that year,  Drotrecogin alfa (activated) , a recombinant human activated protein\u00a0C, became the first drug approved by the U.S.  FDA   for treating severe  sepsis . [ 27 ]  In 2002,  Science  published an article that first showed protein\u00a0C activates  protease-activated receptor-1  (PAR-1) and this process accounts for the protein's modulation of the immune system. [ 16 ] :\u200a2382\u200a [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1631", "text": "The biologic instructions for synthesising protein\u00a0C in humans are encoded in the gene officially named \"protein\u00a0C (inactivator of coagulation factors Va and VIIIa)\". The gene's symbol approved by the  HUGO Gene Nomenclature Committee  is \"PROC\" from \" pro tein  C \". It is located on the second  chromosome  (2q13-q14) and comprises nine  exons . [ 8 ] [ 16 ] :\u200a2383\u200a  The nucleotide sequence that codes for human protein\u00a0C is approximately 11,000\u00a0bases long. [ 8 ] :\u200a4675"}
{"_id": "WikiPedia_Hematology$$$corpus_1632", "text": "Human protein\u00a0C is a vitamin K-dependent glycoprotein structurally similar to other vitamin K-dependent proteins affecting blood clotting, [ 29 ]  such as  prothrombin ,  Factor VII ,  Factor IX  and  Factor X . [ 21 ] :\u200a1215\u200a  Protein\u00a0C synthesis occurs in the liver and begins with a single-chain precursor molecule: a 32 amino acid  N-terminus   signal peptide  preceding a  propeptide . [ 30 ] :\u200aS11\u200a  Protein\u00a0C is formed when a  dipeptide  of Lys 198  and Arg 199  is removed; this causes the transformation into a  heterodimer  with  N -linked carbohydrates on each chain. The protein has one light chain (21  kDa ) and one heavy chain (41 kDa) connected by a  disulfide bond  between Cys 183  and Cys 319 ."}
{"_id": "WikiPedia_Hematology$$$corpus_1633", "text": "Inactive protein\u00a0C comprises 419\u00a0amino acids in multiple  domains : [ 16 ] :\u200a2383\u200a  one  Gla domain  (residues 43\u201388); a helical  aromatic  segment (89\u201396); two  epidermal growth factor (EGF)-like domains  (97\u2013132 and 136\u2013176); an activation peptide (200\u2013211); and a  trypsin -like serine protease domain (212\u2013450). The light chain contains the Gla- and EGF-like domains and the aromatic segment. The heavy chain contains the protease domain and the activation petide. It is in this form that 85\u201390% of protein\u00a0C circulates in the plasma as a  zymogen , waiting to be activated. [ 5 ] :\u200a6822\u200a  The remaining protein\u00a0C zymogen comprises slightly modified forms of the protein. Activation of the enzyme occurs when a thrombin molecule cleaves away the activation peptide from the  N-terminus  of the heavy chain. [ 8 ] :\u200a4673\u200a \n [ 30 ] :\u200aS11\u200a  The active site contains a  catalytic triad  typical of serine proteases (His 253 , Asp 299  and Ser 402 ). [ 16 ] :\u200a2833"}
{"_id": "WikiPedia_Hematology$$$corpus_1634", "text": "The Gla domain is particularly useful for binding to negatively charged  phospholipids  for anticoagulation and to EPCR for  cytoprotection . One particular  exosite  augments protein\u00a0C's ability to inactivate Factor V a  efficiently. Another is necessary for interacting with thrombomodulin. [ 16 ] :\u200a2833"}
{"_id": "WikiPedia_Hematology$$$corpus_1635", "text": "Post-translational modifications . Human Protein C has at least five types of  post-translational modifications : (1) gamma- carboxylation  on the first nine  glutamic acid  residues in the protein sequence. This modification event is performed by a vitamin K-dependent microsomal carboxylase. The full complement of Gla is required to give full activity to protein C. (2) beta- Hydroxylation  of Asp71 in one of the two  EGF-like domains  to give erythro-L-beta-hydroxy-aspartate (bHA). The modification is required for functional activity as was demonstrated by mutating Asp71 to Glu. (3) N-linked  glycosylation  at three possible glycosylation sites. Plasma human Protein C has been reported to be 23% carbohydrate by weight. (4) Disulfide formation. (5) Multiple  proteolytic cleavages  of the polypeptide backbone to remove an 18 amino acid  signal peptide , a 24 amino acid propeptide and then cleavages at amino acids 155-156 and 157-158 to yield the two-chain structure of the circulating zymogen. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1636", "text": "The activation of protein\u00a0C is strongly promoted by  thrombomodulin  and  endothelial protein\u00a0C receptor  (EPCR), the latter of which is found primarily on  endothelial cells  (cells on the inside of blood vessels). The presence of thrombomodulin accelerates activation by several orders of magnitude, [ 7 ] :\u200a34\u200a  and EPCR speeds up activation by a factor of 20. If either of these two proteins is absent in  murine  specimens, the mouse dies from excessive blood-clotting while still in an  embryonic  state. [ 32 ] :\u200a1983\u200a [ 33 ] :\u200a43335\u200a  On the endothelium, APC performs a major role in regulating blood clotting, inflammation, and cell death ( apoptosis ). [ 34 ] :\u200a28S\u200a  Because of the accelerating effect of thrombomodulin on the activation of protein\u00a0C, the protein may be said to be activated not by thrombin but the thrombin\u2013thrombomodulin (or even thrombin\u2013thrombomodulin\u2013EPCR) complex. [ 16 ] :\u200a2381\u200a  Once in active form, APC may or may not remain bound to EPCR, to which it has approximately the same affinity as the protein zymogen. [ 9 ] :\u200a3162"}
{"_id": "WikiPedia_Hematology$$$corpus_1637", "text": "Protein\u00a0C in  zymogen  form is present in normal adult human  blood plasma  at concentrations between 65 and 135\u00a0 IU / dL . Activated protein\u00a0C is found at levels approximately 2000 times lower than this. [ 9 ] :\u200a3161\u200a   Mild protein\u00a0C deficiency corresponds to plasma levels above 20\u00a0IU/dL, but below the normal range. Moderately severe deficiencies describe blood concentrations between 1 and 20 IU/dL; severe deficiencies yield levels of protein\u00a0C that are below 1\u00a0IU/dL or are undetectable. Protein\u00a0C levels in a healthy  term infant  average 40\u00a0IU/dL. The concentration of protein\u00a0C increases until six months, when the mean level is 60\u00a0IU/dL; the level stays low through childhood until it reaches adult levels after  adolescence . [ 21 ] :\u200a1216\u200a  The  half-life  of activated protein\u00a0C is around 15\u00a0minutes. [ 5 ] :\u200a6823"}
{"_id": "WikiPedia_Hematology$$$corpus_1638", "text": "The protein\u00a0C pathways are the specific chemical reactions that control the level of expression of APC and its activity in the body. [ 7 ] :\u200a34\u200a  Protein\u00a0C is  pleiotropic , with two main classes of functions: anticoagulation and cytoprotection (its direct effect on cells). Which function protein\u00a0C performs depends on whether or not APC remains bound to EPCR after it is activated; the anticoagulative effects of APC occur when it does not. In this case, protein\u00a0C functions as an anticoagulant by irreversibly proteolytically inactivating  Factor V a  and  Factor VIII a , turning them into Factor V i  and Factor VIII i  respectively. When still bound to EPCR, activated protein\u00a0C performs its cytoprotective effects, acting on the  effector   substrate  PAR-1,  protease-activated receptor-1 . To a degree, APC's anticoagulant properties are independent of its cytoprotective ones, in that expression of one pathway is not affected by the existence of the other. [ 9 ] :\u200a3162\u200a [ 34 ] :\u200a26S"}
{"_id": "WikiPedia_Hematology$$$corpus_1639", "text": "The activity of protein\u00a0C may be  down-regulated  by reducing the amount either of available thrombomodulin or of EPCR. This may be done by inflammatory  cytokines , such as  interleukin-1\u03b2   (IL-1\u03b2 ) and  tumor necrosis factor-\u03b1  (TNF-\u03b1). Activated leukocytes release these inflammatory mediators during inflammation, inhibiting the creation of both thrombomodulin and EPCR, and inducing their shedding from the endothelial surface. Both of these actions down-regulate protein\u00a0C activation. Thrombin itself may also have an effect on the levels of EPCR. In addition, proteins released from cells can impede protein\u00a0C activation, for example  eosinophil , which may explain thrombosis in  hypereosinophilic  heart disease. [\u03b2]  Protein\u00a0C may be  up-regulated  by  platelet factor 4 . This cytokine is conjectured to improve activation of protein\u00a0C by forming an  electrostatic bridge  from protein\u00a0C's Gla domain to the  glycosaminoglycan  (GAG) domain of thrombomodulin, reducing the  Michaelis constant  (K M ) for their reaction. [ 16 ] :\u200a2386\u200a [ 34 ] :\u200a29S\u200a  In addition, Protein\u00a0C is inhibited by  protein\u00a0C inhibitor . [ 35 ] :\u200a369"}
{"_id": "WikiPedia_Hematology$$$corpus_1640", "text": "Protein\u00a0C is a major component in anticoagulation in the human body. It acts as a  serine protease   zymogen : APC proteolyses peptide bonds in activated  Factor V  and  Factor VIII  (Factor V a  and Factor VIII a ), and one of the amino acids in the bond is  serine . [ 16 ] :\u200a2381\u200a  These proteins that APC inactivates, Factor V a  and Factor VIII a , are highly procoagulant cofactors in the generation of  thrombin , which is a crucial element in blood clotting; together they are part of the  prothrombinase complex . [ 34 ] :\u200a26S\u200a  Cofactors in the inactivation of Factor V a  and Factor VIII a  include  protein S , Factor V,  high-density lipoprotein , anionic  phospholipids  and  glycosphingolipids . [ 9 ] :\u200a3161"}
{"_id": "WikiPedia_Hematology$$$corpus_1641", "text": "Factor V a  binds to  prothrombin  and Factor X a , increasing the rate at which thrombin is produced by four orders of magnitude (10,000x). Inactivation of Factor V a  thus practically halts the production of thrombin. Factor VIII, on the other hand, is a cofactor in production of activated Factor X, which in turn converts prothrombin into thrombin. Factor VIII a  augments Factor X activation by a factor of around 200,000. Because of its importance in clotting, Factor VIII is also known as anti-haemophilic factor, and deficiencies of Factor VIII cause  haemophilia A . [ 16 ] :\u200a2382,\u200a3"}
{"_id": "WikiPedia_Hematology$$$corpus_1642", "text": "APC inactivates Factor V a  by making three cleavages (Arg 306 , Arg 506 , Arg 679 ). The cleavages at both Arg 306  and Arg 506  diminish the molecule's attraction to Factor X a , and though the first of these sites is slow to be cleaved, it is entirely necessary to the functioning of Factor V. Protein S aids this process by catalysing the proteolysis at Arg 306 , in which the A2 domain of Factor V is dissociated from the rest of the protein. [ 36 ]  Protein S also binds to Factor X a , inhibiting the latter from diminishing APC's inactivation of Factor V a . [ 16 ] :\u200a2386"}
{"_id": "WikiPedia_Hematology$$$corpus_1643", "text": "The inactivation of Factor VIII a  is not as well understood. The half-life of Factor VIII a  is only around two minutes unless Factor IX a  is present to stabilise it. Some have questioned the significance of APC's inactivation of Factor VIII a , and it is unknown to what degree Factor V and protein S are cofactors in its proteolysis. It is known that APC works on Factor VIII a  by cleaving at two sites, Arg 336  and Arg 562 , either of which is sufficient to disable Factor VIII a  and convert it to Factor VIII i . [ 16 ] :\u200a2387"}
{"_id": "WikiPedia_Hematology$$$corpus_1644", "text": "When APC is bound to EPCR, it performs a number of important cytoprotective (i.e. cell-protecting) functions, most of which are known to require EPCR and PAR-1. These include regulating gene expression, anti-inflammatory effects, antiapoptotic effects and protecting endothelial barrier function. [ 9 ] :\u200a3162"}
{"_id": "WikiPedia_Hematology$$$corpus_1645", "text": "Treatment of cells with APC demonstrates that its gene expression modulation effectively controls major pathways for inflammatory and apoptotic behaviour. There are about 20 genes that are up-regulated by protein\u00a0C, and 20 genes that are down-regulated: the former are generally anti-inflammatory and antiapoptotic pathways, while the latter tend to be proinflammatory and proapoptotic. APC's mechanisms for altering gene expression profiles are not well understood, but it is believed that they at least partly involve an inhibitory effect on  transcription factor  activity. [ 9 ] :\u200a3162,\u200a4\u200a  Important proteins that APC up-regulates include  Bcl-2 ,  eNOS  and  IAP . APC effects significant down-regulation of  p53  and  Bax . [ 16 ] :\u200a2388"}
{"_id": "WikiPedia_Hematology$$$corpus_1646", "text": "APC has anti-inflammatory effects on  endothelial  cells and  leukocytes . APC affects endothelial cells by inhibiting  inflammatory mediator release  and down-regulating  vascular adhesion molecules . This reduces leukocyte adhesion and infiltration into tissues, while also limiting damage to underlying tissue. APC supports endothelial barrier function and reduces  chemotaxis . APC inhibits the release of inflammatory-response mediators in leukocytes as well as endothelial cells, by reducing cytokine response, and maybe diminishing systemic inflammatory response, such as is seen in  sepsis . Studies on both rats and humans have demonstrated that APC reduces  endotoxin -induced pulmonary injury and inflammation. [ 9 ] :\u200a3164"}
{"_id": "WikiPedia_Hematology$$$corpus_1647", "text": "Scientists recognise activated protein\u00a0C's antiapoptotic effects, but are unclear as to the exact mechanisms by which apoptosis is inhibited. It is known that APC is  neuroprotective . Antiapoptosis is achieved with diminished activation of  caspase 3  and  caspase 8 , improved Bax/Bcl-2 ratio and down-regulation of p53. [ 16 ] :\u200a2388"}
{"_id": "WikiPedia_Hematology$$$corpus_1648", "text": "Activated protein\u00a0C also provides much protection of endothelial barrier function. Endothelial barrier breakdown, and the corresponding increase in endothelial permeability, are associated with  swelling ,  hypotension  and inflammation, all problems of sepsis. APC protects endothelial barrier function by inducing PAR-1 dependent  sphingosine kinase-1  activation and up-regulating  sphingosine-1-phosphate  with  sphingosine kinase . [ 9 ] :\u200a3165"}
{"_id": "WikiPedia_Hematology$$$corpus_1649", "text": "Several studies have indicated that the proteolytic activity of APC contributes to the observed cytoprotective properties of APC, but variants that are proteolytically inactive also are able to regulate formation of PAR-activators thrombin and factor Xa and express cytoprotective properties in vitro and in vivo. [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1650", "text": "A genetic  protein\u00a0C deficiency , in its mild form associated with  simple heterozygosity , causes a significantly increased risk of  venous thrombosis  in adults. If a fetus is  homozygous  or  compound heterozygous  for the deficiency, there may be a presentation of  purpura fulminans , severe  disseminated intravascular coagulation  and simultaneous  venous thromboembolism  in the womb; [ 21 ] :\u200a1214\u200a   this is very severe and usually fatal. [ 39 ] :\u200a211s\u200a  Deletion of the protein\u00a0C gene in mice causes fetal death around the time of birth. Fetal mice with no protein\u00a0C develop normally at first, but experience severe bleeding,  coagulopathy , deposition of  fibrin  and  necrosis  of the liver. [ 9 ] :\u200a3161"}
{"_id": "WikiPedia_Hematology$$$corpus_1651", "text": "The frequency of protein\u00a0C deficiency among asymptomatic individuals is between 1 in 200 and 1 in 500. In contrast, significant symptoms of the deficiency are detectable in 1 in 20,000 individuals. No racial nor ethnic biases have been detected. [ 21 ] :\u200a1215"}
{"_id": "WikiPedia_Hematology$$$corpus_1652", "text": "At least 177 disease-causing mutations in this gene have been discovered. [ 40 ]   Activated protein\u00a0C resistance  occurs when APC is unable to perform its functions. This disease has similar symptoms to protein\u00a0C deficiency. The most common mutation leading to activated protein\u00a0C resistance among Caucasians is at the cleavage site in Factor V for APC. There, Arg 506  is replaced with Gln, producing  Factor V Leiden . This mutation is also called a R506Q. [ 16 ] :\u200a2382\u200a  The mutation leading to the loss of this cleavage site actually stops APC from effectively inactivating both Factor V a  and Factor VIII a . Thus, the person's blood clots too readily, and he is perpetually at an increased risk for thrombosis. [ 41 ] :\u200a3\u200a  Individuals heterozygous for the Factor V Leiden  mutation carry a risk of venous thrombosis 5\u20137 times higher than in the general population. Homozygous subjects have a risk 80 times higher. [ 7 ] :\u200a40\u200a  This mutation is also the most common hereditary risk for venous thrombosis among  Caucasians . [ 16 ] :\u200a2382"}
{"_id": "WikiPedia_Hematology$$$corpus_1653", "text": "Around 5% of APC resistance are not associated with the above mutation and Factor V Leiden . Other genetic mutations cause APC resistance, but none to the extent that Factor V Leiden  does. These mutations include various other versions of Factor V, spontaneous generation of  autoantibodies  targeting Factor V, and dysfunction of any of APC's cofactors. [ 16 ] :\u200a2387\u200a  Also, some acquired conditions may reduce the efficacy of APC in performing its anticoagulative functions. [ 7 ] :\u200a33\u200a  Studies suggest that between 20% and 60% of thrombophilic patients suffer from some form of APC resistance. [ 7 ] :\u200a37"}
{"_id": "WikiPedia_Hematology$$$corpus_1654", "text": "Warfarin necrosis  is an acquired protein\u00a0C deficiency due to treatment with  warfarin , which is a vitamin K antagonist and an anticoagulant itself. However, warfarin treatment may produce paradoxical skin lesions similar to those seen in purpura fulminans. A variant of this response presents as venous limb  gangrene  when warfarin is used to treat deep vein thrombosis associated with cancer. In these situations, warfarin may be restarted at a low dosage to ensure that the protein\u00a0C deficiency does not present before the vitamin K coagulation factors II, IX and X are suppressed. [ 39 ] :\u200a211s"}
{"_id": "WikiPedia_Hematology$$$corpus_1655", "text": "Activated protein C cleaves  Plasmodium falciparum   histones  which are released during infection: cleavage of these histones eliminates their pro inflammatory effects. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1656", "text": "In November 2001, the  Food and Drug Administration  approved  Drotrecogin alfa-activated  (DrotAA) for the clinical treatment of adults suffering from severe sepsis and with a high risk of death. [ 43 ] :\u200a1332\u200a  Drotrecogin alfa-activated is a  recombinant  form of human activated protein\u00a0C (rhAPC). It is marketed as Xigris by  Eli Lilly and Company , [ 27 ] :\u200a224"}
{"_id": "WikiPedia_Hematology$$$corpus_1657", "text": "Drotrecogin alfa-activated was the subject of significant controversy while it was approved for clinical use as it was found to increase bleeding and not to reduce mortality. [ 44 ] [ needs update ]  In October 2011 rhAPC (Xigris) was withdrawn from the market by Eli Lilly due to a higher mortality in a trial among adults. [ 12 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1658", "text": "APC has been studied as way of treating  lung  injury, after studies showed that in patients with lung injury, reduced APC levels in specific parts of the lungs correlated with worse outcomes. [ 9 ] :\u200a3167,\u200a8\u200a  APC also has been considered for use in improving patient outcome in cases of  ischemic stroke , a medical emergency in which arterial blockage deprives a region of brain of oxygen, causing tissue death. Promising studies suggest that APC could be coupled with the only currently approved treatment,  tissue plasminogen activator  (tPA), to protect the brain from tPA's very harmful  side effects , in addition to preventing cell death from lack of oxygen ( hypoxia ). [ 45 ] :\u200a211\u200a  Clinical use of APC has also been proposed for improving the outcome of  pancreatic islet transplantation  in treating  type I diabetes . [ 16 ] :\u200a2392"}
{"_id": "WikiPedia_Hematology$$$corpus_1659", "text": "Ceprotin was approved for medical used in the European Union in July 2001. [ 46 ]  Ceprotin is indicated in purpura fulminans and coumarin-induced skin necrosis in people with severe congenital protein C deficiency. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1660", "text": "Prothrombin activator  is a complex of a dozen blood coagulation factors that functions in catalyzing  prothrombin  into  thrombin . Prothrombin activator is released in the body by a cascade of chemical reactions in response to damage in a blood vessel."}
{"_id": "WikiPedia_Hematology$$$corpus_1661", "text": "In  hematology ,  red cell agglutination  or  autoagglutination  is a phenomenon in which  red blood cells  clump together, forming aggregates. It is caused by the surface of the red cells being coated with  antibodies . [ 1 ] :\u200a98\u200a  This often occurs in  cold agglutinin disease , a type of  autoimmune hemolytic anemia  in which people produce antibodies (termed cold agglutinins) that bind to their red blood cells at cold temperatures and destroy them. People may develop cold agglutinins from  lymphoproliferative disorders , from infection with  Mycoplasma pneumoniae  or  Epstein\u2013Barr virus , or  idiopathically  (without any apparent cause). Red cell agglutination can also occur in  paroxysmal nocturnal hemoglobinuria [ 2 ] :\u200a13\u200a [ 3 ]  and  warm autoimmune hemolytic anemia . [ 4 ] :\u200a88\u200a  In cases of red cell agglutination, the  direct antiglobulin test  can be used to demonstrate the presence of antibodies bound to the red cells. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1662", "text": "Red blood cell aggregates are counted as single cells by the  automated analyzers  used to run  complete blood count  tests. This leads to a markedly decreased  red blood cell  count and  hematocrit  and markedly elevated  mean cell volume  and  mean cell hemoglobin concentration . [ 5 ] :\u200a32\u20133\u200a   Red cell agglutination also interferes with routine methods for  blood typing  and  blood compatibility testing , which rely on agglutination reactions. People with red cell agglutination may exhibit spontaneous agglutination reactions during testing, leading to a false positive result. [ 6 ] :\u200a141,\u200a262\u200a  If the causative antibodies are only active at room temperature, the agglutination can be reversed by heating the blood sample to 37\u00a0\u00b0C (99\u00a0\u00b0F). People with  warm autoimmune hemolytic anemia  may exhibit red cell agglutination that does not resolve on warming. [ 4 ] :\u200a88"}
{"_id": "WikiPedia_Hematology$$$corpus_1663", "text": "Rheopheresis  is a process to change the viscosity of blood by filtering blood to remove some components such as  fibrinogen ,  alpha-2-macroglobulin ,  von Willebrand factor ,  LDL cholesterol  and  immunoglobulin M . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1664", "text": "It is an experimental treatment for dry  age-related macular degeneration , [ 2 ]  and acute ischemic stroke. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1665", "text": "This  medical treatment \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1666", "text": "Riboflavin carrier proteins  (RFCPs) together with  human serum albumin  transport  flavin mononucleotide  (FMN) in the  blood circuit . RFCPs are important in  pregnancy ."}
{"_id": "WikiPedia_Hematology$$$corpus_1667", "text": "Studies from India have identified a riboflavin carrier protein (RCP) present in bird (e.g., chicken) eggs, which is considered to be specific for riboflavin, and is essential for normal embryological development. If this protein is rendered ineffective (e.g., by immuno-neutralization) by treatment of the bird with a specific antibody, then embryonic development ceases and the embryo dies. A genetic mutant lacking RCP is likewise infertile. A homologous protein, which can be rendered ineffective by the antibody to pure chicken riboflavin carrier protein, has been shown to occur in several mammalian species, including two species of monkeys, and also in humans. Very recent studies have suggested that circulating RCP levels and the immunohistochemical staining of RCP in biopsy specimens may provide new markers for  breast cancer diagnosis and prognosis . Termination of pregnancy has been demonstrated by immuno-neutralization of RCP in monkeys. There remains some controversy over the roles of RCP, however, the other, less specific riboflavin binders in blood, including gamma-gobulins, also seem to play an important role. These studies have provided an intriguing example of the role of specific vitamin-transporting mechanisms, designed to ensure that the vitamin needs of the developing embryo will be efficiency met. Further evidence of the special needs of developing embryos has been provided by the demonstration that riboflavin analogs can cause teratogenic changes, even in the absence of any detectable damage to maternal tissues. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1668", "text": "RCP in chicken eggs is in both the  yolk  and  whites . The RCP found in the yolk differs from that of the egg white. The difference in amino acid structure of RCP attributes to the cite of production and the destination of the RCP\u2014the yolk-RCP (made in the  liver ) had 11-13 less amino acid compared to the whites-RCP (made in the  oviducts ). [ 2 ]   [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1669", "text": "The concentration of RCP in chickens depends on the concentration of  estradiol  injected and an increased production of RCP can be induced. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1670", "text": "The dependence of RCP production on estrogen enables a potential role in the detection of  breast cancer .  [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1671", "text": "Romanowsky staining  is a prototypical  staining  technique that was the forerunner of several distinct but similar stains widely used in  hematology  (the study of blood) and  cytopathology  (the study of diseased cells). Romanowsky-type stains are used to differentiate  cells  for microscopic examination in  pathological  specimens, especially  blood  and  bone marrow  films, [ 1 ]  and to detect parasites such as  malaria  within the blood. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1672", "text": "The staining technique is named after the Russian physician  Dmitri Leonidovich Romanowsky  (1861\u20131921), who was one of the first to recognize its potential for use as a blood stain. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1673", "text": "Stains that are related to or derived from the Romanowsky-type stains include  Giemsa ,  Jenner ,  Wright ,  Field ,  May\u2013Gr\u00fcnwald ,  Pappenheim  and  Leishman  stains. They differ in protocols and additives and their names are often confused with one another in practice."}
{"_id": "WikiPedia_Hematology$$$corpus_1674", "text": "The value of Romanowsky staining lies in its ability to produce a wide range of hues, allowing cellular components to be easily differentiated. This phenomenon is referred to as the  Romanowsky effect , or more generally as  metachromasia . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1675", "text": "Eosin part of the stain is responsible for pink-orange hue of  erythrocytes  and granules inside  cytoplasms  of  eosinophilic leukocytes ."}
{"_id": "WikiPedia_Hematology$$$corpus_1676", "text": "In 1891 Romanowsky [ 8 ] [ 9 ] [ 10 ]  developed a stain using a mixture of  eosin  (typically  eosin Y ) and aged solutions of  methylene blue  that formed hues unattributable to the staining components alone: distinctive shades of purple in the  chromatin  of the cell nucleus and within granules in the  cytoplasm  of some  leukocytes . This became known as the Romanowsky effect. [ 11 ] [ 12 ] [ 6 ] [ 13 ] [ 4 ]  Eosin and pure methylene blue alone (or in combination) do not produce the Romanowsky effect, [ 13 ] [ 4 ]  and the active stains which produce the effect are now considered to be  azure B  and eosin. [ 14 ] [ 3 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1677", "text": "Romanowsky-type stains can be made from either a combination of pure dyes, or from methylene blue that has been subject to  oxidative   demethylation , which results in the breakdown of methylene blue into multiple other stains, some of which are necessary to produce the Romanowsky effect. [ 15 ] [ 4 ]  Methylene blue that has undergone this oxidative process is known as \"polychromed methylene blue\". [ 15 ] [ 4 ]  Polychromed methylene blue may contain up to 11 dyes, including  methylene blue ,  azure A , azure B, azure C,  thionine , methylene violet Bernthesen, methyl thionoline and thionoline. [ 4 ]  The exact composition of polychromed methylene blue depends on the method used, and even batches of the stain from the same manufacturer may vary in composition. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1678", "text": "Common method of rapid oxidation uses increasing pH of the solution with  potassium carbonate  and boiling it, which introduces atmospheric  oxygen . [ 16 ]  Other methods have been employed, as well, such as oxidation in acidic medium with  dichromate anion ."}
{"_id": "WikiPedia_Hematology$$$corpus_1679", "text": "Although azure B and eosin have been shown to be the required components to produce the Romanowsky effect, [ 14 ] [ 3 ] [ 13 ]  these stains in their pure forms have not always been used in the formulation of the staining solutions. [ 4 ]  The original sources of azure B (one of the oxidation products of methylene blue) were from polychromed methylene blue solutions, which were treated with oxidizing agents or allowed to naturally age in the case of Romanowsky. [ 3 ] [ 13 ]   Ernst Malachowsky  in 1891 was the first to purposely polychrome methylene blue for use in a Romanowsky-type stain. [ 15 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1680", "text": "Wright's stain can be used alone or in combination with the Giemsa stain, which is known as the Wright-Giemsa stain. [ 1 ]  Wright's stain is named after  James Homer Wright  who in 1902 [ 18 ]  published a method using heat to produce polychromed methylene blue, which is combined with eosin Y. [ 19 ] [ 20 ] [ 21 ] [ 1 ]  The polychromed methylene blue is combined with eosin and allowed to precipitate, forming an eosinate which is redissolved in  methanol . [ 4 ]  The addition of Giemsa to Wright's stain increases the brightness of the \"reddish-purple\" color of the cytoplasmic granules. [ 1 ] [ 21 ]  The Wright's and Wright-Giemsa stains are two of the Romanowsky-type stains in common use in the United States and are mainly used for the staining of blood and bone marrow films. [ 21 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1681", "text": "Jenner's stain is used in  microscopy  for  staining   blood smears . The stain is dark blue and results in very observable clearly stained nucleus."}
{"_id": "WikiPedia_Hematology$$$corpus_1682", "text": "Giemsa stain is composed of \"Azure II\" and eosin Y with methanol and glycerol as the solvent. [ 15 ]  \"Azure II\" is thought to be a mixture of azure B (which Giemsa called \"azure I\") and methylene blue, although the exact composition of \"azure I\" is considered a trade secret. [ 4 ] [ 15 ]  Comparable formulations using known dyes have been published and are commercially available. Giemsa stain is considered to be the standard stain for detection and identification of the malaria parasite. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1683", "text": "The May-Gr\u00fcnwald-Giemsa is used for the  staining  of slides obtained by  fine-needle aspiration  in a histopathology lab for the diagnosis of tumorous cells."}
{"_id": "WikiPedia_Hematology$$$corpus_1684", "text": "This method is a combination of May-Gr\u00fcnwald and Giemsa staining."}
{"_id": "WikiPedia_Hematology$$$corpus_1685", "text": "In 1901  William Leishman [ 22 ]  developed a stain that was similar to Louis Jenner's but with the replacement of pure methylene blue with polychromed methylene blue. [ 19 ] [ 15 ] [ 4 ]  Leishman's stain is prepared from the eosinate of polychromed methylene blue and eosin Y using methanol as the solvent. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1686", "text": "Field stain is used for staining thick blood films in order to discover  malarial  parasites."}
{"_id": "WikiPedia_Hematology$$$corpus_1687", "text": "Romanowsky-type stains are widely used in the examination of blood, in the form of  blood films , and in the microscopic  examination of bone marrow   biopsies  and aspirate smears. [ 1 ] [ 23 ]  Examination of both blood and bone marrow can be of importance in the diagnosis of a variety of blood diseases. [ 1 ] [ 23 ]  In the United States the Wright and Wright-Giemsa variants of the Romanowsky-type stains are widely used, [ 1 ]  while in Europe Giemsa stain is commonly employed. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1688", "text": "Of the Romanowsky-type stains, the Giemsa stain is especially important in  the detection and identification of malaria parasites in blood samples . [ 5 ] [ 15 ]   Malaria antigen detection tests  are an alternative to the staining and microscopic examination of blood films for the detection of malaria. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1689", "text": "Romanowsky-type stains are also used for the staining of  cytopathologic  specimens such as those produced from  fine-needle aspirates  and  cerebrospinal fluid  from  lumbar punctures . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1690", "text": "Although debate exists as to who deserves credit for this general staining method, popular usage has attributed it to  Dmitri Leonidovich Romanowsky . [ 14 ] [ 17 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1691", "text": "In the 1870s  Paul Ehrlich  used a mixture of acidic and basic dyes including  acid fuchsin  (acid dye) and  methylene blue  (basic dye) to examine blood films. [ 25 ] [ 26 ] [ 27 ] [ 28 ] [ 17 ]  In 1888 Cheslav Ivanovich Chenzinsky used methylene blue, but substituted the acid fuchsin used by Ehrlich with eosin. [ 14 ] [ 27 ] [ 28 ]  Chenzinsky's stain combination was able to stain the  malaria  parasite (a member of the  genus   Plasmodium ). [ 28 ] [ 19 ]  Neither Ehrlich's or Chenzinsky's stains produced the Romanowsky effect as the methylene blue they used was not polychromed. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1692", "text": "Dmitri Romanowsky in 1890 published preliminary findings of his blood stain (a combination of aged methylene blue and eosin), including the results when applied to malaria infected blood. [ 6 ]  This use of polychromed methylene blue differentiated Romanowsky's stain (and the subsequent formulations) from those of Ehrlich and Chenzinsky, which lacked the purple hue associated with the Romanowsky effect. [ 17 ]  Romanowsky's 1890 publication did not include a description of how he modified his methylene blue solution, [ 6 ] [ 17 ]  but in his 1891 doctoral thesis he described methylene blue best as used after mold began forming on the surface. [ 6 ] [ 17 ]  Other than the use of an aged methylene blue solution, Romanowsky's stain was based on Chenzinsky's stain technique. [ 17 ]  Romanowsky's use of his method to study the malaria parasite has been attributed to the continued interest in his staining method. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1693", "text": "Ernst Malachowsky  has been credited with independently observing the same stain combination as Dmitri Romanowsky in 1891, [ 6 ] [ 13 ]  although he has also been credited with being the first to do so. [ 17 ] [ 19 ]  Malachowsky was the first to use a deliberately polychromed methylene blue solution, [ 15 ]  which Malachowsky accomplished by the addition of  borax  to the staining mixture. [ 17 ]  Malachowsky is reported to have demonstrated the stain on June 15, 1890, and in the same year to have published a paper \"describing his public demonstration\". [ 19 ]  Both the Romanowsky and Malachowsky methods were able to stain the  nucleus  and  cytoplasm  of the  malaria   parasite , when until this point the stains used had only colored the cytoplasm. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1694", "text": "In 1899,  Louis Leopold Jenner  developed a more stable version of the methylene blue and eosin stain by collecting the  precipitate  that forms in water-based mixtures and redissolving it in  methanol . [ 28 ] [ 15 ] [ 4 ]  Romanowsky-type stains prepared from the collected precipitates are sometimes known as  eosinates . [ 4 ]  Besides increasing the stability of the stain, the use of methanol in  Jenner's stain  had the effect of  fixing  the blood samples, [ 4 ]  although Jenner's version of the stain does not produce the Romanowsky effect. [ 28 ] [ 19 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1695", "text": "Richard May and  Ludwig Gr\u00fcnwald  in 1892 published a version of the stain (now known as the  May\u2013Gr\u00fcnwald stain ) which is similar to the version proposed by Jenner in 1899, and likewise does not produce the Romanowsky effect. [ 28 ] [ 19 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1696", "text": "In 1901, both  Karl Reuter  and  William Leishman [ 22 ]  developed stains that combined Louis Jenner's use of alcohol as the solvent and Malachowsky's use of polychromed methylene blue. [ 19 ] [ 15 ] [ 4 ]  Reuter's stain differed from Jenner's in using  ethyl alcohol  instead of methanol, and Leishman's differed from Jenner's by using  eosin B  instead of  eosin Y . [ 19 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1697", "text": "James Homer Wright  in 1902 published [ 18 ]  a method using heat to polychrome the methylene blue, which he combined with eosin Y. This technique is known as  Wright's stain . [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1698", "text": "Gustav Giemsa's  name has also become associated with the stain as he is credited with publishing a useful formulation and protocol in 1902. [ 13 ] [ 6 ] [ 26 ]  Giemsa attempted to use combinations of pure dyes rather than polychromed methylene blue solutions which are highly variable in composition. [ 20 ] [ 19 ] [ 15 ]  Giemsa sold the rights to produce his stain, but never fully published details on how he produced it, [ 19 ]  although it is thought that he used a combination of azure B and methylene blue. [ 15 ]  Giemsa published a number of modifications of his stains between 1902 and 1934. In 1904 [ 29 ]  he suggested adding glycerin to his stain, along with the methanol, to increase its stability. [ 23 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1699", "text": "Giemsa stain powders produced in Germany were widely used in the United States until the interruption of the supply during  World War I , which caused increased utilization of James Homer Wright's method for polychroming methylene blue. [ 19 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1700", "text": "Splenic aspiration  is the removal of fluid from the  spleen , often with the use of a fine-needle. It is rarely practiced in modern medicine. [ 1 ]  It is indicated only in cases of  hypersplenism , or other cases of unexplained  spleen  enlargement. The Moeschlin technique is a common technique for performing a splenic aspiration. There are reports of using this technique in patients with  kala azar ."}
{"_id": "WikiPedia_Hematology$$$corpus_1701", "text": "Streptolysins  are two  homogenous   exotoxins  from  Streptococcus pyogenes . [ 1 ] [ 2 ]  Types include streptolysin O (SLO;  slo ), which is oxygen-labile, and streptolysin S (SLS;  sagA ), which is oxygen-stable. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1702", "text": "SLO is part of the  thiol-activated cytolysin  family. [ 4 ]  It is hemolytically active only in a reversibly reduced state. It is antigenic, so its antibody  antistreptolysin O  can be detected in an  antistreptolysin O titre ."}
{"_id": "WikiPedia_Hematology$$$corpus_1703", "text": "SLS is stable in the presence of oxygen. It is not antigenic due to its small size. It is sometimes considered a  bacteriocin  due to similarities in the synthesis pathway. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1704", "text": "Streptolysin O (SLO;  slo),  is a bacterial toxin that has four  protein domains  which is known to make the plasma membranes in animal cells permeable. It does this by creating pore complexes within the membrane by first binding a monomer to the cholesterol found in the target membrane and then forming an  oligomeric  transmembrane pore. [ 6 ]  This toxin excreted by a  Gram-positive bacteria   Streptococcus pyogenes ,  under the classification of  Thiol-activated cytolysin  or CDCs. In order for Streptolysin O to work effectively, it needs a significant amount of cholesterol to be present in the target membrane. Unlike other  Cholesterol-dependent cytolysins , SLO contains a 60  Amino acid  N-terminal domain that makes it easier to identify."}
{"_id": "WikiPedia_Hematology$$$corpus_1705", "text": "Human serum albumin  has been demonstrated to neutralize the cytotoxic and hemolytic effects of SLO through its binding in a non-conventional site located in domain II, previously reported to interact also with  C. difficile  toxins. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1706", "text": "This toxin contains highly antigenic effects which causes it to produce the antibody  anti-streptolysin O . Clinically, the presence of these antibodies can indicate a recent  Group A streptococcal infection . Streptolysin O is also known to facilitate apoptosis in  Keratinocytes . It is able to do this by translocating  NAD+ glycohydrolase  (SPN) across the target cells membrane. It then removes the N-terminal domain which stops SPN translocation leading to SPN mediated apoptosis. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1707", "text": "Group A streptococcal infections  are responsible for 517,000 deaths annually across the world. Not much is known about the exact mechanism of action in natural infections however, once the infection is present within the cells it can cause devastating effects. When tested in human endometrium cells, 50% of the cells were killed within the first two hours as a result of processes stimulated by Streptolysin O and SpeB proteases. It has also been observed that both Steptolysin O and SpeB protease limit the innate immune response. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1708", "text": "Streptolysin S (SLS;  sagA ), is a cytolytic  virulence  factor which is a membe of the thiazole/oxadole-modified microcin (TOMM) family. This cytolysin is a  post-translationally modified  peptide was synthesized through a natural evolutionary pathway. SLS is responsible for  Streptococcus pyogenes'   \u03b2-hemolytic appearance when grown on blood agar plates. Its biosynthesis is not fully known; however, it is a critical virulence factor for  Streptococcus pyogenes  infections. [ 10 ]  SLS brings about its virulence by damaging soft tissue and it can also act as a signaling molecule. When introduced to a host it will affect its phagocytes and also help to introduce GAS across the skin barrier. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1709", "text": "Streptolysin O (SLO)  is integral to the development of assays designed to detect Anti-Streptolysin O (ASO) antibodies in clinical settings. These assays are critical for diagnosing post-streptococcal diseases, such as acute rheumatic fever and post-streptococcal glomerulonephritis. The SLO antigen, when coupled with latex particles, induces a visible agglutination reaction in the presence of ASO antibodies, allowing for the precise measurement of antibody levels in patient samples."}
{"_id": "WikiPedia_Hematology$$$corpus_1710", "text": "Superficial vein thrombosis  ( SVT ) is a  blood clot  formed in a  superficial vein , a  vein  near the surface of the body. Usually there is  thrombophlebitis , which is an  inflammatory reaction  around a thrombosed vein, presenting as a painful  induration  (thickening of the skin) with  redness . SVT itself has limited significance (in terms of direct  morbidity  and  mortality ) when compared to a  deep vein thrombosis  (DVT), which occurs deeper in the body at the  deep venous system level . However, SVT can lead to serious complications (as well as signal other serious problems, such as genetic mutations that increase one's risk for clotting), and is therefore no longer regarded as a benign condition. If the blood clot is too near the  saphenofemoral junction  there is a higher risk of  pulmonary embolism , a potentially life-threatening complication."}
{"_id": "WikiPedia_Hematology$$$corpus_1711", "text": "SVT has risk factors similar to those for other thrombotic conditions and can arise from a variety of causes. Diagnosis is often based on symptoms. There are multiple possible treatments, with the goal of providing symptomatic relief and preventing complications."}
{"_id": "WikiPedia_Hematology$$$corpus_1712", "text": "SVT is recognized by the presence of pain, warmth, redness, and tenderness over a superficial vein. [ 1 ]  The SVT may present as a \"cord-like\" structure upon palpation. [ 1 ]  The affected vein may be hard along its entire length. [ 2 ]  SVTs tend to involve the legs, though they can affect any superficial vein (e.g. those in the arms). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1713", "text": "SVT in the lower extremities can lead to a dangerous complication in which the clot travels to the lungs, called  pulmonary embolism  (PE). [ 3 ]  This is because lower limb SVTs can migrate from superficial veins into deeper veins. [ 3 ]  In a French population, the percent of people with SVTs that also suffered from PEs was 4.7%. [ 3 ]  In the same population,  deep vein thrombosis  (DVT) was found in 24.6% of people with SVTs. [ 3 ]  However, because superficial veins lack muscular support, any clots that form are far less likely to be squeezed by muscle contraction, dislodged, and induce a PE. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1714", "text": "SVTs can recur after they resolve, which is termed \"migratory thrombophlebitis.\" [ 2 ]  Migratory thrombophlebitis is a complication that may be due to more serious disorders, such as cancer and other hypercoagulable states. [ 2 ] [ a ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1715", "text": "SVTs of the legs are often due to  varicose veins , though most people with varicose veins do not develop SVTs. [ 2 ]  SVTs of the arms are often due to the placement of intravenous catheters. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1716", "text": "Many of the risk factors that are associated with SVT are also associated with other thrombotic conditions (e.g. DVT). These risk factors include age,  cancer , history of  thromboembolism ,  pregnancy , use of  oral contraceptive  medications (containing estrogen), [ 4 ]   hormone replacement therapy , recent surgery, and certain  autoimmune diseases  (especially  Beh\u00e7et's  and  Buerger's  diseases). [ 3 ]  Other risk factors include immobilization (stasis) and  laparoscopy . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1717", "text": "Hypercoagulable states  due to genetic conditions that increase the risk of clotting may contribute to the development of SVT, such as  factor V Leiden ,  prothrombin 20210A  mutation, and  protein C ,  S , and  antithrombin III  and  factor XII deficiency . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1718", "text": "The mechanism for the development of an SVT depends upon the specific etiology of the SVT. For example, varicose veins and prolonged bed rest both may induce SVTs due to slowing the flow of blood through superficial veins. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1719", "text": "SVTs may be diagnosed based upon clinical criteria by a healthcare professional. [ 1 ]  A more specific evaluation can be made by  ultrasound . [ 1 ]  An ultrasound can be useful in situations in which an SVT occurs above the knee and is not associated with a varicose vein, because ultrasounds can detect more serious clots like DVTs. [ 2 ]  The diagnostic utility of  D-dimer  testing in the setting of SVTs has yet to be fully established. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1720", "text": "SVTs can be classified as either  varicose vein  (VV) or non-varicose (NV) associated. [ 1 ]  NV-SVTs are more likely to be associated with genetic procoagulable states compared to VV-SVTs. [ 1 ]  SVTs can also be classified by  pathophysiology . That is, primary SVTs are characterized by inflammation that is localized to the veins. Secondary SVTs are characterized by systemic inflammatory processes. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1721", "text": "A subclass of SVTs are  septic thrombophlebitis , which are SVTs that occur in the setting of an infection. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1722", "text": "The goal of treatment in SVT is to reduce local inflammation and prevent the SVT from extending from its point of origin. [ 1 ]  Treatment may entail the use of compression, physical activity, medications, or surgical interventions. [ 1 ]  The optimal treatment for many SVT sites (i.e. upper limbs, neck, abdominal and thoracic walls, and the penis) has not been determined. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1723", "text": "Multiple compression bandages exist. Fixed compression bandages, adhesive short stretch bandages, and graduated elastic  compression stockings  have all be used in the treatment of SVTs. [ 1 ]  The benefit of compression stockings is unclear, though they are frequently used. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1724", "text": "Inactivity is contraindicated in the aftermath of an SVT. [ 1 ]  Uninterrupted periods of sitting or standing may cause the SVT to elongate from its point of origin, increasing the risk for complications and clinical worsening. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1725", "text": "Medications used for the treatment of SVT include  anticoagulants ,  NSAIDs  (except  aspirin ),  antibiotics , and  corticosteroids . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1726", "text": "SVTs that occur within the  great saphenous vein  within 3\u00a0cm of the  saphenofemoral junction  are considered to be equivalent in risk to DVTs. [ 3 ]   These high risk SVTs are treated identically with therapeutic anticoagulation. [ 3 ]  Anticoagulation is also used for intermediate risk SVTs that are greater than 3\u00a0cm from the saphenofemoral junction or are greater than 4\u20135\u00a0cm in length. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1727", "text": "Anticoagulation for high risk SVTs includes the use of  vitamin K antagonists  or  novel oral anticoagulants (NOACs)  for 3 months. [ 3 ]  Anticoagulation for intermediate risk SVTs includes  fondaparinux  2.5\u00a0mg daily for 45 days or the use of intermediate to therapeutic dose  low molecular weight heparin  for 4\u20136 weeks. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1728", "text": "NSAIDs  (non-steroidal anti-inflammatory drugs) can be used in both oral or topical formulations for the relief of SVT symptoms. [ 3 ]  The British Committee for Standards in Haematology guidelines recommend the use of NSAIDs for low-risk SVTs (thrombus <4\u20135\u00a0cm in length, no additional risk factors for thromboembolic events). [ 3 ]  NSAIDs are used for treatment durations of 8\u201312 days. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1729", "text": "Antibiotics are used in the treatment of  septic SVT . [ 1 ]   Corticosteroids  are used for the treatment of SVTs in the setting of vasculitic and autoimmune syndromes. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1730", "text": "Surgical interventions are used for both symptomatic relief of the SVT as well as for preventing the development of more serious complications (e.g. pulmonary embolism). [ 3 ]  Surgical interventions include  ligation  of the saphenofemoral junction, ligation and  stripping  of the affected veins, and local  thrombectomy . [ 3 ]  Because of the risk of symptomatic pulmonary embolism with surgery itself, surgical interventions are not recommended for the treatment of lower limb SVTs by the 2012  American College of Chest Physicians  guidelines and the 2012  British Committee for Standards in Haematology  guidelines. [ 3 ]  The use of surgery for the treatment of SVT is controversial. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1731", "text": "SVT is often a mild, self-resolving medical condition. [ 1 ]  The inflammatory reaction may last up to 2\u20133 weeks, with possible recanalization of the thrombosed vein occurring in 6\u20138 weeks. [ 1 ]  The superficial vein may continue to be hyperpigmented for several months following the initial event. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1732", "text": "In a French population, SVT occurred in 0.64 per 1000 persons per year. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1733", "text": "SVTs have been historically considered to be benign diseases, for which treatment was limited to conservative measures. [ 6 ]  However, an increased awareness of the potential risks of SVTs developing into more serious complications has prompted more research into the diagnosis, classification, and treatment of SVTs. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1734", "text": "A Cochrane review recommends that future research investigate the utility of oral, topical, and surgical treatments for preventing the progression of SVTs and the development of thromboembolic complications. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1735", "text": "Tamponade  ( / \u02cc t \u00e6 m . p \u0259 \u02c8 n e\u026a d / [ 1 ] ) is the closure or blockage (as of a wound or body cavity) by or as if by a  tampon , especially to stop bleeding. [ 2 ] \nTamponade is a useful method of stopping a  hemorrhage . This can be achieved by applying an absorbent dressing directly into a wound, thereby absorbing excess blood and creating a blockage, or by applying direct pressure with a hand or a  tourniquet . \nNot to be confused with a tamponade that occurs as a result of health problems. For example:  cardiac tamponade  is a condition where fluid collects in the  pericardial sac  increasing pressure within the pericardium which in turn prevents the  ventricles  from expanding fully significantly reducing the efficiency of the heart. It is considered a medical emergency and if left unchecked is fatal."}
{"_id": "WikiPedia_Hematology$$$corpus_1736", "text": "Bladder tamponade  is obstruction of the  urinary bladder  outlet due to heavy  blood clot  formation within it. [ 3 ]  It generally requires surgery. [ 3 ]  Such heavy bleeding is usually due to  bladder cancer . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1737", "text": "Pressing  bone wax  into bleeding bone is considered hemostasis by tamponade, as opposed to methods which physically or biochemically activate the clotting cascade."}
{"_id": "WikiPedia_Hematology$$$corpus_1738", "text": "Gas tamponade has been used  for  retinal detachment  surgery, helping reduce the rate of fluid flow through retinal tears. Research suggests that patients undergoing surgery with tamponade agents of  C 3 F 8  gas and standard silicone oil had the best visual and anatomic outcomes, over other tamponade agents. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1739", "text": "THP-1  is a human  monocytic   cell line  derived from an  acute monocytic leukemia  patient. It is used to test  leukemia  cell lines in  immunocytochemical  analysis of protein-protein interactions, and  immunohistochemistry . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1740", "text": "Although THP-1 cells are of the same lineage, mutations can cause differences as the progeny proliferates. In general, THP-1 cells exhibit a large, round, single-cell morphology. The cells were derived from the peripheral blood of a 1-year-old human male with acute monocytic leukemia. Some of their characteristics are: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1741", "text": "THP-1 can provide continuous culture when grown in suspension;  RPMI  1640 + 10% FBS + 2mM L-Glutamine. The average doubling time is 19 to 50 hours.\n1 mM sodium pyruvate, penicillin (100 units/ml) and streptomycin (100 \u03bcg/ml) are also commonly added to inhibit bacterial contamination. Cultures should be maintained at cell densities in the range 2-9x10 5  cells/ml at 37\u00a0\u00b0C, 5% CO 2 . Cells are non-adherent. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1742", "text": "THP-1 cells are of human origin, and no evidence has been found for the presence of infectious viruses or toxic products. The ATCC Biosafety recommendation is level 1. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1743", "text": "THP-1 cells are used as a models to study the monocyte-macrophage differentiation process, [ 6 ]  antigen presentation [ 7 ] [ 8 ]  and as a model to examine some macrophage-related physiological processes, for example the macrophage cholesterol efflux. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1744", "text": "Thromboembolism  is a condition in which a blood clot ( thrombus ) breaks off from its original site and travels through the bloodstream (as an  embolus ) to obstruct a blood vessel, causing tissue  ischemia  and organ damage. Thromboembolism can affect both the venous and arterial systems, with different clinical manifestations and management strategies. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1745", "text": "Venous thromboembolism (VTE)  BD72  comprises the following conditions: [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1746", "text": "VTE is a common cardiovascular disorder with significant  morbidity  and mortality. [ 3 ] [ 4 ] [ 5 ]  VTE can present with various symptoms, such as painful leg swelling, chest pain,  dyspnea ,  hemoptysis ,  syncope , and even death, depending on the location and extent of the thrombus. [ 4 ] [ 6 ]  VTE can also cause long-term complications, such as recurrent VTE, post-PE syndrome, chronic thromboembolic pulmonary hypertension (CTEPH), and post-thrombotic syndrome (PTS). The mainstay of VTE management is anticoagulation therapy, which prevents thrombus propagation and embolization. Such treatment reduces the risk of recurrence. [ 5 ] [ 4 ] [ 1 ]  The choice and duration of anticoagulation depend on the individual patient's risk factors, bleeding risk, and preferences.  Direct oral anticoagulants  (DOACs) have emerged as an essential alternative to conventional anticoagulants, such as  vitamin K antagonists  (VKAs) and  low-molecular-weight heparins  (LMWHs), due to their rapid onset of action, predictable pharmacokinetics, fixed dosing, and lower risk of bleeding. DOACs can also facilitate home treatment and extended therapy for selected patients. In addition to anticoagulation, some patients with VTE may benefit from adjunctive therapies, such as  thrombolysis , catheter-directed interventions, or  inferior vena cava (IVC) filters , to remove or prevent thrombus migration. However, these therapies are associated with higher risks of bleeding and complications. These therapies are not routinely recommended by the current guidelines except for specific indications, such as massive PE, iliofemoral DVT, or contraindications to anticoagulation. The optimal duration of anticoagulation for VTE is determined by the balance between the risk of recurrence and the risk of bleeding, and should be individualized for each patient. In general, VTE provoked by a transient or reversible risk factor, such as surgery, trauma, or immobilization, should be treated for three months, while VTE provoked by a persistent or progressive risk factor, such as cancer, should be treated indefinitely. Unprovoked VTE, which occurs in the absence of any identifiable risk factor, has a high risk of recurrence and may require indefinite anticoagulation, depending on the patient's characteristics and preferences. [ 4 ] [ 7 ] [ 8 ]  Factors that favor indefinite anticoagulation include male sex, presentation as PE (especially with concomitant DVT), positive d-dimer test after stopping anticoagulation, presence of antiphospholipid antibodies, low bleeding risk, and patient preference. [ 3 ]  The type of anticoagulant used for indefinite therapy is of secondary importance, but low-dose DOACs may offer a convenient and safer option for some patients. [ 4 ] [ 7 ] [ 8 ]  For cancer-associated VTE, full-dose DOACs are now preferred over LMWHs, unless there are gastrointestinal lesions that increase the risk of bleeding. [ 4 ] [ 7 ] [ 8 ]   Graduated compression stockings  are elastic garments that apply a gradient of pressure to the lower limbs, reducing venous stasis and improving blood flow, still these stockings are not routinely indicated after DVT, but may be helpful if there is persistent leg swelling or symptomatic improvement with a trial of stockings. [ 3 ] [ 9 ]  Medications, such as  pentoxifylline , have a limited role in the treatment of PTS. After PE, patients should be monitored for signs and symptoms of CTEPH, which is a rare but serious complication of VTE. [ 4 ] [ 7 ] [ 8 ]  Ventilation-perfusion scanning and echocardiography are the initial diagnostic tests for CTEPH, and patients with confirmed or suspected CTEPH should be evaluated for potential treatments, such as  pulmonary thromboendarterectomy ,  balloon pulmonary angioplasty , or vasodilator therapies. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1747", "text": "Arterial thromboembolism  (ATE) is a less common but more severe form of thromboembolism, which can affect various organs, such as the brain, heart, kidneys, limbs, and mesentery. ATE can cause life-threatening conditions, such as stroke, myocardial infarction, acute kidney injury, limb ischemia, and mesenteric ischemia. ATE is usually caused by  atherosclerosis , which leads to plaque rupture and thrombus formation, or by cardioembolism, which results from the embolization of a cardiac thrombus, such as in atrial fibrillation, valvular disease, or myocardial dysfunction. The management of ATE depends on the location and severity of the ischemia and the underlying etiology. The main goals of ATE management are to restore blood flow, prevent further thrombosis, and treat the underlying cause. The treatment options for ATE include antithrombotic therapy, revascularization procedures, and risk factor modification. Antithrombotic therapy consists of antiplatelet agents, such as aspirin or clopidogrel, or anticoagulants, such as heparin or DOACs, depending on the indication and contraindications. Revascularization procedures include thrombolysis, thrombectomy, angioplasty, stenting, or bypass surgery and are indicated for patients with severe or limb-threatening ischemia or failed medical therapy. Risk factor modification involves lifestyle changes, such as smoking cessation, exercise, and diet, and pharmacological interventions, such as statins, antihypertensives, and glucose-lowering agents, to reduce the risk of recurrent ATE and improve the prognosis. The duration of antithrombotic therapy for ATE is variable, depending on the type and location of the thrombus, the presence of a prosthetic device, and the bleeding risk. In general, patients with ATE receive lifelong antiplatelet therapy unless there is a specific indication or contraindication for anticoagulation. [ 2 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1748", "text": "Property of a  material  (or substance) that induces and/or promotes the formation of a thrombus. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1749", "text": "Thrombogenicity  refers to the tendency of a material in contact with the blood to produce a  thrombus , or clot.  It not only refers to fixed thrombi but also to emboli, thrombi which have become detached and travel through the bloodstream.  Thrombogenicity can also encompass events such as the activation of immune pathways and the  complement system .  All materials are considered to be thrombogenic [ citation needed ]  with the exception of the normal state of  endothelial cells  which line  blood vessels . [ 2 ]   Certain medical implants appear non-thrombogenic due to high flow rates of blood past the implant, but in reality all are thrombogenic to a degree. Various  surface treatments  are available to minimize these thrombogenic effects."}
{"_id": "WikiPedia_Hematology$$$corpus_1750", "text": "A thrombogenic implant will eventually be covered by a fibrous capsule, the thickness of this capsule can be considered one measure of thrombogenicity, and if extreme can lead to the failure of the implant."}
{"_id": "WikiPedia_Hematology$$$corpus_1751", "text": "Thromboregulation  is the series of mechanisms in how a primary clot is regulated. These mechanisms include, competitive inhibition or negative feedback. It includes primary  hemostasis , which is the process of how blood platelets adhere to the endothelium of an injured blood vessel. [ 1 ] [ 2 ]   Platelet  aggregation is fundamental to repair vascular damage and the initiation of the blood thrombus formation. The elimination of clots is also part of thromboregulation. Failure in platelet clot regulation may cause hemorrhage or thrombosis. Substances called thromboregulators control every part of these events. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1752", "text": "One primary function of thromboregulation is the control of primary  hemostasis , which is the platelet aggregation process. Some thromboregulators enhance platelet aggregation and some others inhibit the process. Platelet aggregation plays a critical role in the genesis of a resulting  thrombus . Adhesion should remain local, but platelet aggregation must grow exponentially to form a platelet thrombus and prevent blood loss. Platelet aggregation factors are the regulators that enhance the adhesion and stimulate the platelets to secrete its granules. It has been shown that collagen, exposed after the injury to the endothelial cover of the vessel, plays as an agonist in platelet adhesion and its activation. The binding of platelets to the sub-endothelial collagen stimulates the secretion of  ADP ,  TXA2 , and  serotonin  present in the platelet granules. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1753", "text": "ADP-dependent aggregation is mediated by two receptors: the purinergic  P2Y1 , coupled to G\u03b1q, mediates the shape in the structure of platelets and triggers the aggregation process. [ 5 ]   Thromboxane A2  (TX2) has a positive feedback in platelet activation. It is produced by the oxygenation of arachidonic acid by two enzymes:  cycloxygenase  and thromboxane A2 synthase. TX2 effects are mediated by G protein-coupled receptors, subtypes TP\u03b1 and TP\u03b2. Both receptors mediate  phospholipase C  stimulation causing an increase of intracellular levels of  inositol 1,4,5-triphosphate  and  diacylglycerol . Inositol 1,4,5-triphosphate causes an increase in Ca concentration and the release of diacylglycerol activates  PKC . TP\u03b1 stimulates cAMP levels whereas TP\u03b2 inhibits the level of intracellular cAMP. [ 6 ]  Serotonin, 5-HT, is an amine synthesized in the gut and it is released into the bloodstream after the activation of presynaptic neurons or  enterochromaffin cells  stimulation. Later, it is sequestered by the platelets using antidepressant-sensitive 5-HT transporters (SERTs) and into platelet\u2019s granules by the  vesicular monoamine transporter  (VMAT).  After the secretion, 5-HT increases the effects of prothrombotic agents by its binding with 5-HT2 receptors  [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1754", "text": "Thromboregulation is also in charge of regulating the process of clot elimination, called primary hemostasis inhibition. These inhibitors are substances that prevent the clot formation by preventing platelet adhesion. Platelet inhibition is important to prevent thrombotic episodes or the formation of blood clot and consequently preventing heart attacks and strokes. Some primary hemostasis inhibitors are cAMP, prostacyclin,  PGE1 , and kistrin.  cAMP,  cyclic adenosine monophosphate , phosphorylate messengers via protein kinase A (PKA). These signaling elements include  thromboxane A2 , receptor type \u03b1, phospholipase C\u03b23, and IP3 receptors. Signalization in platelets is very sensitive in cAMP levels. [ 8 ] [ 9 ]   Nitric oxide  (NO) stimulates cGMP production and therefore the activation  cGMP-dependent protein kinase  (G kinase). This kinase inhibits G\u03b1q-phospholipase C-inositol 1,4,5-triphosphate signaling and the mobilization of calcium inside the cell for thromboxane A2. [ 10 ]   PGI2,  prostacyclin , binds to IP receptors that catalyze cAMP formation. This process is mediated via GTP-binding protein Gs and  adenylyl cyclase .  PGE1  binds to IP receptors. IP receptors bind with  ionophores  that induce ADP and serotonin secretion. PGE1 inhibits the secretion of factors that stimulate platelet aggregation by competitive inhibition. [ 11 ] [ 12 ]  Kistrin is a protein inhibitor of platelet aggregation. It belongs to the homologous family of glycoprotein IIb-IIa antagonists. Kistrin has an adhesion site that binds to GP IIb-IIIa. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1755", "text": "Thrombosis  (from  Ancient Greek     \u03b8\u03c1\u03cc\u03bc\u03b2\u03c9\u03c3\u03b9\u03c2  (thr\u00f3mb\u014dsis) \u00a0'clotting') is the formation of a  blood clot  inside a  blood vessel , obstructing the flow of  blood  through the  circulatory system . When a blood vessel (a  vein  or an  artery ) is injured, the body uses  platelets  (thrombocytes) and  fibrin  to form a  blood clot  to prevent blood loss.  Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an  embolus . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1756", "text": "Thrombosis may occur in  veins  ( venous thrombosis ) or in  arteries  ( arterial thrombosis ). Venous thrombosis (sometimes called DVT,  deep vein thrombosis ) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery ( ischemia  and  necrosis ). A piece of either an arterial or a venous thrombus can break off as an  embolus , which could then travel through the circulation and lodge somewhere else as an  embolism . This type of embolism is known as a  thromboembolism . Complications can arise when a venous thromboembolism (commonly called a VTE) lodges in the lung as a  pulmonary embolism . An arterial embolus may travel further down the affected blood vessel, where it can lodge as an embolism. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1757", "text": "Thrombosis is generally defined by the type of blood vessel affected (arterial or venous thrombosis) and the precise location of the blood vessel or the organ supplied by it. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1758", "text": "Deep vein thrombosis (DVT) is the formation of a blood  clot  within a  deep vein . It most commonly affects leg veins, such as the  femoral vein ."}
{"_id": "WikiPedia_Hematology$$$corpus_1759", "text": "Three factors are important in the formation of a blood clot within a deep vein\u2014these are:"}
{"_id": "WikiPedia_Hematology$$$corpus_1760", "text": "Classical signs of DVT include  swelling , pain and redness of the affected area. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1761", "text": "Paget-Schroetter disease  or upper extremity DVT (UEDVT) is the obstruction of an  arm  vein (such as the  axillary vein  or  subclavian vein ) by a thrombus. The condition usually comes to light after vigorous exercise and usually presents in younger, otherwise healthy people. Men are affected more than women. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1762", "text": "Budd-Chiari syndrome  is the blockage of a  hepatic vein  or of the hepatic part of the  inferior vena cava . This form of thrombosis presents with  abdominal pain ,  ascites  and  enlarged liver . Treatment varies between therapy and surgical intervention by the use of  shunts . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1763", "text": "Portal vein thrombosis affects the  hepatic portal vein , which can lead to portal  hypertension  and reduction of the blood supply to the  liver . [ 6 ]  It usually happens in the setting of another disease such as  pancreatitis ,  cirrhosis ,  diverticulitis  or  cholangiocarcinoma . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1764", "text": "Renal vein thrombosis is the obstruction of the  renal vein  by a thrombus. This tends to lead to reduced drainage from the  kidney . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1765", "text": "Cerebral venous sinus thrombosis (CVST) is a rare form of  stroke  which results from the blockage of the  dural venous sinuses  by a thrombus. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body and  seizures . The diagnosis is usually made with a  CT  or  MRI scan . The majority of persons affected make a full recovery. The  mortality rate  is 4.3%. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1766", "text": "Jugular vein  thrombosis is a condition that may occur due to infection, intravenous drug use or malignancy. Jugular vein thrombosis can have a varying list of complications, including:  systemic sepsis ,  pulmonary embolism , and  papilledema . Though characterized by a sharp pain at the site of the vein, it can prove difficult to diagnose, because it can occur at random. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1767", "text": "Cavernous sinus thrombosis  is a specialised form of cerebral venous sinus thrombosis, where there is thrombosis of the  cavernous sinus  of the basal skull dura, due to the retrograde spread of infection and endothelial damage from the  danger triangle  of the face. The facial veins in this area anastomose with the  superior  and  inferior  ophthalmic veins of the orbit, which drain directly posteriorly into the cavernous sinus through the  superior orbital fissure .  Staphyloccoal  or  Streptococcal  infections of the face, for example nasal or upper lip pustules may thus spread directly into the cavernous sinus, causing stroke-like symptoms of  double vision ,  squint , as well as spread of infection to cause  meningitis . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1768", "text": "Arterial thrombosis is the formation of a thrombus within an  artery . In most cases, arterial thrombosis follows rupture of  atheroma  (a fat-rich deposit in the blood vessel wall), and is therefore referred to as  atherothrombosis .  Arterial embolism  occurs when clots then migrate downstream and can affect any organ. [ 12 ]  Alternatively, arterial occlusion occurs as a consequence of embolism of blood clots originating from the heart (\"cardiogenic\" emboli). The most common cause is  atrial fibrillation , which causes a blood stasis within the atria with easy thrombus formation, but blood clots can develop inside the heart for other reasons too as infective endocarditis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1769", "text": "A stroke is the rapid decline of brain function due to a disturbance in the supply of blood to the brain. [ 13 ]  This can be due to  ischemia , thrombus,  embolus  (a lodged particle) or  hemorrhage  (a bleed). [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1770", "text": "In thrombotic stroke, a thrombus (blood clot) usually forms around  atherosclerotic  plaques. Since blockage of the artery is gradual, the onset of symptomatic thrombotic strokes is slower. Thrombotic stroke can be divided into two categories \u2014 large vessel disease or small vessel disease. The former affects vessels such as the  internal carotids ,  vertebral  and the  circle of Willis . The latter can affect smaller vessels, such as the branches of the circle of Willis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1771", "text": "Myocardial infarction (MI), or heart attack, is caused by ischemia (restriction in the blood supply), which is often due to the obstruction of a  coronary artery  by a thrombus. This restriction gives an insufficient supply of oxygen to the heart muscle which then results in tissue death (infarction). A lesion is then formed which is the  infarct . MI can quickly become fatal if emergency medical treatment is not received promptly. If diagnosed within 12 hours of the initial episode (attack) then  thrombolytic therapy  is initiated. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1772", "text": "An arterial thrombus or embolus can also form in the limbs, which can lead to  acute limb ischemia . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1773", "text": "Hepatic artery thrombosis  usually occurs as a devastating complication after  liver transplantation . [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1774", "text": "Thrombosis prevention is initiated with assessing the risk for its development.  Some people have a higher risk  of developing thrombosis and its possible development into  thromboembolism . [ 16 ]  Some of these risk factors are related to  inflammation ."}
{"_id": "WikiPedia_Hematology$$$corpus_1775", "text": "\" Virchow's triad \" has been suggested to describe the three factors necessary for the formation of thrombosis:"}
{"_id": "WikiPedia_Hematology$$$corpus_1776", "text": "Some risk factors predispose for venous thrombosis while others increase the risk of arterial thrombosis. [ citation needed ]  Newborn babies in the neonatal period are also at risk of a thromboembolism. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1777", "text": "The main causes of thrombosis are given in  Virchow's triad  which lists  thrombophilia ,  endothelial cell  injury, and disturbed  blood flow . Generally speaking the risk for thrombosis increases over the life course of individuals, depending on life style factors like smoking, diet, and physical activity, the presence of other diseases like cancer or autoimmune disease, while also platelet properties change in aging individuals which is an important consideration as well. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1778", "text": "Hypercoagulability or  thrombophilia , is caused by, for example,  genetic deficiencies  or  autoimmune disorders . Recent studies indicate that white blood cells play a pivotal role in deep vein thrombosis, mediating numerous pro-thrombotic actions. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1779", "text": "Any inflammatory process, such as trauma, surgery or infection, can cause damage to the  endothelial lining  of the vessel's wall. The main mechanism is exposure of  tissue factor  to the blood coagulation system. [ 33 ]  Inflammatory and other stimuli (such as  hypercholesterolemia ) can lead to changes in  gene expression  in endothelium producing to a pro-thrombotic state. [ 34 ]  When this occurs, endothelial cells  downregulate  substances such as  thrombomodulin , which is a key modulator of thrombin activity. [ 35 ]  The result is a sustained activation of thrombin and reduced production of  protein C  and tissue factor inhibitor, which furthers the pro-thrombotic state. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1780", "text": "Endothelial injury is almost invariably involved in the formation of thrombi in arteries, as high rates of blood flow normally hinder clot formation. In addition, arterial and cardiac clots are normally rich in platelets\u2013which are required for clot formation in areas under high stress due to blood flow. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1781", "text": "Causes of disturbed blood flow include stagnation of blood flow past the point of injury, or  venous stasis  which may occur in heart failure, [ 33 ]  or after long periods of sedentary behaviour, such as sitting on a long airplane flight. Also,  atrial fibrillation , causes stagnant blood in the left atrium (LA), or  left atrial appendage  (LAA), and can lead to a  thromboembolism . [ 33 ]   Cancers  or  malignancies  such as  leukemia  may cause increased risk of thrombosis by possible activation of the coagulation system by cancer cells or secretion of procoagulant substances ( paraneoplastic syndrome ), by external compression on a blood vessel when a solid tumor is present, or (more rarely) extension into the vasculature (for example, renal cell cancers extending into the renal veins). [ 33 ]  Also, treatments for cancer (radiation, chemotherapy) often cause additional hypercoagulability. [ 33 ]  There are scores that correlate different aspects of patient data (comorbidities, vital signs, and others) to risk of thrombosis, such as the POMPE-C, which stratifies risk of mortality due to pulmonary embolism in patients with cancer, who typically have higher rates of thrombosis. [ 37 ]  Also, there are several predictive scores for thromboembolic events, such as Padua, [ 38 ]  Khorana, [ 39 ] [ 40 ]  and  ThroLy score . [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1782", "text": "Fibrinolysis  is the physiological breakdown of blood clots by enzymes such as  plasmin ."}
{"_id": "WikiPedia_Hematology$$$corpus_1783", "text": "Organisation: following the thrombotic event, residual vascular thrombus will be re-organised histologically with several possible outcomes. For an occlusive thrombus (defined as thrombosis within a small vessel that leads to complete occlusion),  wound healing  will reorganise the occlusive thrombus into collagenous  scar  tissue, where the scar tissue will either permanently obstruct the vessel, or contract down with  myofibroblastic  activity to unblock the  lumen . For a mural thrombus (defined as a thrombus in a large vessel that restricts the blood flow but does not occlude completely), histological reorganisation of the thrombus does not occur via the classic  wound healing  mechanism. Instead, the  platelet-derived growth factor  degranulated by the clotted  platelets  will attract a layer of  smooth muscle  cells to cover the clot, and this layer of mural smooth muscle will be vascularised by the blood inside the vessel lumen rather than by the  vasa vasorum . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1784", "text": "Ischemia/infarction: if an arterial thrombus cannot be lysed by the body and it does not embolise, and if the thrombus is large enough to impair or occlude blood flow in the involved artery, then local  ischemia  or  infarction  will result. A  venous thrombus  may or may not be ischemic, since veins distribute deoxygenated blood that is less vital for cellular metabolism. Nevertheless, non-ischemic venous thrombosis may still be problematic, due to the swelling caused by blockage to venous drainage. In  deep vein thrombosis  this manifests as pain, redness, and swelling; in  retinal vein occlusion  this may result in  macular oedema  and  visual acuity  impairment, which if severe enough can lead to blindness."}
{"_id": "WikiPedia_Hematology$$$corpus_1785", "text": "A thrombus may become detached and enter circulation as an  embolus , finally lodging in and completely obstructing a blood vessel, which unless treated very quickly will lead to tissue necrosis (an  infarction ) in the area past the occlusion. Venous thrombosis can lead to pulmonary embolism when the migrated embolus becomes lodged in the lung. In people with a \"shunt\" (a connection between the pulmonary and systemic circulation), either in the heart or in the lung, a venous clot can also end up in the arteries and cause arterial embolism. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1786", "text": "Arterial embolism can lead to obstruction of blood flow through the blood vessel that is obstructed by it, and a lack of oxygen and nutrients ( ischemia ) of the downstream tissue. The tissue can become irreversibly damaged, a process known as  necrosis . This can affect any organ; for instance, arterial embolism of the brain is one of the causes of stroke. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1787", "text": "The use of  heparin  following surgery is common if there are no issues with bleeding. Generally, a risk-benefit analysis is required, as all anticoagulants lead to an increased risk of bleeding. [ 42 ]  In people admitted to hospital, thrombosis is a major cause for complications and occasionally death. In the UK, for instance, the Parliamentary  Health Select Committee  heard in 2005 that the annual rate of death due to thrombosis was 25,000, with at least 50% of these being hospital-acquired. [ 43 ]  Hence  thromboprophylaxis  (prevention of thrombosis) is increasingly emphasized. In patients admitted for surgery, graded  compression stockings  are widely used, and in severe illness, prolonged immobility and in all  orthopedic surgery ,  professional guidelines  recommend  low molecular weight heparin  (LMWH) administration, mechanical calf compression or (if all else is contraindicated and the patient has recently developed deep vein thrombosis) the insertion of a  vena cava filter . [ 44 ] [ 45 ]  In patients with medical rather than surgical illness, LMWH too is known to prevent thrombosis, [ 45 ] [ 46 ]  and in the United Kingdom the  Chief Medical Officer  has issued guidance to the effect that preventative measures should be used in medical patients, in anticipation of formal guidelines. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1788", "text": "The treatment for thrombosis depends on whether it is in a vein or an artery, the impact on the person, and the risk of complications from treatment. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1789", "text": "Warfarin  and  vitamin K antagonists  are  anticoagulants  that can be taken orally to reduce thromboembolic occurrence. Where a more effective response is required, heparin can be given (by injection) concomitantly. As a side effect of any anticoagulant, the risk of bleeding is increased, so the  international normalized ratio  of blood is monitored. Self-monitoring and self-management are safe options for competent patients, though their practice varies. In Germany, about 20% of patients were self-managed while only 1% of U.S. patients did home self-testing (according to one 2012 study). [ 47 ]  Other medications such as  direct thrombin inhibitors  and  direct Xa inhibitors  are increasingly being used instead of warfarin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1790", "text": "Thrombolysis  is the pharmacological destruction of blood clots by administering  thrombolytic drugs  including  recombinant tissue plasminogen activator , which enhances the normal destruction of blood clots by the body's enzymes. This carries an increased risk of bleeding so is generally only used for specific situations (such as severe stroke or a massive pulmonary embolism). [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1791", "text": "Arterial thrombosis may require surgery if it causes  acute limb ischemia . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1792", "text": "Mechanical clot retrieval and catheter-guided thrombolysis are used in certain situations. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1793", "text": "Arterial thrombosis is platelet-rich, and inhibition of platelet aggregation with  antiplatelet drugs  such as  aspirin  may reduce the risk of recurrence or progression. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1794", "text": "With reperfusion comes ischemia/reperfusion (IR) injury (IRI), which paradoxically causes cell death in reperfused tissue [ 51 ]  and contributes significantly to post-reperfusion mortality and morbidity. [ 52 ] [ 53 ]  For example, in a feline model of intestinal ischemia, four\u2009hours of ischemia resulted in less injury than three\u2009hours of ischemia followed by one\u2009hour of reperfusion. [ 51 ]  In ST-elevation myocardial infarction (STEMI), IRI contributes up to 50% of final infarct size despite timely primary percutaneous coronary intervention. This is a key reason for the continued high mortality and morbidity in these conditions, despite endovascular reperfusion treatments and continuous efforts to improve timeliness and access to these treatments. Hence, protective therapies are required to attenuate IRI alongside reperfusion in acute ischemic conditions to improve clinical outcomes. [ 54 ]  Therapeutic strategies that have potential to improve clinical outcomes in reperfused STEMI patients include  remote ischemic conditioning  (RIC), exenatide, and metoprolol. These have emerged amongst a multitude of cardioprotective interventions investigated with largely neutral clinical data. [ 55 ]  Of these, RIC has the most robust clinical evidence, especially in the context of STEMI, but also emerging for other indications such as acute ischemic stroke and aneurysmal subarachnoid hemorrhage. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1795", "text": "Treatment options for full-term and preterm babies who develop thromboembolism include expectant management (with careful observation), nitroglycerin ointment,  pharmacological therapy  (thrombolytics and/or anticoagulants), and surgery. [ 19 ]  The evidence supporting these treatment approaches is weak. For anticoagulant treatment, it is not clear if unfractionated and/or low molecular weight heparin treatment is effective at decreasing mortality and serious adverse events in this population. [ 19 ]   There is also insufficient evidence to understand the risk of adverse effects associated with these treatment approaches in term or preterm infants. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1796", "text": "Thrombosis prevention  or  thromboprophylaxis  is  medical treatment  to prevent the development of  thrombosis  ( blood clots  inside  blood vessels ) in those considered at risk for developing thrombosis. [ 1 ]  Some people are at a higher  risk  for the formation of blood clots than others, such as those with  cancer  undergoing a surgical procedure. [ 2 ] [ 3 ]  Prevention measures or interventions are usually begun after surgery as the associated immobility will increase a person's risk. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1797", "text": "Blood thinners  are used to prevent clots, these blood thinners have different effectiveness and safety profiles. A 2018 systematic review found 20 studies that included 9771 people with cancer. The evidence did not identify any difference between the effects of different blood thinners on death, developing a clot, or  bleeding . [ 2 ]  A 2021 review found that  low molecular weight heparin  (LMWH) was superior to unfractionated  heparin  in the initial treatment of  venous thromboembolism  for people with cancer. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1798", "text": "There are medication-based  interventions  and non-medication-based interventions. [ 4 ]  The risk of developing blood clots can be lowered by life style modifications, the discontinuation of  oral contraceptives , and  weight loss . In those at high risk both interventions are often used. [ 1 ]  The treatments to prevent the formation of blood clots is balanced against the risk of bleeding. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1799", "text": "One of the goals of blood clot prevention is to limit  venous stasis  as this is a significant risk factor for forming blood clots in the  deep veins  of the legs. [ 6 ]  Venous stasis can occur during the long periods of  not moving . Thrombosis prevention is also recommended during air travel. [ 7 ]  Thrombosis prophylaxis is effective in preventing the formation of blood clots, their lodging in the veins, and their developing into  thromboemboli  that can travel through the  circulatory system  to cause blockage and subsequent  tissue death  in other  organs . [ 1 ]   Clarence Crafoord  is credited with the first use of thrombosis prophylaxis in the 1930s."}
{"_id": "WikiPedia_Hematology$$$corpus_1800", "text": "The development of blood clots can be interrupted and prevented by the use of medication, changing  risk factors  and other interventions. Some risk factors can be modified. These would be losing weight, increasing exercise and the cessation of oral contraceptives. Moving during periods of travel is a modifiable behavior. Preventing blood clots includes the use of medications that interrupt the complex  clotting cascade  and changing the proteins that are needed for clotting.  Antiplatelet  drugs also have an effect in preventing the formation of clots. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1801", "text": "Thrombosis prophylaxis is not only used for the prevention of  deep vein thrombosis , but can be initiated for the prevention of the formation of blood clots in other organs and circumstances unrelated to deep vein thrombosis: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1802", "text": "The risk of developing deep vein thrombosis, or pulmonary embolism is different than the total risk of the formation of blood clots. This is due to the observation that not all blood clots form in the lower legs. Most hospitalized medical patients have at least 1 risk factor for thrombosis that progresses to thromboembolism and this risk persists weeks after discharge. Those who remain undiagnosed and not treated prophylactically have a 26% chance of developing a fatal embolism. Another 26% develop another embolism. Between 5% and 10% of all in hospital deaths are due to pulmonary embolism (as a consequence of thrombosis). Estimates of the incidence of pulmonary embolism in the US is 0.1% persons/year. Hospital admissions in the US for pulmonary embolism are 200,000 to 300,000 yearly. [ 10 ]  Thrombosis that develops into DVT will affect 900,000 people and kill up to 100,000 in the US. On average 28,726 hospitalized adults aged 18 and older with a VTE blood clot diagnosis die each year. [ 11 ]  Risk of thrombosis is related to hospitalization. [ 4 ]  In 2005 the UK the Parliamentary  Health Select Committee  determined the annual rate of death due to thrombosis was 25,000 with at least 50% being hospital-acquired. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1803", "text": "The type of surgery performed prior to the formation of blood clots influences the risk.\nWithout prophylactic interventions, the calculated incidence of clot formation in the lower leg veins after surgery is:"}
{"_id": "WikiPedia_Hematology$$$corpus_1804", "text": "As the population of the US ages, the development of blood clots is becoming more common. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1805", "text": "Some risk factors for developing blood clots are considered higher that others. One scoring system analyzes the probability for clot formation by assigning a point value system to significant risk factors. [ 15 ]  The benefit of treating those who are at low risk of developing blood clots may not outweigh the higher risks of significant bleeding. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1806", "text": "[ 1 ] [ 20 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1807", "text": "Developing blood clots is more probable after the first episode. Risk assessment and intervention for those with one or more episodes of deep vein thrombosis or blood clots in the veins utilizes the Well's test. It has been inconsistently modified by a number of publishers with the results listed below: [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1808", "text": "Scoring:"}
{"_id": "WikiPedia_Hematology$$$corpus_1809", "text": "The  Centers for Disease Control and Prevention  have issued general guidelines describing the interventions that can be taken to reduce the risk of the formation of blood clots:"}
{"_id": "WikiPedia_Hematology$$$corpus_1810", "text": "The Centers for Disease Control and Prevention recommend the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_1811", "text": "Seat-edge pressure from the seat on an airplane on the  popliteal area  may contribute to vessel wall damage as well as  venous stasis .  Coagulation  activation may result from an interaction between cabin conditions (such as  hypobaric   hypoxia ) and individual risk factors for the formation of blood clots. Studies of the  pathophysiologic mechanisms  for the increased risk of  Venous thrombosis embolism  or VTE after long-distance travel have not produced consistent results, but venous stasis appears to play a major role; other factors specific to air travel may increase coagulation activation, particularly in passengers with individual risk factors for VTE. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1812", "text": "Mechanical compression devices are used for prevention of thrombosis and are beneficial enough to be used by themselves with patients at low to moderate risk. [ 4 ]  The use of fitted  intermittent pneumatic compression devices  before, during and after procedures is used in inpatient settings. It consists of an air pump and inflatable auxiliary compartments that sequentially inflates and deflated to provide an external 'pump' that returns venous blood toward the heart. [ 31 ]  The use of intermittent pneumatic compression is common. [ 31 ] [ 19 ] [ 5 ]  These devices are also placed on a surgical patient in the operating room (the intra-surgical period) and remain on the person while recovering from the surgery. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1813", "text": "The application of  antiembolism stockings  can be used to prevent thrombosis. [ 4 ]  The correct use and properly fitted graded compression stockings can reduce the rate of thrombosis by 50%. [ 15 ] [ 19 ] :\u200a745\u201346\u200a  Contraindications for the use of antiembolism stockings include the presence of advanced peripheral and obstructive arterial disease, septic phlebitis, heart failure, open wounds, dermatitis and peripheral neuropathy. [ 33 ]  Differences between the use of thigh-high compression stockings and shorter types to prevent blood clots exist, but remain inconsistent. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1814", "text": "There has been some success in preventing blood clots by an early risk assessment upon admission to the hospital, which is a strategy recognized by the Centers for Disease Control and Prevention. Hospitals that have participated in this effort to reduce the incidence of thrombosis found that rates of DVT decreased in some instances. [ 34 ]  Some hospitals developed a mandatory assessment quantifying the risk for developing blood clots and a plan of care developed from the results. The person's risk for developing blood clots is entered into their record, 'following' them through their treatment regime. If the hospital stay exceeds three days, the person will be reassessed for risk. Clinicians are then able to apply protocols for prevention based upon best clinical practices. [ 35 ] [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1815", "text": "Immobility is a significant risk factor in the development of thrombosis. [ 37 ] [ 38 ] [ 22 ] [ 25 ]  Immediate post-surgical interventions, such as out of bed orders (OOB), are typically ordered by the physician to prevent thrombosis. These orders, typically delegated to a nurse, but may include the participation of a physical therapist and others trained to perform the intervention, are to perform range of motion (ROM) activities that include: muscle contractions of the lower legs for those who are very weak, moving the feet, wiggling the toes, bending the knees, raise and lower the legs. In addition, changes in positioning prevents immobility and shifts areas of venous stasis. If the person is too weak to perform these preventative activities, hospital personnel will perform these movements independently. Exercise of the lower extremities is a post-operative method of prophylaxis. Nursing personnel will often perform range of motion exercises and encourage frequent moving of the legs, feet, and ankles. Frequent positioning changes and adequate fluid intake. After a surgical procedure, ambulation as soon as possible is prophylactic in preventing the formation of blood clots. [ 38 ] [ 22 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1816", "text": "Early ambulation also prevents venous stasis and physicians order OOB activities on the same day of surgery. This is accomplished in increments. The progression of increasing mobility proceeds by: raising the head of the bed, sitting up in bed, moving to the edge of the bed, dangling the legs off the bed and then ambulating to a close chair. [ 19 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1817", "text": "Patient education and compliance reduces the risk of developing blood clots. These exercises and use of equipment and follow up by clinicians reduces the risk of developing blood clots. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1818", "text": "Note that if a blood clot has already formed in the deep veins of the leg, bedrest is usually prescribed and the treatment to prevent bloods with physical intervention is  contraindicated . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1819", "text": "Thromboprophylaxis, such as  anticoagulants  or perioperative heparin, is effective for hospitalized patients at risk for VTE. [ 2 ] [ 39 ]  Additional risk factors such as obesity, disease, malignancies, long surgeries, and immobility may influence the prescribed dosage. Anticoagulant medications may prevent the formation of blood clots in people who are at high risk for their development. [ 4 ]  Treating blood clots that have already formed is managed by the use of anti-hemolytic (\"clot busters\"). Despite its effectiveness, the use of thromboprophylaxis remains under-utilized, though alerts (computer or human) in hospitals are associated with increased prescription and reductions in symptomatic VTE. [ 39 ]  The list below describes some of the more common medications used to prevent blood clots. [ 24 ]  Note that generally since blood clotting is inhibited, a side effect typically is increased bleeding, though it can be reversed by administering a medication that stops the bleeding or by discontinuation of the medication itself. Anti-coagulant administration is often given before the start of the operation. [ 25 ]  Medications that inhibit blood clot formation include:"}
{"_id": "WikiPedia_Hematology$$$corpus_1820", "text": "Adding heparin to the use of compression stockings may prevent thrombosis for those of higher risk. [ 4 ] [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1821", "text": "The discontinuation of contraceptives also prevents blood clots. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1822", "text": "The therapeutic effects of warfarin may be decreased by  valerian . Anticoagulants can be affected by  chamomile .  Dong quai , garlic,  ginger ,  Ginkgo biloba ,  bilberry   and  feverfew  can increase bleeding time. These same  herbal supplements  taken with warfarin increased  prothrombin time . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1823", "text": "By containing significant content of  vitamin K , some foods act as  antagonists  to antiplatelet and anticoagulant medications; these include green leafy vegetables, like  spinach ,  legumes , and  broccoli . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1824", "text": "Preventing blood clots with medication is not considered safe in the following circumstances:"}
{"_id": "WikiPedia_Hematology$$$corpus_1825", "text": "An international registry and risk assessment calculator is being used to centralize data on post-surgical venous thrombosis and its prevention. [ 53 ]  Hospitals are implementing a  multi-disciplinary approach  to prevent of blood clots. This includes adequate assessment of the risks, follow up on missed doses of medication and instituting a 'patient-centered' approach endorsed by the  Joint Commission . [ 34 ]  Recommendations regarding the prevention of blood clots vary widely between clinicians and treatment facilities. Research continues to clarify these discrepancies. [ 5 ]  The metabolic state of hypercoagulability (the tendency to form blood clots) tests are being developed. These include the evaluation of the  thrombin\u2013antithrombin complexes  (TAT), low levels of the anticoagulants ATIII and protein C, but these tests are not yet widely available. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1826", "text": "Using Wikipedia for Research"}
{"_id": "WikiPedia_Hematology$$$corpus_1827", "text": "A  thrombus  ( pl.   thrombi ), colloquially called a  blood clot , is the final product of the  blood coagulation  step in  hemostasis . There are two components to a thrombus: aggregated  platelets  and  red blood cells  that form a plug, and a mesh of cross-linked  fibrin  protein. The substance making up a thrombus is sometimes called  cruor . A thrombus is a healthy response to  injury  intended to stop and prevent further bleeding, but can be harmful in  thrombosis , when a clot obstructs blood flow through a healthy  blood vessel  in the  circulatory system ."}
{"_id": "WikiPedia_Hematology$$$corpus_1828", "text": "In the  microcirculation  consisting of the very small and smallest blood vessels the  capillaries , tiny thrombi known as microclots can obstruct the flow of blood in the capillaries. This can cause a number of problems particularly affecting the  alveoli  in the  lungs  of the  respiratory system  resulting from reduced oxygen supply. Microclots have been found to be a characteristic feature in severe cases of  COVID-19  and in  long COVID . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1829", "text": "Mural thrombi are thrombi that adhere to the wall of a large  blood vessel  or  heart chamber . [ 2 ]  They are most commonly found in the  aorta , the largest  artery  in the body, more often in the  descending aorta , and less often in the  aortic arch  or  abdominal aorta . [ 2 ]  They can restrict blood flow but usually do not block it entirely. They appear grey-red along with alternating light and dark lines (known as  lines of Zahn ) which represent bands of white blood cells and red blood cells (darker) entrapped in layers of fibrin. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1830", "text": "Thrombi are classified into two major groups depending on their location and the relative amount of platelets and red blood cells. [ 4 ]  The two major groups are:"}
{"_id": "WikiPedia_Hematology$$$corpus_1831", "text": "In the  microcirculation  consisting of the very small and smallest blood vessels, the  capillaries , tiny thrombi (microthrombi) [ 5 ]  known as microclots can obstruct the flow of blood in the capillaries. Microclots are small clumps of blood that form within the circulation, usually as a result of a larger thrombus breaking down into smaller pieces. They can be a cause for concern as they can lead to blockages in small vessels and restrict blood flow, leading to tissue damage and potentially causing  ischemic events . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1832", "text": "Microclots can cause a number of problems particularly affecting the  alveoli  in the  lungs  of the  respiratory system , resulting from reduced oxygen supply. Microclots have been found to be a characteristic feature in severe cases of  COVID-19 , and in  long COVID . [ 1 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1833", "text": "Mural thrombi form and adhere on the inner wall of a large  blood vessel  or  heart chamber , often as a result of blood stasis. [ 2 ]  They are most commonly found in the  aorta , the largest  artery  in the body, more often in the  descending aorta , and less often in the  aortic arch  or  abdominal aorta . [ 2 ]  They can restrict blood flow but usually do not block it entirely. Mural thrombi are usually found in vessels already damaged by  atherosclerosis . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1834", "text": "A mural thrombus can affect any heart chamber. When found in the  left ventricle  it is often a result of a heart attack complication. The thrombus in this case can separate from the chamber, be carried through arteries and block a blood vessel. [ 2 ]  They appear grey-red with alternating light and dark lines (known as  lines of Zahn ) which represent bands of white blood cells and red blood cells (darker) entrapped in layers of  fibrin . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1835", "text": "It was suggested over 150 years ago that thrombus formation is a result of abnormalities in blood flow, vessel wall, and blood components. This concept is now known as  Virchow's triad . The three factors have been further refined to include circulatory stasis, vascular wall injury, and hypercoagulable state, all of which contribute to increased risk for venous thromboembolism and other cardiovascular diseases. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1836", "text": "Virchow's triad  describes the  pathogenesis  of thrombus formation: [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1837", "text": "Disseminated intravascular coagulation  (DIC) involves widespread microthrombi formation throughout the majority of the blood vessels. This is due to excessive consumption of coagulation factors and subsequent activation of  fibrinolysis  using all of the body's available  platelets  and clotting factors. The result is hemorrhaging and ischemic necrosis of tissue/organs. Causes are  septicaemia , acute  leukaemia ,  shock , snake bites,  fat emboli  from broken bones, or other severe traumas. DIC may also be seen in  pregnant females . Treatment involves the use of  fresh frozen plasma  to restore the level of clotting factors in the blood, as well as platelets and heparin to prevent further thrombi formation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1838", "text": "A thrombus occurs when the hemostatic process, which normally occurs in response to injury, becomes activated in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut off (termed an occlusive thrombus), resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is considered an  embolus . [ citation needed ]  If an embolus becomes trapped within a blood vessel, it blocks blood flow and is termed as an embolism. Embolisms, depending on their specific location, can cause more significant effects like strokes, heart attacks, or even death. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1839", "text": "Some of the conditions which increase the risk of blood clots developing include  atrial fibrillation  (a form of  cardiac arrhythmia ), heart valve replacement, a recent  heart attack  (also known as a  myocardial infarction ), extended periods of inactivity (see  deep venous thrombosis ), and genetic or disease-related deficiencies in the blood's clotting abilities. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1840", "text": "Platelet activation occurs through injuries that damage the  endothelium  of the blood vessels, exposing the enzyme called  factor VII , a protein normally circulating within the vessels, to the  tissue factor , which is a protein encoded by the\u00a0F3\u00a0gene.\nThe platelet activation can potentially cause a cascade, eventually leading to the formation of the thrombus. [ 12 ]  This process is regulated through  thromboregulation ."}
{"_id": "WikiPedia_Hematology$$$corpus_1841", "text": "Anticoagulants  are drugs used to prevent the formation of blood clots, reducing the risk of  stroke ,  heart attack  and  pulmonary embolism .  Heparin  and  warfarin  are used to inhibit the formation and growth of existing thrombi, with the former used for acute anticoagulation while the latter is used for long-term anticoagulation. [ 8 ]  The mechanism of action of heparin and warfarin are different as they work on different pathways of the  coagulation cascade . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1842", "text": "Heparin works by binding to and activating the enzyme inhibitor  antithrombin III , an enzyme that acts by inactivating thrombin and factor Xa. [ 13 ]  In contrast, warfarin works by inhibiting  vitamin K epoxide reductase , an enzyme needed to synthesize vitamin K dependent clotting factors II, VII, IX, and X. [ 13 ] [ 14 ]  Bleeding time with heparin and warfarin therapy can be measured with the partial thromboplastin time (PTT) and  prothrombin time  (PT), respectively. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1843", "text": "Once clots have formed, other drugs can be used to promote  thrombolysis  or clot breakdown.  Streptokinase , an enzyme produced by  streptococcal bacteria , is one of the oldest thrombolytic drugs. [ 14 ]  This drug can be administered  intravenously  to dissolve blood clots in  coronary vessels . However, streptokinase causes systemic fibrinolytic state and can lead to bleeding problems.  Tissue plasminogen activator  (tPA) is a different enzyme that promotes the degradation of fibrin in clots but not free fibrinogen. [ 14 ]  This drug is made by transgenic bacteria and converts plasminogen into the clot-dissolving enzyme,  plasmin . [ 15 ]  Recent research indicates that tPA could have toxic effects in the central nervous system. In cases of severe stroke, tPA can cross the  blood\u2013brain barrier  and enter interstitial fluid, where it then increases excitotoxicity, potentially affecting permeability of the blood\u2013brain barrier, [ 16 ]  and causing cerebral hemorrhage. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1844", "text": "There are also some anticoagulants that come from animals that work by dissolving  fibrin . For example,  Haementeria ghilianii , an  Amazon   leech , produces an enzyme called  hementin  from its  salivary glands . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1845", "text": "Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1846", "text": "Toxic granulation  refers to dark coarse granules found in  granulocytes , particularly  neutrophils , in patients with inflammatory conditions. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1847", "text": "Along with  D\u00f6hle bodies  and  toxic vacuolation , which are two other findings in the  cytoplasm  of granulocytes, toxic granulation is a  peripheral blood film  finding suggestive of an  inflammatory process . [ 1 ]  Toxic granulation is often found in patients with  bacterial infection  and  sepsis , [ 1 ] [ 2 ]  although the finding is nonspecific. [ 3 ]  Patients being treated with  chemotherapy [ 3 ]  or  granulocyte colony stimulating factor , a  cytokine  drug, may also exhibit toxic granulation. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1848", "text": "Toxic granules are mainly composed of  peroxidase  and  acid hydrolase  enzymes, [ 3 ]  and are similar in composition to the primary granules found in immature granulocytic cells like  promyelocytes . [ 4 ] [ 5 ]  Although normal, mature neutrophils do contain some primary granules, the granules are difficult to identify by light microscopy because they lose their dark blue colour as the cells mature. Toxic granulation thus represents abnormal maturation of neutrophils. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1849", "text": "Patients with the inherited condition  Alder-Reilly anomaly  exhibit very large, darkly staining granules in their neutrophils, which can be confused with toxic granulation. [ 2 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1850", "text": "Toxic vacuolation , also known as  toxic vacuolization , [ 1 ]  is the formation of  vacuoles  in the  cytoplasm  of  neutrophils  in response to severe  infections  or  inflammatory conditions . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1851", "text": "Toxic vacuolation is associated with  sepsis , particularly when accompanied by  toxic granulation . [ 4 ]  The finding is also associated with bacterial infection, [ 3 ]  alcohol toxicity, liver failure, [ 4 ]  and treatment with  granulocyte colony-stimulating factor , a  cytokine  drug used to increase the  absolute neutrophil count  in patients with  neutropenia . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1852", "text": "The formation of toxic vacuoles represents increased  phagocytic  activity, which is stimulated by the release of  cytokines  in response to inflammation or tissue injury. Toxic vacuolation frequently occurs in conjunction with  toxic granulation  and  D\u00f6hle bodies  in inflammatory states, and these findings are collectively referred to as  toxic changes . [ 5 ]   Neutrophilia  and  left shift  (the presence of immature neutrophil precursors such as  band neutrophils  and  metamyelocytes  in the peripheral blood) often accompany toxic changes, as these phenomena also occur in response to inflammation. [ 1 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1853", "text": "It has been suggested that neutrophil vacuoles not be labelled \"toxic vacuoles\" unless they are accompanied by other toxic changes, as vacuolation can occur in other conditions. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1854", "text": "Vacuoles may form in neutrophils if a blood sample is left standing for several hours prior to  blood smear  preparation, but this is an artifactual change with no clinical significance. [ 4 ]  Artifactual vacuoles are small and of uniform size and distribution, in contrast to toxic vacuoles whose size and placement are variable. [ 1 ]  Individuals with  neutral lipid storage disease  may exhibit persistent lipid-filled vacuoles in neutrophils and other granulocytes, which is a distinct phenomenon termed  Jordans' anomaly . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1855", "text": "Red blood cells ( erythrocytes ) from donors contain normal  hemoglobin  (HbA), and transfusion of normal red blood cells into people with  sickle cell disease  reduces the percentage of red cells in the circulation containing the abnormal hemoglobin (HbS). [ 1 ]  Although transfusion of donor red blood cells can ameliorate and even prevent complications of sickle cell disease in certain circumstances, transfusion therapy is not universally beneficial in sickle cell disease. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1856", "text": "There are two main types of transfusion, simple red cell transfusion and exchange transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_1857", "text": "Involves transfusing red blood cells without removing any of the patient\u2019s blood. [ 3 ]  It is used when the patient's hemoglobin is much lower than normal, for example an  aplastic crisis . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1858", "text": "Exchange transfusion involves removal of the patient\u2019s blood and replacement with donor red blood cells. [ 3 ]  It is used to treat life-threatening complications of sickle cell disease such as  stroke  or acute chest crisis. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1859", "text": "There are three main benefits of an exchange transfusion compared to a simple transfusion, these relate primarily to the ability to remove  hemoglobin S  containing red blood cells: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1860", "text": "However, there are also potential risks associated with an exchange transfusion:"}
{"_id": "WikiPedia_Hematology$$$corpus_1861", "text": "The exchange is performed using a machine ( pheresis ). This method rapidly and substantially reduces the concentration of sickle cells within the blood without increasing the overall  hematocrit  or  blood viscosity . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1862", "text": "The exchange is performed manually. It refers to manually phlebotomizing a percentage of the patient\u2019s blood prior to or concomitantly with giving a red cell transfusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1863", "text": "Red cell transfusions can be further classified as episodic or chronic. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1864", "text": "Episodic transfusion is used either acutely in response to a complication of sickle cell disease such as acute chest syndrome or to prevent complications prior to surgery. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1865", "text": "Chronic transfusion is used when sustained, low levels of HbS are needed to prevent sickle cell-related complications, most commonly stroke in children. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1866", "text": "Transfusion therapy for sickle-cell disease entails the use of red blood cell transfusions in the management of acute cases of sickle cell disease and as a prophylaxis to prevent complications by decreasing the number of red blood cells (RBC) that can sickle by adding normal red blood cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1867", "text": "In children prophylactic chronic red blood cell (RBC) transfusion therapy has been shown to be efficacious to a certain extent in reducing the risk of first stroke or  silent stroke  when  transcranial Doppler  (TCD)  ultrasonography  shows abnormal increased cerebral blood flow velocities. In those who have sustained a prior stoke event it also reduces the risk of recurrent stroke and additional silent strokes. [ 6 ] [ 7 ] [ 8 ]  There is no evidence for the use of red blood cell transfusion in adults to prevent primary stroke, although it is recommended to prevent secondary stroke. [ 8 ] [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1868", "text": "In children and adults red blood cell transfusion to increase the hemoglobin level to 100 g/L has been shown to decrease the risk of sickle cell-related complications. [ 2 ]  However, this has not been seen in all studies, and has only been demonstrated for African  haplotypes  of Hemoglobin SS. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1869", "text": "In children who have been given transfusions to prevent stroke there was also a reduction in the number of children who developed acute chest crises. [ 13 ]  There is no evidence about whether or not red cell transfusions prevent chronic lung complications. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1870", "text": "This should be suspected if there is a significant drop in the hemoglobin level compared to the patient's usual hemoglobin level which is associated with a low level of  reticulocytes . This is usually due to infection with  erythrovirus B19  (previously known as parvovirus B19). [ 11 ]  The  anemia  is usually severe with an average drop in hemoglobin of 40 g/L, and is usually treated with a simple transfusion. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1871", "text": "Acute splenic and hepatic sequestration associated with severe anemia requires a simple transfusion to raise the hemoglobin. [ 3 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1872", "text": "Red cell transfusions are used to treat patients with acute chest crisis and  respiratory compromise . [ 9 ] [ 2 ]  Exchange transfusion is recommended for those patients who have a higher hemoglobin (> 90g/L), those who have not improved after a simple transfusion, or those who have severe respiratory compromise. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1873", "text": "Red cell alloimmunisation is common in people with sickle cell disease who receive transfusions in Europe and North America. [ 4 ]  This is because there are ethnic differences in the frequencies of  blood group antigens . [ 4 ]  Blood donors are usually  Caucasian  whereas the blood transfusion recipients usually have an African or Afro-Caribbean ancestry. [ 4 ] [ 15 ]  Extended phenotype matching of red blood cells (matching  Rh  and  Kell  blood groups as well as  ABO ) decreases the risk of alloimmunisation, but it still occurs. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1874", "text": "Each unit of transfused blood has approximately 250\u00a0mg of iron, with each successive transfusion, patients receiving chronic transfusion therapy accumulate iron in various tissues in the body as the body has no way to excrete the excess, this is a cause of increased morbidity and mortality. [ 16 ]  The effects of iron overload are countered by  chelation therapy [ 17 ]  Guidelines recommend if patients are receiving regular or intermittent transfusions they should be monitored for iron overload. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1875", "text": "In  hemocytometry ,  T\u00fcrk's solution  (or  T\u00fcrk's fluid ) is a  hematological stain  (either  crystal violet  or aqueous  methylene blue ) prepared in 99%  acetic acid  (glacial) [ 1 ]  and  distilled water . The solution destroys the\n red blood cells  and platelets within a blood sample (acetic acid being the main  lyzing agent ), and stains the nuclei of the  white blood cells , making them easier to see and count. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1876", "text": "T\u00fcrk's solution is intended for use in determining total leukocyte count in a defined volume of blood. Erythrocytes are hemolyzed while leukocytes are stained for easy visualization. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1877", "text": "Composition of T\u00fcrk's solution is as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_1878", "text": "Vascular occlusion  is a blockage of a blood vessel, usually with a  clot .  It differs from  thrombosis  in that it can be used to describe any form of blockage, not just one formed by a clot.  When it occurs in a major  vein , it can, in some cases, cause  deep vein thrombosis .  The condition is also relatively common in the  retina , and can cause partial or total loss of vision.  An occlusion can often be diagnosed using  Doppler sonography  (a form of  ultrasound ). [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1879", "text": "Some medical procedures, such as  embolisation , involve occluding a blood vessel to treat a particular condition.  This can be to reduce pressure on  aneurysms  (weakened blood vessels) or to restrict a  haemorrhage .  It can also be used to reduce blood supply to tumours or growths in the body, and therefore restrict their development.  Occlusion can be carried out using a  ligature ; by implanting small coils which stimulate the formation of clots; or, particularly in the case of  cerebral aneurysms , by  clipping . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1880", "text": "This medical  symptom  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_1881", "text": "In medicine,  venipuncture  or  venepuncture  is the process of obtaining intravenous access for the purpose of venous  blood sampling  (also called  phlebotomy ) or  intravenous therapy . In healthcare, this procedure is performed by  medical laboratory scientists ,  medical practitioners , some  EMTs ,  paramedics ,  phlebotomists ,  dialysis  technicians, and other nursing staff. [ 1 ]  In  veterinary medicine , the procedure is performed by  veterinarians  and  veterinary technicians ."}
{"_id": "WikiPedia_Hematology$$$corpus_1882", "text": "It is essential to follow a standard procedure for the collection of blood specimens to get accurate laboratory results. Any error in collecting the blood or filling the test tubes may lead to erroneous laboratory results. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1883", "text": "Venipuncture is one of the most routinely performed invasive procedures and is carried out for any of five reasons:"}
{"_id": "WikiPedia_Hematology$$$corpus_1884", "text": "Blood analysis  is an important diagnostic tool available to clinicians within healthcare."}
{"_id": "WikiPedia_Hematology$$$corpus_1885", "text": "Blood is most commonly obtained from the superficial veins of the upper limb. [ 1 ]  The  median cubital vein , which lies within the  cubital fossa  anterior to the elbow, is close to the surface of the skin without many large nerves positioned nearby. Other veins that can be used in the cubital fossa for venipuncture include the  cephalic ,  basilic , and  median antebrachial veins . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1886", "text": "Minute quantities of blood may be taken by  fingerstick sampling  and collected from infants by means of a  heelprick  or from scalp veins with a  winged infusion needle ."}
{"_id": "WikiPedia_Hematology$$$corpus_1887", "text": "Phlebotomy (incision into a vein) is also the treatment of certain diseases such as  hemochromatosis  and primary and secondary  polycythemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_1888", "text": "A 1996 study of blood donors (a larger needle is used in blood donation than in routine venipuncture) found that 1 in 6,300 donors sustained a nerve injury. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1889", "text": "Risk and side affects can include a variety of things. Dizziness, sweating, and a drop in your heart rate and blood pressure.  [1] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1890", "text": "There are many ways in which blood can be drawn from a vein, and the method used depends on the person's age, the equipment available, and the type of tests required."}
{"_id": "WikiPedia_Hematology$$$corpus_1891", "text": "Most  blood collection  in the US, UK, Canada and Hong Kong is done with an evacuated tube system. Two common systems are  Vacutainer  (Becton, Dickinson and company) and Vacuette (Greiner Bio-One). The equipment consists of a plastic adapter, also known as a tube or needle holder/hub, a hypodermic needle and a vacuum tube. Under certain circumstances, a syringe may be used, often with a  butterfly needle , which is a plastic catheter attached to a short needle. In the developing world, the evacuated tube system is the preferred method of drawing blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1892", "text": "Greiner Bio-One manufactured the first ever plastic evacuated blood collection tube in 1985 under the VACUETTE brand name. Today, many companies sell vacuum tubes as the patent for this device is now in the public domain. These tubes are manufactured with a specific volume of gas removed from the sealed tube. When a needle from a hub or transfer device is inserted into the stopper, the tube's vacuum automatically pulls in the required volume of blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1893", "text": "The basic Evacuated Tube System (ETS) consists of a needle, a tube holder, and the evacuated tubes. The needle is attached to the tube holder by the phlebotomist prior to collection, or may come from the manufacturer as one unit. The needle protrudes through the end of the tube holder, and has a needle on each end. After first cleaning the venipuncture site and applying a tourniquet, the phlebotomist uncaps the needle attached to the tube holder, inserts the needle into the vein, then slides evacuated tubes into the tube holder, where the tube's stopper is pierced by the back end of the needle. The vacuum in the tube then automatically draws the needed blood directly from the vein. Multiple vacuum tubes can be attached to and removed in turn from a single needle, allowing multiple samples to be obtained from a single procedure. This is possible due to the multiple sample sleeve, which is a flexible rubber fitting over the posterior end of the needle  cannula  which seals the needle until it is pushed out of the way. This keeps blood from freely draining out of the back of the needle inserted in the vein, as each test tube is removed and the next impaled.  OSHA  safety regulations require that needles or tube holders come equipped with a safety device to cover the needle after the procedure to prevent accidental needle stick injury. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1894", "text": "Fittings and adapters used to fill evacuated tubes from butterfly needle kits and syringes are also available. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1895", "text": "There are several needle gauges for a phlebotomist to choose from. The most commonly used are as follows: a 21g (green top) needle, a 22g (black top) needle, a 21g (green label) butterfly needle, a 23g (light blue label) butterfly needle, and a 25g (orange or dark blue label) butterfly needle (however this needle is only used in pediatrics or extreme cases as it is so small that it can often result in hemolyzing the blood sample). There are also a variety of tube and bottle sizes and volumes for different test requirements. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1896", "text": "The test tubes in which blood is collected may contain one or more of several additives. In general, tests requiring whole blood call for blood samples collected in test tubes containing some form of the anticoagulant  EDTA . EDTA  chelates  calcium to prevent clotting. EDTA is preferred for hematology tests because it does minimum damage to cell morphology. Sodium citrate is the anticoagulant used in specimens collected for coagulation tests. The majority of chemistry and immunology tests are performed on serum, which is produced by clotting and then separating the blood specimen via centrifuge. These specimens are collected in either a non-additive tube or one containing a  clotting  activator. This clotting activator can interfere with some  assays , and so a plain tube is recommended in these cases, but will delay testing. Tubes containing lithium heparin or sodium heparin are also commonly used for a variety of chemistry tests, as they do not require clotting and can be centrifuged immediately after collection. A combination of  sodium fluoride  and potassium oxalate is used for glucose tests, as these additives both prevent clotting and stop glycolosis, so that blood glucose levels are preserved after collection. [ 9 ]  Another specialty tube is an opaque amber colored tube used to collect blood for light sensitive analytes, such as  bilirubin . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1897", "text": "Test tubes are labeled with the additive they contain, but the stopper on each tube is color coded according to additive as well. While colors vary between manufacturers, stopper colors generally are associated with each additive as listed below. Because the additives from each tube can be left on the needle used to fill the tubes, they must be drawn in a specific order to ensure that cross contamination will not negatively affect testing of the samples if multiple tubes are to be drawn at once. The \"order of draw\" varies by collection method. Below in the order of draw generally required for the Evacuated Tube System (ETS) collection method are the most common tubes, listing additive and color: [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1898", "text": "(\"light blue\")"}
{"_id": "WikiPedia_Hematology$$$corpus_1899", "text": "(weak calcium chelator/ anticoagulant )"}
{"_id": "WikiPedia_Hematology$$$corpus_1900", "text": "Plasma separator gel"}
{"_id": "WikiPedia_Hematology$$$corpus_1901", "text": "(\"navy\")"}
{"_id": "WikiPedia_Hematology$$$corpus_1902", "text": "Fluoride Oxalate"}
{"_id": "WikiPedia_Hematology$$$corpus_1903", "text": "Grey, Green, Yellow, Purple"}
{"_id": "WikiPedia_Hematology$$$corpus_1904", "text": "1. Grey (nil) tube \n2. Green (TB1 antigen) tube \n3. Yellow (TB2 antigen) tube \n4. Purple (mitogen) tube"}
{"_id": "WikiPedia_Hematology$$$corpus_1905", "text": "Use of lidocaine  iontophoresis  is effective for reducing pain and alleviating distress during venipuncture in children. [ 19 ]  A needle-free powder  lignocaine  delivery system has been shown to decrease the pain of venipuncture in children. [ 20 ] [ 21 ]  Rapid dermal anesthesia can be achieved by local anesthetic infiltration, but it may evoke anxiety in children frightened by needles or distort the skin, making vascular access more difficult and increasing the risk of needle exposure to health care workers. Dermal anesthesia can also be achieved without needles by the topical application of local anesthetics or by lidocaine iontophoresis. By contrast, noninvasive dermal anesthesia can be established in 5\u201315 min without distorting underlying tissues by lidocaine iontophoresis, where a direct electric current facilitates dermal penetration of positively charged lidocaine molecules when placed under the positive electrode. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1906", "text": "One study concluded that the iontophoretic administration of  lidocaine  was safe and effective in providing dermal anesthesia for venipuncture in children 6\u201317 years old. This technique may not be applicable to all children. Future studies may provide information on the minimum effective iontophoretic dose for dermal anesthesia in children and the comparison of the anesthetic efficacy and satisfaction of lidocaine iontophoresis with topical anesthetic creams and subcutaneous infiltration. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1907", "text": "Non-pharmacological treatments for pain associated with venipuncture in children includes  hypnosis  and distraction. These treatments reduced self reported pain and when combined with  cognitive-behavioural therapy  (CBT) the reduction of pain was even greater.  Other interventions have not been found to be effective and these are suggestion, blowing out air, and distraction with parent coaching did not differ from control for pain and distress. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1908", "text": "Some health care workers prefer to use a  syringe -needle technique for venipuncture.  Sarstedt  manufactures a blood-drawing system (S-Monovette) that uses this principle. [ 23 ]  This method can be preferred on the elderly, those with cancer, severe burns, obesity, or where the veins are unreliable or fragile. Because syringes are manually operated, the amount of suction applied may be easily controlled. This is particularly helpful when veins are small which may collapse under the suction of an evacuated tube. In children or other circumstances where the quantity of blood gained may be limited it can be helpful to know how much blood can be obtained before distributing it amongst the various additives that the laboratory will require. Another alternative is drawing blood from indwelling cannulae. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1909", "text": "There are times when a blood culture collection is required. The culture will determine if there are pathogens in the blood. Normally blood is sterile. When drawing blood from cultures use a sterile solution such as  Betadine  rather than  alcohol . This is done using sterile gloves, while not wiping away the surgical solution, touching the puncture site, or in any way compromising the sterile process. It is vital that the procedure is performed in as sterile a manner as possible as the persistent presence of skin  commensals  in blood cultures could indicate  endocarditis  but they are most often found as contaminants.\nIt is encouraged to use an abrasive method of skin preparation. This removes the upper layers of dead skin cells along with their contaminating bacteria. [ 25 ]  Povidone-iodine has traditionally been used but in the UK a 2%  chlorhexidine  in 70% ethanol or isopropyl alcohol solution is preferred and time must be allowed for it to dry. The tops of any containers used when drawing a blood culture should also be disinfected using a similar solution. Some labs will actively discourage iodine use where iodine is thought to degrade the rubber stopper through which blood enters the bottle, thus allowing contaminates to enter the container. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1910", "text": "The blood is collected into special transport bottles, which are like vacuum tubes but shaped differently. The blood culture bottle contains transport media to preserve any microorganisms present while they are being transported to the laboratory for cultures. Because it is unknown whether the pathogens are  anaerobic  (living without oxygen) or  aerobic  (living with oxygen), blood is collected to test for both. The aerobic bottle is filled first, and then the anaerobic bottle is filled. However, if the collection is performed using a syringe, the anaerobic bottle is filled first. If a butterfly collection kit is used, the aerobic bottle is filled first, so that any air in the tubing is released into the oxygen-containing bottle. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1911", "text": "Specially designed blood culture collection bottles eliminate the need for either the syringe or butterfly collection method. These specially designed bottles have long necks that fit into the evacuated tubes holders that are use for regular venipuncture collection. These bottles also allow for collection of other blood specimens via evacuated tubes, to be collected without additional venipuncture. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1912", "text": "The amount of blood that is collected is critical for the optimal recovery of microorganisms. Up to 10mL of blood is typical, but can vary according to the recommends of the manufacturer of the collection bottle. Collection from infants and children are 1 to 5 mL. If too little blood is collected, the ratio of blood-to-nutrient broth will inhibit the growth of microorganisms. If too much blood is collected, there is the risk of a hospital-induced anemia and the ratio of blood-to-nutrient broth will tilt in the opposite direction, which also is not conductive to optimal growth. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1913", "text": "The bottles are then incubated in specialized units for 24 hours before a lab technician studies and/or tests it. This step allows the very small numbers of bacteria (potentially 1 or 2 organisms) to multiply to a level which is sufficient for identification +/-antibiotic resistance testing. Modern blood culture bottles have an indicator in the base which changes color in the presence of bacterial growth and can be read automatically by machine. (For this reason the barcoded stickers found on these bottles should not be removed as they are used by the laboratory's automated systems.) [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1914", "text": "Blood samples from living laboratory animals may be collected using following methods: [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1915", "text": "The volume of the blood sample collection is very important in experimental animals. All nonterminal blood collection without replacement of fluids is limited up to 10% of total circulating blood volume in healthy, normal, adult animals on a single occasion and collection may be repeated after three to four weeks. In case repeated blood samples are required at short intervals, a maximum of 0.6\u00a0ml/kg/day or 1.0% of an animal's total blood volume can be removed every 24 hours. The estimated blood volume in adult animals is 55 to 70\u00a0ml/kg body weight. Care should be taken for older and obese animals. If blood collection volume exceeds more than 10% of total blood volume, fluid replacement may be required. Lactated Ringer's solution (LRS) is recommended as the best fluid replacement by National Institutes of Health (NIH). If the volume of blood collection exceeds more than 30% of the total circulatory blood volume, adequate care should be taken so that the animal does not develop hypovolemia. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1916", "text": "It is generally not advisable to use  isopropyl alcohol  to cleanse the venipuncture site when obtaining a specimen for a  blood alcohol  test. This has been related largely to the potential legal implications associated with the use of alcohol-based cleaners that could theoretically impact analysis. Numerous police alcohol collection kits have been marketed that incorporate a sodium fluoride/potassium oxalate preservative and non-alcohol-based cleansing agents to ensure proper collection. Using soap and hot water or a  povidone-iodine  swab are advisable alternatives to isopropyl alcohol in this case. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1917", "text": "Venous thrombosis  is the blockage of a  vein  caused by a  thrombus  (blood clot). A common form of venous thrombosis is  deep vein thrombosis  (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off ( embolizes ) and flows to the lungs to lodge there, it becomes a  pulmonary embolism  (PE), a blood clot in the lungs. The conditions of DVT only, DVT with PE, and PE only, are all captured by the term  venous thromboembolism  (VTE). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1918", "text": "The initial treatment for VTE is typically either  low-molecular-weight heparin  (LMWH) or  unfractionated heparin , or increasingly with  direct acting oral anticoagulants  (DOAC). Those initially treated with heparins can be switched to other  anticoagulants  ( warfarin , DOACs), although pregnant women and some people with cancer receive ongoing heparin treatment.  Superficial venous thrombosis  or phlebitis affects the superficial veins of the upper or lower extremity and only require anticoagulation in specific situations, and may be treated with anti-inflammatory pain relief only."}
{"_id": "WikiPedia_Hematology$$$corpus_1919", "text": "There are other less common forms of venous thrombosis, some of which can also lead to pulmonary embolism. Venous  thromboembolism  and superficial vein thrombosis account for about 90% of venous thrombosis. Other rarer forms include  retinal vein thrombosis , mesenteric vein thrombosis (affecting veins draining blood from the gastrointestinal organs),  cerebral venous sinus thrombosis ,  renal vein thrombosis , and ovarian vein thrombosis. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1920", "text": "Superficial venous thromboses  cause discomfort but generally not serious consequences, as do the  deep vein thromboses  (DVTs) that form in the deep veins of the legs or in the pelvic veins. Nevertheless, they can progress to the deep veins through the  perforator veins   or, they can be responsible for a lung embolism mainly if the head of the clot is poorly attached to the vein wall and is situated near the  sapheno-femoral junction . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1921", "text": "When a blood clot breaks loose and travels in the blood, this is called a  thromboembolism . The abbreviation DVT/PE refers to a VTE where a deep vein thrombosis (DVT) has moved to the lungs (PE or pulmonary embolism). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1922", "text": "Since the veins return  blood  to the  heart , if a piece of a blood clot formed in a vein breaks off it can be transported to the right side of the heart, and from there into the  lungs . A piece of thrombus that is transported in this way is an  embolus : the process of forming a thrombus that becomes embolic is called a  thromboembolism . An embolism that lodges in the lungs is a  pulmonary embolism  (PE). A pulmonary embolism is a very serious condition that can be fatal depending on the dimensions of the embolus. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1923", "text": "While venous thrombosis of the legs is the most common form, venous thrombosis may occur in other veins. These may have particular specific risk factors: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1924", "text": "Systemic embolism of venous origin can occur in patients with an  atrial  or  ventricular septal defect , or an arteriovenous connection in the lung, through which an embolus may pass into the arterial system. Such an event is termed a  paradoxical embolism . When this affects the blood vessels of the brain it can cause  stroke . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1925", "text": "Venous thrombi are caused mainly by a combination of  venous stasis  and  hypercoagulability \u2014but to a lesser extent endothelial damage and  activation . [ 7 ]  The three factors of stasis, hypercoagulability, and alterations in the blood vessel wall represent  Virchow's triad , and changes to the vessel wall are the least understood. [ 8 ]  Various risk factors increase the likelihood of any one individual developing a thrombosis:"}
{"_id": "WikiPedia_Hematology$$$corpus_1926", "text": "The overall absolute risk of venous thrombosis per 100,000 woman years in current use of  combined oral contraceptives  is approximately 60, compared to 30 in non-users. [ 23 ]  The risk of thromboembolism varies with different types of birth control pills; Compared with combined oral contraceptives containing levonorgestrel (LNG), and with the same dose of estrogen and duration of use, the rate ratio of deep vein thrombosis for combined oral contraceptives with  norethisterone  is 0.98, with  norgestimate  1.19, with  desogestrel  (DSG) 1.82, with  gestodene  1.86, with  drospirenone  (DRSP) 1.64, and with  cyproterone acetate  1.88. [ 23 ]  Venous thromboembolism occurs in 100\u2013200 per 100,000 pregnant women every year. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1927", "text": "Regarding family history, age has substantial  effect modification . For people with two or more affected siblings, the highest incidence rate is found among those \u226570 years of age (390 per 100,000 in men and 370 per 100,000 in women), whereas the highest incidence ratios compared to those without affected siblings occurred at much younger ages (ratio of 4.3 among men 20 to 29 years of age and 5.5 among women 10 to 19 years of age). [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1928", "text": "In contrast to the understanding for how arterial thromboses occur, as with  heart attacks , venous thrombosis formation is not well understood. [ 26 ]  With arterial thrombosis, blood vessel wall damage is required for thrombosis formation, as it initiates  coagulation , [ 26 ]  but the majority of venous thrombi form without any injured epithelium. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1929", "text": "Red blood cells  and  fibrin  are the main components of venous thrombi, [ 7 ]  and the thrombi appear to attach to the blood vessel wall  endothelium , normally a non-thrombogenic surface, with fibrin. [ 26 ]   Platelets  in venous thrombi attach to downstream fibrin, while in arterial thrombi, they compose the core. [ 26 ]  As a whole, platelets constitute less of venous thrombi when compared to arterial ones. [ 7 ]  The process is thought to be initiated by  tissue factor -affected thrombin production, which leads to fibrin deposition. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1930", "text": "The valves of veins are a recognized site of VT initiation. Due to the blood flow pattern, the base of the valve sinus is particularly deprived of oxygen ( hypoxic ). Stasis exacerbates hypoxia, and this state is linked to the activation of white blood cells ( leukocytes ) and the endothelium. Specifically, the two pathways of  hypoxia-inducible factor-1  (HIF-1) and  early growth response 1  (EGR-1) are activated by hypoxia, and they contribute to  monocyte  and endothelial activation. Hypoxia also causes  reactive oxygen species  (ROS) production that can activate HIF-1, EGR-1, and  nuclear factor-\u03baB  (NF-\u03baB), which regulates HIF-1 transcription. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1931", "text": "HIF-1 and EGR-1 pathways lead to monocyte association with endothelial proteins, such as  P-selectin , prompting monocytes to release tissue factor-filled  microvesicles , which presumably initiate fibrin deposition (via thrombin) after binding the endothelial surface. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1932", "text": "Numerous medications have been shown to reduce the risk of a person having a VTE, however careful decision making is required in order to decide if a person's risk of having a VTE outweighs the risks associated with most  thromboprophylaxis  treatment approaches (medications to prevent venous thrombosis).  It is recommended that people should be assessed at their hospital discharge for persistent high-risk of venous thrombosis and that people who adopt a heart-healthy lifestyle might lower their risk of venous thrombosis. [ 27 ]  Clinical policy from the American College of Physicians states a lack of support for any performance measures that incentivize physicians to apply universal prophylaxis without regard to the risks. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1933", "text": "Evidence supports the use of  heparin  in people following surgery who have a high risk of thrombosis to reduce the risk of DVTs; however, the effect on PEs or overall mortality is not known. [ 29 ]  In hospitalized non-surgical patients, mortality does not appear to change. [ 30 ] [ 31 ] [ 32 ]  It does not appear, however, to decrease the rate of symptomatic DVTs. [ 30 ]  Using both heparin and compression stockings appears better than either one alone in reducing the rate of DVT. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1934", "text": "In hospitalized people who have had a  stroke  and not had surgery, mechanical measures ( compression stockings ) resulted in skin damage and no clinical improvement. [ 30 ]  Data on the effectiveness of compression stockings among hospitalized non-surgical patients without stroke is scarce. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1935", "text": "The  American College of Physicians  (ACP) gave three strong recommendations with moderate quality evidence on VTE prevention in non-surgical patients:"}
{"_id": "WikiPedia_Hematology$$$corpus_1936", "text": "In adults who have had their lower leg casted, braced, or otherwise immobilized for more than a week, LMWH may decrease the risk and severity of deep vein thrombosis, but does not have any effect on the incidence of  pulmonary embolism . [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1937", "text": "Following the completion of warfarin in those with prior VTE, the use of long-term aspirin has been shown to be beneficial. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1938", "text": "People who have cancer have a higher risk of VTE and may respond differently to anticoagulant preventative treatments and prevention measures. [ 36 ]  The American Society of Hematology strongly suggests that people undergoing chemotherapy for cancer who are at low risk of a VTE avoid medications to prevent thrombosis ( thromboprophylaxis ). [ 37 ]  For people undergoing chemotherapy for cancer that do not require a hospital stay ( those undergoing ambulatory care ), there is low certainty evidence to suggest that treatment with  direct factor Xa inhibitors  may help prevent symptomatic VTEs, however this treatment approach may also lead to an increase in the risk of a major bleed compared to a  placebo  medication. [ 38 ]  There is stronger evidence to suggest that LMWH helps prevent symptomatic VTE, however this treatment approach also comes with a higher risk of a major bleed compared to a placebo medication or no treatments to prevent VTE. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1939", "text": "For people who are having surgery for cancer, it is recommended that they receive anticoagulation therapy (preferably LMWH) in order to prevent a VTE. [ 39 ]  LMWH is recommended for at least 7\u201310 days following cancer surgery, and for one month following surgery for people who have a high risk of VTEs. [ 40 ] [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1940", "text": "Specifically for patients with various types of lymphoma, there is a risk assessment model,  ThroLy , to help providers determine how likely a thromboembolic event is to occur. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1941", "text": "American evidence-based clinical guidelines were published in 2016 for the treatment of VTE. [ 42 ]  In the UK, guidelines by the  National Institute for Health and Care Excellence  (NICE) were published in 2012, updated in 2020. [ 43 ]  These guidelines do not cover rare forms of thrombosis, for which an individualized approach is often needed. [ 5 ]  Central and branch retinal vein occlusion does not benefit from anticoagulation in the way that other venous thromboses do. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1942", "text": "If diagnostic testing cannot be performed swiftly, many are commenced on empirical treatment. [ 43 ]  Traditionally this was heparin, but several of the DOACs are licensed for treatment without initial heparin use. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1943", "text": "If heparin is used for initial treatment of VTE, fixed doses with  low-molecular-weight heparin  (LMWH) may be more effective than adjusted doses of  unfractionated heparin  (UFH) in reducing blood clots. [ 44 ]  No differences in mortality, prevention of major bleeding, or preventing VTEs from recurring were observed between LMWH and UFH. [ 45 ]  No differences have been detected in the route of administration of UFH ( subcutaneous  or  intravenous ). [ 44 ]  LMWH is usually administered by a  subcutaneous injection , and a person's blood clotting factors do not have to be monitored as closely as with UFH. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1944", "text": "Once the diagnosis is confirmed, a decision needs to be made about the nature of the ongoing treatment and its duration. USA recommendations for those without cancer include  anticoagulation  (medication that prevents further blood clots from forming) with the DOACs  dabigatran ,  rivaroxaban ,  apixaban , or  edoxaban  rather than  warfarin  or  low molecular weight heparin  (LMWH). [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1945", "text": "For those with cancer, LMWH is recommended, [ 42 ]  although DOACs appear safe in the majority of situations. [ 43 ]  For long-term treatment in people with cancer, LMWH is probably more effective at reducing VTEs when compared to vitamin K antagonists. [ 36 ]  People with cancer have a higher risk of experiencing reoccurring VTE episodes (\"recurrent VTE\"), even while taking preventative anticoagulation medication. These people should be given therapeutic doses of LMWH medication, either by switching from another anticoagulant or by taking a higher dose of LMWH. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1946", "text": "In pregnancy, warfarin and DOACs are not considered suitable and LMWH is recommended. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1947", "text": "For those with a small pulmonary embolism and few risk factors, no anticoagulation is needed. [ 42 ]  Anticoagulation is, however, recommended in those who do have risk factors. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1948", "text": "Thrombolysis  is the administration of medication (a recombinant enzyme) that activates  plasmin , the body's main enzyme that breaks down blood clots. This carries a risk of bleeding and is therefore reserved for those who have a form of thrombosis that may cause major complications. In pulmonary embolism, this applies in situations where heart function is compromised due to lack of blood flow through the lungs (\"massive\" or \"high risk\" pulmonary embolism), leading to  low blood pressure . [ 42 ]  Deep vein thrombosis may require thrombolysis if there is a significant risk of  post-thrombotic syndrome . [ 42 ]  Thrombolysis may be administered by intravenous catheter directly into the clot (\"catheter-directed thrombolysis\"); this requires a lower dose of the medication and may carry a lower bleeding risk but evidence for its benefit is limited. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1949", "text": "Inferior vena cava filters  (IVCFs) are not recommended in those who are on anticoagulants. [ 42 ]  IVCFs may be used in clinical situations where a person has a high risk of experiencing a pulmonary embolism, but cannot be on anticoagulants due to a high risk of bleeding, or they have active bleeding. [ 46 ] [ 47 ]  Retrievable IVCFs are recommended if IVCFs must be used, and a plan should be created to remove the filter when it is no longer needed. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1950", "text": "While topical treatments for  superficial venous thrombosis  are widely used, the evidence is strongest for the heparin-like drug  fondaparinux  (a  factor Xa  inhibitor), which reduces extension and recurrence of  superficial venous thrombosis  as well as progression to symptomatic embolism. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1951", "text": "After an episode of unprovoked VTE, the risk of further episodes after completing treatment remains elevated, although this risk diminishes over time. Over ten years, 41% of men and 29% of women can expect to experience a further episode. For each episode, the risk of death is 4%. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1952", "text": "Virchow's triad  or the  triad of Virchow  ( / \u02c8 f \u026a\u0259r k o\u028a / ) describes the three broad categories of factors that are thought to contribute to  thrombosis . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1953", "text": "It is named after the renowned  German   physician   Rudolf Virchow  (1821\u20131902). However, the elements comprising Virchow's triad were not proposed by Virchow. Neither did he ever suggest a triad to describe the pathogenesis of venous thrombosis. In fact, it was not until decades after Virchow's death that a consensus was reached proposing that thrombosis is the result of alterations in blood flow, vascular endothelial injury, or alterations in the constitution of the blood. Still, the modern understanding of the factors leading to embolism is similar to the description provided by Virchow. Virchow's triad remains a useful concept for clinicians and pathologists alike in understanding the contributors to thrombosis. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1954", "text": "The triad consists of three components:"}
{"_id": "WikiPedia_Hematology$$$corpus_1955", "text": "The origin of the term \"Virchow's Triad\" is of historical interest, and has been subject to reinterpretation in recent years. [ 7 ]  While both Virchow's and the modern triads describe  thrombosis , the previous triad has been characterized as \"the consequences of thrombosis\", and the modern triad as \"the causes of thrombosis\". [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1956", "text": "Rudolf Virchow elucidated the etiology of  pulmonary embolism , whereby  thrombi  occurring within the  veins , particularly those of the extremities, become dislodged and migrate to the pulmonary vasculature. He published his description in 1856. [ 9 ]  In detailing the  pathophysiology  surrounding pulmonary embolism, he alluded to many of the factors known to contribute to venous thrombosis. While these factors had already been previously established in the medical literature by others, [ 10 ] [ 11 ]  for unclear reasons they ultimately became known as Virchow's triad. This  eponym  did not emerge in the literature until long after Virchow's death. One estimate of the first use of the phrase dates it to the early 1950s. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1957", "text": "Although the concept of the triad is usually attributed to Virchow, he did not include endothelial injury in his description. [ 12 ]  This has been attributed to a dispute Virchow had with  Jean Cruveilhier , who considered local trauma of primary importance in the development of pulmonary artery thrombosis. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1958", "text": "A  welt  is a bloodshot stripe on the skin. They are  hematoma , a special form of a  bruise ."}
{"_id": "WikiPedia_Hematology$$$corpus_1959", "text": "Welts occur when blunt force is applied to the body with elongated objects without sharp edges. Like other haematomas, welts change their colors as they heal, which usually takes two to four weeks. The colors include purplish black, reddish blue, brown or yellowish green. That makes it possible to determine their approximate age. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1960", "text": "A special form of welts\u2014when the impact tool is not flat\u2014are double welts. They occur after blows with stick-like, long objects, such as a cane for  caning , a  riding crop  or a  garden hose . The energy of the striking tool hitting the skin forces the tissue fluid or tissue matrix to the outside of the instrument. This leaves a rather anemic, brighter area of skin, so the area of impact of the striking tool on the skin is usually free of injury. [ 2 ]  However, capillary vessels located under the skin at the edges of the impacting object rupture, resulting in two parallel, striated skin lacerations. Such double straps in a child indicate abuse and require clarification. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1961", "text": "Alimentary toxic aleukia  is a  mycotoxin -induced condition characterized by  nausea , vomiting,  diarrhea ,  leukopenia  (aleukia),  hemorrhaging , skin inflammation, and sometimes death. [ 1 ]  Alimentary toxic aleukia almost always refers to the human condition associated with presence of  T-2 Toxin . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1962", "text": "Alimentary toxic aleukia manifests in inflammation of the  gastric  and  intestinal mucosa , a severe progressive  leukopenia ,  anemia , and an increased  erythrocyte sedimentation rate . Subsequently  petechial hemorrhages  of both the skin and  mucosa  as well as  enlarged lymph nodes  are seen. Symptoms of the respiratory system include  bronchopneumonia ,  pulmonary hemorrhages ,  sepsis , and  lung abscesses . Vomiting,  bloody stools ,  lassitude , and incoordination are also observed. [ 1 ]  The severity of the disease and its course was determined by the quantity of the  toxin  and the various reactive properties of various tissues and organs to the toxin. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1963", "text": "There are four stages of ATA. The first stage is acute intoxication. The  leukopenia  stage is the next. The third stage is distinguished by distinct clinical symptoms (anginal- hemorrhagic  stage), and the fourth by recovery and possible complications. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1964", "text": "Local and systemic symptoms can appear immediately or several hours after consuming a meal prepared with the toxic wintered grain. Local symptoms include a bitter taste in the mouth, which leads to a complete  loss of taste ,  tongue   numbness  or swelling, a burning sensation in the mouth, and pain when swallowing. If no more hazardous grain was consumed, the foregoing symptoms subsided within 2 or 3 days, but they resurfaced as soon as the patient resumed consumption of this grain. Toxemia manifested as  weakness ,  malaise ,  rheumatic -like pain,  hyperhidrosis , a condition similar to  alcohol intoxication , and  insomnia . These symptoms typically go away in 3 to 5 days. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1965", "text": "There were isolated cases of acute  food poisoning  resulting in acute  esophagitis ,  gastritis , or  gastroenteritis , with  hypersalivation ,  nausea , vomiting, esophageal and  stomach pain ,  diarrhea , and fevers of up to 39 degrees.  Giddiness , headache,  mydriasis ,  tachycardia ,  cyanosis , limb coldness, and  convulsions  were also reported. There were also  hemorrhagic diathesis  with cutaneous and  mucosal  hemorrhages and  epistaxis . In such circumstances, the blood count can indicate  hematopoiesis  alterations as quickly as 1-4 days; this was followed by  neutropenia  and relative  lymphocytosis ,  thrombocytopenia , and some  erythrocyte sedimentation rate  acceleration. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1966", "text": "With the subsequent ingesting of the toxic grain, the disease advances and enters the second stage within a few days. Because there is no habituation to the harmful substance, local symptoms may reoccur. The duration of the ATA leukopenia stage could vary from 2-3 weeks to 6-8 weeks and even 3-4 months. Clinically, the  leukopenia  stage manifests as symptoms of the  central  and  vegetative nervous systems . Patients reported  fatigue ,  apathy ,  vertigo , headache, and  poor sleep . The patients' skin would appear pale, and dry, and the symptoms of late dermographism  mydriasis  would be clearly visible. The patients showed a  petechial rash  towards the end of the  leukopenia  stage. The  petechial  patches were initially quite little, but as the disease advanced, they grew in size. When the  leukopenia  stage was treated promptly and adequately, it was often followed by recovery. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1967", "text": "Acute symptoms such as  rash ,  hemorrhages ,  necrotic   angina ,  high temperature , and  tachycardia  mark the third ATA stage. The  leukocyte  count continues to fall.  Bleeding time  increases, and the  coagulability  of the blood is delayed.  Hemorrhages  occur in the nose,  pharynx ,  esophagus , gut,  kidney ,  bladder , and  uterus .  Hemorrhages  can be severe and difficult to control, resulting in significant blood loss and even death. Patients develop  angina  several days following the formation of the petechial rash, which in severe cases might be necrotic or gangrenous. The tonsils completely decomposed, followed by acute edema of the  laryngeal vestibule  and blockage within 3-8 days with  necrotic  masses and  blood clots .  Asphyxia  and  aphonia  ensued, and many people died as a result. The  gangrenous  process progressed to the  soft palate , gums, tongue, lips, cheeks, and  nasal cavity , resulting in  tooth loss  and cheek perforation. These symptoms were particularly prevalent in individuals who had an imbalanced diet and in children. Severe  anginal  symptoms were followed by an increase in  hemorrhagic diathesis . Acute  hepatitis  typically manifests itself during the third ATA stage. The  liver  would become slightly enlarged, while the  spleen  would remain normal. There was  microhematuria  and, on rare occasions,  hematuria . Even in the most severe cases, significant improvements and even recovery within 1-2 weeks was feasible. Heart paralysis, uncontrollable  hemorrhages ,  suffocation ,  pneumonia  with pulmonary abscesses, and  gangrene  all contributed to death. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1968", "text": "When  pathogenetic  therapy was administered, the condition advanced to the fourth stage, which lasted 10-14 days. The  necrotic  fool began to mend and  hemorrhages  stopped during this pealed; a reduction of fever showed recovery from acute toxemia. However, lingering toxic symptoms ( tachycardia ,  hypotension , apical  systolic murmur , left heart dilatation,  dyspnea ,  weakness ,  vertigo ,  gastritis ,  gastroenteritis ,  hepatitis ,  central  and  vegetative nervous system  problems) persisted for an extended period of time. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1969", "text": "At the early stages of the condition, therapeutic measures include excluding various wintered grain products and flour from the diet and monitoring  erythrocyte ,  platelet , and  leukocyte  differential counts. In the second stage, therapeutic interventions include balanced nutrition, which includes biologically beneficial  proteins  and  Vitamins  such as  ascorbic acid ,  thiamine ,  riboflavin ,  niacin ,  vitamin B ,  folacin , and  vitamin E . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1970", "text": "When the condition reaches the third stage, the patient is immediately hospitalized and placed on a balanced diet. Early prescription or large doses of  sulfamide  compounds and adequate  antibiotics  were required, as well as the use of general and  hemopoiesis -stimulated  blood transfusion  and  autohemotherapy , the administration of  hemostatic , detoxicating, and  cardiovascular  activity-stimulating agents, and the local treatment of  necrotic  foci. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1971", "text": "In the fourth stage, medical treatments would be focused on increasing the body's response capacity through general bracing and  hemopoiesis  stimulation, as well as eradicating toxic residual effects with detoxication medications. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1972", "text": "Alimentary toxic aleukia was first characterized in the early 20th century after affecting a large population in the  Orenburg Oblast  of the former  USSR  in 1933 and during  World War II . The sick people had eaten overwintered grain colonized with  Fusarium sporotrichioides  and  Fusarium poae . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1973", "text": "Aplasia  ( / \u0259 \u02c8 p l e\u026a \u0292 \u0259 /   \u24d8 ; from  Greek   a , \"not\", \"no\" +  plasis , \"formation\") is a  birth defect  where an  organ  or  tissue  is wholly or largely absent. It is caused by a defect in a developmental process. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1974", "text": "Aplastic anemia  is the failure of the body to produce blood cells. It may occur at any time, and has multiple causes. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1975", "text": "Pure red cell aplasia  (PRCA)\u00a0is caused by the selective destruction or inhibition of  erythroid progenitor  or  precursor cells . It is characterized by  anemia  and  reticulocytopenia  and can be chronic or acute. [ 3 ] \u00a0 Diamond\u2013Blackfan anemia  is a type of PRCA that occurs at birth. PRCA can be acquired as a primary disorder or as a result of another disorder. [ 4 ] \u00a0Immunosuppressive drugs, particularly corticosteroids, will usually result in a temporary or permanent remission. The final outcome is primarily determined by the underlying disorder. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1976", "text": "Aplasia cutis congenita  is a condition in which some or large portions\u00a0of the skin is missing at birth.  The disorder is most commonly seen on the scalp, often as a solitary lesion without other abnormalities. The condition may be caused by  epidermolysis bullosa , specific  teratogens , or  intrauterine infections , or it may be caused by  chromosomal abnormalities ,  ectodermal dysplasias , or other malformation syndromes. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1977", "text": "Radial aplasia  is a condition in which\u00a0the  radius  does not form. The radius runs from your elbow to your wrist, where your thumb is located. With radial aplasia, the\u00a0arm can look misshapen and bent. The\u00a0thumb could also be absent or shorter than usual. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1978", "text": "Sertoli cell-only syndrome (SCOS), also known as germ cell aplasia, is defined by  azoospermia  where the testicular  seminiferous tubules  are lined solely with  sertoli cells . [ 7 ]   Sertoli cells  contribute to the formation of the  blood-testis barrier  and aid in sperm generation. These cells respond to  follicle-stimulating hormone , which is secreted by the  hypothalamus  and aids in  spermatogenesis . [ 8 ] \nMen often learn they have Sertoli cell-only syndrome between the ages of 20 and 40 when they are checked for  infertility  and found to produce\u00a0no sperm. Other signs and symptoms are uncommon, yet in some cases, an underlying cause of SCO syndrome, such as  Klinefelter syndrome , may produce other symptoms. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1979", "text": "Most cases of SCO syndrome are  idiopathic , however,\u00a0causes may include deletions of genetic material on  Y-chromosome  regions, particularly the  azoospermia factor  area. Other factors include  chemical or toxin exposure , previous exposure to\u00a0 radiation therapy , and a history of severe trauma. A testicular  biopsy  confirms the diagnosis of SCO syndrome. Although there is no effective treatment at the moment, assisted reproductive technology may help some men with SCO syndrome reproduce. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1980", "text": "Pulmonary aplasia is a rare congenital pathology characterized by the unilateral or bilateral absence of lung tissue. It is distinct from  pulmonary agenesis , which, while similar, has a short-blind ending  bronchus  in aplasia. Because bilateral pulmonary aplasia is not feasible, it is usually unilateral. It is frequently associated with other congenital abnormalities, primarily cardiovascular, and has been shown to occur with the  VACTERL syndrome ."}
{"_id": "WikiPedia_Hematology$$$corpus_1981", "text": "Thymic aplasia is a rare  primary immunodeficiency  with autosomal or X-linked recessive inheritance, characterized by  thymus   atrophy  in the absence of other congenital abnormalities, profound  T-cell deficiency , and normal or increased serum  immunoglobulin  levels. Patients present with chronic or recurring infections in infancy, such as  candidiasis , skin, pulmonary, and  urinary tract infections ,  chronic diarrhea , and  failure to thrive . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1982", "text": "Optic nerve aplasia (ONA) is a congenital  optic nerve  anomaly defined as the absence of the  optic nerve head , the  retinal  blood vessels,  ganglion cells of the retina , and optic  nerve fibers  in an otherwise normal eye. Clinically, the condition is characterized by a lack of  light perception , an  afferent pupillary defect , and a  fundus  appearance of an absent optic nerve head and retinal vessels, as well as other ocular and nonocular abnormalities. Bilateral ONA has been linked to systemic anomalies, whereas unilateral ONA is seen in otherwise healthy people. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1983", "text": "Aplastic anemia  is a  bone marrow failure  syndrome characterized by peripheral  pancytopenia  and  bone marrow  hypoplasia. Although the  anemia  is usually  normocytic , mild  macrocytosis  can be seen in conjunction with stress  erythropoiesis  and raised  fetal hemoglobin  levels. Aplastic anemia patients present with symptoms related to a decrease in  hematopoietic cell  production in the  bone marrow . The onset is gradual, and the first symptom is frequently  anemia  or bleeding, though a  high temperature  or  infections  may be present at the onset. The following are examples of specific manifestations: [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1984", "text": "The majority of cases of aplastic anemia are idiopathic, and seeking\u00a0a possible cause\u00a0is frequently unproductive. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1985", "text": "Aplasia is a rare condition.  Radial aplasia  and  pure red cell aplasia , particularly the acquired form of pure red cell aplasia, are the most common types. Radial aplasia affects about one in every 30,000 newborns. Radial ray deficiencies, such as radial aplasia, are one of the most common congenital arm disabilities. Congenital pure red cell aplasia is uncommon, with an estimated 5 to 7 cases per million births. The acquired form is more prevalent. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1986", "text": "Atypical hemolytic uremic syndrome  ( aHUS ), also known as  complement-mediated   hemolytic   uremic   syndrome  (not to be confused with  hemolytic\u2013uremic syndrome ), is an extremely  rare , life-threatening,  progressive disease  that frequently has a  genetic component . In most cases, it can be effectively controlled by interruption of the complement cascade. Particular  monoclonal antibodies , discussed later in the article, have proven efficacy in many cases."}
{"_id": "WikiPedia_Hematology$$$corpus_1987", "text": "aHUS is usually caused by chronic, uncontrolled activation of the  complement system , [ 1 ] [ 2 ]  a branch of the body's immune system that destroys and removes foreign particles. [ 3 ]  The disease affects both children and adults and is characterized by systemic  thrombotic microangiopathy (TMA) , the formation of  blood clots  in  small blood vessels  throughout the body, which can lead to  stroke ,  heart attack , kidney failure, and death. [ 1 ] [ 4 ] [ 5 ]  The complement system activation may be due to mutations in the complement regulatory proteins ( factor H ,  factor I , or  membrane cofactor protein (CD46) ), [ 6 ] [ 5 ] [ 7 ]  or occasionally due to acquired neutralizing autoantibody inhibitors of these complement system components (e.g.  anti\u2013factor H antibodies ). [ 8 ] :\u200a1933\u200a  Prior to availability of  eculizumab (Soliris)  and  ravulizumab (Ultomiris) , an estimated 33\u201340% of patients developed  end-stage renal disease (ESRD)  or died (despite the use of supportive care, e.g.  plasmapheresis ) with the first clinical bout of aHUS. Including subsequent relapses, a total of approximately two-thirds (65%) of patients required  dialysis , had permanent renal damage, or died within the first year after diagnosis despite  plasma exchange or plasma infusion (PE/PI) . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1988", "text": "Clinical signs and symptoms of complement-mediated TMA can include abdominal pain, [ 9 ]   confusion , [ 9 ]   fatigue , [ 5 ]   edema (swelling) , [ 10 ]  nausea/vomiting [ 11 ]  and diarrhea. [ 12 ]   aHUS often presents with  malaise  and fatigue, as well as microangiopathic anemia. [ 8 ] :\u200a1931\u200a  However, severe abdominal pain and  bloody diarrhea  are unusual. [ 8 ] :\u200a1931\u200a   Laboratory tests may also reveal low levels of platelets (cells in the blood that aid in clotting), [ 1 ]  elevated  lactate dehydrogenase  (LDH, a chemical released from damaged cells, and which is therefore a marker of  cellular damage ), [ 7 ]  decreased  haptoglobin  (indicative of the breakdown of red blood cells), [ 7 ]  anemia (low red blood cell count)/schistocytes (damaged red blood cells), [ 1 ] [ 7 ]  elevated creatinine (indicative of kidney dysfunction), [ 13 ]  and proteinuria (indicative of kidney injury). [ 14 ]  Patients with aHUS often present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, [ 1 ]  hypertension (high blood pressure), [ 5 ]  myocardial infarction (heart attack), [ 15 ]  stroke, [ 9 ]  lung complications, [ 15 ]  pancreatitis (inflammation of the pancreas), [ 11 ]  liver necrosis (death of liver cells or tissue), [ 5 ]  encephalopathy (brain dysfunction), [ 5 ]  seizure, [ 16 ]  or coma. [ 17 ]  Failure of neurologic, cardiac, kidney, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression. [ 1 ] [ 14 ] [ 18 ] [ 19 ] [ 20 ]  For example, approximately 1 in 6 patients with aHUS will initially present with proteinuria or hematuria without acute kidney failure. [ 14 ]  Patients who survive the presenting signs and symptoms endure a chronic thrombotic and inflammatory state, which puts many of them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death. [ 10 ] [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1989", "text": "Although many patients experience aHUS as a single disease, comorbidities are common. In one study, 25% (47/191) of patients with no known family history of aHUS were found to have a coexisting disease or condition. Comorbidities in this study included malignant hypertension (30%), TMA with a history of transplant (23%), TMA associated with pregnancy (21%),  glomerulopathy  (17%), systemic disease such as  systemic lupus erythematosus (SLE)  or  progressive systemic sclerosis (PSS)  (6%), and malignancy (1%). [ 5 ]  The presence of mutations in complement regulatory proteins, or of disease-associated variations in the genes encoding these proteins (i.e., in most patients with comorbid conditions as well as in patients with aHUS as a single disease), suggests that deviations from the normal genetic coding of these factors could result in a genetic predisposition to TMA. Individuals so predisposed could have aHUS episodes precipitated by one of the known disease triggers (e.g., infection, pregnancy, surgery, trauma) as well as by other systemic diseases (e.g., malignant hypertension, SLE, cancer). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1990", "text": "In healthy individuals, complement is used to attack foreign substances, and the complement system is highly regulated to prevent it from damaging healthy tissues and organs. [ 1 ] [ 18 ]  However, in most patients with aHUS, it has been demonstrated that chronic, uncontrolled, and excessive activation of complement can result from production of anti-factor H autoantibodies or from genetic mutations in any of several complement regulatory proteins (e.g., factor H, factor HR1 or HR3, membrane cofactor protein, factor I, factor B, complement C3, and  thrombomodulin ). [ 18 ]  This results in platelet activation, damage to  endothelial cells  (cells that line the blood vessels), and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count,  hemolysis  (breakdown of red blood cells), damage to multiple organs, and often, death. [ 14 ] [ 19 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1991", "text": "aHUS is not the only condition that causes systemic TMA, a fact that makes differential diagnosis essential. Historically, the clinical diagnosis of TMA-causing diseases was grouped into a broad category that (in addition to aHUS) included  thrombotic thrombocytopenic purpura  (TTP) and Shiga-toxin-producing Escherichia coli hemolytic uremic syndrome ( STEC-HUS ). [ 19 ] [ 21 ]  However, it is now understood that although aHUS, STEC-HUS, and TTP have similar clinical presentations, they have distinct causes and specific tests can be conducted to differentiate these diseases. In addition, there are other conditions that can cause TMA as a secondary manifestation; these entities include systemic lupus erythematosus (SLE), malignant hypertension, progressive systemic sclerosis (PSS, also known as scleroderma), pregnancy-associated HELLP (hemolysis, liver dysfunction, and low platelets) syndrome, and toxic drug reactions (e.g., to cocaine, cyclosporine, or tacrolimus). Nevertheless, aHUS should be suspected in patients presenting with systemic TMA, and appropriate diagnostic work-up should be undertaken. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1992", "text": "The neurological and kidney-related signs and symptoms of aHUS overlap with those of TTP. [ 13 ] [ 23 ]  However, unlike aHUS, TTP is primarily an autoimmune disorder in which the presence of an inhibitory autoantibody results in severe deficiency of  ADAMTS13 , an enzyme that cleaves von Willebrand factor (vWF, a large protein involved in blood clotting) into smaller pieces. [ 22 ]  TTP also can be a genetic disorder characterized by mutations in the ADAMTS13 gene leading to severe ADAMTS13 deficiency. This congenital cause of ADAMTS13 deficiency is called  Upshaw-Schulman syndrome . [ 24 ] ) A lab test showing ADAMTS13 activity levels of \u22645% is indicative of TTP. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1993", "text": "Similarly, the gastrointestinal (GI) signs and symptoms of aHUS overlap with those of STEC-HUS. [ 12 ] [ 25 ] [ 26 ]  Stool samples from patients with diarrhea or other GI symptoms should be tested for STEC and the presence of Shiga-toxin. However, a positive identification of Shiga-toxin, which is required to diagnose STEC-HUS, does not rule out aHUS. Nevertheless, in the appropriate clinical setting, a positive identification of Shiga-toxin makes aHUS very unlikely. [ 13 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1994", "text": "aHUS patients report a mean timeline of 29 days for the overall diagnosis process from first noticing symptoms to receiving an aHUS diagnosis. During this time, they report an overall health state drop \u2013 from 88% of patients falling between good and excellent, to 99% falling between good and very poor \u2013 and a decrease in health status index by more than half \u2013 from 3.8 (on a scale of 1 to 5) pre-illness, to 1.4 at diagnosis. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1995", "text": "Although plasma exchange/infusion (PE/PI) is frequently used, there are no controlled trials of its safety or efficacy in aHUS. Even though PE/PI often partially controls some of the hematological manifestations of aHUS in some patients, its effectiveness has not been demonstrated in terms of inducing total disease remission.  PE/PI is associated with significant safety risks, including risk of infection, allergic reactions, thrombosis, loss of vascular access, and poor quality of life. [ 23 ] [ 28 ]  Importantly, terminal complement activation has been shown to be chronically present on the surface of platelets in patients with aHUS who appear to be clinically well while receiving chronic PE/PI. [ 10 ] [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1996", "text": "Guidelines issued by the European Paediatric Study Group for HUS recommend rapid administration of  plasma exchange  or  plasma infusion  (PE/PI), intensively administered daily for 5 days and then with reducing frequency. [ 23 ]  However, the American Society for Apheresis offers a \"weak\" recommendation for plasma exchange to treat aHUS, due to the \"low\" or \"very low\" quality of evidence supporting its use. Although some patients experienced improvements in red blood cell and platelet counts, plasma therapies generally did not result in full remission. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1997", "text": "Eculizumab (Soliris)  appears to be useful for atypical hemolytic uremic syndrome (aHUS). [ 31 ]  In September 2011 the  U.S. Food and Drug Administration  (FDA) approved it as an  orphan drug  to treat people with aHUS. [ 32 ]  This approval was based on two small prospective trials of 17 people and 20 people. [ 31 ]  In the UK,  NICE  issued guidance on the use of Eculizumab for treating aHUS, based on five evidence sources, including those used by the FDA [ 33 ]  No randomised controlled trials were identified. All prospective studies were phase 2, open\u2011label, non\u2011randomised, single\u2011arm studies that included patients with different clinical baseline characteristics. The prospective studies lasted 26 weeks; however, patients were allowed to continue treatment with eculizumab in a long\u2011term extension study. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1998", "text": "Ravulizumab-cwvz (Ultomiris) is a second generation monoclonal antibody for aHUS made by Alexion pharmaceuticals, Inc. [ 34 ]  The target of ravulizumab-cwvz is the same eculizumab (Soliris) with changes to the structure of the antibody resulting in a longer serum half life and therefore reduced dosing regimen. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_1999", "text": "Patients with aHUS who have ESRD are generally consigned to lifelong dialysis, which carries a 5-year survival rate of 34\u201338%, [ 36 ] [ 37 ]  with infections accounting for 14% of deaths. [ 38 ]  These patients also remain at ongoing risk of non-kidney systemic complications of the disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2000", "text": "Despite its history of use in patients with aHUS, kidney transplantation does not address the continued and uncontrolled complement activation that leads to progressive, systemic TMA. As many as 90% of patients with aHUS and who are not treated with Soliris or Ultomiris, experience TMA in the transplanted organ, leading to transplant failure. [ 12 ] [ 39 ]  Patients who have undergone kidney transplantation are still at continued risk of neurological, gastrointestinal, and cardiovascular complications and, importantly, premature mortality. Following kidney transplantation, the ongoing, uncontrolled, chronic complement activation associated with aHUS causes graft loss in 66% of children and 55% of adults, as well as continued inflammatory and TMA insult to other organs. [ 1 ] [ 5 ]  Combined liver-kidney transplantation is only available to very few patients, due to the limited supply of solid organs. In addition, there is a substantial near-term risk of mortality, which many physicians and patients consider excessive. [ 1 ]  In recent years, some transplant centers have begun to administer eculizumab to patients with TMA who receive a kidney transplant. This strategy has been effective in preventing TMA recurrences in these patients. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2001", "text": "Patients using either eculizumab or ravulizumab for the treatment of aHUS showed improvements in kidney function even avoiding dialysis and minimizing death. Markers of disease activity in the blood also had a great improvement. However, the only available evidence has substantial bias and low quality and therefore there should be careful considerations for futures studies in treatment duration, adverse outcomes and risk of disease recurrence associated with this treatment. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2002", "text": "Prior to the use of monoclonal antibodies(e.g., Soliris, Ultomiris) patients with aHUS had an extremely poor prognosis. Among those with the most commonly identified aHUS genetic mutation, the proportion of patients experiencing negative outcomes (e.g., need for dialysis, permanent kidney damage, death) within the first year rose to 70%. [ 7 ]  However, sudden morbidity and mortality could occur regardless of mutational status. aHUS can arise at any age, with more than 40% of cases first reported after 18 years of age. [ 5 ]  The oldest presentation in one study was at age 83. [ 5 ]  As noted above, kidney transplantation for aHUS patients with ESRD was rarely considered because of a high incidence of graft loss due to TMA recurrence in the transplanted organ in up to 90% of patients. [ 12 ] [ 39 ]  Consequently, most untreated aHUS patients develop ESRD and undergo chronic dialysis, which is associated with significant morbidities and worsened prognosis. [ 12 ]  Combined liver-kidney transplantation has been attempted in patients with aHUS, although this high-risk procedure has a mortality rate approaching 50%. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2003", "text": "Prior to availability and usage of the treatments,  quality of life was very poor for patients with aHUS; burdened with fatigue, renal complications, hypertension, neurological impairment, gastrointestinal distress, clotting at the site of venous access, and in worst cases, death. [ 7 ]  PE/PI is also reported to be associated with significant safety risks and is highly disruptive to patients' lives due to the requirements for extensive vascular access and frequent administration. [ 13 ] [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2004", "text": "Since the approval of eculizumab (Soliris) the prognosis for aHUS patients has improved greatly. [ 44 ]  Risk of relapse is present after discontinuation of eculizumab treatment and close monitoring is required. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2005", "text": "aHUS can be inherited or acquired, and does not appear to vary by race, gender, or geographic area. [ 18 ]  As expected with an ultra-rare disease, data on the prevalence of aHUS are extremely limited. A pediatric prevalence of 3.3 cases per million population is documented in one publication of a European hemolytic uremic syndrome (HUS) registry involving 167 pediatric patients. [ 45 ]  Of aHUS cases, approximately 60 percent have genetically inherited aHUS. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2006", "text": "Atypical hemolytic uremic syndrome (aHUS) has also been referred to as diarrhea-negative  hemolytic-uremic syndrome  (D \u2212  HUS). [ 47 ] :\u200a2170"}
{"_id": "WikiPedia_Hematology$$$corpus_2007", "text": "Patient advocacy groups have been helping to determine research priorities. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2008", "text": "The  blood hammer  phenomenon is a sudden increase of the upstream  blood pressure  in a  blood vessel  (especially  artery  or  arteriole ) when the  bloodstream  is abruptly blocked by vessel obstruction. The term \"blood-hammer\" was introduced in  cerebral   hemodynamics [ 1 ] [ 2 ]  by analogy with the  hydraulic  expression \" water hammer \", already used in  vascular   physiology  to designate an arterial pulse variety, the \" water-hammer pulse \". Complete understanding of the relationship between mechanical parameters in vascular occlusions is a critical issue, which can play an important role in the future diagnosis, understanding and treatment of vascular diseases."}
{"_id": "WikiPedia_Hematology$$$corpus_2009", "text": "If the time of shock wave propagation caused by the blood encountering an obstacle is equal to or less than the semilunar valve closure time, this can create a partial blood hammer phenomenon where flow speed oscillation increases without an accompanying abnormal pressure increase, whereas patients without a prolonged aortic valve closure time have the kinetic energy associated with turning around after an obstruction into a pressure peak, with little energy dedicated to increasing flow speed oscillations in a complete blood hammer effect. Flow leakage is also possible in an incomplete blood hammer, which is not seen in the complete blood hammer effect. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2010", "text": "Blood vessel disorder  generally refers to the narrowing, hardening or enlargement of  arteries  and  veins . It is often due to the build-up of fatty deposits in the  lumen  of blood vessels or infection of the vessel wall. This can occur in various locations such as coronary blood vessels, peripheral arteries and veins. The narrowed arteries would block the blood supply to different organs and tissues. [ 1 ]  In severe conditions, it may develop into more critical health problems like  myocardial infarction ,  stroke  or  heart failure , which are some of the major reasons of death. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2011", "text": "There are many causes contributing to blood vessel disorder including high blood  cholesterol  and calcium levels, blood clot formation and inflammation of arteries. It is found that age, sedentary lifestyle, diets rich in lipids, smoking,  diabetes  and family history of  cardiovascular diseases  are common risk factors. [ 3 ]  A mild degree of blood vessel disorder may be asymptomatic. [ 4 ]  Blood tests on cholesterol and calcium level can be performed to monitor the risk of having the disorder. Additionally, techniques such as  angiography  and  ultrasound  imaging are useful tools for diagnosis. [ 5 ]  It can be treated by both medication or surgery, depending on the type of blood vessel disorder. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2012", "text": "Atherosclerosis  is a developmental disease in the large arteries, defined by the accumulation of lipids, macrophages and fibrous materials in the intima. [ 1 ]  When the endothelial cell of blood vessel is damaged, it loses the ability to regulate itself. [ 1 ]  It results in inflammation as the  macrophages  irrupt the vessel wall. [ 1 ]  Macrophages take up lipoprotein to form foam cells and release growth factor  cytokines  to attract more macrophages and smooth muscle cells. [ 1 ]  A plaque is formed and proliferate to a larger size, gradually occluding the blood flow. [ 1 ]  More importantly, it causes different complications that affect the whole body. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2013", "text": "An  aneurysm  is a localized enlargement of arteries, characterized by a balloon-like bulge. [ 6 ]  It results from the abnormal weakening of blood vessel wall. [ 7 ]  Common types of aneurysm include  abdominal aortic aneurysm ,  thoracic aortic aneurysm  and  intracranial aneurysm . [ 7 ]  Most types of aneurysm, except intracranial aneurysm, are mainly caused by atherosclerosis. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2014", "text": "Raynaud\u2019s disease  is a rare peripheral vascular syndrome that narrows blood vessels, generally in the hands and feet, due to cold or stressful emotion. [ 8 ]  It is recognized by the reduction of blood flow to fingers and toes with periodic spasm and results in a drastic color change to white or blue. [ 8 ] [ 9 ]  The disease may further develop into ischaemic pain and  necrosis  of fingers or toes. [ 9 ]  The pathology of Raynaud's disease starts with the activation of sympathetic nervous system triggered by cold or the feeling of stress. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2015", "text": "Venous thromboembolism  (VTE) is a common peripheral venous disease. It is defined by the occlusion of venous blood vessels by blood clots. There are two major types of VTE: deep-vein thrombosis (DVT) and pulmonary embolism. [ 10 ]  DVT is often found in the calf, accompanies with the swelling of limbs along the deep vein while  pulmonary embolism  causes chronic  pulmonary hypertension . [ 11 ]  VTE is the third deadliest cardiovascular disease in the world. [ 11 ]   Haemostasis  is the rapid development of blood clots for the purpose of reducing blood loss. [ 11 ]  On the contrary, venous clots are formed much slower, in terms of several days or even weeks. Abnormality of coagulation during haemostasis, change in blood flow and endothelial failure may trigger VTE. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2016", "text": "Erythromelalgia  is a rare clinical disorder causing redness, burning sensation and intense pain in limbs. [ 12 ]  It is more common to be found in lower limbs than upper limbs. [ 12 ]  Erythromelalgia initiated from dysfunction of peripheral nerves that thickens the blood vessel walls, resulting in hyperaemic flow in limbs. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2017", "text": "Stroke  is a serious condition of blood vessel disorder caused by the stop of blood supply to the brain. Brain cells with ceased oxygen supply from blood will die in millions per second. [ 14 ]  Not only is it one of the major causes of death around the world, it is also the cause of permanent disability. Two major types of stroke include ischemic stroke which is caused by atherosclerosis in the brain and hemorrhagic stroke which is the bleeding in the brain due to weakened blood vessel wall inside the brain. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2018", "text": "It is often asymptomatic in the early stages of blood vessel disorder. [ 4 ]  When the disease develops, a variety of signs can be observed in different body parts. For instance, patients may have pale skin, cold hands and feet, and numb fingertips. These are mainly due to the reduction in blood flow to the limbs, resulting in a decrease in heat distribution to these areas.  Ulcers  and wounds would also take a much longer time to heal because of the impairment in  blood clot formation  process. Muscle weakness and cramping may occur as well, especially in the legs, because of the insufficient oxygen supply to muscle cells for metabolism. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2019", "text": "The vascular system strongly influences the condition of the heart. It is also vital in the rest of the body as the blood vessels are in charge of carrying nutrients and the discard of metabolic wastes. Therefore, blood vessel disorder can cause serious complications in the whole body. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2020", "text": "Coronary arteries  are the blood vessels that supply to the heart for its normal function. Blood vessel disorders occur in coronary arteries would affect cardiac activity. For instance, due to atherosclerosis, the plaque would obstruct and causes  ischaemia  - the reduction of blood flow through the arteries. Ischaemia would then result in the decrease in oxygen supply to the heart, hence weaken the heart. It causes a vicious cycle as a weakened heart contraction would decrease blood supply to the body, including  cardiac muscle  (muscle of heart). Moreover, if the plaque suddenly ruptures in the heart, it will cause a  heart attack . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2021", "text": "Various factors may affect one's susceptibility to blood vessel disorders, including behavioural (e.g. smoking), demographic (e.g. age) and genetic (family history) factors. Most of these risk factors first promote the increase in blood pressure, followed by other symptoms and signs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2022", "text": "The rise of blood pressure is correlated to ageing. [ 3 ]  The arterial  compliance  - the amount of tension produced per stretch of arteries, decreases with age, and the stiffness of arteries increases with age. [ 3 ]  The structural change in blood vessels causes the elderly to be more susceptible to hypertension, which leads to complications in arteries, the heart and even the brain. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2023", "text": "Having  obesity  would increase the risk of atherosclerosis. [ 1 ]  A high-fat and high-cholesterol diet would result in an elevation of lipoprotein level, which is one of the constituents of plaque. Lipoprotein level above > 25\u201330\u00a0mg/dl is considered more susceptible by blood vessel disorders. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2024", "text": "Some of the blood vessel disorders are inherited. For instance, erythromelalgia is caused by the mutation of the SCN9A gene, which alters the neural pathway to blood vessels. [ 8 ]  Genetic disorders that affect the circulatory, immune or neural system may contribute to hereditary blood vessel disorder. If one\u2019s family history shows records of vascular disorders, it is more likely to inherit the same disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2025", "text": "Both  active  or  passive  smoking may bring harm to the vascular system. [ 15 ]  For instance, cigarette smoking,  cannabinoids  and smokeless tobacco use were all found to raise blood pressure and increase the risk of stroke. [ 15 ]  Moreover, cigar and cigarette smoking may also cause arterial stiffness. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2026", "text": "Some medications may have the side effect of increasing blood pressure and may even suppress the effect of anti-inflammatory drugs. Pain and anti-inflammatory drugs like  Indomethacin ,  nonsteroidal anti-inflammatory drugs  and  piroxicam  would retain water in the systemic circulation, raising the blood pressure. [ 16 ]  Other types of medications like antidepressant, hormone and caffeine would also increase blood pressure. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2027", "text": "Doctors may look for signs of narrowed, enlarged or hardened arteries by performing a physical examination. [ 17 ]  If blood vessel disorder is present, there will be a weak or even absent pulse under the narrowed area of the artery. The blood pressure in the affected limb would be lowered and whooshing sounds can be heard over the affected arteries using a  stethoscope . [ 17 ]  After that, the following tests could be adapted to further locate the point of narrowing or enlargement of blood vessels. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2028", "text": "Angiography is a medical imaging technique used to visualize the lumen of blood vessels. [ 18 ]  A  catheter , which is a long and thin tube, is inserted into a large artery in the arm or groin area. It is then guided along the artery to the targeted blood vessel to be examined. An imaging dye is loaded into the blood vessel through the catheter and the movement of the dye in the blood vessel is recorded as an angiogram. [ 18 ]  Doctors could determine if there are any abnormalities in the blood vessel using  fluoroscopy ,  computed tomography (CT) angiography  or  magnetic resonance (MR) angiography . After the catheter is removed, some pressure is applied to the incision site for 10 to 20 minutes to prevent excessive bleeding. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2029", "text": "Vascular ultrasound is a non-invasive imaging method to examine the circulation inside blood vessels. Sound waves are transmitted through the tissues of the targeted area and they reflect on the blood cells moving within blood vessels. [ 19 ]  The waves recorded are displayed as an image of the blood vessel and the speed of waves detected can be used to calculate the speed of blood flow inside the vessel. [ 20 ]  When the rate of blood flow is too low, there may be a blockage of vessel. By evaluating blood flow in vessels, the severity and specific location of blood vessel disorder can be determined. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2030", "text": "Different kinds of treatment should be adopted according to the type and severity of blood vessel disorder. Medications are usually prescribed to relieve specific symptoms arisen from the disease while surgery like angioplasty can be performed to provide a more long-lasting effect. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2031", "text": "Angioplasty  is a procedure used to widen narrowed blood vessels, especially in coronary arteries. A long and thin tube called catheter is inserted into a large artery through an incision in the wrist, arm or groin area. The catheter is guided to the affected artery using a real-time x-ray video. A thin wire is then introduced into the blood vessel, delivering a small balloon to the affected area. The balloon is inflated to stretch the blood vessel and compress the fatty deposits against the wall of artery. [ 21 ]  Hence, the vessel is widened and blood can flow through it freely to maintain adequate blood supply to different tissues. Finally, the balloon is deflated and removed. A stent may also be placed to provide support to the vessel wall and prevent it from re-narrowing. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2032", "text": "Beta blockers  are medications that inhibit the sympathetic nervous system by blocking the beta  adrenergic receptors . They can be used to slow down heart rate and decrease blood pressure by inhibiting beta receptors in the heart. [ 23 ]  These medications also induce vasodilation by relaxing smooth muscle in blood vessels. Examples of beta blockers include  carvedilol ,  metoprolol , and  bisoprolol .  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2033", "text": "Calcium channel blockers  are medications that prevent the movement of calcium ions across calcium channels. They can be used to relieve hypertension by causing vascular smooth muscle relaxation. [ 24 ]  They also reduce the heart rate and contractility to lower the cardiac output, which in turn lower blood pressure.  Amlodipine ,  hydralazine  and  dihydropyridine  are examples of calcium channel blockers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2034", "text": "Other medications such as  angiotensin-converting enzyme  (ACE) inhibitors and diuretics can be used to relieve hypertension. [ 25 ]   Statins  and  fibrates  can also be prescribed to lower blood cholesterol level and hence reducing the risk of plaque formation in blood vessels. [ 26 ]  Anti-platelet medications e.g.  aspirin  help reducing blood clot formation in vessels as well."}
{"_id": "WikiPedia_Hematology$$$corpus_2035", "text": "The  Fugates , commonly known as the \" Blue Fugates \" [ 1 ]  or the \" Blue People of Kentucky \", are an ancestral family living in the hills of  Kentucky  starting in the 19th century, where they are known for having a  genetic trait  that led to the  blood disorder   methemoglobinemia , causing the skin to appear blue."}
{"_id": "WikiPedia_Hematology$$$corpus_2036", "text": "Martin Fugate and Elizabeth Smith, [ 2 ]  who had married and settled near  Hazard, Kentucky , in around 1820, were both carriers of the  recessive  methemoglobinemia (met-H) gene. As a result, four of their nine children exhibited blue skin. Their continued reproduction within the limited local gene pool along with a lack of transportation infrastructure ensured that many descendants of the Fugates were born with met-H. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2037", "text": "The disorder can cause heart abnormalities and seizures if the amount of methemoglobin in the blood exceeds 20 percent, but at levels between 10 and 20 percent it can cause blue skin without other symptoms. Most of the Fugates lived long and healthy lives. The \"bluest\" of the blue Fugates, Luna Stacy, had 13 children and lived to age 84. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2038", "text": "Descendants with the gene continued to live near  Troublesome Creek  and Ball Creek into the 20th century. They eventually came to the attention of the  hematologist  Madison Cawein III, who with the assistance of the nurse Ruth Pendergrass made a detailed study of their condition and ancestry. [ 2 ] [ 7 ]  Based on a report published in the  Journal of Clinical Investigation  in 1960 by a public health physician named E. M. Scott, who had studied a similar phenomenon among  native Alaskans , Cawein concluded that a deficiency of the  enzyme   diaphorase  resulted in an oxygen deficiency in the red blood cells, causing the blood to appear brown, which in turn made the skin of those affected appear blue. [ 5 ]  He treated the family with  methylene blue , which eased their symptoms and reduced the blue coloring of their skin. [ 8 ]  His findings were published in the  Archives of Internal Medicine  in 1964. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2039", "text": "Benjamin Stacy, born in 1975, was the last known descendant of the Fugates to have been born exhibiting the characteristic blue color of the disorder, though he quickly lost his blue skin tone, exhibiting only blue tinges on his lips and fingertips when he became cold or agitated. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2040", "text": "In 2019, the novel  The Book Woman of Troublesome Creek , by  Kim Michele Richardson , described a fictional version of the Fugate family during the  Great Depression ."}
{"_id": "WikiPedia_Hematology$$$corpus_2041", "text": "In 2021, the novel  Blue-Skinned Gods  by  S. J. Sindu  references a family from Kentucky with  methemoglobinemia  but does not use the surname Fugate."}
{"_id": "WikiPedia_Hematology$$$corpus_2042", "text": "A reference to \"the Huntsville subgroup\" is made in the American version of television sitcom  Shameless  when  Kevin Ball  (played by  Steve Howey ) discovers that he may have ancestors from that group. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2043", "text": "Cytopenia  is a reduction in the number of mature  blood cells . It can have many causes, and commonly occurs in people with cancer being treated with  radiation therapy  or  chemotherapy ."}
{"_id": "WikiPedia_Hematology$$$corpus_2044", "text": "There are also two general causes of cytopenia: autoimmune and refractory. Autoimmune cytopenia is caused by an autoimmune disease when your body produces antibodies to destroy the healthy blood cells. Refractory cytopenia is caused by bone marrow not producing healthy blood cells, and can be a result of cancer."}
{"_id": "WikiPedia_Hematology$$$corpus_2045", "text": "The symptoms of cytopenia vary depending on the type."}
{"_id": "WikiPedia_Hematology$$$corpus_2046", "text": "The symptoms of anemia include: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2047", "text": "The symptoms of leukopenia include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2048", "text": "The symptoms of thrombocytopenia include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2049", "text": "Cytopenias can be caused by anything that decreases the production of blood cells or increases the destruction of blood cells. This includes, but is not limited to: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2050", "text": "The treatments for cytopenia vary depending on the type of cytopenia. The treatment for anemia is rest and a diet consisting of high iron foods. Medication can also be used such as: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2051", "text": "People with thrombocytopenia are advised to avoid contact with people who are ill, monitor closely for signs of infection, and take antibiotics when appropriate."}
{"_id": "WikiPedia_Hematology$$$corpus_2052", "text": "Bone marrow and stem cell transplantation are effective for all types of cytopenias. However, when a compatible donor cannot be found,  immunosuppressive therapy  is also common.  Antilymphocyte globulin  (ALG) or  antithymocyte globulin  (ATG) is mixed with  cyclosporine  to promote cell growth.  [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2053", "text": "Primary  fibrinogenolysis  is a  medical condition  that appears with abnormal production of  fibrinogen/fibrin degradation products  (FDP), degradation of  coagulation  factors V, VIII, IX, XI and/or degradation of the  fibrin  present in any pre-existing localized  thrombi  and  hemostatic  clots. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2054", "text": "There are many conditions of or affecting the human  hematologic system \u2014the  biological system  that includes  plasma ,  platelets ,  leukocytes , and  erythrocytes , the major components of blood and the  bone marrow . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2055", "text": "An  anemia  is a decrease in number of  red blood cells  (RBCs) or less than the normal quantity of  hemoglobin  in the blood. [ 2 ] [ 3 ]  However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of  hemoglobin deficiency . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2056", "text": "Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few. The three main classes of anemia include excessive blood loss (acutely such as a  hemorrhage  or chronically through low-volume loss), excessive blood cell destruction ( hemolysis ) or deficient red blood cell production (ineffective  hematopoiesis ). Based on 2005-2006 estimates, the  Centers for Disease Control and Prevention  has stated that approximately 5.5 million Americans a year are either admitted to a hospital or seen by a physician, with some form of anemia as their primary diagnosis. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2057", "text": "Symptoms of anaemia include Plummer\u2013Vinson syndrome, candidal infections. Altered taste sensation, smooth, red painful burning sensation of tongue, filiform followed by fungiform papillae atrophy may also be seen. Others include generalized stomatitis, angular cheilitis and gingivitis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2058", "text": "Oral manifestation of anemia include angular cheilitis, generalized stomatitis, candidiasis and gingivitis. There will be pallor of lips and oral mucosa. Patients might have a smooth, red painful tongue, experience burning sensation of tongue or disturbed taste sensation. Atrophy of filiform and fungiform papillae may also occur. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2059", "text": "A nutritional anemia is a type of anemia that can be directly attributed to either a nutritional disorder or a nutritional deficiency."}
{"_id": "WikiPedia_Hematology$$$corpus_2060", "text": "A blood cancer or hematological malignancy is a type of malignant cancer that originates, affects, or involves the blood, bone marrow, or lymph nodes. [ 64 ]  These cancers include leukemias, lymphomas, and myelomas. These particular types of cancers can arise as defected mature cell types that have differentiated from hematopoietic precursor cells (often in the bone marrow) and begin to quickly proliferate through the bloodstream where it can then often infiltrate other organs and tissues. Others can involve the formation of tumors from  lymphoblasts  from within the lymphoid tissue. [ 65 ]  Incidence of affected people with a form of blood cancer has been steady increasing over recent years; however, due in part to early detection methods and subsequent advancements in the treatment of the diseases, mortality rates have continued to decrease. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2061", "text": "Leukemia is a malignancy producing of white blood cells in bone marrow. It can be a serious disease if not treated early.\nSometimes it can be cured by  chemotherapy  or  stem cell treatment . It can affect our bloodstream, skin, lymph nodes, heart, and brain."}
{"_id": "WikiPedia_Hematology$$$corpus_2062", "text": "is also related with  Blood Clot"}
{"_id": "WikiPedia_Hematology$$$corpus_2063", "text": "Hematological disorders may be caused by a number of infection-related conditions involving the introduction of microorganisms into the host, such as  bacteria ,  viruses ,  microfilaria ,  fungus  and  protozoa . [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2064", "text": "Hematologic diseases  are disorders which primarily affect the  blood  and  blood-forming organs . Hematologic diseases include rare genetic disorders,  anemia ,  HIV ,  sickle cell disease  and complications from chemotherapy or transfusions."}
{"_id": "WikiPedia_Hematology$$$corpus_2065", "text": "Hemochromatosis type 4  is a hereditary  iron overload  disorder that affects  ferroportin , an iron transport protein needed to export iron from cells into circulation. [ 1 ]   Although the disease is rare, it is found throughout the world and affects people from various ethnic groups.  While the majority of individuals with type 4 hemochromatosis have a relatively mild form of the disease, some affected individuals have a more severe form. As the disease progresses, iron may accumulate in the tissues of affected individuals over time, potentially resulting in organ damage. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2066", "text": "Symptoms vary greatly between individuals with type 4 hemochromatosis.  This difference in symptoms is likely due to the different types of SLC40A1 mutations patients may have. [ 3 ]  In general, signs and symptoms of type 4 hemochromatosis are caused by excess iron in cells, which leads to tissue damage. The damage is largely due to iron-catalyzed oxidative reactions.  Iron can exchange electrons with a variety of substrates, which can lead to generation of reactive oxygen species.  This can lead to  oxidative stress ,  lipid peroxidation , and DNA damage, which may result in cell death. [ 4 ]   Two main forms of hemochromatosis type 4 exist (A and B), and the symptoms of these forms are distinct from one another. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2067", "text": "Type 4A hemochromatosis typically has milder symptoms than other types of hemochromatosis. Individuals with type 4A hemochromatosis tend to have hyperferritinemia (elevated ferritin in the blood plasma) and low saturated  transferrin  levels.  These individuals are likely to have liver and spleen iron overload, primarily in  Kupffer cells  and other macrophages. [ 5 ]   Because iron export is impaired, iron is unavailable for transport by circulating transferrin.  This iron unavailability potentially leads to mild anemia in type 4A hemochromatosis patients because iron is necessary for hemoglobin synthesis, and red blood cells have a relatively high turnover rate. [ 4 ]  Over time, iron stores increase, and individuals with type 4A hemochromatosis may develop hepatic fibrosis. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2068", "text": "The symptoms of type 4B hemochromatosis tend to be more severe. They resemble the symptoms of hemochromatosis types 1, 2, and 3. Plasma iron concentration is elevated, and symptoms include joint pain, diabetes, and arrhythmia. Liver iron deposition tends to be greater in type 4B than in type 4A. [ 5 ]   Liver damage occurs more frequently in this form of hemochromatosis than in type 4A, and some individuals develop cirrhosis of the liver. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2069", "text": "Type 4 hemochromatosis is caused by mutations of the SLC40A1 gene, located on the long arm of chromosome 2, specifically at 2q32.2.  The SLC40A1 gene encodes ferroportin, a protein responsible for exporting iron from cells in the intestine, liver, spleen, and kidney, as well as from reticuloendothelial macrophages and the placenta. [ 6 ] [ 7 ]  More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis. [ 7 ]  All reported SLC40A1 mutations are deletions or missense mutations, which lead to amino acid substitution. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2070", "text": "Mutations to SLC40A1 that change the amino acid sequence can result in loss of function or gain of function for the resulting ferroportin protein. The loss of function mutation results in a phenotype that is different from that of a gain of function mutation, and these phenotypes are associated with two different forms of type 4 hemochromatosis.  Loss-of-function mutations are more frequent and are associated with type 4A hemochromatosis.  These mutations lead to a defect in the localization of ferroportin.  Gain-of-function mutations are associated with type 4B and lead to production of ferroportin that resists negative regulation by hepcidin. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2071", "text": "Unlike other forms of hemochromatosis, which have a recessive pattern of inheritance, type 4 is an  autosomal dominant  dominant disorder. The dominant inheritance pattern occurs in hemochromatosis type 4 because ferroportin is multimeric. Consequently, mutant ferroportin can associate with wild-type ferroportin in multimers and interfere with the function of normal ferroportin proteins. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2072", "text": "In normal iron regulation, iron is absorbed in the intestine, and ferroportin transports iron from the cells of the intestinal lining into the bloodstream. Iron in the bloodstream is then bound by transferrin, which carries the iron to target cells. Iron is stored in cells and blood serum in a protein called  ferritin . Reticuloendothelial macrophages, which can phagocytose red blood cells, are important in the iron recycling process. Ferroportin is upregulated in the reticuloendothelial macrophages after phagocytosis occurs so that iron from the degraded red blood cells can be released into the bloodstream and transported to other types of cells as needed.   Hepcidin , a protein synthesized in the liver in response to iron or inflammation, is a regulator of ferroportin expression.  When hepcidin binds ferroportin, ferroportin is phosphorylated, endocytosed, tagged with ubiquitin, and degraded. [ 6 ] [ 7 ]  More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis. [ 7 ]   The misregulation of ferroportin in type 4 hemochromatosis can involve a failure of ferroportin to be properly expressed at the cell membrane, or it can involve a failure of ferroportin to respond to negative regulation by hepcidin. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2073", "text": "Hemochromatosis type 4A is characterized by impaired iron export in cells. Reticuloendothelial macrophages are most affected.  Iron accumulates preferentially in Kupffer cells, which are located in the liver, and serum ferritin increases; less iron is available for circulating transferrin, a protein that binds iron and transports it through the bloodstream to cell receptors. [ 10 ] [ 11 ]   This means that, while iron is trapped in certain types of tissues, it cannot be transported to tissues where it is needed. The accumulation of iron in tissues due to impaired iron export can lead to increasing transferrin iron saturation and liver parenchymal iron overload in advanced stages of the disease. [ 3 ]  More ferritin is produced to suppress oxidative cell damage, although the amount of ferritin that cells can accumulate is limited. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2074", "text": "Hemochromatosis type 4B is characterized by abnormal iron release from macrophages and enterocytes because the mutant ferroportin is resistant to the hepcidin protein, which serves a regulatory function in wild-type ferroportin. [ 9 ]  Intestinal iron absorption and release of iron from macrophages is increased. [ 3 ]   Thus, this form of the disease leads to elevated transferrin saturation levels. [ 9 ]   Systemic iron overload results, and liver iron deposition is primarily in the hepatocytes. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2075", "text": "Diagnosis is based upon identification of symptoms, medical history, family history, and laboratory tests. Blood tests may show high levels of ferritin and low, normal, or high levels of transferrin saturation, depending on the form of hemochromatosis. The diagnosis must be confirmed by  genetic testing  for SLC40A1 mutations. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2076", "text": "Treatment is based on the symptoms and severity of the disease.  Iron chelators may be used to bind excess iron in tissues and allow for excretion of the excess metal. [ 15 ]   Individuals with hemochromatosis type 4B may be treated with therapeutic  phlebotomy . However, individuals with hemochromatosis type 4A may not require treatment. Additionally, therapeutic phlebotomy may not be tolerated in individuals with type 4A because anemia may develop despite the elevated serum ferritin levels typically found in these individuals. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2077", "text": "Ferroportin disease is rare. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2078", "text": "Hemoglobin C  (abbreviated as  HbC ) is an abnormal  hemoglobin  in which  glutamic acid  residue at the 6th position of the  \u03b2-globin  chain is replaced with a  lysine  residue due to a point mutation in the  HBB  gene. [ 1 ]  People with one copy of the gene for hemoglobin C do not experience symptoms, but can pass the abnormal gene on to their children. Those with two copies of the gene are said to have  hemoglobin C disease  and can experience mild  anemia . It is possible for a person to have both the gene for hemoglobin S (the form associated with  sickle cell anemia ) and the gene for hemoglobin C; this state is called  hemoglobin SC disease , and is generally more severe than hemoglobin C disease, but milder than sickle cell anemia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2079", "text": "HbC was discovered by  Harvey Itano  and  James V. Neel  in 1950 in two African-American families. It has since been established that it is most common among people in West Africa. It confers survival benefits as individuals with HbC are  naturally resistant to malaria  caused by  Plasmodium falciparum ,  albeit incompletely."}
{"_id": "WikiPedia_Hematology$$$corpus_2080", "text": "People with one copy of the gene for hemoglobin C (termed  heterozygous ) do not experience significant symptoms, but can pass the abnormal gene onto their children; this condition is called hemoglobin C trait. When two hemoglobin C genes are present (termed  homozygous ), the individual is said to have hemoglobin C disease, and may develop mild  anemia , as red blood cells containing hemoglobin C have a decreased lifespan. The anemia in hemoglobin C disease is classified as  hemolytic , because it is caused by the destruction of red blood cells. An  enlarged spleen , and sometimes jaundice, may also occur. [ 1 ] [ 3 ] [ 4 ]  Some persons with this disease may develop  gallstones  that require treatment. [ 5 ]  Continued  hemolysis  may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2081", "text": "The red blood cells of people with hemoglobin C disease are usually abnormally small ( microcytic ) with a high  mean corpuscular hemoglobin concentration  (MCHC). The high MCHC is caused by a decreased concentration of water inside the cells.  Target cells , microspherocytes, and HbC crystals can be seen on microscopic examination of  blood smears  from homozygous patients. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2082", "text": "HbC can combine with other abnormal hemoglobins and cause serious hemoglobinopathies. Individuals with sickle cell\u2013hemoglobin C (HbSC), have inherited the gene for  sickle cell disease  (HbS) from one parent and the gene for hemoglobin C disease (HbC) from the other parent.  Since HbC does not polymerize as readily as HbS, there is less sickling in most cases. There are fewer acute vaso-occlusive events and therefore in some cases fewer sickle cell crises. The peripheral smear demonstrates mostly target cells, occasional hemoglobin C crystals, and only a few sickle cells.  However, persons with hemoglobin SC disease (HbSC) have more significant retinopathy, ischemic necrosis of bone, and priapism than those with pure SS disease. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2083", "text": "There are also a few cases of HbC in combination with  HbO ,  HbD  and  beta thalassemia . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2084", "text": "Hemoglobin C is produced when a point mutation in the  HBB  gene causes amino acid substitution of glutamic acid to lysine at the 6th position of the  \u03b2-globin  chain of the hemoglobin. The mutation can be homozygous, occurring on both the chromosomes (alleles), or heterozygous, affecting only one allele. [ 1 ]  Under heterozygous condition, people are said to have hemoglobin C  trait , or as hemoglobin C carriers, and they have one gene for HbC with either one HbA gene or HbS gene. Their red blood cells contain both hemoglobin C and either normal  hemoglobin A  or hemoglobin S. Hemoglobin C mutation is an autosomal recessive disorder that results from the biparental inheritance of the allele that encodes for hemoglobin C. [ 6 ]  If both parents are carriers of hemoglobin C, there is a chance of having a child with hemoglobin C disease. Assuming both parents are carriers, there is a 25% chance of having a child with hemoglobin C disease, a 50% chance of having a child who is a carrier of hemoglobin C, and a 25% chance of having a child who is neither a carrier nor affected by hemoglobin C disease. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2085", "text": "This mutated form reduces the normal plasticity of host  erythrocytes  causing a  hemoglobinopathy . In those who are  heterozygous  for the mutation, about 28\u201344% of total hemoglobin (Hb) is HbC, and no  anemia  develops. In  homozygotes , nearly all Hb is in the HbC form, resulting in mild  hemolytic anemia , jaundice and enlargement of spleen. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2086", "text": "Individuals with HbC have reduced risk of  P. falciparum  malaria infection. [ 7 ]  HbC has been described as being more advantageous than HbS because, even in homozygous individuals, it is usually non-fatal. [ 8 ]  However, in contrast to HbS, it does not prevent malaria due to  P. vivax, [ 9 ]  and is less effective in resistance to falciparum malaria in heterozygous conditions. [ 7 ]  Homozygous HbC is more resistant to heterozygous condition, or to thalassemias. [ 10 ] [ 11 ]  But HbC mutation  does not prevent the infection.  P. falciparum  do not survive in red blood cells with homozygous hemoglobins, but can survive in the presence of heterozygous hemoglobins. [ 10 ]  HbC reduced the binding force (cytoadherence) of  P. falciparum  by reducing the activity of  PfEMP1 . [ 12 ]  Evidences indicate that HbC reduced the level of  PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite. [ 13 ]  It has been predicted that with the trend of HbC mutation and falciparum prevalence, HbC would replace HbS in central West Africa in the future. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2087", "text": "Physical examination may show an enlarged spleen. Tests that may be done include:  complete blood count  (CBC),  hemoglobin electrophoresis , and  peripheral blood smear . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2088", "text": "Genetic counseling may be appropriate for high-risk couples who wish to have a baby. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2089", "text": "Usually no treatment is needed.  Folic acid  supplementation may help produce normal red blood cells and improve the symptoms of anemia  [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2090", "text": "Overall, hemoglobin C disease is one of the more  benign   hemoglobinopathies . [ 6 ]  Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia.  Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain. [ 6 ]  People with hemoglobin C disease can expect to lead a normal life. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2091", "text": "Hemoglobin C is found most abundantly in areas of West Africa, such as Nigeria, where  Yorubas  live. [ 15 ] [ 16 ] [ 17 ]  Hemoglobin C gene is found in 2-3% of  African-Americans [ 4 ]  while 8% of African-Americans have hemoglobin S (Sickle) gene. Thus Hemoglobin SC disease is significantly more common than Hemoglobin CC disease. The trait also affects people whose ancestors came from  Italy ,  Greece ,  Latin America , and the  Caribbean  region. [ 4 ]  However, it is possible for a person of any race or nationality to have hemoglobin C trait. In terms of geographic distribution, the hemoglobin C allele is found at the highest frequencies in  West Africa , where it has been associated with protection against  malaria . [ 3 ]  Hemoglobin C disease is present at birth, though some cases may not be diagnosed until adulthood. Both males and females are affected equally. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2092", "text": "Studying the molecular basis of  sickle cell disease ,  Linus Pauling  and  Harvey Itano  at the California Institute of Technology discovered in 1949 that the disease was due to abnormal hemoglobin called HBS. [ 18 ] [ 19 ]  In 1950, Itano and  James V. Neel  discovered from two African-American families a different blood condition very similar to sickle cell disease. [ 20 ] [ 21 ]  Five of the ten individuals indicated sickled RBCs. But the condition was harmless as the individuals had no anaemia. Thus, it was not clear whether it was involved in sickle cell disease. Genetically, the abnormal hemoglobin was only in  heterozygous  condition. [ 22 ]  The next year, Neel and his colleagues established that the hemoglobin is associated with sickle cell disease. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2093", "text": "The hemoglobin was named hemoglobin III, [ 24 ]  but hemoglobin C was eventually used. [ 25 ] [ 26 ]  By 1954, it was found that the mutant hemoglobin was highly prevalent in West Africa. [ 27 ] [ 28 ]  In 1960,  Vernon Ingram  and J. A. Hunt at the University of Cambridge discovered that the mutation was a single amino acid replacement of glutamic acid with lysine. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2094", "text": "Hemoglobin D  ( HbD ) is a  variant of hemoglobin , a protein complex that makes up  red blood cells . Based on the locations of the original identification, it has been known by several names such as  hemoglobin D-Los Angeles ,  hemoglobin D-Punjab , [ 1 ]   D-North Carolina ,  D-Portugal ,  D-Oak Ridge , and  D-Chicago. [ 2 ]  Hemoglobin D-Los Angeles was the first type identified by  Harvey Itano  in 1951, and was subsequently discovered that hemoglobin D-Punjab is the most abundant type that is common in the  Sikhs  of Punjab (of both Pakistan and India) and of Gujarat. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2095", "text": "Unlike normal adult human hemoglobin ( HbA ) which has  glutamic acid  at its 121 amino acid position, it has  glutamine  instead. [ 4 ]  The single amino acid substitution can cause various  blood diseases , from fatal genetic anemia to mild  hemolytic anemia , an abnormal destruction of red blood cells. [ 5 ]  Depending on the type of genetic inheritance, it can produce four different conditions: [ 4 ]  heterozygous (inherited in only one of the chromosome 11) HbD trait, HbD- thalassemia , HbS-D ( sickle cell ) disease, and, very rarely, homozygous (inherited in both chromosome 11) HbD disease. [ 6 ]  It is the fourth hemoglobin type discovered after HbA, HbC and HbS; [ 1 ]  the third hemoglobin variant identified after HbC and HbS; [ 2 ]  and the fourth most common hemoglobin variant after HbC, HbS, and HbO. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2096", "text": "Hemoglobin was discovered as some sort of crystal formed from earthworm body fluid and animal blood by German biochemist Friedrich Ludwig H\u00fcnefeld at  Leipzig University  in 1840. [ 7 ] [ 8 ]  When the protein nature was established another German  Felix Hoppe-Seyler  gave the name hemoglobin (literally \"blood protein\") in 1864. [ 9 ] [ 10 ]  Its role as an oxygen transporter was later established. [ 1 ]  While studying  sickle cell disease ,  Linus Pauling  and  Harvey Itano  at the  California Institute of Technology  discovered in 1949 that the disease was due to abnormal hemoglobin, later called hemoglobin S (HbS). [ 11 ] [ 12 ]  In 1950, Itano and  James V. Neel  discovered a slightly different case in which individuals had sickled red blood cells but not anemia. [ 13 ] [ 14 ]  The hemoglobin was named hemoglobin III, [ 15 ]  but later known as hemoglobin C (HbC). [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2097", "text": "In 1934, Jean V. Cooke and J. Keller Mack, pediatricians at St. Louis, USA, reported a case of white American family which had some member suffering from sickle cell anemia. [ 18 ] [ 19 ]  Of six siblings, two children had anemia, while others, including their parents, were healthy. Blood tests indicated the two children had sickled red blood cells, but with uncharacteristically slow process of sickling. The father, who had no disease, was found to have sickled re blood cells. [ 18 ]  With the new techniques for identifying different hemoglobin, Itano investigated the family and found that like their father, three other children had abnormal hemoglobin but without the disease or sickled cells; their hemoglobin giving same mobility (in  electrophoresis ) and but different solubility as sickled cells. He recorded in 1951:"}
{"_id": "WikiPedia_Hematology$$$corpus_2098", "text": "The resent report deals with the identification of still another form of human hemoglobin in five members of a family in which the genetic picture is not typical of sickle cell anemia, although two of the members have in the past been diagnosed as having sickle cell anemia. An earlier study of this family disclosed that the two anemic children and the father, who was not anemic, had sickling erythrocytes while the mother, two sisters and two brothers of the anemic children had non-sickling erythrocytes and were not anemic. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2099", "text": "In the paper published in the  Proceedings of the National Academy of Sciences of the United States of America , Itano presented the need to have naming convention for the different types of hemoglobin, and introduced the alphabet-coding system such as hemoglobin  a  (for normal adult type),  b  (sickle cell type),  c  (sickle cell-associated type) and  d  (for the novel type); as he explained:"}
{"_id": "WikiPedia_Hematology$$$corpus_2100", "text": "In order to facilitate the discussion in the present paper and to avoid confusion in future works, it seems desirable at this time to establish a system of symbols for identifying the various forms of adult human hemoglobin... normal hemoglobin, sickle cell hemoglobin, the abnormal hemoglobin reported by Itano and Neel, and the abnormal hemoglobin reported in the present paper will be designated adult human hemoglobins a, b, c and d, respectively, more briefly as hemoglobins a, b, c and d. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2101", "text": "It was the discovery of hemoglobin D and creation of hemoglobin naming system. [ 3 ]  In 1953, Amoz Immanuel Chernoff at the Washington University School of Medicine, St. Louis, introduced the capitalised-letter designation such as A (for normal adult type), C (second abnormal type), D (third abnormal type), S (sickle cell type) and F (fetal form). [ 21 ]  Although the nomeclature system became a convention, hemoglobin D, in particular, became known by various names, generally based on their origin of identification; like hemoglobin D-Los Angeles for the first discovered, [ 19 ]  hemoglobin D-Punjab, [ 1 ]  D-North Carolina, D-Portugal, D-Oak Ridge, and D-Chicago. [ 2 ]  By 1961, it was known that the structural difference of HbD from HbA was in the \u03b2-chain. [ 22 ]  Around the same time, Corrado Baglioni of Massachusetts Institute of Technology identified the exact abnormality that substitution of glutamic acid with glutamine at position 121 in the \u03b2-chain was the basis of HbD, the findings which he reported in 1962. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2102", "text": "Hemoglobin D has the basic structure and composition of normal adult hemoglobin. It is a globular protein containing  prosthetic  (non-protein) group called heme. There are four individual peptide chains, namely two \u03b1- and two \u03b2-subunits, each made of 141 and 146 amino acid residues, respectively. One heme is associated with each chain and responsible for binding free oxygen in the blood. A single HbD is therefore a  tetramer  (containing four molecules), denoted as \u03b1 2 \u03b2 2 . [ 24 ]  Each subunit has a molecular weight of about 16,000 Da ( daltons ), making the tetramer about 64,000 Da (64,458 g/mol) in size. [ 25 ]  HbD is different from HbA only on the \u03b2-subunit where the amino acid glutamic acid at 121 position is replaced with glutamine (\u03b1 2 \u03b2 2 121Glu\u2192Gln ). [ 4 ]  It has the same chemical characteristic as HbS (a hemoglobin of sickle cell trait), with one fewer negative charge at an alkaline pH than HbA. However, unlike HbS, it does not produce sickled RBC on its own under low level of oxygen. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2103", "text": "Hemoglobin D is synthesised due to mutation in  HBB , the gene that produces \u03b2-subunits of hemoglobin and is present on human chromosome 11. A point mutation in the first base of the 121 codon that normally has GAA sequence for normal hemoglobin is changed to CAA. [ 26 ] [ 27 ]  GAA codes for glutamic acid, while CAA for glutamine. [ 28 ]  This gene mutation makes HbD, which can further give rise to several genetic and disease conditions. The specific mutations can occur at different sites of the gene. According to the Globin Gene Server database, there are other types of HbD such as HbD-Agri ( HBB :c.29C\u2192A;364G\u2192C), HbD-Bushman ( HBB :c.49G\u2192C), HbD-Ouled Rabah ( HBB :c.60C\u2192A or 60C\u2192G), HbD-Iran ( HBB :c.67G\u2192C), HbD-Granada ( HBB :c.68A\u2192T), HbD-Ibadan ( HBB :c.263C\u2192A) and HbD-Neath ( HBB :c.365A\u2192C). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2104", "text": "Depending on the nature of inheritance of HbD mutation there are four conditions, some of which can be deadly diseases: [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2105", "text": "Hemoglobin in combination with normal hemoglobin (heterozygous HBD/HbA) is asymptomatic, causing no effects. Individuals have normal hemoglobin level and their red blood cells are normal spherical structure. [ 29 ]  Homozygous HbD/HbD causes mild hemolytic anemia and chronic non-progressive  splenomegaly  (enlargement of  spleen ). [ 4 ]  Heterozygous HbD/HbS causes sickle cell anemia. However, most cases of the disease are milder than the usual HbS/HbS conditions. The most serious complication noted is stroke. HbD-thalassemia causes microcytic anemia which is generally milder that in typical thalassemia. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2106", "text": "As hemoglobin can be inherited in several conditions, no single diagnostic test can confirm the specific protein completely. Electrophoresis is one of the most commonly used and requires sequential identification with other hemoglobins. All hemoglobins can be separated in cellulose acetate at pH 8.6 and in agarose gel at pH 6.2. In alkaline medium of cellulose acetate, HbD moves slower and can be identified at shorter distance than HbA, but it migrates exactly as HbS. It can be differentiated from HbS in acidic agarose gel in which it moves faster and farther than HbS, but at the same level with HbA. [ 30 ] [ 31 ]   High-performance liquid chromatography  (HPLC) can directly detect the protein, but its specific identification of HbD from other hemoglobins can be inconclusive. [ 32 ]  HPLC coupled with  mass spectrometry  (HPLC-ESI-MS/MS) can accurately detect the protein but the procedure is costly and time consuming. [ 33 ]  Genetic screening can be done with  polymerase chain reaction  that can identify HbS from other hemoglobin variants. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2107", "text": "Hemoglobin D conditions such as homozygous and HbD/HbA heterozygous do not require medical intervention. HbD/HbS and HbD-thalassemia conditions are managed like the typical cases of sickle cell anemia and thalassemia. [ 29 ]  In case of sickle cell anemia, daily treatment with  penicillin  recommended up to five years of age. [ 35 ]  Dietary supplementation of  folic acid  is recommended by the  WHO . [ 36 ]  In 2019,  Crizanlizumab , a monoclonal antibody was approved by the United States FDA for reducing the frequency of blood vessel blockage in 16 years and older individuals. [ 37 ]  For thalassemia, regular lifelong  blood transfusions  is the usual treatment.  Bone marrow transplants  can be curative for some children. [ 38 ]  Medications like  deferoxamine ,  deferiprone  and  luspatercept . [ 39 ]   Gene therapy ,  exagamglogene autotemcel  is approved for medical use in the United Kingdom since November 2023. [ 40 ] [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2108", "text": "Hemoglobin D is most abundant among Sikhs, with occurrence of 2% in Punjab and 1% in Gujarat. It is also found in small number of individuals among Africans, Americans and Europeans who usually had close ethnicity with Indians in the past. [ 5 ]  It is below 2% among the African-Americans. [ 4 ]  Combination with \u03b2-thalassemia and HbS are known in south and east India; the first resulting in thalassemia and the latter in sickle cell anemia. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2109", "text": "There is also high occurrence in China, with prevalence rate of 12.5% in  Chongqing . [ 42 ]  It is sporadically recorded in some Turkish, Algerian, West African, Saudi Arabian, native American, English, and Irish population. [ 29 ]  Rare conditions like HbD/HbJ, [ 43 ]  HbD/ HbQ, [ 44 ]  and HbD/Hb Fontainebleau [ 45 ]  are also found in India. A rare case of HbS/HbD is reported from Pakistan in which individuals are diagnosed with bone infection ( osteomyelitis ). [ 31 ]  An isolated condition of HbD/HbC is recorded in US. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2110", "text": "Hemoglobin H disease , also called  alpha-thalassemia intermedia , is a disease affecting  hemoglobin , the oxygen carrying molecule within  red blood cells . It is a form of  Alpha-thalassemia  which most commonly occurs due to  deletion  of 3 out of 4 of the  \u03b1-globin  genes. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2111", "text": "Hemoglobin H disease is a genetic disorder resulting in absent or impaired production of the  \u03b1-globin  protein, a normal component of the hemoglobin. The disease occurs when the \u03b1-globin  gene expression  is reduced to less than 30% of the normal expression. [ 2 ]  In a healthy individual there are four copies of the gene which encode the alpha-globin protein.  Alpha-globin  is encoded by the  HBA1  (2 copies) and  HBA2  (2 copies) genes. The  genotype  of healthy individuals with four normal copies of \u03b1-globin is annotated as \u03b1\u03b1/\u03b1\u03b1. In individuals with deletional Hb H disease, there is deletion of three of the four  \u03b1-globin  alleles, which is annotated as --/-\u03b1. [ 3 ]  Non-deletional Hb H disease refers to a decreased alpha-globin that has not occurred as a result of the complete deletion of the  DNA sequences  encoding HBA1 and HBA2, and this is more rare than the deletional type. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2112", "text": "The most common hemoglobin found within adult  red blood cells  is  Hemoglobin A . The structure of Hb A consists of two  \u03b1-globin  chains bound to two  \u03b2-globin  chains to form a  tetramer  (a protein made up four protein chains). [ 3 ]  When there is lower than normal production of  \u03b1-globin , as in Hb H disease, the excess  \u03b2-globin  form \u03b2 4 -tetramers, termed Hemoglobin H. These \u03b2 4 -tetramers accumulate in red blood cells and precipitate to form Hb H  inclusion bodies . The inclusion bodies in the mature red blood cells are removed by the  spleen  and this results in an early destruction of these red blood cells. This destruction of red blood cells by the spleen is termed  extravascular hemolysis . [ 4 ]   Hemoglobin F  is the predominant form in the  fetus  and it also contains  \u03b1-globin , thus, in severe cases the disease can affect  fetal development . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2113", "text": "The prevalence of Hemoglobin H disease mirrors that of the  hemoglobinopathies .  As a whole, they are most prevalent in individuals of Asian, African, and Mediterranean decent. [ 5 ]  There is a protective effect against malaria for individuals carrying thalassemia genes, which explains the high frequency of thalassemia within the worldwide population. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2114", "text": "Patients with Hemoglobin H Disease present with chronic  hemolytic anemia  that ranges in severity form mild to moderate disease.  Anemia  is the most common presenting symptom of patients with Hb H disease . Other common clinical features include jaundice, splenomegaly, hepatomegaly, and gallstones. All of these symptoms are related to the destruction of the red blood cells in the spleen and the associated increased  hemoglobin metabolism . Patients with non-deletional Hb H disease are more likely to be symptomatic and have severe disease presentation when compared to individuals with deletional Hb H disease. Disease presentation varies from asymptomatic individuals to  neonatal  growth retardation and death in the most severe cases. Death in the neonatal period occurs due to the severe anemia resulting in  Hydrops Fetalis . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2115", "text": "Patients most often present initially due to hemolytic episodes that occur during times of  infection  or  inflammation . During these episodes, patients may develop hemolytic crisis, in which there is a rapid drop in the hemoglobin due to increased red blood cell destruction. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2116", "text": "Hemoglobin analysis, with tests such as  high-performance liquid chromatography , along with  genetic testing  are required for the confirmation of Hb H disease. [ 6 ] [ 7 ]  Patients may also laboratory abnormalities indicative of low red blood cells, including changes in hemoglobin,  red cell distribution width ,  hematocrit ,  mean corpuscular hemoglobin , and  mean corpuscular volume . [ 4 ]  A  peripheral blood smear  stained with  brilliant cresyl blue  will show inclusion bodies within the red blood cells. [ 7 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2117", "text": "Due to the fact that Hb H disease does not commonly present with severe anemia, all patients do not require treatment or intervention. Some patients may require  folic acid  supplementation due to the increased turnover of red blood cells. In cases of hemolytic crisis, patients are treated with a  blood transfusion  and treatment of the underlying cause. In severe cases, regular blood transfuions may be needed, and these patients should be monitored for development of  iron overload . For these severe cases,  stem cell transplantation  can be curative. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2118", "text": "Hemoglobin J  is an abnormal  hemoglobin , an  alpha globin  gene variant and present in various geographic locations. It was first reported in a black American family [ 1 ]  in 1956, and later reported from Indonesia, India, and other parts of the world. Hemoglobin J reported from Meerut India shows the  mutation  of 120th  alanine  to  glutamic acid  on  alpha chain . [ 2 ]  Hemoglobin J was also reported from  Chhattisgarh , Central India as revealed by Lingojwar and coworkers in 2016. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2119", "text": "This  gene  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_2120", "text": "Hemoglobin O  ( HbO ) is a rare type of  hemoglobin  in which there is a substitution of  glutamic acid  by  lysine  as in  hemoglobin C , but at different positions. Since the amino acid substitution can occur at different positions of the  \u03b2-globin chain  of the protein, there are several variants. In  hemoglobin O-Arab  (HbO-Arab) substitution occurs at position 121, [ 1 ]  while in hemoglobin O-Padova (HbO-Padova) it is at 11 position, [ 2 ]  and in hemoglobin O Indonesia (HbO Ina ) it is at 116. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2121", "text": "HbO is usually harmless unlike other hemoglobin variants such as  HbS  and  thalassemias , even under combination with these abnormal hemoglobins. Hemoglobin O-Padova is the most severe form and is associated with disease of the RBCs and spleen."}
{"_id": "WikiPedia_Hematology$$$corpus_2122", "text": "Hemoglobin O Indonesia is the first discovered HbO. Lie-Injo Luan Eng at the  University of Indonesia , Djakarta, was the first to notice the abnormal hemoglobin in 1956 among the  Buginese people  of Sulawesi Island in Indonesia. It was found among normal hemoblobin ( HbA ) of the blood samples but different under  electrophoresis . It also showed different characters form HbS and HbC, and did not cause  sickling of RBCs . The discovery went unnoticed as he later remarked, \"This report, however, did not attract any attention as it was written in the Indonesian language.\" [ 4 ]  He again reported his observation in  The Lancet  the next year. [ 3 ]  After consulting  Hermann Lehmann  at the  St Bartholomew's Hospital  in London and T.H.J. Huisman at the  State University of Groningen  in the Netherlands, and letting experimentally verified by  Harvey Itano  at the  California Institute of Technology , he was convinced that his discovery was a new type of hemoglobin. He gave the name \"hemoglobin Buginese X\" as he reported in  The British Medical Journal  in 1958, concluding:"}
{"_id": "WikiPedia_Hematology$$$corpus_2123", "text": "As it has been confirmed by different laboratories that Buginese X differs from all other known haemoglobins, it should be allotted a letter. N was the letter most recently used to designate haemoglobin Liberian I (personal communication by Dr.  James V. Neel ). So far as we know, the letter 0 has not yet been used, and therefore Buginese X should be called Hb 0. Dr. James V. Neel agreed with this choice. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2124", "text": "The same hemoglobin type was found in Iran in 1973. It was found that the protein modification was at position 116 where lysine was present in place of glutamic acid. [ 5 ]  In 1978, a similar case was reported from Italy. [ 6 ]  The hemoglobin was eventually named hemoglobin O Indonesia. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2125", "text": "In 1960, a different but related hemoglobin was found from an 8-year-old Arab boy at  Jisr az-Zarqa  in Israel. [ 8 ] [ 9 ]  As the boy had severe pneumonia and blood abnormality ( hemoglobinopathy ) including sickled RBCs. His Hemoglobin was different from HbC and HbS and was designated as hemoglobin O (HbO). On investigating his family, his father was found to be the HbO carrier (i.e.  heterozygous  HbA/HbO) while her mother HbS carrier. Out of the six siblings, three had no HbO (though one has HbS), one had a heterozygous HbO. The boy and his older sister were diagnosed with sickle cell disease due to inherited HbS/HbO combination. [ 8 ]  It was later found that the amino acid replacement is at position 121 of the hemoglobin. The hemoglobin is now known as hemoglobin O-Arab. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2126", "text": "In 1974, another abnormal hemoglobin which they called hemoglobin O-Padova was identified from an Italian woman in Padova. [ 10 ]  It showed glutamic acid to lysine substitution at position 11. [ 11 ]  The woman was suffering from a complicated blood conditions. The mother and one of the two children indicated the same hemoglobin but without any symptom. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2127", "text": "Hemoglobin O Indonesia is mostly harmless. But some individuals may indicate mild anemia. [ 4 ]  Even under heterozygous condition such as with HbD, no serious symptom is observed. [ 12 ]  With HbS, there can be mild  sickle cell trait  but no symptoms. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2128", "text": "Hemoglobin O-Arab causes sickle cell disease in heterozygous (HbS/HbO) individuals. However, the symptomatic anemia is mild and is not life-threatening. It is even milder than in heterozygous sickle cell trait (HbS/HbA). [ 15 ]  A case of  sickle cell retinopathy  is documented. [ 16 ]  Under  homozygous  condition, it is also linked with  jaundice  (conjugated hyperbilirubinemia), [ 9 ]  and mild anemia. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2129", "text": "Hemoglobin O-Padova in homozygous condition is associated with complex genetic and physiological anomalies. In the first woman diagnosed, severe RBC damage ( dyserythropoietic anemia ), enlargement of spleen ( splenomegaly ), and abnormal RBC (hereditary erythroblastic multinuclearity). [ 10 ]  But heterozygous condition is clinically harmless. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2130", "text": "Hemoglobinopathy  is the medical term for a group of inherited  blood disorders  involving the  hemoglobin , the protein of  red blood cells . [ 1 ]  They are generally  single-gene disorders  and, in most cases, they are inherited as  autosomal   recessive  traits. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2131", "text": "There are two main groups: abnormal structural hemoglobin variants caused by mutations in the hemoglobin genes, and the  thalassemias , which are caused by an underproduction of otherwise normal hemoglobin molecules. The main structural hemoglobin variants are HbS, HbE and HbC. The main types of thalassemia are  alpha-thalassemia  and  beta thalassemia . [ 4 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2132", "text": "Hemoglobin is a  protein  containing  iron  that facilitates the transportation of  oxygen  in  red blood cells . [ 5 ]  Hemoglobin in the  blood  carries oxygen from the  lungs  to the other tissues of the body, where it releases the oxygen to enable  aerobic respiration  which powers the  metabolism . Normal levels of hemoglobin vary according to sex and age in the range 9.5 to 17.2 grams of hemoglobin in every deciliter of blood. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2133", "text": "Hemoglobin also transports other gases. It carries off some of the body's respiratory  carbon dioxide  (about 20\u201325% of the total) [ 7 ]  as  carbaminohemoglobin , in which CO 2  binds to the  heme protein . The molecule also carries the important regulatory molecule  nitric oxide  bound to a  thiol  group in the globin protein, releasing it at the same time as oxygen. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2134", "text": "Normal human hemoglobins are  tetrameric proteins  composed of two pairs of globin chains, each of which contains one \u03b1 (alpha) chain and one \u03b2 (beta) chain. Each globin chain is associated with an iron-containing  heme   moiety . Throughout life, the synthesis of the \u03b1 and the \u03b2 chains is balanced so that their ratio is relatively constant and there is no excess of either type. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2135", "text": "The specific \u03b1 and \u03b2 chains that are incorporated into Hb are highly regulated during development: [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2136", "text": "Hemoglobin structural variants manifest a change in the structure of the Hb molecule. The majority of hemoglobin variants do not cause disease and are most commonly discovered either incidentally or through newborn screening. Hb variants can usually be detected by protein-based  assay  methods such as  electrophoresis , [ 15 ]   isoelectric focusing , [ 16 ]  or  high-performance liquid chromatography . [ 17 ]  Diagnosis is commonly confirmed by  DNA sequencing . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2137", "text": "The hemoglobin structural variants can be broadly classified as follows: [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2138", "text": "Methemoglobinemia  is a condition caused by elevated levels of  methemoglobin  in the blood. Methaemoglobin is a form of hemoglobin that contains the  ferric  [Fe 3+ ] form of iron, instead of the  ferrous  [Fe 2+ ] form . Methemoglobin cannot bind  oxygen , which means it cannot carry oxygen to tissues. In human  blood  a trace amount of methemoglobin is normally produced spontaneously; the enzyme  methemoglobin reductase  is responsible for converting methemoglobin back to  hemoglobin . [ 23 ] [ 24 ]  Methemoglobinemia can be hereditary but more commonly occurs as a side effect of certain medications or by abuse of  recreational drugs . [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2139", "text": "Thalassemias  are quantitative defects that lead to reduced levels of one type of globin chain, creating an imbalance in the ratio of alpha-like chains to beta-like chains. This ratio is normally tightly regulated to prevent excess globin chains of one type from accumulating. The excess chains that fail to incorporate into normal hemoglobin can form non-functional aggregates that precipitate. This can lead to premature RBC destruction in the bone marrow and/or in the peripheral blood. Thalassemia subtypes of clinical significance are  alpha thalassemia  and  beta thalassemia . A third subtype,  delta thalassemia , affects production of HBA2 and is generally asymptomatic. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2140", "text": "The severity of alpha thalassemia depends on how many of the four genes that code for  alpha globin  are faulty. In the fetus, a deficiency of alpha globin results in the production of  Hemoglobin Barts  - a dysfunctional  hemoglobin  that consists of four  gamma globins . In this situation, a fetus will develop  hydrops fetalis  and normally die before or shortly after birth. [ 27 ]  In adults alpha thalassemia manifests as  HbH disease . In this, excess  beta-globin  forms \u03b2 4 -tetramers, which accumulate and precipitate in red blood cells, damaging their membranes. Damaged RBCs are removed by the  spleen  resulting in moderate to severe anemia. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2141", "text": "In beta thalassemia, reduced production of beta globin, combined with a normal synthesis of alpha globin, results in an accumulation of excess unmatched alpha globin. This precipitates in the red cell precursors in the bone marrow, triggering their premature destruction. Anemia in beta thalassemia results from a combination of ineffective production of RBCs, peripheral  hemolysis , and an overall reduction in hemoglobin synthesis. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2142", "text": "A combination hemoglobinopathy occurs when someone inherits two different abnormal hemoglobin genes. If these are different versions of the same gene, one having been inherited from each parent it is an example of  compound heterozygosity ."}
{"_id": "WikiPedia_Hematology$$$corpus_2143", "text": "Both alpha- and beta- thalassemia can coexist with other hemoglobinopathies. Combinations involving alpha thalassemia are generally benign. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2144", "text": "Some examples of clinically significant combinations involving beta thalassemia include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2145", "text": "There are two clinically significant combinations involving the sickle cell gene:"}
{"_id": "WikiPedia_Hematology$$$corpus_2146", "text": "Hemoglobin variants are not necessarily pathological. For example, Hb Lepore-Boston and G-Waimanalo are two variants which are non-pathological. [ 38 ]  There are in excess of 1,000 known hemoglobin variants. [ 39 ]  A research database of hemoglobin variants is maintained by  Penn State University . [ 40 ]  A few of these variants are listed below."}
{"_id": "WikiPedia_Hematology$$$corpus_2147", "text": "Some hemoglobinopathies seem to have given an evolutionary benefit, especially to  heterozygotes , in areas where  malaria  is endemic. Malaria parasites infect red blood cells, but subtly disturb normal cellular function and subvert the immune response. A number of mechanisms have been propsed to explain the increased chance of survival for the carrier of an abnormal hemoglobin trait. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2148", "text": "Hemolytic jaundice , also known as prehepatic jaundice, is a type of  jaundice  arising from  hemolysis  or excessive destruction of red blood cells, when the byproduct  bilirubin  is not excreted by the  hepatic  cells quickly enough. [ 1 ]  Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the  liver  does not contribute to this type of jaundice. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2149", "text": "As one of the three categories of  jaundice , the most obvious sign of hemolytic jaundice is the discolouration or yellowing of the  sclera  and the  skin  of the patient, but additional symptoms may be observed depending on the underlying causes of  hemolysis . Hemolytic causes associated with bilirubin overproduction are diverse and include disorders such as  sickle cell anemia , [ 2 ]   hereditary spherocytosis , [ 3 ]   thrombotic thrombocytopenic purpura , [ 4 ]   autoimmune hemolytic anemia , [ 5 ]  hemolysis secondary to drug toxicity, [ 6 ]   thalassemia minor , [ 7 ]  and  congenital dyserythropoietic anemias . [ 8 ]   Pathophysiology  of hemolytic jaundice directly involves the  metabolism  of  bilirubin , where overproduction of  bilirubin  due to  hemolysis  exceeds the liver's ability to  conjugate  bilirubin to  glucuronic acid . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2150", "text": "Diagnosis  of hemolytic jaundice is based mainly on visual assessment of the yellowing of the patient's  skin  and  sclera , while the cause of  hemolysis  must be determined using laboratory tests. [ 10 ]  Treatment of the condition is specific to the cause of  hemolysis , but intense  phototherapy  and  exchange transfusion  can be used to help the patient excrete accumulated  bilirubin . [ 11 ]  Complications related to hemolytic jaundice include  hyperbilirubinemia  and  chronic bilirubin encephalopathy , which may be deadly without proper treatment. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2151", "text": "The signs and symptoms additional to the development of a yellowish colour in the  sclera  and  skin  are specific to the causes of  hemolysis ."}
{"_id": "WikiPedia_Hematology$$$corpus_2152", "text": "For example, if the patient has hemolytic  jaundice  resulting from  sickle cell disease , vaso-occlusive phenomena like acute vaso-occlusive pain and  acute chest syndrome  may be observed in the acute phases, while in  anemia , neurologic deficits and various  pulmonary  conditions may manifest in the  chronic  phase. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2153", "text": "Regardless of the causes, laboratory-confirmed elevation is predominantly seen in unconjugated  bilirubin . [ 10 ]  Serum  bilirubin  concentration rarely exceeds 4\u00a0mg/dL, unless the patient has concurrent liver disease. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2154", "text": "The underlying causes of hemolytic jaundice, as its name suggests, are disorders associated with  hemolysis . Such disorders are manifold and the common causes include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2155", "text": "Other less commonly observed causes of hemolysis include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2156", "text": "The above list is not exhaustive, and rare causes of  hemolysis  such as  Bartonella infection , [ 18 ]   hemolysis  due to  transfusion reactions , [ 19 ]  and  microangiopathic hemolytic anemia [ 20 ]  should be suspected when symptoms specific to those causes manifest."}
{"_id": "WikiPedia_Hematology$$$corpus_2157", "text": "The mechanisms by which  bilirubin  is overproduced in hemolytic jaundice can be understood in relation to the two major sites of  hemolysis : intravascular and extravascular."}
{"_id": "WikiPedia_Hematology$$$corpus_2158", "text": "During  intravascular hemolysis , red blood cells are broken down within the  vasculature , allowing  hemoglobin  from the ruptured  red blood cells  to form haptoglobin-hemoglobin complexes with  haptoglobin , which will be internalized and degraded by  hepatocytes  and the  spleen . [ 21 ]  If the degree of  hemolysis  is abnormally high, the unbound  hemoglobin  is converted to  methemoglobin  from which the  heme  moiety is bound to  hemopexin  or to  albumin , and both heme-hemopexin and heme-bound albumin are internalized by hepatocytes and subsequently degraded to  bilirubin . [ 22 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2159", "text": "During  extravascular hemolysis ,  red blood cells  are destroyed by  phagocytosis  by  macrophages  in the  reticuloendothelial system  and digested by  phagosomes . [ 23 ]  Hemoglobin within red blood cells are then degraded to release  heme , which will be converted by  microsomal heme oxygenase  to  iron ,  carbon monoxide  and  biliverdin , and are immediately reduced to unconjugated  bilirubin  by  biliverdin reductase  and released into the plasma. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2160", "text": "In both settings of  hemolysis  mentioned above, only low levels of conjugated  bilirubin  may accumulate in the serum, with the amount falling within the normal limits of 4 percent of total bilirubin as conjugated bilirubin can be efficiently excreted in bile through being secreted across canalicular membrane. [ 25 ]  Increased levels of conjugated bilirubin will only be observed with coexisting hepatobiliary abnormalities. Only when the canalicular excretion capacity is exceeded, conjugated bilirubin will accumulate in the plasma. [ 26 ]  As unconjugated bilirubin has a high affinity to albumin, at high level it is not efficiently cleared through  glomerular filtration  and it binds to the  elastic tissue  of the  skin  and  sclera , where high  albumin  content can be found. [ 25 ]  This explains the yellow discolouration observed in these tissues in hemolytic jaundice."}
{"_id": "WikiPedia_Hematology$$$corpus_2161", "text": "Symptoms  of  jaundice  can be observed superficially, thus visual methods are used to identify the condition. [ 27 ]  However, underlying causes of  jaundice  must be diagnosed through laboratory testing. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2162", "text": "In both newborns and adults, yellowing of the skin is a marker for jaundice. [ 27 ]  As most cases of  jaundice  are observed in newborns, healthcare workers use visual methods to identify the presence of this condition. [ 29 ]  A clinical  jaundice  scale, an adapted version of the Kramer's scale, is used to quantify the severity of jaundice through the spread of skin discoloration from zone 1, the head, to zone 5, the palms and soles of the neonate's body. [ 29 ] [ 30 ]  Cephalocaudal progression of jaundice to zone 4 and 5 of the Kramer's scale shows a significant positive correlation with serum  bilirubin  concentration of at least 11.0\u00a0mg per 100 ml, indicating the need for treatment. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2163", "text": "Conjunctival icterus  can be quantified by the Jaundice Eye Colour Index (JECI) through digital photography of the  sclera , where a JECI of 0 indicates a white colour, and a JECI of 0.1 indicates an intense yellow colour, which is a sign of hemolytic jaundice. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2164", "text": "Multiple tests can be used to diagnose  jaundice , but results of different parameters must be compared to determine its  etiology . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2165", "text": "When a patient shows signs of  jaundice  such as the yellowing of the  skin  and  sclera , a  urine test  is performed to check the levels of  urobilinogen  present. [ 32 ]  The presence of  urobilinogen \u00a0and its increased levels indicate that there are more than normal amounts of  bilirubin  in the  intestine , showing that  jaundice  observed is not due to the blockage of bile flow, and is of pre-hepatic or hepatic causes. [ 32 ]  Normal colour of the patient's  urine  indicates the absence of unconjugated  bilirubin . [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2166", "text": "Results from the urine test should be confirmed by a  complete blood count  (CBC) and serum testing for total serum bilirubin and fractionated bilirubin. [ 32 ]  Increased  reticulocytes  and the presence of  schistocytes  in the  blood smear  of the patient observed during CBC indicates  hemolysis . [ 28 ]  If the patient has hemolytic jaundice, serum testing will show that conjugated bilirubin will only account for less than 15% of the total serum bilirubin due to the increase of unconjugated bilirubin. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2167", "text": "Analysis of liver biopsies will show the levels of  alkaline phosphatase ,  aspartate transaminase , and  alanine transaminase  in the patient, which has a negative correlation with liver function. [ 27 ]  Normal levels of these enzymes indicate that there is no significant hepatocellular damage. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2168", "text": "When an  infant  is suspected to have hemolytic jaundice, abnormal  morphologies  of  erythrocytes  can be analyzed to find out the causes of  hemolysis . [ 34 ]  A  Coomb's test  should be performed, and end-tidal  carbon monoxide  concentration should be monitored to understand the rate of  hemolysis  in the infant's body. [ 35 ]  If chronic hemolytic jaundice is diagnosed in a newborn, development of  anemia  and bilirubin cholelithiasis should be monitored as well. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2169", "text": "If other symptoms of anemia is present, the amount of serum  haptoglobin  in the patient can be measured to test for  hemolysis . [ 36 ]  During  hemolysis ,  hemoglobin  in  blood  dissociates and forms complexes with  haptoglobins  in the plasma, which are then catabolized. [ 37 ]  Low levels of  haptoglobin  resulting from the test shows that there are large amounts of  free hemoglobin  in the  blood  to be bound, acting as an indicator of  hemolysis . [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2170", "text": "As  jaundice  is not common in adults, most treatment methods for this condition are centered around  neonates , of which 50% develop  jaundice . [ 27 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2171", "text": "Intensive  phototherapy  at saturation dose is used as a first-line clinical treatment which decreases the amount of accumulated unconjugated  bilirubin  in the infant's serum by the addition of  oxygen , thus allowing it to dissolve in  water  so the  liver  can more easily convert it into products which can be  excreted  without further  metabolism . [ 38 ]  For infants with hemolytic jaundice, severe and prolonged cases of  hyperbilirubinemia , or high serum  bilirubin  that does not decrease after  phototherapy ,  blood exchange transfusion  is carried out at the  umbilical venous catheter  to mechanically remove  bilirubin . [ 38 ] [ 39 ] [ 40 ]  In cases of immune hemolytic jaundice,  intravenous immunoglobulin therapy  may be used to treat the condition. [ 41 ]  Administration of  intravenous immunoglobulin  can block monocyte  Fc-receptors , preventing or reducing further  hemolysis . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2172", "text": "In adults, hemolytic jaundice is uncommon, and medical treatment methods should be determined by recognizing the underlying causes of  hemolysis  in the patient. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2173", "text": "In cases where patients receive poor or no treatment of  jaundice , neurodevelopmental complications may follow the condition, eventually leading to  hearing loss ,  visual impairment , and in severe cases, mortality. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2174", "text": "Hyperbilirubinemia  may be observed when  hemolysis  produces too much  bilirubin  through the excessive breakdown of  red blood cells , and the  bilirubin  builds up in the patient's  blood  and  tissue fluids  without proper  excretion . [ 43 ]  Untreated or inadequately treated  hyperbilirubinemia  will lead to other complications such as  kernicterus . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2175", "text": "Chronic bilirubin encephalopathy , also known as  kernicterus , is a brain-damaging complication associated with both  preterm  and  full term  infants with  jaundice , where the large amounts of unconjugated  bilirubin  in the infants become  neurotoxic . [ 39 ] [ 44 ]   Kernicterus  affects mainly the  basal ganglia , and its effects can spread to the  hippocampus ,  geniculate nuclei , and  cranial nerve nuclei . [ 13 ]  Symptoms of  kernicterus  include  athetoid cerebral palsy  and in severe cases, may lead to death of the patient. [ 39 ]  Most cases of  kernicterus  develop in infants following early hospital discharge from  phototherapy . [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2176", "text": "Hemolytic\u2013uremic syndrome  ( HUS ) is a group of  blood disorders  characterized by  low red blood cells ,  acute kidney injury  (previously called acute renal failure), and  low platelets . [ 1 ] [ 3 ]  Initial symptoms typically include  bloody diarrhea ,  fever ,  vomiting , and weakness. [ 1 ] [ 2 ]  Kidney problems and low platelets then occur as the diarrhea progresses. [ 1 ]  Children are more commonly affected, but most children recover without permanent damage to their health, although some children may have serious and sometimes life-threatening complications. [ 6 ]  Adults, especially the elderly, may show a more complicated presentation. [ 2 ] [ 6 ]  Complications may include  neurological problems  and  heart failure . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2177", "text": "Most cases occur after  infectious diarrhea  due to a specific type of  E. coli  called  O157:H7 . [ 2 ]  Other causes include  S. pneumoniae ,  Shigella ,  Salmonella , and certain medications. [ 1 ] [ 2 ] [ 3 ]  The underlying mechanism typically involves the production of  Shiga toxin  by the bacteria. [ 1 ] [ 2 ]   Atypical hemolytic uremic syndrome  (aHUS) is often due to a  genetic mutation  and presents differently. [ 1 ] [ 2 ]  However, both can lead to widespread  inflammation  and multiple  blood clots  in small  blood vessels , a condition known as  thrombotic microangiopathy . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2178", "text": "Treatment involves  supportive care  and may include  dialysis ,  steroids ,  blood transfusions , or  plasmapheresis . [ 1 ] [ 2 ]  About 1.5 per 100,000 people are affected per year. [ 5 ] [ 1 ]  Less than 5% of those with the condition die. [ 1 ]  Of the remainder, up to 25% have ongoing kidney problems. [ 1 ]  HUS was first defined as a  syndrome  in 1955. [ 1 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2179", "text": "After eating contaminated food, the first symptoms of infection can emerge anywhere from 1 to 10 days later, but usually after 3 to 4 days. [ 9 ]  These early symptoms can include diarrhea (which is often bloody), stomach cramps, mild fever, [ 10 ]  or vomiting that results in dehydration and reduced urine. [ 9 ]  HUS typically develops about 5\u201310 days after the first symptoms, but can take up to 3 weeks to manifest, and occurs at a time when the diarrhea is improving. [ 10 ]  Related symptoms and signs include lethargy,  decreased urine output ,  blood in the urine ,  kidney failure ,  low platelets , (which are needed for blood clotting), and destruction of red blood cells ( microangiopathic hemolytic anemia ).  High blood pressure ,  jaundice  (a yellow tinge in skin and the whites of the eyes), seizures, and bleeding into the skin can also occur. [ 10 ]  In some cases, there are prominent neurologic changes. [ 11 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2180", "text": "People with HUS commonly exhibit the symptoms of  thrombotic microangiopathy  (TMA), which can include abdominal pain, [ 14 ]  low platelet count, [ 15 ]  elevated  lactate dehydrogenase  LDH, (an enzyme released from damaged cells, and which is therefore a marker of cellular damage) [ 16 ]  decreased haptoglobin (indicative of the breakdown of red blood cells) [ 16 ]  anemia (low red blood cell count), schistocytes (damaged red blood cells), [ 15 ] [ 16 ]  elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally), [ 17 ]  proteinuria (indicative of kidney injury), [ 18 ]  confusion, [ 14 ]  fatigue, [ 19 ]   swelling , [ 20 ]  nausea/vomiting, [ 21 ]  and diarrhea. [ 22 ]  Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, [ 15 ]   hypertension  (high blood pressure), [ 19 ]  myocardial infarction (heart attack), [ 23 ]  stroke, [ 14 ]  lung complications, [ 23 ]   pancreatitis  (inflammation of the pancreas), [ 21 ]  liver necrosis (death of liver cells or tissue), [ 15 ] [ 19 ]   encephalopathy  (brain dysfunction), [ 19 ]  seizure, [ 24 ]  and coma. [ 25 ]  Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression. [ 5 ] [ 7 ] [ 15 ] [ 18 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2181", "text": "Shiga-toxin producing E. coli  (STEC) HUS occurs after ingestion of a strain of bacteria expressing  Shiga toxin  such as enterohemorrhagic  Escherichia coli  (EHEC), of which  E. coli O157:H7  is the most common  serotype . [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2182", "text": "Atypical HUS (aHUS) represents 5\u201310% of HUS cases [ 5 ]  and is largely due to one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of the  complement system , [ 5 ]  which is a group of immune signaling factors that promote inflammation, enhance the ability of  antibodies  and  phagocytic cells  to clear microbes and damaged cells from the body, and directly attack the pathogen's cell membrane. This results in  platelet  activation,  endothelial cell  damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count,  hemolysis  (breakdown of red blood cells), damage to multiple organs, and ultimately death. [ 7 ] [ 18 ] [ 28 ]  Early signs of systemic complement-mediated TMA include  thrombocytopenia  (platelet count below 150,000 or a decrease from baseline of at least 25%) [ 16 ]  and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin (the oxygen-containing component of blood), and/or the presence of schistocytes. [ 7 ] [ 29 ] [ 16 ]  Despite the use of supportive care, an estimated 33\u201340% of patients will die or have  end-stage renal disease  (ESRD) with the first clinical manifestation of aHUS, [ 22 ] [ 23 ]  and 65% of patients will die, require dialysis, or have permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI) therapy. [ 22 ]  Patients who survive the presenting signs and symptoms of aHUS endure a chronic thrombotic and inflammatory state, which puts them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death. [ 29 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2183", "text": "Historically, treatment options for aHUS were limited to  plasma exchange  or plasma infusion (PE/PI) therapy, which carries significant risks [ 30 ] [ 31 ]  and has not been proven effective in any controlled trials. People with aHUS and ESRD have also had to undergo lifelong dialysis, which has a 5-year survival rate of 34\u201338%. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2184", "text": "HUS is caused by ingestion of bacteria that produce  Shiga toxins , with Shiga-toxin producing E. coli (STEC) being the most common type. [ 34 ]   E. coli  can produce shigatoxin-1, shigatoxin-2, or both; with shigatoxin-2 producing organisms being more virulent and being much more likely to cause HUS. [ 34 ]  Once ingested, the bacteria move to the intestines where they produce the Shiga toxins. The bacteria and toxins damage the mucosal lining of the intestines, and thus are able to gain entry into the circulation. [ 34 ]  Shiga toxin enters the mesenteric microvasculature lining the intestines where it releases inflammatory cytokines including  IL-6 ,  IL-8 ,  TNF\u03b1 , and  IL-1\u03b2 . [ 34 ]  These inflammatory mediators lead to inflammation and vascular injury with microthrombi that are seen with HUS. It also further damages the intestinal barrier leading to diarrhea (usually bloody) and further entry of Shiga toxin from the intestines to the bloodstream as the intestinal barrier is compromised. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2185", "text": "Once Shiga toxin enters the circulation it can travel throughout the body and cause the wide array of end organ damage and the multitude of symptoms seen with HUS. Shiga toxin gains entry to cells by binding to  globotriaosylceramide  (Gb3) which is a  globoside  found on cell membranes, it is found throughout the body including the surface of the glomerular endothelium of the kidney. [ 35 ]  Shiga toxin gains entry to the cell via Gb3 and  endocytosis , it then is transported to the  Golgi apparatus  where  furin  cleaves the A subunit of the Shiga toxin. [ 34 ]  It is then transported to the  endoplasmic reticulum  where it is further cleaved, leaving the A1 subunit of Shiga toxin free. The A1 subunit of Shiga toxin inhibits the  28s subunit  of the ribosomal  rRNA , this leads to inhibited protein production by the ribosomes. [ 34 ]  With the cell's protein synthesis inhibited by Shiga toxin, the cell is destroyed. [ 34 ]  This leads to vascular injury (including in the kidneys where Gb3 is concentrated). The vascular injury facilitates the formation of vascular microthrombi which are characteristic of TTP. [ 34 ]  The TTP leads to platelet trapping (and thrombocytopenia), red blood cell destruction (and anemia), and end organ damage that is characteristically seen with HUS and TTP. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2186", "text": "HUS is one of the  thrombotic microangiopathies , a category of disorders that includes STEC-HUS, aHUS, and  thrombotic thrombocytopenic purpura  (TTP). The release of  cytokines  and  chemokines  (IL-6, IL-8, TNF-\u03b1, IL-1\u03b2) that are commonly released by Shiga toxin are implicated in platelet activation and TTP. [ 36 ]  The presence of schistocytes is a key finding that helps to diagnose HUS."}
{"_id": "WikiPedia_Hematology$$$corpus_2187", "text": "Shiga-toxin directly activates the alternative complement pathway and also interferes with complement regulation by binding to complement factor H, an inhibitor of the complement cascade.  Shiga-toxin causes complement-mediated platelet, leukocyte, and endothelial cell activation, resulting in systemic hemolysis, inflammation and thrombosis. [ 37 ] [ 38 ] [ 39 ]  Severe clinical complications of TMA have been reported in patients from 2 weeks to more than 44 days after presentation with STEC-HUS, with improvements in clinical condition extending beyond this time frame, suggesting that complement activation persists beyond the acute clinical presentation and for at least 4 months. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2188", "text": "The consumption of platelets as they adhere to the thrombi lodged in the small vessels typically leads to mild or moderate thrombocytopenia with a platelet count of less than 60,000 per microliter. [ 41 ]  As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the  microvasculature  leads to reduced blood flow to vital organs, and  ischemia  may develop. [ 11 ]  The  kidneys  and the  central nervous system  (brain and spinal cord) are the parts of the body most critically dependent on high blood flow, and are thus the most likely organs to be affected. However, in comparison to TTP, the kidneys tend to be more severely affected in HUS, and the central nervous system is less commonly affected. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2189", "text": "In contrast with typical  disseminated intravascular coagulation  seen with other causes of  sepsis  and occasionally with advanced cancer,  coagulation factors  are not consumed in HUS (or TTP) and the  coagulation screen ,  fibrinogen  level, and assays for  fibrin degradation products  such as \"D-Dimers\", are generally normal despite the low platelet count (thrombocytopenia). [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2190", "text": "HUS occurs after 3\u20137% of all sporadic  E. coli  O157:H7 infections and up to approximately 20% or more of epidemic infections. [ 43 ]  Children and adolescents are commonly affected. [ 44 ]  One reason could be that children have more Gb3 receptors than adults which may be why children are more susceptible to HUS. Cattle, swine, deer, and other mammals do not have GB3 receptors, but can be asymptomatic carriers of Shiga toxin-producing bacteria. Some humans can also be asymptomatic carriers. Once the bacteria colonizes, diarrhea followed by bloody  diarrhea , hemorrhagic colitis, typically follows. Other serotypes of STEC also cause disease, inlduding HUS, as occurred with  E. coli  O104:H4, which triggered a 2011 epidemic of STEC-HUS in  Germany . [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2191", "text": "Grossly, the kidneys may show patchy or diffuse  renal cortical necrosis .  Histologically , the  glomeruli  show thickened and sometimes split capillary walls due largely to endothelial swelling. Large deposits of fibrin-related materials in the capillary lumens, subendothelially, and in the  mesangium  are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal  hyperplasia  and are often occluded by thrombi. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2192", "text": "STEC-HUS most often affects infants and young children, but also occurs in adults. The most common form of transmission is ingestion of undercooked meat, unpasteurized fruits and juices, contaminated produce, contact with unchlorinated water, and person-to-person transmission in daycare or long-term care facilities. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2193", "text": "Unlike typical HUS, aHUS does not follow STEC infection and is thought to result from one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of complement. [ 5 ]  This leads to  platelet  activation,  endothelial cell  damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count,  hemolysis , damage to multiple organs, and ultimately, death. [ 7 ] [ 18 ] [ 28 ]  Early signs of systemic complement-mediated TMA include  thrombocytopenia  (platelet count below 150,000 or a decrease from baseline of at least 25%) [ 16 ]  and evidence of  microangiopathic  hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased  hemoglobin , and/or the presence of schistocytes. [ 7 ] [ 29 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2194", "text": "The similarities between HUS, aHUS, and TTP make differential diagnosis essential. [ 7 ] [ 29 ]  All three of these systemic TMA-causing diseases are characterized by thrombocytopenia [ 16 ]  and microangiopathic hemolysis, [ 5 ] [ 16 ]  plus one or more of the following: neurological symptoms (e.g., confusion, [ 5 ] [ 24 ]  cerebral convulsions, [ 24 ]  seizures [ 21 ] ); renal impairment [ 16 ]  (e.g., elevated creatinine, [ 17 ]  decreased estimated glomerular filtration rate [eGFR], [ 17 ]  abnormal urinalysis [ 46 ] ); and gastrointestinal (GI) symptoms (e.g., diarrhea, [ 19 ] [ 22 ]  nausea/vomiting, [ 21 ]  abdominal pain, [ 21 ]  gastroenteritis [ 16 ] [ 19 ] ).The presence of diarrhea does not exclude aHUS as the cause of TMA, as 28% of patients with aHUS present with diarrhea and/or gastroenteritis. [ 18 ] [ 19 ]  First diagnosis of aHUS is often made in the context of an initial, complement-triggering infection, and Shiga-toxin has also been implicated as a trigger that identifies patients with aHUS. [ 40 ]  Additionally, in one study, mutations of genes encoding several complement regulatory proteins were detected in 8 of 36 (22%) patients diagnosed with STEC-HUS. [ 47 ]  However, the absence of an identified complement regulatory gene mutation does not preclude aHUS as the cause of the TMA, as approximately 50% of patients with aHUS lack an identifiable mutation in complement regulatory genes. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2195", "text": "Diagnostic work-up supports the differential diagnosis of TMA-causing diseases. A positive Shiga-toxin/EHEC test confirms a cause for STEC-HUS, [ 25 ] [ 27 ]  and severe  ADAMTS13  deficiency (i.e., \u22645% of normal ADAMTS13 levels) confirms a diagnosis of TTP. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2196", "text": "The effect of antibiotics in shiga toxin producing  E. coli  is unclear. [ 1 ]  While some early studies raised concerns more recent studies show either no effect or a benefit. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2197", "text": "Treatment involves  supportive care  and may include  dialysis ,  steroids ,  blood transfusions , and  plasmapheresis . [ 1 ] [ 2 ]  Early  IV fluid  hydration is associated with better outcomes including shorter hospital stays and reducing the risk of dialysis. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2198", "text": "Empiric antibiotics are not indicated in those who are immunocompetent, and may worsen the HUS. [ 34 ]   Antidiarrheals  and narcotic medications to slow the gut are not recommended as they are associated with worsening symptoms, increased risk of HUS in those with STEC infection, and adverse neurologic reactions. [ 34 ]  Platelet transfusions should not be used as the may drive the process of microangiopathy leading to worsening TTP. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2199", "text": "While  eculizumab  is being used to treat atypical hemolytic uremic syndrome, no evidence as of 2018 supports its use in the main forms of HUS. [ 1 ]  Scientists are trying to understand how useful it would be to immunize humans or cattle. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2200", "text": "Acute renal failure occurs in 55\u201370% of people with STEC-HUS, although up to 70\u201385% recover renal function. [ 50 ]  With aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. STEC-HUS is associated with a 3% mortality rate among young children and a 20% mortality rate in middle age or older adults. [ 34 ]  15-20% of children infected with STEC develop HUS, with the highest risk being in children younger than 5 years old. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2201", "text": "Patients with aHUS generally have poor outcomes, with up to 50% progressing to  end-stage renal disease  (ESRD) or irreversible brain damage; as many as 25% die during the acute phase. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2202", "text": "HUS is now considered as a part of the broader group of Thrombotic microangiopathies (TMA).  Thrombotic thrombocytopenic purpura  (TTP), a TMA, was first described by the Hungarian born, American pathologist and physician  Eli Moschcowitz  (1879\u20131964). In 1924, [ 51 ]  Moschcowitz first described TTP as a distinct clinicopathologic condition that can mimic the clinical characteristics of Hemolytic\u2013uremic syndrome (HUS). That was in a 16-year-old girl who died 2 weeks after the abrupt onset and progression of petechial bleeding, pallor, fever, paralysis, hematuria and coma; and called \"Moschcowitz disease\". [ 52 ] [ 53 ]  Moreover, Moschcowitz was among the first to work in psychosomatic medicine, and he presented a paper in 1935 on the psychological origins of physical disease. HUS was first described by Conrad Gasser in 1955, and the systemic character of HUS was subsequently defined. [ 54 ]  Bernard Kaplan identified several distinct entities that can manifest as HUS and emphasized that HUS was a syndrome with a common pathologic outcome. Kaplan is a Canadian professor and director of Pediatric Nephrology. He has an international reputation for his studies, over the past 34 years, on the hemolytic uremic syndromes. [ 55 ]  The discovery that endothelial cell injury underlies this broad spectrum of TMA disorders has come into focus during the last two decades. In the 1980s, Mohamed Karmali (1945\u20132016) was the first to make the association between Stx, diarrheal E. coli infection and the idiopathic hemolytic uremic syndrome of infancy and childhood. Karmali's work showed that the hemolytic uremic syndrome the children in Canada was caused by this particular bacteria. Karmali also developed the system of classifying strains of E.coli and determining which cause disease in humans. He defined the presence of microvascular injury in diarrhea-associated HUS and the critical role of a verotoxin produced by specific strains of Escherichia coli. [ 56 ]  This verotoxin was subsequently found to be a member of a family of toxins first identified with Shigella and known as Shiga toxin (Stx). [ 57 ]  This relationship and the eventual link of TTP to abnormally high levels of ultra-large Von Willebrand factor (vWF) multimers caused by congenital or acquired reductions in ADAMTS13 activity was established at approximately the same time. In 1924, a Finnish physician  Erik Adolf von Willebrand  (1870\u20131949) was consulted about a young girl with a bleeding disorder. Von Willebrand described this disorder in 1926, distinguishing it from hemophilia. The disorder was named after him, becoming known as von Willebrand disease. The cause of the disease was later discovered to be a deficiency of a protein, now known as von Willebrand factor, that enables hemostasis. Paul Warwicker is an English nephrologist, whilst in Newcastle in the mid-1990s his research in molecular genetics with Professors Tim and Judith Goodship led to the genetic mapping of the familial form of atypical HUS and the descriptions of the first HUS-related mutations and polymorphisms in the factor H gene in both familial and sporadic HUS. He was awarded an MD in molecular genetics in 2000, and elected fellow of the Royal College of Physicians in the same year. [ 58 ]  Paul Warwicker confirmed the association of atypical HUS (aHUS) to defects in a region on chromosome 1 that contains the genes for several complement regulatory proteins. [ 59 ]  Later, mutations in complement factor H, complement factor I, membrane cofactor protein, factor B, C3, and thrombomodulin have now been found to cause many of the familial cases of aHUS. These discoveries have allowed a more comprehensive understanding of the pathogenesis, evaluation, and treatment of the entire spectrum of TMA disorders and provide a more rational and effective approach to the care of these children with complicated disease. Prior to the use of monoclonal antibodies patients with aHUS had an extremely poor prognosis. Eculizumab (Soliris\u00ae, Alexion Pharmaceuticals, Inc., Boston, MA, USA) is a humanized monoclonal complement inhibitor that is the first and only approved treatment for patients with aHUS by FDA in September 2011. Eculizumab binds with high affinity to C5, inhibiting C5 cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9, thus inhibiting complement-mediated TMA. Eculizumab was proven to be effective in patients with aHUS in which it resolved and prevented complement-mediated TMA, improving renal function and hematologic outcomes. [ 60 ]  Alexion head of R&D 'John Orloff, M.D. \"The results met the high bar of complete TMA response, defined by hematologic normalization and improved kidney function,\" said Alexion R&D head John Orloff, M.D., who reckons the drug can become the \"new standard of care for patients with aHUS.\" \"We are preparing regulatory submissions for Ultomiris in aHUS in the U.S., European Union and Japan as quickly as possible,\" he added. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2203", "text": "The country with the highest incidence of HUS is Argentina [ 62 ] [ 63 ] [ 64 ] [ 65 ]  and it performs a key role in the research of this condition."}
{"_id": "WikiPedia_Hematology$$$corpus_2204", "text": "In the United States, the overall incidence of HUS is estimated at 2.1 cases per 100,000 persons/year, with a peak incidence between six months and four years of age. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2205", "text": "HUS and the  E. coli  infections that cause it have been the source of much negative publicity for the FDA, meat industries, and fast-food restaurants since the 1990s, especially in the contaminations linked to Jack in the Box restaurants. In 2006, an epidemic of harmful  E. coli  emerged in the United States due to contaminated spinach. In June 2009,  Nestl\u00e9  Toll House cookie dough was linked to an outbreak of  E. coli  O157:H7 in the United States, which sickened 70 people in 30 states. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2206", "text": "In May 2011 an  epidemic  of bloody diarrhea caused by  E. coli  O104:H4-contaminated  fenugreek  seeds hit Germany. Tracing the epidemic revealed more than 3,800 cases, with HUS developing in more than 800 of the cases, including 36 fatal cases. Nearly 90% of the HUS cases were in adults. [ 67 ] [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2207", "text": "Hepatic veno-occlusive disease  ( VOD ) or  veno-occlusive disease with immunodeficiency  is a potentially life-threatening condition in which some of the small  veins  in the  liver  are obstructed. It is a  complication  of high-dose  chemotherapy  given before a  bone marrow transplant  or excessive exposure to hepatotoxic  pyrrolizidine alkaloids . It is classically marked by weight gain due to  fluid retention ,  increased liver size , and raised levels of  bilirubin  in the blood. [ 1 ]  The name  sinusoidal obstruction syndrome  ( SOS ) is preferred if hepatic veno-occlusive disease happens as a result of chemotherapy or bone marrow transplantation. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2208", "text": "Apart from chemotherapy, hepatic veno-occlusive disease may also occur after ingestion of certain plant  alkaloids  such as pyrrolizidine alkaloids (in some herbal teas), [ 1 ]  and has been described as part of a rare  hereditary disease  called  hepatic venoocclusive disease with immunodeficiency  (which results from mutations in the gene coding for a protein called  SP110 ). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2209", "text": "Features of hepatic veno-occlusive disease include weight gain, tender  enlargement of the liver ,  ascites , and  yellow discoloration of the skin ; it often is associated with  acute kidney failure . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2210", "text": "In the bone marrow transplant setting, hepatic veno-occlusive disease is felt to be due to injury to the hepatic venous endothelium from the conditioning regimen. Toxic agents causing veno-occlusive disease include plants as well as the medication  cyclophosphamide . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2211", "text": "Doppler  ultrasound  of the liver is typically utilized to confirm or suggest the diagnosis. Common findings on liver doppler ultrasound include increased phasicity of portal veins with eventual development of portal flow reversal. The liver is usually enlarged but maintained normal  echogenicity . A  liver biopsy  is required for a definitive diagnosis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2212", "text": "Treatment generally includes  supportive care  including pain management and possibly  diuretics . [ 5 ]  In those with severe disease due to a bone marrow transplant,  defibrotide  is a proposed treatment. [ 6 ]  It has been approved for use in severe cases in Europe and the United States. [ 7 ] [ 8 ]  A  placebo controlled trial , however, has not been done as of 2016. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2213", "text": "Mild disease has a risk of death of about 10% while moderate disease has a risk of death of 20%. [ 5 ]  When it occurs as a result of bone marrow transplant and multiorgan failure is present, the risk of death is greater than 80%. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2214", "text": "The first report on veno-occlusive disease, in 1920, was as a result of  senecio  poisoning in  South Africa . [ 9 ]  Subsequent reports were mostly in Jamaicans who had consumed herbal teas. [ 1 ]  With the advent of bone marrow transplantation, most cases since its introduction have been in those undergoing treatment for  leukemia . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2215", "text": "Hyperviscosity syndrome  is a group of symptoms triggered by an increase in the  viscosity  of the  blood . Symptoms of high  blood viscosity  include spontaneous bleeding from  mucous membranes , visual disturbances due to  retinopathy , and neurologic symptoms ranging from  headache  and  vertigo  to  seizures  and  coma ."}
{"_id": "WikiPedia_Hematology$$$corpus_2216", "text": "Hyperviscosity occurs from pathologic changes of either cellular or protein fractions of the blood such as is found in  polycythemias ,  multiple myeloma  (particularly IgA and IgG3),  leukemia ,  monoclonal gammopathies  such as  Waldenstr\u00f6m macroglobulinemia ,  sickle cell anemia , and  sepsis . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2217", "text": "Types of hyperviscosity syndromes vary by pathology; including  serum  hyperviscosity, which may cause neurologic or ocular disorders; polycythemic hyperviscosity, which results in reduced blood flow or capillary  perfusion  and increased organ congestion; and syndromes of hyperviscosity, caused by reduced  deformability  of  red blood cells , often evident in sickle cell anemia. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2218", "text": "High cell counts are seen in conditions such as  polycythemia  (raised red blood cells) or  leukemia  (more  white blood cells , especially in  acute leukemia blast crises )."}
{"_id": "WikiPedia_Hematology$$$corpus_2219", "text": "May occur with a white blood cell count greater than 100,000/mm 3  (100\u00d710 9 /L). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2220", "text": "Although elevated whole blood viscosity is a better measure of hyperviscosity and more common and clinically important, serum viscosity and plasma viscosity are more frequently measured. [ 3 ]  Normal plasma viscosity is between 1.4 and 1.8  centipoise  while symptoms from hyperviscosity typically occur greater than 4 centipoise (about 4 times more viscous than water) and require emergency treatment. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2221", "text": "Patients will also have evidence of their underlying disorder. Those with   myeloma  will typically display a  rouleaux  formation on a peripheral smear and a large  globulin  gap, indicative of a significant  paraprotein  load. Although it used to be the case that test results would take a few days to return, the development of a new generation of automated clinical viscometers means that results can now be obtained within minutes, allowing accurate diagnosis and more targeted therapy. If hyperviscosity is confirmed, treatment can commence early on in the diagnosis. [ 4 ]  Fundoscopic examination reveals dilation of retinal veins and flame shaped retinal hemorrhages. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2222", "text": "Plasmapheresis  may be used to decrease viscosity in the case of myeloma, whereas  leukapheresis  or  phlebotomy  may be employed in a leukemic or polycythemic crisis, respectively.  Blood transfusions  should be used with caution as they can increase serum viscosity. Hydration is a temporizing measure to employ while preparing pheresis. Even after treatment, the condition will recur unless the underlying disorder is treated. [ citation needed ]  Serum viscosity and electrophoresis are recommended before and after plasmapheresis in order to correlate viscosity and M-spike with patient symptoms. This correlation may be useful for anticipating the need for repeat plasmapheresis. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2223", "text": "Hypovolemia , also known as  volume depletion  or  volume contraction , is a state of abnormally low  extracellular fluid  in the body. [ 1 ]  This may be due to either a loss of both salt and water or a decrease in  blood volume . [ 2 ] [ 3 ]  Hypovolemia refers to the loss of extracellular fluid and should not be confused with  dehydration . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2224", "text": "Hypovolemia is caused by a variety of events, but these can be simplified into two categories: those that are associated with  kidney function  and those that are not. [ 5 ]  The signs and symptoms of hypovolemia worsen as the amount of fluid lost increases. [ 6 ]  Immediately or shortly after mild fluid loss (from  blood donation ,  diarrhea ,  vomiting , bleeding from trauma, etc.), one may experience  headache ,  fatigue ,  weakness ,  dizziness , or  thirst . Untreated hypovolemia or excessive and rapid losses of volume may lead to  hypovolemic shock . [ 7 ]  Signs and symptoms of hypovolemic shock include  increased heart rate ,  low blood pressure ,  pale or cold skin , and  altered mental status . When these signs are seen, immediate action should be taken to  restore the lost volume ."}
{"_id": "WikiPedia_Hematology$$$corpus_2225", "text": "Signs and symptoms of hypovolemia progress with increased loss of fluid volume. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2226", "text": "Early symptoms of hypovolemia include headache, fatigue, weakness, thirst, and dizziness. The more severe signs and symptoms are often associated with hypovolemic shock. These include  oliguria ,  cyanosis , abdominal and chest pain,  hypotension ,  tachycardia , cold hands and feet, and progressively altering mental status. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2227", "text": "The causes of hypovolemia can be characterized into two categories: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2228", "text": "The signs and symptoms of hypovolemia are primarily due to the consequences of decreased circulating volume and a subsequent reduction in the amount of blood reaching the tissues of the body. [ 9 ]  In order to properly perform their functions, tissues require the oxygen transported in the blood. [ 10 ]  A decrease in circulating volume can lead to a decrease in bloodflow to the brain, resulting in headache and dizziness. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2229", "text": "Baroreceptors  in the body (primarily those located in the  carotid sinuses  and  aortic arch ) sense the reduction of circulating fluid and send signals to the brain to increase sympathetic response ( see also:  baroreflex ). [ 11 ]  This sympathetic response is to release  epinephrine  and  norepinephrine , which results in peripheral  vasoconstriction  (reducing size of blood vessels) in order to conserve the circulating fluids for organs vital to survival (i.e. brain and heart). Peripheral vasoconstriction accounts for the cold extremities (hands and feet), increased heart rate, increased cardiac output (and associated chest pain). Eventually, there will be less  perfusion  to the kidneys, resulting in decreased urine output. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2230", "text": "Hypovolemia can be recognized by a  fast heart rate ,  low blood pressure , [ 12 ]  and the absence of  perfusion  as assessed by skin signs (skin turning pale) and/or  capillary refill  on  forehead ,  lips  and  nail beds .  The patient may feel dizzy, faint, nauseated, or very thirsty.  These signs are also characteristic of most types of  shock . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2231", "text": "In children, compensation can result in an artificially high blood pressure despite hypovolemia (a decrease in blood volume). Children typically are able to compensate (maintain blood pressure despite hypovolemia) for a longer period than adults, but deteriorate rapidly and severely once they are unable to compensate ( decompensate ). [ 14 ]  Consequently, any possibility of  internal bleeding  in children should be treated aggressively. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2232", "text": "Signs of external bleeding should be assessed, noting that individuals can bleed internally without external blood loss or otherwise apparent signs. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2233", "text": "There should be considered possible mechanisms of injury that may have caused internal bleeding, such as ruptured or bruised internal organs. If trained to do so and if the situation permits, there should be conducted a  secondary survey  and checked the chest and abdomen for pain, deformity, guarding, discoloration or swelling.  Bleeding into the abdominal cavity can cause the classical bruising patterns of  Grey Turner's sign  (bruising along the sides) or  Cullen's sign  (around the navel). [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2234", "text": "In a hospital, physicians respond to a case of hypovolemic shock by conducting these examinations: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2235", "text": "Untreated hypovolemia can lead to shock (see also:  hypovolemic shock ). Most sources state that there are 4 stages of hypovolemia and subsequent shock; [ 18 ]  however, a number of other systems exist with as many as 6 stages. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2236", "text": "The 4 stages are sometimes known as the \"Tennis\" staging of hypovolemic shock, as the stages of blood loss (under 15% of volume, 15\u201330% of volume, 30\u201340% of volume and above 40% of volume) mimic the scores in a game of  tennis : 15, 15\u201330, 30\u201340 and 40. [ 20 ]  It is basically the same as used in classifying  bleeding  by blood loss. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2237", "text": "The signs and symptoms of the major stages of hypovolemic shock include: [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2238", "text": "The most important step in treatment of hypovolemic shock is to identify and control the source of bleeding. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2239", "text": "Medical personnel should immediately supply emergency oxygen to increase efficiency of the patient's remaining blood supply. This intervention can be life-saving. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2240", "text": "Also, the respiratory pump is especially important during hypovolemia as spontaneous breathing may help reduce the effect of this loss of blood pressure on stroke volume by increasing venous return. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2241", "text": "The use of  intravenous fluids  (IVs) may help compensate for lost fluid volume, but IV fluids cannot carry oxygen the way blood does\u2014however, researchers are developing  blood substitutes  that can. Infusing  colloid  or  crystalloid  IV fluids also dilutes  clotting factors  in the blood, increasing the risk of bleeding. Current best practice allow  permissive hypotension  in patients with hypovolemic shock, [ 26 ]  both avoid overly diluting clotting factors and avoid artificially raising blood pressure to a point where it \"blows off\" clots that have formed. [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2242", "text": "Fluid replacement  is beneficial in hypovolemia of stage 2, and is necessary in stage 3 and 4. [ 21 ]  See also the discussion of  shock  and the importance of treating reversible shock while it can still be countered."}
{"_id": "WikiPedia_Hematology$$$corpus_2243", "text": "The following interventions are carried out: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2244", "text": "Vasopressors  (such as  dopamine  and  noradrenaline ) should generally be avoided, as they may result in further tissue  ischemia  and don't correct the primary problem. Fluids are the preferred choice of therapy. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2245", "text": "In cases where loss of blood volume is clearly attributable to bleeding (as opposed to, e.g., dehydration), most medical practitioners prefer the term  exsanguination  for its greater specificity and descriptiveness, with the effect that the latter term is now more common in the relevant context. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2246", "text": "The term  leukemoid reaction  describes an increased\n white blood cell  count (> 50,000 cells/\u03bcL), which is a physiological response to stress or infection (as opposed to a primary blood  malignancy , such as  leukemia ). It often describes the presence of immature cells such as myeloblasts or red blood cells with nuclei in the peripheral blood."}
{"_id": "WikiPedia_Hematology$$$corpus_2247", "text": "It may be  lymphoid  or  myeloid . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2248", "text": "As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2249", "text": "Conventionally, a leukocytosis exceeding 50,000 WBC/mm 3  with a significant increase in early  neutrophil  precursors is referred to as a leukemoid reaction. [ 2 ]  The peripheral blood smear may show  myelocytes ,  metamyelocytes ,  promyelocytes , and rarely  myeloblasts ; however, there is a mixture of early mature neutrophil precursors, in contrast to the immature forms typically seen in  acute leukemia .  Serum leukocyte  alkaline phosphatase  is normal or elevated in leukemoid reaction, but is depressed in  chronic myelogenous leukemia . The  bone marrow  in a leukemoid reaction, if  examined , may be hypercellular but is otherwise typically unremarkable. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2250", "text": "Leukemoid reactions are generally  benign  and are not dangerous in and of themselves, although they are often a response to a significant disease state (see  Causes  above). However, leukemoid reactions can resemble more serious conditions such as  chronic myelogenous leukemia  (CML), which can present with identical findings on the peripheral blood smear. Historically, various clues including the  leukocyte alkaline phosphatase  score and the presence of  basophilia  were used to distinguish CML from a leukemoid reaction. However, at present the test of choice in adults to distinguish CML is an assay for the presence of the  Philadelphia chromosome , either via  cytogenetics  and  FISH , or via  PCR  for the BCR/ABL fusion gene. The LAP (leukocyte alkaline phosphatase) score is high in reactive states but is low in CML.  In cases where the diagnosis is uncertain, a qualified  hematologist  or  oncologist  should be consulted. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2251", "text": "Treatment of underlying condition. If drug induced, discontinue drug. If the reaction is found to be from anything besides drug use, certain anti neoplastic drugs may be indicated. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2252", "text": "aggressive:   S\u00e9zary disease"}
{"_id": "WikiPedia_Hematology$$$corpus_2253", "text": "Leukocytosis  is a condition in which the white cell ( leukocyte ) count is above the normal range in the  blood . [ 1 ] [ 2 ]  It is frequently a sign of an  inflammatory response , [ 3 ]  most commonly the result of  infection , but may also occur following certain parasitic infections or  bone tumors  as well as  leukemia . It may also occur after strenuous exercise, convulsions such as epilepsy, emotional stress, pregnancy and labor, anesthesia, as a side effect of medication (e.g.,  lithium ), and epinephrine administration. [ 1 ]  There are five principal types of leukocytosis: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2254", "text": "This increase in leukocyte (primarily neutrophils) is usually accompanied by a  \"left upper shift\"  in the ratio of immature to mature neutrophils and macrophages. The proportion of immature leukocytes increases due to proliferation and inhibition of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF.\nAlthough it may indicate illness, leukocytosis is considered a laboratory finding instead of a separate  disease .  This classification is similar to that of  fever , which is also a test result instead of a disease. [ citation needed ] \n \"Right shift\"  in the ratio of immature to mature  neutrophils  is considered with reduced count or lack of \"young neutrophils\" (metamyelocytes, and  band neutrophils ) in  blood smear , associated with the presence of \"giant neutrophils\". This fact shows suppression of bone marrow activity, as a hematological sign specific for  pernicious anemia  and  radiation sickness . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2255", "text": "A leukocyte count above 50 \u00d7 10 9 / L  is termed a  leukemoid reaction , which is the reaction of a healthy bone marrow to extreme stress, trauma, or infection. It is different from  leukemia  and from  leukoerythroblastosis , in which either immature white blood cells (acute leukemia) or mature, yet non-functional, white blood cells (chronic leukemia) are present in peripheral blood.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2256", "text": "Leukocytosis can be subcategorized by the type of white blood cell that is increased in number. Leukocytosis in which  neutrophils  are elevated is  neutrophilia ; leukocytosis in which  lymphocyte  count is elevated is  lymphocytosis ; leukocytosis in which  monocyte  count is elevated is  monocytosis ; and leukocytosis in which  eosinophil  count is elevated is  eosinophilia . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2257", "text": "An extreme form of leukocytosis, in which the WBC count exceeds 100,000/\u03bcL, is  leukostasis . In this form there are so many WBCs that clumps of them block  blood flow . This leads to  ischemic  problems including  transient ischemic attack  and  stroke . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2258", "text": "Leukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications or chemicals including steroids. For lung diseases such as pneumonia and tuberculosis, WBC count is very important for the diagnosis of the disease, as leukocytosis is usually present. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2259", "text": "The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from  bone marrow  storage pools, decreased margination of leukocytes onto vessel walls, decreased  extravasation  of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2260", "text": "Certain medications, including  corticosteroids ,  lithium  and  beta agonists , may cause leukocytosis. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2261", "text": "Leukocytosis is an expected finding in healthy women during the post-partum period and is not a cause for alarm unless accompanied by clinical manifestations of infection. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2262", "text": "Below are  blood reference ranges  for various types of leukocytes/WBCs. [ 12 ]  The 97.5 percentile (right limits in intervals in image, showing 95%  prediction intervals ) is a common limit for defining leukocytosis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2263", "text": "While treatment is usually not necessary in the majority of cases, hyperleukocytosis (WBC count > 50 or 100 \u00d7 10 9 /L), which can be seen in some leukemic patients, is treated to prevent  leukostasis . [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2264", "text": "Leukopenia  (from  Greek     \u03bb\u03b5\u03c5\u03ba\u03cc\u03c2  (leukos) \u00a0'white' and    \u03c0\u03b5\u03bd\u03af\u03b1  (penia) \u00a0'deficiency') is a decrease in the number of  leukocytes  ( WBC ). Found in the blood, they are the  white blood cells , and are the body's primary defense against an  infection . Thus the condition of leukopenia places individuals at increased risk of infection."}
{"_id": "WikiPedia_Hematology$$$corpus_2265", "text": "Symptoms may include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2266", "text": "Neutropenia , a subtype of leukopenia, refers to a decrease in the number of circulating  neutrophil granulocytes , the most abundant white blood cells. The terms  leukopenia  and  neutropenia  may occasionally be used interchangeably, as the neutrophil count is the most important indicator of infection risk.  Agranulocytosis  is an acute form of neutropenia. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2267", "text": "Low white cell count may be due to acute viral infections, such as a cold or  influenza . It has been associated with  chemotherapy ,  radiation therapy ,  myelofibrosis ,  aplastic anemia  (failure of white cell, red cell and platelet production), stem cell transplant, bone marrow transplant,  HIV ,  AIDS , and steroid use. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2268", "text": "Other causes of low white blood cell count include  systemic lupus erythematosus ,  Hodgkin's lymphoma , some types of  cancer ,  typhoid ,  malaria ,  tuberculosis ,  dengue ,  rickettsial infections , enlargement of the  spleen ,  folate  deficiencies,  psittacosis ,  sepsis ,  Sj\u00f6gren syndrome  and  Lyme disease . It has also been shown to be caused by deficiency in certain  minerals , such as  copper  and  zinc . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2269", "text": "Pseudoleukopenia can develop upon the onset of infection. The leukocytes (primarily neutrophils, responding to injury first) start migrating toward the site of infection, where they can be scanned. Their migration causes bone marrow to produce more WBCs to combat infection as well as to restore the leukocytes in circulation, but as the blood sample is taken upon the onset of infection, it contains low amount of WBCs, which is why it is termed \"pseudoleukopenia\". [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2270", "text": "Certain medications can alter the number and function of white blood cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2271", "text": "Medications that can cause leukopenia include  clozapine , an  antipsychotic  medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils).  Minocycline , a commonly prescribed antibiotic, is another drug known to cause leukopenia. There are also reports of leukopenia caused by divalproex sodium or  valproic acid  (Depakote), a drug used for epilepsy (seizures), mania (with bipolar disorder) and migraine. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2272", "text": "The  anticonvulsant  drug,  lamotrigine , has been associated with a decrease in white blood cell count. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2273", "text": "The FDA monograph for  metronidazole  states that this medication can also cause leukopenia, and the prescriber information suggests a complete blood count, including differential cell count, before and after, in particular, high-dose therapy. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2274", "text": "Immunosuppressive  drugs, such as  sirolimus ,  mycophenolate mofetil ,  tacrolimus ,  ciclosporin ,  leflunomide  and  TNF inhibitors , have leukopenia as a known complication. [ 4 ]   Interferons  used to treat  multiple sclerosis , such as  interferon beta-1a  and  interferon beta-1b , can also cause leukopenia. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2275", "text": "Chemotherapy  targets cells that grow rapidly, such as tumors, but can also affect white blood cells, because they are characterized by bone marrow as rapid growing. [ 5 ]  A common side effect of cancer treatment is  neutropenia , the lowering of  neutrophils  (a specific type of white blood cell). [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2276", "text": "Decreased white blood cell count may be present in cases of  arsenic toxicity . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2277", "text": "Leukopenia can be identified with a  complete blood count . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2278", "text": "Below are  blood reference ranges  for various types leucocytes/WBCs. [ 9 ]  The 2.5 percentile (right limits in intervals in image, showing 95%  prediction intervals ) is a common limit for defining  leukocytosis ."}
{"_id": "WikiPedia_Hematology$$$corpus_2279", "text": "peripheral:   Purine nucleoside phosphorylase deficiency"}
{"_id": "WikiPedia_Hematology$$$corpus_2280", "text": "Leukostasis  (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen in patients with  acute myeloid leukemia . It is characterized by an extremely elevated  blast cell  count and symptoms of decreased  tissue perfusion . The pathophysiology of leukostasis is not well understood, but inadequate delivery of oxygen to the body's cells is the result. Leukostasis is diagnosed when white cell plugs are seen in the  microvasculature . The most common symptoms are  dyspnea  and  hypoxia , usually accompanied by visual changes, headaches, dizziness, confusion, somnolence, and coma. Prompt treatment is required since, if left untreated, it has a very high mortality rate. Treatments aim to rapidly reduce white blood cell counts while also treating the underlying disorder."}
{"_id": "WikiPedia_Hematology$$$corpus_2281", "text": "Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously high  blast cell  count along with symptoms of decreased tissue  perfusion . Leukostasis is associated with people who have bone and blood disorders and is very common among people with  acute myeloid leukemia  or  chronic myeloid leukemia . Leukostasis is a pathologic diagnosis that inhibits efficient flow to the  microvasculature  of the body. Continued and untreated leukostasis presents  respiratory  and  neurological  distress simultaneously and is a medical emergency, with untreated patient mortality rates reaching a minimum of 20 and a maximum of 40 percent. A leukemia blood cell count greater than 50 x 10^9/ L (50,000 / microL) or 100 x 10^9 L / (100,000/ microL) signifies hyperleukocytosis. Symptoms of leukostasis start when blood levels of leukocytes reach over 100 x 10^9 / L (100,000 / microL). As stated before, these counts are critical and associated with  Leukemias . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2282", "text": "When a patient has symptomatic leukocytosis, specifically caused by a form of leukemia, it is common to find leukostasis in all their organs. The majority of the time a patient dies from neurological complications (40% of patients die due to neurological conditions) as opposed to particular organ damage. The lungs alone account for approximately 30 percent of leukostasis fatalities. All other organs combined attribute to 30 percent of deaths, with the major outliers being neurological and  respiratory failure  equating to 70 percent of all death rates. Damage to the  microvasculature  of the body is the primary cause of death by leukostasis. Microvasculature damage to the lungs is only second to neurological damage because the body is already experiencing hypoxic conditions, which lead to lung tissue damage as the second leading cause of fatalities. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2283", "text": "Pulmonary signs  -  Dyspnea  and  hypoxia  with or without diffuse interstitial or alveolar infiltrates on imaging studies."}
{"_id": "WikiPedia_Hematology$$$corpus_2284", "text": "Neurological signs  - visual changes, headaches, dizziness,  tinnitus , gait instability, confusion,  somnolence , coma."}
{"_id": "WikiPedia_Hematology$$$corpus_2285", "text": "The most common symptom is the patient is usually  febrile , which is often linked with inflammation and possible infection."}
{"_id": "WikiPedia_Hematology$$$corpus_2286", "text": "Less common signs include:  myocardial ischemia  / right  ventricular  overload, increased  acute kidney injury ,  priapism , acute limb  ischemia  and bowel  infarction ."}
{"_id": "WikiPedia_Hematology$$$corpus_2287", "text": "Hyperleukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including  viral ,  bacterial ,  fungal , or  parasitic infection , cancer, hemorrhage, and exposure to certain medications."}
{"_id": "WikiPedia_Hematology$$$corpus_2288", "text": "For lung diseases such as  pneumonia  and  tuberculosis , white blood cell count is crucial for the diagnosis of the disease, as leukocytosis is usually present."}
{"_id": "WikiPedia_Hematology$$$corpus_2289", "text": "Specific medications, including  corticosteroids ,  lithium  and  beta-agonists  can cause hyperleukocytosis. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2290", "text": "The mechanism in which hyperleukocytosis or leukostasis manifests and disrupts  homeostasis  is greatly associated with leukemia's but multiple other factors may cause leukocytosis. Major types of leukocytosis and their mechanisms depend on the types of leukemia that cause them.  White blood cell  levels either rise in distinct white blood levels or in unison with others, a patient may have  neutrophilia ,  lymphocytosis ,  monocytosis ,  eosinophilia ,  basophilia  or a rise in immature  blast cells . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2291", "text": "Acute myeloid leukemia  - 10 to 20 percent of patients newly diagnosed with this type leukemia have hyperleukocytosis."}
{"_id": "WikiPedia_Hematology$$$corpus_2292", "text": "Acute lymphoblastic leukemia  - 20 to 30 percent of patients newly diagnosed with this type of leukemia have hyperleukocytosis."}
{"_id": "WikiPedia_Hematology$$$corpus_2293", "text": "Chronic lymphocytic leukemia  - Exact percentage of people diagnosed with chronic  lymphocytic  leukemia is unknown but a significant number also have hyperleukocytosis."}
{"_id": "WikiPedia_Hematology$$$corpus_2294", "text": "Chronic myeloid leukemia  - The majority of patients with chronic myeloid leukemia usually have hyperleukocytosis."}
{"_id": "WikiPedia_Hematology$$$corpus_2295", "text": "The primary pathophysiology of leukostasis is not completely understood, but there are two possible theories."}
{"_id": "WikiPedia_Hematology$$$corpus_2296", "text": "Increased blood viscosity due to large leukemic blast populations which are less deformable than mature leukocytes may lead to leukostasis. The accumulation of less malleable blast products in the bloodstream accumulate within the microcirculation causing an accumulation of blockages leading to leukostasis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2297", "text": "Hypoxic events in body regions may increase the high metabolic activity of dividing  blast cells  and lead to an increase in  cytokine  production. The increasing levels of  cytokines  within tissues may result in endothelial damage and subsequent  hemorrhage . Therefore, hypoxia, in addition to various cytokine accumulations, act in unison to further damage tissue and attract leukemic blast cells to form a triad of damage. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2298", "text": "The combination of these theories, in addition to other events, may lead to hyperleukocytosis."}
{"_id": "WikiPedia_Hematology$$$corpus_2299", "text": "White blood counts exceeding 100 x 10^9 / L (100,000 / microL) present symptoms of tissue hypoxia and may signal possible neurological and respiratory distress. Ongoing research has shown that patients have experienced hypoxia at leukocyte levels below 100 x 10^9 / L (100,000 / microL), therefore patients with leukemia need regular neurological and respiratory monitoring when leukocyte counts are approaching 100 x 10^9 / L (100,000 / microL) to decrease chances of tissue hypoxia."}
{"_id": "WikiPedia_Hematology$$$corpus_2300", "text": "Acquired  biopsies  are examined for damage to microvasculature, which serves as evidence of hypoxia through the identification of leukocyte blockage within the tissue. Due to the  biopsy 's invasive nature and the risks associated with the procedure, it is only used when deemed necessary. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2301", "text": "Measurements for arterial pO2 have shown to be falsely decreased in patients with hyperleukocytosis because of white blood cells ability to utilize oxygen.  Pulse oximetry  should be used to more accurately assess  pO2  levels of a patient suspected to have leukocytosis. Automated blood cell counters may be inaccurate due to fragments of  blast cells  being labeled on  blood smears  as  platelets . The most accurate form of confirming platelet counts is by using a manual platelet count and a review of a peripheral smear. Serum potassium levels may also be artificially elevated by a release from leukemic blasts during  in vitro  clotting process, therefore serum potassium levels should be monitored by  heparinized  (the addition of  heparin  prevents  coagulation ) plasma samples in order to obtain accurate results of potassium levels.  Disseminated intravascular coagulation  may occur in a significant number of patients with presentation of various degrees of  thrombin  generation, followed by decreased fibrinogen and increased fibrinolysis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2302", "text": "Spontaneous  tumor lysis syndrome  is present in approximately 10 percent of patients with leukostasis. Lab tests are used to measure the potential of elevated serum concentrations such as  uric acid ,  potassium ,  phosphate , and  hypocalcemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_2303", "text": "Disseminated intravascular coagulation  and spontaneous  tumor lysis syndrome  can develop before and after chemotherapy treatment. Patients undergoing this type of therapy need to be closely monitored before and after, in addition to undergoing prophylactic measures to prevent possible complications."}
{"_id": "WikiPedia_Hematology$$$corpus_2304", "text": "Since leukostasis and hyperleukostasis are associated with leukemia, preventive treatments are taken upon diagnosis. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2305", "text": "Patients with hyperleukocytosis associated with leukemia are always considered candidates for tumor lysis syndrome prophylaxis in addition to aggressive intravenous hydration with allopurinol or  rasburicase  to decrease serum uric acid levels."}
{"_id": "WikiPedia_Hematology$$$corpus_2306", "text": "Treatment includes utilization of  prophylactic  methods if the patient has been diagnosed with hyperleukocytosis. This is usually in combination with other treatments, which are dependent on the type of leukemia. Specific treatments include lysis syndrome treatment in addition to aggressive  intravenous  hydration with  allopurinol  or  rasburicase  to decrease serum uric acid levels. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2307", "text": "Hematopoietic  cell transplants are critical to correct leukostasis and leukemia.  Cytoreduction  is also a critical course of treatment in order to rapidly decrease white blood cell counts. Twenty to forty percent of patients diagnosed with hyperleukocytosis die within the first week of symptom presentation. Patients with the best outcome have none or limited symptoms of respiratory or neurological distress. An accumulation of these symptoms lead to decreased levels of statistical survival compared to patients diagnosed with asymptomatic hyperleukocytosis alone. Cytoreduction methods include chemotherapy, utilizing the drug  hydroxyurea  (Hydroxyurea is usually used in asymptomatic hyperleukocytosis), and the less common  leukapheresis  procedure. This procedure is often utilized for asymptomatic hyperleukocytosis patients who have induction chemotherapy postponed for patient-specific factors. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2308", "text": "Variants of  chemotherapy , including  induction chemotherapy , are used to treat both elevated white blood cells counts while simultaneously targeting  leukemia  cells in the  bone marrow . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2309", "text": "Prognosis of patients with hyperleukocytosis is dependent on the cause and type of leukemia the patient has. Patients diagnosed with asymptomatic hyperleukocytosis have significantly better survival rates than symptomatic hyperleukocytosis (leukostasis). Preventative measures and contentious monitoring of patients diagnosed with leukemia is critical in receiving treatment as early as possible to prevent and treat hyperleukocytosis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2310", "text": "Recent and continuing research has shown that patients have had hypoxia at leukocyte levels below 100 x 10^9 / L (100,000 / microL), therefore patients with leukemia need regular neurological and respiratory monitoring when leukocyte counts are approaching 100 x 10^9 / L (100,000 / microL) to decrease chances of hypoxia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2311", "text": "Leukemia and population types are also believed to be associated with possible symptoms and may require a change in treatment. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2312", "text": "Results of Tumor lysis/ consumption of coagulopathy in patients with acute leukemia is much more often than in patients with chronic malignant hematological diseases. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2313", "text": "Leukostasis , also known as  symptomatic hyperleukocytosis , is a life-threatening complication of various  leukemias  characterized by an  excess  of  white blood cells  in the bloodstream. Hyperleukocytosis is arbitrarily defined as greater than 100,000 white blood cells per microliter of blood. The condition is characterized by abnormal aggregation and clumping of white blood cells in the blood vessels resulting in impaired blood flow and delivery of oxygen to the body's cells. The  brain  and  lungs  are the two most commonly affected organs. [ 6 ]  Leukostasis most commonly occurs with  acute myeloid leukemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_2314", "text": "Hyperleukocytosis/leukostasis occurs more commonly, and at lower white blood cell (WBC) counts, in acute myeloid leukemia than in  acute lymphocytic leukemia , because the cells of acute myeloid leukemia have a larger corpuscular (cell) volume than those of acute lymphocytic leukemia, and the cells of acute myeloid leukemia have more surface adhesion molecules than those of acute lymphocytic leukemia (i.e., the cancer cells in AML are \"stickier\")."}
{"_id": "WikiPedia_Hematology$$$corpus_2315", "text": "Individuals affected by leukostasis may present with respiratory symptoms such as  cough ,  difficulty breathing ,  breathing too quickly , or  inadequate levels of oxygen in the blood  requiring support with a  mechanical ventilator . [ 6 ] [ 7 ]  Neurologic symptoms, such as  temporary confusion , blurry vision, dizziness,  ringing in the ears ,  ataxia , stupor,  sleepiness ,  headaches , and  coma , may be seen. Neurologic signs such as  seizures , focal neurologic deficits (e.g., weakness in one arm or leg),  swelling of the retina , retinal bleeding, and dilated blood vessels on  inspection of the back of the eye . [ 7 ]  Rare complications of leukostasis include  renal vein thrombosis ,  priapism , and acute ischemia of the leg. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2316", "text": "The pathophysiology of leukostasis is not well understood.  Inadequate delivery of oxygen to the body's cells  is thought to be the main abnormal result of leukostasis. [ 7 ]  Proposed mechanisms for this include increased blood viscosity due to the high number of white blood cells circulating in the blood and a higher proportion of cells with a greater  mean corpuscular volume  (larger cells) with decreased deformability occupying the blood vessels. [ 6 ]  However, certain studies have demonstrated that the blood viscosity of affected individuals is not increased due to a compensatory decrease in the number of  red blood cells  sometimes resulting in  anemia  and a decreased  hematocrit . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2317", "text": "The clinical signs and symptoms of leukostasis are non-specific but should be suspected in susceptible individuals with leukemia, a high white blood cell count (e.g., over 100,000), and new-onset neurologic or respiratory signs or symptoms.  Rales  may be heard when  listening to the lungs with a stethoscope . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2318", "text": "A  chest x-ray  can be normal in those with leukostasis or may demonstrate an alveolar pattern of infiltrates. [ 7 ]  Brain imaging with  computed tomography  (CT) or  magnetic resonance imaging  (MRI) is useful and can demonstrate areas of bleeding,  ischemic stroke , or masses. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2319", "text": "Laboratory abnormalities seen in those with leukostasis include a markedly elevated white blood cell count (hyperleukocytosis) and  electrolyte  abnormalities seen with  tumor lysis syndrome  such as  high concentrations of potassium ,  phosphorus , and  uric acid  in the blood and a low level of  calcium  in the blood (due to being bound by high amounts of circulating phosphorus). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2320", "text": "It is an  acute  syndrome requiring aggressive  cytoreductive   modalities  including  chemotherapy  and/or  leukapheresis  to both reduce the number of circulating leukocytes and to break apart any aggregates that have already formed. Such rapid and massive  lysis  of tissue poses a risk of  complications  ( tumor lysis syndrome ), but it is necessary to avoid a  stroke ."}
{"_id": "WikiPedia_Hematology$$$corpus_2321", "text": "Leukostasis is different from leukemic infiltration, which is a  neoplastic  process where leukemic cells invade organs. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2322", "text": "Leukostasis is a high-risk condition and can lead to significant complications resulting from occlusion of blood vessels, including  transient ischemic attacks  and  strokes ."}
{"_id": "WikiPedia_Hematology$$$corpus_2323", "text": "The incidence and prevalence of hyperleukocytosis and leukostasis vary depending on the form of leukemia. [ 7 ]  Hyperleukocytosis is common in  chronic myelogenous leukemia  and  chronic lymphocytic leukemia , but leukostasis rarely occurs. [ 7 ]  Similarly, the incidence of hyperleukocytosis in people with  acute lymphoblastic leukemia  is between 10 and 30% but rarely does this progress to symptomatic leukostasis. [ 7 ]  The incidence of hyperleukocytosis in  acute myeloid leukemia  (AML) ranges between 5-20% but leukostasis is less common than hyperleukocytosis in this population; leukostasis tends to occur more often in people with AML with monocytic features. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2324", "text": "Light chain deposition disease  ( LCDD ) is a rare blood cell disease which is characterized by deposition of fragments of infection-fighting  immunoglobulins ,  called  light chains  (LCs), in the body. LCs are normally  cleared  by the kidneys, but in LCDD, these light chain deposits damage organs and cause disease. The kidneys are almost always affected and this often leads to kidney failure.  About half of people with light chain deposition disease also have a  plasma cell dyscrasia , a spectrum of diseases that includes  multiple myeloma ,  Waldenstr\u00f6m's macroglobulinemia , and the  monoclonal gammopathy of undetermined significance   premalignant  stages of these two diseases. [ 1 ] [ 2 ]   Unlike in  AL amyloidosis , in which light chains are laid down in characteristic  amyloid  deposits, in LCDD, light chains are deposited in non-amyloid granules. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2325", "text": "Light chain  deposition disease can affect any organ. [ 3 ]  Renal involvement is always present and can be identified by microscopic  hematuria  and  proteinuria . Due to the gradual buildup of light chains from plasma filtration, renal function rapidly declines in the majority of patients with LCDD as either acute  tubulointerstitial nephritis  or rapidly progressing  glomerulonephritis . This condition can include  nephrotic syndrome ,  proteinuria , and/or  renal failure . [ 4 ]  Regardless of the degree of light chain excretion,  renal failure  happens with a comparable frequency. Furthermore,  hypertension  may be present at the time of diagnosis in patients with LCDD. [ 5 ]  Deposits may form in the skin,  lungs ,  gastrointestinal tract ,  thyroid glands ,  pancreas ,  bone marrow ,  spleen ,  lymph nodes , and  adrenal glands . [ 3 ]  Extrarenal deposition with symptoms is uncommon. It is unclear if localized LCDD is a real condition or if it is the first sign of a silent systemic LCDD. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2326", "text": "The  liver  is the most common extra-renal site in LCDD, although involvement is not always limited to this organ. There appears to be no relationship between the degree of light chain deposition within the liver and the severity of liver dysfunction. [ 7 ]  In addition to  portal hypertension  and  hepatic insufficiency , affected patients may die from  hepatic failure . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2327", "text": "Cardiac involvement may be linked to  paroxysmal atrial fibrillation , [ 9 ]  severe  congestive heart failure , and  restrictive cardiomyopathy . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2328", "text": "The lungs are rarely affected by light chain deposition disease, which typically damages the  parenchyma ; [ 11 ]  bronchial involvement seems to be extremely uncommon. [ 12 ]  However recent reports have indicated that the major airways are involved. There have been descriptions of nodular as well as diffuse pulmonary interstitial diseases; however, the literature has only reported seven occurrences of pulmonary nodular-type LCDD to date. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2329", "text": "The effects of systemic protein deposition on the nerves are comparable to those of  amyloidosis , which is clinically characterized by  polyneuropathy . [ 14 ]  Deposits may form in the  choroid plexus  and along  nerve fibers . [ 15 ]  Additionally, isolated LCDD within the brain has been reported. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2330", "text": "LCDD develops as a result of overproduction and thus deposition of abnormal  immunoglobulins . About 60% of cases develop in the context of  plasmacytoma ,  multiple myeloma , and other  lymphoproliferative disorders . However, in many cases, an underlying cause cannot be identified. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2331", "text": "The main  light chain  structure in LCDD presumably dictates how the disease manifests in the body. Though \u03baI-IV has been described, [ 17 ]  the sequenced kappa light chains in LCDD are more likely to belong to the V-region subtype, of which V\u03baIV appears to be overrepresented. [ 18 ]  The pathogenicity of these proteins has not been linked to any particular structural pattern or residue, but a number of recurring characteristics have been identified. [ 19 ]  Firstly,  somatic mutations , not  germline mutations , are the source of the  amino acid substitutions . Secondly, the region that determines complementarity is where substitutions happen most frequently. [ 17 ]  Third,  hydrophobic residues  are more likely to be introduced by the mutations reported in both the kappa and  light chains . [ 20 ]  This could disrupt protein-protein interactions and destabilize the protein, leading to protein deposition in tissues. [ 21 ]  The propensity for aggregation is exemplified in a  murine  model of LCDD where light chain deposition was observed in the kidney of transfected mice using vectors that contained kappa light chain sequence from an individual with LCDD with the V\u03baIV subtype. [ 22 ]  Lastly, because some patients with LCDD have isolates of kappa light chains with mutations that produce new  N-glycosylation  sites, posttranslational modification can be linked to the creation of pathologic light chains. [ 23 ]  It is possible that the new  hydrophobic residues  along with  N-glycosylation  sites will make it more likely for the light chains to accumulate in the affected tissues'  basement membranes . [ 24 ]  The  mesangial cell  is also thought to play a role in the pathogenesis of LCDD. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2332", "text": "A number of laboratory tests are required in order to assist in diagnosing LCDD. Blood and urine samples are collected for evaluation of kidney and liver function and determination of the presence of a monoclonal protein. Imaging studies such as  echocardiography  and an  ultrasound  of the abdomen will be performed. A  CT scan ,  magnetic resonance imaging (MRI)  or  positron emission tomography  (PET) may also be indicated. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2333", "text": "Patients suspected of having LCDD should be evaluated using the screening panel for plasma cell proliferative disorders. [ 27 ]  However, the sensitivity of laboratory testing strategies for detecting  monoclonal gammopathies  has increased with the development of quantitative serum assays to test for  immunoglobulin free light chain ; [ 28 ]  this increased diagnostic sensitivity is easily noticeable in the  monoclonal light chain  diseases. [ 29 ]  The most recent diagnostic screening guidelines state that serum  immunofixation  in addition to  immunoglobulin free light chain  is an adequate screening panel for plasma cell proliferative disorders apart from  AL amyloidosis  and LCDD due to the increased sensitivity for free light chain diseases. It is advised, nevertheless, that urine  immunofixation  be used in addition to LCDD and  AL amyloidosis  screening. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2334", "text": "The  immunohistologic  examination of tissue from an afflicted organ\u2014which is not congophilic in nature\u2014confirms the diagnosis of LCDD. The tissue's light chain restriction evaluation will determine whether the heavy or light chain is  monoclonal . An  abdominal ultrasound  and  echocardiography  should be part of the workup when an individual is diagnosed with LCDD in order to evaluate the  spleen ,  liver , and  lymph nodes . A  bone marrow aspirate  as well as biopsy are necessary to rule out  light amyloidosis  and/or  multiple myeloma . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2335", "text": "Similar to  cardiac amyloid ,  diastolic dysfunction  and a decrease in myocardial compliance may be discovered via  echocardiography  and  catheterization . [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2336", "text": "By using specific  light chain  stains in  glomeruli  as well as negative  Congo red stain , tubular  basement membranes , and punctate amorphous, ground-pepper-like appearance of deposits on  electron microscopy , LCDD can be differentiated from other causes of  nodular sclerosis  and mesangial expansion.  Diabetic nephropathy  exhibits no deposits; fibrillary  glomerulonephritis  is  Congo red  negative and has a proliferative appearance along with polyclonal  immunoglobulin G ; other  monoclonal immunoglobulin deposition disease  exhibit both light and  heavy chain  staining or just heavy chain staining. Additional reasons for a  membranoproliferative glomerulonephritis  pattern exhibit  electron microscopy  appearances and  immunofluorescence  specific to the disease. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2337", "text": "Decreasing production of the organ-damaging light chains is the treatment goal. Options include chemotherapy using  bortezomib ,  autologous stem cell transplantation ,  immunomodulatory drugs , and  kidney transplant . [ 32 ]  There is no standard treatment for LCDD. High-dose  melphalan  in conjunction with autologous stem cell transplantation has been used in some patients. A regimen of  bortezomib  and  dexamethasone  has also been examined. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2338", "text": "Different  light chain  deposition does not appear to have an impact on the clinical course of LCDD patients, as the clinical presentation is known to depend on the quantity and type of affected organs. [ 33 ]  The median survival time is roughly four years. Following a median follow-up of 27 months, the most comprehensive series to date found that 59% of cases resulted in death and 57% of cases reached  uremia . [ 4 ]  LCDD prognostic factors include age, extrarenal light chain deposition, and  plasma cell myeloma . [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2339", "text": "Being a relatively rare condition, LCDD is commonly misdiagnosed as a protein disease. Up to 50% of patients receive an LCDD diagnosis as a result of  lymphoproliferative disorders  such as  multiple myeloma . [ 35 ]  LCDD is diagnosed at a median age of 58 years. [ 4 ]  LCDD affects men 2.5 times more than women [ 8 ]  and is frequently linked with  monoclonal gammopathies of unknown significance  in 17% of patients. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2340", "text": "Macroamylasemia  is the presence of macroamylase in the blood. Macroamylase is a complex of the enzyme  amylase  bound to other proteins forming a larger  molecule . [ 1 ]  Macroamylase is typically composed of  immunoglobulin A  (IgA, 70%) and less often of  immunoglobulin G  (IgG, 30%). The association of amylase with some drugs has also been reported.\n [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2341", "text": "The macroamylase molecules are unable to pass through the  kidneys  and are therefore retained in the blood, leading to elevated levels of  amylase  in the  bloodstream . In contrast, amylase urine levels are normal. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2342", "text": "Macroamylasemia is usually a benign condition, and people usually do not experience any symptoms or health problems. In fact, it is often discovered incidentally during a routine blood test. However, in some rare cases, macroamylasemia can cause recurrent  abdominal pain  or other gastrointestinal symptoms."}
{"_id": "WikiPedia_Hematology$$$corpus_2343", "text": "Macroamylasemia is a relatively rare condition, and in most cases, the exact cause is unknown. It can occur in completely healthy individuals without symptoms, in association with autoimmune diseases (such as  systemic lupus erythematosus ) and other diseases (cancer or inflammatory diseases). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2344", "text": "However, there are some risk factors that can increase the likelihood of developing the condition: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2345", "text": "Diagnosis of macroamylasemia is typically made by measuring the  amylase  levels in the blood and urine and performing additional tests to confirm the presence of macroamylase. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2346", "text": "Treatment is usually not necessary unless the patient is experiencing symptoms or complications related to the condition. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2347", "text": "Macroglobulinemia  is the presence of increased levels of  macroglobulins  in the circulating  blood .\nIt is a  plasma cell dyscrasia , resembling  leukemia , with cells of lymphocytic, plasmacytic, or intermediate morphology, which secrete a monoclonal  immunoglobulin M  component. There is diffuse infiltration by the malignant cells of the bone marrow and also, in many cases, of the spleen, liver, or lymph nodes. The circulating macroglobulin can produce symptoms of hyperviscosity syndrome: weakness, fatigue, bleeding disorders, and visual disturbances. Peak incidence of macroglobulinemia is in the sixth and seventh decades of life. (Dorland, 28th ed)"}
{"_id": "WikiPedia_Hematology$$$corpus_2348", "text": "Methaemalbuminaemia  is a clinical condition that can be caused by severe  intravascular   haemolysis  or acute  haemorrhagic   pancreatitis . This can be due to  proteolytic  breakdown of  haemoglobin  to form both  haem  and methaem. Methaem combines with  blood plasma   albumin  to form  methemalbumin  which is found in trace amount in the blood.\nBleeding into the  abdominal cavity  is another known cause of methaemalbuminaemia.\nMethaemalbumin in blood is detected by carrying out a test known as  Schumm test  which is a  spectroscopic  identification on addition of  ammonium sulphide ."}
{"_id": "WikiPedia_Hematology$$$corpus_2349", "text": "Neutropenia  is an abnormally low concentration of  neutrophils  (a type of  white blood cell ) in the blood. [ 4 ]  Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against  infections  by destroying  bacteria , bacterial fragments and  immunoglobulin -bound  viruses  in the  blood . [ 5 ]  People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening ( neutropenic sepsis ). [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2350", "text": "Neutropenia can be divided into congenital and acquired, with  severe congenital neutropenia  (SCN) and  cyclic neutropenia  (CyN) being autosomal dominant and mostly caused by heterozygous mutations in the ELANE gene ( neutrophil elastase ). [ 7 ]  Neutropenia can be  acute  (temporary) or  chronic  (long lasting). The term is sometimes used interchangeably with \" leukopenia \" (\"deficit in the number of white blood cells\"). [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2351", "text": "Decreased production of neutrophils is associated with deficiencies of  vitamin B12  and  folic acid ,  aplastic anemia ,  tumors , drugs, metabolic disease, nutritional deficiencies (including minerals such as copper), and immune mechanisms. In general, the most common oral manifestations of neutropenia include ulcer,  gingivitis , and periodontitis.  Agranulocytosis  can be presented as whitish or greyish necrotic ulcer in the oral cavity, without any sign of inflammation. Acquired agranulocytosis is much more common than the congenital form. The common causes of acquired agranulocytosis including drugs (non-steroidal anti-inflammatory drugs, antiepileptics, antithyroid, and antibiotics) and viral infection. Agranulocytosis has a mortality rate of 7\u201310%. To manage this, the application of granulocyte colony stimulating factor (G-CSF) or  granulocyte transfusion  and the use of broad-spectrum antibiotics to protect against bacterial infections are recommended. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2352", "text": "Signs and symptoms of neutropenia include  fever ,  painful swallowing ,  gingival  pain, skin  abscesses , and  otitis . These symptoms may exist because individuals with neutropenia often have  infection . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2353", "text": "Children may show signs of  irritability  and  poor feeding . [ 10 ]   Hypotension  has also been observed in individuals with this condition. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2354", "text": "The causes of neutropenia can be divided between problems that are  transient  and those that are  chronic . Causes can be divided into these groups: [ 1 ] [ 2 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2355", "text": "Severe bacterial infections, especially in people with underlying hematological diseases or  alcoholism , can deplete neutrophil reserves and lead to neutropenia. [ 2 ]   Gram-positive bacteria  are present in 60\u201370% of bacterial infections. There are serious concerns regarding  antibiotic-resistant  organisms. These would include as methicillin-resistant  Staphylococcus aureus  ( MRSA ) or vancomycin-resistant Enterococcus ( VRE ). [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2356", "text": "Nutritional deficiencies, such as deficiency in  vitamin B12 ,  folate ,  copper  or  protein-calorie malnutrition  are associated with chronic neutropenia. However, nutritional deficiencies are usually associated with decreases in other cell lines (multiple cytopenia or pancytopenia) rather than isolated neutropenia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2357", "text": "Other causes of congenital neutropenia are  Shwachman\u2013Diamond syndrome , Cyclic neutropenia,  bone marrow  failure syndromes, cartilage\u2013hair hypoplasia, reticular dysgenesis, and  Barth syndrome . Viruses that infect neutrophil progenitors can also be the cause of neutropenia. Viruses identified that have an effect on neutrophils are rubella and cytomegalovirus. [ 1 ]  Though the body can manufacture a normal level of neutrophils, in some cases the destruction of excessive numbers of neutrophils can lead to neutropenia. These are: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2358", "text": "The  pathophysiology  of neutropenia can be divided into  congenital  and  acquired . The  congenital  neutropenia (severe and  cyclic  type) is  autosomal dominant , with mutations in the  ELA2  gene ( neutrophil elastase ) as the most common genetic reason for this condition. [ 7 ]  Acquired neutropenia (immune-associated neutropenia) is due to anti-neutrophil  antibodies  that target neutrophil-specific  antigens , ultimately altering neutrophil function. [ 32 ]  Furthermore, emerging research suggests neutropenia without an identifiable etiology (idiopathic neutropenia) may be the result of a  low-grade, chronic inflammatory process with an abnormal excessive production of myelosuppressive cytokines in a study conducted in the island of Crete. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2359", "text": "Neutropenia fever can complicate the treatment of  cancers . Observations of  children  noted that  fungal  infections are more likely to develop in those with neutropenia. Mortality increases during cancer treatments if neutropenia is also present. [ 6 ] \nCongenital neutropenia is determined by blood neutrophil counts (absolute neutrophil counts or ANC) < 0.5 \u00d7 10 9 /L and recurrent bacterial infections beginning very early in childhood. [ 34 ]  Congenital neutropenia is related to  alloimmunization , sepsis, maternal  hypertension ,  twin-to-twin transfusion syndrome , and  Rh hemolytic disease . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2360", "text": "Neutropenia can be the result of a variety of consequences, including taking certain types of drugs, exposure to environmental toxins, vitamin deficiencies, metabolic abnormalities, as well as cancer, viral or bacterial infections. Neutropenia itself is a rare entity, but can be clinically common in oncology [ 35 ]  and immunocompromised individuals as a result of chemotherapy (drug-induced neutropenia). Additionally, acute neutropenia can be commonly seen from people recovering from a viral infection or in a post-viral state. Meanwhile, several subtypes of neutropenia exist which are rarer and chronic, including acquired (idiopathic) neutropenia, cyclic neutropenia, autoimmune neutropenia, and congenital neutropenia. [ 36 ] [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2361", "text": "Neutropenia that is developed in response to chemotherapy typically becomes evident in seven to fourteen days after treatment, this period is known as the  nadir  or \"low point\". [ 38 ] [ 39 ]  Conditions that indicate the presence of neutropenic fever are implanted devices; leukemia induction; the compromise of mucosal, mucociliary and cutaneous barriers; a rapid decline in absolute neutrophil count, duration of neutropenia >7\u201310 days, and other illnesses that exist in the patient. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2362", "text": "Signs of infection can be subtle. Fevers are a common and early observation. Sometimes overlooked is the presence of  hypothermia , which can be present in sepsis. Physical examination and accessing the history and physical examination is focused on sites of infection. Indwelling line sites, areas of skin breakdown, sinuses, nasopharynx, bronchi and lungs, alimentary tract, and skin are assessed. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2363", "text": "The diagnosis of neutropenia is done via the low neutrophil count detection on a  complete blood count . Generally, other investigations are required to arrive at the right diagnosis. When the diagnosis is uncertain, or serious causes are suspected,  bone marrow biopsy  may be necessary. A bone marrow biopsy can identify abnormalities in myelopoesis contributing to neutropenia such as the stage of arrest in the development of myeloid progenitor cells. [ 2 ]  Bone marrow biopsies can also be used to monitor the development of  myelodysplastic syndrome  (MDS) or  acute myeloid leukemia  (AML) in patients with chronic neutropenia (especially in those with  severe congenital neutropenia  (SCN) which carries a higher risk of MDS and AML)). [ 2 ]  Other investigations commonly performed: serial neutrophil counts for suspected cyclic neutropenia, tests for  antineutrophil antibodies ,  autoantibody  screen (and investigations for  systemic lupus erythematosus ),  vitamin B 12  and  folate  assays. [ 40 ] [ 41 ]  Rectal examinations are usually not performed due to the increased risk of introducing bacteria into the blood stream and the possible development of rectal abscesses. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2364", "text": "Generally accepted  reference range  for  absolute neutrophil count  (ANC) in adults is  1500 to 8000 cells per microliter (\u03bcL) of blood . Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/\u03bcL): [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2365", "text": "Each of these are either derived from laboratory tests or via the formula below:"}
{"_id": "WikiPedia_Hematology$$$corpus_2366", "text": "ANC =  \n \n \n \n \n ( \n % \n n \n e \n u \n t \n r \n o \n p \n h \n i \n l \n s \n + \n % \n b \n a \n n \n d \n s \n ) \n \u00d7 \n ( \n W \n B \n C \n ) \n \n \n ( \n 100 \n ) \n \n \n \n {\\displaystyle (\\%neutrophils+\\%bands)\\times (WBC) \\over (100)} \n \n [ 1 ] [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2367", "text": "A fever, when combined with profound neutropenia ( febrile neutropenia ), is considered a medical emergency and requires broad spectrum antibiotics. An absolute neutrophil count less than 200 is also considered a medical emergency and almost always requires hospital admission and initiation of broad spectrum antibiotics with selection of specific antibiotics based on local resistance patterns. [ 2 ] Precautions to avoid opportunistic infections in those with chronic neutropenia include maintaining proper soap and water hand hygiene, good dental hygiene and avoiding highly contaminated sources that may contain a large fungal reservoirs such as mulch, construction sites and bird or other animal waste. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2368", "text": "Neutropenia can be treated with the hematopoietic growth factor  granulocyte-colony stimulating factor  (G-CSF). These are cytokines that are present naturally in the body. The factors promote neutrophil recovery following anticancer therapy or in chronic neutropenia. [ 1 ]  Recombinant G-CSF factor preparations, such as  filgrastim [ 44 ]  can be effective in people with congenital forms of neutropenia including severe congenital neutropenia and cyclic neutropenia; [ 45 ]  the amount needed (dosage) to stabilize the neutrophil count varies considerably (depending on the individual's condition). [ 46 ]  Guidelines for neutropenia regarding diet are currently being studied. [ 47 ]  Those who have chronic neutropenia and fail to respond to G-CSF or who have an increased risk of developing MDS or AML (due to increased dosage requirements of G-CSF or having abnormal precursor cells in the bone marrow)  often require  hematopoietic stem cell transplantation  as a treatment. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2369", "text": "Most cases of neonatal neutropenia are temporary. Antibiotic prophylaxis is not recommended because of the possibility of encouraging the development of multidrug-resistant bacterial strains. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2370", "text": "These are cytokines that are present naturally in the body. The factors promote neutrophil recovery following anticancer therapy. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2371", "text": "The administration of intravenous immunoglobulins (IVIGs) has had some success in treating neutropenias of alloimmune and autoimmune origins with a response rate of about 50%. Blood transfusions have not been effective. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2372", "text": "Patients with neutropenia caused by cancer treatment can be given antifungal drugs. A Cochrane review  [ 48 ]  found that lipid formulations of amphotericin B had fewer side effects than conventional amphotericin B, though it is not clear whether there are particular advantages over conventional amphotericin B if given under optimal circumstances. Another Cochrane review  [ 49 ]  was not able to detect a difference in effect between amphotericin B and fluconazole because available trial data analysed results in a way that disfavoured amphotericin B."}
{"_id": "WikiPedia_Hematology$$$corpus_2373", "text": "Trilaciclib, a  CDK4/6 inhibitor , administered approximately thirty minutes before chemotherapy, has been shown in three clinical trials to significantly reduce the occurrence of chemotherapy-induced neutropenia and the associated need for interventions such as the administration of  G-CSF 's. [ 50 ]  The drug was approved in February 2021  by the FDA for use in patients with extensive-stage small cell lung cancer. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2374", "text": "In November 2023, FDA approved  efbemalenograstim alfa . [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2375", "text": "If left untreated, people with fever and absolute neutrophil count <500 have a mortality of up to 70% within 24 hours. [ 31 ]  The prognosis of neutropenia depends on the cause.  Antibiotic  agents have improved the prognosis for individuals with severe neutropenia.  Neutropenic fever  in individuals treated for cancer has a mortality of 4\u201330%. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2376", "text": "Neutropenia is usually detected shortly after birth, affecting 6% to 8% of all newborns in  neonatal  intensive care units (NICUs). Out of the approximately 600,000 neonates annually treated in NICUs in the United States, 48,000 may be diagnosed as neutropenic. The incidence of neutropenia is greater in premature infants. Six to fifty-eight percent of preterm neonates are diagnosed with this auto-immune disease. The incidence of neutropenia correlates with decreasing birth weight. The disorder is seen up to 38% in infants that weigh less than 1000g, 13% in infants weighing less than 2500g, and 3% of term infants weighing more than 2500 g. Neutropenia is often temporary, affecting most newborns in only first few days after birth. In others, it becomes more severe and chronic indicating a deficiency in innate immunity. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2377", "text": "Furthermore, the prevalence of chronic neutropenia in the general public is rare. In a study conducted in Denmark, over 370,000 people were assessed for the presence of neutropenia. Results published demonstrated only 1% of those evaluated were neutropenic, and were commonly seen in those with HIV, viral infections, acute leukemias, and  myelodysplastic syndromes . The study concluded the presence of neutropenia is an ominous sign that warrants further investigation and follow-up. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2378", "text": "No reflow phenomenon  is the failure of blood to  reperfuse  an  ischemic  area after the physical obstruction has been removed or bypassed. The underlying mechanism is related to arterial microvasculature damage. It is primarily seen during  percutaneous coronary intervention (PCI)  in the setting of  acute myocardial infarction (AMI) , but has also been observed in other organs, including the brain and kidneys. [ 1 ]  Coronary no-reflow phenomenon is specifically related to reduced antegrade coronary blood flow despite proximal coronary artery patency. It is an independent predictor of worse clinical outcomes including heart failure, fatal arrhythmias, myocardial infarction, and increased mortality rates. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2379", "text": "The underlying mechanism of no reflow phenomenon is centered around the damage caused by microvascular obstruction (MVO). There have been two proposed underlying causes of no reflow phenomenon:"}
{"_id": "WikiPedia_Hematology$$$corpus_2380", "text": "In both types of no reflow phenomenon, the extent of damage to the microvasculature is directly proportional to the length of time the tissue is ischemic, with longer periods of ischemia related to greater damage to the arterial microvasculature. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2381", "text": "Ornithinaemia  is a  blood disorder  characterized by high levels of  ornithine .  Also known as hyperornithinemia, it may be associated with  psychomotor retardation  or  epileptic  episodes. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2382", "text": "Pancytopenia  is a  medical condition  in which there is significant reduction in the number of almost all blood cells ( red blood cells ,  white blood cells ,  platelets ,  monocytes ,  lymphocytes , etc.)."}
{"_id": "WikiPedia_Hematology$$$corpus_2383", "text": "If only two parameters from the  complete blood count  are low, the term  bicytopenia  can be used.  The diagnostic approach is the same as for pancytopenia."}
{"_id": "WikiPedia_Hematology$$$corpus_2384", "text": "Iatrogenic causes of pancytopenia include chemotherapy for malignancies if the drug or drugs used cause  bone marrow suppression . Rarely, drugs ( antibiotics , blood pressure medication, heart medication) can cause pancytopenia.\nFor example, the antibiotic  chloramphenicol  can cause pancytopenia in some individuals. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2385", "text": "Rarely, pancytopenia may have other causes, such as  mononucleosis  or other viral diseases. Increasingly,  HIV  is itself a cause of pancytopenia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2386", "text": "The mechanism of pancytopenia involves either haemopoiesis itself, decreasing blood cell productions in number (aplastic anemia), haemopoietic stem cells are displaced by malignant cells (Leukemia, lymphoma, MDS) or they are being pooled (sequestrated) (spleen)/destroyed (immune) outside bone marrow. The mechanisms for pancytopenia differ according to the  etiology . For example, in  hemophagocytic lymphohistiocytosis  (HLH) there is marked inappropriate and ineffective  T cell  activation that leads to an increased hemophagocytic activity. The T cell activated  macrophages  engulf erythrocytes, leukocytes, platelets, as well as their  progenitor cells . Along with pancytopenia, HLH is characterized by  fever ,  splenomegaly , and hemophagocytosis in  bone marrow ,  liver , or  lymph nodes . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2387", "text": "Pancytopenia usually requires a  bone marrow biopsy  in order to distinguish among different causes. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2388", "text": "Treatment is done to address the underlying cause. To tide over immediate crisis  blood transfusion  with  packed red blood cells  (PRBC) or platelet transfusion may be done. Sometimes there are obvious clinical clues to suggest underlying B12 deficiency for a cause of  pancytopenia. [ 6 ]  In this selected cases even with severe anemia blood product transfusions can be avoided and vitamin B12 treatment itself suffice. [ 7 ]  In other situations like acute leukemia, Myelodysplastic syndrome, aplastic anemia etc. disease specific therapy is needed. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2389", "text": "Pseudothrombocytopenia  (PTCP) or  spurious thrombocytopenia  is an  in-vitro  sampling problem which may mislead the diagnosis towards the more critical condition of  thrombocytopenia . The phenomenon may occur when the  anticoagulant  used while testing the blood sample causes clumping of  platelets  which mimics a low platelet count. [ 1 ] \nThe phenomenon has first been reported in 1969. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2390", "text": "EDTA-dependent agglutination"}
{"_id": "WikiPedia_Hematology$$$corpus_2391", "text": "In some individuals, clinically insignificant antibodies may cause  in vitro  agglutination of platelets. As a result of platelet clumping, platelet counts reported by automated counters may be much lower than the actual count in the blood because these devices cannot differentiate platelet clumps from individual cells.\nPseudothrombocytopenia has been reported in association with the use of  EDTA  as an anticoagulant, with platelet cold agglutinins, and with  multiple myeloma . [ citation needed ] \nOther risk factors associated with pseudothrombocytopenia are  autoimmune diseases ,  infections , pregnancy and the treatment with some medications such as  low-molecular-weight heparin ,  valproic acid ,  insulin ,  antibiotics  and chemotherapy medications like  sunitinib . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2392", "text": "The prevalence of pseudothrombocytopenia in K2-EDTA reported in different studies ranges from 0.03 to 0.27 percent in outpatients, [ 3 ]  which accounts for 15 to 30 percent of all cases of isolated thrombocytopenia.\nTests can mistake small clumps of platelets for leukocytes, thus showing a pseudo\u00ad leukocytosis  in blood counts. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2393", "text": "Platelet satellitism"}
{"_id": "WikiPedia_Hematology$$$corpus_2394", "text": "Platelet rosetting, or satelliting, around  white blood cells  can lead to undercounting by automated analyzers. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2395", "text": "Clotted samples"}
{"_id": "WikiPedia_Hematology$$$corpus_2396", "text": "Coagulation within the sample leads to undercounting, because the analyzer samples the liquid part of the blood, while some of the platelets remain in the tube, trapped in the clot. \u2003Overfilling the sample, or inadequately mixing with anticoagulant, may allow small clots to form.  Unlike platelet clumps, clots usually cannot be detected by reviewing the peripheral blood smear, but may be detected by probing with wooden sticks, including checking under the cap. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2397", "text": "A pseudothrombocytopenia false-positive result may occur when automated platelet counting devices are used. As a means of double checking the results, the patient's blood sample is often examined under a microscope.  If the clumping is visible and the number of platelets appears normal, pseudothrombocytopenia may be concluded. A second sample run with a different anticoagulant such as sodium citrate (blue top tube) to confirm the finding of pseudothrombocytopenia may be requested if there are doubts or concerns. [ 7 ]  Other alternative anticoagulants are  sodium fluoride , CPT ( trisodium citrate ,  pyridoxal 5\u2032-phosphate  and  tris ), CTAD (citrate,  theophylline ,  adenosine , and  dipyridamole ),  magnesium sulfate  and  acid-citrate-dextrose . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2398", "text": "Rh disease  (also known as  rhesus  isoimmunization ,  Rh (D) disease , or  rhesus incompatibility , and blue baby disease) is a type of  hemolytic disease of the fetus and newborn  (HDFN).  HDFN due to anti-D antibodies is the proper and currently used name for this disease as the Rh blood group system actually has more than 50 antigens and not only the D-antigen. The term \"Rh Disease\" is commonly used to refer to HDFN due to anti-D antibodies, and prior to the discovery of anti-Rh o (D)  immune globulin, it was the most common type of HDFN. The disease ranges from mild to severe, and occurs in the second or subsequent pregnancies of  Rh-D negative  women when the biologic father is Rh-D positive."}
{"_id": "WikiPedia_Hematology$$$corpus_2399", "text": "Due to several advances in modern medicine, HDFN due to anti-D is preventable by treating the mother during pregnancy and soon after delivery with an  injection  of  anti-Rh o (D) immune globulin  (Rhoclone, Rhogam, AntiD).  With successful mitigation of this disease by prevention through the use of anti-Rh o (D)  immune globulin, other antibodies are more commonly the cause of HDFN today."}
{"_id": "WikiPedia_Hematology$$$corpus_2400", "text": "During pregnancy, there is normally a barrier between maternal and fetal blood called the placenta, a temporary organ that connects a mother\u2019s uterus to the umbilical cord to provide nutrients and oxygen to the fetus. However, in certain circumstances, small amounts of fetal blood cells may enter the mother\u2019s circulation. Certain types of events where this occurs are during childbirth, miscarriage or abortion, trauma, and invasive procedures such as amniocentesis. Once the fetal Rh-positive red blood cells enter the bloodstream of a Rh-negative mother, they are recognized as foreign. The mother\u2019s immune system reacts to the Rh-positive red blood cells the same way that it would respond to something like a virus or bacteria, activating B cells \u2014 a type of white blood cell that is key to the triggering of an immune response. These activated B cells then differentiate into plasma cells, which produce anti-D antibodies. After the primary exposure, some of these B cells become memory cells, that remember the original exposure and produce IgG antibodies, which are smaller and can cross the placental barrier. Once they cross this barrier, they are into the fetal bloodstream, binding to fetal Rh-positive cells, triggering opsonization, which marks the red blood cells for destruction. The fetal spleen and liver then begin to break down those red blood cells, thinking that they are a foreign invader when in reality they are they are just mismatched. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2401", "text": "Symptoms of Rh disease include yellowish amniotic fluid and enlarged spleen, liver or heart or buildup of fluid in the abdomen of the fetus. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2402", "text": "During the first pregnancy, the Rh- mother's initial exposure to fetal Rh+ red blood cells (RBCs) is usually not sufficient to activate her Rh-recognizing B cells. However, during delivery, the placenta separates from the uterine wall, causing umbilical cord blood to enter the maternal circulation, which results in the mother's proliferation of IgM-secreting plasma B cells to eliminate the fetal Rh+ cells from her blood stream.  IgM   antibodies  do not cross the  placental barrier , which is why no effects to the fetus are seen in first pregnancies for Rh-D mediated disease. However, in subsequent pregnancies with Rh+ fetuses, the IgG memory B cells mount an immune response when re-exposed, and these  IgG  anti-Rh(D) antibodies  do  cross the placenta and enter  fetal circulation . These antibodies are directed against the  Rhesus (Rh) factor , a protein found on the surface of the fetal RBCs. The antibody-coated RBCs are destroyed by IgG antibodies binding and activating complement pathways. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2403", "text": "The resulting anemia has multiple sequelae: [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2404", "text": "The destruction of RBCs leads to elevated bilirubin levels ( hyperbilirubinemia ) as a byproduct. This is not generally a problem during pregnancy, as the maternal circulation can compensate. However, once the infant is delivered, the immature system is not able to handle this amount of bilirubin alone and  jaundice  or  kernicterus  (bilirubin deposition in the brain) can develop which may lead to brain damage or death. Sensitizing events during pregnancy include  c-section ,  miscarriage ,  therapeutic abortion ,  amniocentesis ,  ectopic pregnancy , abdominal trauma and  external cephalic version . However, in many cases there was no apparent sensitizing event. Approximately 50% of Rh-D positive infants with circulating anti-D are either unaffected or only mildly affected requiring no treatment at all and only monitoring. An additional 20% are severely affected and require transfusions while still in the uterus. This pattern is similar to other types of HDFN due to other commonly encountered antibodies (anti-c, anti-K, and Fy(a)). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2405", "text": "In the United States, it is a standard of care to test all expecting mothers for the presence or absence of the RhD protein on their RBCs. However, when medical care is unavailable or prenatal care not given for any other reason, the window to prevent the disease may be missed. In addition, there is more widespread use of molecular techniques to avoid missing women who appear to be Rh-D positive but are actually missing portions of the protein or have hybrid genes creating altered expression of the protein and still at risk of HDFN due to Anti-D. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2406", "text": "Blood is generally drawn from the biological father to help determine fetal antigen status. [ 11 ]  If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDFN. If he is heterozygous, there is a 50% chance of offspring to be positive for the antigen. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2407", "text": "The protection that is offered today against Rh incompatibility involved preventive measures that primarily utilize Rh immunoglobulin, also known as RhoGAM. [ 13 ]  The aim of these treatments are to prevent the mother\u2019s immune system from becoming sensitized to the Rh antigen, which reduces the risk of hemolytic disease in future pregnancies. RhoGAM, Rh Immunoglobulin Administration, is a product that contains antibodies to the Rh D antigen, it is used to prevent the mother from developing an immune response to fetal red blood cells. RhIg \u2018coats\u2019 any Rh-positive fetal red blood cells that enter the mother\u2019s bloodstream, effectively \u2018hiding\u2019 them from the mother\u2019s immune system. RhoGAM is typically administered at around 28 weeks of pregnancy, then again within 72 hours after childbirth. It is also given during other events that happen during pregnancy like miscarriages, ectopic pregnancies, amniocentesis, and abdominal trauma  [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2408", "text": "In Arar, Saudi Arabia, results of a study showed that women had a low level of knowledge regarding maternal-fetal blood incompatibility (about 38% of the studied mothers during the research, had knowledge about Rh incompatibility). Regarding their knowledge about anti-D, researchers found that; 68.5% of the mothers had knowledge about it, while only 51% of the mothers had knowledge about the administration of prophylactic anti D after delivery. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2409", "text": "As medical management advances in this field, it is important that these patients be followed by high risk obstetricians/maternal-fetal medicine, and skilled neonatologists postpartum to ensure the most up to date and appropriate standard of care [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2410", "text": "In 1939 Drs.  Philip Levine  and  Rufus E. Stetson  published their findings about a 25-year-old mother who had a  stillborn  baby that died of  hemolytic disease of the newborn . [ 19 ]  Both parents were  blood group  O, so the husband's blood was used to give his wife a  blood transfusion  due to blood loss during delivery. However, she had a severe  transfusion reaction . Since both parents were blood group O, which was believed to be compatible for transfusion, they concluded that there must be a previously undiscovered blood group  antigen  that was present on the husband's red blood cells (RBCs) but not present on his wife's. This suggested for the first time that a mother could make blood group antibodies because of immune sensitization to her  fetus 's RBCs as her only previous exposure would be the earlier pregnancy. They did not name this blood group antigen at the time, which is why the discovery of the  rhesus  blood type is credited to Drs.  Karl Landsteiner  and  Alexander S. Wiener [ 20 ]  with their first publication of  their tables  for  blood-typing  and cross-matching in 1940, which was the culmination of years of work. However, there were multiple participants in this scientific race and almost simultaneous publications on this topic. Levine published his theory that the disease known as erythroblastosis fetalis was due to Rh alloimmunization in 1941 while Landsteiner and Wiener published their method to type patients for an antibody causing transfusion reactions, known as \u201cRh\". [ 21 ] [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2411", "text": "The first treatment for Rh disease was an  exchange transfusion  invented by Wiener [ 24 ]  and later refined by Dr. Harry Wallerstein. [ 25 ]  Approximately 50,000 infants received this treatment. However, this could only treat the disease after it took root and did not do anything to prevent the disease. In 1960,  Ronald Finn , in  Liverpool , England proposed that the disease might be prevented by injecting the at-risk mother with an antibody against fetal red blood cells (anti-RhD). [ 26 ]  Nearly simultaneously, Dr. William Pollack, [ 27 ]  an immunologist and protein chemist at  Ortho Pharmaceutical Corporation , and Dr. John Gorman (blood bank director at Columbia-Presbyterian) with Dr. Vincent Freda (an obstetrician at  Columbia-Presbyterian Medical Center ), came to the same realization in New York City. The three of them set out to prove it by injecting a group of male prisoners at  Sing Sing Correctional Facility  with antibody provided by Ortho, obtained by a fractionation technique developed by Pollack. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2412", "text": "Animal studies had previously been conducted by Dr. Pollack using a rabbit model of Rh. [ 29 ]  This model, named the rabbit HgA-F system, was an animal model of human Rh, and enabled Pollack's team to gain experience in preventing hemolytic disease in rabbits by giving specific HgA antibody, as was later done with Rh-negative mothers. One of the needs was a dosing experiment that could be used to determine the level of circulating Rh-positive cells in an Rh-negative pregnant female derived from her Rh-positive fetus. This was first done in the rabbit system, but subsequent human tests at the University of Manitoba conducted under Dr. Pollack's direction confirmed that anti-Rh o (D) immune globulin could prevent alloimmunization during pregnancy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2413", "text": "Ms. Marianne Cummins was the first at risk woman to receive a prophylactic injection of anti-Rh o (D) immune globulin (RHIG) after its regulatory approval. [ 30 ]  Clinical trials were set up in 42 centers in the US, Great Britain, Germany, Sweden, Italy, and Australia. RHIG was finally approved in England and the United States in 1968. [ 31 ]  The FDA approved the drug under the brand name RhoGAM, with a fixed dose of 300 \u03bcg, to be given within three days (72 hours) postpartum. Subsequently, a broader peripartum period was approved for dosing which included prophylaxis during pregnancy. Within a year, the antibody had been injected with great success into more than 500,000 women. Time magazine picked it as one of the top ten medical achievements of the 1960s. By 1973, it was estimated that in the US alone, over 50,000 babies' lives had been saved. The use of Rh immune globulin to prevent the disease in babies of Rh negative mothers has become standard practice, and the disease, which used to claim the lives of 10,000 babies each year in the US alone, has been virtually eradicated in the developed world. In 1980,  Cyril Clarke ,  Ronald Finn ,  John G. Gorman , Vincent Freda, and William Pollack each received an  Albert Lasker Award  for Clinical Medical Research for their work on rhesus blood types and the prevention of Rh disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2414", "text": "RUNX1  Familial Platelet Disorder  (RUNX1- FPD )  also known as Familial platelet disorder with associated myeloid malignancies, FPDMM ,  is a rare inherited disease caused by one of over 100 known  variants  (i.e.,  mutations ) in an individual\u2019s  RUNX1  gene . Low platelets and dysfunctional platelets, which cause heavier than average bruising and bleeding, are hallmarks of the disorder. [ 1 ]  Individuals with  RUNX1 -FPD have a lifetime risk of being diagnosed with a  hematologic malignancy  of 35-45%. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2415", "text": "The most common hematologic malignancy diagnosed for these individuals is  acute myeloid leukemia (AML)  and  Myelodysplastic syndrome (MDS) . Additional HMs include  Acute lymphoblastic leukemia (ALL) ,  Chronic myelomonocytic leukemia ,  hairy-cell leukemia  and  Non-Hodgkin lymphoma (NHL) . [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2416", "text": "RUNX1 -FPD patients often face a range of additional health issues including eczema, [ citation needed ]  arthritis, [ 6 ]  psoriasis, [ 7 ]  asthma, allergies, autoimmune disorders and gastrointestinal problems. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2417", "text": "Shwachman\u2013Diamond syndrome  ( SDS ), or  Shwachman\u2013Bodian\u2013Diamond syndrome , is a rare congenital disorder characterized by  exocrine pancreatic insufficiency ,  bone marrow  dysfunction,  skeletal  and cardiac abnormalities and  short stature . After  cystic fibrosis  (CF), it is the second most common cause of exocrine pancreatic insufficiency in children. It is associated with the  SBDS  gene and has autosomal recessive inheritance. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2418", "text": "The syndrome shows a wide range of abnormalities and symptoms. The main characteristics of the syndrome are  exocrine pancreatic dysfunction , hematologic abnormalities and growth retardation. Only the first two of these are included in the clinical diagnostic criteria. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2419", "text": "Shwachman\u2013Diamond syndrome is characterized by an  autosomal recessive  mode of inheritance. The gene that is mutated in this syndrome,  SBDS , [ 2 ] [ 3 ] [ 4 ]  lies on the long arm of  chromosome 7  at  cytogenetic  position 7q11. [ 5 ] [ 6 ]  It is composed of five exons and has an associated  mRNA  transcript that is 1.6  kilobase  pairs in length. The  SBDS  gene resides in a block of genomic sequence that is locally duplicated on the chromosome. The second copy contains a non-functional version of the  SBDS  gene that is 97% identical to the original gene, but has accumulated inactivating mutations over time. It is considered to be a  pseudogene . In a study of 158 SDS families, 75% of disease-associated mutations appeared to be the result of  gene conversion , while 89% of patients harbored at least one such mutation. Gene conversion occurs when the intact  SBDS  gene and its pseudogene copy aberrantly  recombine  at  meiosis , leading to an incorporation of pseudogene-like sequences into the otherwise functional copy of the  SBDS  gene, thereby inactivating it. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2420", "text": "Two gene conversion mutations predominate in SDS patients.  One is a  splice site  mutation affecting the 5' splice site of  intron  two, while the second is an  exon  two  nonsense mutation . The marked absence of patients homozygous for the otherwise common nonsense mutation suggested that the SBDS gene is essential.  Consistent with this, knockout of the mouse gene leads to early embryonic lethality. [ 8 ]  This, in turn, suggests that the common splice site mutation seen in patients may be hypomorphic, i.e. that it results in only a partial loss of function, whereas the complete loss of SBDS function is likely to be lethal. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2421", "text": "The  SBDS  gene is expressed in all tissues and encodes a  protein  of 250  amino acid  residues.  A great deal of indirect evidence suggested that the SBDS protein may be involved in an aspect of cellular  RNA  metabolism or  ribosome  assembly or function. The wide occurrence of the gene in all  archaea  and  eukaryotes  supported a role for this protein in a very fundamental and evolutionarily conserved aspect of cellular biology. [ 10 ]  The homologous genes in archaea also tend to be present in conserved cluster enriched for RNA processing and ribosomal genes.  A specific function for SBDS in RNA metabolism or ribosome assembly or function is further supported by its localization to the  nucleolus , the nuclear subdomain where these processes occur. In line with this, the yeast homologue, SdoI, has been shown to be critical for maturation of pre-60S ribosomes, by effecting release and recycling of the nucleolar shuttling factor Tif6. [ 11 ]  This is required for 60S maturation and translational activation of ribosomes. It has also been shown that the  Dictyostelium discoideum  homologue catalyzes the removal of eukaryotic initiation factor 6 (eIF6), which is required for the translational activation of ribosomes. [ 12 ]   Cells from SDS patients were shown to have a defect in assembly of ribosome subunits. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2422", "text": "At present, it is not obvious how disruption of the basic cellular process of translation leads to the tissue- and organ-specific manifestations seen in SDS. However, unusual and combinations of tissues and organs are also affected in  Diamond\u2013Blackfan anemia ,  X-linked   dyskeratosis congenita , and  cartilage\u2013hair hypoplasia \u2014three diseases that may also be linked to defective ribosome function.  Pleiotropic disease features may be the result of cell-specific effects of reduced levels of SBDS activity provided by hypomorphic mutations. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2423", "text": "Initially, the clinical presentation of SDS may appear similar to  cystic fibrosis . However, CF can be excluded with a normal chloride in sweat test but faecal elastase as a marker of pancreatic function will be reduced. The variation, intermittent nature, and potential for long-term improvement of some clinical features make this syndrome difficult to diagnose. SDS may present with either  malabsorption , or hematological problems. Rarely, SDS may present with skeletal defects, including severe rib cage abnormalities that lead to difficulty in breathing. Diagnosis is generally based on evidence of exocrine pancreatic dysfunction and neutropenia. Skeletal abnormalities and short stature are characteristics that can be used to support the diagnosis. The  gene  responsible for the disease has been identified and  genetic testing  is now available. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2424", "text": "Pancreatic exocrine insufficiency may be treated through pancreatic enzyme supplementation, [ 14 ]  while severe skeletal abnormalities may require surgical intervention. Neutropenia may be treated with  granulocyte-colony stimulating factor  (GCSF) to boost peripheral neutrophil counts. However, there is ongoing and unresolved concern that this drug could contribute to the development of  leukemia . Signs of progressive marrow failure may warrant  bone marrow transplantation  (BMT). This has been used successfully to treat hematological aspects of disease. However, SDS patients have an elevated occurrence of BMT-related adverse events, including  graft-versus-host disease  (GVHD) and toxicity relating to the pre-transplant conditioning regimen. In the long run, study of the gene that is mutated in SDS should improve understanding of the molecular basis of disease. This, in turn, may lead to novel therapeutic strategies, including  gene therapy  and other gene- or protein-based approaches. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2425", "text": "A major goal of curative therapy for SDS is to reduce the risk of bone marrow failure and halt the progression of  malignant transformation  toward  myelodysplastic syndrome  (MDS) and  acute myeloid leukemia  (AML), the most detrimental complications of SDS.  Currently, there is no such therapy.  However, several emerging therapeutic strategies, including  gene therapy  and  antisense oligonucleotides  (ASOs), could potentially slow or prevent malignant transformation, at least in theory.  These new therapies have been proven effective for several rare diseases, including  metachromatic leukodystrophy  and  spinal muscular atrophy .  Several SDS patient groups are advocating for better therapies for SDS, [ 15 ] [ 16 ] [ 17 ] [ 18 ]  and one organization is focused on driving the therapy development efforts. [ 19 ]   The challenge is whether the SDS community can come together to support the required research, [ 20 ]  and whether the organizations can successfully execute a strategy that coordinates the efforts for new therapy development. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2426", "text": "It is thought to have an estimated incidence of 1 in 75,000 people. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2427", "text": "The disease was first described as a coherent clinical entity in May 1964 by Bodian, Sheldon, and Lightwood. [ 23 ]  It was subsequently described by Shwachman, Diamond, Oski, and Khaw in November of the same year. [ 24 ]  In 2001, linkage analysis in SDS families indicated that affected gene mapped to a large region of human chromosome seven. [ 25 ]  In 2002, this interval was refined to a region on the long arm of the  chromosome  next to the  centromere . [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2428", "text": "In 2003, a team of researchers led by  Johanna Rommens  at the Hospital of Sick Children (SickKids) in Toronto, Canada, discovered mutations in the  SBDS  gene (Shwachman\u2013Bodian\u2013Diamond syndrome) were associated with disease. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2429", "text": "Shwachman\u2013Diamond syndrome, less commonly known as Shwachman\u2013Bodian\u2013Diamond syndrome, is named for Harry Shwachman (1910 \u2013 September 12, 1986), an American physician, Martin Bodian (1912 \u2013 May 12, 1994), a British ophthalmologist who worked in  New York City , and  Louis Klein Diamond  (May 11, 1902 \u2013 June 14, 1999), an American pediatrician. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2430", "text": "The  trauma triad of death  is a medical term describing the combination of  hypothermia ,  acidosis , and  coagulopathy . [ 1 ]  This combination is commonly seen in patients who have sustained severe  traumatic injuries  and results in a significant rise in the  mortality rate . [ 2 ]  Commonly, when someone presents with these signs,  damage control surgery  is employed to reverse the effects. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2431", "text": "The three conditions share a complex relationship; each factor can compound the others, resulting in high mortality if this  positive feedback  loop continues uninterrupted. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2432", "text": "Severe  bleeding  in trauma diminishes  oxygen delivery , and may lead to  hypothermia . This in turn can halt the  coagulation cascade , preventing  blood from clotting . In the absence of blood-bound oxygen and nutrients ( hypoperfusion ), the body's cells burn glucose  anaerobically  for energy, causing the release of  lactic acid ,  ketone bodies , and other  acidic  compounds into the blood stream, which lower the blood's  pH , leading to  metabolic acidosis . Such an increase in acidity damages the tissues and organs of the body and can reduce  myocardial performance , further reducing the oxygen delivery. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2433", "text": "Tumor lysis syndrome  ( TLS ) is a group of  metabolic abnormalities  that can occur as a  complication  from the treatment of  cancer , where large amounts of  tumor  cells are killed off ( lysed ) from the treatment, releasing their contents into the  bloodstream . [ 1 ]  This occurs most commonly after the treatment of  lymphomas  and  leukemias  and in particular when treating  non-Hodgkin lymphoma ,  acute myeloid leukemia , and  acute lymphoblastic leukemia . [ 2 ] [ 3 ]  This is a potentially fatal complication and people at an increased risk for TLS should be closely monitored while receiving  chemotherapy  and should receive preventive measures and treatments as necessary. [ 4 ] [ 3 ]  TLS can also occur on its own (while not being treated with chemotherapy) although this is less common. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2434", "text": "Tumor lysis syndrome is characterized by high blood potassium ( hyperkalemia ), high blood phosphate ( hyperphosphatemia ), low blood calcium ( hypocalcemia ), high blood uric acid ( hyperuricemia ), and higher than normal levels of blood urea nitrogen ( BUN ). [ 4 ]  These changes in blood  electrolytes  and  metabolites  are a result of the release of cellular contents of dying cells into the bloodstream. [ 4 ]  In this respect, TLS is analogous to  rhabdomyolysis , with comparable mechanism and blood chemistry effects but with different cause. In TLS, the breakdown occurs after  cytotoxic  therapy or from cancers with high cell turnover and tumor proliferation rates. [ 4 ]  The metabolic abnormalities seen in tumor lysis syndrome can ultimately result in serious complications such as  acute uric acid nephropathy ,  acute kidney failure ,  seizures ,  cardiac arrhythmias , and death. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2435", "text": "Acute uric acid nephropathy  (AUAN) due to hyperuricosuria has been a dominant cause of acute kidney failure, but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia.  [ citation needed ]  Two common conditions related to excess  uric acid ,  gout  and  uric acid nephrolithiasis , are not features of tumor lysis syndrome. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2436", "text": "Risk factors for tumor lysis syndrome depend on several different characteristics of the patient, the type of cancer, and the type of chemotherapy used. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2437", "text": "Tumor characteristics:  Tumors with a high cell turnover rate, rapid growth rate, and high tumor bulk tend to be more associated with the development of tumor lysis syndrome. The most common tumors associated with this syndrome are poorly differentiated lymphomas (such as  Burkitt's lymphoma ), other  Non-Hodgkin Lymphomas  (NHL),  acute lymphoblastic leukemia  (ALL), and  acute myeloid leukemia  (AML). [ 3 ]   Other cancers (such as  melanoma ) have also been associated with TLS but are less common."}
{"_id": "WikiPedia_Hematology$$$corpus_2438", "text": "Patient characteristics:  Certain patient-related factors can affect the development of clinical tumor lysis syndrome. These factors include elevated baseline serum  creatinine ,  kidney failure , dehydration, and other issues affecting urinary flow or the acidity of urine. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2439", "text": "Chemotherapy characteristics:  Chemo-sensitive tumors, such as lymphomas, carry a higher risk for the development of tumor lysis syndrome. Those tumors that are more responsive to a chemotherapy agent carry a higher TLS risk. [ 7 ]  Usually, the precipitating medication regimen includes combination  chemotherapy , but TLS can be triggered in cancer patients by  steroid  treatment alone, and sometimes without any treatment\u2014in this case the condition is referred to as \"spontaneous tumor lysis syndrome\". [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2440", "text": "TLS should be suspected in people with large tumor burden who develop acute kidney failure along with hyperuricemia (> 15\u00a0mg/dL) or hyperphosphatemia (> 8\u00a0mg/dL).  [ medical citation needed ]  (Most other acute kidney failure occurs with uric acid < 12\u00a0mg/dL and phosphate < 6\u00a0mg/dL).  [ citation needed ]  Acute uric acid nephropathy is associated with little or no urine output.  [ citation needed ]  The  urinalysis  may show uric acid crystals or amorphous urates.  [ citation needed ]  The hypersecretion of uric acid can be detected with a high urine uric acid - creatinine ratio > 1.0, compared to a value of 0.6\u20130.7 for most other causes of acute kidney failure. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2441", "text": "In 2004, Cairo and Bishop defined a classification system for tumor lysis syndrome. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2442", "text": "A grading scale (0\u20135) is used depending on the presence of lab TLS, serum creatinine, arrhythmias, or seizures."}
{"_id": "WikiPedia_Hematology$$$corpus_2443", "text": "In 2011, Howard proposed a refinement of the standard Cairo-Bishop definition of TLS accounting for 2 limitations: [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2444", "text": "Moreover, any symptomatic hypocalcemia should constitute clinical TLS. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2445", "text": "It is important to prevent life-threatening manifestations associated with TLS which include acute kidney injury, hyperkalemia (which may cause cardiac arrhythmias), and or hypocalcemia (which may cause cardiac arrhythmias and neuromuscular irritability). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2446", "text": "Acute kidney injury:  Patients at risk for developing TLS (e.g. patients about to receive chemotherapy for a cancer with a high cell turnover rate, especially  lymphomas  and  leukemias ) should receive appropriate intravenous hydration in order to improve blood flow to the kidneys, maximize urine output, and ultimately prevent precipitation of uric acid crystals that can lead to acute kidney injury. [ 2 ] [ 4 ]  A diuretic may also be indicated to further increase urine output in addition to intravenous hydration. [ 2 ] [ 4 ]  Another approach to prevent damage to the kidneys is to prevent the buildup of uric acid during TLS, and this can be accomplished with use of  allopurinol  or  rasburicase . [ 2 ]   Allopurinol  (a  xanthine oxidase  inhibitor, which inhibits uric acid production) works by preventing the formation of uric acid following tumor cell lysis. [ 4 ] [ 13 ]   Rasburicase  is a synthetic  urate oxidase  enzyme and acts by degrading uric acid. No current guidelines endorse the concurrent use of allopurinol and rasburicase. [ 16 ] [ 17 ]  It is not recommended to alkalinize urine in the management of TLS: although doing so increases the solubility of urste, it also creates calcium phosphate crystals. [ 2 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2447", "text": "Hyperkalemia:  Monitoring potassium levels in the blood frequently and cardiac monitoring (given the risk of cardiac arrhythmias) are important components in the prevention of adverse consequences in TLS. [ 2 ]  Other strategies, such as limiting oral intake of potassium, and excreting potassium through the gastrointestinal tract using agents such as oral sodium polystyrene sulfonate, can be beneficial. [ 2 ] [ 4 ]   Insulin  therapy (in conjunction with glucose administration) as well as  beta-receptor agonists  (such as  albuterol ) can also be used, but are temporary interventions, [ 2 ]  and potassium is not excreted from the body.  [ citation needed ]   Hemodialysis  and  hemofiltration  can also be used as options to remove potassium from the bloodstream when hyperkalemia is present. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2448", "text": "Hypocalcemia:  Hyperphosphatemia is a common finding in TLS, and high phosphorus levels can in turn contribute to hypocalcemia. Therefore, phosphate binders may be beneficial in preventing this form of hypocalcemia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2449", "text": "Treatment is first targeted at the specific metabolic disorder."}
{"_id": "WikiPedia_Hematology$$$corpus_2450", "text": "In general,  rasburicase  and hydration are the mainstays of treatment in patients with clinical evidence of tumor lysis syndrome. [ 18 ]  A  loop diuretic  may also be indicated to maintain appropriate production of urine by the kidneys. [ 18 ]  Further treatment is targeted towards the specific metabolic abnormalities present in patients with TLS (see \"main articles\" linked above). Mild  hyperkalemia  without symptoms can be treated with a  loop diuretic  and sodium  polystyrene sulfonate , while a temporizing agent such as rapid acting  insulin  (in conjunction with glucose) and an agent to stabilize cardiac membranes such as  calcium carbonate  may be given in cases of severe hyperkalemia. [ 18 ]  Concerning symptoms related to hypocalcemia (e.g. seizures) in TLS patients can be treated with  calcium gluconate . [ 18 ]  Tumor lysis patients may ultimately also require  renal replacement therapy  such as through hemodialysis if indicated. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2451", "text": "The rate of mortality from tumor lysis syndrome may vary widely depending on the type of underlying malignancy. [ 19 ]  However, the occurrence of acute kidney injury is concerning given the high mortality that is generally associated with it. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2452", "text": "X-linked thrombocytopenia , also referred to as  XLT  or  thrombocytopenia 1 , is an inherited clotting disorder that primarily affects males. It is a  WAS -related disorder, meaning it is caused by a mutation in the  Wiskott\u2013Aldrich syndrome  ( WAS ) gene, which is located on the short arm of the  X chromosome . [ 1 ]   WAS -related disorders include Wiskott\u2013Aldrich syndrome, XLT, and X-linked congenital  neutropenia  (XLN). Of the  WAS -related disorders, X-linked thrombocytopenia is considered to be the milder  phenotype . Between 1 and 10 per million males worldwide are affected with this disorder. Females may be affected with this disorder but this is very rare since females have two X chromosomes and are therefore typically carriers of the mutation."}
{"_id": "WikiPedia_Hematology$$$corpus_2453", "text": "X-linked thrombocytopenia is typically diagnosed in infancy. The disease presents as a bleeding disorder with easy bruising, mucosal bleeding, such as nosebleeds, and mild to severe anemia.  Anemia  is a condition in which there is an insufficient number of red blood cells to carry adequate levels of oxygen to the body's tissues. [ 2 ]  X-linked thrombocytopenia is considered to be the milder phenotype of the  WAS -related disorders. As age increases, the severity of symptoms tends to decrease. However, individuals with X-linked thrombocytopenia have an increased risk for life-threatening brain hemorrhages and spontaneous bleeding. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2454", "text": "X-linked thrombocytopenia is inherited on the  X chromosome . Females that are carriers will have a 50% chance of passing the  WAS  gene mutation on to their male offspring. Female offspring also have a 50% chance of receiving the mutated gene from their mothers and are considered carriers in that event. Males with X-linked thrombocytopenia will not pass the condition to their sons since they pass their Y chromosome on to any male offspring. However, any daughters males with this condition have will be carriers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2455", "text": "X-linked thrombocytopenia primarily affects the circulatory system, specifically the  platelets  in the blood. Platelets are cell fragments in the blood that aid in clotting. Platelets are produced in the  bone marrow . Normal platelet counts range from 150,000 to 450,000 platelets per \u03bcL of blood. [ 3 ]  Individuals with XLT usually have drastically reduced platelet counts, typically less than 70,000 platelets per \u03bcL of blood. Not only are there fewer platelets circulating, but individuals with XLT also have smaller platelets. Fewer and smaller platelets causes the efficacy of the clotting mechanism in the body to be seriously compromised, which can lead to bruising and bleeding. X-linked thrombocytopenia is caused by a  mutation  of the  WAS  gene. This mutation causes the decreased, absent, or altered  Wiskott\u2013Aldrich syndrome protein  (WASp). Normal WASp is involved in relaying signals from the  cell membrane  to the actin  cytoskeleton . If WASp is decreased, absent, or altered, then the  hematopoietic  cells it is found in will show signaling and cytoskeleton abnormalities. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2456", "text": "This form of thrombocytopenia is inherited on X chromosome, thus individuals with this disorder are typically males. In regards to the sex chromosomes, males have one X chromosome and one  Y chromosome  while females have two X chromosomes. Because males only have one X chromosome, if they receive an X chromosome with a  WAS  gene mutation from their mother, then they will show phenotype of the condition. Females can be carriers for this disorder, which means that they have one normal X chromosome and one X chromosome with the  WAS  gene mutation. Females that are carriers do not show any signs or symptoms of X-linked thrombocytopenia. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2457", "text": "Males with X-linked thrombocytopenia are also susceptible to severe infections, bleeding,  autoimmune diseases  and malignancies."}
{"_id": "WikiPedia_Hematology$$$corpus_2458", "text": "Aside from observing the symptoms characteristic of X-linked thrombocytopenia in infancy (easy bruising, mild anemia, mucosal bleeding), molecular  genetic testing  would be done to confirm the diagnosis. Furthermore,  flow cytometry  or  western blotting  would be used to test for decreased or absent amounts of WASp. Family history would also assist in diagnosis, with specific attention to maternally related males with  WAS -related disorders. Because  WAS -related disorders are phenotypically similar, it is important to confirm the absence of the diagnostic criteria for Wiskoff-Aldrich syndrome at the outset. [ 4 ]  These diagnostic criteria include  eczema ,  lymphoma ,  autoimmune disorder , recurrent bacterial or viral infections, family history of maternally related males with a  WAS -related disorder, and absent or decreased  WASp . X-linked congenital neutropenia can be diagnostically distinguished from XLT with persistent  neutropenia , arrested development of the bone marrow, and normal  WASp  expression. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2459", "text": "Treatment for individuals with X-linked thrombocytopenia is typically focused on managing symptoms of the disorder.  Splenectomy  has been shown to improve platelet counts but also significantly increases the risk of life-threatening infections for patients with XLT. Therefore, these individuals must take antibiotics for the rest of their life to avoid fatal  bacteremia . In the event of significant bleeding, platelet  transfusions  should be administered. Circumcision should be avoided for infant males with XLT due to the risk of bleeding and infection. Regular follow ups to track blood counts should be utilized as well as confirming that any medications, over the counter or prescription, will not interfere with platelet functioning. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2460", "text": "Recent studies have found that the life expectancy of males with XLT is not significantly affected. [ 5 ]  Individuals with XLT typically experience milder symptoms than those with other  WAS -related disorders. For this reason, the long term prognosis for individuals with XLT is generally positive as long as symptoms are managed appropriately. Enhanced treatment methods in the past two decades have significantly improved the prognosis as well. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2461", "text": "Recent research has suggested that  hematopoietic stem cell transplantation  may be a treatment option for patients with XLT despite associated risks. [ 6 ]  Other studies have shown that treatment with  corticosteroids  or intravenous  immunoglobulin  in any dose or duration may have a beneficial impact on platelet counts, although transiently. [ 7 ]  Furthermore, research has shown that  splenectomy  may not be a good treatment option for patients with XLT as it increases the risk of severe infections. This same research showed that patients with XLT have a high overall survival rate but they are at risk for severe life-threatening complications associated with this disorder, such as serious bleeding events and malignancies. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2462", "text": "A  blood test  is a  laboratory  analysis performed on a  blood  sample that is usually extracted from a  vein  in the arm using a  hypodermic needle , or via  fingerprick . Multiple tests for specific blood components, such as a  glucose test  or a  cholesterol test , are often grouped together into one  test panel  called a  blood panel  or  blood work . Blood tests are often used in  health care  to determine  physiological  and  biochemical  states, such as  disease ,  mineral  content,  pharmaceutical drug  effectiveness, and organ function. Typical  clinical  blood panels include a  basic metabolic panel  or a  complete blood count . Blood tests are also used in  drug tests  to detect drug abuse."}
{"_id": "WikiPedia_Hematology$$$corpus_2463", "text": "A  venipuncture  is useful as it is a  minimally invasive  way to obtain  cells  and  extracellular fluid  ( plasma ) from the body for analysis. Blood flows throughout the body, acting as a medium that provides  oxygen  and nutrients to tissues and carries waste products back to the excretory systems for disposal. Consequently, the state of the bloodstream affects or is affected by, many medical conditions. For these reasons, blood tests are the most commonly performed  medical tests . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2464", "text": "If only a few drops of blood are needed, a  fingerstick  is performed instead of a  venipuncture . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2465", "text": "Indwelling arterial, central venous and peripheral venous lines can also be used to draw blood. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2466", "text": "Phlebotomists ,  laboratory practitioners  and  nurses  are those in charge of extracting blood from a patient. However, in special circumstances, and/or emergency situations,  paramedics  and  physicians  extract the blood. Also,  respiratory therapists  are trained to extract arterial blood to examine  arterial blood gases . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2467", "text": "A  basic metabolic panel  measures  sodium ,  potassium ,  chloride ,  bicarbonate ,  blood urea nitrogen  (BUN),  magnesium ,  creatinine ,  glucose , and sometimes  calcium . Tests that focus on cholesterol levels can determine  LDL  and  HDL cholesterol  levels, as well as  triglyceride  levels. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2468", "text": "Some tests, such as those that measure glucose or a  lipid profile , require fasting (or no food consumption) eight to twelve hours prior to the drawing of the blood sample. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2469", "text": "For the majority of tests, blood is usually obtained from the patient's vein. Other specialized tests, such as the  arterial blood gas  test, require blood extracted from an  artery . Blood gas analysis of arterial blood is primarily used to monitor  carbon dioxide  and  oxygen  levels related to  pulmonary  function, but is also used to measure blood  pH  and  bicarbonate  levels for certain metabolic conditions. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2470", "text": "While the regular  glucose test  is taken at a certain point in time, the  glucose tolerance test  involves repeated testing to determine the rate at which  glucose  is processed by the body. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2471", "text": "Blood tests are also used to identify autoimmune diseases and  Immunoglobulin E -mediated food allergies (see also  Radioallergosorbent test ). [ 10 ] :\u200a1118"}
{"_id": "WikiPedia_Hematology$$$corpus_2472", "text": "Blood tests results should always be interpreted using the ranges provided by the laboratory that performed the test. Example ranges are shown below."}
{"_id": "WikiPedia_Hematology$$$corpus_2473", "text": "Upon completion of a blood test analysis, patients may receive a report with blood test abbreviations. Examples of common blood test abbreviations are shown below."}
{"_id": "WikiPedia_Hematology$$$corpus_2474", "text": "(UK: FBC)"}
{"_id": "WikiPedia_Hematology$$$corpus_2475", "text": "(UK: Full Blood Count)"}
{"_id": "WikiPedia_Hematology$$$corpus_2476", "text": "In 2008, scientists announced that the more cost effective  saliva testing  could eventually replace some blood tests, as saliva contains 20% of the proteins found in blood. [ 15 ]  Saliva testing may not be appropriate or available for all markers. For example, lipid levels cannot be measured with saliva testing."}
{"_id": "WikiPedia_Hematology$$$corpus_2477", "text": "In February 2011, Canadian researchers at the University of Calgary's Schulich School of Engineering announced a microchip for blood tests. Dubbed a microemulsion, a droplet of blood captured inside a layer of another substance. It can control the exact size and spacing of the droplets. The new test could improve the efficiency, accuracy, and speed of laboratory tests while also doing it cheaply. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2478", "text": "In March 2011, a team of researchers from  UC Berkeley ,  DCU  and  University of Valpara\u00edso  have developed  lab-on-a-chip  that can diagnose diseases within 10 minutes without the use of external tubing and extra components. It is called Self-powered Integrated Microfluidic Blood Analysis System (SIMBAS). It uses tiny trenches to separate blood cells from plasma (99 percent of blood cells were captured during experiments). Researchers used plastic components, to reduce manufacturing costs. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2479", "text": "The  Abelin reaction  is a qualitative reaction for demonstrating the presence of  arsphenamine  and  neoarsphenamine  in  blood  and  urine ."}
{"_id": "WikiPedia_Hematology$$$corpus_2480", "text": "It is named for  Isaak Abelin , Swiss physiologist. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2481", "text": "Absolute neutrophil count  (ANC) is a measure of the number of  neutrophil granulocytes [ 1 ]  (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the  blood . Neutrophils are a type of  white blood cell  that fights against  infection ."}
{"_id": "WikiPedia_Hematology$$$corpus_2482", "text": "The ANC is almost always a part of a larger  blood panel  called the  complete blood count . The ANC is calculated from measurements of the total number of white blood cells (WBC), usually based on the combined percentage of mature neutrophils (sometimes called \"segs\", or segmented cells) and  bands , which are immature neutrophils."}
{"_id": "WikiPedia_Hematology$$$corpus_2483", "text": "The  reference range for ANC  in adults varies by study, but 1500 to 8000 cells per microliter is typical. An ANC less than 1500 cells/\u03bcL is defined as neutropenia and increases risk of infection.   Neutropenia  is the condition of a low ANC, and the most common condition where an ANC would be measured is in the setting of chemotherapy for cancer. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2484", "text": "Neutrophilia  indicates an elevated count.  While many clinicians refer to the presence of neutrophilia as a \"left shift\", this is imprecise, as a left shift indicates the presence of immature neutrophil forms, [ citation needed ]  but neutrophilia refers to the entire mass of neutrophils, both mature and immature.  Neutrophilia can be indicative of:"}
{"_id": "WikiPedia_Hematology$$$corpus_2485", "text": "ANC =  \n \n \n \n \n ( \n % \n n \n e \n u \n t \n r \n o \n p \n h \n i \n l \n s \n + \n % \n b \n a \n n \n d \n s \n ) \n \u00d7 \n ( \n W \n B \n C \n ) \n \n \n ( \n 100 \n ) \n \n \n \n {\\displaystyle (\\%neutrophils+\\%bands)\\times (WBC) \\over (100)}"}
{"_id": "WikiPedia_Hematology$$$corpus_2486", "text": "or"}
{"_id": "WikiPedia_Hematology$$$corpus_2487", "text": "ANC = ( Absolute-Polys + Absolute-Bands )"}
{"_id": "WikiPedia_Hematology$$$corpus_2488", "text": "[ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2489", "text": "In some cases, a ratio is reported in addition to the sum. This is known as the \"I/T ratio\". [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2490", "text": "The  ACTH test  (also called the  cosyntropin ,  tetracosactide , or  Synacthen test ) is a  medical test  usually requested and interpreted by  endocrinologists  to assess the functioning of the  adrenal glands ' stress response by measuring the adrenal response to  adrenocorticotropic hormone  (ACTH; corticotropin) or another  corticotropic   agent  such as  tetracosactide  (cosyntropin, tetracosactrin; Synacthen) or  alsactide  (Synchrodyn). [ 1 ] [ 2 ]  ACTH is a hormone produced in the  anterior pituitary gland  that stimulates the adrenal glands to release  cortisol ,  dehydroepiandrosterone  (DHEA),  dehydroepiandrosterone sulfate  (DHEA-S), and  aldosterone . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2491", "text": "During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol (and sometimes aldosterone) that the adrenals produce in response is measured. [ 4 ]  This test may cause mild side effects in some individuals. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2492", "text": "This test is used to diagnose or exclude primary and secondary  adrenal insufficiency ,  Addison's disease , and related conditions. [ 2 ]  In addition to quantifying adrenal insufficiency, the test can distinguish whether the cause is adrenal (low cortisol and aldosterone production) or pituitary (low ACTH production). [ 1 ]  The  insulin tolerance test  is recognized as the gold standard assay of adrenal insufficiency, but due to the cumbersome requirement for a two-hour test and the risks of seizures or myocardial infarction, the ACTH stimulation test is commonly used as an easier, safer, though not as accurate, alternative. [ 7 ]  The test is extremely sensitive (97% at 95% specificity) to primary adrenal insufficiency, but less so to secondary adrenal insufficiency (57\u201361% at 95% specificity); while secondary adrenal insufficiency may thus be dismissed by some interpreters on the basis of the test, additional testing may be called for if the probability of secondary adrenal insufficiency is particularly high. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2493", "text": "Adrenal insufficiency is a potentially life-threatening condition. Treatment should be initiated as soon as the diagnosis is confirmed, or sooner if the patient presents in apparent adrenal crisis. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2494", "text": "This test can be given as a  low-dose short test , a  conventional-dose short test , or as a  prolonged-stimulation test . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2495", "text": "In the low-dose short test, 1\u00a0\u03bcg of an ACTH drug is injected into the patient. In the conventional-dose short test, 250\u00a0\u03bcg of drug are injected. Both of these short tests last for about an hour and provide the same information. Studies have shown the cortisol response of the adrenals is the same for the low-dose and conventional-dose tests. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2496", "text": "The prolonged-stimulation test, which is also called a  long conventional-dose test , can last up to 48 hours. This form of the test can differentiate between primary, secondary, and tertiary adrenal insufficiency. This form of the test is rarely performed because earlier testing of cortisol and ACTH levels in association with the short test may provide all the necessary information. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2497", "text": "The test should not be given if on  glucocorticoids  or adrenal extract supplement, as these will affect test results. Stress and recently administered  radioisotope  scans [ citation needed ]  can artificially increase levels and may invalidate test results.  Spironolactone ,  contraceptives ,  licorice ,  estrogen ,  androgen  (including DHEA) and  progesterone  therapy may also affect both aldosterone and cortisol stimulation test results. To stimulate aldosterone, consumption of salt should be reduced to a minimum, and foods high in sodium avoided for 24 hours prior to testing. Women should ideally undergo testing during the first week of their menstrual cycle as aldosterone (and occasionally cortisol) may be falsely elevated in the luteal cycle secondary to progesterone inhibition, leading to a compensatory rise in aldosterone levels. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2498", "text": "Traditionally, cortisol and ACTH levels (separate lavender top tube) are drawn at baseline (time = 0). Next, synthetic ACTH or another corticotropic agent is injected IM or IV, depending on the agent. [ 12 ]  Approximately 20 mL of heparinized venous blood is collected at 30 and 60 minutes after the synthetic ACTH injection to measure cortisol levels. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2499", "text": "ACTH samples are kept on ice and sent immediately to the laboratory, whereas cortisol does not need to be kept on ice. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2500", "text": "Commonly reported reactions are nausea, anxious sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations (a fast or fluttering heart beat), and facial flushing (may also include arms and torso), but should disappear within a few hours. [ 5 ] [ 6 ]  Rarely seen, but serious side effects include rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2501", "text": "In healthy individuals, the cortisol level should increase above 18\u201320\u00a0\u03bcg/dl within 60 minutes on a 250\u00a0mcg cosyntropin stimulation test. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2502", "text": "In Addison's disease, both the cortisol and  aldosterone  levels are low, and the cortisol will not rise during the cosyntropin stimulation test [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2503", "text": "In secondary adrenal insufficiency, due to exogenous steroid administration suppressing pituitary production of ACTH or due to primary pituitary disorder causing insufficient ACTH production, the adrenal glands will  atrophy  over time and cortisol production will fall and patients will fail stimulation testing. Early in the development of secondary adrenal insufficiency, the adrenals may not have atrophied and can still stimulate, resulting in a normal cosyntropin stimulation test. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2504", "text": "If secondary adrenal insufficiency is diagnosed, the insulin tolerance test (ITT) or the CRH ( corticotropin-releasing hormone ) stimulation test can be used to distinguish between a hypothalamic (tertiary) and pituitary (secondary) cause but is rarely used in clinical practice. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2505", "text": "Measuring a morning, fasting ACTH level helps assess for the etiology of adrenal insufficiency. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2506", "text": "ACTH will be high [ 13 ]  \u2013 usually well above upper limits of reference range."}
{"_id": "WikiPedia_Hematology$$$corpus_2507", "text": "ACTH will be low [ 13 ]  \u2013 usually below 35, but most people with secondary fall within the range limit. This is inappropriately normal for the low cortisol level."}
{"_id": "WikiPedia_Hematology$$$corpus_2508", "text": "In some cases, the actual cause of low ACTH is from low CRH in the hypothalamus. It is possible to have separate ACTH and CRH impairment such as can happen in a head injury. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2509", "text": "The ACTH stimulation test is occasionally used to test adrenal production of aldosterone at the same time as cortisol to also help in determining if primary (hyperreninemic) or secondary (hyporeninemic)  hypoaldosteronism  is present. [ 4 ]  Human ACTH has a slight stimulatory effect on aldosterone, [ 19 ]  but the amount of synthetic ACTH given in the stimulation is equivalent to more than a whole days production of natural ACTH, so the aldosterone response can be easily measured in blood serum. [ 20 ]  Same as cortisol, aldosterone should double from a respectable base value (around 20\u00a0ng/dl, must fast salt 24 hours and sit upright for blood draw) in a healthy individual. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2510", "text": "The aldosterone response in the ACTH stimulation test is blunted or absent in patients with primary adrenal insufficiency including Addison's disease. [ 4 ]  The base value is usually in the mid-teens or less and rise to less than double the base value thus indicating primary hypoaldosteronism ( sodium  low,  potassium  and renin  enzyme  will be high) and is an indicator of primary adrenal insufficiency or Addison's disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2511", "text": "Aldosterone response of several factors from a low base value. This factoring indicates secondary hypoaldosteronism (sodium low, potassium and renin enzyme will be low). Usually doubling to quadrupling from a low base aldosterone value is what is seen in secondary adrenal insufficiency. Decoupling of aldosterone in the ACTH stimulation test is possible (i.e. 2\u00a0ng/dl stimming to 20). [ 21 ]  A result of doubling or more of aldosterone may help in tandem with a cortisol stimulation that doubled or more confirm a diagnosis of secondary adrenal insufficiency. In rare cases, an aldosterone stimulation which did not double, but with the presence of low potassium, low renin and low ACTH indicates atrophy of aldosterone production from the prolonged lack of renin."}
{"_id": "WikiPedia_Hematology$$$corpus_2512", "text": "Similar to the cortisol stimulation in ACTH deficiency, the test interpreter may lack knowledge of how to properly interpret for secondary hypoaldosteronism and think a result of aldosterone doubling or more from a low base value is good."}
{"_id": "WikiPedia_Hematology$$$corpus_2513", "text": "Recent data showed that Synacthen test results can be used to predict future recovery of HPA axis function in patients with reversible causes of Adrenal Insufficiency. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2514", "text": "The test is also used to diagnose  hypoadrenocorticism in dogs  and sometimes cats. [ 27 ] [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2515", "text": "The  activated protein C resistance  ( APCR )  test  is a  coagulation test  used in the evaluation and  diagnosis  of  activated protein C (APC) resistance , a form of  hypercoagulability . [ 1 ] [ 2 ]  Hereditary APC resistance is usually caused by the  factor V Leiden  mutation, whereas acquired APC resistance has been linked to  antiphospholipid antibodies ,  pregnancy , and  estrogen  therapy. [ 3 ] [ 4 ] [ 5 ] [ 6 ]  APC resistance can be measured using either an  activated partial thromboplastin time  (aPTT)-based test or an  endogenous thrombin potential (ETP)-based test . [ 5 ] [ 4 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2516", "text": "The aPTT-based APC resistance test involves a modified aPTT test performed in the presence and absence of  activated protein C  (APC). [ 1 ] [ 5 ]  The ratio of these aPTT values is calculated and is called the APC sensitivity ratio (APCsr) or simply APC ratio (APCr). [ 1 ] [ 5 ]  This ratio is inversely related to the degree of APC resistance. [ 7 ]  The ETP-based APC resistance test involves the addition of APC to a  thrombin generation assay  (TGA). [ 5 ]  This results in an inhibition of  thrombin generation  as measured by reduction of the  endogenous thrombin potential  (ETP; area under the thrombin generation curve). [ 5 ]  The result is expressed as a normalized APC sensitivity ratio (nAPCsr), which corresponds to the ratio of the ETP measured in the presence and absence of APC divided by the same ratio in reference plasma. [ 5 ]  nAPCsr values range from 0 to 10. [ 5 ]  Opposite to the case of the APCsr with the aPTT-based APC resistance test, higher nAPCsr values indicate greater APC resistance. [ 5 ] [ 8 ]  This is the result of the fact that APC prolongs the aPTT but inhibits thrombin generation. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2517", "text": "Whereas the aPTT-based APC resistance test only measures the initiation phase of  coagulation , the ETP-based test is a  global assay  and measures the initiation, propagation, and termination phases of coagulation. [ 5 ] [ 9 ]  The initiation phase accounts for less than 5% of total  thrombin generation , making aPTT-based tests poorly indicative of hypercoagulability in general. [ 10 ] [ 11 ]  The aPTT-based assay is more sensitive to levels of  prothrombin  and  factor VIII , whereas the ETP-based test is more sensitive to levels of  tissue factor pathway inhibitor  (TFPI) and  protein S . [ 5 ]  The ETP-based test has traditionally been performed using methods such as the  calibrated automated thrombogram  (CAT) and has been limitedly available due to its technical difficulty. [ 2 ]  Recently however, a fully automated commercial test system called the  ST Genesia  has been introduced, and it has been said that this should allow for adoption of TGAs and ETP-based APC resistance tests in routine clinical settings. [ 2 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2518", "text": "Estrogens  are well known to increase APC resistance, which has been described as acquired APC resistance. [ 2 ] [ 5 ] [ 4 ] [ 13 ] [ 14 ]  However, the aPTT-based APC resistance test is much less sensitive to the procoagulatory effects of estrogens than is the ETP-based test. [ 13 ] [ 14 ] [ 5 ] [ 4 ] [ 2 ] [ 15 ]   Pregnancy [ 7 ]  and  ethinylestradiol  (EE)-containing  combined birth control pills  increase APC resistance as measured by either the aPTT- or ETP-based test. [ 4 ] [ 5 ] [ 15 ]  EE-containing birth control pills show different degrees of influence on the ETP-based test depending on the  progestin , which may be due to varying degrees of  androgenic  antagonism of ethinylestradiol-mediated procoagulation. [ 5 ] [ 4 ]  In contrast to EE-containing birth control pills, studies have not found increased APC resistance with  menopausal hormone therapy  or with  estetrol - or  estradiol-containing birth control pills  using the aPTT-based test, though increased APC resistance has been shown with the ETP-based test. [ 14 ]  The increase in APC resistance is much greater with  oral  estrogens than with  transdermal   estradiol . [ 14 ]  Increased APC resistance with both the aPTT-based and ETP-based tests has been observed with  feminizing hormone therapy  in  transgender women , which involves higher doses of estradiol than are used in other contexts. [ 16 ] [ 17 ]  EE produces a much stronger increase in APC resistance than does estradiol. [ 18 ] [ 17 ]  In relation to this, ethinylestradiol is associated with a higher risk of  venous thromboembolism  (VTE) than is estradiol. [ 18 ] [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2519", "text": "The aPTT-based APC resistance test was developed in 1993, while the ETP-based test was developed in 1997. [ 5 ]  For many years, the ETP-based APC resistance test suffered from a lack of  standardization  which hampered study-to-study comparison. [ 21 ]  By 2020 however, a validated methodology was developed aiming to propose a standardized and  harmonized  scale for ETP-based APC resistance, the normalized activated protein C sensitivity ratio (nAPCsr). [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2520", "text": "Anisochromia  is a marked variability in the color density of  erythrocytes  (red blood cells), which indicates unequal  hemoglobin  content among the red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_2521", "text": "Sideroblastic anemia  or other severe forms of anemia may cause anisochromatism. It can also be seen after blood transfusions are administered, because blood products from multiple people may have different chromacity. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2522", "text": "Anti-neutrophil cytoplasmic antibodies  ( ANCAs ) are a group of  autoantibodies , mainly of the  IgG  type, against  antigens  in the  cytoplasm  of  neutrophils  (the most common type of  white blood cell ) and  monocytes . They are detected as a  blood test  in a number of  autoimmune disorders , but are particularly associated with systemic  vasculitis , so called ANCA-associated vasculitides (AAV). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2523", "text": "Immunofluorescence  (IF) on ethanol-fixed neutrophils is used to detect ANCA, although formalin-fixed neutrophils may be used to help differentiate ANCA patterns. ANCA can be divided into four patterns when visualised by IF; cytoplasmic ANCA (c-ANCA), C-ANCA (atypical), perinuclear ANCA (p-ANCA) and atypical ANCA (a-ANCA), also known as x-ANCA. c-ANCA shows cytoplasmic granular fluorescence with central interlobular accentuation. C-ANCA (atypical) shows cytoplasmic staining that is usually uniform and has no interlobular accentuation. p-ANCA has three subtypes, classical p-ANCA, p-ANCA without nuclear extension and granulocyte specific-antinuclear antibody (GS-ANA). Classical p-ANCA shows perinuclear staining with nuclear extension, p-ANCA without nuclear extension has perinuclear staining without nuclear extension and GS-ANA shows nuclear staining on granulocytes only. a-ANCA often shows combinations of both cytoplasmic and perinuclear staining. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2524", "text": "The c-ANCA antigen is specifically  proteinase 3  (PR3). p-ANCA antigens include  myeloperoxidase  (MPO) and bacterial permeability increasing factor  Bactericidal/permeability-increasing protein  (BPI). Other antigens exist for c-ANCA (atypical), however many are as yet unknown. Classical p-ANCA occurs with antibodies directed to MPO. p-ANCA without nuclear extension occurs with antibodies to BPI,  cathepsin G ,  elastase ,  lactoferrin  and  lysozyme . GS-ANA are antibodies directed to granulocyte specific nuclear antigens. Atypical ANCA are thought to be antigens similar to that of the p-ANCAs, however may occur due to differences in neutrophil processing. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2525", "text": "Other less common antigens include  HMG1  (p-ANCA pattern),  HMG2  (p-ANCA pattern),  alpha enolase  (p and c-ANCA pattern),  catalase  (p and c-ANCA pattern),  beta glucuronidase  (p-ANCA pattern),  azurocidin  (p and c-ANCA pattern),  actin  (p and a-ANCA) and  h-lamp-2  (c-ANCA). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2526", "text": "Enzyme-linked immunosorbent assay  (ELISA) is used in diagnostic laboratories to detect ANCAs. Although IF can be used to screen for many ANCAs, ELISA is used to detect antibodies to individual antigens. The most common antigens used on an ELISA  microtitre plate  are MPO and PR3, which are usually tested for after a positive IF test. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2527", "text": "It is poorly understood how ANCA are developed, although several hypotheses have been suggested. There is probably a genetic contribution, particularly in genes controlling the level of immune response \u2013 although genetic susceptibility is likely to be linked to an environmental factor, some possible factors including vaccination or exposure to silicates. Two possible mechanisms of ANCA development are postulated, although neither of these theories answers the question of how the different ANCA specificities are developed, and there is much research still being undertaken on the development of ANCA. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2528", "text": "Microbial  superantigens  are molecules expressed by bacteria and other microorganisms that have the power to stimulate a strong immune response by activation of  T-cells . These molecules generally have regions that resemble self-antigens that promote a residual autoimmune response \u2013 this is the theory of molecular mimicry.  Staphylococcal  and  streptococcal   superantigens  have been characterized in autoimmune diseases \u2013 the classical example in post group A streptococcal  rheumatic heart disease , where there is similarity between  M proteins  of  Streptococcus pyogenes  to cardiac  myosin  and  laminin . It has also been shown that up to 70% of patients with  granulomatosis with polyangiitis  are chronic nasal carriers of  Staphylococcus aureus , with carriers having an eight times increased risk of  relapse . [ 4 ]   This would therefore be considered a  type II hypersensitivity  reaction. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2529", "text": "Neutrophil  apoptosis , or programmed cell death, is vital in controlling the duration of the early inflammatory response, thus restricting damage to tissues by the neutrophils. ANCA may be developed either via ineffective apoptosis or ineffective removal of apoptotic cell fragments, leading to the exposure of the immune system to molecules normally sequestered inside the cells. This theory solves the paradox of how it could be possible for antibodies to be raised against the intracellular antigenic targets of ANCA. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2530", "text": "ANCAs are associated with small vessel  vasculitides  including  granulomatosis with polyangiitis ,  microscopic polyangiitis ,  primary pauci-immune necrotizing crescentic glomerulonephritis  (a type of renal-limited microscopic polyangiitis),  eosinophilic granulomatosis with polyangiitis  and drug induced vasculitides. ANCA-associated vasculitides (AAV) have new classification criteria, updated in 2022. [ 5 ] [ 6 ] \nPR3 directed c-ANCA is present in 80-90% of granulomatosis with polyangiitis, 20-40% of microscopic polyangiitis, 20-40% of pauci-immune crescentic glomerulonephritis and 35% of eosinophilic granulomatosis with polyangiitis. c-ANCA (atypical) is present in 80% of cystic fibrosis (with BPI as the target antigen) and also in  inflammatory bowel disease ,  primary sclerosing cholangitis  and  rheumatoid arthritis  (with antibodies to multiple antigenic targets). p-ANCA with MPO specificity is found in 50% of microscopic polyangiitis, 50% of primary pauci-immune necrotizing crescentic glomerulonephritis and 35% of eosinophilic granulomatosis with polyangiitis. p-ANCA with specificity to other antigens are associated with inflammatory bowel disease, rheumatoid arthritis, drug-induced vasculitis,  autoimmune liver disease , drug induced syndromes and parasitic infections. Atypical ANCA is associated with drug-induced systemic vasculitis, inflammatory bowel disease and rheumatoid arthritis. [ 3 ] [ 7 ]  The ANCA-positive rate is much higher in patients with type 1 diabetes mellitus than in healthy individuals. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2531", "text": "Levamisole , which is a common adulterant of  cocaine , can cause an ANCA positive vasculitis. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2532", "text": "The presence or absence of ANCA cannot indicate presence or absence of disease and results are correlated with clinical features. The association of ANCA and disease activity remains controversial; however, the reappearance of ANCA after treatment can indicate a relapse. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2533", "text": "Although the pathogenic role of ANCA is still controversial,  in vitro  and animal models support the idea that the antibodies have a direct pathological role in the formation of small vessel vasculitides. MPO and PR3 specific ANCA can activate  neutrophils  and  monocytes  through their  Fc  and Fab'2 receptors, which can be enhanced by  cytokines  which cause neutrophils to display MPO and PR3 on their surface. Aberrant glycosylation of the MPO and PR3 specific ANCA enhances their ability to interact with activating Fc receptors on neutrophils. [ 12 ]   The activated neutrophils can then adhere to  endothelial cells  where degranulation occurs. This releases free oxygen radicals and lytic enzymes, resulting in damage to the endothelium via the induction of  necrosis  and  apoptosis . Furthermore, neutrophils release chemoattractive signalling molecules that recruit more neutrophils to the endothelium, acting as a positive feedback loop. Animal models have shown that MPO antibodies can induce necrotizing crescentic glomerulonephritis and systemic small vessel vasculitis. In these animal models the formation of glomerulonephritis and vasculitis can occur in the absence of T-cells, however neutrophils must be present. [ 13 ] [ 14 ] [ 15 ] [ 16 ]  Although ANCA titres have been noted to have limited correlation with disease activity, except for kidney disease, and with risk of relapse, this is explained by differences in the  epitopes  and affinity of ANCAs. [ 17 ]  ANCAs induce excess activation of  neutrophils , resulting in the production of neutrophil extracellular traps (NETs), which cause damage to small blood vessels. [ 17 ]  In addition, in patients with active disease, treated with  Rituximab , an anti- CD20  antibody which remove circulating B-cells, clinical remission  correlates more to the decreasing number of circulating B-cells than decrease in ANCA titre, which in some patient does not change during treatment. The same study found that clinical relapse in some patients were in association with the return of circulating B-cells. [ 18 ]  Based on the above observations and that ANCA reactive  B-cells  can be found in circulation in patients with AAV, an alternative hypothesis have been proposed assigning  a direct pathogenic role of these cells, whereby activated neutrophils and ANCA-reactive B-cells engage in intercellular cross-talk, which leads not only to neutrophil degranulation and inflammation but also to the proliferation and differentiation of ANCA-reactive B-cells. [ 19 ]  However, this hypothesis remains to be tested."}
{"_id": "WikiPedia_Hematology$$$corpus_2534", "text": "Avacopan  was approved for medical use in the United States to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis in October 2021. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2535", "text": "ANCAs were originally described in Davies  et al.  in 1982 in  segmental necrotising glomerulonephritis . [ 17 ] [ 21 ]  The Second International ANCA Workshop, held in The Netherlands in May 1989, fixed the nomenclature on perinuclear vs. cytoplasmic patterns, and the antigens MPO and PR3 were discovered in 1988 and 1989, respectively. [ 22 ]  International ANCA Workshops have been carried out every two years. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2536", "text": "An  anticoagulant , commonly known as a  blood thinner , is a  chemical substance  that prevents or reduces the  coagulation  of  blood , prolonging the  clotting time . [ 1 ]  Some occur naturally in  blood-eating  animals, such as  leeches  and  mosquitoes , which help keep the bite area unclotted long enough for the animal to obtain blood. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2537", "text": "As a class of  medications , anticoagulants are used in  therapy  for  thrombotic disorders . [ 4 ]   Oral  anticoagulants (OACs) are taken by many people in  pill  or  tablet  form, and various  intravenous  anticoagulant  dosage forms  are used in hospitals. [ 5 ] [ 6 ]  Some anticoagulants are used in medical equipment, such as sample tubes,  blood transfusion  bags,  heart\u2013lung machines , and  dialysis  equipment. [ 7 ] [ 8 ]  One of the first anticoagulants,  warfarin , was initially approved as a  rodenticide . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2538", "text": "Anticoagulants are closely related to  antiplatelet drugs  and  thrombolytic  drugs by manipulating the various pathways of blood coagulation. [ 10 ]  Specifically, antiplatelet drugs inhibit platelet aggregation (clumping together), whereas anticoagulants inhibit specific pathways of the coagulation cascade, which happens after the initial platelet aggregation but before the formation of fibrin and stable aggregated platelet products. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2539", "text": "Common anticoagulants include warfarin and  heparin . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2540", "text": "The use of anticoagulants is a decision based on the risks and benefits of anticoagulation. [ 14 ]  The biggest risk of anticoagulation therapy is the increased risk of bleeding. [ 15 ]  In otherwise healthy people, the increased risk of bleeding is minimal, but those who have had recent surgery,  cerebral aneurysms , and other conditions may have too great a risk of bleeding. [ 16 ] [ 17 ]  Generally, the benefit of anticoagulation is preventing or reducing the progression of a thromboembolic disease. [ 18 ]  Some indications for anticoagulant therapy that are known to have benefit from therapy include:"}
{"_id": "WikiPedia_Hematology$$$corpus_2541", "text": "In these cases, anticoagulation therapy  prevents the formation  or growth of dangerous clots. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2542", "text": "The decision to begin therapeutic anticoagulation often involves the use of multiple bleeding risk predictable outcome tools as non-invasive pre-test stratifications due to the potential for bleeding while on blood thinning agents. [ 15 ]  Among these tools are  HAS-BLED , [ 31 ]  ATRIA, [ 32 ]  HEMORR2HAGES, [ 33 ]  and  CHA2DS2-VASc . [ 34 ]  The risk of bleeding using the risk assessment tools above must then be weighed against thrombotic risk to formally determine the patient's overall benefit in starting anticoagulation therapy. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2543", "text": "There is no evidence to indicate that adding anticoagulant therapy to standard treatment has a benefit for people with cerebral small vessel disease but not dementia, and there is an increased risk of a person with this disease experiencing a bleed with this approach. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2544", "text": "The most serious and common adverse side effects associated with anticoagulants are increased risk of bleeding, both nonmajor and major bleeding events. [ 37 ]  The bleeding risk depends on the class of anticoagulant agent used, the patient's age, and pre-existing health conditions. Warfarin has an estimated incidence of bleeding of 15-20% per year and a life-threatening bleeding rate of 1-3% per year. [ 38 ]  Newer non-vitamin K antagonist oral anticoagulants appear to have fewer life-threatening bleeding events than warfarin. [ 39 ] [ 40 ]  Additionally, patients aged 80 years or more may be especially susceptible to bleeding complications, with a rate of 13 bleeds per 100 person-years. [ 41 ]  Bleeding risk is especially important to consider in patients with renal impairment and NOAC therapy because all NOACs, to some extent, are excreted by the kidneys. [ 42 ]  Thus, patients with renal impairment may be at higher risk of increased bleeding. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2545", "text": "In people with cancer, a systematic review has found warfarin had no effect on death rate or the risk of blood clots. [ 44 ]  However, it did increase the risk of major bleeding in 107 more people per 1000 population and minor bleeding in 167 more people per 1000 population. [ 44 ]  Apixaban had no effect on mortality, recurrence of blood clots in blood vessels, or major or minor bleeding. However, this finding comes only from one study. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2546", "text": "Nonhemorrhagic adverse events are less common than hemorrhagic adverse events but should still be monitored closely. [ 39 ]  Nonhemorrhagic adverse events of warfarin  include skin  necrosis , limb gangrene, and purple toe syndrome. [ 45 ]  Skin necrosis and limb gangrene are most commonly observed on the third to eighth day of therapy. [ 46 ] [ 47 ]  The exact pathogenesis of skin necrosis and limb gangrene is not completely understood but it is believed to be associated with warfarin's effect on inhibiting the production of protein C and protein S. [ 48 ] [ 49 ]  Purple toe syndrome typically develops three to eight weeks after initiation of warfarin therapy. [ 50 ] [ 51 ]  Other adverse effects of warfarin are associated with depletion of vitamin K, which can lead to inhibition of G1a proteins and growth arrest-specific gene 6, which can lead to increased risk of arterial calcification and heart valve, especially if too much Vitamin D is present. [ 52 ] [ 53 ]  Warfarin's interference with G1a proteins has also been linked to abnormalities in fetal bone development in mothers who were treated with warfarin during pregnancy. [ 54 ] [ 55 ]  Long-term warfarin and heparin usage have also been linked to osteoporosis. [ 56 ] [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2547", "text": "Another potentially severe complication associated with heparin use is called heparin-induced thrombocytopenia (HIT). [ 57 ]  There are two distinct types: HIT 1) immune-mediated and 2) non-immune-mediated. [ 57 ]  Immune-mediated HIT most commonly arises five to ten days after exposure to heparin. [ 58 ]  Pathogenesis of immune-mediated HIT is believed to be caused by heparin-dependent immunoglobulin antibodies binding to platelet factor 4/heparin complexes on platelets, leading to widespread platelet activation. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2548", "text": "Foods and  food supplements  with blood-thinning effects include  nattokinase ,  lumbrokinase ,  beer ,  bilberry ,  celery ,  cranberries ,  fish oil ,  garlic ,  ginger ,  ginkgo ,  ginseng ,  green tea ,  horse chestnut ,  licorice ,  niacin ,  onion ,  papaya ,  pomegranate ,  red clover ,  soybean ,  St. John's wort ,  turmeric ,  wheatgrass , and  willow  bark. [ 60 ] [ 61 ] [ 62 ]  Many herbal supplements have blood-thinning properties, such as  danshen  and  feverfew . [ 63 ]  Multivitamins that do not interact with clotting are available for patients on anticoagulants. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2549", "text": "However, some foods and supplements encourage clotting. [ 65 ]  These include  alfalfa ,  avocado ,  cat's claw ,  coenzyme Q10 , and dark leafy greens such as  spinach . [ 66 ] [ 67 ]  Excessive intake of the food mentioned above should be avoided while taking anticoagulants, or if coagulability is being monitored, their intake should be kept approximately constant so that anticoagulant dosage can be maintained at a level high enough to counteract this effect without fluctuations in coagulability. [ 68 ] [ 69 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2550", "text": "Grapefruit  interferes with some anticoagulant drugs, increasing the time it takes for them to be metabolized out of the body, and should be eaten with caution when on anticoagulant drugs. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2551", "text": "Anticoagulants are often used to treat acute  deep-vein thrombosis . [ 71 ] [ 72 ]  People using anticoagulants to treat this condition should avoid using  bed rest  as a complementary treatment because there are clinical benefits to continuing to walk and remaining mobile while using anticoagulants in this way. [ 73 ]  Bed rest while using anticoagulants can harm patients in circumstances in which it is not medically necessary. [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2552", "text": "Several anticoagulants are available. Warfarin, other coumarins, and heparins have long been used. [ 74 ]  Since the 2000s, several agents have been introduced that are collectively referred to as  direct oral anticoagulants  ( DOACs ), previously named  novel oral anticoagulants  ( NOACs ) or  non-vitamin K antagonist oral anticoagulants . [ 75 ] [ 76 ] [ 77 ] [ 78 ]  These agents include direct thrombin inhibitor ( dabigatran ) and factor Xa inhibitor ( rivaroxaban ,  apixaban ,  betrixaban  and  edoxaban ), and they have been shown to be as good or possibly better than the coumarins with less serious side effects. [ 79 ]  The newer anticoagulants (NOACs/DOACs) are more expensive than the traditional ones and should be used in caring for patients with kidney problems. [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2553", "text": "These oral anticoagulants are derived from  coumarin  found in many plants. A prominent member of this class,  warfarin  (Coumadin), was found to be the anticoagulant most prescribed in a large multispecialty practice. [ 81 ]  The anticoagulant effect takes at least 48 to 72 hours to develop. Where an immediate effect is required,  heparin  is given concomitantly. These anticoagulants are used to treat patients with  deep-vein thrombosis  (DVT) and  pulmonary embolism  (PE) and to prevent emboli in patients with  atrial fibrillation  (AF), and mechanical  prosthetic heart valves . Other examples are  acenocoumarol ,  phenprocoumon ,  atromentin , and  phenindione . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2554", "text": "The coumarins  brodifacoum  and  difenacoum  are used as mammalicides (particularly as  rodenticides ) but are not used medically. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2555", "text": "Heparin is the most widely used intravenous clinical anticoagulant worldwide. [ 82 ]   Heparin  is a naturally occurring  glycosaminoglycan . There are three major categories of heparin: unfractionated heparin (UFH), low molecular weight heparin (LMWH), and ultra-low-molecular weight heparin (ULMWH). [ 83 ]   Unfractionated heparin is usually derived from  pig  intestines and bovine lungs. [ 84 ]  UFH binds to the enzyme inhibitor  antithrombin  III (AT), causing a conformational change that results in its activation. [ 85 ]  The activated AT then inactivates  factor Xa ,  thrombin , and other coagulation factors. [ 86 ]  Heparin can be used  in vivo  (by injection), and also  in vitro  to prevent blood or plasma clotting in or on medical devices. In  venipuncture ,  Vacutainer  brand blood collecting tubes containing heparin usually have a green cap. [ 87 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2556", "text": "Low molecular weight heparin  (LMWH) is produced through a controlled depolymerization of unfractionated heparin. [ 83 ]  LMWH exhibits a higher anti-Xa/anti-IIa activity ratio and is useful as it does not require monitoring of the  APTT   coagulation  parameter and has fewer side effects. [ 83 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2557", "text": "The direct oral anticoagulants (DOACs) were introduced in and after 2008. [ 88 ]  There are five DOACs currently on the market:  dabigatran ,  rivaroxaban ,  apixaban ,  edoxaban  and  betrixaban . [ 89 ]  They were also previously referred to as \"new/novel\" and \"non-vitamin K antagonist\" oral anticoagulants (NOACs). [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2558", "text": "Compared to warfarin, DOACs have a rapid onset action and relatively short half-lives; hence, they carry out their function more rapidly and effectively, allowing drugs to reduce their anticoagulation effects quickly. [ 91 ]   Routine monitoring and dose adjustments of DOACs are less important than for warfarin, as they have better predictable anticoagulation activity. [ 92 ]  DOAC monitoring, including laboratory monitoring and a complete medication review, should generally be conducted before initiation of a DOAC, 1\u20133 months after initiation, and then every 6\u201312 months afterwards. [ 93 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2559", "text": "Both DOACs and warfarin are equivalently effective, but compared to warfarin, DOACs have fewer drug interactions, no known dietary interactions, a wider therapeutic index, and have conventional dosing that does not require dose adjustments with constant monitoring. [ 94 ] [ 92 ]  However, there is no countermeasure for most DOACs, unlike for warfarin; nonetheless, the short half-lives of DOACs will allow their effects to recede swiftly. A reversal agent for dabigatran,  idarucizumab , is currently available and approved for use by the FDA. Rates of adherence to DOACs are only modestly higher than adherence to warfarin among patients prescribed these drugs. Thus, adherence to anticoagulation is often poor despite hopes that DOACs would lead to higher adherence rates. [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2560", "text": "DOACs are significantly more expensive than warfarin, but the patients on DOACs may experience reduced lab costs as they do not need to monitor their INR. [ 93 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2561", "text": "Drugs such as  rivaroxaban ,  apixaban  and  edoxaban  work by inhibiting factor Xa directly (unlike heparins and fondaparinux, which work via antithrombin activation).\nAlso included in this category are  betrixaban  from Portola Pharmaceuticals, the discontinued  darexaban  (YM150) from Astellas, and, more recently,  the discontinued  letaxaban  (TAK-442) from Takeda and  eribaxaban  (PD0348292) from Pfizer.\nBetrixaban is significant as it was in 2018, the only oral factor Xa inhibitor approved by the FDA for use in acutely medically ill patients. [ 96 ]  Darexaban development was discontinued in September 2011; in a trial for prevention of recurrences of myocardial infarction in addition to dual antiplatelet therapy (DAPT), the drug did not demonstrate effectiveness, and the risk of bleeding was increased by approximately 300%. [ 97 ]  The development of letaxaban for acute coronary syndrome was discontinued in May 2011 following negative results from a Phase II study. [ 98 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2562", "text": "Another type of anticoagulant is the  direct thrombin inhibitor . [ 99 ]  Current members of this class include the bivalent drugs  hirudin ,  lepirudin , and  bivalirudin  and the monovalent drugs  argatroban  and  dabigatran . An oral direct thrombin inhibitor,  ximelagatran  (Exanta), was denied approval by the  Food and Drug Administration  (FDA) in September 2004 [ 100 ]  and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks. [ 101 ]  In November 2010,  dabigatran etexilate  was approved by the FDA to prevent thrombosis in  atrial fibrillation ."}
{"_id": "WikiPedia_Hematology$$$corpus_2563", "text": "As in any invasive procedure, patients on anticoagulation therapy have an increased risk for bleeding, and caution should be used along with local  hemostatic  methods to minimize bleeding risk during the operation as well as postoperatively. [ 102 ]  However, with regards to DOACs and invasive dental treatments, there has not been enough clinical evidence and experience to prove any reliable adverse effects, relevance or interaction between these two. [ 103 ]  Further clinical prospective studies on DOACs are required to investigate the bleeding risk and hemostasis associated with surgical and dental procedures. [ 104 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2564", "text": "Recommendations of modifications to the usage/dosage of DOACs before dental treatments are made based on the balance of the bleeding risk of each procedure and also the individual's own bleeding risks and renal functionality. [ 105 ]  With low-bleeding-risk dental procedures, it is recommended that DOACs be continued by the patient to avoid any increase in the risk of a thromboembolic event. [ 106 ] [ 107 ]  For dental procedures with a higher risk of bleeding complications (i.e. complex extractions, adjacent extractions leading to a large wound, or more than three extractions), the recommended practice is for the patient to miss or delay a dose of their DOAC before such procedures to minimize the effect on bleeding risk. [ 108 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2565", "text": "The antithrombin protein is used as a  protein therapeutic  that can be purified from human plasma [ 109 ]  or produced recombinantly (for example, Atryn, produced in the milk of  genetically modified  goats). [ 110 ] [ 111 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2566", "text": "The FDA approves Antithrombin as an anticoagulant for preventing clots before, during, or after surgery or birthing in patients with hereditary antithrombin deficiency. [ 109 ] [ 111 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2567", "text": "Many other anticoagulants exist in  research and development ,  diagnostics , or as drug candidates."}
{"_id": "WikiPedia_Hematology$$$corpus_2568", "text": "With the growing number of patients taking oral anticoagulation therapy, studies into reversal agents are gaining increasing interest due to major bleeding events and the need for urgent anticoagulant reversal therapy. [ 112 ]  Reversal agents for warfarin are more widely studied, and established guidelines for reversal exist due to a longer history of use of warfarin and the ability to get a more accurate measurement of anticoagulation effect in a patient via measuring the INR (International Normalized Ratio). [ 113 ]  In general, vitamin K is most commonly used to reverse the effect of warfarin in non-urgent settings. [ 114 ]  However, in urgent settings or settings with extremely high INR (INR >20), hemostatic reversal agents such as fresh frozen plasma (FFP),  recombinant factor VIIa , and prothrombin complex concentrate (PCC) have been utilized with proven efficacy. [ 115 ]  Specifically with warfarin, four-factor PCC (4F-PCC) has been shown to have superior safety and mortality benefits compared to FPP in lowering INR levels. [ 112 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2569", "text": "Although specific antidotes and reversal agents for DOACs are not as widely studied,  idarucizumab  (for dabigatran) and  andexanet alfa  (for factor Xa inhibitor) have been used in clinical settings with varying efficacy. [ 90 ]   Idarucizumab is a monoclonal antibody, approved by the US FDA in 2015, that reverses the effect of dabigatran by binding to both free and thrombin-bound dabigatran. [ 116 ] [ 117 ]  Andexanet alfa is a recombinant modified human factor Xa decoy that reverses the effect of factor Xa inhibitors by binding at the active sites of factor Xa inhibitor and making it catalytically inactive. [ 118 ] [ 119 ]  Andexanet alfa was approved by the US FDA in 2018. [ 120 ]  Another drug called ciraparantag, a potential reversal agent for direct factor Xa inhibitors, is still under investigation. [ 121 ]  Additionally, hemostatic reversal agents have also been used with varying efficacy to reverse the effects of DOACs. [ 122 ] [ 123 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2570", "text": "A  Bethesda unit  ( BU ) is a measure of blood  coagulation inhibitor  activity. It is the amount of inhibitor that will inactivate half of a  coagulant  during the incubation period. [ 124 ]  It is the standard measure used in the United States and is so named because it was adopted as a standard at a conference in  Bethesda, Maryland . [ 125 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2571", "text": "If blood is allowed to clot,  laboratory  instruments, blood transfusion bags, and medical and surgical equipment will get clogged up and non-operational. In addition, test tubes used for laboratory blood tests will have chemicals added to stop blood clotting. Besides heparin, most of these chemicals  bind   calcium  ions, preventing the coagulation proteins from using them."}
{"_id": "WikiPedia_Hematology$$$corpus_2572", "text": "Dental practitioners play an important role in the early detection of anticoagulant overdose through oral manifestations, as the patient does not show any symptoms. Dental treatment of patients taking anticoagulant or antiplatelet medication raises safety concerns in terms of the potential risk of bleeding complications following invasive dental procedures. Therefore, certain guidelines for the dental care of patients taking these drugs are needed."}
{"_id": "WikiPedia_Hematology$$$corpus_2573", "text": "Detecting overdose"}
{"_id": "WikiPedia_Hematology$$$corpus_2574", "text": "An overdose of anticoagulants usually occurs in people who have heart problems and need to take anticoagulants in the long term to reduce the risk of stroke from their high blood pressure."}
{"_id": "WikiPedia_Hematology$$$corpus_2575", "text": "An  International Normalised Ratio (INR)  test would be recommended to confirm the overdose so that the dosage can be adjusted to an acceptable standard. The INR test measures the time it takes for a clot to form in a blood sample relative to a standard."}
{"_id": "WikiPedia_Hematology$$$corpus_2576", "text": "An INR value of 1 indicates a level of coagulation equivalent to that of an average patient not taking warfarin, and values greater than 1 indicate a longer clotting time and, thus, a longer bleeding time."}
{"_id": "WikiPedia_Hematology$$$corpus_2577", "text": "Assessing bleeding risk"}
{"_id": "WikiPedia_Hematology$$$corpus_2578", "text": "There are two main parts to the assessment of bleeding risk:"}
{"_id": "WikiPedia_Hematology$$$corpus_2579", "text": "Managing bleeding risk"}
{"_id": "WikiPedia_Hematology$$$corpus_2580", "text": "A patient who is on anticoagulants or  antiplatelet  medications may undergo dental treatments which are unlikely to cause bleeding, such as local anesthesia injection, basic gum charting, removal of plaque, calculus and stain above the gum level, direct or indirect fillings which are above the gingiva,  root canal treatment , taking impression for denture or crown and fitting or adjustment of  orthodontic appliances .\u00a0 For all these procedures, it is recommended that the dentist treat the patient following the normal standard procedure and taking care to avoid any bleeding."}
{"_id": "WikiPedia_Hematology$$$corpus_2581", "text": "For a patient who needs to undergo dental treatments which are more likely to cause bleeding, such as simple tooth extractions (1-3 teeth with small wound size), drainage of swelling inside the mouth, periodontal charting,  root planing , \u00a0direct or indirect filling which extends below the gingiva, complex filling, flap raising procedure, gingival recontouring and biopsies, the dentist needs to take extra precautions apart from the standard procedure. The recommendations [ 127 ]  are as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_2582", "text": "There is general agreement that in most cases, treatment regimens with older anticoagulants (e.g., warfarin) and antiplatelet agents (e.g.,  clopidogrel ,  ticlopidine ,  prasugrel ,  ticagrelor , and/or aspirin) should not be altered before dental procedures. The risks of stopping or reducing these medication regimens (i.e.,  thromboembolism ,  stroke ,  myocardial infarction ) far outweigh the consequences of prolonged bleeding, which can be controlled with local measures. In patients with other existing medical conditions that can increase the risk of prolonged bleeding after dental treatment or receiving other therapy that can increase bleeding risk, dental practitioners may wish to consult the patient's physician to determine whether care can safely be delivered in a primary care office. Any suggested modification to the medication regimen before dental surgery should be done in consultation and on the advice of the patient's physician."}
{"_id": "WikiPedia_Hematology$$$corpus_2583", "text": "Based on limited evidence, the consensus appears to be that in most patients who are receiving the newer direct-acting oral anticoagulants (i.e., dabigatran, rivaroxaban, apixaban, or edoxaban) and undergoing dental treatment (in conjunction with usual local measures to control bleeding), no change to the anticoagulant regimen is required. In patients deemed to be at higher risk of bleeding (e.g., patients with other medical conditions or undergoing more extensive procedures associated with higher bleeding risk), consideration may be given, in consultation with and on advice of the patient's physician, to postponing the timing of the daily dose of the anticoagulant until after the procedure; timing the dental intervention as late as possible after last dose of anticoagulant; or temporarily interrupting drug therapy for 24 to 48 hours."}
{"_id": "WikiPedia_Hematology$$$corpus_2584", "text": "A substantial number of compounds are being investigated for use as anticoagulants. The most promising ones act on the  contact activation system  ( factor XIIa  and  factor XIa ); it is anticipated that this may provide agents that prevent thrombosis without conferring a risk of bleeding. [ 128 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2585", "text": "As of November\u00a02021 [update] , the direct factor XIa inhibitor  milvexian  is in Phase II clinical trials for the prevention of an embolism after surgery. [ 129 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2586", "text": "The  alkali denaturation test , also known as  A  or  Apt test , is a medical test used to differentiate fetal or  neonatal  blood from maternal blood found in a newborn's stool or vomit,  or from maternal vaginal blood. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2587", "text": "The test was developed by  Leonard Apt  (1922\u20132013), [ 3 ]  an American pediatric ophthalmologist. The test was originally used to identify the source of bloody stools in newborn infants. It has been modified to distinguish fetal from maternal hemoglobin in blood samples from any source. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2588", "text": "It is used to differentiate whether the blood coming out of vagina is of the mother or fetus during delivery i.e, placenta previa versus vasa previa. It is based on the principle that fetal HbF is resistant to acids and alkali whereas the mother's blood which has HbA is sensitive to acid and alkaline."}
{"_id": "WikiPedia_Hematology$$$corpus_2589", "text": "The test is based on differences between maternal and fetal  hemoglobin . Maternal blood contains adult hemoglobin composed of two alpha and two beta subunits (aka hemoglobin A or HbA; i.e., normal adult hemoglobin). Fetal blood contains fetal hemoglobin composed of two alpha and two gamma subunits (aka hemoglobin F or HbF; i.e., normal fetal hemoglobin). This difference in composition gives the different types of hemoglobin different chemical properties (in addition to the higher affinity HbF has for dissolved blood oxygen over HbA, allowing baby to extract oxygen from the mother's blood). Fetal hemoglobin is resistant to alkali (basic) denaturation, whereas adult hemoglobin is susceptible to such denaturation. Therefore, exposing the blood specimen to sodium hydroxide ( NaOH ) will denature the adult but not the fetal hemoglobin. The fetal hemoglobin will appear as a pinkish color under the microscope while the adult hemoglobin will appear as a yellow-brownish color."}
{"_id": "WikiPedia_Hematology$$$corpus_2590", "text": "The blood is mixed with a small amount of sterile water to cause  hemolysis  of the  RBCs , yielding free  hemoglobin . The sample is next centrifuged for several minutes. The pink hemoglobin-containing supernatant is then mixed with 1 mL of 1%  NaOH  for each 5 mL of supernatant. The color of the fluid is assessed after 2 minutes. Fetal hemoglobin will stay pink and adult hemoglobin will turn yellow-brown since adult hemoglobin is less stable and will convert to  hematin  which has a hydroxide ligand. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2591", "text": "The  Arneth count  or  Arneth index  describes the  nucleus  of a type of  white blood cell  called a  neutrophil  in an attempt to detect disease."}
{"_id": "WikiPedia_Hematology$$$corpus_2592", "text": "Neutrophils  typically have two or three lobes. In general, older neutrophils have more lobes than younger neutrophils. The Arneth count determines the percentage of neutrophils with one, two, three, four, and five or more lobes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2593", "text": "The Arneth count is not commonly used in modern medicine."}
{"_id": "WikiPedia_Hematology$$$corpus_2594", "text": "It is named for  Josef Arneth . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2595", "text": "An  arterial blood gas  ( ABG )  test , or  arterial blood gas analysis  ( ABGA ) measures the amounts of arterial gases, such as  oxygen  and  carbon dioxide . An ABG test requires that a small volume of blood be drawn from the  radial artery  with a  syringe  and a thin  needle , [ 1 ]  but sometimes the  femoral artery  in the  groin  or another site is used. The blood can also be drawn from an  arterial catheter ."}
{"_id": "WikiPedia_Hematology$$$corpus_2596", "text": "An ABG test measures the  blood gas tension  values of the  arterial partial pressure of oxygen  (PaO2), and the  arterial partial pressure of carbon dioxide  (PaCO2), and the  blood's pH . In addition, the arterial  oxygen saturation  (SaO2) can be determined. Such information is vital when caring for patients with critical illnesses or respiratory disease. Therefore, the ABG test is one of the most common tests performed on patients in  intensive-care units . In other  levels of care ,  pulse oximetry  plus transcutaneous carbon-dioxide measurement is a less invasive, alternative method of obtaining similar information. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2597", "text": "An ABG test can indirectly measure the level of  bicarbonate  in the blood.  The bicarbonate level is calculated using the Henderson-Hasselbalch equation. Many blood-gas analyzers will also report concentrations of  lactate ,  hemoglobin , several  electrolytes ,  oxyhemoglobin ,  carboxyhemoglobin , and  methemoglobin . ABG testing is mainly used in  pulmonology  and critical-care medicine to determine  gas exchange  across the alveolar-capillary membrane.  ABG testing also has a variety of applications in other areas of medicine. Combinations of disorders can be complex and difficult to interpret, so calculators, [ 2 ]   nomograms , and rules of thumb [ 3 ]  are commonly used."}
{"_id": "WikiPedia_Hematology$$$corpus_2598", "text": "ABG  samples  originally were sent from the clinic to the  medical laboratory  for analysis. Newer equipment lets the analysis be done also as  point-of-care testing , depending on the equipment available in each clinic."}
{"_id": "WikiPedia_Hematology$$$corpus_2599", "text": "Arterial blood for  blood-gas analysis  is usually drawn by a  respiratory therapist  and sometimes a  phlebotomist , a  nurse , a  paramedic  or a doctor. [ 4 ]  Blood is most commonly drawn from the  radial artery  because it is easily accessible, can be compressed to control bleeding, and has less risk for  vascular occlusion . The selection of which radial artery to draw from is based on the outcome of an  Allen's test . The  brachial artery  (or less often, the  femoral artery ) is also used, especially during emergency situations or with children. Blood can also be taken from an arterial catheter already placed in one of these arteries. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2600", "text": "There are plastic and glass syringes used for blood gas samples. [ 6 ]   Most syringes come pre-packaged and contain a small amount of  heparin , to prevent  coagulation . Other syringes may need to be heparinised, by drawing up a small amount of liquid heparin and squirting it out again to remove air bubbles. Once the sample is obtained, [ 7 ]  care is taken to eliminate visible gas bubbles, as these bubbles can dissolve into the sample and cause inaccurate results.  The sealed syringe is taken to a  blood gas analyzer . [ 8 ]   If a plastic blood gas syringe is used, the sample should be transported and kept at room temperature and analyzed within 30 min.  If prolonged time delays are expected (i.e., greater than 30 min) prior to analysis, the sample should be drawn in a glass syringe and immediately placed on ice. [ 9 ]   Standard blood tests can also be performed on arterial blood, such as measuring  glucose ,  lactate ,  hemoglobins , dyshemoglobins,  bilirubin  and   electrolytes . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2601", "text": "Derived parameters include bicarbonate concentration, SaO2, and base excess.  Bicarbonate concentration is calculated from the measured pH and PCO2 using the Henderson-Hasselbalch equation.  SaO2 is derived from the measured PO2 and calculated based on the assumption that all measured hemoglobin is normal (oxy- or deoxy-) hemoglobin. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2602", "text": "The machine used for analysis aspirates this blood from the syringe and measures the  pH  and the  partial pressures  of oxygen and carbon dioxide. The bicarbonate concentration is also calculated. These results are usually available for interpretation within five minutes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2603", "text": "Two methods have been used in medicine in the management of blood gases  of patients in  hypothermia : pH-stat method and alpha-stat method. Recent studies suggest that the \u03b1-stat method is superior. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2604", "text": "Both the pH-stat and alpha-stat strategies have theoretical disadvantages. \u03b1-stat method is the method of choice for optimal myocardial function. The pH-stat method may result in loss of autoregulation in the brain (coupling of the cerebral blood flow with the metabolic rate in the brain). By increasing the cerebral blood flow beyond the metabolic requirements, the pH-stat method may lead to cerebral microembolisation and intracranial hypertension. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2605", "text": "These are typical  reference ranges , although various analysers and laboratories may employ different ranges."}
{"_id": "WikiPedia_Hematology$$$corpus_2606", "text": "There are two calculations for base excess (extra cellular fluid - BE(ecf); blood - BE(b)).  The calculation used for the BE(ecf) = [ HCO \u2212 3 ]\u2212 24.8 + 16.2 \u00d7 (pH \u2212 7.4). The calculation used for BE(b) = (1 \u2212 0.014 \u00d7  Hgb ) \u00d7 ([ HCO \u2212 3 ]\u2212 24.8 + (1.43 \u00d7 Hgb + 7.7) \u00d7 (pH \u2212 7.4)."}
{"_id": "WikiPedia_Hematology$$$corpus_2607", "text": "Contamination of the sample with room air will result in abnormally low carbon dioxide and possibly elevated oxygen levels, and a concurrent elevation in pH.  Delaying analysis (without chilling the sample) may result in inaccurately low oxygen and high carbon dioxide levels as a result of ongoing cellular respiration."}
{"_id": "WikiPedia_Hematology$$$corpus_2608", "text": "The normal range for pH is 7.35\u20137.45. As the pH decreases (< 7.35), it implies  acidosis , while if the pH increases (> 7.45) it implies  alkalosis . In the context of arterial blood gases, the most common occurrence will be that of  respiratory acidosis .  Carbon dioxide is dissolved in the blood as carbonic acid, a weak acid; however, in large concentrations, it can affect the pH drastically. Whenever there is poor pulmonary ventilation, the carbon dioxide levels in the blood are expected to rise. This leads to a rise of carbonic acid, leading to a decrease in pH. The first buffer of pH will be the plasma proteins, since these can accept some H +  ions to try to maintain  acid-base homeostasis . As carbon dioxide concentrations continue to increase ( Pa CO 2  > 45 mmHg), a condition known as respiratory acidosis occurs. The body tries to maintain homeostasis by increasing the respiratory rate, a condition known as tachypnea. This allows much more carbon dioxide to escape the body through the lungs, thus increasing the pH by having less carbonic acid. If a person is in a critical setting and intubated, one must increase the number of breaths mechanically. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2609", "text": "Respiratory alkalosis  ( Pa  CO 2  < 35 mmHg) occurs when there is too little carbon dioxide in the blood. This may be due to hyperventilation or else excessive breaths given via a  mechanical ventilator  in a critical care setting. The action to be taken is to calm the person and try to reduce the number of breaths being taken to normalize the pH. The respiratory pathway tries to compensate for the change in pH in a matter of 2\u20134 hours. If this is not enough, the metabolic pathway takes place. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2610", "text": "Under normal conditions, the  Henderson\u2013Hasselbalch equation  will give the blood pH"}
{"_id": "WikiPedia_Hematology$$$corpus_2611", "text": "where:"}
{"_id": "WikiPedia_Hematology$$$corpus_2612", "text": "The kidney and the liver are two main organs responsible for the metabolic homeostasis of pH. Bicarbonate is a base that helps to accept excess hydrogen ions whenever there is acidaemia. However, this mechanism is slower than the respiratory pathway and may take from a few hours to 3 days to take effect. In acidaemia, the bicarbonate levels rise, so that they can neutralize the excess acid, while the contrary happens when there is alkalaemia. Thus when an arterial blood gas test reveals, for example, an elevated bicarbonate, the problem has been present for a couple of days, and metabolic compensation took place over a blood acidaemia problem. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2613", "text": "In general, it is much easier to correct acute pH derangement by adjusting respiration. Metabolic compensations take place at a much later stage. However, in a critical setting, a person with a normal pH, a high CO 2 , and a high bicarbonate means that, although there is a high carbon dioxide level, there is metabolic compensation. As a result, one must be careful as to not artificially adjust breaths to lower the carbon dioxide. In such case, lowering the carbon dioxide abruptly means that the bicarbonate will be in excess and will cause a metabolic alkalosis. In such a case, carbon dioxide levels should be slowly diminished. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2614", "text": "Since the advent of  pulse oximetry  which measures oxygen saturation transcutaneously and is non-invasive, arterial blood is seldom used for the determination of oxygenation outside the ICU. Acid base status can be determined with  venous blood   precluding the pain and inconvenience of arterial blood sampling in most cases. When an indwelling arterial line  catheter  is present, arterial blood is easy to obtain and still used.  Venous blood  is generally used otherwise, usually from a   peripheral   vein, such as a forearm vein. \nThe values of pH and HCO3 of venous blood are close enough to arterial blood for direct comparison. The pCO2 of  venous blood  is less reliably compared to arterial blood but may be used in some cases. The PO2 level of venous blood is always significantly lower that arterial and should be reported, labeled and interpreted as venous PO2.\n [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2615", "text": "A  basic metabolic panel  ( BMP )  is a blood test consisting of a set of seven or eight biochemical tests and is one of the most common lab tests ordered by health care providers. Outside the  United States , blood tests made up of the majority of the same biochemical tests are called  urea and electrolytes  ( U&E  or \" U and Es \"), or  urea, electrolytes, creatinine  ( UEC  or  EUC  or  CUE ), and are often referred to as 'kidney function tests' as they also include a calculated estimated  glomerular filtration rate . The BMP provides key information regarding fluid and electrolyte status, kidney function, blood sugar levels, and response to various medications and other medical therapies. It is frequently employed as a screening tool during a  physical exam ."}
{"_id": "WikiPedia_Hematology$$$corpus_2616", "text": "The basic metabolic panel is a simpler version of the  comprehensive metabolic panel  (CMP), which includes tests for liver function."}
{"_id": "WikiPedia_Hematology$$$corpus_2617", "text": "The version with seven tests is often referred to by medical professionals in the United States as the \"CHEM-7\", or \"SMA-7\" (Sequential Multiple Analysis-7). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2618", "text": "The seven parts of a CHEM-7 are tests for:"}
{"_id": "WikiPedia_Hematology$$$corpus_2619", "text": "These levels, taken as a set, can be rapidly performed to indicate several common acute conditions requiring immediate specific medical treatment, such as  dehydration / hypovolemia ,  water intoxication  (which can present with similar symptoms to dehydration but requires the opposite treatment),  diabetic shock  (either  ketoacidosis ,  hyperglycemia  or  hypoglycemia ),  congestive heart failure ,  kidney failure  or  liver failure , various substance overdoses or adverse reactions, and others. A Chem-7 is thus a vital tool when attempting to stabilize a patient. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2620", "text": "Calcium  (Ca 2+ ) is often considered part of the BMP, [ 9 ] [ 10 ]  though, by definition, it is not part of the CHEM-7. A basic metabolic panel including calcium is sometimes colloquially referred to as a \"CHEM-8\". Calcium, as an  alkaline earth metal , is also an electrolyte, but abnormalities are more commonly associated with malnutrition,  osteoporosis , or  malignancy , especially of the  thyroid . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2621", "text": "In countries that do not use the CHEM-7 panel, a UEC typically does not include chloride or bicarbonate as standard components, but will often include an  estimated glomerular filtration rate  (eGFR), and in some laboratories, glucose is also not included but is available as a separate test."}
{"_id": "WikiPedia_Hematology$$$corpus_2622", "text": "The results of a basic metabolic panel are traditionally represented in a standard grid:"}
{"_id": "WikiPedia_Hematology$$$corpus_2623", "text": "Glucose (and sometimes calcium,  magnesium , and  phosphorus ) are listed to the right of this grid, but there is greater variation in how these values are reported. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2624", "text": "The  Beutler test , also known as the  fluorescent spot test , [ 1 ]  is a  screening  test used to identify enzyme defects. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2625", "text": "It can be used in screening for:"}
{"_id": "WikiPedia_Hematology$$$corpus_2626", "text": "The  biological terrain assessment  or  BTA  is a set of tests used to measure the  pH ,  resistivity , and  redox  of a person's  urine ,  blood , and  saliva . [ 1 ] [ 2 ]  The measurements were first used by L.C. Vincent, a  French   hydrologist , in the early 1900s. [ 3 ]  It is often associated with  homeopathy  and  holistic health . The usefulness of the test is debatable and according to physician  Stephen Barrett  BTA is outdated, apart from pH measurement, and is an inferior assessment technique that should not be favored over more modern techniques. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2627", "text": "Proponents of the BTA claim that comparing the pH, resistivity, and  redox  of the blood, urine, and saliva provides a health practitioner an indication of the metabolic processes taking place inside the body. [ 2 ]  There is no scientific evidence that these measurements provide a medically relevant indication of metabolic processes. Multiple manufacturers of BTA equipment have been prevented from selling their equipment in the United States because they lack  Food and Drug Administration  (FDA) approval. However, the FDA has not stated whether the BTA is medically useful or not. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2628", "text": "The Quantitative Fluid Analyzer (QFA) manufactured by Health Science Company does have FDA classification as a \"laboratory instrument for medical purposes\" \"ion selective\", Class 1 510(K) exempt. [ citation needed ]  However it does not have CLIA (Clinical Laboratory improvement Amendment, 1988) waiver. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2629", "text": "This article about  alternative medicine  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_2630", "text": "Birchfield v. North Dakota , 579 U.S. 438 (2016) is a case in which the  Supreme Court of the United States  held that the  search incident to arrest  doctrine permits law enforcement to conduct warrantless breath tests but not blood tests on suspected drunk drivers. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2631", "text": "Birchfield  was a consolidation of three cases:  Birchfield v. North Dakota ,  Bernard v. Minnesota , and  Beylund v. Levi . Birchfield was charged with violation of a North Dakota statute for refusing to submit to blood alcohol content testing; Bernard was charged with a violation of a Minnesota statute for refusing to submit to breath alcohol testing; Beylund underwent a blood alcohol test consistent with North Dakota's  implied consent  law and challenged the constitutionality of that law after an administrative hearing based on the test results led to the revocation of his license."}
{"_id": "WikiPedia_Hematology$$$corpus_2632", "text": "In  Missouri v. McNeely , 569 U.S. 141 (2013), the Court held that in the absence of an argument based on facts specific to the case \"the natural dissipation of alcohol from the bloodstream does not  always  constitute an  exigency  justifying the warrantless taking of a blood sample\". In contrast to the court's 1966 finding in  Schmerber v. California , 384 U. S. 757  [ 2 ]  held that the same exigent circumstance did exist by inferring that an officer might reasonably believe it to exist. The court \"did not address any potential justification for warrantless testing of drunk driving suspects, except for the exception 'at issue in the case,' namely, the exception for exigent circumstances\". [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2633", "text": "The issue before the court was how the \"search incident to arrest doctrine applies to breath and blood tests\". Is warrantless alcohol testing incident to drunk driving arrests to determine  blood alcohol content  a violation of the  Fourth Amendment ?"}
{"_id": "WikiPedia_Hematology$$$corpus_2634", "text": "The Court held that both breath tests and blood tests constitute a search under the Fourth Amendment. The Court then proceeded to analyze both types of tests under the search incident to arrest doctrine, weighing on the one hand \"the degree to which it intrudes upon an individual\u2019s privacy\" and on the other hand \"the degree to which it is needed for the promotion of legitimate governmental interests.\" Applied to breath tests, the Court concluded that breath tests do not implicate significant privacy concerns. Blood tests, on the other hand, are significantly more intrusive. Turning to the government's interest in the tests, the Court concluded that serves the very important function of providing an incentive to cooperate in alcohol testing. Weighing these interests, the Court concluded that requiring breath tests is constitutional; however, requiring blood tests is not, as the goal of traffic safety can be obtained by less invasive means (such as breath tests)."}
{"_id": "WikiPedia_Hematology$$$corpus_2635", "text": "In the majority opinion, in addressing the limits of implied consent laws, the court stated that while their \"prior opinions have referred approvingly to the general concept of implied-consent laws\" that \"there must be a limit to the consequences to which motorists may be deemed to have consented by virtue of a decision to drive on public roads\" and \"that motorists could be deemed to have consented to only those conditions that are 'reasonable' in that they have a 'nexus' to the privilege of driving\"."}
{"_id": "WikiPedia_Hematology$$$corpus_2636", "text": "The Court ruled in favor of Birchfield who was prosecuted for refusing a warrantless blood draw and ruled against Bernard who refused a warrantless breath test.  Beylund, on the other hand consented to a blood test after police advised him that he was required to do.  The court therefore remanded Beylund's case back to the state court \"to reevaluate Beylund's consent given the partial inaccuracy of the officer's advisory.\" The Supreme Court of North Dakota court subsequently avoided the issue by holding that, even assuming the consent was involuntary, the Exclusionary Rule does not apply in the administrative hearing context and thus affirmed suspension of his license for testing over the prohibited level set forth in the implied consent / administrative license suspension statute. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2637", "text": "Justice Clarence Thomas wrote that \"the search-incident-to-arrest exception to the Fourth Amendment\u2019s warrant requirement should apply categorically to all blood alcohol tests, including  blood tests . By drawing an arbitrary line between blood tests and  breath tests , the majority destabilized the law of exceptions to the warrant requirement and made the jobs of both police officers and lower courts more difficult.\" [ 5 ]  The Supreme Court ruled in favor of Birchfield in a 7\u20131 majority stating that the refusal to submit to a warrantless blood test may not be criminalized as it is a violation of the petitioner's  Fourth Amendment right against unlawful searches  and is protected by neither the  search incident to arrest  nor  exigent circumstances  exceptions of the Fourth Amendment's warrant requirement. The Supreme Court also stated that the same rationale applied to the decision of warrantless breath tests was not relevant based on the implication of serious privacy concerns brought about by the administration of blood tests which could be used to obtain information other than the  BAC  of the suspected drunk driver as well as the intrusive process used to obtain a blood sample."}
{"_id": "WikiPedia_Hematology$$$corpus_2638", "text": "Justice Sonia Sotomayor wrote that \"the Fourth Amendment\u2019s prohibition against warrantless searches should apply to breath tests unless exigent circumstances justify one in a particular case. In establishing exceptions to the warrant requirement, the Court has routinely examined whether a legitimate government interest justified the search in light of the individual\u2019s privacy interest and whether that determination should be made based on a case-by-case analysis or a categorical rule.\" [ 5 ]  Justice Sotomayor argued that the administration of a warrantless breath test was not imperative to the prevention of drunk drivers as the suspected drunk driver has already been removed from the roadway and a search warrant could be obtained if necessary. The Supreme Court ruled 6\u20132 in favor of The State of North Dakota stating that warrantless breath tests are protected under the search incident to arrest warrant exception of the Fourth Amendment's warrant requirement and require minimal physical intrusion. The Supreme Court majority also argued that the administration of a warrantless breath tests serves the government's objectives of deterring drunk drivers as well as effectively allowing law enforcement officers to remove already present drunk drivers from the roadways."}
{"_id": "WikiPedia_Hematology$$$corpus_2639", "text": "Bleeding time  is a  medical test  done to assess the function of a person's  platelets . It involves making a patient bleed, then timing how long it takes for them to stop bleeding using a  stopwatch  or other suitable devices."}
{"_id": "WikiPedia_Hematology$$$corpus_2640", "text": "The term  template bleeding time  is used when the test is performed to standardized parameters."}
{"_id": "WikiPedia_Hematology$$$corpus_2641", "text": "A newer alternative to the traditional bleeding time test is the platelet function screen performed on the PFA-100 analyzer. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2642", "text": "The template bleeding time test is a method used when other more reliable and less invasive tests for determining  coagulation  are not available. [ 2 ]  Historically, it was used whenever physicians needed information about platelet activation. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2643", "text": "The test involves cutting the underside of the subject's forearm, in an area where there is no hair or visible  veins . The cut is of a standardized width and depth, and is done quickly by a template device. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2644", "text": "The IVY method is the traditional format for this test. While both the IVY and Duke's method require the use of a  sphygmomanometer , or blood pressure cuff, the IVY method is more invasive than the Duke method, utilizing an  incision  on the ventral side of the forearm, whereas the Duke method involves puncture with a  lancet  or special needle.  In the IVY method, the blood pressure cuff is placed on the upper arm and inflated to 40 mmHg. A lancet or scalpel blade is used to make a shallow incision that is 1 millimeter deep on the underside of the forearm. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2645", "text": "A standard-sized incision is made around 10\u00a0mm long and 1\u00a0mm deep. The time from when the incision is made until all bleeding has stopped is measured and is called the bleeding time. Every 30 seconds, filter paper or a paper towel is used to draw off the blood."}
{"_id": "WikiPedia_Hematology$$$corpus_2646", "text": "The test is finished when bleeding has stopped. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2647", "text": "A prolonged bleeding time may be a result from decreased number of thrombocytes or impaired blood vessels. However, the depth of the puncture or incision may be the source of error."}
{"_id": "WikiPedia_Hematology$$$corpus_2648", "text": "Normal values  fall between 3\u00a0\u2013 10 minutes depending on the method used."}
{"_id": "WikiPedia_Hematology$$$corpus_2649", "text": "A disadvantage of Ivy's method is closure of puncture wound before stoppage of bleeding. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2650", "text": "With the Duke's method, the patient is pricked with a special needle or lancet, preferably on the  earlobe [ 8 ]  or  fingertip , after having been swabbed with alcohol. The prick is about 3\u20134\u00a0mm deep. The patient then wipes the blood every 30 seconds with a filter paper. The test ceases when bleeding ceases. The usual time is about 2\u20135 minutes."}
{"_id": "WikiPedia_Hematology$$$corpus_2651", "text": "This method is not recommended and cannot be standardized because it can cause a large local hematoma. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2652", "text": "Bleeding time may be affected by platelet function, certain vascular disorders and  von Willebrand Disease \u2014not by other  coagulation  factors such as  haemophilia .  Diseases that may cause prolonged bleeding time include  thrombocytopenia ,  disseminated intravascular coagulation  (DIC),  Bernard-Soulier disease , and  Glanzmann's thrombasthenia . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2653", "text": "Aspirin  and other  cyclooxygenase  inhibitors can significantly prolong bleeding time. While  warfarin  and  heparin  have their major effects on coagulation factors, an increased bleeding time is sometimes seen with use of these medications as well."}
{"_id": "WikiPedia_Hematology$$$corpus_2654", "text": "People with  von Willebrand disease  usually experience increased bleeding time, as  von Willebrand factor  is a platelet adhesion protein, but this is not considered an effective diagnostic test for this condition. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2655", "text": "It is also prolonged in  hypofibrinogenemia . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2656", "text": "In the British comedy film  Doctor in the House  (1954), Sir Lancelot Spratt, the intimidating chief of surgery played by  James Robertson Justice  is asking instructional questions of his medical students. He asks a young student, who has been distracted by a pretty nurse, what \"the bleeding time\" is. The student looks at his watch and answers \"Ten past ten, sir.\""}
{"_id": "WikiPedia_Hematology$$$corpus_2657", "text": "Blood compatibility testing  is conducted in a  medical laboratory  to identify potential incompatibilities between  blood group systems  in  blood transfusion . It is also used to diagnose and prevent some  complications of pregnancy  that can occur when the baby has a different blood group from the mother. Blood compatibility testing includes  blood typing , which detects the  antigens  on  red blood cells  that determine a person's blood type; testing for unexpected  antibodies  against blood group antigens ( antibody screening and identification ); and, in the case of blood transfusions, mixing the recipient's  plasma  with the donor's red blood cells to detect incompatibilities ( crossmatching ). Routine blood typing involves determining the  ABO  and  RhD  (Rh factor) type, [ note 1 ]  and involves both identification of ABO antigens on red blood cells (forward grouping) and identification of ABO antibodies in the plasma (reverse grouping).  Other blood group antigens  may be tested for in specific clinical situations."}
{"_id": "WikiPedia_Hematology$$$corpus_2658", "text": "Blood compatibility testing makes use of  reactions between blood group antigens and antibodies \u2014specifically the ability of antibodies to cause red blood cells to clump together when they bind to antigens on the cell surface, a phenomenon called  agglutination . Techniques that rely on antigen-antibody reactions are termed  serologic  methods, and several such methods are available, ranging from manual testing using test tubes or slides to fully automated systems. Blood types can also be determined through  genetic testing , which is used when conditions that interfere with serologic testing are present or when a high degree of accuracy in antigen identification is required."}
{"_id": "WikiPedia_Hematology$$$corpus_2659", "text": "Several conditions can cause false or inconclusive results in blood compatibility testing. When these issues affect ABO typing, they are called  ABO discrepancies . ABO discrepancies must be investigated and resolved before the person's blood type is reported. Other sources of error include the \" weak D \" phenomenon, in which people who are positive for the RhD antigen show weak or negative reactions when tested for RhD, and the presence of  immunoglobulin G  antibodies on red blood cells, which can interfere with antibody screening, crossmatching, and typing for some blood group antigens."}
{"_id": "WikiPedia_Hematology$$$corpus_2660", "text": "Blood compatibility testing is routinely performed before a  blood transfusion . The full compatibility testing process involves  ABO  and  RhD  (Rh factor) typing; screening for antibodies against  other blood group systems ; and  crossmatching , which involves testing the recipient's  blood plasma  against the donor's red blood cells as a final check for incompatibility. If an unexpected blood group antibody is detected, further testing is warranted to identify the antibody [ 3 ] :\u200a740\u200a  and ensure that the donor blood is negative for the relevant antigen. [ 1 ] :\u200a261\u200a  Serologic crossmatching may be omitted if the recipient's antibody screen is negative, there is no history of clinically significant antibodies, and their ABO/Rh type has been confirmed against historical records or against a second blood sample; and in emergencies, blood may be transfused before any compatibility testing results are available. [ 1 ] :\u200a262\u20133"}
{"_id": "WikiPedia_Hematology$$$corpus_2661", "text": "Blood compatibility testing is often performed on pregnant women and on the  cord blood  from newborn babies, because incompatibility puts the baby at risk for developing hemolytic disease of the newborn. [ 4 ] [ 5 ]  It is also used before  hematopoietic stem cell transplantation , because blood group incompatibility can be responsible for some cases of acute  graft-versus-host disease . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2662", "text": "Blood types are defined according to the presence or absence of specific  antigens  on the surface of red blood cells. The most important of these in medicine are the  ABO  and  RhD antigens [ 7 ] :\u200a585\u200a  but many other blood group systems exist and may be clinically relevant in some situations. As of 2021, 43 blood groups are officially recognized. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2663", "text": "People who lack certain blood group antigens on their red cells can form  antibodies  against these antigens. For example, a person with type A blood will produce antibodies against the B antigen. The ABO blood group antibodies are naturally occurring, meaning that they are found in people who have not been exposed to incompatible blood. [ 7 ] :\u200a585\u201392\u200a  Antibodies to most other blood group antigens, including RhD, develop after people are exposed to the antigens through transfusion or pregnancy. [ 1 ] :\u200a62\u200a  Some of these antibodies can bind to incompatible red blood cells and  cause them to be destroyed , resulting in  transfusion reactions  and other complications. [ 9 ] :\u200a210\u201311"}
{"_id": "WikiPedia_Hematology$$$corpus_2664", "text": "Serologic  methods for blood compatibility testing make use of these  antibody-antigen reactions . In blood typing,  reagents  containing blood group antibodies, called  antisera , [ 7 ] :\u200a586\u200a  are added to suspensions of blood cells. If the relevant antigen is present, the antibodies in the reagent will cause the red blood cells to  agglutinate  (clump together), which can be identified visually. [ 1 ] :\u200a65\u200a  In antibody screening, the individual's plasma is tested against a set of red blood cells with known antigen profiles; if the plasma agglutinates one of the red blood cells in the panel, this indicates that the individual has an antibody against one of the antigens present on the cells. In crossmatching, a prospective transfusion recipient's plasma is added to the donor red blood cells and observed for agglutination (or hemolysis) to detect antibodies that could cause transfusion reactions. [ 3 ] :\u200a722\u20135"}
{"_id": "WikiPedia_Hematology$$$corpus_2665", "text": "Blood group antibodies occur in two major forms:  immunoglobulin M  (IgM) and  immunoglobulin G  (IgG). Antibodies that are predominantly IgM, such as the ABO antibodies, typically cause immediate agglutination of red blood cells at room temperature. Therefore, a person's ABO blood type can be determined by simply adding the red blood cells to the reagent and centrifuging or mixing the sample, [ 1 ] :\u200a122\u200a  and in crossmatching, incompatibility between ABO types can be detected immediately after centrifugation. [ 3 ] :\u200a725\u200a  RhD typing also typically uses IgM reagents [ 10 ] :\u200a477\u200a  although anti-RhD usually occurs as IgG in the body. [ 1 ] :\u200a161\u200a   Antibodies that are predominantly IgG, such as those directed towards antigens of the  Duffy  and  Kidd  systems, [ 1 ] :\u200a198\u2013200\u200a  generally do not cause immediate agglutination because the small size of the IgG antibody prevents formation of a lattice structure. Therefore, blood typing using IgG antisera and detection of IgG antibodies requires use of the  indirect antiglobulin test  to demonstrate IgG bound to red blood cells. [ 1 ] :\u200a104"}
{"_id": "WikiPedia_Hematology$$$corpus_2666", "text": "In the indirect antiglobulin test, the mixture of antiserum or plasma and red blood cells is incubated at 37\u00a0\u00b0C (99\u00a0\u00b0F), the ideal temperature for reactivity of IgG antibodies. After incubation, the red blood cells are washed with saline to remove unbound antibodies, and anti-human globulin reagent is added. If IgG antibodies have bound to antigens on the cell surface, anti-human globulin will bind to those antibodies, causing the red blood cells to agglutinate after centrifugation. If the reaction is negative, \"check cells\"\u2014reagent cells coated with IgG\u2014are added to ensure that the test is working correctly. If the test result is indeed negative, the check cells should react with the unbound anti-human globulin and demonstrate agglutination. [ 3 ] :\u200a716\u20139"}
{"_id": "WikiPedia_Hematology$$$corpus_2667", "text": "In ABO and Rh typing, reagents  containing antibodies against the A, B, and RhD antigens are added to suspensions of blood cells. If the relevant antigen is present, the red blood cells will demonstrate visible  agglutination  (clumping). [ 1 ] :\u200a65\u200a  In addition to identifying the ABO antigens, which is termed forward grouping, routine ABO blood typing also includes identification of the ABO antibodies in the person's plasma. This is called reverse grouping, [ 1 ] :\u200a120\u200a  and it is done to confirm the ABO blood type. In reverse grouping, the person's plasma is added to type A 1  and type B red blood cells. The plasma should agglutinate the cells that express antigens that the person lacks, while failing to agglutinate cells that express the same antigens as the patient. For example, the plasma of someone with type A blood should react with type B red cells, but not with A 1  cells. If the expected results do not occur, further testing is required. [ 7 ] :\u200a595\u200a  Agglutination is scored from 1+ to 4+ based on the strength of the reaction. In ABO typing, a score of 3+ or 4+ indicates a positive reaction, while a score of 1+ or 2+ is inconclusive and requires further investigation. [ 1 ] :\u200a236"}
{"_id": "WikiPedia_Hematology$$$corpus_2668", "text": "Prior to receiving a blood transfusion, individuals are screened for the presence of antibodies against antigens of non-ABO  blood group systems . [ 5 ]  Blood group antigens besides ABO and RhD that are significant in  transfusion medicine  include the  RhC/c and E/e  antigens and the antigens of the  Duffy ,  Kell ,  Kidd , and  MNS  systems. [ 1 ] :\u200a158\u2013173\u200a  If a clinically significant antibody is identified, the recipient must be transfused with blood that is negative for the corresponding antigen to prevent a transfusion reaction. This requires the donor units to be typed for the relevant antigen. [ 1 ] :\u200a261\u200a  The recipient may also be typed for the antigen to confirm the identity of the antibody, as only individuals who are negative for a blood group antigen should produce antibodies against it. [ 7 ] :\u200a603"}
{"_id": "WikiPedia_Hematology$$$corpus_2669", "text": "In Europe, females who require blood transfusions are often typed for the Kell and extended Rh antigens to prevent sensitization to these antigens, which could put them at risk for developing  hemolytic disease of the newborn  during pregnancy. [ 11 ]  The  American Society of Hematology  recommends that people  with  sickle cell disease  have their blood typed for the RhC/c, RhE/e, Kell, Duffy, Kidd, and MNS antigens prior to transfusion, [ 12 ] :\u200a130\u20131\u200a  because they often require transfusions and may become sensitized to these antigens if transfused with mismatched blood. [ 13 ]  Extended red blood cell phenotyping is also recommended for people with  beta-thalassemia . [ 14 ]  Blood group systems other than ABO and Rh have a relatively small risk of complications when blood is mixed, so in emergencies such as major  hemorrhage , the urgency of transfusion can exceed the need for compatibility testing against other blood group systems (and potentially Rh as well). [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2670", "text": "Antibodies to most blood group antigens besides those of the ABO system develop after exposure to incompatible blood. [ 1 ] :\u200a62\u200a  Such \"unexpected\" blood group antibodies are only found in 0.8\u20132% of people; however, recipients of blood transfusions must be screened for these antibodies to prevent transfusion reactions. Antibody screening is also performed as part of  prenatal care , because antibodies against RhD and other blood group antigens can cause hemolytic disease of the newborn, and because Rh-negative mothers who have developed an anti-RhD antibody are not eligible to receive  Rho(D) immune globulin  (Rhogam). [ 1 ] :\u200a233"}
{"_id": "WikiPedia_Hematology$$$corpus_2671", "text": "In the antibody screening procedure, an individual's plasma is added to a panel of two or three sets of red blood cells which have been chosen to express most clinically significant blood group antigens. Only group O cells are used in antibody screening, as otherwise the cells would react with the naturally occurring ABO blood group antibodies. The mixture of plasma and red cells is incubated at 37\u00b0C and tested via the indirect antiglobulin test. Some antibody screening and identification protocols incorporate a phase of testing after incubation at room temperature, but this is often omitted because most unexpected antibodies that react at room temperature are clinically insignificant. [ 3 ] :\u200a722\u20134"}
{"_id": "WikiPedia_Hematology$$$corpus_2672", "text": "Agglutination of the screening cells by the plasma, with or without the addition of anti-human globulin, indicates that an unexpected blood group antibody is present. If this occurs, further testing using more cells (usually 10\u201311) is necessary to identify the antibody. By examining the antigen profiles of the red blood cells the person's plasma reacts with, it is possible to determine the antibody's identity.  An \"autocontrol\", in which the individual's plasma is tested against their own red cells, is included to determine whether the agglutination is due to an  alloantibody  (an antibody against a foreign antigen), an  autoantibody  (an antibody against one's own antigens), or another interfering substance. [ 3 ] :\u200a722\u20134"}
{"_id": "WikiPedia_Hematology$$$corpus_2673", "text": "The image above shows the interpretation of an antibody panel used in  serology  to detect antibodies towards the most relevant blood group antigens. Each row represents \"reference\" or \"control\" red blood cells of donors which have known antigen compositions and are  ABO group O . The + symbol means that the antigen is present on the reference red blood cells, and 0 means it is absent; nt means \"not tested\". The \"result\" column to the right displays reactivity when mixing reference red blood cells with plasma from the patient in 3 different phases: room temperature, 37\u00b0C and AHG (with anti-human globulin, by the  indirect antiglobulin test ). [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2674", "text": "In this case, the antibody panel shows that anti-Fy a  antibodies are present. This indicates that donor blood typed to be negative for the Fy a  antigen must be used. Still, if a subsequent  cross-matching  shows reactivity, additional testing should be done against previously discounted antigens (in this case potentially E, K, Kp a  and/or Lu a ). [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2675", "text": "When multiple antibodies are present, or when an antibody is directed against a high-frequency antigen, the normal antibody panel procedure may not provide a conclusive identification. In these cases,  hemagglutination inhibition  can be used, wherein a  neutralizing substance  cancels out a specific antigen. [ 17 ]  Alternatively, the plasma may be incubated with cells of known antigen profiles in order to remove a specific antibody (a process termed  adsorption ); or the cells can be treated with  enzymes  such as  ficain  or  papain  which inhibit the reactivity of some blood group antibodies and enhance others. [ 3 ] :\u200a723\u20139\u200a  The effect of ficain and papain on major blood group systems is as follows: [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2676", "text": "People who have tested positive for an unexpected blood group antibody in the past may not exhibit a positive reaction on subsequent testing; however, if the antibody is clinically significant, they must be transfused with antigen-negative blood regardless. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2677", "text": "Crossmatching, which is routinely performed before a blood transfusion, involves adding the recipient's blood plasma to a sample of the donor's red blood cells. If the blood is incompatible, the antibodies in the recipient's plasma will bind to antigens on the donor red blood cells. This antibody-antigen reaction can be detected through visible clumping or destruction of the red blood cells, or by reaction with  anti-human globulin , after centrifugation. [ 7 ] :\u200a600\u20133"}
{"_id": "WikiPedia_Hematology$$$corpus_2678", "text": "If the transfusion recipient has a negative antibody screen and no history of antibodies, an \"immediate spin\" crossmatch is often performed: the red blood cells and plasma are centrifuged immediately after mixing as a final check for incompatibility between ABO blood types. If a clinically significant antibody is detected (or was in the past), or if the immediate spin crossmatch demonstrates incompatibility, a \"full\" or \"IgG crossmatch\" is performed, which uses the indirect antiglobulin test to detect blood group incompatibility caused by IgG antibodies. The IgG crossmatching procedure is more lengthy than the immediate spin crossmatch, and in some cases may take more than two hours. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2679", "text": "Individuals who have a negative antibody screen and no history of antibodies may also undergo an \"electronic crossmatch\", provided that their ABO and Rh type has been determined from the current blood sample and that the results of another ABO/Rh type are on record. In this case, the recipient's blood type is simply compared against that of the donor blood, without any need for serologic testing. [ 7 ] :\u200a600\u20133\u200a  In emergencies, blood may be issued before crossmatching is complete. [ 1 ] :\u200a262\u20133"}
{"_id": "WikiPedia_Hematology$$$corpus_2680", "text": "Blood typing can be performed using test tubes,  microplates , or blood typing slides. The tube method involves mixing a  suspension  of red blood cells with antisera (or plasma, for reverse grouping) in a test tube. The mixture is centrifuged to separate the cells from the reagent, and then resuspended by gently agitating the tube. If the antigen of interest is present, the red blood cells agglutinate, forming a solid clump in the tube. If it is absent, the red blood cells go back into suspension when mixed. [ 7 ] :\u200a611\u201312\u200a [ 9 ] :\u200a214\u200a   The microplate method is similar to the tube method, except rather than using individual test tubes, blood typing is carried out in a plate containing dozens of wells, allowing multiple tests to be performed at the same time. The agglutination reactions are read after the plate is centrifuged. [ 21 ] :\u200a201"}
{"_id": "WikiPedia_Hematology$$$corpus_2681", "text": "Antibody screening and identification can also be carried out by the tube method. In this procedure, the plasma and red cells are mixed together in a tube containing a medium that enhances agglutination reactions, such as  low ionic strength saline  (LISS). The tubes are incubated at body temperature for a defined period of time, then centrifuged and examined for agglutination or hemolysis; first immediately following the incubation period, and then after washing and addition of anti-human globulin reagent. [ 3 ] :\u200a722\u200a  Crossmatching, likewise, may be performed by the tube method; the reactions are read immediately after centrifugation in the immediate spin crossmatch, or after incubation and addition of AHG in the full crossmatching procedure. [ 3 ] :\u200a725"}
{"_id": "WikiPedia_Hematology$$$corpus_2682", "text": "The slide method for blood typing involves mixing a drop of blood with a drop of antisera on a slide. The slide is tilted to mix the cells and reagents together and then observed for agglutination, which indicates a positive result. This method is typically used in under-resourced areas or emergency situations; otherwise, alternative methods are preferred. [ 9 ] :\u200a214\u200a [ 10 ] :\u200a476"}
{"_id": "WikiPedia_Hematology$$$corpus_2683", "text": "Column agglutination techniques for blood compatibility testing (sometimes called the \"gel test\") use cards containing columns of  dextran - polyacrylamide gel . Cards designed for blood typing contain pre-dispensed blood typing reagents for forward grouping, and wells containing only a  buffer solution , to which reagent red blood cells and plasma are added, for reverse grouping. Antibody screening and crossmatching can also be carried out by column agglutination, in which case cards containing anti-human globulin reagent are used. The gel cards are centrifuged (sometimes after incubation, depending on the test), during which red blood cell agglutinates become trapped at the top of the column because they are too large to migrate through the gel. Cells that have not agglutinated collect on the bottom. Therefore, a line of red blood cells at the top of the column indicates a positive result. The strength of positive reactions is scored from 1+ to 4+ depending on how far the cells have travelled through the gel. The gel test has advantages over manual methods in that it eliminates the variability associated with manually re-suspending the cells and that the cards can be kept as a record of the test. [ 1 ] :\u200a269\u201371\u200a  The column agglutination method is used by some  automated analyzers  to perform blood typing automatically. [ 7 ] :\u200a590\u200a  These analyzers  pipette  red blood cells and plasma onto gel cards, centrifuge them, and scan and read the agglutination reactions to determine the blood type. [ 1 ] :\u200a270\u20131"}
{"_id": "WikiPedia_Hematology$$$corpus_2684", "text": "Solid-phase assays (sometimes called the \"antigen capture\" method) use reagent antigens or antibodies affixed to a surface (usually a microplate). [ 9 ] :\u200a214\u200a  Microplate wells coated with anti-A, -B and -D reagents are used for forward grouping. The test sample is added and the microplate is centrifuged; in a positive reaction, the red blood cells adhere to the surface of the well. [ 7 ] :\u200a590\u200a [ 10 ] :\u200a477\u200a  Some automated analyzers use solid phase assays for blood typing. [ 1 ] :\u200a275\u20136"}
{"_id": "WikiPedia_Hematology$$$corpus_2685", "text": "Genetic testing can be used to determine a person's blood type in certain situations where serologic testing is insufficient. For example, if a person has been transfused with large volumes of donor blood, the results of serologic testing will reflect the antigens on the donor cells and not the person's actual blood type. [ 11 ]  Individuals who produce  antibodies against their own red blood cells [ 21 ] :\u200a202\u200a  or who are treated with certain drugs may show spurious agglutination reactions in serologic testing, so genotyping may be necessary to determine their blood type accurately. [ 1 ] :\u200a261\u200a  Genetic testing is required for typing red blood cell antigens for which no commercial antisera are available. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2686", "text": "The  AABB  recommends RhD antigen genotyping for women with serologic  weak D  phenotypes who have the potential to bear children. This is because some people with weak D phenotypes can produce antibodies against the RhD antigen, which can cause hemolytic disease of the newborn, while others cannot. Genotyping can identify the specific type of weak D antigen, which determines the potential for the person to produce antibodies, thus avoiding unnecessary treatment with  Rho(D) immune globulin . [ 22 ] [ 23 ]  Genotyping is preferred to serologic testing for people with sickle cell disease, because it is more accurate for certain antigens and can identify antigens that cannot be detected by serologic methods. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2687", "text": "Genotyping is also used in prenatal testing for hemolytic disease of the newborn. When a pregnant woman has a blood group antibody that can cause HDN, the fetus can be typed for the relevant antigen to determine if it is at risk of developing the disease. Because it is impractical to draw blood from the fetus, the blood type is determined using  an  amniocentesis  sample or  cell-free fetal DNA  isolated from the mother's blood. [ 21 ] :\u200a202\u200a [ 22 ]  The father may also be genotyped to predict the risk of hemolytic disease of the newborn, because if the father is  homozygous  for the relevant antigen (meaning having two copies of the gene) the baby will be positive for the antigen and thus at risk of developing the disease. If the father is  heterozygous  (having only one copy), the baby only has a 50% chance of being positive for the antigen. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2688", "text": "In ABO typing, the results of the forward and reverse grouping should always correspond with each other. An unexpected difference between the two results is termed an ABO discrepancy, and must be resolved before the person's blood type is reported. [ 1 ] :\u200a136"}
{"_id": "WikiPedia_Hematology$$$corpus_2689", "text": "Weak reactions in the forward grouping may occur in people who belong to certain ABO subgroups\u2014variant blood types characterized by decreased expression of the A or B antigens or changes in their structure. Weakened expression of ABO antigens may also occur in  leukemia  and  Hodgkin's lymphoma . Weak reactions in forward grouping can be strengthened by incubating the blood and reagent mixture at room temperature or 4\u00a0\u00b0C (39\u00a0\u00b0F), or by using certain  enzymes  to enhance the antigen-antibody reactions. [ 1 ] :\u200a139"}
{"_id": "WikiPedia_Hematology$$$corpus_2690", "text": "Occasionally, two populations of red blood cells are apparent after reaction with the blood typing antisera. Some of the red blood cells are agglutinated, while others are not, making it difficult to interpret the result. This is called a  mixed field reaction , and it can occur if someone has recently received a blood transfusion with a different blood type (as in a type A patient receiving type O blood), if they have received a  bone marrow  or  stem cell transplant  from someone with a different blood type, or in patients with certain ABO subgroups, such as A 3 . Investigation of the person's medical history can clarify the cause of the mixed field reaction. [ 1 ] :\u200a138\u200a [ 24 ] :\u200a314"}
{"_id": "WikiPedia_Hematology$$$corpus_2691", "text": "People with  cold agglutinin disease  produce antibodies against their own red blood cells that cause them to spontaneously agglutinate at room temperature, leading to false positive reactions in forward grouping. Cold agglutinins can usually be deactivated by warming the sample to 37\u00a0\u00b0C (99\u00a0\u00b0F) and washing the red blood cells with saline. If this is not effective,  dithiothreitol  can be used to destroy the antibodies. [ 1 ] :\u200a141"}
{"_id": "WikiPedia_Hematology$$$corpus_2692", "text": "Cord blood samples may be contaminated with  Wharton's jelly , a viscous substance that can cause red blood cells to stick together, mimicking agglutination. Wharton's jelly can be removed by thoroughly washing the red blood cells. [ 1 ] :\u200a141"}
{"_id": "WikiPedia_Hematology$$$corpus_2693", "text": "In a rare phenomenon known as \"acquired B antigen\", a patient whose true blood type is A may show a weak positive result for B in the forward grouping. This condition, which is associated with gastrointestinal diseases such as  colon cancer [ 1 ] :\u200a139\u200a  and  intestinal obstruction , [ 24 ] :\u200a126\u200a  results from conversion of the A antigen to a structure mimicking the B antigen by bacterial enzymes. [ 10 ] :\u200a477\u200a  Unlike the true B antigen, acquired B antigen does not react with reagents within a certain pH range. [ 1 ] :\u200a139"}
{"_id": "WikiPedia_Hematology$$$corpus_2694", "text": "Infants under 3 to 6 months of age exhibit missing or weak reactions in reverse grouping because they produce very low levels of ABO antibodies. [ 1 ] :\u200a136\u200a  Therefore, reverse grouping is generally not performed for this age group. [ 10 ] :\u200a486\u200a  Elderly people may also exhibit decreased antibody production, as may people with  hypogammaglobulinemia . Weak reactions can be strengthened by allowing the plasma and red cells to incubate at room temperature for 15 to 30 minutes, and if this is not effective, they can be incubated at 4\u00a0\u00b0C (39\u00a0\u00b0F). [ 1 ] :\u200a137\u20138"}
{"_id": "WikiPedia_Hematology$$$corpus_2695", "text": "Approximately 20% of individuals with the blood type A or AB belong to a subgroup of A, termed A 2 , while the more common subgroup, encompassing approximately 80% of individuals, is termed A 1 . Because of small differences in the structure of the A 1  and A 2  antigens, some individuals in the A 2  subgroup can produce an antibody against A 1 . Therefore, these individuals will type as A or AB in the forward grouping, but will exhibit an unexpected positive reaction with the type A 1  red cells in the reverse grouping. The discrepancy can be resolved by testing the person's red blood cells with an anti-A 1  reagent, which will give a negative result if the patient belongs to the A 2  subgroup. Anti-A 1  antibodies are considered clinically insignificant unless they react at 37\u00a0\u00b0C (99\u00a0\u00b0F). Other subgroups of A exist, as well as subgroups of B, but they are rarely encountered. [ 1 ] :\u200a127\u201332"}
{"_id": "WikiPedia_Hematology$$$corpus_2696", "text": "If high levels of  protein  are present in a person's plasma, a phenomenon known as  rouleaux  may occur when their plasma is added to the reagent cells. Rouleaux causes red blood cells to stack together, which can mimic agglutination, causing a false positive result in the reverse grouping. This can be avoided by removing the plasma, replacing it with saline, and re-centrifuging the tube. Rouleaux will disappear once the plasma is replaced with saline, but true agglutination will persist. [ 1 ] :\u200a140\u20131"}
{"_id": "WikiPedia_Hematology$$$corpus_2697", "text": "Antibodies to blood group antigens other than A and B may react with the reagent cells used in reverse grouping. If a  cold-reacting autoantibody  is present, the false positive result can be resolved by warming the sample to 37\u00a0\u00b0C (99\u00a0\u00b0F). If the result is caused by an alloantibody, an antibody screen can be performed to identify the antibody, [ 7 ] :\u200a141\u20132\u200a  and the reverse grouping can be performed using samples that lack the relevant antigen. [ 10 ] :\u200a477"}
{"_id": "WikiPedia_Hematology$$$corpus_2698", "text": "Approximately 0.2 to 1% of people have a \"weak D\" phenotype, [ 25 ]  meaning that they are positive for the RhD antigen, but exhibit weak or negative reactions with some anti-RhD reagents due to decreased antigen expression or atypical variants of antigen structure. If routine serologic testing for RhD results in a score of 2+ or less, the antiglobulin test can be used to demonstrate the presence of RhD. [ 1 ] :\u200a159\u200a  Weak D testing is also performed on blood donors who initially type as RhD negative. [ 22 ]  Historically, blood donors with weak D were treated as Rh positive and patients with weak D were treated as Rh negative in order to avoid potential exposure to incompatible blood. Genotyping is increasingly used to determine the molecular basis of weak D phenotypes, as this determines whether or not individuals with weak D can produce antibodies against RhD or sensitize others to the RhD antigen. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2699", "text": "The  indirect antiglobulin test , which is used for weak D testing and typing of some red blood cell antigens, detects IgG bound to red blood cells. If IgG is bound to red blood cells  in vivo , as may occur in  autoimmune hemolytic anemia , hemolytic disease of the newborn and transfusion reactions, [ 10 ] :\u200a260\u200a  the indirect antiglobulin test will always give a positive result, regardless of the presence of the relevant antigen. [ 10 ] :\u200a477\u20138\u200a  A  direct antiglobulin test  can be performed to demonstrate that the positive reaction is due to sensitization of red cells. [ 26 ] :\u200a289"}
{"_id": "WikiPedia_Hematology$$$corpus_2700", "text": "Some groups of people have specialized transfusion requirements. Fetuses,  very low-birth-weight infants , and  immunocompromised  people are at risk for developing severe infection with  cytomegalovirus  (CMV)\u2015an  opportunistic pathogen  for which approximately 50% of blood donors test positive\u2015and may be transfused with CMV-negative blood to prevent infection. [ 3 ] :\u200a749\u200a [ 27 ]  Those who are at risk of developing  graft-versus-host disease , such as  bone marrow transplant  recipients, receive blood that has been  irradiated  to inactivate the  T lymphocytes  that are responsible for this reaction. People who have had serious  allergic reactions  to blood transfusions in the past may be transfused with blood that has been \"washed\" to remove plasma. [ 1 ] :\u200a342\u20135\u200a  The history of the patient is also examined to see if they have previously identified antibodies and any other serological anomalies."}
{"_id": "WikiPedia_Hematology$$$corpus_2701", "text": "A direct antiglobulin test ( Coombs test ) is also performed as part of the antibody investigation. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2702", "text": "Donor blood is generally screened for  transfusion-transmitted infections  such as  HIV . As of 2018, the  World Health Organization  reported that nearly 100% of blood donations in high- and upper-middle-income countries underwent infectious disease screening, but the figures for lower-middle-income and low-income countries were 82% and 80.3% respectively. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2703", "text": "In 1901,  Karl Landsteiner  published the results of an experiment in which he mixed the serum and red blood cells of five different human donors. He observed that a person's serum never agglutinated their own red blood cells, but it could agglutinate others', and based on the agglutination reactions the red cells could be sorted into three groups: group A, group B, and group C. Group C, which consisted of red blood cells that did not react with any person's plasma, would later be known as group O. [ 30 ] :\u200a5\u200a   A fourth group, now known as AB, was described by Landsteiner's colleagues in 1902. [ 30 ] :\u200a7\u200a  This experiment was the first example of blood typing. [ 1 ] :\u200a120"}
{"_id": "WikiPedia_Hematology$$$corpus_2704", "text": "In 1945,  Robin Coombs , A.E. Mourant and  R.R. Race  published a description of the  antiglobulin test  (also known as the Coombs test). Previous research on blood group antibodies had documented the presence of so-called \"blocking\" or \"incomplete\" antibodies: antibodies that occupied antigen sites, preventing other antibodies from binding, but did not cause red blood cells to agglutinate. Coombs and his colleagues devised a method to easily demonstrate the presence of these antibodies. They injected human  immunoglobulins  into rabbits, which caused them to produce an  anti-human globulin  antibody. The anti-human globulin could bind to antibodies already attached to red blood cells and cause them to agglutinate. The invention of the antiglobulin test led to the discovery of many more blood group antigens. By the early 1950s, companies had begun producing commercial antisera for special antigen testing. [ 30 ] :\u200a62\u201372"}
{"_id": "WikiPedia_Hematology$$$corpus_2705", "text": "A  blood culture  is a  medical laboratory  test used to detect  bacteria  or  fungi  in a person's  blood . Under normal conditions, the blood does not contain  microorganisms : their presence can indicate a  bloodstream infection  such as  bacteremia  or  fungemia , which in severe cases may result in  sepsis . By  culturing  the blood, microbes can be identified and  tested for resistance to antimicrobial drugs , which allows clinicians to provide an effective treatment."}
{"_id": "WikiPedia_Hematology$$$corpus_2706", "text": "To perform the test, blood is drawn into bottles containing a liquid formula that enhances microbial growth, called a  culture medium . Usually, two containers are collected during one draw, one of which is designed for  aerobic organisms  that require oxygen, and one of which is for  anaerobic organisms , that do not. These two containers are referred to as a  set  of blood cultures. Two sets of blood cultures are sometimes collected from two different blood draw sites. If an organism only appears in one of the two sets, it is more likely to represent contamination with  skin flora  than a true bloodstream infection. False negative results can occur if the sample is collected after the person has received  antimicrobial drugs  or if the bottles are not filled with the recommended amount of blood. Some organisms do not grow well in blood cultures and require special techniques for detection."}
{"_id": "WikiPedia_Hematology$$$corpus_2707", "text": "The containers are placed in an  incubator  for several days to allow the organisms to multiply. If microbial growth is detected, a  Gram stain  is conducted from the culture bottle to confirm that organisms are present and provide preliminary information about their identity. The blood is then  subcultured , meaning it is  streaked  onto an  agar plate  to  isolate  microbial colonies for full identification and antimicrobial susceptibility testing. Because it is essential that bloodstream infections are diagnosed and treated quickly, rapid testing methods have been developed using technologies like  polymerase chain reaction  and  MALDI-TOF MS ."}
{"_id": "WikiPedia_Hematology$$$corpus_2708", "text": "Procedures for culturing the blood were published as early as the mid-19th century, but these techniques were labour-intensive and bore little resemblance to contemporary methods. Detection of microbial growth involved visual examination of the culture bottles until automated blood culture systems, which monitor gases produced by microbial metabolism, were introduced in the 1970s. In developed countries, manual blood culture methods have largely been made obsolete by automated systems."}
{"_id": "WikiPedia_Hematology$$$corpus_2709", "text": "Blood is normally  sterile . [ 1 ]  The presence of  bacteria  in the blood is termed  bacteremia , and the presence of  fungi  is called  fungemia . [ 2 ]  Minor damage to the skin [ 3 ]  or  mucous membranes , which can occur in situations like  toothbrushing  or  defecation , [ 4 ] [ 5 ]  can introduce bacteria into the bloodstream, but this bacteremia is normally transient and is rarely detected in cultures because the  immune system  and  reticuloendothelial system  quickly sequester and destroy the organisms. [ 3 ] [ 6 ]  Bacteria can enter the blood from infections such as  cellulitis ,  UTIs  and  pneumonia ; [ 7 ]  and infections within the  vascular system , such as  bacterial endocarditis  or infections associated with  intravenous lines , may result in a constant bacteremia. [ 4 ]  Fungemia occurs most commonly in people with  poorly functioning immune systems . [ 2 ]  If bacteria or fungi are not cleared from the bloodstream, they can spread to other organs and tissues, [ 3 ]  or evoke an  immune response  that leads to a systemic inflammatory condition called  sepsis , which can be life-threatening. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2710", "text": "When sepsis is suspected, it is necessary to draw blood cultures to identify the causative agent and provide targeted  antimicrobial therapy . [ 10 ]  People who are hospitalized and have a fever, a  low body temperature , a  high white blood cell count  or a low count of  granulocytes  (a category of  white blood cells ) commonly have cultures drawn to detect a possible bloodstream infection. [ 11 ] [ 12 ]  Blood cultures are used to detect bloodstream infections in  febrile neutropenia , a common complication of  chemotherapy  in which  fever  occurs alongside a severely low count of  neutrophils  (white blood cells that defend against bacterial and fungal pathogens). [ 13 ] [ 14 ] [ 15 ]  Bacteremia is common in some types of infections, such as  meningitis ,  septic arthritis  and  epidural abscesses , so blood cultures are indicated in these conditions. In infections less strongly associated with bacteremia, blood culture may still be indicated if the individual is at high risk of acquiring an intravascular infection or if cultures cannot be promptly obtained from the main site of infection (for example, a  urine culture  in  pyelonephritis  or a  sputum culture  in severe  community-acquired pneumonia ). [ 16 ] [ 17 ]  Blood culture can identify an underlying microbial cause in cases of  endocarditis [ 18 ]  and  fever of unknown origin . [ 11 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2711", "text": "The pathogens most frequently identified in blood cultures include  Staphylococcus aureus ,  Escherichia coli  and other members of the family  Enterobacteriaceae ,  Enterococcus  species,  Pseudomonas aeruginosa  and  Candida albicans . [ 20 ] [ 21 ]   Coagulase-negative staphylococci  (CNS) are also commonly encountered, although it is often unclear whether these organisms, which constitute part of the normal skin flora, [ 22 ]  are true pathogens or merely contaminants. [ 21 ]  In blood cultures taken from newborn babies and children, CNS can indicate significant infections. [ 23 ]   The  epidemiology  of bloodstream infections varies with time and place; for instance,  Gram-positive  organisms  overtook  Gram-negative  organisms as the predominant cause of bacteremia in the United States during the 1980s and 1990s, [ 24 ]  and rates of fungemia have greatly increased in association with a growing population of people receiving immunosuppressive treatments such as chemotherapy. [ 25 ]  Gram-negative sepsis is more common in Central and South America, Eastern Europe, and Asia than in North America and Western Europe; and in Africa,  Salmonella enterica  is a leading cause of bacteremia. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2712", "text": "Blood cultures are typically drawn through  venipuncture . Collecting the sample from an intravenous line is not recommended, as this is associated with higher contamination rates, although cultures may be collected from both venipuncture and an intravenous line to diagnose catheter-associated infections. [ 11 ] [ 27 ]  Prior to the blood draw, the top of each collection bottle is disinfected using an alcohol swab to prevent contamination. [ 11 ]  The skin around the puncture site is then cleaned and left to dry; some protocols recommend disinfection with an alcohol-based antiseptic followed by either  chlorhexidine  or an  iodine -based preparation, [ note 1 ] [ 27 ] [ 28 ]  while others consider using only an alcohol-containing antiseptic to be sufficient. [ 17 ] [ 29 ]  If blood must be drawn for other tests at the same time as a blood culture, the culture bottles are  drawn first  to minimize the risk of contamination. [ 30 ]  Because antimicrobial therapy can cause false negative results by inhibiting the growth of microbes, it is recommended that blood cultures are drawn before antimicrobial drugs are given, although this may be impractical in people who are critically ill. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2713", "text": "A typical blood culture collection involves drawing blood into two bottles, which together form one \"culture\" or \"set\". One bottle is designed to enhance the growth of  aerobic organisms , and the other is designed to grow  anaerobic organisms . In children, infection with anaerobic bacteria is uncommon, so a single aerobic bottle may be collected to minimize the amount of blood required. [ 31 ]  It is recommended that at least two sets are collected from two separate venipuncture locations. This helps to distinguish infection from contamination, as contaminants are less likely to appear in more than one set than true  pathogens . Additionally, the collection of larger volumes of blood increases the likelihood that microorganisms will be detected if present. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2714", "text": "Blood culture bottles contain a  growth medium , which encourages microorganisms to multiply, and an  anticoagulant  that prevents blood from  clotting . [ 33 ]  Sodium polyanethol sulfonate (SPS) is the most commonly used anticoagulant [ 33 ]  because it does not interfere with the growth of most organisms. [ 28 ]  The exact composition of the growth medium varies, but aerobic bottles use a broth that is enriched with nutrients, such as  brain-heart infusion  or  trypticase soy broth , [ 34 ]  and anaerobic bottles typically contain a  reducing agent  such as  thioglycollate . The empty space in an anaerobic bottle is filled with a gas mixture that does not contain oxygen. [ 33 ] [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2715", "text": "Many commercially manufactured bottles contain a  resin  that absorbs  antibiotics  to reduce their action on the microorganisms in the sample. [ 11 ]  Bottles intended for paediatric use are designed to accommodate lower blood volumes and have additives that enhance the growth of pathogens more commonly found in children. [ 36 ]  Other specialized bottles may be used to detect fungi and  mycobacteria . [ 35 ]  In  low and middle income countries , pre-formulated culture bottles can be prohibitively expensive, and it may be necessary to prepare the bottles manually. It can be difficult to access the proper supplies and facilities, [ 37 ]  and in some regions, it may not be possible to perform blood cultures at all. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2716", "text": "It is important that the bottles are neither underfilled nor overfilled: underfilling can lead to false negative results as fewer organisms are present in the sample, while overfilling can inhibit microbial growth because the ratio of growth medium to blood is comparatively lower. A 1:10 to 1:5 ratio of blood to culture medium is suggested to optimize microbial growth. [ 28 ] [ 39 ]  For routine blood cultures in adults, the  Clinical and Laboratory Standards Institute  (CLSI) recommends the collection of two sets of bottles from two different draws, with 20\u201330 mL of blood drawn in each set. [ 11 ]  In children, the amount of blood to be drawn is often based on the child's age or weight. [ 36 ] [ 40 ]  If endocarditis is suspected, a total of six bottles may be collected. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2717", "text": "After the blood is collected, the bottles are  incubated  at body temperature to encourage the growth of microorganisms. Bottles are usually incubated for up to five days in automated systems, [ 43 ]  although most common bloodstream pathogens are detected within 48 hours. [ 44 ]  The incubation time may be extended further if manual blood culture methods are used or if slower-growing organisms, such as certain bacteria that cause endocarditis, are suspected. [ 43 ] [ 45 ]  In manual systems, the bottles are visually examined for indicators of microbial growth, which might include cloudiness, the production of gas,  the presence of visible microbial colonies, or a change in colour from the digestion of blood, which is called  hemolysis . Some manual blood culture systems indicate growth using a compartment that fills with fluid when gases are produced, or a miniature agar plate which is periodically inoculated by tipping the bottle. [ 46 ]  To ensure that positive blood cultures are not missed, a sample from the bottle is often inoculated onto an agar plate ( subcultured ) at the end of the incubation period regardless of whether or not indicators of growth are observed. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2718", "text": "In developed countries, manual culture methods have largely been replaced by automated systems that provide continuous computerized monitoring of the culture bottles. [ 48 ]  These systems, such as the BACTEC, BacT/ALERT and VersaTrek, consist of an incubator in which the culture bottles are continuously mixed. Growth is detected by sensors that measure the levels of gases inside the bottle\u2014most commonly  carbon dioxide \u2014which serve as an indicator of microbial metabolism. [ 46 ]  An alarm or a visual indicator alerts the microbiologist to the presence of a positive blood culture bottle. [ 49 ]  If the bottle remains negative at the end of the incubation period, it is generally discarded without being subcultured. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2719", "text": "A technique called the lysis-centrifugation method can be used for improved isolation of slow-growing or  fastidious  organisms, such as fungi, mycobacteria, and  Legionella . [ 50 ] [ 51 ]  Rather than incubating the blood in a bottle filled with growth medium, [ 52 ]  this method involves collecting blood into a tube containing an agent that destroys ( lyses ) red and white blood cells, then spinning the sample in a  centrifuge . This process concentrates the solid contents of the sample, including microorganisms if present, into a pellet, which is used to inoculate the subculture media. While lysis-centrifugation offers greater  sensitivity  than conventional blood culture methods, it is prone to contamination because it requires extensive manipulation of the sample. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2720", "text": "If growth is detected, a microbiologist will perform a  Gram stain  on a sample of blood from the bottle for a rapid preliminary identification of the organism. [ 54 ]  The Gram stain classifies bacteria as  Gram-positive  or  Gram-negative  and provides information about  their shape \u2014whether they are rod-shaped (referred to as  bacilli ),  spherical (referred to as  cocci ), or spiral-shaped ( spirochetes )\u2014as well as their arrangement. [ 55 ]   Gram-positive cocci in clusters, for example, are typical of  Staphylococcus  species. [ 56 ]   Yeast  and other fungi may also be identified from the Gram stain. [ 57 ] [ 58 ]  A Gram stain identifying microbial growth from a blood culture is considered a critical result and must immediately be reported to the clinician. [ 59 ]  The Gram stain provides information about the possible identity of the organism, which assists the clinician in the selection of a more appropriate antimicrobial treatment before the full culture and sensitivity results are complete. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2721", "text": "In traditional methods, the blood is then subcultured onto  agar plates  to  isolate  the organism for further testing. The Gram stain results inform microbiologists about what  types of agar plates  should be used and what tests might be appropriate to identify the organism. [ 60 ]  In some cases, no organisms are seen on the Gram stain despite the culture bottle showing indicators of growth or being reported as positive by automated instruments. This may represent a false positive result, but it is possible that organisms are present but cannot easily be visualized microscopically. Positive bottles with negative Gram stains are subcultured before being returned to the incubator, often using special culture media that promotes the growth of slow-growing organisms. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2722", "text": "It typically takes 24 to 48 hours for sufficient growth to occur on the subculture plates for definitive identification to be possible. [ 57 ]  At this point, the microbiologist will assess  the appearance of the bacterial or fungal colonies [ 62 ]  and carry out tests that provide information about the metabolic and biochemical features of the organism, which permit identification to the  genus  or species level. For example, the  catalase test  can distinguish  streptococci  and staphylococci (two  genera  of Gram-positive cocci) [ 63 ]  from each other, and the  coagulase test  can differentiate  Staphylococcus aureus , a common culprit of bloodstream infections, from the less pathogenic coagulase-negative staphylococci. [ 29 ] [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2723", "text": "Microorganisms may also be identified using automated systems, such as instruments that perform panels of biochemical tests, [ 65 ]  or  matrix-assisted laser desorption/ionization time-of-flight mass spectrometry  (MALDI-TOF MS), in which microbial proteins are  ionized  and characterized on the basis of their  mass-to-charge ratios ; each microbial species exhibits a characteristic pattern of proteins when analyzed through  mass spectrometry . [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2724", "text": "Because bloodstream infections can be life-threatening, timely diagnosis and treatment is critical, [ 67 ]  and to this end several rapid identification methods have been developed. [ 57 ]  MALDI-TOF can be used to identify organisms directly from positive blood culture bottles after separation and concentration procedures, [ 68 ]  or from preliminary growth on the agar plate within a few hours of subculturing. [ 69 ]  Genetic methods such as  polymerase chain reaction  (PCR) and  microarrays  can identify microorganisms by detection of  DNA sequences  specific to certain species in blood culture samples. Several systems designed for the identification of common blood culture pathogens are commercially available. [ 70 ]  Some biochemical and immunologic tests can be performed directly on positive blood cultures, such as the  tube coagulase  test for identification of  S. aureus [ 57 ]  or  latex agglutination  tests for  Streptococcus pneumoniae , [ 71 ]  and unlike PCR and MALDI-TOF, these methods may be practical for laboratories in low and middle income countries. [ 42 ]  It is also possible to directly inoculate microbial identification panels with blood from a positive culture bottle, although this is not as reliable as testing subcultured bacteria because additives from the growth media can interfere with the results. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2725", "text": "Even faster diagnosis could be achieved through bypassing culture entirely and detecting pathogens directly from blood samples. A few direct testing systems are commercially available as of 2018, but the technology is still in its infancy. Most panels detect only a limited number of pathogens, and the sensitivity can be poor compared to conventional blood culture methods. Culturing remains necessary in order to carry out full antimicrobial sensitivity testing. [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2726", "text": "Antimicrobial treatment of bloodstream infections is initially  empiric , meaning it is based on the clinician's suspicion about the causative agent of the disease and local patterns of antimicrobial resistance. Carrying out  antibiotic susceptibility testing  (AST) on pathogens isolated from a blood culture allows clinicians to provide a more targeted treatment and to discontinue  broad-spectrum antibiotics , which can have undesirable side effects. [ 8 ] [ 10 ]  In traditional AST methods, such as the  disk diffusion test , pure colonies of the organism are selected from the subculture plate and used to inoculate a secondary medium. These methods require overnight incubation before results can be obtained. [ 74 ]  There are automated systems which use pre-formulated antibiotic panels, measure microbial growth automatically, and determine the sensitivity results using algorithms; some of these can provide results in as little as five hours, but others require overnight incubation as well. [ 65 ] [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2727", "text": "Rapid administration of effective antimicrobial drugs is crucial in the treatment of sepsis, [ 8 ]  so several methods have been developed to provide faster antibiotic sensitivity results. Conventional AST methods can be carried out on young growth from the subculture plate, [ 76 ]  pellets of microorganisms obtained from concentration and purification of the positive blood culture, or directly from the culture bottle. [ 77 ] [ 78 ]  Because direct testing methods do not isolate the organisms, they do not provide accurate results if more than one microorganism is present, although this is an infrequent occurrence in blood cultures. [ 76 ]  Another source of error is the difficulty in standardizing the amount of bacteria in the sample (the  inoculum ), which has a profound effect on the test results. [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2728", "text": "Genetic testing  can be used for rapid detection of certain antimicrobial resistance markers. [ 80 ]  Methods such as PCR and microarrays, which can be performed directly on positive blood culture samples, [ 70 ]  detect DNA sequences associated with genes that confer resistance, such as the  mecA  gene found in  methicillin-resistant  Staphylococcus aureus  or the  vanA  and  vanB  genes of  vancomycin-resistant enterococci . [ 68 ]  MALDI-TOF has been explored as a rapid antimicrobial sensitivity testing method; principles involve measuring microbial growth in the presence of antibiotics, identifying the breakdown of antibiotics by microbial  enzymes , and detecting protein spectra associated with bacterial strains that exhibit antibiotic resistance. [ 79 ]  Some of these methods can be performed on pellets from positive blood culture bottles. [ 81 ]  However, the lack of established methodologies for AST by MALDI-TOF limits its use in clinical practice, [ 82 ]  and direct AST by MALDI-TOF, unlike genetic testing methods, had not been approved by the  Food and Drug Administration  as of 2018. [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2729", "text": "Blood cultures are subject to both false positive and false negative errors. In automated culture systems, identification of positive bottles is based on the detection of gases produced by cellular metabolism, so samples with high numbers of  white blood cells  may be reported as positive when no bacteria are present. Inspection of the growth curve produced by the instrument can help to distinguish between true and false positive cultures, but Gram staining and subculturing are still necessary for any sample that is flagged as positive. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2730", "text": "Blood cultures can become contaminated with microorganisms from the skin or the environment, which multiply inside the culture bottle, giving the false impression that those organisms are present in the blood. [ 11 ]  Contamination of blood cultures can lead to unnecessary antibiotic treatment and longer hospital stays. [ 29 ]  The frequency of contamination can be reduced by following established protocols for blood culture collection, but it cannot be eliminated; [ 83 ]  for instance, bacteria can survive in deeper layers of the skin even after meticulous disinfection of the blood draw site. [ 29 ]  The CLSI defines an acceptable contamination rate as no greater than 3% of all blood cultures. [ 11 ]  The frequency of contamination varies widely between institutions and between different departments in the same hospital; [ 83 ]  studies have found rates ranging from 0.8 to 12.5 percent. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2731", "text": "When faced with a positive blood culture result, clinicians must decide whether the finding represents contamination or genuine infection. Some organisms, such as  S. aureus  or  Streptococcus pneumoniae , are usually considered to be pathogenic when detected in a blood culture, while others are more likely to represent contamination with skin flora; but even common skin organisms such as coagulase-negative staphylococci can cause bloodstream infections under certain conditions. When such organisms are present, interpretation of the culture result involves taking into account the person's clinical condition and whether or not multiple cultures are positive for the same organism. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2732", "text": "False negatives may be caused by drawing blood cultures after the person has received antibiotics or collecting an insufficient amount of blood. The volume of blood drawn is considered the most important variable in ensuring that pathogens are detected: the more blood that is collected, the more pathogens are recovered. [ 11 ]  However, if the amount of blood collected far exceeds the recommended volume, bacterial growth may be inhibited by natural inhibitors present in the blood and an inadequate amount of growth medium in the bottle. Over-filling of blood culture bottles may also contribute to  iatrogenic anemia . [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2733", "text": "Not all pathogens are easily detected by conventional blood culture methods. Particularly  fastidious organisms , such as  Brucella  and  Mycobacterium  species, may require prolonged incubation times or special culture media. Some organisms are exceedingly difficult to culture or do not grow in culture at all, so  serology testing  or molecular methods such as PCR are preferred if infection with these organisms is suspected. [ 45 ] [ 84 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2734", "text": "Early blood culture methods were labour-intensive. [ 86 ]  One of the first known procedures, published in 1869, recommended that  leeches  be used to collect blood from the patient. [ 87 ]  A microbiology textbook  from 1911 noted that decontamination of the draw site and equipment could take over an hour, and that due to a lack of effective methods for preserving blood, the cultures would sometimes have to be prepared at the patient's bedside. In addition to subculturing the broth, some protocols specified that the blood be mixed with melted agar and the mixture poured into a petri dish. [ 86 ]  In 1915, a blood culture collection system consisting of glass vacuum tubes containing  glucose  broth and an anticoagulant was described.  Robert James Valentine Pulvertaft  published a seminal work on blood cultures in 1930, [ 88 ]  specifying\u2014among other insights\u2014an optimal blood-to-broth ratio of 1:5, which is still accepted today. [ 87 ]  The use of SPS as an anticoagulant and preservative was introduced in the 1930s and 40s and resolved some of the logistical issues with earlier methods. [ 86 ]  From the 1940s through the 1980s, a great deal of research was carried out on broth formulations and additives, with the goal of creating a growth medium that could accommodate all common bloodstream pathogens. [ 87 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2735", "text": "In 1947, M.R. Casta\u00f1eda invented a \"biphasic\" culture bottle for the identification of  Brucella  species, which contained both broth and an agar slant, allowing the agar to be easily subcultured from the broth; [ 42 ]  this was a precursor of some contemporary systems for manual blood cultures. [ 43 ]  E.G. Scott in 1951 published a protocol described as \"the advent of the modern blood culture set\". [ 86 ]  Scott's method involved inoculating blood into two rubber-sealed glass bottles; one for aerobes and one for anaerobes. The aerobic bottle contained trypticase soy broth and an agar slant, and the anaerobic bottle contained thioglycollate broth. The lysis-centrifugation method was introduced in 1917 by Mildred Clough, but it was rarely used in clinical practice until commercial systems were developed in the mid-1970s. [ 86 ] [ 89 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2736", "text": "Automated blood culture systems first became available in the 1970s. [ 90 ]  The earliest of these\u2014the BACTEC systems, produced by Johnston Laboratories (now  Becton Dickinson )\u2014used culture broths containing nutrients  labelled  with  radioactive isotopes . Microbes that fed on these substrates would produce radioactive carbon dioxide, and growth could be detected by monitoring its concentration. [ 50 ] [ 91 ]  Before this technique was applied to blood cultures, it had been proposed by  NASA  as a method for detecting life on Mars. [ 86 ]   Throughout the 1970s and 80s several manufacturers attempted to detect microbial growth by measuring changes in the  electrical conductivity  of the culture medium, but none of these methods were commercially successful. [ 91 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2737", "text": "A major issue with the early BACTEC systems was that they produced  radioactive waste , which required special disposal procedures, [ 50 ]  so in 1984 a new generation of BACTEC instruments was released that used  spectrophotometry  to detect CO 2 . [ 91 ]  The BacT/ALERT system, which indirectly detects production of CO 2  by measuring the decrease in the medium's pH, was approved for use in the US in 1991. Unlike the BACTEC systems available at the time, the BacT/ALERT did not require a needle to be introduced into the bottle for sampling; this reduced the frequency of contamination [ 91 ]  and made it the first system to provide truly continuous monitoring of blood cultures. [ 92 ]  This non-invasive measurement method was adopted in 1992 by the BACTEC 9000 series, which used fluorescent indicators to detect pH changes. [ 93 ]  The Difco ESP, a direct predecessor of the contemporary VersaTREK system [ 86 ]  which detects gas production by measuring pressure changes, was also first approved in 1992. [ 91 ]  By 1996, an international study found that 55% of 466 laboratories surveyed were using the BACTEC or BacT/ALERT systems, with other automated systems accounting for 10% of the total. [ 94 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2738", "text": "A  blood smear ,  peripheral blood smear  or  blood film  is a thin layer of  blood  smeared on a glass  microscope slide  and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the investigation of  hematological  (blood) disorders and are routinely employed to look for blood  parasites , such as those of  malaria  and  filariasis ."}
{"_id": "WikiPedia_Hematology$$$corpus_2739", "text": "A blood smear is made by placing a drop of blood on one end of a slide, and using a  spreader slide  to disperse the blood over the slide's length. The aim is to get a region, called a monolayer, where the cells are spaced far enough apart to be counted and differentiated. The monolayer is found in the \"feathered edge\" created by the spreader slide as it draws the blood forward. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2740", "text": "The slide is left to air dry, after which the blood is  fixed  to the slide by immersing it briefly in  methanol . The fixative is essential for good staining and presentation of cellular detail. After fixation, the slide is  stained  to distinguish the cells from each other. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2741", "text": "Routine analysis of blood in medical laboratories is usually performed on blood films stained with  Romanowsky stains  such as  Wright's stain ,  Giemsa stain , or  Diff-Quik . Wright-Giemsa combination stain is also a popular choice. These stains allow for the detection of  white blood cell ,  red blood cell , and  platelet  abnormalities.  Hematopathologists  often use other specialized stains to aid in the differential diagnosis of blood disorders. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2742", "text": "After staining, the monolayer is viewed under a microscope using magnification up to 1000 times. Individual cells are examined and their morphology is characterized and recorded. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2743", "text": "Blood smear examination is usually performed in conjunction with a  complete blood count  in order to investigate abnormal results or confirm results that the  automated analyzer  has flagged as unreliable. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2744", "text": "Microscopic examination of the shape, size, and coloration of red blood cells is useful for determining the cause of  anemia . Disorders such as  iron deficiency anemia ,  sickle cell anemia ,  megaloblastic anemia  and  microangiopathic hemolytic anemia  result in characteristic abnormalities on the blood film. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2745", "text": "The proportions of different types of  white blood cells  can be determined from the blood smear. This is known as a manual  white blood cell differential . The white blood cell differential can reveal abnormalities in the proportions of white blood cell types, such as  neutrophilia  and  eosinophilia , as well as the presence of abnormal cells such as the circulating  blast cells  seen in  acute leukemia . [ 4 ]   Qualitative abnormalities of white blood cells, like  toxic granulation , are also visible on the blood smear. Modern complete blood count analyzers can provide an automated white blood cell differential, but they have a limited ability to differentiate immature and abnormal cells, so manual examination of the blood smear is frequently indicated. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2746", "text": "Blood smear examination is the preferred diagnostic method for certain parasitic infections, such as malaria and  babesiosis . [ 7 ]  Rarely, bacteria may be visible on the blood smear in patients with severe  sepsis . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2747", "text": "The preferred and most reliable diagnosis of malaria is microscopic examination of blood smears, because each of the four major parasite species has distinguishing characteristics.  Two sorts of blood smear are traditionally used. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2748", "text": "From the thick smear, an experienced microscopist can detect all parasites they encounter. Microscopic diagnosis can be difficult because the early trophozoites (\"ring form\") of all four species look identical and it is never possible to diagnose species on the basis of a single ring form; species identification is always based on several trophozoites. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2749", "text": "The biggest pitfall in most laboratories in developed countries is leaving too great a delay between taking the blood sample and making the blood smears.  As blood cools to room temperature, male gametocytes will divide and release  microgametes : these are long sinuous filamentous structures that can be mistaken for organisms such as  Borrelia . If the blood is kept at warmer temperatures,  schizonts  will rupture and merozoites invading erythrocytes will mistakenly give the appearance of the accol\u00e9 form of  P. falciparum . If  P. vivax  or  P. ovale  is left for several hours in EDTA, the buildup of acid in the sample will cause the parasitised erythrocytes to shrink and the parasite will roll up, simulating the appearance of  P. malariae . This problem is made worse if  anticoagulants  such as  heparin  or  citrate  are used.  The anticoagulant that causes the least problems is  EDTA . Romanowsky stain or a variant stain is usually used. Some laboratories mistakenly use the same staining pH as they do for routine haematology blood films ( pH  6.8): malaria blood films must be stained at pH 7.2, or  Sch\u00fcffner's dots  and  James'  dots will not be seen. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2750", "text": "Immunochromatographic  capture procedures (rapid diagnostic tests such as the  malaria antigen detection tests ) are nonmicroscopic diagnostic options for the laboratory that may not have appropriate microscopy expertise available. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2751", "text": "The  blood sugar level ,  blood sugar concentration ,   blood glucose level , or  glycemia  is the measure of  glucose  concentrated in the  blood . The body tightly  regulates blood glucose levels  as a part of metabolic  homeostasis . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2752", "text": "For a 70\u00a0kg (154\u00a0lb) human, approximately four grams of  dissolved  glucose (also called \"blood glucose\") is maintained in the  blood plasma  at all times. [ 2 ]  Glucose that is not circulating in the blood is stored in  skeletal muscle  and  liver  cells in the form of  glycogen ; [ 2 ]  in  fasting  individuals, blood glucose is maintained at a constant level by releasing just enough glucose from these glycogen stores in the liver and skeletal muscle in order to maintain homeostasis. [ 2 ]  Glucose can be transported from the intestines or liver to other tissues in the body via the bloodstream. [ 2 ]  Cellular glucose uptake is primarily regulated by  insulin , a  hormone  produced in the  pancreas . [ 2 ]  Once inside the cell, the glucose can now act as an energy source as it undergoes the process of  glycolysis ."}
{"_id": "WikiPedia_Hematology$$$corpus_2753", "text": "In humans, properly maintained glucose levels are necessary for normal function in a number of tissues, including the  human brain , which consumes approximately 60% of blood glucose in fasting, sedentary individuals. [ 2 ]  A persistent elevation in blood glucose leads to glucose toxicity, which contributes to cell dysfunction and the pathology grouped together as complications of  diabetes . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2754", "text": "Glucose levels are usually lowest in the morning, before the first meal of the day, and rise after meals for an hour or two by a few  millimoles  per litre."}
{"_id": "WikiPedia_Hematology$$$corpus_2755", "text": "Abnormal persistently high glycemia is referred to as  hyperglycemia ; low levels are referred to as  hypoglycemia .  Diabetes mellitus  is characterized by persistent hyperglycemia from a variety of causes, and it is the most prominent disease related to the failure of blood sugar regulation. Diabetes mellitus is also characterized by frequent episodes of low sugar, or  hypoglycemia . There are different methods of  testing  and measuring blood sugar levels."}
{"_id": "WikiPedia_Hematology$$$corpus_2756", "text": "Drinking  alcohol  causes an initial surge in blood sugar and later tends to cause levels to fall. Also, certain drugs can increase or decrease glucose levels. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2757", "text": "There are two ways of measuring blood glucose levels: In the United Kingdom and Commonwealth countries (Australia, Canada, India, etc.) and ex-USSR countries  molar concentration , measured in  mmol/L  (millimoles per litre, or millimolar, abbreviated mM). In the United States, Germany, Japan and many other countries  mass concentration  is measured in mg/dl (milligrams per  decilitre ). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2758", "text": "Unit conversion formula from mmol/L to mg/dL [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2759", "text": "m \n g \n \n / \n \n d \n L \n = \n m \n m \n o \n l \n \n / \n \n L \n \u00d7 \n m \n o \n l \n e \n c \n u \n l \n a \n r \n \u00a0 \n w \n e \n i \n g \n h \n t \n \u00f7 \n 10 \n \n \n {\\displaystyle mg/dL=mmol/L\\times molecular\\ weight\\div 10}"}
{"_id": "WikiPedia_Hematology$$$corpus_2760", "text": "Since the  molecular mass  of glucose C 6 H 12 O 6  is 180.156 g/mol, the factor between the two units is about 18, so 1 mmol/L of glucose is equivalent to 18 mg/dL."}
{"_id": "WikiPedia_Hematology$$$corpus_2761", "text": "m \n g \n \n / \n \n d \n L \n = \n m \n m \n o \n l \n \n / \n \n L \n \u00d7 \n 18 \n \n \n {\\displaystyle mg/dL=mmol/L\\times 18}"}
{"_id": "WikiPedia_Hematology$$$corpus_2762", "text": "Normal blood glucose level (tested while fasting) for non-diabetics should be 3.9\u20135.5 mmol/L (70\u2013100 mg/dL). [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2763", "text": "According to the  American Diabetes Association , the fasting blood glucose target range for diabetics, should be 3.9 - 7.2 mmol/L (70 - 130 mg/dL) and less than 10\u00a0mmol/L (180\u00a0mg/dL)  two hours after meals (as measured by a blood glucose monitor). [ 6 ] [ 7 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2764", "text": "Normal value ranges  may vary slightly between laboratories.  Glucose homeostasis , when operating normally, restores the blood sugar level to a narrow range of about 4.4 to 6.1\u00a0mmol/L (79 to 110\u00a0mg/dL) (as measured by a  fasting blood glucose test ). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2765", "text": "The global mean fasting plasma blood glucose level in humans is about 5.5\u00a0mmol/L (100\u00a0mg/dL); [ 11 ] [ 12 ]  however, this level fluctuates throughout the day. Blood sugar levels for those without diabetes and who are not fasting should be below 6.9\u00a0mmol/L (125\u00a0mg/dL). [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2766", "text": "Despite widely variable intervals between meals or the occasional consumption of meals with a substantial  carbohydrate  load, human blood glucose levels tend to remain within the normal range. However, shortly after eating, the blood glucose level may rise, in non-diabetics, temporarily up to 7.8\u00a0mmol/L (140\u00a0mg/dL) or slightly more."}
{"_id": "WikiPedia_Hematology$$$corpus_2767", "text": "The actual amount of glucose in the blood and body fluids is very small. In a healthy adult male of 75\u00a0kg (165\u00a0lb) with a blood volume of 5\u00a0L, a blood glucose level of 5.5\u00a0mmol/L (100\u00a0mg/dL) amounts to 5\u00a0g, equivalent to about a teaspoonful of sugar. [ 14 ]  Part of the reason why this amount is so small is that, to maintain an influx of glucose into cells,  enzymes  modify glucose by adding  phosphate  or other groups to it. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2768", "text": "In general, ranges of blood sugar in common domestic  ruminants  are lower than in many  monogastric  mammals. [ 15 ]    However this generalization does not extend to wild ruminants or  camelids .  For serum glucose in mg/dL, reference ranges of 42 to 75 for cows, 44 to 81 for sheep, and 48 to 76 for goats, but 61 to 124 for cats; 62 to 108 for dogs, 62 to 114 for horses, 66 to 116 for pigs, 75 to 155 for rabbits, and 90 to 140 for llamas have been reported. [ 16 ]   A 90 percent reference interval for serum glucose of 26 to 181\u00a0mg/dL has been reported for captured mountain goats ( Oreamnos americanus ), where no effects of the pursuit and capture on measured levels were evident. [ 17 ]   For beluga whales, the 25\u201375 percent range for serum glucose has been estimated to be 94 to 115\u00a0mg/dL. [ 18 ]   For the white rhinoceros, one study has indicated that the 95 percent range is 28 to 140\u00a0mg/dL. [ 19 ]   For harp seals, a serum glucose range of 4.9 to 12.1\u00a0mmol/L [i.e. 88 to 218\u00a0mg/dL] has been reported; for hooded seals, a range of 7.5 to 15.7\u00a0mmol/L [i.e. about 135 to 283\u00a0mg/dL] has been reported. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2769", "text": "The body's  homeostatic  mechanism keeps blood glucose levels within a narrow range. It is composed of several interacting systems, of which hormone regulation is the most important. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2770", "text": "There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels:"}
{"_id": "WikiPedia_Hematology$$$corpus_2771", "text": "These hormones are secreted from  pancreatic islets  (bundles of endocrine tissues), of which there are four types: alpha (A) cells, beta (B) cells, Delta (D) cells and F cells. Glucagon is secreted from alpha cells, while insulin is secreted by beta cells. Together they regulate the blood-glucose levels through negative feedback, a process where the end product of one reaction stimulates the beginning of another reaction. In blood-glucose levels, insulin lowers the concentration of glucose in the blood. The lower blood-glucose level (a product of the insulin secretion) triggers glucagon to be secreted, and repeats the cycle. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2772", "text": "In order for blood glucose to be kept stable, modifications to insulin, glucagon, epinephrine and cortisol are made. Each of these hormones has a different responsibility to keep blood glucose regulated; when blood sugar is too high, insulin tells muscles to take up excess glucose for storage in the form of  glycogen . Glucagon responds to too low of a blood glucose level; it informs the tissue to release some glucose from the glycogen stores. Epinephrine prepares the muscles and respiratory system for activity in the case of a \"fight or flight\" response. Lastly, cortisol supplies the body with fuel in times of heavy stress. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2773", "text": "If blood sugar levels remain too high the body suppresses appetite over the short term. Long-term  hyperglycemia  causes many health problems including heart disease, cancer, [ 25 ]  eye, kidney, and nerve damage. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2774", "text": "Blood sugar levels above 16.7 \u00a0 mmol/L (300 \u00a0 mg/dL) can cause fatal reactions. Ketones will be very high (a magnitude higher than when eating a very low carbohydrate diet) initiating  ketoacidosis . The ADA (American Diabetes Association) recommends seeing a doctor if blood glucose reaches 13.3 mmol/L (240 mg/dL), [ 27 ]  and it is recommended to seek emergency treatment at 15 \u00a0 mmol/L (270 \u00a0 mg/dL) blood glucose if Ketones are present. [ 28 ]  The most common cause of hyperglycemia is  diabetes . When diabetes is the cause, physicians typically recommend an  anti-diabetic medication  as treatment. From the perspective of the majority of patients, treatment with an old, well-understood diabetes drug such as  metformin  will be the safest, most effective, least expensive, and most comfortable route to managing the condition. Treatment will vary for the distinct forms of Diabetes and can differ from person to person based on how they are reacting to treatment. [ 29 ]  Diet changes and exercise implementation may also be part of a treatment plan for diabetes. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2775", "text": "Some medications may cause a rise in blood sugars of diabetics, such as steroid medications, including cortisone, hydrocortisone, prednisolone, prednisone, and dexamethasone. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2776", "text": "When the blood sugar level is below 70\u00a0mg/dL, this is referred to as having low blood sugar. Low blood sugar is very frequent among type 1 diabetics. There are several causes of low blood sugar, including, taking an excessive amount of insulin, not  consuming enough carbohydrates, drinking alcohol, spending time at a high elevation, puberty, and menstruation. [ 32 ]  If blood sugar levels drop too low, a potentially fatal condition called  hypoglycemia  develops. Symptoms may include  lethargy , impaired mental functioning;  irritability ; shaking, twitching, weakness in arm and leg muscles; pale complexion; sweating;  loss of consciousness . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2777", "text": "Mechanisms that restore satisfactory blood glucose levels after extreme  hypoglycemia  (below 2.2\u00a0mmol/L or 40\u00a0mg/dL) must be quick and effective to prevent extremely serious consequences of insufficient glucose: confusion or unsteadiness and, in the extreme (below 0.8\u00a0mmol/L or 15\u00a0mg/dL)  loss of consciousness and seizures. Without discounting the potentially quite serious conditions and risks due to or oftentimes accompanying hyperglycemia, especially in the long-term (diabetes or pre-diabetes, obesity or overweight,  hyperlipidemia ,  hypertension , etc.), it is still generally more dangerous to have too little glucose \u2013 especially if levels are very low \u2013 in the blood than too much, at least temporarily, because glucose is so important for metabolism and nutrition and the proper functioning of the body's organs. This is especially the case for those organs that are metabolically active or that require a constant, regulated supply of blood sugar (the liver and brain are examples). Symptomatic hypoglycemia is most likely associated with  diabetes  and  liver disease  (especially overnight or postprandial), without treatment or with wrong treatment, possibly in combination with carbohydrate malabsorption, physical over-exertion or drugs. Many other less likely illnesses, like cancer, could also be a reason. Starvation, possibly due to eating disorders, like anorexia, will also eventually lead to hypoglycemia. Hypoglycemic episodes can vary greatly between persons and from time to time, both in severity and swiftness of onset. For severe cases, prompt medical assistance is essential, as damage to brain and other tissues and even death will result from sufficiently low blood-glucose levels. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2778", "text": "In the past to measure blood glucose it was necessary to take a blood sample, as explained below, but since 2015 it has also been possible to use a  continuous glucose monitor , which involves an electrode placed under the skin. Both methods, as of 2023, cost hundreds of dollars or euros per year for supplies needed. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2779", "text": "Glucose testing  in a fasting individual shows comparable levels of glucose in arterial, venous, and capillary blood. But following meals, capillary and arterial blood glucose levels can be significantly higher than venous levels. Although these differences vary widely, one study found that following the consumption of 50 grams of glucose, \"the mean capillary blood glucose concentration is higher than the mean venous blood glucose concentration by 35%.\" [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2780", "text": "Glucose is measured in whole blood,  plasma  or  serum . Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report plasma or serum glucose levels. Because  red blood cells  (erythrocytes) have a higher concentration of protein (e.g., hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiplication by 1.14 [ 35 ]  has been shown to generally give the serum/plasma level."}
{"_id": "WikiPedia_Hematology$$$corpus_2781", "text": "To prevent contamination of the sample with  intravenous fluids , particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted. Alternatively, blood can be drawn from the same arm with an IV line after the IV has been turned off for at least 5 minutes, and the arm has been elevated to drain infused fluids away from the vein. Inattention can lead to large errors, since as little as 10% contamination with a 5%  glucose  solution (D5W) will elevate glucose in a sample by 500\u00a0mg/dL or more. The actual concentration of glucose in blood is very low, even in the hyperglycemic. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2782", "text": "Two major methods have been used to measure glucose. The first, still in use in some places, is a chemical method exploiting the nonspecific reducing property of glucose in a reaction with an indicator substance that changes color when reduced. Since other blood compounds also have reducing properties (e.g., urea, which can be abnormally high in uremic patients), this technique can produce erroneous readings in some situations (5\u201315\u00a0mg/dL has been reported). The more recent technique, using enzymes specific to glucose, is less susceptible to this kind of error. The two most common employed enzymes are glucose oxidase and hexokinase. [ 36 ]  Average blood glucose concentrations can also be measured. This method measures the level of  glycated hemoglobin , which is representative of the average blood glucose levels over the last, approximately, 120 days. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2783", "text": "In either case, the chemical system is commonly contained on a test strip which is inserted into a meter, and then has a blood sample applied. Test-strip shapes and their exact chemical composition vary between meter systems and cannot be interchanged. Formerly, some test strips were read (after timing and wiping away the blood sample) by visual comparison against a color chart printed on the vial label. Strips of this type are still used for urine glucose readings, but for blood glucose levels they are obsolete. Their error rates were, in any case, much higher. Errors when using test strips were often caused by the age of the strip or exposure to high temperatures or humidity. [ 37 ]  More precise blood glucose measurements are performed in a  medical laboratory , using hexokinase, glucose oxidase, or glucose dehydrogenase enzymes."}
{"_id": "WikiPedia_Hematology$$$corpus_2784", "text": "Urine glucose  readings, however taken, are much less useful. In properly functioning kidneys, glucose does not appear in urine until the  renal threshold  for glucose has been exceeded. This is substantially above any normal glucose level, and is evidence of an existing severe hyperglycemic condition. However, as urine is stored in the bladder, any glucose in it might have been produced at any time since the last time the bladder was emptied. Since metabolic conditions change rapidly, as a result of any of several factors, this is delayed news and gives no warning of a developing condition. [ 38 ]  Blood glucose monitoring is far preferable, both clinically and for home monitoring by patients. Healthy urine glucose levels were first standardized and published in 1965 [ 39 ]  by  Hans Renschler ."}
{"_id": "WikiPedia_Hematology$$$corpus_2785", "text": "A noninvasive method of sampling to monitor glucose levels has emerged using an  exhaled breath condensate . However this method does need highly sensitive glucose biosensors. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2786", "text": "G \n l \n u \n c \n o \n s \n e \n \n + \n \n A \n T \n P \n \n \n \n \u2192 \n \n \n \n P \n h \n o \n s \n p \n h \n o \n r \n y \n l \n a \n t \n i \n o \n n \n \n \n \n \n \n H \n e \n x \n o \n k \n i \n n \n a \n s \n e \n \n + \n \n \n M \n g \n \n \n 2 \n + \n \n \n \n \n \n \n \n \n G-6PO \n \n \n \n 4 \n \n \n + \n \n A \n D \n P \n \n \n \n \n \n \n \n \n \n G-6PO \n \n \n \n 4 \n \n \n + \n \n N \n A \n D \n P \n \n \n \n \u2192 \n \n \n \n O \n x \n i \n d \n a \n t \n i \n o \n n \n \n \n \n \n \n G-6PD \n \n \n \n \n \n \n 6-Phosphogluconate \n \n \n + \n \n N \n A \n D \n P \n H \n \n + \n \n \n H \n \n \n + \n \n \n \n \n \n \n \n \n {\\displaystyle {\\begin{alignedat}{2}&\\mathrm {Glucose} +\\mathrm {ATP} {\\xrightarrow[{\\mathrm {Phosphorylation} }]{\\mathrm {Hexokinase} +\\mathrm {Mg} ^{2+}}}{\\textrm {G-6PO}}_{4}+\\mathrm {ADP} \\\\&{\\textrm {G-6PO}}_{4}+\\mathrm {NADP} {\\xrightarrow[{\\mathrm {Oxidation} }]{\\textrm {G-6PD}}}{\\textrm {6-Phosphogluconate}}+\\mathrm {NADPH} +\\mathrm {H} ^{+}\\\\\\end{alignedat}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_2787", "text": "The fasting blood glucose level, which is measured after a fast of 8 hours, is the most commonly used indication of overall glucose homeostasis, largely because disturbing events such as food intake are avoided. Conditions affecting glucose levels are shown in the table below. Abnormalities in these test results are due to problems in the multiple control mechanism of glucose regulation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2788", "text": "The metabolic response to a carbohydrate challenge is conveniently assessed by a postprandial glucose level drawn 2 hours after a meal or a glucose load. In addition, the glucose tolerance test, consisting of several timed measurements after a standardized amount of oral glucose intake, is used to aid in the diagnosis of  diabetes . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2789", "text": "Error rates for blood glucose measurements systems vary, depending on laboratories, and on the methods used. Colorimetry techniques can be biased by color changes in test strips (from airborne or finger-borne contamination, perhaps) or interference (e.g., tinting contaminants) with light source or the light sensor. Electrical techniques are less susceptible to these errors, though not to others. In home use, the most important issue is not accuracy, but trend. Thus if a meter / test strip system is consistently wrong by 10%, there will be little consequence, as long as changes (e.g., due to exercise or medication adjustments) are properly tracked. In the US, home use blood test meters must be approved by the federal  Food and Drug Administration  before they can be sold. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2790", "text": "Finally, there are several influences on blood glucose level aside from food intake. Infection, for instance, tends to change blood glucose levels, as does stress either physical or psychological. Exercise, especially if prolonged or long after the most recent meal, will have an effect as well. In the typical person, maintenance of blood glucose at near constant levels will nevertheless be quite effective. [ clarification needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2791", "text": "The  Bodansky unit  is an obsolete measure of  alkaline phosphatase  concentration in blood. It is defined as the quantity of alkaline phosphatase that liberates 1 \u00a0 mg of phosphate ion during the first hour of incubation with a buffered substrate containing  sodium \u03b2-glycerophosphate . [ 1 ]  This technique was the first test to measure blood alkaline phosphatase levels, and was developed by  Aaron Bodansky  in the early 1930s. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2792", "text": "Other units that were used in the past as a measure of blood alkaline phosphatase levels are King-Armstrong units, Kind-King units, and International units. [ 3 ]  However, the Bodansky unit and those other units have become outdated, and the current standard for measuring alkaline phosphatase is units per liter (U/L). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2793", "text": "1B09 ,  1GNH ,  1LJ7 ,  3L2Y ,  3PVN ,  3PVO"}
{"_id": "WikiPedia_Hematology$$$corpus_2794", "text": "1401"}
{"_id": "WikiPedia_Hematology$$$corpus_2795", "text": "12944"}
{"_id": "WikiPedia_Hematology$$$corpus_2796", "text": "ENSG00000132693"}
{"_id": "WikiPedia_Hematology$$$corpus_2797", "text": "ENSMUSG00000037942"}
{"_id": "WikiPedia_Hematology$$$corpus_2798", "text": "P02741"}
{"_id": "WikiPedia_Hematology$$$corpus_2799", "text": "P14847"}
{"_id": "WikiPedia_Hematology$$$corpus_2800", "text": "NM_000567 NM_001329057 NM_001329058 NM_001382703"}
{"_id": "WikiPedia_Hematology$$$corpus_2801", "text": "NM_007768"}
{"_id": "WikiPedia_Hematology$$$corpus_2802", "text": "NP_000558 NP_001315986 NP_001315987 NP_001369632"}
{"_id": "WikiPedia_Hematology$$$corpus_2803", "text": "NP_031794"}
{"_id": "WikiPedia_Hematology$$$corpus_2804", "text": "C-reactive protein  ( CRP ) is an annular (ring-shaped)  pentameric protein  found in  blood plasma , whose  circulating concentrations  rise in response to  inflammation . It is an  acute-phase protein  of  hepatic  origin that increases following  interleukin-6  secretion by  macrophages  and  T cells . Its physiological role is to bind to  lysophosphatidylcholine  expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the  complement system  via  C1q . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2805", "text": "CRP is synthesized by the  liver [ 6 ]  in response to factors released by  macrophages , T cells and fat cells ( adipocytes ). [ 7 ]  It is a member of the  pentraxin  family of proteins. [ 6 ]  It is not related to  C-peptide  (insulin) or  protein C  (blood coagulation). C-reactive protein was the first  pattern recognition receptor  (PRR) to be identified. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2806", "text": "Discovered by  Tillett  and Francis in 1930, [ 9 ]  it was initially thought that CRP might be a pathogenic secretion since it was elevated in a variety of illnesses, including  cancer . [ 6 ]  The later discovery of hepatic synthesis (made in the liver) demonstrated that it is a native protein. [ 10 ] [ 11 ] [ 12 ]  Initially, CRP was measured using the  quellung reaction  which gave a positive or a negative result. More precise methods nowadays use  dynamic light scattering  after reaction with CRP-specific antibodies. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2807", "text": "CRP was so named because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the  cell wall   polysaccharide  (C-polysaccharide) of  pneumococcus . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2808", "text": "It is a member of the small  pentraxins  family (also known as short pentraxins). [ 15 ]  The polypeptide encoded by this gene has 224 amino acids. [ 16 ]  The full-length polypeptide is not present in the body in significant quantities due to  signal peptide , which is removed by  signal peptidase  before  translation  is completed. The complete protein, composed of five monomers, has a total mass of approximately 120,000\u00a0Da.  In serum, it assembles into stable pentameric structure with a discoid shape. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2809", "text": "CRP binds to the  phosphocholine  expressed on the surface of bacterial cells such as pneumococcus  bacteria . This activates the  complement system , promoting  phagocytosis  by macrophages, which clears  necrotic  and  apoptotic  cells and bacteria. [ 18 ] [ 13 ]  With this mechanism, CRP also binds to ischemic/hypoxic cells, which could regenerate with more time. However, the binding of CRP causes them to be disposed of prematurely. [ 19 ] [ 20 ]  CRP binds to the Fc-gamma receptor IIa, to which IgG isotype antibodies also bind. [ 21 ]  In addition, CRP activates the classical complement pathway via C1q binding. [ 22 ] [ 23 ]  CRP thus forms immune complexes in the same way as IgG antibodies."}
{"_id": "WikiPedia_Hematology$$$corpus_2810", "text": "This so-called  acute phase response  occurs as a result of increasing concentrations of  interleukin-6  (IL-6), which is produced by  macrophages [ 6 ]  as well as  adipocytes [ 7 ]  in response to a wide range of acute and chronic inflammatory conditions such as  bacterial ,  viral , or  fungal  infections;  rheumatic  and other  inflammatory diseases ;  malignancy ; and tissue injury and necrosis. These conditions cause release of IL-6 and other  cytokines  that trigger the synthesis of CRP and  fibrinogen  by the liver."}
{"_id": "WikiPedia_Hematology$$$corpus_2811", "text": "CRP binds to phosphocholine on micro-organisms. It is thought to assist in  complement  binding to foreign and damaged cells and enhances phagocytosis by macrophages ( opsonin-mediated phagocytosis ), which express a receptor for CRP. It plays a role in  innate immunity  as an early defense system against infections. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2812", "text": "Traditional CRP measurement only detected CRP in the range of 10\u00a0to\u00a01,000\u00a0mg/L, whereas high sensitivity CRP (hs-CRP) detects CRP in the range of 0.5\u00a0to\u00a010\u00a0mg/L. [ 25 ]  hs-CRP can detect  cardiovascular disease  risk when in excess of 3\u00a0mg/L, whereas below 1\u00a0mg/L would be low risk. [ 26 ]  Traditional CRP measurement is faster and less costly than hs-CRP, and can be adequate for some applications, such as monitoring  hemodialysis  patients. [ 27 ]  Current immunoassay methods for CRP have similar precision to hsCRP performed by nephelometry and could probably replace hsCRP for cardiovascular risk assessment, [ 28 ]  however, in the United States this would represent off-label use, making it a laboratory-developed test under FDA regulations. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2813", "text": "In healthy adults, the normal concentrations of CRP varies between 0.8\u00a0mg/L and 3.0\u00a0mg/L. However, some healthy adults show elevated CRP at 10\u00a0mg/L. CRP concentrations also increase with age, possibly due to  subclinical  conditions. There are also no  seasonal variations  of CRP concentrations.  Gene polymorphism  of  interleukin-1 family ,  interleukin 6 , and polymorphic GT repeat of the CRP gene do affect the usual CRP concentrations when a person does not have any medical illnesses. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2814", "text": "When there is a stimulus, the CRP level can increase 10,000-fold from less than 50\u00a0\u03bcg/L to more than 500\u00a0mg/L. Its concentration can increase to 5\u00a0mg/L by 6 hours and peak at 48 hours. The plasma half-life of CRP is 19 hours, and is constant in all medical conditions. [ 30 ]  Therefore, the only factor that affects the blood CRP concentration is its production rate, which increases with inflammation, infection, trauma, necrosis, malignancy, and  allergic reactions . [ citation needed ]  Other inflammatory mediators that can increase CRP are  TGF beta 1 , and  tumor necrosis factor alpha . In acute inflammation, CRP can increase as much as 50 to 100\u00a0mg/L within 4 to 6 hours in mild to moderate inflammation or an insult such as  skin infection ,  cystitis , or  bronchitis [ clarification needed ] . It can double every 8 hours and reaches its peak at 36 to 50 hours following injury or inflammation. CRP between 100 and 500\u00a0mg/L is considered highly predictive of inflammation due to bacterial infection.  Once inflammation subsides, CRP level falls quickly because of its relatively short half-life. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2815", "text": "CRP concentrations between 2 and 10\u00a0mg/L are considered as metabolic inflammation: metabolic pathways that cause  arteriosclerosis [ 31 ]  and  type II diabetes mellitus . [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2816", "text": "CRP is used mainly as an inflammation marker. Apart from  liver failure , there are few known factors that interfere with CRP production. [ 6 ]   Interferon alpha  inhibits CRP production from liver cells which may explain the relatively low levels of CRP found during viral infections compared to bacterial infections  [ 33 ] [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2817", "text": "Measuring and charting CRP values can prove useful in determining disease progress or the effectiveness of treatments.  ELISA  and  radial immunodiffusion  methods are available for research use, while  immunoturbidimetry  is used clinically for CRP and  nephelometry  is typically used for hsCRP. [ 35 ] [ 26 ] Cutoffs for cardiovascular risk assessment have included:"}
{"_id": "WikiPedia_Hematology$$$corpus_2818", "text": "Normal levels increase with  aging . [ 36 ]  Higher levels are found in late  pregnant  women, mild  inflammation  and  viral infections  (10\u201340\u00a0mg/L), active inflammation, bacterial infection (40\u2013200\u00a0mg/L), severe  bacterial infections  and  burns  (>200\u00a0mg/L). [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2819", "text": "CRP cut-off levels indicating bacterial from non-bacterial illness can vary due to  co-morbidities  such as  malaria ,  HIV  and  malnutrition  and the stage of disease presentation. [ 38 ]  In patients presenting to the emergency department with suspected sepsis, a CRP/albumin ratio of less than 32 has a negative predictive value of 89% for ruling out sepsis. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2820", "text": "CRP is a more sensitive and accurate reflection of the acute phase response than the ESR [ 40 ]  ( erythrocyte sedimentation rate ). ESR may be normal while CRP is elevated. CRP returns to normal more quickly than ESR in response to therapy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2821", "text": "Recent research suggests that patients with elevated basal levels of CRP are at an increased risk of  diabetes , [ 41 ] [ 42 ]   hypertension  and  cardiovascular disease . A study of over 700 nurses showed that those in the highest  quartile  of  trans fat  consumption had blood levels of CRP that were 73% higher than those in the lowest quartile. [ 43 ]  Although one group of researchers indicated that CRP may be only a moderate risk factor for cardiovascular disease, [ 44 ]  this study (known as the Reykjavik Study) was found to have some problems for this type of analysis related to the characteristics of the population studied, and there was an extremely long follow-up time, which may have attenuated the association between CRP and future outcomes. [ 45 ]  Others have shown that CRP can exacerbate  ischemic   necrosis  in a  complement -dependent fashion and that CRP inhibition can be a safe and effective therapy for  myocardial  and  cerebral   infarcts ; this has been demonstrated in animal models and humans. [ 46 ] [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2822", "text": "It has been hypothesized that patients with high CRP levels might benefit from use of  statins . This is based on the  JUPITER trial  that found that elevated CRP levels without hyperlipidemia benefited. Statins were selected because they have been proven to reduce levels of CRP. [ 6 ] [ 49 ]  Studies comparing effect of various statins in hs-CRP revealed similar effects of different statins. [ 50 ] [ 51 ]  A subsequent trial however failed to find that CRP was useful for determining statin benefit. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2823", "text": "In a  meta-analysis  of 20 studies involving 1,466 patients with  coronary artery disease , CRP levels were found to be reduced after exercise interventions. Among those studies, higher CRP concentrations or poorer lipid profiles before beginning exercise were associated with greater reductions in CRP. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2824", "text": "To clarify whether CRP is a bystander or active participant in  atherogenesis , a 2008 study compared people with various genetic CRP variants. Those with a high CRP due to genetic variation had no increased risk of cardiovascular disease compared to those with a normal or low CRP. [ 54 ]  A study published in 2011 shows that CRP is associated with lipid responses to low-fat and high-polyunsaturated fat diets. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2825", "text": "Arterial damage results from  white blood cell  invasion and  inflammation  within the wall. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk. Since many things can cause elevated CRP, this is not a very  specific  prognostic indicator. [ 56 ] [ 57 ]  Nevertheless, a level above 2.4\u00a0mg/L has been associated with a doubled risk of a coronary event compared to levels below 1\u00a0mg/L; [ 6 ]  however, the study group in this case consisted of patients who had been diagnosed with unstable angina pectoris; whether elevated CRP has any predictive value of acute coronary events in the general population of all age ranges remains unclear. Currently, C-reactive protein is not recommended as a cardiovascular disease screening test for average-risk adults without symptoms. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2826", "text": "The  American Heart Association  and U.S.  Centers for Disease Control and Prevention  have defined risk groups as follows: [ 59 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2827", "text": "But hs-CRP is not to be used alone and should be combined with elevated levels of  cholesterol ,  LDL-C ,  triglycerides , and glucose level.  Smoking , hypertension and diabetes also increase the risk level of cardiovascular disease."}
{"_id": "WikiPedia_Hematology$$$corpus_2828", "text": "Scleroderma ,  polymyositis , and  dermatomyositis  elicit little or no CRP response. [ citation needed ]  CRP levels also tend not to be elevated in  systemic lupus erythematosus  (SLE) unless  serositis  or  synovitis  is present. Elevations of CRP in the absence of clinically significant inflammation can occur in  kidney failure . CRP level is an independent risk factor for atherosclerotic disease. Patients with high CRP concentrations are more likely to develop  stroke ,  myocardial infarction , and severe  peripheral vascular disease . [ 60 ]  Elevated level of CRP can also be observed in  inflammatory bowel disease  (IBD), including  Crohn's disease  and  ulcerative colitis . [ 40 ] [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2829", "text": "High levels of CRP has been associated to point mutation Cys130Arg in the  APOE  gene, coding for  apolipoprotein E , establishing a link between  lipid  values and inflammatory markers modulation. [ 62 ] [ unreliable medical source? ] [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2830", "text": "The role of inflammation in cancer is not well understood. Some organs of the body show greater risk of cancer when they are chronically inflamed. [ 63 ]   While there is an association between increased levels of C-reactive protein and risk of developing cancer, there is no association between genetic polymorphisms influencing circulating levels of CRP and cancer risk. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2831", "text": "In a 2004  prospective cohort study  on colon cancer risk associated with CRP levels, people with  colon cancer  had higher average CRP concentrations than people without colon cancer. [ 65 ]  It can be noted that the average CRP levels in both groups were well within the range of CRP levels usually found in healthy people. However, these findings may suggest that low inflammation level can be associated with a lower risk of colon cancer, concurring with previous studies that indicate  anti-inflammatory drugs  could lower colon cancer risk. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2832", "text": "C-reactive protein (CRP), a marker of systemic inflammation, is also increased in  obstructive sleep apnea  (OSA).  CRP and interleukin-6 (IL-6) levels were significantly higher in patients with OSA compared to obese control subjects. [ 67 ]  Patients with OSA have higher plasma CRP concentrations that increased corresponding to the severity of their  apnea-hypopnea index  score.  Treatment of OSA with CPAP ( continuous positive airway pressure ) significantly alleviated the effect of OSA on CRP and IL-6 levels. [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2833", "text": "In the context of  rheumatoid arthritis  (RA), CRP is one of the acute phase reactants, whose assessment is defined as part of the joint 2010 ACR/ EULAR  classification criteria for RA with abnormal levels accounting for a single point within the criteria.  [ 68 ]  Higher levels of CRP are associated with more severe disease and a higher likelihood of radiographic progression. Rheumatoid arthritis associated antibodies together with 14-3-3\u03b7  YWHAH  have been reported to complement CRP in predicting clinical and radiographic outcomes in patients with recent onset inflammatory polyarthritis. [ 69 ]  Elevated levels of CRP appear to be associated with common comorbidities including cardiovascular disease,  metabolic syndrome , diabetes and interstitial lung (pulmonary) disease. Mechanistically, CRP also appears to influence  osteoclast  activity leading to  bone resorption  and also stimulates  RANKL  expression in peripheral blood  monocytes . [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2834", "text": "It has previously been speculated that  single-nucleotide polymorphisms  in the CRP gene may affect clinical decision-making based on CRP in rheumatoid arthritis, e.g. DAS28 (Disease Activity Score 28 joints). A recent study showed that CRP  genotype  and  haplotype  were only marginally associated with serum CRP levels and without any association to the DAS28 score. [ 71 ]  Thus, that DAS28, which is the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2835", "text": "Increased blood CRP levels were higher in people with  avian flu   H7N9  compared to those with  H1N1  (more common) influenza, [ 72 ]  with a review reporting that severe H1N1 influenza had elevated CRP. [ 73 ]  In 2020, people infected with  COVID-19  in  Wuhan, China , had elevated CRP. [ 74 ] [ 75 ] [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2836", "text": "The  calibrated automated thrombogram  ( CAT  or  CT ) is a  thrombin generation assay  (TGA) and  global coagulation assay  (GCA) which can be used as a  coagulation test  to assess  thrombotic  risk. [ 1 ] [ 2 ]  It is the most widely used TGA. [ 3 ]  The CAT is a  semi-automated  test performed in a  96-well plate  and requires specialized  technologists  to be performed. [ 3 ]  As a result, it has seen low implementation in routine laboratories and has been more limited to research settings. [ 3 ] [ 4 ]  Lack of  standardization  with the CAT has also led to difficulties in study-to-study comparisons in research. [ 3 ] [ 5 ]  However, efforts have recently been made towards standardization of the assay. [ 5 ] [ 6 ] [ 7 ] [ 8 ]  An example of a specific commercial CAT is the Thrombinoscope by Thrombinoscope BV (now owned by Diagnostica Stago). [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2837", "text": "The CAT can be used to measure  thrombogram parameters  such as the  endogenous thrombin potential  (ETP) [ 2 ] [ 10 ]  and to assess  activated protein C resistance  (APCR). [ 5 ]  The CAT ETP-based  APC resistance test  is especially sensitive to  estrogen -induced  procoagulation , such as with  combined oral contraceptives . [ 2 ] [ 5 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2838", "text": "In 2018, a commercial fully-automated TGA system and alternative to the CAT called the  ST Genesia  debuted. [ 3 ]  It has been said that this system should allow for more widespread adoption of TGAs in clinical laboratories. [ 3 ] [ 12 ]  The ST Genesia system also shows improved  reproducibility  compared to the CAT. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2839", "text": "Cancer Likelihood in Plasma  (CLiP) refers to a set of  ensemble learning  methods for integrating various genomic features useful for the noninvasive detection of early cancers from blood  plasma . [ 1 ]  An application of this technique for early detection of  lung cancer  (Lung-CLiP) was originally described by Chabon et al. (2020) [ 2 ]  from the labs of  Ash Alizadeh  and Max Diehn at  Stanford . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2840", "text": "This method relies on several improvements to cancer personalized profiling by deep sequencing ( CAPP-Seq ) [ 5 ]  for analysis of  circulating tumor DNA  (ctDNA). The CLiP technique integrates multiple distinctive genomic features of a cancer of interest findings within a machine-learning framework for cancer detection. For example, studies have shown that the majority of somatic mutations found in cell-free DNA (cfDNA) are not tumor derived, but instead reflect  clonal hematopoeisis  (also known as CHIP). [ 2 ] [ 6 ]  Even though  CHIP  tends to target specific genes, it also involves many generally non-recurrent mutations that can be shed from  leukocytes  and detected in cfDNA, regardless of whether profiling patients with cancer and healthy adults. [ 2 ]   However, genuine tumor derived  ctDNA mutations  can be distinguished from CHIP-derived mutations. This is because unlike tumor-derived mutations, CHIP-derived mutations that are shed from leukocytes into plasma tend to occur on longer cfDNA fragments, and to lack specific  mutational signatures  such as those associated with tobacco smoking in lung cancer that are also found in tumor derived ctDNA molecules. CLiP integrates these features within hierarchical ensemble  machine learning  models that consider  somatic mutations  and  copy number alternations , among other features. [ 2 ]  While the CLiP method is unique in relying exclusively on mutations and copy number alterations, it is related to a variety of other liquid biopsy methods being commercially developed for early cancer detection using ctDNA and proteins (e.g., CancerSEEK / DETECT-A  [ 7 ] ), cfDNA fragmentation patterns (e.g., DELFI), [ 8 ] [ 9 ]  and DNA methylation (e.g., cfMeDIP-Seq, [ 10 ]  Grail [ 11 ] )."}
{"_id": "WikiPedia_Hematology$$$corpus_2841", "text": "While the CLiP method has not yet been broadly applied for population-based cancer screening, it has been shown to distinguish discriminate early-stage lung cancers from risk-matched controls across multiple cohorts of patients enrolled across the US. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2842", "text": "The  captopril challenge test  ( CCT ) is a non-invasive medical test that measures the change in  renin   plasma -levels in response to administration of  captopril , an  angiotensin converting enzyme inhibitor . It is used to assist in the diagnosis of  renal artery stenosis . It is not generally considered a useful test for children, [ 1 ]  and more suitable options are available for adult cases."}
{"_id": "WikiPedia_Hematology$$$corpus_2843", "text": "Plasma concentration of renin is measured prior to and following the administration of captopril. The CCT is considered positive if the renin levels increase substantially or the baseline renin level is abnormally high. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2844", "text": "CCT in adults is known to have high  sensitivity , but a low  specificity . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2845", "text": "Subtraction angiography  is considered a more suitable test for renal artery stenosis in adults. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2846", "text": "The  captopril suppression test  ( CST ) is a non-invasive medical test that measures  plasma  levels of  aldosterone . [ 1 ] \nAldosterone production is suppressed by captopril through the  renin\u2013angiotensin\u2013aldosterone system . CST results are used to assist in the diagnososis of  primary aldosteronism  (Conn syndrome)."}
{"_id": "WikiPedia_Hematology$$$corpus_2847", "text": "CO 2  content  (also known as \"Total  CO 2 \") is a  blood test  that usually appears on a \"Chem 19\" or an  electrolyte  panel. The value measures the total dissolved  Carbon dioxide  ( CO 2 ) in blood. It is determined by combining the  Bicarbonate  ( HCO \u2212 3 ) and the  partial pressure  of  CO 2  multiplied by a factor which estimates the amount of pure  CO 2  that is dissolved in its natural form (usually 0.03). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2848", "text": "One given reference range is 24\u201332 mEq/L. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2849", "text": "A  coagulation screen  is a combination of  screening laboratory tests , designed to provide rapid non-specific information, which allows an initial broad categorization of  haemostatic  problems. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2850", "text": "The basic screen consists of:"}
{"_id": "WikiPedia_Hematology$$$corpus_2851", "text": "Two other tests are regularly performed at the same time:"}
{"_id": "WikiPedia_Hematology$$$corpus_2852", "text": "These tests may miss mild abnormalities but they will detect major disorders. The results of these screening tests, in conjunction with the  clinical history  (especially  bleeding  history), will then direct the selection of further, more detailed and specific coagulation tests, such as:"}
{"_id": "WikiPedia_Hematology$$$corpus_2853", "text": "Blood clotting tests  are the tests used for diagnostics of the  hemostasis  system.\nCoagulometer is the medical laboratory analyzer used for testing of the hemostasis system. Modern coagulometers realize different methods of activation and observation of development of blood clots in blood or in blood plasma. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2854", "text": "Substantially all coagulometers used in laboratory diagnostics are based on the methods of testing of the hemostasis system created more than fifty years ago. The majority of these methods are good to detect defects in one of the hemostasis components, without diagnosing other possible defects. Another problem of the actual hemostasis system diagnostics is the  thrombosis  prediction, i.e. sensitivity to the patient's prethrombotic state. All the diversity of clinical tests of the blood coagulation system can be divided into 2 groups: global (integral, general) tests, and \u00ablocal\u00bb (specific) tests. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2855", "text": "Global tests, also known as  global coagulation assays  (GCAs), [ 1 ]  characterize the results of work of the whole clotting cascade. They suit to diagnose the general state of the blood coagulation system and the intensity of pathologies, and to simultaneously record all attendant influences. Global methods play the key role at the first stage of diagnostics: they provide an integral picture of alterations within the coagulation system and allow predicting a tendency to hyper- or hypo-coagulation in general. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2856", "text": "Local tests characterize the results of work of the separate components of the blood coagulation system cascade, as well as of the separate coagulation factors. They are essential for the possibility to specify the pathology localization within the accuracy of coagulation factor. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2857", "text": "A  D-dimer  (product of thrombi degradation) test can be specified separately. The rise of D-dimers concentration in the patient's blood states the possibility of the completed thrombosis.\nTo obtain a complete picture of the work of hemostasis by a patient, the doctor should have a possibility to choose which test is necessary. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2858", "text": "According to the type of the investigated object, the following complementary groups of methods can be specified: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2859", "text": "A  combined rapid anterior pituitary evaluation panel  or  triple bolus test  or a  dynamic pituitary function test  is a medical diagnostic procedure used to assess a patient's  pituitary  function.\nA triple bolus test is usually ordered and interpreted by  endocrinologists . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2860", "text": "In rare cases, it has been associated with  pituitary apoplexy . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2861", "text": "Three  hormones [ 2 ]  (usually synthetic  analogues ) are injected as a  bolus  into the patient's vein to stimulate the  anterior pituitary  gland:"}
{"_id": "WikiPedia_Hematology$$$corpus_2862", "text": "The gland's response is assessed by measuring the rise in  cortisol  and  growth hormone  (GH) in response to the hypoglycaemia caused by insulin, rises in  prolactin  and  thyroid-stimulating hormone  (TSH) caused by TRH and rises in  luteinizing hormone  (LH) and  follicle-stimulating hormone  (FSH) caused by GnRH.  Blood  glucose  levels are also monitored to ensure appropriate levels of  hypoglycemia  are achieved. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2863", "text": "The triple bolus test was introduced in 1973 by physicians from the London  Royal Postgraduate Medical School  and  Queen Elizabeth Hospital, Birmingham . [ 3 ]  It followed earlier reports combining insulin and  vasopressin  analogues in the diagnosis of hypopituitarism. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2864", "text": "The  complement fixation test  is an  immunological   medical  test that can be used to detect the presence of either specific  antibody  or specific  antigen  in a patient's  serum , based on whether  complement fixation  occurs. It was widely used to diagnose infections, particularly with microbes that are not easily detected by culture methods, and in rheumatic diseases. However, in clinical diagnostics labs it has been largely superseded by other serological methods such as  ELISA  and by DNA-based methods of pathogen detection, particularly  PCR ."}
{"_id": "WikiPedia_Hematology$$$corpus_2865", "text": "The  complement system  is a system of serum proteins that react with antigen-antibody complexes. If this reaction occurs on a cell surface, it will result in the formation of trans-membrane pores and therefore destruction of the cell.  The basic steps of a complement fixation test are as follows: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2866", "text": "If the patient's serum contains antibodies against the antigen of interest, they will bind to the antigen in step 3 to form antigen-antibody complexes.  The complement proteins will react with these complexes and be depleted.  Thus when the sRBC-antibody complexes are added in step 4, there will be no complement left in the serum.  However, if no antibodies against the antigen of interest are present, the complement will not be depleted and it will react with the sRBC-antibody complexes added in step 4, lysing the sRBCs and spilling their contents into the solution, thereby turning the solution pink. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2867", "text": "While detection of antibodies is the most common test format, it is equally possible to test for the presence of antigen. In this case, the patient's serum is supplemented with specific antibody to induce formation of complexes; addition of complement and indicator sRBC is performed as before. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2868", "text": "The test can be made quantitative by setting up a series of dilutions of patient serum and determining the highest dilution factor that will still yield a positive CF test. This dilution factor corresponds to the  titer . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2869", "text": "A  complete blood count  ( CBC ), also known as a  full blood count  ( FBC ), is a set of  medical laboratory  tests that provide  information about the cells  in a person's  blood . The CBC indicates the counts of  white blood cells ,  red blood cells  and  platelets , the concentration of  hemoglobin , and the  hematocrit  (the volume percentage of red blood cells). The  red blood cell indices , which indicate the average size and hemoglobin content of red blood cells, are also reported, and a  white blood cell differential , which counts the different types of white blood cells, may be included."}
{"_id": "WikiPedia_Hematology$$$corpus_2870", "text": "The CBC is often carried out as part of a medical assessment and can be used to monitor health or diagnose diseases. The results are interpreted by comparing them to  reference ranges , which vary with sex and age. Conditions like  anemia  and  thrombocytopenia  are defined by abnormal complete blood count results. The red blood cell indices can provide information about the cause of a person's anemia such as  iron deficiency  and  vitamin B12 deficiency , and the results of the white blood cell differential can help to diagnose  viral ,  bacterial  and  parasitic infections  and  blood disorders  like  leukemia . Not all results falling outside of the reference range require medical intervention."}
{"_id": "WikiPedia_Hematology$$$corpus_2871", "text": "The CBC is usually performed by an  automated hematology analyzer , which  counts cells  and collects information on their size and structure. The concentration of hemoglobin is measured, and the red blood cell indices are calculated from measurements of red blood cells and hemoglobin. Manual tests can be used to independently confirm abnormal results. Approximately 10\u201325% of samples require a manual  blood smear  review, [ 5 ]  in which the blood is  stained  and viewed under a  microscope  to verify that the analyzer results are consistent with the appearance of the cells and to look for abnormalities. The hematocrit can be determined manually by  centrifuging  the sample and measuring the proportion of red blood cells, and in laboratories without access to automated instruments, blood cells are counted under the microscope using a  hemocytometer ."}
{"_id": "WikiPedia_Hematology$$$corpus_2872", "text": "In 1852,  Karl Vierordt  published the first procedure for performing a blood count, which involved spreading a known volume of blood on a microscope slide and counting every cell. The invention of the hemocytometer in 1874 by  Louis-Charles Malassez  simplified the microscopic analysis of blood cells, and in the late 19th century,  Paul Ehrlich  and  Dmitri Leonidovich Romanowsky  developed techniques for staining white and red blood cells that are still used to examine blood smears. Automated methods for measuring hemoglobin were developed in the 1920s, and  Maxwell Wintrobe  introduced the Wintrobe hematocrit method in 1929, which in turn allowed him to define the red blood cell indices. A landmark in the automation of blood cell counts was the  Coulter principle , which was patented by  Wallace H. Coulter  in 1953. The Coulter principle uses  electrical impedance  measurements to count blood cells and determine their sizes; it is a technology that remains in use in many automated analyzers. Further research in the 1970s involved the use of  optical  measurements to count and identify cells, which enabled the automation of the white blood cell differential."}
{"_id": "WikiPedia_Hematology$$$corpus_2873", "text": "Blood is composed of a fluid portion, called  plasma , and a cellular portion that contains  red blood cells ,  white blood cells  and  platelets . [ note 1 ] [ 7 ]  The complete blood count evaluates the three cellular components of blood. Some medical conditions, such as  anemia  or  thrombocytopenia , are defined by marked increases or decreases in blood cell counts. [ 8 ]  Changes in many  organ systems  may affect the blood, so CBC results are useful for investigating a wide range of conditions. Because of the amount of information it provides, the complete blood count is one of the most commonly performed  medical laboratory  tests. [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2874", "text": "The CBC is often used to  screen  for diseases as part of a medical assessment. [ 12 ]  It is also called for when a healthcare provider suspects a person has a disease that affects blood cells, such as an  infection , a  bleeding disorder , or some  cancers . People who have been diagnosed with disorders that may cause abnormal CBC results or who are receiving treatments that can affect blood cell counts may have a regular CBC performed to monitor their health, [ 4 ] [ 12 ]  and the test is often performed each day on people who are hospitalized. [ 13 ]  The results may indicate a need for a  blood  or  platelet transfusion . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2875", "text": "The complete blood count has specific applications in many  medical specialties . It is often performed before a person undergoes  surgery  to detect anemia, ensure that platelet levels are sufficient, and screen for infection, [ 15 ] [ 16 ]  as well as after surgery, so that  blood loss  can be monitored. [ 12 ] [ 17 ]  In  emergency medicine , the CBC is used to investigate numerous symptoms, such as   fever ,  abdominal pain , and  shortness of breath , [ 18 ] [ 19 ] [ 20 ]  and to assess bleeding and  trauma . [ 21 ] [ 22 ]  Blood counts are closely monitored in people undergoing  chemotherapy  or  radiation therapy  for cancer, because these treatments  suppress the production of blood cells in the bone marrow  and can produce severely low levels of white blood cells, platelets and  hemoglobin . [ 23 ]  Regular CBCs are necessary for people taking some  psychiatric drugs , such as  clozapine  and  carbamazepine , which in rare cases can cause a life-threatening drop in the number of white blood cells ( agranulocytosis ). [ 24 ] [ 25 ]  Because anemia during pregnancy can result in poorer outcomes for the mother and her baby, the complete blood count is a routine part of  prenatal care ; [ 26 ]   and in  newborn babies , a CBC may be needed to investigate  jaundice  or to count the number of immature cells in the  white blood cell differential , which can be an indicator of  sepsis . [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2876", "text": "The complete blood count is an essential tool of  hematology , which is the study of the cause, prognosis, treatment, and prevention of diseases related to blood. [ 29 ]  The results of the CBC and smear examination reflect the functioning of the  hematopoietic system \u2014the organs and  tissues  involved in the production and development of blood cells, particularly the  bone marrow . [ 9 ] [ 30 ]  For example, a low count of all three cell types ( pancytopenia ) can indicate that blood cell production is being affected by a marrow disorder, and a  bone marrow examination  can further investigate the cause. [ 31 ]  Abnormal cells on the  blood smear  might indicate  acute leukemia  or  lymphoma , [ 30 ]  while an abnormally high count of neutrophils or lymphocytes, in combination with indicative symptoms and blood smear findings, may raise suspicion of a  myeloproliferative disorder  or  lymphoproliferative disorder . Examination of the CBC results and blood smear can help to distinguish between causes of anemia, such as  nutritional deficiencies ,  bone marrow disorders ,  acquired hemolytic anemias  and inherited conditions like  sickle cell anemia  and  thalassemia . [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2877", "text": "The  reference ranges  for the complete blood count represent the range of results found in 95% of apparently healthy people. [ note 2 ] [ 35 ]  By definition, 5% of results will always fall outside this range, so some abnormal results may reflect natural variation rather than signifying a medical issue. [ 36 ]  This is particularly likely if such results are only slightly outside the reference range, if they are consistent with previous results, or if there are no other related abnormalities shown by the CBC. [ 37 ]  When the test is performed on a relatively healthy population, the number of clinically insignificant abnormalities may exceed the number of results that represent disease. [ 38 ]  For this reason, professional organizations in the United States, United Kingdom and Canada recommend against pre-operative CBC testing for low-risk surgeries in individuals without relevant medical conditions. [ 15 ] [ 39 ] [ 40 ]  Repeated blood draws for hematology testing in hospitalized patients can contribute to  hospital-acquired anemia  and may result in unnecessary transfusions. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2878", "text": "The sample is collected by drawing blood into a tube containing an  anticoagulant \u2014typically  EDTA \u2014to stop its natural  clotting . [ 41 ]  The blood is usually taken from a  vein , but when this is difficult it may be collected from  capillaries  by a  fingerstick , or by a  heelprick  in babies. [ 42 ] [ 43 ]  Testing is typically performed on an automated analyzer, but manual techniques such as a blood smear examination or manual hematocrit test can be used to investigate abnormal results. [ 44 ]  Cell counts and hemoglobin measurements are performed manually in laboratories lacking access to automated instruments. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2879", "text": "On board the analyzer, the sample is agitated to evenly distribute the cells, then diluted and partitioned into at least two channels, one of which is used to count red blood cells and platelets, the other to count white blood cells and determine the hemoglobin concentration. Some instruments measure hemoglobin in a separate channel, and additional channels may be used for differential white blood cell counts,  reticulocyte  counts and specialized measurements of platelets. [ 46 ] [ 47 ] [ 48 ]  The cells are suspended in a fluid stream and their properties are measured as they flow past sensors in a technique known as  flow cytometry . [ note 3 ] [ 49 ] [ 52 ]   Hydrodynamic focusing  may be used to isolate individual cells so that more accurate results can be obtained: the diluted sample is injected into a stream of low-pressure fluid, which causes the cells in the sample to line up in single file through  laminar flow . [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2880", "text": "To measure the hemoglobin concentration, a  reagent  chemical is added to the sample to destroy ( lyse ) the red cells in a channel separate from that used for red blood cell counts. On analyzers that perform white blood cell counts in the same channel as hemoglobin measurement, this permits white blood cells to be counted more easily. [ 55 ]  Hematology analyzers measure hemoglobin using  spectrophotometry  and are based on the  linear relationship  between the  absorbance  of light and the amount of hemoglobin present. Chemicals are used to convert different forms of hemoglobin, such as  oxyhemoglobin  and  carboxyhemoglobin , to one stable form, usually  cyanmethemoglobin , and to create a permanent colour change. The absorbance of the resulting colour, when measured at a specific wavelength\u2014usually 540  nanometres \u2014corresponds with the concentration of hemoglobin. [ 56 ] [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2881", "text": "Sensors count and identify the cells in the sample using two main principles:  electrical impedance  and  light scattering . [ 58 ]  Impedance-based cell counting operates on the  Coulter principle : cells are suspended in a fluid carrying an  electric current , and as they pass through a small opening (an aperture), they cause decreases in current because of their poor  electrical conductivity . The  amplitude  of the  voltage  pulse generated as a cell crosses the aperture correlates with the amount of fluid displaced by the cell, and thus the cell's volume, [ 59 ] [ 60 ]  while the total number of pulses correlates with the number of cells in the sample. The distribution of cell volumes is plotted on a  histogram , and by setting volume thresholds based on the typical sizes of each type of cell, the different cell populations can be identified and counted. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2882", "text": "In light scattering techniques, light from a  laser  or a  tungsten-halogen lamp  is directed at the stream of cells to collect information about their size and structure. Cells scatter light at different angles as they pass through the beam, which is detected using  photometers . [ 62 ]  Forward scatter, which refers to the amount of light scattered along the beam's axis, is mainly caused by  diffraction  of light and correlates with cellular size, while side scatter (light scattered at a 90-degree angle) is caused by  reflection  and  refraction  and provides information about cellular complexity. [ 62 ] [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2883", "text": "Radiofrequency -based methods can be used in combination with impedance. These techniques work on the same principle of measuring the interruption in current as cells pass through an aperture, but since the  high-frequency  RF current penetrates into the cells, the amplitude of the resulting pulse relates to factors like the relative size of the  nucleus , the nucleus's structure, and the amount of granules in the  cytoplasm . [ 64 ] [ 65 ]  Small red cells and cellular debris, which are similar in size to platelets, may interfere with the platelet count, and large platelets may not be counted accurately, so some analyzers use additional techniques to measure platelets, such as  fluorescent  staining, multi-angle light scatter and  monoclonal antibody  tagging. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2884", "text": "Most analyzers directly measure the average size of red blood cells, which is called the  mean cell volume  (MCV), and calculate the hematocrit by multiplying the red blood cell count by the MCV. Some measure the hematocrit by comparing the total volume of red blood cells to the volume of blood sampled, and derive the MCV from the hematocrit and red blood cell count. [ 66 ]  The hemoglobin concentration, the red blood cell count and the hematocrit are used to calculate the average amount of hemoglobin within each red blood cell, the  mean corpuscular hemoglobin  (MCH); and its concentration, the  mean corpuscular hemoglobin concentration  (MCHC). [ 67 ]  Another calculation, the  red blood cell distribution width  (RDW), is derived from the  standard deviation  of the mean cell volume and reflects variation in cellular size. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2885", "text": "After being treated with reagents, white blood cells form three distinct peaks when their volumes are plotted on a histogram. These peaks correspond roughly to populations of  granulocytes , lymphocytes, and other  mononuclear cells , allowing a three-part differential to be performed based on cell volume alone. [ 69 ] [ 70 ]  More advanced analyzers use additional techniques to provide a five- to seven-part differential, such as light scattering or radiofrequency analysis, [ 70 ]  or using dyes to stain specific chemicals inside cells\u2014for example,  nucleic acids , which are found in higher concentrations in immature cells [ 71 ]  or  myeloperoxidase , an  enzyme  found in cells of the  myeloid lineage . [ 72 ] [ 73 ]   Basophils  may be counted in a separate channel where a reagent destroys other white cells and leaves basophils intact. The data collected from these measurements is analyzed and plotted on a  scattergram , where it forms clusters that correlate with each white blood cell type. [ 70 ] [ 72 ]  Another approach to automating the differential count is the use of digital microscopy software, [ 74 ]  which uses  artificial intelligence  to classify white blood cells from  photomicrographs  of the blood smear. The cell images are displayed to a human operator, who can manually re-classify the cells if necessary. [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2886", "text": "Most analyzers take less than a minute to run all the tests in the complete blood count. [ 58 ]  Because analyzers sample and count many individual cells, the results are very precise. [ 76 ]  However, some abnormal cells may not be identified correctly, requiring manual review of the instrument's results and identification by other means of abnormal cells the instrument could not categorize. [ 5 ] [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2887", "text": "Point-of-care testing  refers to tests conducted outside of the laboratory setting, such as at a person's bedside or in a clinic. [ 78 ] [ 79 ]  This method of testing is faster and uses less blood than conventional methods, and does not require specially trained personnel, so it is useful in emergency situations and in areas with limited access to resources. Commonly used devices for point-of-care hematology testing include the  HemoCue , a portable analyzer that uses spectrophotometry to measure the hemoglobin concentration of the sample, and the  i-STAT , which derives a hemoglobin reading by estimating the concentration of red blood cells from the conductivity of the blood. [ 79 ]   Hemoglobin and hematocrit can be measured on point-of-care devices designed for  blood gas testing , but these measurements sometimes correlate poorly with those obtained through standard methods. [ 78 ]  There are simplified versions of hematology analyzers designed for use in clinics that can provide a complete blood count and differential. [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2888", "text": "The tests can be performed manually when automated equipment is not available or when the analyzer results indicate that further investigation is needed. [ 45 ]  Automated results are flagged for manual blood smear review in 10\u201325% of cases, which may be due to abnormal cell populations that the analyzer cannot properly count, [ 5 ]  internal flags generated by the analyzer that suggest the results could be inaccurate, [ 81 ]  or numerical results that fall outside set thresholds. [ 77 ]  To investigate these issues, blood is spread on a microscope slide, stained with a  Romanowsky stain , and examined under a  microscope . [ 82 ]  The appearance of the red and white blood cells and platelets is assessed, and qualitative abnormalities are reported if present. [ 83 ]  Changes in the appearance of red blood cells can have considerable diagnostic significance\u2014for example, the presence of sickle cells is indicative of  sickle cell disease , and a high number of fragmented red blood cells ( schistocytes ) requires urgent investigation as it can suggest a  microangiopathic hemolytic anemia . [ 84 ]  In some inflammatory conditions and in  paraprotein  disorders like  multiple myeloma , high levels of protein in the blood may cause red blood cells to appear stacked together on the smear, which is termed  rouleaux . [ 85 ]  Some  parasitic diseases , such as  malaria  and  babesiosis , can be detected by finding the causative organisms on the blood smear, [ 86 ]  and the platelet count can be estimated from the blood smear, which is useful if the automated platelet count is inaccurate. [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2889", "text": "To perform a manual white blood cell differential, the microscopist counts 100 cells on the blood smear and classifies them based on their appearance; sometimes 200 cells are counted. [ 87 ]  This gives the percentage of each type of white blood cell, and by multiplying these percentages by the total number of white blood cells, the absolute number of each type of white cell can be obtained. [ 88 ]   Manual counting is subject to  sampling error  because so few cells are counted compared with automated analysis, [ 76 ]  but it can identify abnormal cells that analyzers cannot, [ 72 ] [ 77 ]  such as the  blast cells  seen in acute leukemia. [ 89 ]  Clinically significant features like  toxic granulation  and  vacuolation  can also be ascertained from microscopic examination of white blood cells. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2890", "text": "The hematocrit can performed manually by filling a capillary tube with blood, centrifuging it, and measuring the percentage of the blood that consists of red blood cells. [ 66 ]  This is useful in some conditions that can cause automated hematocrit results to be incorrect, such as  polycythemia  (a highly elevated red blood cell count) [ 66 ]  or severe  leukocytosis  (a highly elevated white blood cell count, which interferes with red blood cell measurements by causing white blood cells to be counted as red cells). [ 91 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2891", "text": "Red and white blood cells and platelets can be counted using a  hemocytometer , a microscope slide containing a chamber that holds a specified volume of diluted blood. The hemocytometer's chamber is etched with a calibrated grid to aid in cell counting. The cells seen in the grid are counted and divided by the volume of blood examined, which is determined from the number of squares counted on the grid, to obtain the concentration of cells in the sample. [ 45 ] [ 92 ]  Manual cell counts are labour-intensive and inaccurate compared to automated methods, so they are rarely used except in laboratories that do not have access to automated analyzers. [ 45 ] [ 92 ]  To count white blood cells, the sample is diluted using a fluid containing a compound that lyses red blood cells, such as  ammonium oxalate ,  acetic acid , or  hydrochloric acid . [ 93 ]  Sometimes a stain is added to the diluent that highlights the nuclei of white blood cells, making them easier to identify. Manual platelet counts are performed in a similar manner, although some methods leave the red blood cells intact. Using a  phase-contrast microscope , rather than a  light microscope , can make platelets easier to identify. [ 94 ]  The manual red blood cell count is rarely performed, as it is inaccurate and other methods such as hemoglobinometry and the manual hematocrit are available for assessing red blood cells; but if it is necessary to do so, red blood cells can be counted in blood that has been diluted with saline. [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2892", "text": "Hemoglobin can be measured manually using a  spectrophotometer  or  colorimeter . To measure hemoglobin manually, the sample is diluted using reagents that destroy red blood cells to release the hemoglobin. Other chemicals are used to convert different types of hemoglobin to one form, allowing it to be easily measured. The solution is then placed in a measuring  cuvette  and the absorbance is measured at a specific wavelength, which depends on the type of reagent used. A reference standard containing a known amount of hemoglobin is used to determine the relationship between the absorbance and the hemoglobin concentration, allowing the hemoglobin level of the sample to be measured. [ 96 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2893", "text": "In rural and economically disadvantaged areas, available testing is limited by access to equipment and personnel. At  primary care  facilities in these regions, testing may be limited to examination of red cell morphology and manual measurement of hemoglobin, while more complex techniques like manual cell counts and differentials, and sometimes automated cell counts, are performed at district laboratories. Regional and provincial hospitals and academic centres typically have access to automated analyzers. Where laboratory facilities are not available, an estimate of hemoglobin concentration can be obtained by placing a drop of blood on a standardized type of absorbent paper and comparing it to a colour scale. [ 97 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2894", "text": "Automated analyzers have to be regularly  calibrated . Most manufacturers provide preserved blood with defined parameters and the analyzers are adjusted if the results are outside defined thresholds. [ 98 ]  To ensure that results continue to be accurate, quality control samples, which are typically provided by the instrument manufacturer, are tested at least once per day. The samples are formulated to provide specific results, and laboratories compare their results against the known values to ensure the instrument is functioning properly. [ 99 ] [ 100 ]  For laboratories without access to commercial quality control material, an Indian regulatory organization recommends running patient samples in duplicate and comparing the results. [ 101 ]  A  moving average  measurement, in which the average results for patient samples are measured at set intervals, can be used as an additional quality control technique. Assuming that the characteristics of the patient population remain roughly the same over time, the average should remain constant; large shifts in the average value can indicate instrument problems. [ 99 ] [ 100 ]  The MCHC values are particularly useful in this regard. [ 102 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2895", "text": "In addition to analyzing internal  quality control  samples with known results, laboratories may receive  external quality assessment  samples from regulatory organizations. While the purpose of internal quality control is to ensure that analyzer results are  reproducible  within a given laboratory, external quality assessment verifies that results from different laboratories are consistent with each other and with the target values. [ 103 ]  The expected results for external quality assessment samples are not disclosed to the laboratory. [ 104 ]  External quality assessment programs have been widely adopted in North America and western Europe, [ 99 ]  and laboratories are often required to participate in these programs to maintain  accreditation . [ 105 ]  Logistical issues may make it difficult for laboratories in under-resourced areas to implement external quality assessment schemes. [ 106 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2896", "text": "The CBC measures the amounts of platelets and red and white blood cells, along with the hemoglobin and hematocrit values. Red blood cell indices\u2014MCV, MCH and MCHC\u2014which describe the size of red blood cells and their hemoglobin content, are reported along with the red blood cell distribution width (RDW), which measures the amount of variation in the sizes of red blood cells. A white blood cell differential, which enumerates the different types of white blood cells, may be performed, and a count of immature red blood cells (reticulocytes) is sometimes included. [ 4 ] [ 107 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2897", "text": "Red blood cells deliver  oxygen  from the  lungs  to the tissues and on their return carry  carbon dioxide  back to the lungs where it is exhaled. These functions are mediated by the cells' hemoglobin. [ 109 ]  The analyzer counts red blood cells, reporting the result in units of 10 6  cells per microlitre of blood (\u00d7 10 6 /\u03bcL) or 10 12  cells per litre (\u00d7 10 12 /L), and measures their average size, which is called the  mean cell volume  and expressed in  femtolitres  or cubic micrometres. [ 4 ]  By multiplying the mean cell volume by the red blood cell count, the hematocrit (HCT) or packed cell volume (PCV), a measurement of the percentage of blood that is made up of red blood cells, can be derived; [ 66 ]  and when the hematocrit is performed directly, the mean cell volume may be calculated from the hematocrit and red blood cell count. [ 110 ] [ 111 ]  Hemoglobin, measured after the red blood cells are lysed, is usually reported in units of grams per litre (g/L) or grams per decilitre (g/dL). [ 112 ]  Assuming that the red blood cells are normal, there is a constant relationship between hemoglobin and hematocrit: the hematocrit percentage is approximately three times greater than the hemoglobin value in g/dL, plus or minus three. This relationship, called the  rule of three , can be used to confirm that CBC results are correct. [ 113 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2898", "text": "Two other measurements are calculated from the red blood cell count, the hemoglobin concentration, and the hematocrit: the  mean corpuscular hemoglobin  and the  mean corpuscular hemoglobin concentration . [ 114 ] [ 115 ]  These parameters describe the hemoglobin content of each red blood cell. The MCH and MCHC can be confusing; in essence the MCH is a measure of the average amount of hemoglobin per red blood cell. The MCHC gives the average proportion of the cell that is hemoglobin. The MCH does not take into account the size of the red blood cells whereas the MCHC does. [ 116 ]  Collectively, the MCV, MCH, and MCHC are referred to as the  red blood cell indices . [ 114 ] [ 115 ]  Changes in these indices are visible on the blood smear: red blood cells that are abnormally large or small can be identified by comparison to the sizes of white blood cells, and cells with a low hemoglobin concentration appear pale. [ 117 ]  Another parameter is calculated from the initial measurements of red blood cells: the red blood cell distribution width or RDW, which reflects the degree of variation in the cells' size. [ 118 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2899", "text": "An abnormally low hemoglobin, hematocrit, or red blood cell count indicates anemia. [ 119 ]  Anemia is not a diagnosis on its own, but it points to an underlying condition affecting the person's red blood cells. [ 88 ]  General causes of anemia include blood loss, production of defective red blood cells (ineffective  erythropoeisis ), decreased production of red blood cells (insufficient erythropoeisis), and increased destruction of red blood cells ( hemolytic anemia ). [ 120 ]  Anemia reduces the blood's ability to carry oxygen, causing symptoms like tiredness and shortness of breath. [ 121 ]   If the hemoglobin level falls below thresholds based on the person's clinical condition, a blood transfusion may be necessary. [ 122 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2900", "text": "An increased number of red blood cells, leading to an increase in the hemoglobin and hematocrit, [ note 4 ]  is called  polycythemia . [ 126 ]   Dehydration  or use of  diuretics  can cause a \"relative\" polycythemia by decreasing the amount of plasma compared to red cells. A true increase in the number of red blood cells, called absolute polycythemia, can occur when the body produces more red blood cells to compensate for chronically  low oxygen levels  in conditions like  lung  or  heart disease , or when a person has abnormally high levels of  erythropoietin , a hormone that stimulates production of red blood cells. In  polycythemia vera , the bone marrow produces red cells and other blood cells at an excessively high rate. [ 127 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2901", "text": "Evaluation of red blood cell indices is helpful in determining the cause of anemia. If the MCV is low, the anemia is termed  microcytic , while anemia with a high MCV is called  macrocytic anemia . Anemia with a low MCHC is called  hypochromic anemia . If anemia is present but the red blood cell indices are normal, the anemia is considered  normochromic  and  normocytic . [ 117 ]  The term  hyperchromia , referring to a high MCHC, is generally not used. Elevation of the MCHC above the upper reference value is rare, mainly occurring in conditions such as  spherocytosis , sickle cell disease and  hemoglobin C disease . [ 115 ] [ 128 ]  An elevated MCHC can also be a false result from conditions like  red blood cell agglutination  (which causes a false decrease in the red blood cell count, elevating the MCHC) [ 129 ] [ 130 ]  or highly elevated amounts of  lipids  in the blood (which causes a false increase in the hemoglobin result). [ 128 ] [ 131 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2902", "text": "Microcytic anemia is typically associated with iron deficiency, thalassemia, and   anemia of chronic disease , while macrocytic anemia is associated with  alcoholism ,  folate  and  B12 deficiency , use of some drugs, and some bone marrow diseases. Acute blood loss, hemolytic anemia, bone marrow disorders, and various chronic diseases can result in anemia with a normocytic blood picture. [ 115 ] [ 132 ]  The MCV serves an additional purpose in laboratory quality control. It is relatively stable over time compared to other CBC parameters, so a large change in MCV may indicate that the sample was drawn from the wrong patient. [ 133 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2903", "text": "A low RDW has no clinical significance, but an elevated RDW represents increased variation in red blood cell size, a condition known as  anisocytosis . [ 118 ]  Anisocytosis is common in nutritional anemias such as  iron deficiency anemia  and anemia due to vitamin B12 or folate deficiency, while people with thalassemia may have a normal RDW. [ 118 ]  Based on the CBC results, further steps can be taken to investigate anemia, such as a  ferritin  test to confirm the presence of iron deficiency, or  hemoglobin electrophoresis  to diagnose a  hemoglobinopathy  such as thalassemia or sickle cell disease. [ 134 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2904", "text": "White blood cells defend against infections and are involved in the  inflammatory response . [ 136 ]  A high white blood cell count, which is called leukocytosis, often occurs in infections, inflammation, and states of  physiologic stress . It can also be caused by diseases that involve abnormal production of blood cells, such as  myeloproliferative  and  lymphoproliferative disorders . [ 137 ]  A decreased white blood cell count, termed  leukopenia , can lead to an increased risk of acquiring infections, [ 138 ]  and occurs in treatments like chemotherapy and radiation therapy and many conditions that inhibit the production of blood cells. [ 139 ]  Sepsis is associated with both leukocytosis and leukopenia. [ 140 ]  The total white blood cell count is usually reported in cells per microlitre of blood (/\u03bcL) or 10 9  cells per litre (\u00d7 10 9 /L). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2905", "text": "In the white blood cell differential, the different types of white blood cells are identified and counted. The results are reported as a percentage and as an absolute number per unit volume. Five types of white blood cells\u2014 neutrophils ,  lymphocytes ,  monocytes ,  eosinophils , and  basophils \u2014are typically measured. [ 141 ]  Some instruments report the number of immature granulocytes, which is a classification consisting of precursors of neutrophils; specifically,  promyelocytes ,  myelocytes  and  metamyelocytes . [ note 5 ] [ 144 ]  Other cell types are reported if they are identified in the manual differential. [ 145 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2906", "text": "Differential results are useful in diagnosing and monitoring many medical conditions. For example, an elevated neutrophil count ( neutrophilia ) is associated with bacterial infection, inflammation, and myeloproliferative disorders, [ 146 ] [ 147 ]  while a decreased count ( neutropenia ) may occur in individuals who are undergoing chemotherapy or taking certain drugs, or who have diseases affecting the bone marrow. [ 148 ] [ 149 ]  Neutropenia can also be caused by some  congenital disorders  and may occur transiently after viral or bacterial infections in children. [ 150 ]  People with severe neutropenia and clinical signs of infection are treated with antibiotics to prevent potentially life-threatening disease. [ 151 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2907", "text": "An increased number of  band neutrophils \u2014young neutrophils that lack segmented nuclei\u2014or immature granulocytes is termed  left shift  and occurs in sepsis and some blood disorders, but is normal in pregnancy. [ 152 ] [ 153 ]  An elevated lymphocyte count ( lymphocytosis ) is associated with  viral infection [ 6 ]   and lymphoproliferative disorders like  chronic lymphocytic leukemia ; [ 154 ]  elevated monocyte counts ( monocytosis ) are associated with chronic inflammatory states; [ 155 ]  and the eosinophil count is often increased ( eosinophilia ) in parasitic infections and allergic conditions. [ 156 ]  An increased number of basophils, termed  basophilia , can occur in myeloproliferative disorders like  chronic myeloid leukemia  and polycythemia vera. [ 147 ]  The presence of some types of abnormal cells, such as blast cells or lymphocytes with  neoplastic  features, is suggestive of a  hematologic malignancy . [ 89 ] [ 157 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2908", "text": "Platelets play an essential role in clotting. When the wall of a  blood vessel  is damaged, platelets adhere to the exposed surface at the site of injury and plug the gap. Simultaneous activation of the  coagulation cascade  results in the formation of  fibrin , which reinforces the platelet plug to create a stable  clot . [ 158 ]   A low platelet count, known as thrombocytopenia, may cause bleeding if severe. [ 159 ]  It can occur in individuals who are undergoing treatments that suppress the bone marrow, such as chemotherapy or radiation therapy, or taking certain drugs, such as heparin, that can induce the immune system to destroy platelets. Thrombocytopenia is a feature of many blood disorders, like acute leukemia and  aplastic anemia , as well as some  autoimmune diseases . [ 160 ] [ 161 ]  If the platelet count is extremely low, a platelet transfusion may be performed. [ 162 ]   Thrombocytosis , meaning a high platelet count, may occur in states of inflammation or trauma, [ 163 ]  as well as in iron deficiency, [ 164 ]  and the platelet count may reach exceptionally high levels in people with  essential thrombocythemia , a rare blood disease. [ 163 ]  The platelet count can be reported in units of cells per microlitre of blood (/\u03bcL), [ 165 ]  10 3  cells per microlitre  (\u00d7 10 3 /\u03bcL) , or  10 9  cells per litre  (\u00d7 10 9 /L). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2909", "text": "The mean platelet volume (MPV) measures the average size of platelets in femtolitres. It can aid in determining the cause of thrombocytopenia; an elevated MPV may occur when young platelets are released into the bloodstream to compensate for increased destruction of platelets, while decreased production of platelets due to dysfunction of the bone marrow can result in a low MPV. The MPV is also useful for differentiating between congenital diseases that cause thrombocytopenia. [ 118 ] [ 166 ]  The immature platelet fraction (IPF) or reticulated platelet count is reported by some analyzers and provides information about the rate of platelet production by measuring the number of immature platelets in the blood. [ 167 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2910", "text": "Reticulocytes are immature red blood cells, which, unlike the mature cells, contain  RNA . A reticulocyte count is sometimes performed as part of a complete blood count, usually to investigate the cause of a person's anemia or evaluate their response to treatment. Anemia with a high reticulocyte count can indicate that the bone marrow is producing red blood cells at a higher rate to compensate for blood loss or hemolysis, [ 74 ]  while anemia with a low reticulocyte count may suggest that the person has a condition that reduces the body's ability to produce red blood cells. [ 168 ]   When people with nutritional anemia are given nutrient supplementation, an increase in the reticulocyte count indicates that their body is responding to the treatment by producing more red blood cells. [ 169 ]  Hematology analyzers perform reticulocyte counts by staining red blood cells with a dye that binds to RNA and measuring the number of reticulocytes through light scattering or fluorescence analysis. The test can be performed manually by staining the blood with  new methylene blue  and counting the percentage of red blood cells containing RNA under the microscope. The reticulocyte count is expressed as an absolute number [ 168 ]  or as a percentage of red blood cells. [ 170 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2911", "text": "Some instruments measure the average amount of hemoglobin in each reticulocyte; a parameter that has been studied as an indicator of iron deficiency in people who have conditions that interfere with standard tests. [ 171 ]  The immature reticulocyte fraction (IRF) is another measurement produced by some analyzers which quantifies the maturity of reticulocytes: cells that are less mature contain more RNA and thus produce a stronger fluorescent signal. This information can be useful in diagnosing anemias and evaluating red blood cell production following anemia treatment or  bone marrow transplantation . [ 172 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2912", "text": "During their formation in bone marrow, and in the  liver  and spleen in fetuses, [ 173 ]  red blood cells contain a cell nucleus, which is usually absent in the mature cells that circulate in the bloodstream. Nucleated red blood cells are normal in newborn babies, [ 174 ]  but when detected in children and adults, they indicate an increased demand for red blood cells, which can be caused by bleeding, some cancers and anemia. [ 118 ]  Most analyzers can detect these cells as part of the differential cell count. High numbers of nucleated red cells can cause a falsely high white cell count, which will require adjusting. [ 175 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2913", "text": "Advanced hematology analyzers generate novel measurements of blood cells which have shown diagnostic significance in research studies but have not yet found widespread clinical use. [ 171 ]  For example, some types of analyzers produce  coordinate  readings indicating the size and position of each white blood cell cluster. These parameters (termed cell population data) [ 176 ]  have been studied as potential markers for blood disorders, bacterial infections and malaria. Analyzers that use  myeloperoxidase  staining to produce differential counts can measure white blood cells' expression of the enzyme, which is altered in various disorders. [ 75 ]  Some instruments can report the percentage of red blood cells that are hypochromic in addition to reporting the average MCHC value, or provide a count of fragmented red cells ( schistocytes ), [ 171 ]  which occur in some types of hemolytic anemia. [ 177 ]  Because these parameters are often specific to particular brands of analyzers, it is difficult for laboratories to interpret and compare results. [ 171 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2914", "text": "(4\u20137 years old)"}
{"_id": "WikiPedia_Hematology$$$corpus_2915", "text": "(0\u20131 days old)"}
{"_id": "WikiPedia_Hematology$$$corpus_2916", "text": "The complete blood count is interpreted by comparing the output to reference ranges, which represent the results found in 95% of apparently healthy people. [ 35 ]  Based on a statistical  normal distribution , the tested samples' ranges vary with sex and age. [ 179 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2917", "text": "On average, adult females have lower hemoglobin, hematocrit, and red blood cell count values than males; the difference lessens, but is still present, after  menopause . [ 180 ]  CBC results for children and newborn babies differ from those of adults. Newborns' hemoglobin, hematocrit, and red blood cell count are extremely high to compensate for low oxygen levels in the womb and the high proportion of  fetal hemoglobin , which is less effective at delivering oxygen to tissues than mature forms of hemoglobin, inside their red blood cells. [ 181 ] [ 182 ]  The MCV is also increased, and the white blood cell count is elevated with a preponderance of neutrophils. [ 181 ] [ 183 ]  The red blood cell count and related values begin to decline shortly after birth, reaching their lowest point at about two months of age and increasing thereafter. [ 184 ] [ 185 ]  The red blood cells of older infants and children are smaller, with a lower MCH, than those of adults. In the pediatric white blood cell differential, lymphocytes often outnumber neutrophils, while in adults neutrophils predominate. [ 181 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2918", "text": "Other differences between populations may affect the reference ranges: for example, people living at higher altitudes have higher hemoglobin, hematocrit, and RBC results, and people of African heritage have lower white blood cell counts on average. [ 186 ]  The type of analyzer used to run the CBC affects the reference ranges as well. Reference ranges are therefore established by individual laboratories based on their own patient populations and equipment. [ 187 ] [ 188 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2919", "text": "Some medical conditions or problems with the blood sample may produce inaccurate  results. If the sample is visibly clotted, which can be caused by poor  phlebotomy  technique, it is unsuitable for testing, because the platelet count will be falsely decreased and other results may be abnormal. [ 189 ] [ 190 ]  Samples stored at room temperature for several hours may give falsely high readings for MCV ( mean corpuscular volume ), [ 191 ]  because red blood cells swell as they absorb water from the plasma; and platelet and white blood cell differential results may be inaccurate in aged specimens, as the cells degrade over time. [ 91 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2920", "text": "Samples drawn from individuals with very high levels of  bilirubin  or  lipids  in their plasma (referred to as an icteric sample or a lipemic sample, respectively) [ 192 ]  may show falsely high readings for hemoglobin, because these substances change the colour and opacity of the sample, which interferes with hemoglobin measurement. [ 193 ]  This effect can be mitigated by replacing the plasma with saline. [ 91 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2921", "text": "Some individuals produce an  antibody  that causes their platelets to form clumps when their blood is drawn into tubes containing EDTA, the anticoagulant typically used to collect CBC samples. Platelet clumps may be counted as single platelets by automated analyzers, leading to a falsely decreased platelet count. This can be avoided by using an alternative anticoagulant such as  sodium citrate  or  heparin . [ 194 ] [ 195 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2922", "text": "Another antibody-mediated condition that can affect complete blood count results is  red blood cell agglutination . This phenomenon causes red blood cells to clump together because of antibodies bound to the cell surface. [ 196 ]  Red blood cell aggregates are counted as single cells by the analyzer, leading to a markedly decreased red blood cell count and hematocrit, and markedly elevated MCV and MCHC ( mean corpuscular hemoglobin concentration ). [ 53 ]  Often, these antibodies are only active at room temperature (in which case they are called  cold agglutinins ), and the agglutination can be reversed by heating the sample to 37\u00a0\u00b0C (99\u00a0\u00b0F). Samples from people with  warm autoimmune hemolytic anemia  may exhibit red cell agglutination that does not resolve on warming. [ 130 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2923", "text": "While blast and lymphoma cells can be identified in the manual differential, microscopic examination cannot reliably determine the cells'  hematopoietic lineage . This information is often necessary for diagnosing blood cancers. After abnormal cells are identified, additional techniques such as  immunophenotyping  by flow cytometry can be used to identify  markers  that provide additional information about the cells. [ 197 ] [ 198 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2924", "text": "Before automated cell counters were introduced, complete blood count tests were performed manually: white and red blood cells and platelets were counted using microscopes. [ 200 ]  The first person to publish microscopic observations of blood cells was  Antonie van Leeuwenhoek , [ 201 ]  who reported on the appearance of red cells in a 1674 letter to the  Proceedings of the Royal Society of London . [ 202 ]   Jan Swammerdam  had described red blood cells some years earlier, but did not publish his findings at the time. Throughout the 18th and 19th centuries, improvements in microscope technology such as  achromatic lenses  allowed white blood cells and  platelets  to be counted in unstained samples. [ 203 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2925", "text": "The physiologist  Karl Vierordt  is credited with performing the first blood count. [ 8 ] [ 204 ] [ 205 ]   His technique, published in 1852, involved aspirating a carefully measured volume of blood into a capillary tube and spreading it onto a microscope slide coated with  egg white . After the blood dried, he counted every cell on the slide; this process could take more than three hours to complete. [ 206 ]  The hemocytometer, introduced in 1874 by  Louis-Charles Malassez , simplified the microscopic counting of blood cells. [ 207 ]  Malassez's hemocytometer consisted of a microscope slide containing a flattened capillary tube. Diluted blood was introduced to the capillary chamber by means of a rubber tube attached to one end, and an  eyepiece  with a scaled grid was attached to the microscope, permitting the microscopist to count the number of cells per volume of blood. In 1877,  William Gowers  invented a hemocytometer with a built-in counting grid, eliminating the need to produce specially calibrated eyepieces for each microscope. [ 208 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2926", "text": "In the 1870s,  Paul Ehrlich  developed a staining technique using a combination of an acidic and basic dye that could distinguish different types of white blood cells and allow red blood cell  morphology  to be examined. [ 203 ]   Dmitri Leonidovich Romanowsky  improved on this technique in the 1890s, using a mixture of  eosin  and aged  methylene blue  to produce a wide range of hues not present when either of the stains was used alone. This became the basis for Romanowsky staining, the technique still used to stain blood smears for manual review. [ 209 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2927", "text": "The first techniques for measuring hemoglobin were devised in the late 19th century, and involved visual comparisons of the colour of diluted blood against a known standard. [ 205 ]  Attempts to automate this process using spectrophotometry and  colorimetry  were limited by the fact that hemoglobin is present in the blood in many different forms, meaning that it could not be measured at a single  wavelength . In 1920, a method to convert the different forms of hemoglobin to one stable form (cyanmethemoglobin or hemiglobincyanide) was introduced, allowing hemoglobin levels to be measured automatically. The cyanmethemoglobin method remains the reference method for hemoglobin measurement and is still used in many automated hematology analyzers. [ 57 ] [ 210 ] [ 211 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2928", "text": "Maxwell Wintrobe  is credited with the invention of the hematocrit test. [ 66 ] [ 212 ]  In 1929, he undertook a PhD project at the  University of Tulane  to determine normal ranges for red blood cell parameters, and invented a method known as the Wintrobe hematocrit. Hematocrit measurements had previously been described in the literature, but Wintrobe's method differed in that it used a large tube that could be mass-produced to precise specifications, with a built-in scale. The fraction of red blood cells in the tube was measured after  centrifugation  to determine the hematocrit. The invention of a reproducible method for determining hematocrit values allowed Wintrobe to define the red blood cell indices. [ 205 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2929", "text": "Research into automated cell counting began in the early 20th century. [ 211 ]  A method developed in 1928 used the amount of light  transmitted  through a diluted blood sample, as measured by photometry, to estimate the red blood cell count, but this proved inaccurate for samples with abnormal red blood cells. [ 8 ]  Other unsuccessful attempts, in the 1930s and 1940s, involved photoelectric detectors attached to microscopes, which would count cells as they were scanned. [ 211 ]  In the late 1940s,  Wallace H. Coulter , motivated by a need for better red blood cell counting methods following the  bombing of Hiroshima and Nagasaki , [ 213 ]  attempted to improve on photoelectric cell counting techniques. [ note 7 ]   His research was aided by his brother, Joseph R. Coulter, in a basement laboratory in Chicago. [ 60 ]  Their results using photoelectric methods were disappointing, and in 1948, after reading a paper relating the conductivity of blood to its red blood cell concentration, Wallace devised the Coulter principle\u2014the theory that a cell suspended in a conductive medium generates a drop in current proportional to its size as it passes through an aperture. [ 213 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2930", "text": "That October, Wallace built a counter to demonstrate the principle. Owing to financial constraints, the aperture was made by burning a hole through a piece of cellophane from a cigarette package. [ 60 ] [ 213 ]  Wallace filed a patent for the technique in 1949, and in 1951 applied to the  Office of Naval Research  to fund the development of the  Coulter counter . [ 213 ]  Wallace's patent application was granted in 1953, and after improvements to the aperture and the introduction of a mercury  manometer  to provide precise control over sample size, the brothers founded Coulter Electronics Inc. in 1958 to market their instruments. The Coulter counter was initially designed for counting red blood cells, but with later modifications it proved effective for counting white blood cells. [ 60 ]  Coulter counters were widely adopted by medical laboratories. [ 211 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2931", "text": "The first analyzer able to produce multiple cell counts simultaneously was the  Technicon   SMA 4A\u22127A , released in 1965. It achieved this by partitioning blood samples into two channels: one for counting red and white blood cells and one for measuring hemoglobin. However, the instrument was  unreliable and difficult to maintain. In 1968, the Coulter Model\u00a0S analyzer was released and gained widespread use. Similarly to the Technicon instrument, it used two different reaction chambers, one of which was used for the red cell count, and one of which was used for the white blood cell count and hemoglobin determination. The Model\u00a0S also determined the mean cell volume using impedance measurements, which allowed the red blood cell indices and hematocrit to be derived. Automated platelet counts were introduced in 1970 with Technicon's Hemalog-8 instrument and were adopted by Coulter's S\u00a0Plus series analyzers in 1980. [ 214 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2932", "text": "After basic cell counting had been automated, the white blood cell differential remained a challenge. Throughout the 1970s, researchers explored two methods for automating the differential count: digital image processing and flow cytometry. Using technology developed in the 1950s and 60s to automate the reading of  Pap smears , several models of image processing analyzers were produced. [ 215 ]  These instruments would scan a stained blood smear to find cell nuclei, then take a higher resolution snapshot of the cell to analyze it through  densitometry . [ 216 ]  They were expensive, slow, and did little to reduce workload in the laboratory because they still required blood smears to be prepared and stained, so flow cytometry-based systems became more popular, [ 217 ] [ 218 ]  and by 1990, no digital image analyzers were commercially available in the United States or western Europe. [ 219 ]  These techniques enjoyed a resurgence in the 2000s with the introduction of more advanced image analysis platforms using  artificial neural networks . [ 220 ] [ 221 ] [ 222 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2933", "text": "Early flow cytometry devices shot beams of light at cells in specific wavelengths and measured the resulting absorbance, fluorescence or light scatter, collecting information about the cells' features and allowing cellular contents such as  DNA  to be quantified. [ 223 ]  One such instrument\u2014the Rapid Cell Spectrophotometer, developed by Louis Kamentsky in 1965 to automate cervical cytology\u2014could generate blood cell scattergrams using cytochemical staining techniques. Leonard Ornstein, who had helped to develop the staining system on the Rapid Cell Spectrophotometer, and his colleagues later created the  first commercial flow cytometric white blood cell differential analyzer, the Hemalog\u00a0D. [ 224 ] [ 225 ]  Introduced in 1974, [ 226 ] [ 227 ]  this analyzer used light scattering, absorbance and cell staining to identify the five normal white blood cell types in addition to \"large unidentified cells\", a classification that usually consisted of  atypical lymphocytes  or blast cells. The Hemalog\u00a0D could count 10,000 cells in one run, a marked improvement over the manual differential. [ 225 ] [ 228 ]  In 1981, Technicon combined the Hemalog\u00a0D with the Hemalog-8 analyzer to produce the Technicon\u00a0H6000, the first combined complete blood count and differential analyzer. This analyzer was unpopular with hematology laboratories because it was labour-intensive to operate, but in the late 1980s to early 1990s similar systems were widely produced by other manufacturers such as  Sysmex ,  Abbott ,  Roche  and  Beckman Coulter . [ 229 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2934", "text": "The  comprehensive metabolic panel , or  chemical screen  ( CMP ;  CPT  code 80053), is a  panel  of 14  blood tests  that serves as an initial broad medical  screening  tool. The CMP provides a rough check of  kidney  function,  liver  function, diabetic and parathyroid status, and  electrolyte  and  fluid balance , but this type of screening has its limitations. Abnormal values from a CMP are often the result of  false positives  and thus the CMP may need to be repeated (or a more specific test performed), requiring a second blood drawing procedure and possibly additional expense for the patient, even though no disease is present. This test is also known as SMA12+2 test."}
{"_id": "WikiPedia_Hematology$$$corpus_2935", "text": "The CMP is an expanded version of the  basic metabolic panel  (BMP), which does not include liver tests. A CMP (or BMP) can be ordered as part of a routine  physical examination , or may be used to monitor a patient with a chronic disease, such as  diabetes mellitus  or  hypertension ."}
{"_id": "WikiPedia_Hematology$$$corpus_2936", "text": "Previous names for the panel of tests have been  Chem 12 ,  Chemistry panel ,  Chemistry screen ,  SMA 12 ,  SMA 20  and  SMAC  (Sequential Multiple Analysis - Computer). [ 1 ]   The tests are performed on machines based on the  AutoAnalyzer  invented in 1957."}
{"_id": "WikiPedia_Hematology$$$corpus_2937", "text": "Typically, the patient  fasts  for ten or twelve hours before the blood is drawn for the test\u2014this is particularly important for getting a useful blood glucose measurement. CMPs are also frequently performed on nonfasting patients, but the glucose level in those cases is not as useful. The following tests are then performed: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2938", "text": "These tests help screen for a wide variety of problems. The  glucose  test in particular helps screen for diabetes mellitus and pre-diabetes. The calcium test can indicate or monitor bone diseases or diseases of the parathyroid gland or kidneys. Calcium salts, lithium, thiazide diuretics, thyroxine, and vitamin D can all increase levels and may interfere with this test. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2939", "text": "Electrolyte  levels and the balance among them are tightly regulated by the body. Both individual values and ratios among the values are significant; abnormalities among either can indicate problems such as an  electrolyte disturbance ,  acid-base  imbalance, or kidney dysfunction."}
{"_id": "WikiPedia_Hematology$$$corpus_2940", "text": "Tests of  protein  levels in the blood help screen for both kidney and liver disorders."}
{"_id": "WikiPedia_Hematology$$$corpus_2941", "text": "The  National Institutes of Health  provides ranges considered within normal limits, though optimal levels may vary by individual. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2942", "text": "Compare also the ranges given at  Reference ranges for blood tests ."}
{"_id": "WikiPedia_Hematology$$$corpus_2943", "text": "0.7\u20131.3 (men)"}
{"_id": "WikiPedia_Hematology$$$corpus_2944", "text": "The direct and indirect  Coombs tests , also known as  antiglobulin test  ( AGT ), are  blood tests  used in  immunohematology . The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. [ 1 ]  Since these antibodies sometimes destroy red blood cells they can cause  anemia ; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. [ 1 ]  These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a  blood transfusion . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2945", "text": "The direct Coombs test is used to test for  autoimmune hemolytic anemia , a condition where the immune system breaks down  red blood cells , leading to anemia. The direct Coombs test is used to detect antibodies or  complement proteins  attached to the surface of red blood cells. To perform the test, a blood sample is taken and the red blood cells are washed (removing the patient's plasma and unbound antibodies from the red blood cells) and then incubated with anti-human globulin (\"Coombs reagent\"). If the red cells then  agglutinate , the test is positive, a visual indication that antibodies or complement proteins are bound to the surface of red blood cells and may be causing destruction of those cells."}
{"_id": "WikiPedia_Hematology$$$corpus_2946", "text": "The indirect Coombs test is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. The test detects antibodies against foreign red blood cells. In this case,  serum  is extracted from a blood sample taken from the patient. The serum is incubated with foreign red blood cells of known  antigenicity . Finally, anti-human globulin is added. If agglutination occurs, the indirect Coombs test is positive. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2947", "text": "The two Coombs tests are based on anti-human  antibodies  binding to human antibodies, commonly  IgG  or  IgM . These anti-human antibodies are produced by  plasma cells  of non-human animals after immunizing them with  human plasma . Additionally, these anti-human antibodies will also bind to human antibodies that may be fixed onto  antigens  on the surface of  red blood cells  (RBCs). In the appropriate test tube conditions, this can lead to  agglutination  of RBCs and allowing for visualisation of the resulting clumps of RBCs. If clumping is seen, the Coombs test is positive; if not, the Coombs test is negative. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2948", "text": "Common clinical uses of the Coombs test include the preparation of blood for  transfusion  in  cross-matching , atypical antibodies in the  blood plasma  of  pregnant  women as part of  antenatal care , and detection of antibodies for the diagnosis of immune-mediated  hemolytic anemias . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2949", "text": "Coombs tests are performed using RBCs or serum (direct or indirect, respectively) from venous whole blood samples which are taken from patients by  venipuncture . The venous blood is taken to a laboratory (or blood bank), where trained scientific technical staff do the Coombs tests.  The clinical significance of the result is assessed by the  physician  who requested the Coombs test, perhaps with assistance from a laboratory-based  hematologist . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2950", "text": "The direct Coombs test, also referred to as the direct antiglobulin test (DAT), is used to detect if antibodies or  complement system  factors have bound to  RBCs  surface antigens. [ 5 ]  The DAT is not required for pre-transfusion testing [ 6 ]  but may be carried out by some laboratories. [ clarification needed ]  Before transfusion, an  indirect  Coombs test is often done."}
{"_id": "WikiPedia_Hematology$$$corpus_2951", "text": "The direct Coombs test is used clinically when immune-mediated  hemolytic anemia  (antibody-mediated destruction of RBCs) is suspected. A positive Coombs test indicates that an immune mechanism is attacking the patient's  RBCs . This mechanism could be  autoimmunity ,  alloimmunity  or a drug-induced immune-mediated mechanism. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2952", "text": "(A  memory device  to remember that the  DAT  tests the  RBCs  and is used to test infants for  haemolytic disease of the newborn  is:\n R h  D isease ;  R  = RBCs,  D  = DAT.)"}
{"_id": "WikiPedia_Hematology$$$corpus_2953", "text": "The patient's  RBCs  are washed (removing the patient's own  serum ) and then centrifuged with  antihuman globulin  (also known as Coombs reagent).  If  immunoglobulin  or complement factors have been fixed on to the RBC surface  in-vitro , the antihuman globulin will  agglutinate  the RBCs and the direct Coombs test will be positive. (A visual representation of a positive direct Coombs test is shown in the upper half of the schematic). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2954", "text": "The indirect Coombs test, also referred to as the indirect antiglobulin test (IAT), is used to detect  in-vitro  antibody-antigen reactions.  It is used to detect very low concentrations of antibodies present in a patient's plasma/serum prior to a blood transfusion. In antenatal care, the IAT is used to screen pregnant women for antibodies that may cause  hemolytic disease of the newborn .  The IAT can also be used for  compatibility testing , antibody identification, RBC phenotyping, and titration studies. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2955", "text": "The indirect Coombs test is used to screen for antibodies in the preparation of  blood  for  blood transfusion .  The donor's and recipient's blood must be  ABO  and Rh D compatible.  Donor blood for transfusion is also screened for infections in separate processes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2956", "text": "A blood sample from the recipient and a blood sample from every unit of  donor  blood are screened for antibodies with the indirect Coombs test.  Each sample is incubated against a wide range of RBCs that together exhibit a full range of surface antigens (i.e.  blood types )."}
{"_id": "WikiPedia_Hematology$$$corpus_2957", "text": "The indirect Coombs test is used to test a sample of the recipient's serum for antibodies against a sample of the  blood donor's  RBCs.  This is sometimes called  cross-matching  blood."}
{"_id": "WikiPedia_Hematology$$$corpus_2958", "text": "The indirect Coombs test is used to screen pregnant women for  IgG   antibodies  that are likely to pass through the  placenta  into the fetal blood and cause  haemolytic disease of the newborn . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2959", "text": "The IAT is a two-stage test. (A cross match is shown visually in the lower half of the schematic as an example of an indirect Coombs test). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2960", "text": "Nonpatient, washed  red blood cells  (RBCs) with known antigens are incubated with patient serum containing unknown antibody content.  If the serum contains  antibodies  to antigens on the RBC surface, the antibodies will bind to the surface of the RBCs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2961", "text": "The RBCs are washed three or four times with isotonic saline solution and then incubated with antihuman globulin.  If antibodies have bound to RBC surface antigens in the first stage, RBCs will agglutinate when incubated with the  antihuman globulin  (also known Coombs reagent) in this stage, and the indirect Coombs test will be positive."}
{"_id": "WikiPedia_Hematology$$$corpus_2962", "text": "By diluting a serum containing antibodies the quantity of the antibody in the serum can be gauged.  This is done by performing  serial dilutions  of the serum and finding the maximum dilution of test serum that is able to produce agglutination of relevant RBCs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2963", "text": "Coombs reagent (also known as  Coombs antiglobulin  or  antihuman globulin ) is used in both the direct Coombs test and the indirect Coombs test.  Coombs reagent is antihuman  globulin .  It is made by injecting human globulin into animals, which produce  polyclonal antibodies  specific for human immunoglobulins and human complement system factors.  More specific Coombs reagents or  monoclonal antibodies  can be used. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2964", "text": "Both  IgM  and  IgG   antibodies  bind strongly with their complementary antigens.  IgG  antibodies are most reactive at 37\u00b0C.  IgM antibodies are easily detected in  saline  at  room temperature  as IgM antibodies are able to bridge between RBC's owing to their large size, efficiently creating what is seen as  agglutination .  IgG antibodies are smaller and require assistance to bridge well enough to form a visual  agglutination  reaction.  Reagents used to enhance IgG detection are referred to as potentiators.  RBCs have a net negative charge called zeta potential which causes them to have a natural repulsion for one another. Potentiators reduce the zeta potential of RBC membranes. Common potentiators include low ionic strength solution (LISS),  albumin ,  polyethylene glycol  (PEG), and proteolytic  enzymes ."}
{"_id": "WikiPedia_Hematology$$$corpus_2965", "text": "The Coombs test was first described in 1945 by  Cambridge   immunologists   Robin Coombs  (after whom it is named),  Arthur Mourant  and  Rob Race . [ 8 ]   Historically, it was done in  test tubes .  Today, it is commonly done using automated solid phase or gel technology."}
{"_id": "WikiPedia_Hematology$$$corpus_2966", "text": "Counterimmunoelectrophoresis  is a  laboratory technique  used to evaluate the binding of an  antibody  to its  antigen , it is similar to  immunodiffusion , but with the addition of an applied  electrical field  across the diffusion medium, usually an  agar  or  polyacrylamide  gel.  The effect is rapid migration of the antibody and antigen out of their respective wells towards one another to form a line of precipitation, or a  precipitin  line, indicating binding. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2967", "text": "The  COVID-19 Immunity Task Force  ( CITF ) is one of the  Government of Canada 's early efforts to track the 2020  coronavirus pandemic . [ 1 ]  An external, dedicated secretariat was established in order to maximize the efficiency of the CITF's work. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2968", "text": "The CITF was to use a  serology  \"to survey representative samples of the population for the presence of antibodies to the virus\". [ 3 ]  Trudeau's press release on 23 April 2020, on the initiation of the CCITF listed several goals it would help to achieve notably that it would: [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2969", "text": "establish priorities and oversee the coordination of a series of country-wide  blood test surveys  that will tell us how widely the virus has spread in Canada and provide reliable estimates of potential immunity and vulnerabilities in Canadian populations."}
{"_id": "WikiPedia_Hematology$$$corpus_2970", "text": "A Vaccine Surveillance Reference Group (VSRG) was also established within the CITF to monitor the safety and effectiveness of  COVID-19 vaccines  made available in Canada. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2971", "text": "The CITF Board is composed of doctors, infectious disease experts, and policy makers. [ 1 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2972", "text": "The CCITF leadership group expanded on 2 May 2020. [ 6 ]  Its additional members as of March 2022 are:"}
{"_id": "WikiPedia_Hematology$$$corpus_2973", "text": "This article about an organization in Canada is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_2974", "text": "The  CPK-MB test  (creatine phosphokinase-MB), also known as  CK-MB test , is a  cardiac marker [ 3 ]  used to assist diagnoses of an  acute myocardial infarction ,  myocardial ischemia , or  myocarditis . It measures the blood level of CK-MB (creatine kinase myocardial band), the bound combination of two variants (isoenzymes  CKM  and  CKB ) of the enzyme  phosphocreatine kinase . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2975", "text": "In some locations, the test has been superseded by the  troponin test . However, recently, there have been improvements to the test that involve measuring the ratio of the CK-MB1 and CK-MB2 isoforms. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2976", "text": "The newer test detects different  isoforms  of the B subunit specific to the myocardium whereas the older test detected the presence of cardiac-related  isoenzyme  dimers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2977", "text": "Many cases of CK-MB levels exceeding the blood level of total CK have been reported, especially in newborns with cardiac malformations, especially ventricular septal defects. This reversal of ratios is in favor of pulmonary emboli or vasculitis. An autoimmune reaction creating a complex molecule of CK and IgG should be taken into consideration. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2978", "text": "Cytometry  is the  measurement  of number and characteristics of  cells . Variables that can be measured by cytometric methods include  cell size ,  cell count , cell morphology (shape and structure),  cell cycle  phase,  DNA  content, and the existence or absence of specific  proteins  on the cell surface or in the  cytoplasm . [ 1 ]  Cytometry is used to characterize and count  blood cells  in common  blood tests  such as the  complete blood count . In a similar fashion, cytometry is also used in cell biology research and in medical diagnostics to characterize cells in a wide range of applications associated with diseases such as  cancer  and  AIDS . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2979", "text": "Image cytometry is the oldest form of cytometry. Image cytometers operate by statically imaging a large number of\ncells using  optical microscopy . Prior to analysis, cells are commonly stained to enhance contrast or\nto detect specific molecules by labeling these with  fluorochromes . Traditionally,\ncells are viewed within a  hemocytometer  to aid manual counting. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2980", "text": "Since the introduction of the  digital camera , in the mid-1990s, the automation level of\nimage cytometers has steadily increased. This has led to the commercial availability of automated image cytometers, ranging from simple cell counters to sophisticated  high-content screening  systems."}
{"_id": "WikiPedia_Hematology$$$corpus_2981", "text": "Due to the early difficulties of automating microscopy, the  flow cytometer  has since\nthe mid-1950s been the dominating cytometric device. [ 2 ] \nFlow cytometers operate by aligning single cells using flow techniques. The cells are characterized\noptically or by the use of an  electrical impedance  method called the  Coulter principle .\nTo detect specific molecules when optically characterized, cells are in most cases stained with the same\ntype of fluorochromes that are used by image cytometers. Flow cytometers generally provide\nless data than image cytometers, but have a significantly higher throughput. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2982", "text": "Cell sorters are flow cytometers capable of sorting cells according to their characteristics.\nThe sorting is achieved by using technology similar to what is used in  inkjet printers .\nThe fluid stream is broken up into droplets by a mechanical vibration.\nThe droplets are then electrically charged according to the characteristics of the cell contained\nwithin the droplet. Depending on their charge, the droplets are finally deflected by an electric field into\ndifferent containers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2983", "text": "A key characteristic of time-lapse cytometers is their use of non heat-generating light sources such as  light-emitting diodes .\nThis allows a time-lapse cytometer to be placed inside a conventional  cell culture incubator \nto facilitate continuous observation of cellular processes without heat building up inside the incubator."}
{"_id": "WikiPedia_Hematology$$$corpus_2984", "text": "The early history of cytometry is closely associated with the development of the blood cell counting.\nThrough the work of  Karl von Vierordt ,  Louis-Charles Malassez ,  Karl B\u00fcrker  and others blood cell\nconcentration could by the late 19th century be accurately measured using a blood cell counting chamber,\nthe  hemocytometer , and an  optical microscope . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2985", "text": "Until the 1950s the hemocytometer was the standard method to count blood cells. [ 5 ] \nIn blood cell counting applications the hemocytometer has now been replaced by  electronic cell counters .\nHowever, the hemocytometer is still being used to count cells in cell culture laboratories.\nSuccessively the manual task of counting, using a microscope, is taken over by small automated image cytometers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2986", "text": "In 1904,  Moritz von Rohr  and  August K\u00f6hler  at  Carl Zeiss  in Jena constructed the first ultraviolet microscope.\nThe intent of the microscope was to obtain higher optical resolution by using illumination with a shorter wavelength than visual light.\nHowever, they experienced difficulties with  autofluorescence  when observing biological material. Fortunately,\nK\u00f6hler saw the potential of fluorescence.\nA filtering technique for fluorescence excitation light was developed by\n Heinrich Lehmann  at Zeiss in 1910, based on work by\n Robert Wood . However, the \"Lumineszenzmikroskop\" he developed was only second on the market, after the one independently developed by  Oskar Heimst\u00e4dt  who worked at C Reichert, Optische Werke AG in Vienna, which today is a part of  Leica Microsystems . [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2987", "text": "By the early 1930s various firms manufactured ultraviolet fluorescent microscopes. The stage was\nset for cytometry to now go beyond the now established hemocytometer. At this time,  Torbj\u00f6rn Caspersson ,\nworking at the Karolinska Institute in Stockholm, developed a series of progressively more sophisticated\ninstruments called  cytophotometers . These instruments combined a fluorescent microscope with a  spectrophotometer \nto quantify cellular nucleic acids and their relation to cell growth and function. Caspersson\u2019s early\napparatus now seems hopelessly primitive. But, even this primitive apparatus got results, and attracted\nthe attention of other researchers. Many of the advances in analytical cytology from the 1940s and on-wards\nwere made by people who made the pilgrimage to Stockholm. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2988", "text": "The first attempts to automate cell counting were made around World War II.\nGucker et al. builds a device to detect bacteria in aerosols. [ 10 ]  Lagercrantz builds an automated\ncell counter based on microscopy [ 11 ]  and identifies the difficulties\nin aligning cells to be individually counted using microscopy, as Moldavan had proposed in 1934. [ 12 ] \nJoseph and  Wallace Coulter  circumnavigates these difficulties by inventing the principle\nof using electrical impedance to count and size microscopic particles suspended in a fluid. [ 5 ] [ 13 ]  This principle is today\nknown as the  Coulter principle  and was used in the automated blood cell counter released by  Coulter Electronics \nin 1954. The \u201c Coulter counter \u201d was the first commercial flow cytometer. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2989", "text": "During the 1960s Dittrich, G\u00f6hde and Kamentsky improves the design pioneered by Caspersson 30 years earlier.\nDittrich and G\u00f6hde\u2019s  pulse cytophotometer  was built around a Zeiss fluorescent microscope and commercialized\nas the ICP\u00a011 by  Partec GmbH  in 1968.\nKamentsky\u2019s device was commercialized by Bio/Physics Systems Inc. as the Cytograph in 1970. [ 14 ] [ 15 ] \nThese devices were able to count cells, like the earlier Coulter counter. But more importantly, they were also capable of measuring cellular characteristics.\nHowever, these early cytophotometers where microscopy-based. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2990", "text": "In 1953 Crosland-Taylor published an unsuccessful attempt to count red blood cells using microscopy in which he solved the problem of aligning cells by using  sheath fluid  to  hydrodynamically focus  the cells. [ 2 ]  In the late 1960s, Van Dilla at  Los Alamos National Laboratory  built the first non microscopy-based cytophotometer. He did this by combining Crosland-Taylor's breakthrough with the fluorescent dyes originally developed for microscopy and a laser-based fluorescent detection system \u2014 the flow cytometer as we know it today. [ 17 ] [ 18 ] [ 19 ]  Fulwyler, at Los Alamos as well, combines the Coulter principle with  continuous inkjet printer technology  to create the first cell sorter in 1965. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2991", "text": "In 1973 Steinkamp and the team at Los Alamos follow up with a fluorescence-based cell sorter. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2992", "text": "In 1978, at the Conference of the American Engineering Foundation in Pensacola, Florida, the name  pulse cytophotometry \nwas changed to  flow cytometry , a term which quickly became popular. [ 22 ]  At that point pulse cytophotometry had evolved\ninto the modern form of flow cytometry, pioneered by Van Dilla ten years earlier. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2993", "text": "D-dimer  (or  D dimer ) is a  dimer  that is a  fibrin degradation product  (FDP), a small protein fragment present in the blood after a  blood clot  is degraded by  fibrinolysis . It is so named because it contains two D fragments of the  fibrin  protein joined by a  cross-link , hence forming a  protein dimer . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2994", "text": "D-dimer concentration may be determined by a  blood test  to help diagnose  thrombosis . [ 2 ]  Since its introduction in the 1990s, it has become an important test performed in people with suspected thrombotic disorders, such as  venous thromboembolism . [ 2 ] [ 3 ]  While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but does not exclude other potential causes. [ 3 ]  Its main use, therefore, is to exclude  thromboembolic  disease where the probability is low. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2995", "text": "D-dimer levels are used as a predictive  biomarker  for the blood disorder  disseminated intravascular coagulation  and in the coagulation disorders associated with  COVID-19 infection . [ 1 ] [ 3 ]  A four-fold increase in the protein is an indicator of poor prognosis in people hospitalized with  COVID-19 . [ 1 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2996", "text": "Coagulation , the formation of a blood clot or  thrombus , occurs when the proteins of the  coagulation cascade  are activated, either by contact with a damaged blood vessel wall and exposure to collagen in the tissue space (intrinsic pathway) or by activation of  factor VII  by  tissue activating factors  (extrinsic pathway). Both pathways lead to the generation of  thrombin , an enzyme that turns the soluble blood protein  fibrinogen  into fibrin, which aggregates into protofibrils. Another thrombin-generated enzyme,  factor XIII , then crosslinks the fibrin protofibrils at the D fragment site, leading to the formation of an insoluble gel that serves as a scaffold for blood clot formation. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2997", "text": "The circulating enzyme  plasmin , the main enzyme of  fibrinolysis , cleaves the fibrin gel in a number of places. The resultant fragments, \"high molecular weight polymers\", are digested several times more by plasmin to lead to intermediate and then to small polymers ( fibrin degradation products  or FDPs). The cross-link between two D fragments remains intact, however, and these are exposed on the surface when the fibrin fragments are sufficiently digested. The structure of D-dimer is either a 180  kDa [ 6 ]  or 195 kDa [ 7 ]  molecule of two D domains, or a 340 kDa [ 7 ]  molecule of two D domains and one E domain of the original fibrinogen molecule. [ 1 ]  The  half-life  of D-dimer in blood is approximately 6 to 8\u00a0hours. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2998", "text": "D-dimers are not normally present in human blood plasma, except when the coagulation system has been activated, for instance, because of the presence of  thrombosis  or  disseminated intravascular coagulation . The D-dimer assay depends on the binding of a  monoclonal antibody  to a particular  epitope  on the D-dimer fragment. Several detection kits are commercially available; all of them rely on a different monoclonal antibody against D-dimer. For some of these, the area of the D-dimer to which the antibody binds is known. The binding of the antibody is then measured quantitatively by one of various laboratory methods. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_2999", "text": "D-dimer testing is of clinical use when there is a suspicion of  deep venous thrombosis  (DVTl),  pulmonary embolism  (PE) or  disseminated intravascular coagulation  (DIC). [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3000", "text": "For DVT and PE, there are possible various scoring systems that are used to determine the  a priori  clinical probability of these diseases; the best-known is the  Wells score . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3001", "text": "In some hospitals, they are measured by laboratories after a form is completed showing the probability score and only if the probability score is low or intermediate. This reduces the need for unnecessary tests in those who are high-probability. [ 11 ]  Performing the D-dimer test first can avoid a significant proportion of imaging tests and is less invasive. Since the D-dimer can exclude the need for imaging,  specialty   professional organizations  recommend that physicians use D-dimer testing as an initial diagnostic. [ 12 ] [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3002", "text": "The following are  reference ranges  for D-dimer: [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3003", "text": "D-dimer increases with age. It has therefore been suggested to use a cutoff equal to patient\u2019s age in years \u00d7 10 \u03bcg/L (or x 0.056 nmol/L) for patients aged over 50 years for the suspicion of venous thromboembolism (VTE), as it decreases the  false positive  rate without substantially increasing the  false negative  rate. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3004", "text": "An alternative measurement of D-dimer is in fibrinogen equivalent units (FEU). The molecular weight of the fibrinogen molecule is about twice the size of the D-dimer molecule, and therefore 1.0 mcg/mL FEU is equivalent to 0.5 mcg/mL of d-dimer. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3005", "text": "Various kits have a 93 to 95%  sensitivity  (true positive rate). For hospitalized patients, one study found the  specificity  to be about 50% (related to false positive rate) in the diagnosis of thrombotic disease. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3006", "text": "In interpretation of the D-dimer, for patients over age 50, a value of (patient's age) \u00d7 10 \u03bcg/L may be abnormal. [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3007", "text": "D-dimer was originally identified, described and named in the 1970s ( Fibrinolysis, Dr P J Gaffney ) and found its diagnostic application in the 1990s. [ 1 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3008", "text": "Dilute Russell's viper venom time  ( dRVVT ) is a laboratory test often used for detection of  lupus anticoagulant  (LA). It is an assessment of the time for blood to clot in the presence of a diluted amount of venom from  Russell's viper  ( Daboia russelii ), a highly venomous snake native to the Indian subcontinent and named after the herpetologist  Patrick Russell . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3009", "text": "Russell's viper venom (RVV) was known to clot blood many years ago. [ 2 ]  It was widely used as a styptic to clot minor wounds when razor blades were more commonly used for shaving (e.g. \"Stypven\", Burroughs-Wellcome Pharma). RVV came to be useful in laboratory tests for blood clotting factors V, X, prothrombin and phospholipid. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3010", "text": "It was first used in clotting tests for lupus anticoagulant (LA) in an individual case in 1975. [ 4 ]  The \"dilute Russell's viper venom time (dRVVT)\" test was then applied in 1985 to detect LA in a large number of patients and it became more widely used for this purpose. This multi-step method involved adding individual solutions of dilute  phospholipid , RVV and calcium chloride to a test plasma and then measuring how long it took for the mixture to clot. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3011", "text": "In 1989, researchers at  Westmead Hospital  developed a simpler assay by combining the venom, phospholipid, and calcium into a single reagent. Its first use on LA patients was reported in 1990. [ 6 ]  It was commercialized as \"LA Screen\" by Gradipore Ltd, Sydney (later Life Diagnostics) and distributed widely by American Diagnostica Inc (New York) as \"dVVTest\"."}
{"_id": "WikiPedia_Hematology$$$corpus_3012", "text": "The reagent was improved in 1992 by making it resistant to the widely used interfering anticoagulant  heparin . A new LA resistant version with increased phospholipid was also released at that time. This was introduced as \"LA-Confirm\" by Gradipore and \"dVVConfirm\" by American Diagnostica. Results with this high phospholipid reagent were not prolonged by most LA, but remained similarly affected as in the \"screen\" test by all other variables in test plasmas (Gradipore product information). The combination of screening and confirmatory dRVVT reagents made identification of LA more simple. [ 7 ]  Manufacture of these reagents has since passed on to the major diagnostic companies such as Diagnostica Stago, Precision Biologic, and IL/Werfen."}
{"_id": "WikiPedia_Hematology$$$corpus_3013", "text": "The dRVVT assay relies on the venom of the  Russelli viper . The venom contains enzymes (RVV-X) that directly activates clotting  factor X  (bypassing  intrinsic  and  extrinsic  cascades). [ 8 ]  In the presence of calcium and phospholipids, these factors convert  prothrombin  into  thrombin , leading to  fibrin  clot formation. The assay uses low concentrations of venom and phospholipids, resulting in a standard  clotting time  of 35 to 37 seconds. The test has three phases: In screening phase a lower phospholipid quantity is used (35\u201337 seconds clotting time) to enhance sensitivity to lupus anticoagulant. [ 9 ]  In confirmatory phase full phospholipid dose (30\u201335 seconds clotting time) helps validate results. In a  mixing study , the patient plasma is mixed with normal pooled plasma (NPP) in a 1:1 ratio to assess clotting factor deficiency. If clotting time prolongs during screening, lupus antibodies may be present. Mixing study differentiates between lupus antibodies and factor deficiency. Excess phospholipids in the confirmatory phase shorten clotting time if lupus antibodies are present. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3014", "text": "Through the three phases, following ratios are calculated which help interpret the diagnosis:"}
{"_id": "WikiPedia_Hematology$$$corpus_3015", "text": "By using these ratios and analyzing the possible result combinations, the test's interpretation and reporting are conducted. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3016", "text": "Additional calculations are made using percentage correction of dRVVT and normalized percentage correction as under:"}
{"_id": "WikiPedia_Hematology$$$corpus_3017", "text": "Normalized percentage correction of >10% is taken as positive and suggests the presence of lupus anticoagulant. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3018", "text": "dRVVT tests are strongly affected by the new direct oral anticoagulants (DOACs) and false positive LA results are obtained particularly with  rivaroxaban . [ 13 ]  It is now possible to specifically remove DOACs from test plasmas with activated carbon and enable the correct diagnosis of LA with the dRVVT system despite their initial presence. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3019", "text": "The dRVVT is one component of a workup of a suspected  antiphospholipid antibody , the other component being the  serological  testing for  anticardiolipin antibodies  and  anti-\u03b22 glycoprotein-I antibodies  using  ELISA  technology. The Sapporo criteria require at least one of the above laboratory tests to be positive and the patient to have at least one clinical manifestation of  antiphospholipid syndrome , such as vascular thrombosis or fetal mortality/morbidity, in order to diagnose the antiphospholipid syndrome. [ 15 ]  Positive laboratory test results should be seen on two occasions at least 12 weeks apart in order for diagnosis.  Antiphospholipid antibody syndrome is an important marker for recurrent thrombosis, and often warrants indefinite  anticoagulant  (blood thinner) therapy. Warfarin appears to be preferable to DOACs as the latter have recently been found less effective than expected. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3020", "text": "The criteria were defined in 1999, and revised in 2006. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3021", "text": "A  direct agglutination test  ( DAT ) is any test that uses whole organisms as a means of looking for  serum   antibodies .  The abbreviation, DAT, is most frequently used for the  serological  test for  visceral leishmaniasis . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3022", "text": "Dried blood spot testing  (DBS) is a form of  biosampling  where blood samples are blotted and dried on filter paper. The dried samples can easily be shipped to an  analytical laboratory  and analysed using various methods such as  DNA amplification  or  high-performance liquid chromatography . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3023", "text": "Ivar Bang first described the DBS as an unusual sampling method in 1913. [ 1 ]  The concept that capillary blood, obtained from pricking the heel or finger and blotted onto filter paper, could be used to screen for metabolic diseases in large populations of neonates was introduced in Scotland by  Robert Guthrie  in 1963. Neonatal screening for  phenylketonuria  became nationwide in 1969\u201370. Since then,  Guthrie  card samples have been collected routinely from infants in over 20 countries to screen for phenylketonuria and more recently for  congenital hypothyroidism ,  sickle cell disorders  and HIV infection. The limitations of sensitivity and specificity when screening such small volumes of blood restricted the use of dried blood spots for many years. However, recent advances such as the production of  monoclonal antibodies , expression of synthetic proteins, and the introduction of the polymerase chain reaction have overcome many of these problems. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3024", "text": "This type of blood testing is now available for use at home by consumers in the U.S.  Available blood tests include vitamin D, estrogen, testosterone, cortisol, TSH and lipids.  New York is the only state that prohibits home blood spot testing. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3025", "text": "By 2001, over 175 analytes had been measured using DBS, ranging from acylcarnitines and C-reactive protein to cyclosporine A, cytokines, hepatitis B virus, glucose, and antibodies for over 30 viruses and microorganisms. Other analytes included gentamicin, lipoproteins, prolactin, selenium, trace elements, vitamin A, and zinc protoporphyrin were also measured. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3026", "text": "In the 20th century, the use of blood and serum collected and dried on a filter paper for serologic testing for syphilis was already reported. Both field and home sample collections were described. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3027", "text": "The first report of blood absorbed onto filter paper for enzyme measurements was published in 1953. [ 3 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3028", "text": "In 1962, Berry explored the use of filter paper urine samples for population-based screening programs. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3029", "text": "In 1980, an immunochemical test for colorectal cancer screening using fecal occult blood smears on specially treated filter paper was introduced. [ 3 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3030", "text": "In 1987, successful extraction of DNA from blood collected on \u201cblotter\u201d paper and dried was first reported by McCabe. [ 3 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3031", "text": "Dried blood spot specimens are collected by applying a few drops of blood, drawn by lancet from the finger, heel or toe, onto specially manufactured absorbent filter paper. The blood is allowed to thoroughly saturate the paper. It is air dried for several hours. [ 9 ]  Specimens are stored in low gas-permeability plastic bags with  desiccant  added to reduce humidity, and may be kept at ambient temperature, even in tropical climates. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3032", "text": "Once in the laboratory, technicians separate a small disc of saturated paper from the sheet using an automated or manual hole punch, dropping the disc into a flat bottomed microtitre plate.  The blood is eluted out in phosphate buffered saline containing 0.05%  Tween 80  and 0.005%  sodium azide , overnight at 4\u00a0\u00b0C. The resultant plate containing the eluates forms the \"master\" from which dilutions can be made for subsequent testing. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3033", "text": "As an alternative to punching out a paper disc, recent automation solutions extract the sample by flushing an eluent through the filter without punching it out. [ 10 ] [ 11 ]  An automation including the application of an internal standard prior extraction was developed by the Swiss company CAMAG. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3034", "text": "The technology holds promise for expanding diagnostic services to HIV-infected infants in resource-poor settings due to the samples' longer lifespan with reduced need for refrigeration and the less invasive nature of the test compared with other methods.  Unlike  ELISA  testing for HIV-antibodies in the blood, which may be transmitted to infants in pregnancy independently of the virus itself, dried blood spot testing can be used to detect the genetic material of the actual virus, thereby avoiding the likelihood of a  false positive  result.\nDried blood spot testing for HIV is not considered sensitive enough for diagnostic testing, but may be useful in estimating the prevalence of HIV through surveillance.\nDBS specimens also pose less of a biohazard risk to handlers, and are easier to transport or store than liquid blood specimens. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3035", "text": "The reason for the stability of DNA, RNA or protein could be attributed to the fact that the biological material binds to the matrix of the filter paper and the process of drying excludes water which is an important factor necessary for protease or nuclease to act. Binding of the biological material also binds several inhibitors which may interfere with various nucleic acid amplification methods. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3036", "text": "DBS has important characteristics that make it suitable for current and future applications.  It presents minimal potential risk of bacterial contamination and/or hemolysis. It is an easy, non-invasive and economical collection method. DBS samples can be stored for extended periods with almost no deterioration of the analytes, they require less blood compared to conventional venipuncture. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3037", "text": "However, there are some concerns associated with DBS biosampling. These include challenges related to sample volume, analyte recovery, the hematocrit effect, sample homogeneity, and the characteristics of the filter paper used. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3038", "text": "Ecarin clotting time  ( ECT ) is a laboratory test used to monitor anticoagulation during treatment with  hirudin , an  anticoagulant   medication  which was originally isolated from  leech  saliva. Ecarin, the primary reagent in this assay, is derived from the venom of the saw-scaled viper,  Echis carinatus . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3039", "text": "In the clinical assay, a known quantity of  ecarin  is added to the plasma of a patient treated with hirudin. Ecarin activates  prothrombin  through a specific proteolytic cleavage, which produces meizothrombin, a prothrombin-thrombin intermediate which retains the full molecular weight of prothrombin, but possesses a low level of procoagulant enzymatic activity. Crucially, this activity is inhibited by hirudin and other direct thrombin inhibitors, but not by  heparin . The ECT is also unaffected by prior treatment with  warfarin  or the presence of phospholipid-dependent anticoagulants, such as  lupus anticoagulant . Thus, the ECT is prolonged in a specific and linear fashion with increasing concentrations of hirudin. An enhancement of the ECT is the ecarin chromogenic assay (ECA) in which diluted sample is mixed with an excess of purified prothrombin and the generated meizothrombin is measured with a specific chromogenic substrate. This assay shows no interference from prothrombin or fibrinogen in the sample and is suitable for the measurement of all direct thrombin inhibitors. [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3040", "text": "Epitope Detection in Monocytes (EDIM)  is a technology that uses the  innate immune system 's mechanisms to detect  biomarkers  or  antigens  in  immune cells . It is a non-invasive form of liquid  biopsy , i.e. biopsy from blood, which analyzes activated  macrophages  ( CD14+ / CD16+ ) for disease-specific epitopes, such as tumor cell components. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3041", "text": "Macrophages are part of the human immune system. They are involved in the detection, phagocytosis and destruction of organisms which are deemed harmful. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3042", "text": "In case of cancerous tumors,  macrophages  ingest tumor cells and dissolve them with the help of enzymes, storing tumor proteins intracellularly, even when little tumor mass is present. With the help of EDIM technologie, activated macrophages containing intracellular tumor epitopes can be detected using CD14 and CD16 specific antibodies. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3043", "text": "Currently, EDIM technology is used for the blood test PanTum Detect. Here, the method is applied to examine which individuals would benefit from further cancer detection examinations with imaging procedures ( MRI ,  PET/CT ) to clarify a possible tumor disease. The two biomarkers used for PanTum Detect are  TKTL1  and  DNaseX ."}
{"_id": "WikiPedia_Hematology$$$corpus_3044", "text": "The PanTum Detect blood test exploits the EDIM technology utilizing the fact that activated monocytes/macrophages phagocytose tumor cells and contain tumor proteins intracellularly. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3045", "text": "This  biotechnology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_3046", "text": "An  electrolyte  is a substance that conducts  electricity  through the movement of  ions , but not through the movement of  electrons . [ 1 ] [ 2 ] [ 3 ]  This includes most soluble  salts ,  acids , and  bases , dissolved in a  polar solvent  like water. Upon dissolving, the substance separates into  cations  and  anions , which disperse uniformly throughout the solvent. [ 4 ]   Solid-state electrolytes  also exist. In medicine and sometimes in chemistry, the term electrolyte refers to the substance that is dissolved. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3047", "text": "Electrically, such a solution is neutral. If an  electric potential  is applied to such a solution, the cations of the solution are drawn to the  electrode  that has an abundance of  electrons , while the anions are drawn to the electrode that has a deficit of electrons. The movement of anions and cations in opposite directions within the solution amounts to a current. Some gases, such as  hydrogen chloride  (HCL), under conditions of high temperature or low pressure can also function as electrolytes. [ clarification needed ]  Electrolyte solutions can also result from the dissolution of some biological (e.g.,  DNA ,  polypeptides ) or  synthetic polymers  (e.g.,  polystyrene sulfonate ), termed \" polyelectrolytes \", which contain charged  functional groups . A substance that dissociates into ions in solution or in the melt acquires the capacity to conduct electricity.  Sodium ,  potassium ,  chloride ,  calcium ,  magnesium , and  phosphate  in a liquid phase are examples of electrolytes."}
{"_id": "WikiPedia_Hematology$$$corpus_3048", "text": "In medicine,  electrolyte replacement  is needed when a person has prolonged  vomiting  or  diarrhea , and as a response to sweating due to strenuous athletic activity. Commercial electrolyte solutions are available, particularly for sick children (such as  oral rehydration  solution,  Suero Oral , or  Pedialyte ) and athletes ( sports drinks ). Electrolyte monitoring is important in the treatment of  anorexia  and  bulimia ."}
{"_id": "WikiPedia_Hematology$$$corpus_3049", "text": "In science, electrolytes are one of the main components of  electrochemical cells . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3050", "text": "In clinical  medicine , mentions of electrolytes usually refer  metonymically  to the ions, and (especially) to their  concentrations  (in blood, serum, urine, or other fluids). Thus, mentions of electrolyte levels usually refer to the various ion concentrations, not to the fluid volumes."}
{"_id": "WikiPedia_Hematology$$$corpus_3051", "text": "The word  electrolyte  derives from  Ancient Greek  \u03ae\u03bb\u03b5\u03ba\u03c4\u03c1\u03bf- ( \u0113lectro -), prefix originally meaning  amber  but in modern contexts related to electricity, and \u03bb\u03c5\u03c4\u03cc\u03c2 ( lytos ), meaning \"able to be untied or loosened\". [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3052", "text": "In his 1884 dissertation,  Svante Arrhenius  put forth his explanation of solid crystalline salts disassociating into paired charged particles when dissolved, for which he won the 1903  Nobel Prize  in Chemistry. [ 7 ] [ 8 ] [ 9 ] [ 10 ]  Arrhenius's explanation was that in forming a solution, the salt dissociates into charged particles, to which  Michael Faraday  (1791-1867) had given the name \" ions \" many years earlier. Faraday's belief had been that ions were produced in the process of  electrolysis . Arrhenius proposed that, even in the absence of an electric current, solutions of salts contained ions. He thus proposed that chemical reactions in solution were reactions between ions. [ 8 ] [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3053", "text": "Shortly after Arrhenius's hypothesis of ions,  Franz Hofmeister  and Siegmund Lewith [ 11 ] [ 12 ] [ 13 ]  found that different ion types displayed different effects on such things as the solubility of proteins. A consistent ordering of these different ions on the magnitude of their effect arises consistently in many other systems as well. This has since become known as the  Hofmeister series ."}
{"_id": "WikiPedia_Hematology$$$corpus_3054", "text": "While the origins of these effects are not abundantly clear and have been debated throughout the past century, it has been suggested that the charge density of these ions is important [ 14 ]  and might actually have explanations originating from the work of  Charles-Augustin de Coulomb  over 200 years ago."}
{"_id": "WikiPedia_Hematology$$$corpus_3055", "text": "Electrolyte solutions are normally formed when salt is placed into a  solvent  such as water and the individual components dissociate due to the  thermodynamic  interactions between solvent and solute molecules, in a process called \" solvation \". For example, when table salt ( sodium chloride ), NaCl, is placed in water, the salt (a solid) dissolves into its component ions, according to the dissociation reaction: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3056", "text": "It is also possible for substances to react with water, producing ions.  For example,  carbon dioxide  gas dissolves in water to produce a solution that contains  hydronium ,  carbonate , and  hydrogen carbonate  ions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3057", "text": "Molten salts  can also be electrolytes as, for example, when sodium chloride is molten, the liquid conducts electricity. In particular, ionic liquids, which are molten salts with melting points below 100\u00a0\u00b0C, [ 15 ]  are a type of highly conductive non-aqueous electrolytes and thus have found more and more applications in fuel cells and batteries. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3058", "text": "An electrolyte in a solution may be described as \"concentrated\" if it has a high concentration of ions, or \"dilute\" if it has a low concentration. If a high proportion of the solute dissociates to form free ions, the electrolyte is strong; if most of the solute does not dissociate, the electrolyte is weak. The properties of electrolytes may be exploited using electrolysis to extract constituent elements and compounds contained within the solution. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3059", "text": "Alkaline earth metals form hydroxides that are strong electrolytes with limited solubility in water, due to the strong attraction between their constituent ions. This limits their application to situations where high solubility is required. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3060", "text": "In 2021, researchers have found that electrolyte can \"substantially facilitate electrochemical corrosion studies in less conductive media\". [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3061", "text": "In  physiology , the primary ions of electrolytes are  sodium  (Na + ),  potassium  (K + ),  calcium  (Ca 2+ ),  magnesium  (Mg 2+ ),  chloride  (Cl \u2212 ),  hydrogen phosphate  (HPO 4 2\u2212 ), and  hydrogen carbonate  (HCO 3 \u2212 ). [ 19 ] [ failed verification ]  The electric charge symbols of plus (+) and minus (\u2212)  indicate that the substance is ionic in nature and has an imbalanced distribution of electrons, the result of  chemical dissociation . Sodium is the main electrolyte found in extracellular fluid and potassium is the main intracellular electrolyte; [ 20 ]  both are involved in fluid balance and  blood pressure  control. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3062", "text": "All known multicellular lifeforms require a subtle and complex electrolyte balance between the  intracellular  and  extracellular  environments. [ 19 ]  In particular, the maintenance of precise  osmotic   gradients  of electrolytes is important. Such gradients affect and regulate the  hydration  of the body as well as  blood pH , and are critical for  nerve  and  muscle  function. Various mechanisms exist in living species that keep the concentrations of different electrolytes under tight control. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3063", "text": "Both muscle tissue and  neurons  are considered electric tissues of the body. Muscles and neurons are activated by electrolyte activity between the  extracellular fluid  or  interstitial fluid , and  intracellular fluid . Electrolytes may enter or leave the cell membrane through specialized protein structures embedded in the  plasma membrane  called \" ion channels \". For example,  muscle contraction  is dependent upon the presence of calcium (Ca 2+ ), sodium (Na + ), and potassium (K + ). Without sufficient levels of these key electrolytes, muscle weakness or severe muscle contractions may occur. [ citation needed ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3064", "text": "Electrolyte balance is maintained by oral, or in emergencies, intravenous (IV) intake of electrolyte-containing substances, and is regulated by  hormones , in general with the  kidneys  flushing out excess levels. In humans, electrolyte  homeostasis  is regulated by hormones such as  antidiuretic hormones ,  aldosterone  and  parathyroid hormones . Serious  electrolyte disturbances , such as  dehydration  and  overhydration , may lead to cardiac and neurological complications and, unless they are rapidly resolved, will result in a  medical emergency ."}
{"_id": "WikiPedia_Hematology$$$corpus_3065", "text": "Measurement of electrolytes is a commonly performed diagnostic procedure, performed via  blood testing   with  ion-selective electrodes  or  urinalysis  by  medical technologists . The interpretation of these values is somewhat meaningless without analysis of the  clinical history  and is often impossible without parallel measurements of  renal function . The electrolytes measured most often are sodium and potassium. Chloride levels are rarely measured except for  arterial blood gas  interpretations since they are inherently linked to sodium levels. One important test conducted on urine is the  specific gravity  test to determine the occurrence of an  electrolyte imbalance . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3066", "text": "According to a study paid for by the  Gatorade Sports Science Institute , electrolyte drinks containing sodium and potassium salts replenish the body's water and electrolyte concentrations after dehydration caused by  exercise ,  excessive alcohol consumption ,  diaphoresis  (heavy sweating), diarrhea, vomiting,  intoxication  or starvation; the study says that athletes exercising in extreme conditions (for three or more hours continuously, e.g. a  marathon  or  triathlon ) who do not consume electrolytes risk  dehydration  (or  hyponatremia ). [ 24 ] [ needs\u00a0independent\u00a0confirmation ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3067", "text": "A home-made electrolyte drink can be made by using water, sugar and salt  in precise proportions . [ 25 ]  It is important to include  glucose  (sugar) to utilise the co-transport mechanism of sodium and glucose. Commercial preparations are also available [ 26 ]  for both human and veterinary use."}
{"_id": "WikiPedia_Hematology$$$corpus_3068", "text": "Electrolytes are commonly found in  fruit juices , sports drinks, milk, nuts, and many fruits and vegetables (whole or in juice form) (e.g., potatoes,  avocados )."}
{"_id": "WikiPedia_Hematology$$$corpus_3069", "text": "When  electrodes  are placed in an electrolyte and a  voltage  is applied, the electrolyte will conduct electricity. Lone  electrons  normally cannot pass through the electrolyte; instead, a chemical reaction occurs at the  cathode , providing electrons to the electrolyte.   Another reaction occurs at the  anode , consuming electrons from the electrolyte. As a result, a negative charge cloud develops in the electrolyte around the cathode, and a positive charge develops around the anode. The ions in the electrolyte neutralize these charges, enabling the electrons to keep flowing and the reactions to continue. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3070", "text": "For example, in a solution of ordinary table salt (sodium chloride, NaCl) in water, the cathode reaction will be"}
{"_id": "WikiPedia_Hematology$$$corpus_3071", "text": "and  hydrogen  gas will bubble up; the anode reaction is"}
{"_id": "WikiPedia_Hematology$$$corpus_3072", "text": "and  chlorine  gas will be liberated into solution where it reacts with the sodium and hydroxyl ions to produce  sodium hypochlorite  - household  bleach . The positively charged sodium ions Na +  will react toward the cathode, neutralizing the negative charge of OH \u2212  there, and the negatively charged hydroxide ions OH \u2212  will react toward the anode, neutralizing the positive charge of Na +  there. Without the ions from the electrolyte, the charges around the electrode would slow down continued electron flow;  diffusion  of H +  and OH \u2212  through water to the other electrode takes longer than movement of the much more prevalent salt ions.\nElectrolytes dissociate in water because water molecules are dipoles and the dipoles orient in an energetically favorable manner to  solvate  the ions."}
{"_id": "WikiPedia_Hematology$$$corpus_3073", "text": "In other systems, the electrode reactions can involve the metals of the electrodes as well as the ions of the electrolyte."}
{"_id": "WikiPedia_Hematology$$$corpus_3074", "text": "Electrolytic conductors are used in electronic devices where the chemical reaction at a metal-electrolyte interface yields useful effects."}
{"_id": "WikiPedia_Hematology$$$corpus_3075", "text": "Solid electrolytes can be mostly divided into four groups described below."}
{"_id": "WikiPedia_Hematology$$$corpus_3076", "text": "Gel electrolytes \u2013 closely resemble liquid electrolytes. In essence, they are liquids in a flexible  lattice framework . Various  additives  are often applied to increase the  conductivity  of such systems. [ 27 ] [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3077", "text": "Solid ceramic electrolytes \u2013  ions  migrate through the ceramic phase by means of vacancies or  interstitials  within the  lattice . There are also  glassy-ceramic  electrolytes."}
{"_id": "WikiPedia_Hematology$$$corpus_3078", "text": "Dry polymer electrolytes differ from liquid and gel electrolytes in that salt is dissolved directly into the solid medium. Usually it is a relatively high- dielectric constant   polymer  ( PEO ,  PMMA ,  PAN ,  polyphosphazenes ,  siloxanes , etc.) and a salt with low  lattice energy . In order to increase the  mechanical strength  and conductivity of such electrolytes, very often  composites  are made, and inert ceramic phase is introduced. There are two major classes of such electrolytes: polymer-in-ceramic, and ceramic-in-polymer. [ 30 ] [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3079", "text": "Organic ionic plastic crystals \u2013 are a type  organic salts  exhibiting  mesophases  (i.e. a  state of matter  intermediate between liquid and solid), in which mobile ions are orientationally or rotationally disordered while their centers are located at the ordered sites in the crystal structure. [ 28 ]  They have various forms of disorder due to one or more solid\u2013solid  phase transitions  below the  melting point  and have therefore  plastic  properties and good mechanical flexibility as well as an improved electrode-electrolyte interfacial contact. In particular, protic organic ionic plastic crystals (POIPCs), [ 28 ]  which are solid  protic  organic salts formed by  proton  transfer from a  Br\u00f8nsted acid  to a Br\u00f8nsted base and in essence are protic  ionic liquids  in the  molten state , have found to be promising solid-state  proton conductors  for  fuel cells . Examples include  1,2,4-triazolium   perfluorobutanesulfonate [ 28 ]  and  imidazolium   methanesulfonate . [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3080", "text": "Enzyme multiplied immunoassay technique  ( EMIT ) is a common method for qualitative and quantitative determination of therapeutic and recreational drugs and certain proteins in  serum  and  urine . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3081", "text": "It is an  immunoassay  in which a drug or metabolite in the sample competes with a drug/metabolite labelled with an enzyme, to bind to an antibody. The more drug there is in the sample, the more free enzyme there will be, and the increased enzyme activity causes a change in color. [ 2 ] :\u200a70"}
{"_id": "WikiPedia_Hematology$$$corpus_3082", "text": "Determination of drug levels in serum is particularly important when the difference in the concentrations needed to produce a therapeutic effect and adverse side reactions (the  therapeutic window ) is small. EMIT therapeutic drug monitoring tests provide accurate information about the concentration of such drugs such as  immunosuppressant  drugs and some antibiotics. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3083", "text": "EMIT urine assays for drugs such as cannabinoids, morphine, and amphetamine are designed to detect the drug itself or a metabolite of the drug present in a concentration above a pre-specified minimum detection cutoff limit. [ 5 ]   In the U.S., the cutoff limits must be set in accordance with Mandatory Guidelines for Federal Workplace Drug Testing Programs that were developed by SAMHSA (The Substance Abuse and Mental Health Services Administration is a branch of the U.S. Department of Health and Human Services).  The setting of reasonable cutoff limits help reduce false positive results that occur from assay limitations. Because of the social and legal consequences, a positive test result must be confirmed by an alternative method, usually Gas Chromatography/Mass spectrometry. As an example the SAMHSA cutoffs for cannabinoids are 50\u00a0ng/ml for the immunoassay and 15\u00a0ng/ml as confirmed by GC/MS. [ 6 ]  Immunoassays that do not conform with SAMHSA, featuring a cutoff of 20\u00a0ng/ml, have been shown to produce false positives from passive inhalation of marijuana smoke. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3084", "text": "Erythrocyte fragility  refers to the propensity of  erythrocytes  (red blood cells, RBC) to hemolyse (rupture) under stress. It can be thought of as the degree or proportion of  hemolysis  that occurs when a sample of  red blood cells  are subjected to stress (typically physical stress, and most commonly osmotic and/or mechanical stress). Depending on the application as well as the kind of fragility involved, the amount of stress applied and/or the significance of the resultant hemolysis may vary. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3085", "text": "When multiple levels of stress are applied to a given population/sample of cells, a  fragility profile  can be obtained by measuring the relative or absolute extent of hemolysis existing at each such level, [ 1 ]  in addition to finding one or more single-number  indexes [ 2 ]  (either measured directly or interpolated) associated with particular respective levels of hemolysis and/or corresponding stress. Fragility testing can be useful to assess cells' ability (or lack thereof) to withstand sustained or repeated stress. Moreover, it can be used to assess how fragility itself varies under different or changing environmental or stress conditions, during or prior to the inducement of the hemolysis. Low fragility is often termed \" stability ,\" though technically stability refers to cells' resistance to  both  stress-induced lysis  and  spontaneous auto-lysis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3086", "text": "Osmotic fragility  (OF) refers to the degree or proportion of  hemolysis  that occurs when a sample of  red blood cells  are subjected to osmotic stress by being placed in a  hypotonic  solution. Osmotic fragility is affected by various factors, including membrane composition and integrity as well as the cells' sizes or surface-area-to-volume ratios. [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3087", "text": "The osmotic fragility test is common in  hematology , and is often performed to aid with diagnosis of diseases associated with RBC membrane abnormalities. Some diseases linked to  increased  OF include  hereditary spherocytosis  and  hypernatremia , while some linked to  decreased  OF include chronic liver disease, iron deficiency anemia, thalassemia, hyponatremia, polycythemia vera, hereditary xerocytosis, [ 6 ]  and sickle cell anemia after splenectomy. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3088", "text": "New approaches to testing OF are under development to better facilitate its use in disease diagnosis and screening, such as by utilizing microfluidic devices along with cell counting. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3089", "text": "Mechanical fragility  (MF) refers to the degree or proportion of  hemolysis  that occurs when a sample of  red blood cells  are subjected to mechanical stress, such as (typically) some kind of  shear stress . Yet unlike with osmotic fragility, no single approach for testing mechanical fragility has yet gained sufficient acceptance to enable standardization. [ 9 ]   This has led to some insurance companies not currently covering the test. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3090", "text": "Uses of erythrocyte mechanical fragility can include diagnostic testing, [ 11 ]  calibrations to aid comparisons of hemolysis caused by blood-handling devices, [ 9 ]  or assessment of sublethal (i.e., non-hemolysing) damage caused to cells from devices that manipulate blood (such as for dialysis [ 12 ]  or intraoperative autotransfusion [ 13 ] ). It can also help in assessing damage of stored RBC product [ 14 ]  (so-called \"storage lesion\"), leading to applications in  blood transfusion  and  blood banking ."}
{"_id": "WikiPedia_Hematology$$$corpus_3091", "text": "It's also notable that there can be a  qualitative  difference between a mechanical fragility test involving a comparatively lower energy stress, such as by agitating one or more beads in the presence of the sample (a common approach [ 15 ] ), versus a higher energy stress, such as by applying ultrasound to the sample. [ 16 ]  The difference is that the lower-energy category of stress can more prominently reflect cell membrane properties, whereas the higher-energy category largely reflects other properties like hemoglobin viscosity and cell size. Viscous or fluidic-mechanical stresses can be of either sort. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3092", "text": "Mechanical fragility is increased  in the cases of sickle cell anemia, thalassemia, hereditary spherocytosis etc. ."}
{"_id": "WikiPedia_Hematology$$$corpus_3093", "text": "Susceptibility to hemolysis from causes  other than  osmotic or mechanical forces are not as common, but may sometimes be referred to in terms of fragility or stability.  For example, photons or radicals can induce hemolysis.Erythrocytes/RBC may also be tested for related membrane properties aside from fragility, including  erythrocyte deformability  and cell morphology. Morphology can be measured by indexes which characterize shape changes of differences among cells. Deformability testing involves measuring the degree or ease of cells' contortion or shape change under a given level of applied force - or some indirect inference of the like. Other related red blood cell properties can include adhesion and aggregation, which along with deformability are often classed as RBC \"flow properties.\" [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3094", "text": "Erythrocyte rosetting  or  E-rosetting  is a phenomenon seen through a  microscope  where  red blood cells   (erythrocytes)  are arranged around a central cell to form a cluster that looks like a flower.  The red blood cells surrounding the cell form the  petal,  while the central cell forms the  stigma  of the flower shape.  This formation occurs due to an  immunological  reaction between an epitope on the central cell's surface and a receptor or antibody on a red cell. [ 1 ]   The presence of E-rosetting can be used as a test for  T cells  although more modern tests such as  immunohistochemistry  are available. Rosetting is caused by parasites in the genus  Plasmodium  and is a cause of some malaria-associated symptoms. [ 2 ] [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3095", "text": "Three types of rosette techniques have been developed and used experimentally. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3096", "text": "The  Rosette test  is performed on postpartum maternal blood to estimate the volume of  fetal-maternal hemorrhage  in case of an  Rh negative  mother and an Rh positive child. This estimate, in turn, also estimates the required amount of  Rho(D) immune globulin  to administer. [ 3 ]  In this test, a sample of maternal blood is incubated with Rho(D) immune globulin, which will bind to any fetal Rh positive  red blood cells , if present. [ 4 ]  Upon addition of enzyme-treated cDE indicator cells, the presence of Rh positive fetal blood causes rosetting, which can be seen by  light microscopy . [ 4 ]  The test is recommended for Rh negative mothers within 72 hours of giving birth to an Rh-positive infant. [ 3 ]  In a positive test, it is recommended that a  Kleihauer\u2013Betke test  should be performed to confirm and quantify any positive rosette tests. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3097", "text": "E-rosetting is used in the identification of T cells where a T cells  CD2  surface protein is bound to a sugar based  LFA-3  homologue on the surface of a sheep red blood cell. [ 1 ]   Because the LFA-3 homologue is only present on the surface of sheep red blood cells other species red blood cells can not be used in this type of rosetting. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3098", "text": "Erythrocyte antibody rosetting (EA-rosetting), occurs when an antibody molecule that is specific for an epitope on another cell is embedded in the membrane of a red blood cell and then reacted against a cell carrying the epitope that the antibody is specific for. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3099", "text": "Erythrocyte antibody complement rosetting (EAC-rosetting), occurs when antibody in the presence of complement is bound to the surface of a red blood cell.  The complement binds to the tail region (Fc region) of the antibody.  Finally T-cells with a complement receptor are added and the T-cells bind to the complement on the antibody completing the rosette. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3100", "text": "The  erythrocyte sedimentation rate  ( ESR  or  sed rate ) is the rate at which  red blood cells  in anticoagulated  whole blood  descend in a standardized tube over a period of one hour. It is a common  hematology  test, and is a non-specific measure of  inflammation .\nTo perform the test,  anticoagulated  blood is traditionally placed in an upright tube, known as a Westergren tube, and the distance which the red blood cells fall is measured and reported in  millimetres  at the end of one hour. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3101", "text": "Since the introduction of  automated analyzers  into the clinical laboratory, the ESR test has been automatically performed."}
{"_id": "WikiPedia_Hematology$$$corpus_3102", "text": "The ESR is influenced by the aggregation of red blood cells: blood plasma proteins, mainly  fibrinogen , promote the formation of red cell clusters called  rouleaux  or larger structures (interconnected rouleaux, irregular clusters). As according to  Stokes' law  the sedimentation velocity varies like the square of the object's diameter, larger aggregates settle faster. While aggregation already takes place at normal physiological fibrinogen levels, these tend to increase when an inflammatory process is present, leading to increased ESR."}
{"_id": "WikiPedia_Hematology$$$corpus_3103", "text": "The ESR is increased in inflammation,  pregnancy ,  anemia ,  autoimmune disorders  (such as  rheumatoid arthritis  and  lupus ), infections, some kidney diseases and some cancers (such as  lymphoma  and  multiple myeloma ). The ESR is decreased in  polycythemia ,  hyperviscosity ,  sickle cell anemia ,  leukemia ,  chronic fatigue syndrome , [ 4 ]  low  plasma protein  (due to liver or kidney disease) and  congestive heart failure . Although increases in immunoglobulins usually increase the ESR, very high levels can reduce it again due to hyperviscosity of the plasma. [ 5 ]  This is especially likely with  IgM -class paraproteins, and to a lesser extent,  IgA -class. The basal ESR is slightly higher in females. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3104", "text": "Erythrocyte sedimentation rate (ESR) is the measure of ability of erythrocytes ( red blood cell ) to fall through the  blood plasma  and accumulate together at the base of container in one hour. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3105", "text": "There are three stages in erythrocyte sedimentation: [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3106", "text": "In normal conditions, the red blood cells are negatively charged and therefore repel each other rather than stacking. ESR is also reduced by high blood  viscosity , which slows the rate of fall. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3107", "text": "The rate of erythrocyte sedimentation is affected by both  inflammatory  and non-inflammatory conditions."}
{"_id": "WikiPedia_Hematology$$$corpus_3108", "text": "In inflammatory conditions,  fibrinogen , other clotting proteins, and  alpha globulin  are positively charged, thus increasing the ESR. [ 9 ]  ESR begins to rise at 24 to 48 hours after the onset of acute self-limited inflammation, decreases slowly as inflammation resolves, and can take weeks to months to return to normal levels. For ESR values more than 100\u00a0mm/hour, there is a 90% probability that an underlying cause would be found upon investigation. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3109", "text": "In non-inflammatory conditions, plasma albumin concentration, size, shape, and number of red blood cells, and the concentration of  immunoglobulin  can affect the ESR. Non-inflammatory conditions that can cause raised ESR include  anemia ,  kidney failure ,  obesity , ageing, and female sex. [ 7 ]  ESR is also higher in women during  menstruation  and  pregnancy . [ 9 ]  The value of ESR does not change whether dialysis is performed or not. Therefore, ESR is not a reliable measure of inflammation in those with kidney injuries as the ESR value is already elevated. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3110", "text": "An increased number of red blood cells (polycythemia) causes reduced ESR as blood viscosity increases.  Hemoglobinopathy  such as  sickle-cell disease  can have low ESR due to an improper shape of red blood cells that impairs stacking. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3111", "text": "ESR can sometimes be useful in diagnosing diseases, such as multiple myeloma,  temporal arteritis ,  polymyalgia rheumatica , various autoimmune diseases,  systemic lupus erythematosus ,  rheumatoid arthritis , inflammatory bowel disease [ 11 ]  and chronic kidney diseases.  In many of these cases, the ESR may exceed 100\u00a0mm/hour. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3112", "text": "It is commonly used for a differential diagnosis for  Kawasaki's disease  (from  Takayasu's arteritis ; which would have a markedly elevated ESR) and it may be increased in some chronic infective conditions like  tuberculosis  and infective  endocarditis . It is also elevated in subacute  thyroiditis  also known as DeQuervain's."}
{"_id": "WikiPedia_Hematology$$$corpus_3113", "text": "In markedly increased ESR of over 100\u00a0mm/h, infection is the most common cause (33% of cases in an American study), followed by cancer (17%), kidney disease (17%) and noninfectious inflammatory disorders (14%). [ 13 ]  Yet, in  pneumonia  the ESR stays under 100. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3114", "text": "The usefulness of the ESR in current practice has been questioned by some, as it is a relatively imprecise and non-specific test compared to other available diagnostic tests. [ 15 ]  Current literature suggests that and ESR should be \"obtained on all patients over the age of 50\" who have an intense headache. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3115", "text": "It is a component of the  PCDAI  (pediatric Crohn's disease activity index), an index for assessment of the severity of inflammatory bowel disease in children. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3116", "text": "The clinical usefulness of ESR is limited to monitoring the response to therapy in certain inflammatory diseases such as temporal arteritis, polymyalgia rheumatica and rheumatoid arthritis. It can also be used as a crude measure of response in  Hodgkin's lymphoma . Additionally, ESR levels are used to define one of the several possible adverse prognostic factors in the staging of Hodgkin's lymphoma. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3117", "text": "Note: mm/h. = millimeters per hour."}
{"_id": "WikiPedia_Hematology$$$corpus_3118", "text": "Westergren's original normal values (men 3\u00a0mm/h and women 7\u00a0mm/h) [ 17 ]  made no allowance for a person's age. Later studies from 1967 confirmed that ESR values tend to rise with age and to be generally higher in women. [ 18 ] \nValues of the ESR also appear to be slightly higher in normal populations of African-Americans than Caucasians of both genders. [ 19 ]  Values also appear to be higher in anemic individuals than non-anemic individuals. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3119", "text": "The widely used [ 21 ]  rule calculating normal maximum ESR values in adults (98% confidence limit) is given by a formula devised in 1983 from a study of \u22481000 individuals over the age of 20: [ 22 ]  The normal values of ESR in men is age (in years) divided by 2; for women, the normal value is age (in years) plus 10, divided by 2. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3120", "text": "Other studies confirm a dependence of ESR on age and gender, as seen in the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_3121", "text": "ESR reference ranges from a large 1996 study of 3,910 healthy adults (NB. these use 95% confidence intervals rather than the 98% intervals used in the study used to derive the formula above, and because of the skewness of the data, these values appear to be less than expected from the above formula): [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3122", "text": "Normal values of ESR have been quoted as 1 [ 24 ]  to 2 [ 25 ]  mm/h at birth, rising to 4\u00a0mm/h 8 days after delivery, [ 25 ]  and then to 17\u00a0mm/h by day 14. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3123", "text": "Typical normal ranges quoted are: [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3124", "text": "C-reactive protein  (CRP) is an  acute phase protein . Therefore, it is a better marker for acute phase reaction than ESR. While ESR and CRP generally together correlate with the degree of inflammation, this is not always the case and results may be discordant [ 9 ]  in 12.5% of the cases. [ 7 ]  Cases with raised CRP but normal ESR may demonstrate a combination of infection and some other tissue damage such as  myocardial infarction , and  venous thromboembolism . Such inflammation may not be enough to raise the level of ESR. Those with high ESR usually do not have demonstrable inflammation. However, in cases of low grade bacterial infections of bone and joints such as coagulase negative  staphylococcus  (CoNS), and systemic lupus erythematosus (SLE), ESR can be a good marker for the inflammatory process. This may be due to the production of  Interferon type I  that inhibits the CRP production in liver cells during SLE. [ 27 ]  CRP is a better marker for other autoimmune diseases such as polymyalgia rheumatica,  giant cell arteritis , [ 7 ]  post-operative sepsis, and  neonatal sepsis . ESR may be reduced in those who are taking  statins  and  non-steroidal anti-inflammatory drugs  (NSAIDs). [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3125", "text": "Bone and joint infections"}
{"_id": "WikiPedia_Hematology$$$corpus_3126", "text": "Ischemic stroke"}
{"_id": "WikiPedia_Hematology$$$corpus_3127", "text": "Waldenstrom's macroglobulinemia"}
{"_id": "WikiPedia_Hematology$$$corpus_3128", "text": "Multiple myeloma"}
{"_id": "WikiPedia_Hematology$$$corpus_3129", "text": "IgG4 related disease"}
{"_id": "WikiPedia_Hematology$$$corpus_3130", "text": "Chronic kidney disease"}
{"_id": "WikiPedia_Hematology$$$corpus_3131", "text": "Low serum albumin"}
{"_id": "WikiPedia_Hematology$$$corpus_3132", "text": "Myocardial infarction"}
{"_id": "WikiPedia_Hematology$$$corpus_3133", "text": "Venous thromboembolic disease"}
{"_id": "WikiPedia_Hematology$$$corpus_3134", "text": "Rheumatoid arthritis"}
{"_id": "WikiPedia_Hematology$$$corpus_3135", "text": "The test was invented in 1897 by the Polish pathologist  Edmund Biernacki . [ 28 ] [ 29 ]  In some parts of the world the test continues to be referred to as Biernacki's Reaction ( Polish :  odczyn Biernackiego , OB). [ 30 ]  In 1918, Dr Robert F\u00e5hr\u00e6us noted that ESR differed only during pregnancy. Therefore, he suggested that ESR could be used as an indicator of pregnancy. In 1921, Dr Alf Vilhelm Albertsson Westergren used ESR to measure the disease outcome of  tuberculosis . He defined the measurement standards of ESR which is still being used today. [ 7 ]  Robert F\u00e5hr\u00e6us and Alf Vilhelm Albertsson Westergren are eponymously remembered for the 'Fahraeus-Westergren test' (abbreviated as FW test; in the UK, usually termed Westergren test), [ 30 ]  which uses  sodium citrate-anti-coagulated specimens. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3136", "text": "According to a study released in 2015, a  stop gain mutation  in  HBB  gene (p. Gln40stop) was shown to be associated with ESR values in  Sardinian population . The red blood cell count, whose values are inversely related to ESR, is affected in carriers of this  SNP . This mutation is almost exclusive of the inhabitants of Sardinia and is a common cause of  beta thalassemia . [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3137", "text": "According to a 2010 study, there is a reverse correlation between ESR and  general intelligence  (IQ) in Swedish males aged 18\u201320. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3138", "text": "The  euglobulin lysis time  ( ELT ) is a test that measures overall  fibrinolysis . The test is performed by mixing citrated platelet-poor  plasma  with acid in a glass test tube. This acidification causes the precipitation of certain  clotting factors  in a complex called the  euglobulin fraction . The euglobulin fraction contains the important  fibrinolytic  factors  fibrinogen ,  PAI-1 ,  tissue plasminogen activator  (tPA),  plasminogen , and to a lesser extent  \u03b1 2 -antiplasmin . The euglobulin fraction also contains  factor VIII . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3139", "text": "After precipitation, the euglobulin fraction is resuspended in a borate solution. Clotting is then activated by the addition of calcium chloride at 37\u00a0\u00b0C. Historically, subsequent amount of fibrinolysis was determined by eye, by observing the clot within the test tube at ten-minute intervals until complete lysis had occurred. [ 1 ]  Newer automated methods have also been developed. These methods use the same principle as the older technique, but use a  spectrophotometer  to track clot lysis as a function of  optical density . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3140", "text": "Fecal occult blood  ( FOB ) refers to  blood  in the  feces  that is not visibly apparent (unlike other types of  blood in stool  such as  melena  or  hematochezia ). A fecal occult blood test (FOBT) checks for hidden (occult) blood in the stool (feces). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3141", "text": "The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the  fecal immunochemical test  (FIT). [ 2 ]   The newer and recommended tests look for  globin ,  DNA , or other blood factors including  transferrin , while conventional  stool guaiac tests  look for  heme ."}
{"_id": "WikiPedia_Hematology$$$corpus_3142", "text": "Fecal occult blood testing (FOBT), as its name implies, aims to detect subtle blood loss in the  gastrointestinal tract , anywhere from the  mouth  to the  colon . Positive tests (\"positive stool\") may result from either  upper gastrointestinal bleeding  or  lower gastrointestinal bleeding  and warrant further investigation for  peptic ulcers  or a  malignancy  (such as  colorectal cancer  or  gastric cancer ). The test does not directly detect  colon cancer  but is often used in clinical  screening  for that disease. It can also be used to look for active occult blood loss in  anemia [ 3 ]  or when there are gastrointestinal symptoms. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3143", "text": "An estimated 1\u20135% of large tested populations have a positive fecal occult blood test. [ citation needed ]  Of those, about 2\u201310% have cancer, while 20\u201330% have  adenomas .  Screening  methods for colon cancer depend on detecting either precancerous changes such as certain kinds of polyps or on finding early and thus more treatable cancer. The extent to which screening procedures reduce the risk of gastrointestinal cancer or deaths depends on the rate of precancerous and cancerous disease in that population. gFOBT (guaiac fecal occult blood test) and flexible sigmoidoscopy screening have each shown benefit. Other colon cancer screening tools such as iFOBT (immunochemical fecal occult blood test) or colonoscopy are also included in guidelines. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3144", "text": "In 2009, the  American College of Gastroenterology  (ACG) suggested that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a  colonoscopy  every ten years in average-risk individuals, beginning at age 50. [ 2 ]  The ACG suggests that cancer detection tests such as any type of FOB are an alternative that is less preferred, and if a colonoscopy is declined, the FIT (fecal immunochemical test, or iFOBT) should be offered instead. The 2017 US Multi-Society Task Force (MSTF)'s recommended first-tier tests are a colonoscopy every 10 years or annual FIT test. [ 6 ]  If FIT is utilized, proper steps must be taken to ensure appropriate use and follow-up of abnormal FIT results. [ 7 ]  FIT tests however are not that useful in picking up adenomas, even when advanced. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3145", "text": "The  United States Preventive Services Task Force  (USPSTF)'s 2016 recommendation, instead of emphasizing specific screening approaches, has instead chosen to highlight that there is convincing evidence that colorectal cancer screening substantially reduces deaths from the disease among adults aged 50 to 75 years and that not enough adults are using this effective preventive intervention. [ 9 ]  The ACG and MSTF also included CT colonography every five years, and fecal DNA testing as considerations. All three recommendation panels recommended replacing any older low-sensitivity, guaiac-based fecal occult blood testing (gFOBT) with either newer high-sensitivity guaiac-based fecal occult blood testing (hs gFOBT) or fecal immunochemical testing (FIT). MSTF looked at six studies that compared high-sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there was no clear difference in overall performance between these methods."}
{"_id": "WikiPedia_Hematology$$$corpus_3146", "text": "The English  National Health Service  (NHS) introduced a Bowel Cancer Screening Program in 2006. [ 10 ]  It is now offered to patients aged 60\u201374 years. In 2019 FIT was introduced as the primary screening test in England and Wales, replacing gFOBt.  [ 11 ] [ 12 ]  However, research carried out in the UK has suggested that the FIT threshold for further investigation is set at a point that may miss more than half of bowel cancer cases and only identifies one in four high-risk polyps. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3147", "text": "The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the fecal immunochemical test. [ 2 ]  Though the FIT test is preferred, even the guaiac FOB testing of average risk populations may have been sufficient to reduce the mortality associated with  colon cancer  by about 25%. [ 15 ]  With this lower efficacy, it was not always cost-effective to screen a large population with gFOBT. [ 16 ] [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3148", "text": "If colon cancer is suspected in an individual (such as in someone with an unexplained  anemia ), fecal occult blood tests may not be clinically helpful. If a doctor suspects colon cancer, more rigorous investigation is necessary, whether or not the test is positive. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3149", "text": "In 2006, the Australian Government introduced the National Bowel Cancer Program which has been updated several times since; targeted screening will be done of all Australians aged from 50 to 74 by 2020. Cancer Council Australia recommended that FOBT should be done every two years. People over 50 not yet eligible for the national program can arrange with their doctor for an FOBT. [ 20 ] \nThe  Canadian Cancer Society  recommends that men and women aged 50 and over have an FOBT at least every two years. [ 21 ] \nIn colon cancer screening, using only one sample of feces collected by a doctor performing a  digital rectal examination  is discouraged. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3150", "text": "The use of the  M2-PK Test  is encouraged over gFOBT for routine screening, as it may pick up tumors whether or not they are bleeding. [ 23 ]  It is able to detect 80 percent of colorectal cancers and 44 percent for adenoma > 1 centimeter, while gFOBT picks up 13 to 50 percent of colorectal cancers. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3151", "text": "Gastrointestinal bleeding  has many potential sources, and positive results usually result in further testing for the bleeding site, usually looking for  lower gastrointestinal bleeding  before  upper gastrointestinal bleeding  causes unless there are other clues. [ 24 ]  Colonoscopy is usually preferred to computerized tomographic colonography. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3152", "text": "A positive test can result from  upper gastrointestinal bleeding  or  lower gastrointestinal bleeding . The common causes are:"}
{"_id": "WikiPedia_Hematology$$$corpus_3153", "text": "In the event of a positive fecal occult blood test, the next step in the workup is a form of visualization of the gastrointestinal tract by one of several means:"}
{"_id": "WikiPedia_Hematology$$$corpus_3154", "text": "The use of an FOBT for bleeding from the mouth, nose, esophagus, lungs, stomach and the initial portion of the small intestine, while the same as fecal testing, is discouraged, due to technical considerations including poorly characterized test performance characteristics such as sensitivity, specificity, and analytical interference. [ 29 ]  However, chemical confirmation that coloration is due to blood rather than coffee, beets, medications, or food additives can be of significant clinical assistance."}
{"_id": "WikiPedia_Hematology$$$corpus_3155", "text": "Gastrointestinal (GI) complaints and low-intensity GI bleeding frequently occur in marathon runners. [ 30 ]  Strenuous exercise, particularly in elite athlete runners and less frequently in other exercise activities, can cause acute incapacitating gastrointestinal symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and gastrointestinal bleeding. [ 31 ]  Approximately one third of endurance runners experience transient but exercise-limiting symptoms, and repetitive gastrointestinal bleeding occasionally causes iron deficiency and anaemia. [ 32 ] [ 33 ]  Runners can sometimes experience significant symptoms including  hematemesis . [ 34 ]  Exercise is associated with extensive changes in gastrointestinal (GI) tract physiology, including diversion of blood flow from the GI tract to muscles and lungs, decreased GI absorption and small intestinal motility, increased colonic transit, neuroimmunoendocrine changes in hormones and peptides such as  vasoactive intestinal peptide ,  secretin  and peptide-histidine-methionine. [ 35 ]  Substantial changes occur in stress hormones including cortisol, in circulating concentrations and metabolic behavior of various  leucocytes , and in  immunoglobulin  levels and  major histocompatibility complex  expression. [ 36 ]  Symptoms can be exacerbated by dehydration or by pre-exercise ingestion of certain foods and  hypertonic  liquids, and lessened by adequate training. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3156", "text": "Ingestion of 800 \u00a0 mg of  cimetidine  two hours before running a marathon did not significantly affect the frequency of gastrointestinal symptoms or occult gastrointestinal bleeding. [ 37 ]  Conversely, 800 \u00a0 mg of cimetidine 1 hr before the start and again at 50 miles of a 100-mile running race substantially decreased GI symptoms and post-race guaiac test positivity but did not affect race performance. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3157", "text": "There are four methods in clinical use to test for occult blood in feces. These look at different properties, such as  antibodies ,  heme ,  globin , or  porphyrins  in blood, or at  DNA  from cellular material such as from lesions of the intestinal mucosa."}
{"_id": "WikiPedia_Hematology$$$corpus_3158", "text": "Additional methods of looking for occult blood are being explored, including  transferrin  dipstick [ 48 ]  and stool  cytology . [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3159", "text": "The estimates for test performance characteristics are based on comparison with a variety of  reference methods  including 51-chromium studies, [ citation needed ]  analytical recovery studies in spiked stool samples, analytical recovery after ingestion of autologous blood, rarer studies of carefully quantified blood instilled at bowel surgery  [ citation needed ] , as well as other research approaches. [ citation needed ]  Additionally, clinical studies look at a variety of additional factors."}
{"_id": "WikiPedia_Hematology$$$corpus_3160", "text": "In healthy people about 0.5 to 1.5 \u00a0 ml of blood escapes blood vessels into the stool each day. [ 50 ] [ 51 ] [ 52 ]  Significant amounts of blood can be lost without producing visible blood in the stool, estimated as 200 \u00a0 ml in the stomach, [ 53 ]  100 \u00a0 ml in the duodenum, and lesser amounts in the lower intestine. Tests for occult blood identify lesser blood loss."}
{"_id": "WikiPedia_Hematology$$$corpus_3161", "text": "Fecal immunochemical testing (FIT) can identify as little as 0.3 \u00a0 ml of daily blood in the stool; yet this test threshold does not cause undue false positives from normal upper intestinal blood leakage because it does not detect occult blood from the stomach and upper small intestine. Thus, the FIT test is much more specific for bleeding from the colon or lower gastrointestinal tract than alternatives. [ 54 ]  The detection rate of the test decreases if the time from sample collection to laboratory processing is delayed; processing the sample in under five days from collection is recommended. [ 55 ]  It does not appear to be affected by aspirin, anticoagulants, or nonsteroidal anti-inflammatory drugs. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3162", "text": "Stool guaiac test  for fecal occult blood (gFOBT) sensitivity varies depending on the site of bleeding. Moderately sensitive gFOBT can pick up a daily blood loss of about 10 \u00a0 ml (about two teaspoonfuls), and higher sensitivity gFOBT can pick up lesser amounts, requires at least 2 \u00a0 ml to become positive. The sensitivity of a single-stool guaiac test to pick up bleeding has been quoted at 10 to 30%, but if a standard three tests are done as recommended the sensitivity rises to 92%. [ 57 ]  Reduced patient compliance with the collection of three samples hampers the usefulness of this test. Further discussion of sensitivity and specificity issues that relate particularly to the guaiac method is found in the  stool guaiac test  article."}
{"_id": "WikiPedia_Hematology$$$corpus_3163", "text": "Fecal  porphyrin  quantification by HemoQuant can yield a  false positive  result due to exogenous blood and various porphyrins. HemoQuant is the most sensitive test for upper gastrointestinal bleeding and therefore may be most appropriate fecal occult blood test to use in the evaluation of iron deficiency. [ 58 ]  It is advisable to stop ingesting red meat and aspirin for three days prior to specimen collection. [ 59 ]  False positives can occur with myoglobin, catalase, or protohemes [ 60 ]  and in certain types of porphyria. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3164", "text": "Fecal DNA tests as of 2008 had not been studied enough to support widespread use. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3165", "text": "Safety regulations from US accreditor  the Joint Commission  may have unintentionally decreased digital rectal examination and FOBT in hospital settings such as Emergency Departments. [ 62 ] [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3166", "text": "Ferritin  is a universal intracellular and extracellular  protein  that stores  iron  and releases it in a controlled fashion. The protein is produced by almost all living organisms, including  archaea ,  bacteria ,  algae ,  higher plants , and  animals . It is the primary  intracellular iron-storage protein  in both  prokaryotes  and  eukaryotes , keeping iron in a soluble and non-toxic form. In humans, it acts as a buffer against  iron deficiency  and  iron overload . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3167", "text": "Ferritin is found in most tissues as a  cytosolic  protein, but small amounts are secreted into the  serum  where it functions as an iron carrier. Plasma ferritin is also an indirect  marker  of the total amount of iron stored in the body; hence, serum ferritin is used as a  diagnostic test  for  iron-deficiency anemia  and  iron overload . [ 4 ]  Aggregated ferritin transforms into a water insoluble, crystalline and amorphous form of storage iron called  hemosiderin . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3168", "text": "Ferritin is a  globular protein  complex consisting of 24  protein subunits  forming a hollow spherical nanocage with multiple metal\u2013protein interactions. [ 6 ]  Ferritin with iron removed is called  apoferritin . [ 7 ] :\u200ae10"}
{"_id": "WikiPedia_Hematology$$$corpus_3169", "text": "Ferritin genes are highly  conserved  between species. All vertebrate ferritin genes have three  introns  and four  exons . [ 8 ]  In human ferritin, introns are present between  amino acid   residues  14 and 15, 34 and 35, and 82 and 83; in addition, there are one to two hundred  untranslated bases  at either end of the combined exons. [ 9 ]  The  tyrosine  residue at amino acid position 27 is thought to be associated with  biomineralization . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3170", "text": "Ferritin is a hollow  globular protein  of mass 474\u00a0 kDa  and comprising 24 subunits. Typically it has internal and external diameters of about 8 and 12\u00a0nm, respectively. [ 11 ]  The nature of these subunits varies by class of organism:"}
{"_id": "WikiPedia_Hematology$$$corpus_3171", "text": "All the aforementioned ferritins are similar, in terms of their primary sequence, with the vertebrate H-type. [ 12 ]  In  E. coli , a 20% similarity to human H-ferritin is observed. [ 12 ]  Some ferritin complexes in vertebrates are  hetero-oligomers  of two highly related  gene  products with slightly different  physiological  properties. The ratio of the two  homologous  proteins in the complex depends on the relative expression levels of the two genes."}
{"_id": "WikiPedia_Hematology$$$corpus_3172", "text": "Cytosolic ferritin  shell (apoferritin) is a heteropolymer of 24 subunits of heavy (H) and light (L) peptides that form a hollow spherical nanocage that covers an iron core composed of  crystallites  together with  phosphate  and  hydroxide  ions. The resulting particle is similar to  ferrihydrite  (5Fe 2 O 3 \u00b79H 2 O). Each ferritin complex can store about 4500 iron (Fe 3+ ) ions. [ 9 ] [ 12 ]  The proportion of H to L subunits varies in ferritin from different tissues, explaining its heterogeneity on isoelectric focusing. L-rich ferritins (from spleen and liver) are more basic than H-rich ferritins (from heart and red blood cells)."}
{"_id": "WikiPedia_Hematology$$$corpus_3173", "text": "Serum ferritin , which is typically iron-poor, consists almost exclusively of L subunits. Serum ferritin is heterogeneous due to glycosylation. The glycosylation and direct relationship of serum ferritin concentration to iron storage in macrophages suggest it is secreted by macrophages in response to changing iron levels."}
{"_id": "WikiPedia_Hematology$$$corpus_3174", "text": "Human  mitochondrial ferritin , MtF, was found to express as a  pro-protein . [ 14 ]  When a mitochondrion takes it up, it processes it into a mature protein similar to the ferritins found in the  cytoplasm , which it assembles to form functional ferritin shells. Unlike other human ferritins, it is a homopolymer of H type ferritin  and appears to have no introns (intronless) in its genetic code. The mitochondrial ferritin's  Ramachandran plot [ 15 ]  shows its structure to be mainly  alpha helical  with a low prevalence of  beta sheets . It accumulates in large amounts in the erythroblasts of subjects with impaired heme synthesis."}
{"_id": "WikiPedia_Hematology$$$corpus_3175", "text": "Ferritin is present in every cell type. [ 9 ]  It serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required. [ 16 ]  The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by the amount and stability of  messenger RNA  (mRNA), but also by changes in how the mRNA is stored and how efficiently it is transcribed. [ 9 ]  One major trigger for the production of many ferritins is the mere presence of iron; [ 9 ]  an exception is the yolk ferritin of  Lymnaea sp. , which lacks an iron-responsive unit. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3176", "text": "Free iron is  toxic  to  cells  as it acts as a  catalyst  in the formation of  free radicals  from  reactive oxygen species  via the  Fenton reaction . [ 17 ]  Hence vertebrates have an elaborate set of protective mechanisms to bind iron in various  tissue  compartments [ discuss ] . Within cells, iron is stored in a protein complex as ferritin or the related complex  hemosiderin . Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the  reticuloendothelial system , protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells, although hemosiderin is less readily available. Under  steady-state  conditions, the level of ferritin in the  blood serum  correlates with total body stores of iron; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3177", "text": "Because iron is an important mineral in mineralization, ferritin is employed in the shells of organisms such as  molluscs  to control the concentration and distribution of iron, thus sculpting shell morphology and colouration. [ 18 ] [ 19 ]  It also plays a role in the  haemolymph  of the  polyplacophora , where it serves to rapidly transport iron to the mineralizing  radula . [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3178", "text": "Iron is released from ferritin for use by ferritin degradation, which is performed mainly by  lysosomes . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3179", "text": "Vertebrate ferritin consists of two or three subunits which are named based on their molecular weight: L \"light\", H \"heavy\", and M \"middle\" subunits. The M subunit has only been reported in bullfrogs. In bacteria and archaea, ferritin consists of one subunit type. [ 22 ]  H and M subunits of eukaryotic ferritin and all subunits of bacterial and archaeal ferritin are H-type and have ferroxidase activity, which means they are able to convert iron from the ferrous (Fe 2+ ) to ferric (Fe 3+ ) forms. This limits the deleterious reaction which occurs between ferrous iron and  hydrogen peroxide  known as the Fenton reaction which produces the highly damaging  hydroxyl radical . The ferroxidase activity occurs at a diiron binding site in the middle of each H-type subunits. [ 22 ] [ 23 ]  After oxidation of Fe(II), the Fe(III) product stays metastably in the ferroxidase center and is displaced by Fe(II), [ 23 ] [ 24 ]  a mechanism that appears to be common among ferritins of all three domains of life. [ 22 ]  The light chain of ferritin has no ferroxidase activity but may be responsible for the electron transfer across the protein cage. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3180", "text": "Ferritin concentrations increase drastically in the presence of an infection or cancer.  Endotoxins  are an up-regulator of the gene coding for ferritin, thus causing the concentration of ferritin to rise. By contrast, organisms such as  Pseudomonas , although possessing endotoxin, cause plasma ferritin levels to drop significantly within the first 48 hours of infection. Thus, the iron stores of the infected body are denied to the infective agent, impeding its metabolism. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3181", "text": "The concentration of ferritin has been shown to increase in response to stresses such as  anoxia , [ 27 ]  which implies that it is an  acute phase protein . [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3182", "text": "Mitochondrial ferritin  has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3183", "text": "In some snails, the protein component of the egg yolk is primarily ferritin. [ 29 ]  This is a different ferritin, with a different genetic sequence, from the somatic ferritin.  It is produced in the midgut glands and secreted into the haemolymph, whence it is transported to the eggs. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3184", "text": "In vertebrates, ferritin is usually found within cells, although it is also present in smaller quantities in the plasma. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3185", "text": "Serum  ferritin levels are measured in  medical laboratories  as part of the iron studies workup for  iron-deficiency anemia . [ 6 ]  They are measured in nanograms per milliliter (ng/mL) or micrograms per liter (\u03bcg/L); the two units are equivalent."}
{"_id": "WikiPedia_Hematology$$$corpus_3186", "text": "The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of  anemia of chronic disease , where ferritin is elevated in its capacity as an inflammatory  acute phase protein  and not as a marker for iron overload. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3187", "text": "A normal ferritin blood level, referred to as the  reference interval  is determined by many  testing laboratories . The ranges for ferritin can vary between laboratories but typical ranges would be between 40 and 300\u00a0ng/mL (=\u03bcg/L) for males, and 20\u2013200\u00a0ng/mL (=\u03bcg/L) for females. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3188", "text": "According to a 2014 review in the  New England Journal of Medicine  stated that a ferritin level below 30\u00a0ng/mL indicates  iron deficiency , while a level below 10\u00a0ng/mL indicates iron-deficiency anemia. [ 30 ]  A 2020 World Health Organization guideline states that ferritin indicates iron deficiency below 12\u00a0ng/mL in apparently-healthy children under 5 and 15\u00a0ng/mL in apparently-healthy individuals of 5 and over. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3189", "text": "Some studies suggest that women with  fatigue  and ferritin below 50\u00a0ng/mL see reduced fatigue after iron supplementation. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3190", "text": "In the setting of anemia, low serum ferritin is the most specific lab finding for  iron-deficiency anemia . [ 34 ]  However it is less sensitive, since its levels are increased in the blood by infection or any type of chronic inflammation, [ 35 ]  and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range. A  falsely low  blood ferritin (equivalent to a  false positive  test) is very uncommon, [ 35 ]  but can result from a  hook effect  of the measuring tools in extreme cases. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3191", "text": "Low ferritin may also indicate  hypothyroidism , [ 37 ]   vitamin C deficiency  or  celiac disease . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3192", "text": "Low serum ferritin levels are seen in some patients with  restless legs syndrome , not necessarily related to anemia, but perhaps due to low iron stores short of anemia. [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3193", "text": "Vegetarianism  is not a cause of low serum ferritin levels, according to the American Dietetic Association's position in 2009: \"Incidence of iron-deficiency anemia among vegetarians is similar to that of non-vegetarians. Although vegetarian adults have lower iron stores than non-vegetarians, their serum ferritin levels are usually within the normal range.\" [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3194", "text": "If  ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signaling body iron overload."}
{"_id": "WikiPedia_Hematology$$$corpus_3195", "text": "Ferritin is also used as a  marker  for  iron overload disorders , such as  hemochromatosis  or  hemosiderosis .  Adult-onset Still's disease , some  porphyrias , and  hemophagocytic lymphohistiocytosis / macrophage activation syndrome  are diseases in which the ferritin level may be abnormally raised."}
{"_id": "WikiPedia_Hematology$$$corpus_3196", "text": "As ferritin is also an  acute-phase reactant , it is often elevated in the course of disease. A normal  C-reactive protein  can be used to exclude elevated ferritin caused by acute phase reactions.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3197", "text": "Ferritin has been shown to be elevated in some cases of  COVID-19  and may correlate with worse clinical outcome. [ 41 ] [ 42 ]  Ferritin and  IL-6  are considered to be possible immunological biomarkers for severe and fatal cases of COVID-19. Ferritin and C-reactive protein may be possible screening tools for early diagnosis of  systemic inflammatory response syndrome  in cases of COVID-19. [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3198", "text": "According to a study of  anorexia nervosa  patients, ferritin can be elevated during periods of acute  malnourishment , perhaps due to iron going into storage as intravascular volume and thus the number of red blood cells falls. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3199", "text": "Another study suggests that due to the catabolic nature of anorexia nervosa, isoferritins may be released. Furthermore, ferritin has significant non-storage roles within the body, such as protection from  oxidative damage . The rise of these isoferritins may contribute to an overall increase in ferritin concentration. The measurement of ferritin through  immunoassay  or immunoturbidimeteric methods may also be picking up these isoferritins thus not a true reflection of iron storage status. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3200", "text": "Studies reveal that a transferrin saturation (serum iron concentration \u00f7 total iron binding capacity) over 60 percent in men and over 50 percent in women identified the presence of an abnormality in iron metabolism ( hereditary hemochromatosis , heterozygotes, and homozygotes) with approximately 95 percent accuracy. This finding helps in the early diagnosis of hereditary hemochromatosis, especially while serum ferritin still remains low. The retained iron in hereditary hemochromatosis is primarily deposited in parenchymal cells, with reticuloendothelial cell accumulation occurring very late in the disease. This is in contrast to transfusional iron overload in which iron deposition occurs first in the reticuloendothelial cells and then in parenchymal cells. This explains why ferritin levels remain relative low in hereditary hemochromatosis, while transferrin saturation is high. [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3201", "text": "Hematological abnormalities often associate with chronic liver diseases. Both iron overload and iron deficient anemia have been reported in patients with liver cirrhosis. [ 49 ] [ 50 ]  The former is mainly due to reduced  hepcidin  level caused by the decreased synthetic capacity of the liver, while the latter is due to acute and chronic bleeding caused by  portal hypertension . Inflammation is also present in patients with advanced chronic liver disease. As a consequence, elevated hepatic and serum ferritin levels are consistently reported in chronic liver diseases. [ 51 ] [ 52 ] [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3202", "text": "Studies showed association between high serum ferritin levels and increased risk of short-term mortality in cirrhotic patients with acute decompensation [ 54 ]  and acute-on-chronic liver failure. [ 55 ]  An other study found association between high serum ferritin levels and increased risk of long-term mortality in compensated and stable decompensated cirrhotic patients. [ 56 ]  The same study demonstrated that increased serum ferritin levels could predict the development of bacterial infection in stable decompensated cirrhotic patients, while in compensated cirrhotic patients the appearance of the very first acute decompensation episode showed higher incidence in patients with low serum ferritin levels. This latter finding was explained by the association between chronic bleeding and increased portal pressure. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3203", "text": "Ferritin was discovered in 1937 by the  Czechoslovakian  scientist  Vil\u00e9m Laufberger \u00a0[ cs ] . [ 57 ] [ 7 ] :\u200ae9\u200a   Sam Granick  and  Leonor Michaelis  produced apoferritin in 1942 [ 7 ] :\u200ae10"}
{"_id": "WikiPedia_Hematology$$$corpus_3204", "text": "Ferritin is used in  materials science  as a precursor in making iron  nanoparticles  (NP) for  carbon nanotube  growth by  chemical vapor deposition .  It has also been shown to effectively store electrons for hours and  [ 58 ]  to facilitate electron tunneling under ambient conditions, [ 59 ]  properties that may be involved in biological processes. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3205", "text": "Cavities formed by ferritin and mini-ferritins ( Dps ) proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles. [ 61 ] [ 62 ] [ 63 ] [ 64 ]   Protein  shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications. [ 6 ] [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3206", "text": "Experimental COVID-19 vaccines have been produced that display the  spike protein 's receptor binding domain on the surface of ferritin nanoparticles. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3207", "text": "The primary peptide sequence of human ferritin is: [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3208", "text": "The  fibrinopeptides ,  fibrinopeptide A  ( FpA ) and  fibrinopeptide B  ( FpB ), are  peptides  which are located in the central region of the  fibrous   glycoprotein   fibrinogen  (factor I) and are  cleaved  by the  enzyme   thrombin  (factor IIa) to convert fibrinogen into  covalently-linked   fibrin  (factor IA)  monomers . [ 1 ] [ 2 ]  The  N-terminal  FpA is cleaved from the  A\u03b1 chains  of fibrinogen and FpB from the  B\u03b2 chains  of fibrinogen, with FpA released before FpB. [ 3 ] [ 4 ]  Subsequent to their formation, fibrin monomers are converted to cross-linked fibrin  polymers  by the action of thrombin-activated  factor XIII  (fibrin stabilizing factor), and these fibrin polymers form the backbone of a  thrombus  (blood clot). [ 2 ]  Hence, the fibrinopeptides are sensitive markers of  fibrinogenesis  (fibrin generation),  thrombin  activity, and  coagulation . [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3209", "text": "FpA is a 16- amino acid  peptide. [ 8 ]  The  half-life  of FpA is very short at approximately 3 to 5\u00a0minutes. [ 5 ] [ 8 ]  Hence, FpA levels provide a relatively transient measure of coagulation activation. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3210", "text": "Levels of FpA increase with age. [ 5 ]  FpA levels also gradually increase throughout  pregnancy . [ 9 ] [ 10 ]  Likewise, FpA levels have been reported to increase with  estrogen  therapy, including with  combined birth control pills  and  menopausal hormone therapy , although research on FpA levels with these therapies appears to be relatively limited. [ 11 ] [ 12 ] [ 13 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3211", "text": "FibroTest , known as FibroSure in the US, is a  biomarker  test that uses the results of six  blood serum  tests to generate a score that is correlated with the degree of  liver  damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy.  FibroSure uses quantitative results of five serum biochemical markers, \u03b12-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, gamma glutamyl transpeptidase (GGT),  with a patient\u2019s age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver."}
{"_id": "WikiPedia_Hematology$$$corpus_3212", "text": "FibroTest has been evaluated in relation to  liver biopsy  (the current reference standard in liver disease assessment) in people with  hepatitis C ,  hepatitis B , [ 1 ]   alcoholic liver disease , [ 2 ]  and  non-alcoholic fatty liver disease . [ 3 ]  They are most useful for  cirrhosis  and less useful for other stages of liver disease. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3213", "text": "By 2008 it had been used in over 350,000 patients. [ 5 ]  In 2006, the French National Authority for Health recommended the use of FibroTest as one of a number of first-line assessment tool for fibrosis with untreated chronic hepatitis C. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3214", "text": "The FibroTest score is calculated from the results of a six-parameter blood test, combining six serum markers with the age and gender of the patient:  Alpha-2-macroglobulin ,  Haptoglobin ,  Apolipoprotein A1 ,  Gamma-glutamyl transpeptidase  (GGT), Total  bilirubin , and  Alanine transaminase  (ALT). ALT is used in a second assessment called ActiTest that is part of FibroTest. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3215", "text": "The equation for calculating the FibroTest score regression coefficient ( logistic regression ) is: [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3216", "text": "z \n = \n 4.467 \n \u00d7 \n \n log \n \n 10 \n \n \n \u2061 \n [ \n A \n l \n p \n h \n a \n 2 \n M \n ( \n g \n \n / \n \n L \n ) \n ] \n \u2212 \n 1.357 \n \u00d7 \n \n log \n \n 10 \n \n \n \u2061 \n [ \n H \n a \n p \n t \n o \n g \n l \n o \n b \n u \n l \n i \n n \n ( \n g \n \n / \n \n L \n ) \n ] \n + \n 1.017 \n \u00d7 \n \n log \n \n 10 \n \n \n \u2061 \n [ \n G \n G \n T \n ( \n I \n U \n \n / \n \n L \n ) \n ] \n + \n 0.0281 \n \u00d7 \n [ \n A \n g \n e \n ] \n \n \n {\\displaystyle z=4.467\\times \\log _{10}[Alpha2M(g/L)]-1.357\\times \\log _{10}[Haptoglobulin(g/L)]+1.017\\times \\log _{10}[GGT(IU/L)]+0.0281\\times [Age]}"}
{"_id": "WikiPedia_Hematology$$$corpus_3217", "text": "where B=1 for male and B=0 for female. The score (between 0 and 1) is then"}
{"_id": "WikiPedia_Hematology$$$corpus_3218", "text": "F \n = \n 1 \n \n / \n \n ( \n 1 \n + \n \n e \n \n \u2212 \n z \n \n \n ) \n \n \n {\\displaystyle F=1/(1+e^{-z})}"}
{"_id": "WikiPedia_Hematology$$$corpus_3219", "text": "Due to variability of components assays and analyzers, FibroTest assays can only be performed in validated laboratories. [ 8 ]  FibroTest cannot be used without algorithms that detects false positives and false negatives; the equation alone is not a diagnosis tool. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3220", "text": "The laboratory or physician connects to the BioPredictive website [ 9 ]  for calculation of the test results and prints the results sheet, which is available immediately and is accompanied by an interpretation aid and precautions for use."}
{"_id": "WikiPedia_Hematology$$$corpus_3221", "text": "Over 95% of tests are interpretable and allow a diagnosis of fibrosis and liver activity. In less than 5% of cases, likely false positives or false negatives are highlighted. FibroTest has been validated for chronic  hepatitis C , [ 10 ]  chronic  hepatitis B , [ 5 ]  chronic hepatitis C or B with HIV co-infection, [ 11 ]  alcoholic liver diseases (steatosis and steatohepatitis), [ 2 ]  and non-alcoholic steatohepatitis (diabetes, overweight, hypertriglyceridemia, hypercholesterolemia, hypertension). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3222", "text": "FibroTest is independent of ethnic origin, sex, genotype, viral load, transaminases or the presence of comorbidities. The test has been validated in those over the age of 65 years, [ 12 ]  children, [ 13 ]  people with  chronic kidney disease  or  kidney transplantation ,  hemophiliacs , patients with chronic inflammatory disease, and the general population."}
{"_id": "WikiPedia_Hematology$$$corpus_3223", "text": "The tests are not applicable in 1 to 5% of cases. These cases can be detected by laboratory safety algorithms and when detected they are indicated on the results sheet: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3224", "text": "The conversion of FibroTest score into stages according to the three most used histological classifications (METAVIR, Knodell and Ishak) for  liver biopsies  is:"}
{"_id": "WikiPedia_Hematology$$$corpus_3225", "text": "Liver biopsy  is an imperfect tool; due to sampling errors, biopsy size (5 to 30\u00a0mm) and intra- and interobservor variability, it is now agreed that biopsy is an \"imperfect  Gold Standard \n\" (citation required).  Biopsy continues to present inconveniences: 30% of patients complain of pain, up to 3% have been noted to have complications severe enough to require hospitalization [ 14 ] [ 15 ]  and a 0.01-0.3% rate of deaths has been reported. [ 16 ] [ 17 ] [ 18 ]  There is a mean discordance of 25% between FibroTest and biopsy. Half of these discordances are attributable to an error of the biopsy, often too small, and the other half to FibroTest. [ 19 ]  The inventors report that FibroTest has comparable diagnostic and prognostic value as a 25\u00a0mm biopsy, while being noninvasive and easily repeatable. [ 10 ] [ 2 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3226", "text": "In  medicine , some  blood tests  are conducted on capillary blood obtained by  fingerstick  (or  fingerprick ) (or, for  neonates , by an analogous  heelprick ). The site, free of surface  arterial flow , where the blood is to be collected is sterilized with a  topical   germicide , and the skin pierced with a sterile  lancet . [ 1 ]  After a droplet has formed,  capillary blood  is captured in a  capillary tube  (usually relying on  surface tension ). Blood cells drawn from fingersticks have a tendency to undergo  hemolysis , especially if the finger is \"milked\" to obtain more blood. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3227", "text": "Tests commonly conducted on the  capillary blood  collected are:"}
{"_id": "WikiPedia_Hematology$$$corpus_3228", "text": "Fingersticks are routine for hardy [ citation needed ]  adults, but are generally performed on children and the elderly only if a small amount of blood suffices for needed tests.  Neonates  are given heelpricks instead, as this is less likely to cause permanent damage. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3229", "text": "Flow cytometry  ( FC ) is a technique used to detect and measure the physical and chemical characteristics of a population of  cells  or particles. [ 1 ] [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3230", "text": "In this process, a sample containing cells or particles is suspended in a fluid and injected into the flow  cytometer  instrument. The sample is focused to ideally flow one cell at a time through a laser beam, where the light scattered is characteristic to the cells and their components. Cells are often labeled with fluorescent markers so light is absorbed and then emitted in a band of wavelengths. Tens of thousands of cells can be quickly examined and the data gathered are processed by a computer. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3231", "text": "Flow cytometry is routinely used in basic research, clinical practice, and  clinical trials . Uses for flow cytometry include:"}
{"_id": "WikiPedia_Hematology$$$corpus_3232", "text": "A flow cytometry analyzer is an instrument that provides quantifiable data from a sample. Other instruments using flow cytometry include cell sorters which physically separate and thereby purify cells of interest based on their optical properties."}
{"_id": "WikiPedia_Hematology$$$corpus_3233", "text": "The first  impedance -based flow cytometry device, using the  Coulter principle , was disclosed in U.S. Patent 2,656,508, issued in 1953, to  Wallace H. Coulter . Mack Fulwyler was the inventor of the forerunner to today's flow cytometers \u2013 particularly the cell sorter. [ 6 ]  Fulwyler developed this in 1965 with his publication in  Science . [ 7 ]  The first fluorescence-based flow cytometry device (ICP 11) was developed in 1968 by Wolfgang G\u00f6hde from the  University of M\u00fcnster , filed for patent on 18 December 1968 [ 8 ]  and first commercialized in 1968/69 by German developer and manufacturer Partec through Phywe AG in  G\u00f6ttingen . At that time,  absorption  methods were still widely favored by other scientists over  fluorescence  methods. [ 9 ]  Soon after, flow cytometry instruments were developed, including the Cytofluorograph (1971) from Bio/Physics Systems Inc. (later: Ortho Diagnostics), the PAS 8000 (1973) from Partec, the first FACS (fluorescence-activated cell sorting) instrument from  Becton Dickinson  (1974), the ICP 22 (1975) from Partec/Phywe and the Epics from  Coulter  (1977/78). The first label-free high-frequency  impedance flow cytometer  based on a patented microfluidic \"lab-on-chip\", Ampha Z30, was introduced by Amphasys (2012). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3234", "text": "The original name of the fluorescence-based flow cytometry technology was \"pulse cytophotometry\" ( German :  Impulszytophotometrie ), based on the first patent application on fluorescence-based flow cytometry. At the 5th American Engineering Foundation Conference on Automated Cytology in Pensacola (Florida) in 1976 \u2013 eight years after the introduction of the first fluorescence-based flow cytometer (1968) \u2013 it was agreed to commonly use the name \"flow cytometry\", a term that quickly became popular. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3235", "text": "Modern flow cytometers are able to analyze many thousands of particles per second, in \"real time\" and, if configured as cell sorters, can actively separate and isolate particles with specified optical properties at similar rates. A flow cytometer is similar to a  microscope , except that, instead of producing an image of the cell, flow cytometry offers high-throughput, automated  quantification  of specified optical parameters on a cell-by-cell basis. To analyze solid  tissues , a single-cell suspension must first be prepared. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3236", "text": "A flow cytometer has five main components: a flow cell, a measuring system, a detector, an amplification system, and a computer for analysis of the signals. The flow cell has a liquid stream (sheath fluid), which carries and aligns the cells so that they pass single file through the light beam for sensing. The measuring system commonly uses measurement of impedance (or conductivity) and optical systems \u2013 lamps ( mercury ,  xenon ); high-power water-cooled lasers ( argon ,  krypton , dye laser); low-power air-cooled lasers (argon (488\u00a0nm), red-HeNe (633\u00a0nm), green-HeNe, HeCd (UV));  diode lasers  (blue, green, red, violet) resulting in light signals. The detector and analog-to-digital conversion (ADC) system converts analog measurements of forward-scattered light (FSC) and side-scattered light (SSC) as well as dye-specific fluorescence signals into digital signals that can be processed by a computer. The amplification system can be  linear  or  logarithmic . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3237", "text": "The process of collecting data from samples using the flow cytometer is termed \"acquisition\". Acquisition is mediated by a computer physically connected to the flow cytometer, and the software which handles the digital interface with the cytometer. The software is capable of adjusting parameters (e.g., voltage, compensation) for the sample being tested, and also assists in displaying initial sample information while acquiring sample data to ensure that parameters are set correctly. Early flow cytometers were, in general, experimental devices, but technological advances have enabled widespread applications for use in a variety of both clinical and research purposes. Due to these developments, a considerable market for instrumentation, analysis software, as well as the reagents used in acquisition such as  fluorescently labeled   antibodies  have been developed."}
{"_id": "WikiPedia_Hematology$$$corpus_3238", "text": "Modern instruments usually have multiple lasers and fluorescence detectors. The current record for a commercial instrument is ten lasers [ 11 ]  and 30 fluorescence detectors. [ 12 ]  Increasing the number of lasers and detectors allows for multiple antibody labeling, and can more precisely identify a target population by their  phenotypic  markers. Certain instruments can even take digital images of individual cells, allowing for the analysis of fluorescent signal location within or on the surface of cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3239", "text": "Cells must pass uniformly through the center of focused laser beams to accurately measure optical properties of cells in any flow cytometer. [ 13 ] [ 14 ] [ 15 ]  The purpose of the fluidic system is to move the cells one by one through the lasers beam and throughout the instrument. Fluidics in a flow cytometer with cell sorting capabilities also use the stream to carry sorted cells into collection tubes or wells. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3240", "text": "For precise positioning of cells in a liquid jet, hydrodynamic focusing is used in most cytometers. [ 13 ] [ 14 ]  The cells in suspension enter into the instrument enclosed by an outer sheath fluid. The sample core is maintained in the center of the sheath fluid. The sample input rate or how fast the cells flow through to the laser interrogation can be controlled by the pressure of the sheath fluid on the sample core. Under optimal conditions, the central fluid stream and sheath fluid do not mix. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3241", "text": "Acoustic focusing technology is used in some flow cytometers to support hydrodynamic focusing. [ 13 ] [ 15 ]  Acoustic waves (>2\u00a0MHz) pre-focus the sample before introduction to sheath fluid. The pre-focused sample is then injected into the hydrodynamic core and flowed through the instrument. This may help with increasing data accuracy under high sample input rates."}
{"_id": "WikiPedia_Hematology$$$corpus_3242", "text": "Light emitted from  fluorophores  are in a spectrum of wavelengths, so combining multiple fluorophores may cause overlap. To add specificity,  optical filters  and  dichroic mirrors  are used to filter and move light to the detectors such as  photomultiplier tubes  (PMTs) or  avalanche photodiodes  (APD). [ 13 ]  Optical filters are designed as band pass (BP), long pass (LP), or short pass (SP) filters. Most flow cytometers uses dichroic mirrors and band pass filters to select specific bands of the optical spectrum."}
{"_id": "WikiPedia_Hematology$$$corpus_3243", "text": "Spectral flow cytometry uses  prisms  or  diffraction gratings  to disperse the emitted light of a marker across a detector array. [ 13 ] [ 16 ]  This allows for the full spectra from each particle to be measured. The measured spectra from single cells are subsequently unmixed by using reference spectra of all used dyes and the autofluorescence spectrum. This may allow for a wider panel design and the application of new biological markers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3244", "text": "Imaging flow cytometry (IFC) captures multichannel images of cells. [ 13 ] [ 17 ]  Detectors used in imaging platforms can be equipped with  charge-coupled device  (CCD) or complementary metal\u2013oxide\u2013semiconductor (CMOS) to capture images of individual cells."}
{"_id": "WikiPedia_Hematology$$$corpus_3245", "text": "Each fluorochrome has a broad fluorescence spectrum. When more than one fluorochrome is used, an overlap between fluorochromes can occur. This situation is called spectrum overlap, and must be corrected. For example, the emission spectrum for FITC and PE is one in which the light emitted by the fluorescein overlaps the same wavelength as it passes through the filter used for PE. This spectral overlap is corrected by removing a portion of the FITC signal from the PE signals or vice versa. This process is called color compensation, which calculates a fluorochrome as a percentage to measure itself. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3246", "text": "Compensation is the mathematical process by which spectral overlap of multiparameter flow cytometric data is corrected. Since fluorochromes can have wide-ranging spectrum, they can overlap, causing the undesirable result of confusion during the analysis of data. This overlap, known as spillover and quantified in the spillover coefficient, is usually caused by detectors for a certain fluorochrome measuring a significant peak in wavelength from a different fluorochrome. Linear algebra is most often used to make this correction. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3247", "text": "In general, when graphs of one or more parameters are displayed, it is to show that the other parameters do not contribute to the distribution shown. Especially when using the parameters which are more than double, this problem is more severe. Currently, no tools have been discovered to efficiently display multidimensional parameters. Compensation is very important to see the distinction between cells."}
{"_id": "WikiPedia_Hematology$$$corpus_3248", "text": "[ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3249", "text": "The data generated by flow cytometers can be plotted in a single  dimension  to produce a  histogram , or in two-dimensional dot plots, or even in three dimensions. The regions on these plots can be sequentially separated, based on fluorescence  intensity , by creating a series of subset extractions, termed \"gates.\" Specific gating  protocols  exist for diagnostic and clinical purposes, especially in relation to  hematology . Individual single cells are often distinguished from cell doublets or higher aggregates by their \"time-of-flight\" (denoted also as a \"pulse-width\") through the narrowly focused laser beam [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3250", "text": "The plots are often made on logarithmic scales. Because different fluorescent dyes' emission spectra overlap, [ 20 ] [ 21 ]  signals at the detectors have to be compensated electronically as well as computationally. Data accumulated using the flow cytometer can be analyzed using software. Once the data is collected, there is no need to stay connected to the flow cytometer and analysis is most often performed on a separate computer. [ citation needed ]  This is especially necessary in core facilities where usage of these machines is in high demand. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3251", "text": "Recent progress on automated population identification using computational methods has offered an alternative to traditional gating strategies. Automated identification systems could potentially help findings of rare and hidden populations. Representative automated methods include FLOCK [ 22 ]  in Immunology Database and Analysis Portal (ImmPort), [ 23 ]  SamSPECTRAL [ 24 ]  and flowClust [ 25 ] [ 26 ] [ 27 ]  in  Bioconductor , and FLAME [ 28 ]  in  GenePattern . T-Distributed Stochastic Neighbor Embedding (tSNE) is an algorithm designed to perform  dimensionality reduction , to allow visualization of complex multi-dimensional data in a two-dimensional \"map\". [ 29 ]  Collaborative efforts have resulted in an open project called FlowCAP (Flow Cytometry: Critical Assessment of Population Identification Methods, [ 30 ] ) to provide an objective way to compare and evaluate the flow cytometry data clustering methods, and also to establish guidance about appropriate use and application of these methods."}
{"_id": "WikiPedia_Hematology$$$corpus_3252", "text": "Fluorescence minus one (FMO) controls are important for data interpretation when building multi-color panels \u2013 in which a cell is stained with multiple fluorochromes simultaneously. FMO controls provide a measure of fluorescence spillover in a given channel and allow for compensation. To generate a FMO control, a sample is stained with all the fluorochromes except the one that is being tested \u2013 meaning if you are using 4 different fluorochromes your FMO control must contain only 3 of them (example: fluorochromes \u2013 A, B, C, D; FMOs \u2013 ABC_, AB_D, A_CD, _BCD). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3253", "text": "Cell sorting  is a method to purify cell populations based on the presence or absence of specific physical characteristics. [ 13 ] [ 15 ] [ 31 ]  In flow cytometers with sorting capabilities, the instrument detects cells using parameters including cell size, morphology, and protein expression, and then droplet technology to sort cells and recover the subsets for post-experimental use. [ 13 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3254", "text": "The first prototype sorter was built at the  Los Alamos National Laboratory  (LANL) in 1965 by physicist Mack J. Fulwyler by joining a Coulter volume sensor with the newly invented ink jet printer. [ 32 ]  Live cell cell sorter or fluorescence-activated cell sorter (FACS) [ a ]  was generated by  Len Herzenberg , who subsequently won the  Kyoto Prize  in 2006 for his seminal work. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3255", "text": "Flow cytometry cell sorters have a collection system unlike flow cytometry analyzers. The collection process starts when a sample is injected into a stream of sheath fluid that passes through the flow cell and laser intercepts. [ 35 ] \u00a0The stream then carries the cell through a vibrating nozzle which generates droplets with most containing either one cell or no cells. An electrical charging ring is placed just at the point where the stream breaks into droplets and a  charge  is placed on the ring based immediately prior to fluorescence intensity being measured; the opposite charge is trapped on the droplet as it breaks from the stream and the droplets are therefore charged. The charged droplets then fall through an  electrostatic deflection  system that diverts droplets into containers based on their charge. In some systems, the charge is applied directly to the stream, and the droplet breaking off retains charge of the same sign as the stream. The stream is then returned to neutral after the droplet breaks off. After collecting, these cells can be further cultured, manipulated, and studied. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3256", "text": "Flow cytometry uses the light properties scattered from cells or particles for identification or quantitative measurement of physical properties. Labels, dyes, and stains can be used for multi-parametric analysis (understand more properties about a cell).  Immunophenotyping  is the analysis of heterogeneous populations of cells using labeled  antibodies [ 36 ]  and other fluorophore containing reagents such as dyes and stains."}
{"_id": "WikiPedia_Hematology$$$corpus_3257", "text": "A wide range of fluorophores can be used as labels in flow cytometry. [ 20 ]  Fluorophores, or simply \"fluors\", [ citation needed ]  are typically attached to an antibody that recognizes a target feature on or in the cell; they may also be attached to a chemical entity with affinity for the  cell membrane  or another cellular structure. Each fluorophore has a characteristic peak  excitation  and  emission  wavelength, and the emission spectra often overlap. Consequently, the combination of labels which can be used depends on the wavelength of the lamp(s) or laser(s) used to excite the fluorochromes and on the detectors available. [ 37 ]  Flow cytometry uses fluorescence as a quantitative tool; the utmost sensitivity of flow cytometry is unmatched by other fluorescent detection platforms such as  confocal microscopy . Absolute fluorescence sensitivity is generally lower in  confocal microscopy  because out-of-focus signals are rejected by the confocal optical system and because the image is built up serially from individual measurements at every location across the cell, reducing the amount of time available to collect signal. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3258", "text": "Quantum dots  are sometimes used in place of traditional fluorophores because of their narrower emission peaks. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3259", "text": "Mass cytometry overcomes the fluorescent labeling limit by utilizing  lanthanide  isotopes attached to antibodies. This method could theoretically allow the use of 40 to 60 distinguishable labels and has been demonstrated for 30 labels. [ 39 ]  Mass cytometry is fundamentally different from flow cytometry: cells are introduced into a  plasma , ionized, and associated isotopes are quantified via  time-of-flight mass spectrometry . Although this method permits the use of a large number of labels, it currently has lower throughput capacity than flow cytometry. It also destroys the analysed cells, precluding their recovery by sorting. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3260", "text": "In addition to the ability to label and identify individual cells via fluorescent antibodies, cellular products such as cytokines, proteins, and other factors may be measured as well. Similar to  ELISA  sandwich assays, cytometric bead array ( CBA ) assays use multiple bead populations typically differentiated by size and different levels of fluorescence intensity to distinguish multiple analytes in a single assay. The amount of the analyte captured is detected via a biotinylated antibody against a secondary epitope of the protein, followed by a streptavidin-R-phycoerythrin treatment. The fluorescent intensity of R-phycoerythrin on the beads is quantified on a flow cytometer equipped with a 488\u00a0nm excitation source. Concentrations of a protein of interest in the samples can be obtained by comparing the fluorescent signals to those of a standard curve generated from a serial dilution of a known concentration of the analyte. Commonly also referred to as cytokine bead array (CBA)."}
{"_id": "WikiPedia_Hematology$$$corpus_3261", "text": "Impedance -based single cell analysis systems are commonly known as  Coulter counters . They represent a well-established method for counting and sizing virtually any kind of cells and particles. The label-free technology has recently been enhanced by a \" lab-on-a-chip \" based approach and by applying high frequency  alternating current  (AC) in the radio frequency range (from 100\u00a0kHz to 30\u00a0MHz) instead of a static  direct current  (DC) or low frequency AC field. [ 40 ] [ 41 ]  This patented technology allows a highly accurate cell analysis and provides additional information like membrane  capacitance  and  viability . The relatively small size and robustness allow battery powered on-site use in the field."}
{"_id": "WikiPedia_Hematology$$$corpus_3262", "text": "Measurable factors in cellular analysis and flow cytometry include a diverse set of traits and indicators that provide important insights into cell biology and function. Flow cytometry techniques can quantify and evaluate these factors, allowing researchers to investigate and analyze various aspects of cells. Here are some important quantifiable parameters that are frequently investigated:"}
{"_id": "WikiPedia_Hematology$$$corpus_3263", "text": "The technology has applications in a number of fields, including  molecular biology ,  pathology ,  immunology , virology, [ 44 ]   plant biology  and  marine biology . [ 45 ]  It has broad application in  medicine  especially in transplantation, hematology, tumor immunology and chemotherapy, prenatal diagnosis, genetics and  sperm sorting  for  sex preselection . Flow cytometry is widely applied to detect sperm cells abnormality associated with  DNA fragmentation [ 46 ]  in  male fertility  assays. [ 47 ]  Also, it is extensively used in research for the detection of  DNA damage , [ 48 ] [ 49 ]  caspase cleavage and  apoptosis . [ 50 ]   Photoacoustic flow cytometry  is used in the study of multi-drug-resistant bacteria (most commonly MRSA) to detect, differentiate, and quantify bacteria in the blood marked with dyed bacteriophages. [ 51 ]  In  neuroscience , co-expression of cell surface and intracellular antigens can also be analyzed. [ 52 ]  In microbiology, it can be used to screen and sort transposon mutant libraries constructed with a GFP-encoding transposon (TnMHA), [ 53 ]  or to assess viability. [ 54 ]  In protein engineering, flow cytometry is used in conjunction with  yeast display  and  bacterial display  to identify cell surface-displayed protein variants with desired properties.\nThe main advantages of flow cytometry over histology and IHC is the possibility to precisely measure the quantities of antigens and the possibility to stain each cell with multiple antibodies-fluorophores, in current laboratories around 10 antibodies can be bound to each cell. This is much less than mass cytometer where up to 40 can be currently measured, but at a higher price and a slower pace."}
{"_id": "WikiPedia_Hematology$$$corpus_3264", "text": "In aquatic systems, flow cytometry is used for the analysis of autofluorescing cells or cells that are fluorescently-labeled with added stains. This research started in 1981 when  Clarice Yentsch  used flow cytometry to measure the fluorescence in a red tide producing dinoflagellate. [ 55 ]  The next year researchers published flow cytometric measurements of multiple algal species which could be distinguished based on their fluorescence characteristics. [ 56 ]  By 1983, marine researchers were assembling their own flow cytometers [ 57 ]  or using commercially available flow cytometers on seawater samples collected off Bermuda to demonstrate that phytoplankton cells could be distinguished from non-living material and that cyanobacteria could be sorted from a mixed community and subsequently cultured in the lab. [ 58 ]  Flow cytometry also allowed marine researchers to distinguish between dimly-fluorescing  Prochlorococcus  and heterotrophic microorganisms, a distinction that is difficult with microscopy-based assessments. [ 59 ]  Advances in technology now allow aquatic scientists to use flow cytometers continuously during research cruises [ 60 ]  and flow cytometers are used to provide images of individual phytoplankton cells. [ 61 ] [ 62 ]  Marine scientists use the sorting ability of flow cytometers to make discrete measurements of cellular activity and diversity, [ 63 ] [ 64 ]  to conduct investigations into the mutualistic relationships between microorganisms that live in close proximity, [ 65 ]  and to measure biogeochemical rates of multiple processes in the ocean. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3265", "text": "Cell proliferation is the major function in the immune system. Often it is required to analyse the proliferative nature of the cells in order to make some conclusions. One such assay to determine the cell proliferation is the tracking dye carboxyfluorescein diacetate succinimidyl ester (CFSE). It helps to monitor proliferative cells. This assay gives quantitative as well as qualitative data during time-series experiments. [ 67 ]  This dye binds covalently with the long-lived molecules present inside the cell. When the cells divide, the molecules divide too and, the daughter cells possess half the dye than the parent population. This decrease in the intensity can be visualized by flow cytometry. [ 68 ]  In literature, this powerful technique of flow cytometry and CFSE has been used to find the efficiency of T-cells in killing the target cells in cancer such as leukemia. In order to visualize the target cell death, both rapid and slow, scientists have used CFSE labelling with antibody staining of certain kinds of cells and fluorescently labelled microbeads. This also gave information regarding the proliferation of the target cells upon the treatment of certain cytokines. [ 69 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3266", "text": "Flow cytometry has been used to measure  genome sizes , or more precisely: the amount of  DNA  in a  cell  or  nucleus . Although genomes can be analyzed with more precision by  genome sequencing , this is often difficult due to a high fraction of  micro-chromosomes  or  repetitive sequences  which may be missed by sequencing (or which get filtered out during the analysis step when they cannot be assigned to  chromosomes ). However, flow cytometry is not perfect either. The resulting genome sizes may differ based on the dye used. An analysis of fish genomes resulted in significantly different genome sizes when  propidium iodide  (PI) and  DAPI  were used, respectively. For instance, the genome of  Anguilla japonica  was found to contain 1.09 pg of DNA with PI vs. 1.25 pg with DAPI. Similarly, the genome of  Myxocyprinus asiaticus  was found to contain 2.75 pg of DNA (PI) vs. 3.08 pg (DAPI). That is, the differences were on the order of 12\u201314%. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3267", "text": "Fluorescein-labeled proaerolysin  ( FLAER ) is used in a flow cytometric assay to diagnose  paroxysmal nocturnal hemoglobinuria  (PNH). [ 1 ] [ 2 ]   The assay takes advantage of the action of proaerolysin, a prototoxin of  aerolysin , a virulence factor  of the bacterium   Aeromonas hydrophila . Proaerolysin binds to the  glycophosphatidylinositol (GPI) anchor in the  plasma membrane  of cells.  Cells affected by PNH lack GPI anchoring proteins, and thus are not bound by proaerolysin.  Of note, the FLAER-based assay is not suitable for evaluation of  erythrocytes  and  platelets  in PNH but flow cytometry assays based on  CD55 ,  CD59  and others are suitable. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3268", "text": "Fructosamines  are compounds that result from  glycation  reactions between glucose and a  primary amine , followed by  isomerization  via the  Amadori rearrangement . Biologically, fructosamines are recognized by  fructosamine-3-kinase , which may trigger the degradation of  advanced glycation end-products  (though the true clinical significance of this pathway is unclear). Fructosamine can also refer to the specific compound 1-amino-1-deoxy-D-fructose ( isoglucosamine ), first synthesized by Nobel laureate  Hermann Emil Fischer  in 1886. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3269", "text": "Most commonly, fructosamine refers to a laboratory test for  diabetes management  that is rarely used in human clinical practice (simple  blood glucose monitoring  or  hemoglobin A1c  testing are preferred). In small animal veterinary practice however it is part of the diabetic cat or dog diagnosis and monitoring [ 1 ]  giving an indication of blood glucose levels over the previous week. [ 2 ]  Many  direct-to-consumer  lab testing companies sell fructosamine tests."}
{"_id": "WikiPedia_Hematology$$$corpus_3270", "text": "In  diabetes , maintaining a normal  blood glucose  is essential to preventing many medical complications, including  heart attacks ,  diabetic nephropathy ,  diabetic neuropathy , and  diabetic retinopathy  eventually leading to  blindness . Most commonly, blood sugars are measured by either  blood glucose monitoring  which measures the current blood glucose level, or by  glycated hemoglobin  (HbA1c) which measures average glucose levels over approximately 3 months. In a similar way to hemoglobin A1c testing (which measures the  glycation  of hemoglobin), fructosamine testing determines the fraction of total  serum  proteins that have undergone glycation (the  glycated serum proteins ). Since albumin is the most abundant protein in blood, fructosamine levels typically reflect albumin glycation. (Some fructosamine tests specifically quantify the glycation of albumin, or  glycated serum albumin  instead of all proteins.). Because albumin has a  half-life  of approximately 20 days, the plasma fructosamine concentration reflects relatively recent (1\u20132 week) changes in blood glucose. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3271", "text": "In patients with diseases that reduce red blood cell lifespan, such as  hemolytic anaemia  or  hemoglobinopathies  such as  sickle-cell disease , a hemoglobin-based A1c test can be misleadingly low. A1c results may also be falsely high or low in  hemoglobinopathies  because abnormal hemoglobin variants can interfere in the analysis. In these cases, fructosamine measurement can be used as a marker of  blood sugar  levels, as its measurements are based on albumin instead of hemoglobin. However, any condition that changes serum albumin (such as the  nephrotic syndrome ) will affect the fructosamine result. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3272", "text": "In practice, fructosamine is rarely measured clinically (even in individuals with hemoglobinopathies or other red cell disorders) due to a number of pragmatic concerns. First, diabetes care is rarely changed in short (1\u20134 week) intervals, since diabetes medications can take months to reach a  steady state . An exception to this is pregnancy, where medication needs can change more rapidly and fructosamine may help provide closer short-term monitoring. Second, fructosamine has higher variability than A1c tests. Third, the overwhelming majority of studies in diabetes care are based on A1c measurements, which can make fructosamine results difficult to interpret. Fourth, the A1c test is very well standardized [ 3 ]  and trusted due to its nearly universal use. A variety of more advanced forms of the A1c test (e.g. some types of  HPLC ,  immunoassay , and  capillary electrophoresis ) can more accurately assay A1c levels during complex hemoglobinopathies and other conditions. [ 4 ]  However this does not overcome the effect of shortened red blood cell lifespan on A1c results. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3273", "text": "Because glycated albumin (GA) has a shorter half-life than glycated hemoglobin (HbA1c), glycated albumin reflects recent glycemic control more accurately and usefully for monitoring patients with diabetic  end-stage renal disease  (ESRD) ( hemodialysis  and  peritoneal dialysis  patients). It can be used less often than blood sugar testing. An average blood glucose level of 155\u2013160\u00a0mg/dL could be matched to a GA value of 18\u201319% in patients with ESRD. The ratio of GA/HbA1c is 3.0 approximately. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3274", "text": "There is no standard reference range available for this test. The reference values depend upon the factors of patient age, gender, sample population, and test method. Hence, each laboratory report will include the patient's specific reference range for the test. An increase in fructosamine in lab testing results usually means an increase in glucose in the blood."}
{"_id": "WikiPedia_Hematology$$$corpus_3275", "text": "On average, each change of 3.3\u00a0mmol (60\u00a0mg/dL) in average blood sugar levels will give rise to changes of 2% HbA1c and 75 \u03bcmol fructosamine values. [ 6 ]  However, this overemphasizes the upper limit of many laboratories' reference ranges of 285 \u03bcmol/L as equivalent to HbA1c 7.5% rather than 6.5%. A comparative study, [ 7 ]  which has been used in official advice for  Quality and Outcomes Framework  guidance in the UK [ 8 ]  and summarized by the United States'  National Quality Measures Clearinghouse , [ 9 ]  gives the following formula and resulting values:"}
{"_id": "WikiPedia_Hematology$$$corpus_3276", "text": "Protein electrophoresis  is a method for analysing the proteins in a fluid or an extract. The  electrophoresis  may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium, namely  agarose  or  polyacrylamide . Variants of  gel electrophoresis  include  SDS-PAGE ,  free-flow electrophoresis ,  electrofocusing ,  isotachophoresis ,  affinity electrophoresis ,  immunoelectrophoresis ,  counterelectrophoresis , and  capillary electrophoresis . Each variant has many subtypes with individual advantages and limitations. Gel electrophoresis is often performed in combination with  electroblotting  or  immunoblotting  to give additional information about a specific protein. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3277", "text": "SDS-PAGE,  sodium dodecyl sulfate  polyacrylamide gel electrophoresis, describes a collection of related techniques to separate  proteins  according to their  electrophoretic mobility  (a function of the molecular weight of a polypeptide chain) while in the  denatured  (unfolded) state. In most proteins, the binding of SDS to the polypeptide chain imparts an even distribution of charge per unit mass, thereby resulting in a fractionation by approximate size during electrophoresis. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3278", "text": "SDS is a strong detergent agent used to denature native proteins to unfolded, individual  polypeptides . When a protein mixture is heated to 100\u00a0\u00b0C in presence of SDS, the  detergent  wraps around the polypeptide backbone. In this process, the intrinsic charges of polypeptides becomes negligible when compared to the negative charges contributed by SDS. Thus polypeptides after treatment become rod-like structures possessing a uniform charge density, that is same net negative charge per unit length. The electrophoretic mobilities of these proteins will be a linear function of the  logarithms  of their molecular weights. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3279", "text": "Native gels, also known as non-denaturing gels, analyze proteins that are still in their folded state. Thus, the electrophoretic mobility depends not only on the charge-to-mass ratio, but also on the physical shape and size of the protein. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3280", "text": "BN-PAGE is a native  PAGE  technique, where the  Coomassie brilliant blue  dye provides the necessary  charges  to the protein complexes for the electrophoretic separation. [ 5 ] [ 6 ]  The disadvantage of Coomassie is that in binding to proteins it can act like a  detergent  causing complexes to  dissociate . Another drawback is the potential  quenching  of  chemoluminescence  (e.g. in subsequent  western blot  detection or activity assays) or  fluorescence  of proteins with  prosthetic groups  (e.g.  heme  or  chlorophyll ) or labelled with fluorescent dyes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3281", "text": "CN-PAGE (commonly referred to as Native PAGE) separates acidic water-soluble and membrane  proteins  in a  polyacrylamide  gradient gel. It uses no charged dye so the electrophoretic mobility of proteins in CN-PAGE (in contrast to the charge shift technique BN-PAGE) is related to the intrinsic charge of the proteins. [ 7 ]  The migration distance depends on the protein charge, its size and the pore size of the gel. In many cases this method has lower resolution than BN-PAGE, but CN-PAGE offers advantages whenever  Coomassie  dye would interfere with further analytical techniques, for example it has been described as a very efficient microscale separation technique for  FRET  analyses. [ 8 ]  Additionally, as CN-PAGE does not require the harsh conditions of BN-PAGE, it can retain the  supramolecular assemblies  of  membrane protein  complexes that would be  dissociated  in BN-PAGE. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3282", "text": "The  folded   protein complexes  of interest separate cleanly and predictably without the risk of denaturation due to the specific  properties  of the polyacrylamide gel, electrophoresis buffer solution, electrophoretic equipment and standardized parameters used. The separated proteins are continuously  eluted  into a physiological eluent and transported to a fraction collector. In four to five PAGE fractions each the different metal cofactors can be identified and absolutely quantified by high-resolution  ICP-MS . The associated structures of the isolated  metalloproteins  in these fractions can be specifically determined by solution  NMR  spectroscopy. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3283", "text": "Most protein separations are performed using a \"discontinuous\" (or DISC)  buffer  system that significantly enhances the sharpness of the bands within the gel. During electrophoresis in a discontinuous gel system, an ion gradient is formed in the early stage of electrophoresis that causes all of the proteins to focus into a single sharp band. The formation of the ion gradient is achieved by choosing a pH value at which the ions of the buffer are only moderately charged compared to the SDS-coated proteins. These conditions provide an environment in which  Kohlrausch's  reactions determine the  molar conductivity . As a result, SDS-coated proteins are concentrated to several fold in a thin zone of the order of 19\u00a0\u03bcm within a few minutes. At this stage all proteins migrate at the same migration speed by  isotachophoresis . This occurs in a region of the gel that has larger pores so that the gel matrix does not retard the migration during the focusing or \"stacking\" event. [ 10 ] [ 11 ]  Separation of the proteins by size is achieved in the lower, \"resolving\" region of the gel. The resolving gel typically has a much smaller pore size, which leads to a sieving effect that now determines the electrophoretic mobility of the proteins. At the same time, the separating part of the gel also has a pH value in which the buffer ions on average carry a greater charge, causing them to \"outrun\" the SDS-covered proteins and eliminate the ion gradient and thereby the stacking effect. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3284", "text": "A very widespread discontinuous buffer system is the tris-glycine or \" Laemmli \" system that stacks at a  pH  of 6.8 and resolves at a  pH  of ~8.3-9.0. A drawback of this system is that these pH values may promote  disulfide  bond formation between  cysteine  residues in the proteins because the  pKa  of cysteine ranges from 8-9 and because reducing agent present in the loading buffer doesn't co-migrate with the proteins. Recent advances in buffering technology alleviate this problem by resolving the proteins at a pH well below the pKa of cysteine (e.g.,  bis-tris , pH 6.5) and include reducing agents (e.g. sodium bisulfite) that move into the gel ahead of the proteins to maintain a reducing environment. An additional benefit of using buffers with lower pH values is that the acrylamide gel is more stable at lower pH values, so the gels can be stored for long periods of time before use. [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3285", "text": "As voltage is applied, the anions (and negatively charged sample molecules) migrate toward the positive electrode (anode) in the lower chamber, the leading ion is  Cl \u2212  ( high mobility and high concentration); glycinate is the trailing ion (low mobility and low concentration). SDS-protein particles do not migrate freely at the border between the Cl \u2212  of the gel buffer and the  Gly \u2212  of the cathode buffer.  Friedrich Kohlrausch  found that  Ohm's law  also applies to dissolved  electrolytes . Because of the voltage drop between the Cl \u2212  and Glycine-buffers,  proteins are compressed (stacked) into micrometer thin layers. [ 14 ]  The boundary moves through a pore gradient and the protein stack gradually disperses due to a frictional resistance increase of the gel matrix. Stacking and unstacking occurs continuously in the gradient gel, for every protein at a different position. For a complete protein unstacking the polyacrylamide-gel concentration must exceed 16% T. The two-gel system of \"Laemmli\" is a simple gradient gel. The pH discontinuity of the buffers is of no significance for the separation quality, and a \"stacking-gel\" with a different pH is not needed. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3286", "text": "The most popular protein stain is  Coomassie brilliant blue . It is an anionic dye, which non-specifically binds to proteins. Proteins in the gel are fixed by acetic acid and simultaneously stained. The excess dye incorporated into the gel can be removed by destaining with the same solution without the dye. The proteins are detected as blue bands on a clear background. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3287", "text": "When more sensitive method than staining by Coomassie is needed, silver staining is usually used. Silver staining is a sensitive procedure to detect trace amounts of proteins in gels, but can also visualize nucleic acid or polysaccharides. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3288", "text": "Visualization methods without using a dye such as Coomassie and silver are available on the market. [ 18 ]  For example  Bio-Rad Laboratories  markets \u201dstain-free\u201d gels for SDS-PAGE gel electrophoresis. Alternatively, reversible fluorescent dyes, such as those from  Azure Biosystems  such as AzureRed or Azure TotalStain Q can be used. [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3289", "text": "Similarly as in nucleic acid gel electrophoresis,  tracking dye  is often used. Anionic dyes of a known electrophoretic mobility are usually included in the sample buffer. A very common tracking dye is  Bromophenol blue . This dye is coloured at alkali and neutral pH and is a small negatively charged molecule that moves towards the anode. Being a highly mobile molecule it moves ahead of most proteins. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3290", "text": "In  medicine ,  protein electrophoresis  is a method of analysing the  proteins  mainly in  blood serum .  Before the widespread use of  gel electrophoresis , protein electrophoresis was performed as free-flow electrophoresis (on paper) or as immunoelectrophoresis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3291", "text": "Traditionally, two classes of  blood proteins  are considered:  serum albumin  and  globulin . They are generally equal in proportion, but  albumin  as a molecule is much smaller and lightly, negatively-charged, leading to an accumulation of albumin on the electrophoretic gel. A small band before albumin represents  transthyretin  (also named prealbumin). Some forms of medication or body chemicals can cause their own band, but it usually is small. Abnormal bands (spikes) are seen in  monoclonal gammopathy of undetermined significance  and  multiple myeloma , and are useful in the diagnosis of these conditions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3292", "text": "The globulins are classified by their banding pattern (with their main representatives): [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3293", "text": "Blood glucose monitoring  is the use of a  glucose meter  for testing the concentration of  glucose  in the blood ( glycemia ). Particularly important in  diabetes management , a blood glucose test is typically performed by piercing the  skin  (typically, via  fingerstick ) to draw blood, then applying the blood to a chemically active disposable 'test-strip'. The other main option is  continuous glucose monitoring  (CGM). Different manufacturers use different technology, but most systems measure an electrical characteristic and use this to determine the glucose level in the blood. Skin-prick methods measure capillary blood glucose (i.e., the level found in capillary blood), whereas CGM correlates interstitial fluid glucose level to blood glucose level. Measurements may occur after  fasting  or at random nonfasting intervals ( random glucose tests ), each of which informs diagnosis or monitoring in different ways."}
{"_id": "WikiPedia_Hematology$$$corpus_3294", "text": "Healthcare professionals advise patients with  diabetes mellitus  on the appropriate monitoring regimen for their condition. Most people with  type 2 diabetes  test at least once per day. The  Mayo Clinic  generally recommends that diabetics who use insulin (all  type 1 diabetics  and many  type 2 diabetics ) test their blood sugar more often (4\u20138 times per day for type 1 diabetics, 2 or more times per day for type 2 diabetics), [ 1 ]  both to assess the effectiveness of their prior insulin dose and to help determine their next insulin dose."}
{"_id": "WikiPedia_Hematology$$$corpus_3295", "text": "Blood glucose monitoring reveals individual patterns of blood glucose changes, and helps in the planning of meals, activities, and at what time of day to take medications. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3296", "text": "Also, testing allows for a quick response to high blood sugar ( hyperglycemia ) or low blood sugar ( hypoglycemia ). This might include diet adjustments, exercise, and insulin (as instructed by the health care provider). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3297", "text": "A  blood glucose meter  is an electronic device for measuring the blood glucose level. A relatively small drop of blood is placed on a disposable test strip which interfaces with a digital meter. Within several seconds, the level of blood glucose will be shown on the digital display. Needing only a small drop of blood for the meter means that the time and effort required for testing are reduced and the compliance of diabetic people to their testing regimens is improved significantly. Blood glucose meters provide results in various units such as eAG (mg/dL) and eAG (mmol/L), and may also estimate A1C levels. These measurements can aid in classifying blood glucose levels as normal, prediabetic, or diabetic, facilitating effective diabetes management for users. While some models offer interpretative features that indicate the health status based on these results, not all meters provide this functionality, focusing instead on providing raw glucose measurements. Users of blood glucose meters without interpretative features can utilize online calculators to determine their blood glucose status based on measured values.  [ 3 ]  The cost of using blood glucose meters is believed to be a cost-benefit relative to the avoided medical costs of the  complications of diabetes . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3298", "text": "Recent advances include: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3299", "text": "A  continuous glucose monitor  determines glucose levels on a continuous basis (every few minutes). [ 6 ]  A typical system consists of:"}
{"_id": "WikiPedia_Hematology$$$corpus_3300", "text": "Continuous glucose monitors measure the concentration of glucose in a sample of  interstitial fluid .  Shortcomings of CGM systems due to this fact are:"}
{"_id": "WikiPedia_Hematology$$$corpus_3301", "text": "Patients, therefore, require traditional fingerstick measurements for calibration (typically twice per day) and are often advised to use fingerstick measurements to confirm hypo- or hyperglycemia before taking corrective action."}
{"_id": "WikiPedia_Hematology$$$corpus_3302", "text": "The lag time discussed above has been reported to be about 5 minutes. [ 8 ] [ 9 ] [ 10 ]   Anecdotally, some users of the various systems report lag times of up to 10\u201315 minutes. This lag time is insignificant when blood sugar levels are relatively consistent. However, blood sugar levels, when changing rapidly, may read in the normal range on a CGM system while in reality the patient is already experiencing symptoms of an out-of-range blood glucose value and may require treatment. Patients using CGM are therefore advised to consider both the absolute value of the blood glucose level given by the system as well as any trend in the blood glucose levels. For example, a patient using CGM with a blood glucose of 100\u00a0mg/dl on their CGM system might take no action if their blood glucose has been consistent for several readings, while a patient with the same blood glucose level but whose blood glucose has been dropping steeply in a short period of time might be advised to perform a fingerstick test to check for hypoglycemia. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3303", "text": "Continuous monitoring allows examination of how the blood glucose level reacts to insulin, exercise, food, and other factors. The additional data can be useful for setting correct  insulin  dosing ratios for food intake and correction of hyperglycemia. Monitoring during periods when blood glucose levels are not typically checked (e.g. overnight) can help to identify problems in insulin dosing (such as basal levels for insulin pump users or long-acting insulin levels for patients taking injections). Monitors may also be equipped with alarms to alert patients of hyperglycemia or hypoglycemia so that a patient can take corrective action(s) (after fingerstick testing, if necessary) even in cases where they do not feel symptoms of either condition. While the technology has its limitations, studies have demonstrated that patients with continuous sensors experience a smaller number of hyperglycemic and hypoglycemic events, a reduction in their  glycated hemoglobin  levels and a decrease in glycemic variability. [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ]  Compared to intermittent testing, it is likely to help reduce hypertensive complications during pregnancy. [ 16 ]  In a recent systematic review with meta-analysis  about glycaemia monitoring in critical patients [ 17 ]  who are haemodynamically unstable and require intensive monitoring of glycaemia it concluded that should be undertaken using arterial blood samples and POC blood gas analysers, as this is more reliable and is not affected by the variability of different confusion factors. Determining glycaemia in capillary blood using glucometry may be suitable in stable patients or when close monitoring of glycaemia is not required."}
{"_id": "WikiPedia_Hematology$$$corpus_3304", "text": "Continuous blood glucose monitoring is not automatically covered by  health insurance  in the United States in the same way that most other diabetic supplies are covered (e.g. standard glucose testing supplies,  insulin , and  insulin pumps ). However, an increasing number of insurance companies do cover continuous glucose monitoring supplies (both the receiver and disposable sensors) on a case-by-case basis if the patient and doctor show a specific need. The lack of insurance coverage is exacerbated by the fact that disposable sensors must be frequently replaced. Some sensors have been U.S.  Food and Drug Administration  (FDA) approved for 7- and 3-day use, (although some patients wear sensors for longer than the recommended period) and the receiving meters likewise have finite lifetimes (less than 2 years and as little as 6 months). This is one factor in the slow uptake in the use of sensors that have been marketed in the United States. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3305", "text": "The principles, history and recent developments of operation of electrochemical glucose biosensors are discussed in a chemical review by  Joseph Wang . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3306", "text": "Investigations on the use of test strips have shown that the required self-injury acts as a psychological barrier restraining the patients from sufficient glucose control. [ 19 ]  As a result,  secondary diseases  are caused by excessive glucose levels. A significant improvement of diabetes therapy might be achieved with an implantable sensor that would continuously monitor blood sugar levels within the body and transmit the measured data outside. The burden of regular blood testing would be taken from the patient, who would instead follow the course of their glucose levels on an intelligent device like a laptop or a smartphone. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3307", "text": "Glucose concentrations do not necessarily have to be measured in blood vessels, but may also be determined in the  interstitial fluid , where the same levels prevail \u2013 with a time lag of a few minutes \u2013 due to its connection with the  capillary system . However, the enzymatic glucose detection scheme used in single-use test strips is not directly suitable for  implants . One main problem is caused by the varying supply of oxygen, by which glucose is converted to  glucono lactone  and H 2 O 2  by  glucose oxidase . Since the implantation of a sensor into the body is accompanied by growth of encapsulation tissue, [ 20 ]  the diffusion of oxygen to the reaction zone is continuously diminished. This decreasing oxygen availability causes the sensor reading to drift, requiring frequent re-calibration using finger-sticks and test strips."}
{"_id": "WikiPedia_Hematology$$$corpus_3308", "text": "One approach to achieving long-term glucose sensing is to measure and compensate for the changing local oxygen concentration. [ 21 ]  Other approaches replace the troublesome glucose oxidase reaction with a reversible sensing reaction, known as an  affinity assay . This scheme was originally put forward by Schultz & Sims in 1978. [ 22 ] [ 23 ]  A number of different affinity assays have been investigated, [ 24 ] [ 25 ] [ 26 ]  with  fluorescent assays  proving most common. [ 27 ] [ 28 ] [ 29 ]   MEMS  technology has recently allowed for smaller and more convenient alternatives to fluorescent detection, via measurement of  viscosity . [ 30 ]  Investigation of affinity-based sensors has shown that encapsulation by body tissue does not cause a drift of the sensor signal, but only a time lag of the signal compared to the direct measurement in blood. [ 31 ]  A new implantable continuous glucose monitor based on affinity principles and fluorescence detection is the Eversense device manufactured by Senseonics Inc. This device has been approved by the FDA for 90 day implantation. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3309", "text": "Some new technologies to monitor blood glucose levels will not require access to blood to read the glucose level.  Non-invasive  technologies include microwave/RF sensing, [ 34 ] [ 35 ]   near IR  detection, [ 36 ]   ultrasound [ 37 ]  and  dielectric spectroscopy . [ 38 ]  These may free the person with diabetes from finger sticks to supply the drop of blood for blood glucose analysis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3310", "text": "Most [ citation needed ]  of the non-invasive methods under development are continuous glucose monitoring methods and offer the advantage of providing additional information to the subject between the conventional finger stick, blood glucose measurements, and overtime periods where no finger stick measurements are available (i.e. while the subject is sleeping)."}
{"_id": "WikiPedia_Hematology$$$corpus_3311", "text": "For patients with  diabetes mellitus type 2 , the importance of monitoring and the optimal frequency of monitoring are not clear. A 2011 study found no evidence that blood glucose monitoring leads to better patient outcomes in actual practice. [ 39 ]  Randomized controlled trials found that self-monitoring of blood glucose did not improve  glycated hemoglobin  (HbA1c) among \"reasonably well controlled non-insulin treated patients with type 2 diabetes\" [ 40 ]  or lead to significant changes in quality of life. [ 41 ]   However a recent meta-analysis of 47 randomized controlled trials encompassing 7677 patients showed that self-care management intervention improves glycemic control in diabetics, with an estimated 0.36% (95% CI, 0.21\u20130.51) reduction in their glycated hemoglobin values. [ 42 ]  Furthermore, a recent study showed that patients described as being \"Uncontrolled Diabetics\" (defined in this study by HbA1C levels >8%) showed a statistically significant decrease in the HbA1C levels after a 90-day period of seven-point self-monitoring of blood glucose (SMBG) with a relative risk reduction (RRR) of 0.18% (95% CI, 0.86\u20132.64%, p<.001). [ 43 ]  Regardless of lab values or other numerical parameters, the purpose of the clinician is to improve quality of life and patient outcomes in diabetic patients. A recent study included 12 randomized controlled trials and evaluated outcomes in 3259 patients. The authors concluded through a qualitative analysis that SMBG on quality of life showed no effect on patient satisfaction or the patients' health-related quality of life.  Furthermore, the same study identified that patients with type 2 diabetes mellitus diagnosed greater than one year prior to initiation of SMBG, who were not on insulin, experienced a statistically significant reduction in their HbA1C of 0.3% (95% CI, -0.4 \u2013  -0.1) at six months follow up, but a statistically insignificant reduction of 0.1% (95% CI, -0.3 \u2013 0.04) at twelve months follow up.  Conversely, newly diagnosed patients experienced a statistically significant reduction of 0.5% (95% CI, -0.9 \u2013 -0.1) at 12 months follow up. [ 44 ]  A recent study found that a treatment strategy of intensively lowering blood sugar levels (below 6%) in patients with additional  cardiovascular disease  risk factors poses more harm than benefit. [ 45 ]   For type 2 diabetics who are not on insulin, exercise and diet are the best tools. [ citation needed ]  Blood glucose monitoring is, in that case, simply a tool to evaluate the success of diet and exercise. Insulin-dependent type 2 diabetics do not need to monitor their blood sugar as frequently as type 1 diabetics. [ 46 ]  In a recent systematic review with meta-analysis, about glycaemia monitoring in critical patients who are haemodynamically unstable and require intensive monitoring of glycaemia it concluded that should be undertaken using arterial blood samples and POC blood gas analysers, as this is more reliable and is not affected by the variability of different confusion factors. Determining glycaemia in capillary blood using glucometry may be suitable in stable patients or when close monitoring of glycaemia is not required."}
{"_id": "WikiPedia_Hematology$$$corpus_3312", "text": "The  National Institute for Health and Clinical Excellence  (NICE), UK released updated diabetes recommendations on 30 May 2008, which recommend that self-monitoring of plasma glucose levels for people with newly diagnosed type 2 diabetes must be integrated into a structured self-management education process. [ 47 ]  The recommendations have been updated in August 2015 for children and young adults with type 1 diabetes. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3313", "text": "The  American Diabetes Association (ADA) , which produces guidelines for diabetes care and  clinical practice recommendations , recently updated its \"Standards of Medical Care\" in January 2019 to acknowledge that routine self-monitoring of blood glucose in people who are not using insulin is of limited additional clinical benefit. [ 49 ]  A randomized controlled trial evaluated once-daily self-monitoring that included tailored patient messaging and did not show that this strategy led to significant changes in A1C after a year. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3314", "text": "Many types of  glucose tests  exist and they can be used to estimate  blood sugar levels  at a given time or, over a longer period of time, to obtain average levels or to see how fast the body is able to normalize changed  glucose  levels. Eating food for example leads to elevated blood sugar levels. In healthy people, these levels quickly return to normal via increased  cellular  glucose uptake which is primarily mediated by increase in blood  insulin  levels. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3315", "text": "Glucose tests can reveal temporary/long-term  hyperglycemia  or  hypoglycemia . These conditions may not have obvious symptoms and can damage organs in the long-term. Abnormally high/low levels, slow return to normal levels from either of these conditions and/or inability to normalize blood sugar levels means that the person being tested probably has some kind of medical condition like  type 2 diabetes  which is caused by cellular insensitivity to insulin. Glucose tests are thus often used to diagnose such conditions."}
{"_id": "WikiPedia_Hematology$$$corpus_3316", "text": "Tests that can be performed at home are used in  blood glucose monitoring  for illnesses that have already been diagnosed medically so that these illnesses can be maintained via medication and meal timing. Some of the home testing methods include [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3317", "text": "Laboratory tests are often used to diagnose illnesses and such methods include"}
{"_id": "WikiPedia_Hematology$$$corpus_3318", "text": "Some laboratory tests don't measure glucose levels directly from body fluids or tissues but still indicate elevated blood sugar levels. Such tests measure the levels of  glycated hemoglobin , other  glycated  proteins,  1,5-anhydroglucitol  etc. from blood. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3319", "text": "Glucose testing can be used to diagnose or indicate certain medical conditions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3320", "text": "High blood sugar  may indicate"}
{"_id": "WikiPedia_Hematology$$$corpus_3321", "text": "Low blood sugar  may indicate"}
{"_id": "WikiPedia_Hematology$$$corpus_3322", "text": "Fasting  prior to glucose testing may be required with some test types. Fasting blood sugar test, for example, requires 10\u201316 hour-long period of not eating before the test. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3323", "text": "Blood sugar levels can be affected by some drugs and prior to some glucose tests these medications should be temporarily given up or their dosages should be decreased. Such drugs may include  salicylates  (Aspirin),  birth control pills ,  corticosteroids ,  tricyclic antidepressants ,  lithium ,  diuretics  and  phenytoin . [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3324", "text": "Some foods contain  caffeine  ( coffee ,  tea ,  colas ,  energy drinks  etc.). Blood sugar levels of healthy people are generally not significantly changed by caffeine, but in diabetics caffeine intake may elevate these levels via its ability to stimulate the  adrenergic nervous system . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3325", "text": "A level below 5.6\u00a0mmol/L (100\u00a0mg/dL) 10\u201316 hours without eating is normal. 5.6\u20136\u00a0mmol/L (100\u2013109\u00a0mg/dL) may indicate  prediabetes  and  oral glucose tolerance test  (OGTT) should be offered to high-risk individuals (old people, those with  high blood pressure  etc.). 6.1\u20136.9\u00a0mmol/L (110\u2013125\u00a0mg/dL) means OGTT should be offered even if other indicators of diabetes are not present. 7\u00a0mmol/L (126\u00a0mg/dL) and above indicates diabetes and the fasting test should be repeated. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3326", "text": "The  glucose tolerance test  (GTT, not to be confused with  GGT test ) is a  medical test  in which  glucose  is given and  blood  samples taken afterward to determine how quickly it is cleared from the blood. [ 1 ]  The test is usually used to test for  diabetes ,  insulin resistance , impaired  beta cell function , [ 2 ]  and sometimes  reactive hypoglycemia  and  acromegaly , or rarer disorders of  carbohydrate metabolism . In the most commonly performed version of the test, an  oral glucose tolerance test  (OGTT), a standard dose of glucose is ingested by mouth and blood levels are checked two hours later. [ 3 ]  Many variations of the GTT have been devised over the years for various purposes, with different standard doses of glucose, different routes of administration, different intervals and durations of sampling, and various substances measured in addition to blood glucose."}
{"_id": "WikiPedia_Hematology$$$corpus_3327", "text": "The glucose tolerance test was first described in 1923 by  Jerome W. Conn . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3328", "text": "The test was based on the previous work in 1913 by A. T. B. Jacobson in determining that carbohydrate ingestion results in blood glucose fluctuations, [ 5 ]  and the premise (named the  Staub-Traugott Phenomenon  after its first observers H. Staub in 1921 and K. Traugott in 1922) that a normal patient fed glucose will rapidly return to normal levels of blood glucose after an initial spike, and will see improved reaction to subsequent glucose feedings. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3329", "text": "Since the 1970s, the  World Health Organization  and other organizations interested in diabetes agreed on a standard dose and duration. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3330", "text": "The patient is instructed not to restrict  carbohydrate  intake in the days or weeks before the test. [ 9 ]  The test should not be done during an illness, as results may not reflect the patient's glucose metabolism when healthy. A full adult dose should not be given to a person weighing less than 42.6\u00a0kg (94\u00a0lb), or the excessive glucose may produce a  false positive  result. Usually the OGTT is performed in the morning as glucose tolerance can exhibit a diurnal rhythm with a significant decrease in the afternoon. The patient is instructed to  fast  (water is allowed) for 8\u201312 hours prior to the tests. Medication such as large doses of  salicylates ,  diuretics ,  anticonvulsants , and  oral contraceptives  affect the glucose tolerance test. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3331", "text": "If  renal glycosuria  (sugar excreted in the urine despite normal levels in the blood) is suspected, urine samples may also be collected for testing along with the fasting and 2 hour blood tests. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3332", "text": "For  gestational diabetes , the  American College of Obstetricians and Gynecologists  (ACOG) recommends a two-step procedure, wherein the first step is a 50\u00a0g glucose dose. [ 12 ] [ 16 ]  If after 1 hour the blood glucose level is more than 7.8\u00a0mmol/L (140\u00a0mg/dL), [ 12 ]  it is followed by a 100\u00a0g glucose dose. [ 12 ]  The diagnosis of gestational diabetes is then defined by a blood glucose level meeting or exceeding the cutoff values on at least two intervals, [ 12 ]  with cutoffs as follows: [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3333", "text": "The diagnosis criteria stated above by the World Health Organization (WHO) are for venous samples only (a blood sample taken from a vein in the arm). An increasingly popular method for measuring blood glucose is to sample capillary or finger-prick blood, which is less invasive, more convenient for the patient and requires minimal training to conduct. Though fasting blood glucose levels have been shown to be similar in both capillary and venous samples, postprandial blood glucose levels (those measured after a meal) can vary. [ 17 ]  The diagnosis criteria issued by the WHO are only suitable for venous blood samples. Given the increasing popularity of capillary testing, the WHO has recommended that a conversion factor between the two sample types be calculated, but as of 2017 [update]  no conversion factor had been issued by the WHO, despite some medical professionals adopting their own. [ citation needed ]  A 2020 study on pregnant women for gestational diabetes mellitus (GDM) found that 0-hour venous and capillary levels were similar, but that 2-hour samples were different. The authors compared their study with others, and concluded that capillary samples could be used for diagnosis of GDM during pregnancy using corrected cutoffs with acceptable accuracy in an antenatal care setting. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3334", "text": "A standard two-hour GTT (glucose tolerance test) is sufficient to diagnose or exclude all forms of diabetes mellitus at all but the earliest stages of development."}
{"_id": "WikiPedia_Hematology$$$corpus_3335", "text": "Longer tests have been used for a variety of other purposes, such as detecting reactive hypoglycemia or defining subsets of  hypothalamic obesity . Insulin levels are sometimes measured to detect insulin resistance or deficiency. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3336", "text": "The GTT (glucose tolerance test) is of limited value in the diagnosis of reactive hypoglycemia, since normal levels do not preclude the diagnosis, abnormal levels do not prove that the patient's other symptoms are related to a demonstrated atypical OGTT, and many people without symptoms of reactive hypoglycemia may have the late low glucose. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3337", "text": "The oral glucose challenge test (OGCT) is a short version of the OGTT, used to check pregnant women for signs of  gestational diabetes . [ 3 ] [ 20 ]  It can be done at any time of day, not on an empty stomach. [ 3 ]  The test involves 50\u00a0g of glucose, with a reading after one hour. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3338", "text": "The OGTT does not distinguish between insulin resistance in peripheral tissues and reduced capacity of the pancreas  beta-cells  to produce insulin. The OGTT is less accurate than the  hyperinsulinemic-euglycemic clamp technique  (the \"gold standard\" for measuring insulin resistance), or the  insulin tolerance test , but is technically less difficult. Neither of the two technically demanding tests can be easily applied in a clinical setting or used in epidemiological studies. HOMA-IR ( homeostatic model assessment ) is a convenient way of measuring insulin resistance in normal subjects, which can be used in epidemiological studies, but can give erroneous results for diabetic patients. [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3339", "text": "Glycated hemoglobin  (also called  glycohemoglobin ) is a form of  hemoglobin  (Hb) that is chemically linked to a sugar. (\"Glycosylated haemoglobin\" is a misnomer because  glycation  and  glycosylation  are different processes, of which only the former is relevant in this case.)"}
{"_id": "WikiPedia_Hematology$$$corpus_3340", "text": "Most  monosaccharides , including  glucose ,  galactose , and  fructose , spontaneously (that is,  non-enzymatically ) bond with hemoglobin when they are present in the bloodstream. However, glucose is only 21% as likely to do so as galactose and 13% as likely to do so as fructose, which may explain why glucose is used as the primary metabolic fuel in humans. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3341", "text": "The formation of excess sugar-hemoglobin linkages indicates the presence of excessive sugar in the bloodstream and is an indicator of  diabetes  or other hormone diseases in high concentration (HbA1c >6.4%). [ 3 ]  A1c is of particular interest because it is easy to detect. The process by which sugars attach to hemoglobin is called  glycation  and the reference system is based on HbA1c, defined as beta-N-1-deoxy fructosyl hemoglobin as component. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3342", "text": "There are several ways to measure glycated hemoglobin, of which  HbA1c  (or simply  A1c ) is a standard single test. [ 5 ]  HbA1c is measured primarily to determine the three-month average  blood sugar level  and is used as a standard diagnostic test for evaluating the risk of complications of  diabetes  and as an assessment of  glycemic control . [ 5 ] [ 6 ]  The test is considered a three-month average because the average lifespan of a red blood cell is three to four months. Normal levels of glucose produce a normal amount of glycated hemoglobin. As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. In diabetes, higher amounts of glycated hemoglobin, indicating higher of blood glucose levels, have been associated with  cardiovascular disease ,  nephropathy ,  neuropathy , and  retinopathy . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3343", "text": "Glycated  hemoglobin is preferred over  glycosylated  hemoglobin to reflect the correct (non-enzymatic) process. Early literature often used  glycosylated  as it was unclear which process was involved until further research was performed. The terms are still sometimes used interchangeably in English-language literature. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3344", "text": "The naming of HbA1c derives from hemoglobin type A being separated on  cation exchange chromatography . The first fraction to separate, probably considered to be pure hemoglobin A, was designated HbA0, and the following fractions were designated HbA1a, HbA1b, and HbA1c, in their order of  elution . Improved separation techniques have subsequently led to the isolation of more  subfractions . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3345", "text": "Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a  chromatographic column . [ 10 ]  It was first characterized as a  glycoprotein  by Bookchin and Gallop in 1968. [ 11 ]  Its increase in diabetes was first described in 1969 by  Samuel Rahbar   et al . [ 12 ]  The reactions leading to its formation were characterized by Bunn and his coworkers in 1975. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3346", "text": "The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by  Anthony Cerami , Ronald Koenig, and coworkers. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3347", "text": "Glycated hemoglobin causes an increase of highly reactive  free radicals  inside blood cells, altering the properties of their  cell membranes . This leads to  blood cell aggregation  and increased blood  viscosity , which results in impaired blood flow. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3348", "text": "Another way glycated hemoglobin causes damage is via  inflammation , which results in  atherosclerotic  plaque ( atheroma ) formation. Free-radical build-up promotes the  excitation  of  Fe 2+ -hemoglobin through  Fe 3+ -Hb  into abnormal  ferryl  hemoglobin (Fe 4+ -Hb). Fe 4+  is unstable and reacts with specific  amino acids  in hemoglobin to regain its Fe 3+   oxidation state . Hemoglobin molecules clump together via  cross-linking reactions , and these hemoglobin clumps (multimers) promote cell damage and the release of Fe 4+ -hemoglobin into the  matrix  of innermost layers ( subendothelium ) of arteries and veins. This results in increased permeability of interior surface ( endothelium ) of blood vessels and production of pro-inflammatory  monocyte   adhesion  proteins, which promote  macrophage  accumulation in blood vessel surfaces, ultimately leading to harmful plaques in these vessels. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3349", "text": "Highly glycated Hb- AGEs  go through  vascular smooth muscle  layer and inactivate  acetylcholine -induced endothelium-dependent relaxation, possibly through binding to  nitric oxide  (NO), preventing its normal function. NO is a potent  vasodilator  and also inhibits formation of plaque-promoting  LDLs  (sometimes called \"bad cholesterol\")  oxidized  form. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3350", "text": "This overall degradation of blood cells also releases  heme  from them. Loose heme can cause oxidation of endothelial and LDL proteins, which results in plaques. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3351", "text": "Glycation of proteins is a frequent occurrence, but in the case of hemoglobin, a nonenzymatic condensation reaction occurs between glucose and the N-end of the  beta chain . This reaction produces a  Schiff base  ( R\u2212N=CHR' , R=beta chain, CHR'=glucose-derived), which is itself converted to 1-deoxyfructose. This second conversion is an example of an  Amadori rearrangement . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3352", "text": "When blood glucose levels are high,  glucose  molecules attach to the hemoglobin in  red blood cells . The longer hyperglycemia occurs in blood, the more glucose binds to hemoglobin in the red blood cells and the higher the glycated hemoglobin. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3353", "text": "Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell, therefore, reflects the average level of glucose to which the cell has been exposed during its  life-cycle . Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation."}
{"_id": "WikiPedia_Hematology$$$corpus_3354", "text": "A1c is a weighted average of blood glucose levels during the life of the red blood cells (117 days for men and 106 days in women [ 18 ] ). Therefore, glucose levels on days nearer to the test contribute substantially more to the level of A1c than the levels in days further from the test. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3355", "text": "This is also supported by data from clinical practice showing that HbA1c levels improved significantly after 20 days from start or intensification of glucose-lowering treatment. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3356", "text": "Several techniques are used to measure hemoglobin A1c. Laboratories may use  high-performance liquid chromatography ,  immunoassay ,  enzymatic  assay,  capillary electrophoresis , or  boronate affinity chromatography .  Point of care  (e.g., doctor's office) devices use immunoassay boronate affinity chromatography. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3357", "text": "In the United States, HbA 1c  testing laboratories are certified by the National Glycohemoglobin Standardization Program to standardize them against the results of the 1993  Diabetes Control and Complications Trial  (DCCT). [ 21 ]  An additional percentage scale, Mono S has previously been in use by Sweden and KO500 is in use in Japan. [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3358", "text": "The American Diabetes Association,  European Association for the Study of Diabetes , and  International Diabetes Federation  have agreed that, in the future, HbA 1c  is to be reported in the  International Federation of Clinical Chemistry and Laboratory Medicine  (IFCC) units. [ 24 ]  IFCC reporting was introduced in Europe except for the UK in 2003; [ 25 ]  the UK carried out dual reporting from 1 June 2009  [ 26 ]  until 1 October 2011."}
{"_id": "WikiPedia_Hematology$$$corpus_3359", "text": "Conversion between DCCT and IFCC is by the following equation: [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3360", "text": "Laboratory results may differ depending on the analytical technique, the age of the subject, and biological variation among individuals. Higher levels of HbA 1c  are found in people with persistently elevated blood sugar, as in  diabetes mellitus . While diabetic patient treatment goals vary, many include a target range of HbA 1c  values. A diabetic person with good glucose control has an HbA 1c  level that is close to or within the reference range. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3361", "text": "The International Diabetes Federation and the American College of Endocrinology recommend HbA 1c  values below 48\u00a0mmol/mol (6.5 DCCT\u00a0%), while the  American Diabetes Association  recommends HbA 1c  be below 53\u00a0mmol/mol (7.0 DCCT\u00a0%) for most patients. [ 28 ]  Results from large trials in  2008\u201309  suggested that a target below 53\u00a0mmol/mol (7.0 DCCT\u00a0%) for older adults with type 2 diabetes may be excessive: Below 53\u00a0mmol/mol, the health benefits of reduced A1c become smaller, and the intensive glycemic control required to reach this level leads to an increased rate of dangerous hypoglycemic episodes. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3362", "text": "A retrospective study of 47,970 type 2 diabetes patients, aged 50 years and older, found that patients with an HbA 1c  more than 48\u00a0mmol/mol (6.5 DCCT\u00a0%) had an increased mortality rate, [ 30 ]  but a later international study contradicted these findings. [ 31 ] [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3363", "text": "A review of the  UKPDS , Action to Control Cardiovascular Risk in Diabetes (ACCORD), Advance and Veterans Affairs Diabetes Trials (VADT) estimated that the risks of the main complications of diabetes ( diabetic retinopathy ,  diabetic nephropathy ,  diabetic neuropathy , and  macrovascular disease ) decreased by about 3% for every 1\u00a0mmol/mol decrease in HbA 1c . [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3364", "text": "However, a trial by ACCORD designed specifically to determine whether reducing HbA 1c  below 42\u00a0mmol/mol (6.0 DCCT\u00a0%) using increased amounts of medication would reduce the rate of cardiovascular events found higher mortality with this intensive therapy, so much so that the trial was terminated 17 months early. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3365", "text": "Practitioners must consider patients' health, their risk of hypoglycemia, and their specific health risks when setting a target HbA 1c  level. Because patients are responsible for averting or responding to their own hypoglycemic episodes, their input and the doctors' assessments of the patients'  self-care  skills are also important. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3366", "text": "Persistent elevations in blood sugar (and, therefore, HbA 1c ) increase the risk of long-term vascular complications of diabetes, such as  coronary disease ,  heart attack ,  stroke ,  heart failure ,  kidney failure ,  blindness ,  erectile dysfunction ,  neuropathy  (loss of sensation, especially in the feet),  gangrene , and  gastroparesis  (slowed emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery such as poor  wound healing . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3367", "text": "All-cause mortality  is higher above 64\u00a0mmol/mol (8.0 DCCT%) HbA1c as well as below 42\u00a0mmol/mol (6.0 DCCT\u00a0%) in diabetic patients, and above 42\u00a0mmol/mol (6.0 DCCT\u00a0%) as well as below 31\u00a0mmol/mol (5.0 DCCT\u00a0%) in non-diabetic persons, indicating the risks of  hyperglycemia  and  hypoglycemia , respectively. [ 7 ]  Similar risk results are seen for  cardiovascular disease . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3368", "text": "The 2022 ADA guidelines reaffirmed the recommendation that HbA1c should be maintained below 7.0% for most patients. Higher target values are appropriate for children and adolescents, patients with extensive co-morbid illness and those with a history of severe hypoglycemia.  More stringent targets (<6.0%) are preferred for pregnant patients if this can be achieved without significant hypoglycemia. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3369", "text": "Lower-than-expected levels of HbA 1c  can be seen in people with shortened red blood cell lifespans, such as with  glucose-6-phosphate dehydrogenase deficiency ,  sickle-cell disease , or any other condition causing premature red blood cell death. For these patients, alternate assessment with  fructosamine  or glycated  albumin  is recommended; these methods reflect glycemic control over the preceding 2-3 weeks. [ 37 ]  Blood donation will result in rapid replacement of lost RBCs with newly formed red blood cells. Since these new RBCs will have only existed for a short period of time, their presence will lead HbA 1c  to underestimate the actual average levels. There may also be distortions resulting from  blood donation  during the preceding two months, due to an abnormal synchronization of the age of the RBCs, resulting in an older than normal average blood cell life (resulting in an overestimate of actual average blood glucose levels). Conversely, higher-than-expected levels can be seen in people with a longer red blood cell lifespan, such as with iron deficiency. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3370", "text": "Results can be unreliable in many circumstances, for example after blood loss, after surgery, blood transfusions, anemia, or high erythrocyte turnover; in the presence of chronic renal or liver disease; after administration of high-dose vitamin C; or  erythropoetin  treatment. [ 39 ]   Hypothyroidism  can artificially raise the A1c. [ 40 ] [ 41 ] [ 42 ]  In general, the  reference range  (that found in healthy young persons), is about 30\u201333\u00a0mmol/mol (4.9\u20135.2 DCCT\u00a0%). [ 43 ]  The mean HbA 1c  for diabetics type 1 in Sweden in 2014 was 63\u00a0mmol/mol (7.9 DCCT%) and for type 2, 61\u00a0mmol/mol (7.7 DCCT%). [ 44 ]  HbA1c levels show a small, but statistically significant, progressive uptick with age; the clinical importance of this increase is unclear. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3371", "text": "The approximate mapping between HbA 1c  values given in DCCT percentage (%) and eAG (estimated average glucose) measurements is given by the following equation: [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3372", "text": "The 2010  American Diabetes Association  Standards of Medical Care in Diabetes added the HbA 1c  \u2265 48\u00a0mmol/mol (\u22656.5 DCCT\u00a0%) as another criterion for the diagnosis of diabetes. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3373", "text": "Glycated hemoglobin testing is recommended for both checking the blood sugar control in people who might be prediabetic and monitoring blood sugar control in patients with more elevated levels, termed diabetes mellitus. For a single blood sample, it provides far more revealing information on glycemic behavior than a fasting blood sugar value. However, fasting blood sugar tests are crucial in making treatment decisions. The American Diabetes Association guidelines are similar to others in advising that the glycated hemoglobin test be performed at least twice a year in patients with diabetes who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients with diabetes whose therapy has changed or who are not meeting glycemic goals. [ 48 ] [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3374", "text": "Glycated hemoglobin measurement is not appropriate where a change in diet or treatment has been made within six weeks. Likewise, the test assumes a normal red blood cell aging process and mix of hemoglobin subtypes (predominantly HbA in normal adults). Hence, people with recent blood loss,  hemolytic anemia , or genetic differences in the hemoglobin molecule ( hemoglobinopathy ) such as  sickle-cell disease  and other conditions, as well as those who have donated blood recently, are not suitable for this test. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3375", "text": "Due to glycated hemoglobin's variability (as shown in the table above), additional measures should be checked in patients at or near recommended goals. People with HbA 1c  values at 64\u00a0mmol/mol or less should be provided additional testing to determine whether the HbA 1c  values are due to averaging out high blood glucose ( hyperglycemia ) with low blood glucose ( hypoglycemia ) or the HbA 1c  is more reflective of an elevated blood glucose that does not vary much throughout the day. Devices such as continuous  blood glucose monitoring  allow people with diabetes to determine their blood glucose levels on a continuous basis, testing every few minutes. Continuous use of blood glucose monitors is becoming more common, and the devices are covered by many health insurance plans, including  Medicare  in the United States. The supplies tend to be expensive, since the sensors must be changed at least every 2 weeks. Another useful test in determining if HbA 1c  values are due to wide variations of blood glucose throughout the day is  1,5-anhydroglucitol , also known as  GlycoMark . GlycoMark reflects only the times that the person experiences hyperglycemia above 180\u00a0mg/dL over a two-week period. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3376", "text": "Concentrations of hemoglobin A1 (HbA1) are increased, both in diabetic patients and in patients with  kidney failure , when measured by  ion-exchange chromatography . The thiobarbituric acid method (a chemical method specific for the detection of glycation) shows that patients with kidney failure have values for glycated hemoglobin similar to those observed in normal subjects, suggesting that the high values in these patients are a result of binding of something other than glucose to hemoglobin. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3377", "text": "In  autoimmune hemolytic anemia , concentrations of HbA1 is undetectable. Administration of  prednisolone  will allow the HbA1 to be detected. [ 51 ]  The alternative  fructosamine  test may be used in these circumstances and it also reflects an average of blood glucose levels over the preceding 2 to 3 weeks. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3378", "text": "All the major institutions such as the International Expert Committee Report, drawn from the International Diabetes Federation, the European Association for the Study of Diabetes, and the American Diabetes Association, suggest the HbA 1c  level of 48\u00a0mmol/mol (6.5 DCCT\u00a0%) as a diagnostic level. [ 53 ]  The Committee Report further states that, when HbA 1c  testing cannot be done, the fasting and glucose-tolerance tests be done. Screening for diabetes during pregnancy continues to require fasting and glucose-tolerance measurements for  gestational diabetes  at 24 to 28 weeks gestation, although glycated hemoglobin may be used for screening at the first prenatal visit. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3379", "text": "Meta-analysis  has shown  probiotics  to cause a statistically significant reduction in glycated hemoglobin in  type-2 diabetics . [ 54 ]  Trials with multiple strains of probiotics had statistically significant reductions in glycated hemoglobin, whereas trials with single strains did not. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3380", "text": "Most clinical studies recommend the use of HbA1c assays that are traceable to the DCCT assay. [ 55 ]  The National Glycohemoglobin Standardization Program (NGSP) and IFCC have improved assay standardization. [ 37 ]  For initial diagnosis of diabetes, only HbA1c methods that are NGSP-certified should be used, not  point-of-care testing  devices. [ 36 ]  Analytical performance has been a problem with earlier  point-of-care  devices for HbA1c testing, specifically large standard deviations and negative bias. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3381", "text": "HbA1c testing has not been found useful in the monitoring during the treatment of cats and dogs with diabetes, and is not generally used; monitoring of  fructosamine  levels is favoured instead. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3382", "text": "Glycogen phosphorylase isoenzyme BB  (abbreviation:  GPBB ) is an  isoenzyme  of  glycogen phosphorylase . This isoform of the enzyme exists in cardiac (heart) and brain tissue."}
{"_id": "WikiPedia_Hematology$$$corpus_3383", "text": "The enzyme is one of the \"new  cardiac markers \" which are discussed to improve early diagnosis in  acute coronary syndrome . A rapid rise in blood levels can be seen in  myocardial infarction  and  unstable angina ."}
{"_id": "WikiPedia_Hematology$$$corpus_3384", "text": "Other enzymes related to glycogen phosphorylase are abbreviated as  GPLL  (liver) and  GPMM  (muscle)."}
{"_id": "WikiPedia_Hematology$$$corpus_3385", "text": "The  T-Lymphocyte Helper/Suppressor Profile  (Helper/Suppressor ratio, T4:T8 ratio, CD4:CD8 ratio) is a basic laboratory test in which the percentage of  CD3 -positive  lymphocytes  in the blood positive for  CD4  ( T helper cells ) and  CD8  (a class of  regulatory T cells ) are counted and compared.  Normal values (95% confidence intervals) are approximately 30-60% CD4 and 10-30% CD8 depending on age (ratio 0.9 to 3.7 in adults). [ 1 ]   One reason for abnormal results is the loss of CD4-positive cells to the  human immunodeficiency virus  (HIV) infection. The loss of CD4-positive cells to HIV infection can result in various distortions in the ratio, as in the initial period, production of HIV specific CD8 positive cells will cause a large fall in the ratio, but subsequent immunosuppression over time may lead to overall non production of immune cells and inversion of the ratio. It has been shown that the degree of inversion of this ratio in individuals on antiretroviral therapy is indicative of the age of the infection and independently predictive of mortality associated with non HIV events. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3386", "text": "The  hematocrit  ( / h \u026a \u02c8 m \u00e6 t \u0259 k r \u026a t / ) ( Ht  or  HCT ), also known by  several other names , is the  volume percentage  (vol%) of  red blood cells  (RBCs) in  blood , [ 1 ] [ 2 ]  measured as part of a  blood test . [ 3 ]  The measurement depends on the number and size of red blood cells. [ 3 ]  It is normally 40.7\u201350.3% for males and 36.1\u201344.3% for females. [ 3 ]  It is a part of a person's  complete blood count  results, [ 4 ]  along with  hemoglobin  concentration,  white blood cell  count and  platelet  count."}
{"_id": "WikiPedia_Hematology$$$corpus_3387", "text": "Because the purpose of red blood cells is to transfer oxygen from the lungs to body tissues, a blood sample's hematocrit\u2014the red blood cell volume percentage\u2014can become a point of reference of its capability of delivering oxygen. Hematocrit levels that are too high or too low can indicate a blood disorder,  dehydration , or other medical conditions. [ 4 ]  An abnormally low hematocrit may suggest  anemia , a decrease in the total amount of red blood cells, while an abnormally high hematocrit is called  polycythemia . [ 5 ]  Both are potentially life-threatening disorders."}
{"_id": "WikiPedia_Hematology$$$corpus_3388", "text": "There are other names for the hematocrit, such as  packed cell volume  (PCV),  volume of packed red cells  (VPRC), or  erythrocyte volume fraction  (EVF). The term  hematocrit  (or  haematocrit  in  British English ) comes from the  Ancient Greek  words  haima  ( \u03b1\u1f37\u03bc\u03b1 , \"blood\") and  krit\u0113s  ( \u03ba\u03c1\u03b9\u03c4\u03ae\u03c2 , \"judge\"), and hematocrit means \"to separate blood\". [ 6 ] [ 7 ]  It was coined in 1891 by Swedish physiologist  Magnus Blix  as  haematokrit , [ 8 ] [ 9 ] [ 10 ]  modeled after  lactokrit ."}
{"_id": "WikiPedia_Hematology$$$corpus_3389", "text": "With modern lab equipment, the hematocrit can be calculated by an  automated analyzer  or directly measured, depending on the analyzer manufacturer. Calculated hematocrit is determined by multiplying the red cell count by the  mean cell volume . The hematocrit is slightly more accurate, as the PCV includes small amounts of  blood plasma  trapped between the red cells. An estimated hematocrit as a percentage may be derived by tripling the  hemoglobin  concentration in  g / dL  and dropping the units. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3390", "text": "The packed cell volume (PCV) can be determined by  centrifuging   EDTA -treated or  heparinized  blood in a  capillary tube  (also known as a microhematocrit tube) at 10,000\u00a0 RPM  for five minutes. [ 12 ]  This separates the blood into layers. The volume of packed red blood cells divided by the total volume of the blood sample gives the PCV. Since a tube is used, this can be calculated by measuring the lengths of the layers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3391", "text": "Another way of measuring hematocrit levels is by optical methods such as  spectrophotometry . [ 13 ]  Through differential spectrophotometry, the differences in optical densities of a blood sample flowing through small-bore glass tubes at  isosbestic  wavelengths for deoxyhemoglobin and oxyhemoglobin and the product of the luminal diameter and hematocrit create a linear relationship that is used to measure hematocrit levels. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3392", "text": "Other than potential bruising at the puncture site, and/or dizziness, there are no complications associated with this test. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3393", "text": "While known hematocrit levels are used in detecting conditions, it may fail at times due to hematocrit being the measure of concentration of red blood cells through volume in a blood sample. It does not account for the mass of the red blood cells, and thus the changes in mass can alter a hematocrit level or go undetected while affecting a subject's condition. [ 15 ]  Additionally, there have been cases in which the blood for testing was inadvertently drawn proximal to an intravenous line that was infusing packed red cells or fluids. In these situations, the hemoglobin level in the blood sample will not be the true level for the patient because the sample will contain a large amount of the infused material rather than what is diluted into the circulating whole blood. That is, if packed red cells are being supplied, the sample will contain a large amount of those cells and the hematocrit will be artificially very high. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3394", "text": "Hematocrit can vary from the determining factors of the number of red blood cells. These factors can be from the age and sex of the subject. [ clarification needed ] [ 16 ]  The normal hematocrit level is around 40% for adult women and about 45% for adult men. In newborns, it is approximately 55% and drops to around 35% by 2 months of age. After that, it gradually increases during development, reaching adult levels at puberty. [ 17 ]  Following this, the hematocrit level gradually decreases with aging. [ 18 ]  Typically, a higher hematocrit level signifies the blood sample's ability to transport oxygen, [ 19 ]  which has led to reports that an \"optimal hematocrit level\" may exist. Optimal hematocrit levels have been studied through combinations of assays on blood sample's hematocrit itself, viscosity, and hemoglobin level. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3395", "text": "Hematocrit levels also serve as an indicator of health conditions. Thus, tests on hematocrit levels are often carried out in the process of diagnosis of such conditions, [ 3 ]  and may be conducted prior to surgery. [ 6 ]  Additionally, the health conditions associated with certain hematocrit levels are the same as ones associated with certain hemoglobin levels. As blood flows from the arterioles into the capillaries, a change in pressure occurs. In order to maintain pressure, the capillaries branch off to a web of vessels that carry blood into the venules. Through this process blood undergoes micro-circulation. In micro-circulation, the  F\u00e5hr\u00e6us effect  will take place, resulting in a large change in hematocrit. As blood flows through the arterioles, red cells will act a feed hematocrit (Hf), while in the capillaries, a tube hematocrit (Ht) occurs. In tube hematocrit, plasma fills most of the vessel while the red cells travel through in somewhat of a single file line. From this stage, blood will enter the venules increasing in hematocrit, in other words the discharge hematocrit (Hd).In large vessels with low hematocrit, viscosity dramatically drops and red cells take in a lot of energy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3396", "text": "Relationships between hematocrit, viscosity, and shear rate are important factors to put into consideration. Since blood is non-Newtonian, the viscosity of the blood is in relation to the hematocrit, and as a function of shear rate. This is important when it comes to determining shear force, since a lower hematocrit level indicates that there is a need for more force to push the red blood cells through the system. This is because shear rate is defined as the rate to which adjacent layers of fluid move in respect to each other. [ 20 ]  Plasma is a more viscous material than typically red blood cells, since they are able to adjust their size to the radius of a tube; the shear rate is purely dependent on the amount of red blood cells being forced in a vessel. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3397", "text": "Generally at both sea levels and high altitudes, hematocrit levels rise as children mature. [ 22 ]  These health-related causes and impacts of elevated hematocrit levels have been reported:"}
{"_id": "WikiPedia_Hematology$$$corpus_3398", "text": "Hematocrit levels were also reported to be correlated with social factors that influence subjects. In the 1966\u201380 Health Examination Survey, there was a small rise in mean hematocrit levels in female and male adolescents that reflected a rise in annual family income. Additionally, a higher education in a parent has been put into account for a rise in mean hematocrit levels of the child. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3399", "text": "Lowered hematocrit levels also pose health impacts. These causes and impacts have been reported:"}
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{"_id": "WikiPedia_Hematology$$$corpus_3402", "text": "Hemoglobin electrophoresis  is a  blood test  that can detect different types of  hemoglobin . The test can detect hemoglobin S, the form associated with  sickle cell disease , as well as other abnormal types of hemoglobin, such as  hemoglobin C . It can also be used to investigate  thalassemias , which are disorders caused by defective hemoglobin production."}
{"_id": "WikiPedia_Hematology$$$corpus_3403", "text": "The test uses the principles of  gel electrophoresis  to separate out the various types of hemoglobin and is a type of  native gel electrophoresis . After the sample has been treated to release the hemoglobin from the red cells, it is introduced into a porous gel (usually made of  agarose  or  cellulose acetate ) and subjected to an  electrical field , most commonly in an  alkaline  medium. Different hemoglobins have different charges, and according to those charges, they move at different speeds in the gel and eventually form discrete bands (see  electrophoretic migration patterns ). A  quality control  sample containing hemoglobins A, F, S, and C is run along with the patient sample to aid in identifying the different bands. [ 1 ] [ 2 ]  The relative amounts of each type of hemoglobin can be estimated by measuring the  optical density  of the bands, though this method is not reliable for hemoglobins that are present in low quantities. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3404", "text": "Because hemoglobins exhibit different migration patterns depending on the  pH  level, testing the same sample at both an acid and an alkaline pH can help to identify some abnormal hemoglobins that would otherwise be impossible to distinguish from others. [ 3 ] :\u200a437"}
{"_id": "WikiPedia_Hematology$$$corpus_3405", "text": "Adult human blood normally contains three types of hemoglobin:  hemoglobin A , which makes up approximately 95% of the total;  hemoglobin A 2 , which accounts for less than 3.5%; and a minute amount of  hemoglobin F . [ 3 ] :\u200a140\u200a  If abnormal hemoglobin variants such as hemoglobin S (which occurs in  sickle cell disease ),  C  or  E  are present, they will appear as unexpected bands on electrophoresis (provided they do not migrate to the same place as other hemoglobins). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3406", "text": "Hemoglobin electrophoresis can also be used to investigate  thalassemias , which are caused by decreased production of subunits of the hemoglobin molecule. Hemoglobin A 2  levels are typically elevated in  beta-thalassemia minor  and hemoglobin F may be slightly increased. In  beta-thalassemia major , hemoglobin A is decreased (or in some cases absent) and hemoglobin F is markedly elevated; A 2  levels are variable. [ 3 ] :\u200a461\u20132\u200a  In  hemoglobin H disease , a form of  alpha-thalassemia , an abnormal band of hemoglobin H can be detected, and sometimes a band of  Hemoglobin Barts ; but in the milder  alpha-thalassemia trait , electrophoresis results are effectively normal. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3407", "text": "Linus Pauling  is credited with the invention of hemoglobin electrophoresis in 1949. Newer alternatives to conventional hemoglobin electrophoresis include  isoelectric focusing ,  capillary zone electrophoresis , and  high-performance liquid chromatography . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3408", "text": "Hemoximetry  is the monitoring of  hemoglobin  and  oxygen saturation , especially during procedures such as  cardiac catheterization . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3409", "text": "Hemoximetry presents hemoglobin oxygen saturation, dyshemoglobines, and total hemoglobin concentration data. The functional oxygen saturation measured by this procedure is the basis for calibrating  pulse oximeters . Pulse oximeters cannot be calibrated using physical procedures, but only by directly comparing the reported measurements and the parallel arterial oxygen saturation measured by hemoximetry in a group of healthy subjects. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3410", "text": "INR self-monitoring  is a medical kit that is used by patients both on long-term and on lifetime anti-coagulation therapy to measure their INR ( International Normalized Ratio ) levels themselves at your premises without going to a clinic. People who self-monitor their INR levels use a portable INR monitor as in a clinic. It requires the patient to test a drop of blood, drawn from a finger at scheduled times, and record the INR level measured by a monitor."}
{"_id": "WikiPedia_Hematology$$$corpus_3411", "text": "People on anti-coagulation therapy who are self-testing provide the INR upi antem76102824@axl reading they obtain from their monitor to their healthcare professionals at an agreed time, generally by telephone. The healthcare professional decides if any change to the  warfarin  dose is required and lets the person know what action is needed. A PT/INR meter can be obtained by contacting an Independent Diagnostic Testing Facility (IDTF). [ 1 ]  They are able to provide patients with all necessary testing equipment and bill the insurance for test results reported. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3412", "text": "People who  self-manage  adjust their warfarin doses themselves, following training with their healthcare professional. This means that if the INR reading obtained from their monitor is out of the normal  therapeutic range , they are able to make an adjustment to their own warfarin dose by themselves. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3413", "text": "International normalized ratio (INR) which is a derivative of prothrombin time is a measurement of blood coagulation in the circulatory system. Both are used to determine the  clotting  rate of blood, which can be affected by anticoagulant usage, liver damage and Vitamin K levels. The preferred range of INR levels for a patient on anticoagulation therapy is usually between 2 and 3, but it tends to vary depending on the patient's requirements. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3414", "text": "Patients who self-monitor tend to choose this route for the greater control they feel it gives them over their lives and their condition. This helps to reduce the number of visits being made to their anticoagulation clinic for routine appointments to measure their INR levels. This is a lengthy process in comparison to self-testing and management. Results of clinical studies, which have been recognized by the National Patients Safety Authority (NPSA), show that people who self-monitor keep more frequently within their  therapeutic range  and have fewer complications including clots and bleeding, compared with people who have their INR levels tested only at their anticoagulation clinic. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3415", "text": "Patient self-care is a key initiative in the  NHS Plan  for a patient-centered health service and an important component in supporting people with long-term conditions. [ 3 ]  It is seen to provide:"}
{"_id": "WikiPedia_Hematology$$$corpus_3416", "text": "Self-monitoring may be a suitable option for a variety of people who are on long term anticoagulation therapy and want the convenience of being able to monitor their own INR levels at a time and place of their own choosing (e.g. if travelling abroad either with work or on vacation). They do have continuous support from their healthcare professionals and there are no upper age limits for self-monitoring and parents can take charge for their children. Self-monitoring is ideal if: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3417", "text": "In the past 5 years, there have been a number of clinical trials to highlight the advantages of self-monitoring, whether self-testing or self-managing. It also gives an indication of what improvements the self-testing and self-management can do to INR levels. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3418", "text": "\" Quality of life changed in a positive way. Independence and better organisation of vacation and spare time were most frequently mentioned advantages .\""}
{"_id": "WikiPedia_Hematology$$$corpus_3419", "text": "Extract from a study into the impact of self-monitoring on the quality of life of patients under anticoagulation therapy. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3420", "text": "\" Patient self-testing . . . is an effective method of monitoring oral anticoagulation therapy, providing outcomes at least as good as, and possibly better than, those achieved with an anti-coagulation clinic. \""}
{"_id": "WikiPedia_Hematology$$$corpus_3421", "text": "From international consensus guidelines prepared by the International Self-Monitoring Association for Oral Anti-coagulation. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3422", "text": "\" Self-monitoring can improve the quality of oral anti-coagulation therapy, with patients more frequently in the therapeutic range, while improving benefits and decreasing harm .\""}
{"_id": "WikiPedia_Hematology$$$corpus_3423", "text": "From the conclusions of a review of studies of self-monitoring in oral anti-coagulation therapy. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3424", "text": "The results of the study  Effect of Home Testing of International Normalized Ratio on Clinical Events  (2010), comparing whether weekly home-testing of the INR-level offers any advantage over monthly testing in a clinic, reduces the risk of a major hemorrhage event (i.e.  stroke , major bleeding, or death), indicated that the time to the first primary-event (stroke, major bleeding, or death) was not significantly longer in the self-testing group of patients than in the clinic-testing group of patients (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; p=0.14). The study was a prospective, randomized, non-blinded trial for which the patients were randomized into two groups, (i) weekly INR self-testing and (ii) monthly INR clinic-testing, using a stratified method of adaptive-allocation that was determined according to the duration of anti-coagulation and the indication for  Warfarin . Although the study was non-blinded, blinding is less critical because the objective outcomes of the study: stroke, major bleeding episode, and death. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3425", "text": "Patients who are self-monitoring have to use a monitor in order to measure their INR level. There are a range of INR testing monitors on the market, such as the CoaguChek XS, [ 11 ] [ 12 ]  MicroINR., [ 13 ]  INRatio2, [ 14 ]  and  QLabs [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3426", "text": "An  insulin tolerance test  ( ITT ) is a medical diagnostic procedure during which  insulin  is injected into a patient's vein, after which blood glucose is measured at regular intervals. This procedure is performed to assess  pituitary  function,  adrenal  function,  insulin sensitivity , [ 1 ] [ 2 ]  and sometimes for other purposes. An ITT is usually ordered and interpreted by an  endocrinologist ."}
{"_id": "WikiPedia_Hematology$$$corpus_3427", "text": "When used to assess insulin sensitivity, a standard dose of insulin is administered, and blood glucose is monitored with frequent sampling. The plasma glucose disappearance rate (KITT) indicates the degree of whole-body insulin sensitivity, and correlates well with the gold-standard  glucose clamp technique . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3428", "text": "When used for assessing the integrity of the  hypothalamic\u2013pituitary\u2013adrenal axis  (HPA), insulin injections are continued to the point of inducing extreme  hypoglycemia  below 2.2\u00a0mmol/L (40\u00a0mg/dL).  Patient must have symptomatic neuroglycopenia to trigger counter-regulatory cascade. Glucose levels below 2.2\u00a0mmol/L are insufficient absent symptoms. The brain must register low glucose levels.  In response,  adrenocorticotropic hormone  (ACTH) and  growth hormone  (GH) are released as a part of the stress mechanism. ACTH elevation causes the  adrenal cortex  to release  cortisol . Normally, both cortisol and GH serve as  counterregulatory hormones , opposing the action of insulin, i.e. acting against the hypoglycemia. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3429", "text": "ITT to the point of extreme hypoglycemia is considered to be the  gold standard  for assessing the integrity of the HPA. Sometimes ITT is performed to assess the adrenal function, e.g. before  surgery . It is assumed that the ability to respond to insulin-induced hypoglycemia translates into appropriate cortisol rise in the stressful event of acute illness or major surgery. [ 4 ]  The extreme hypoglycemic version of the ITT is potentially very dangerous and must be undertaken with great care, because it can  iatrogenically  induce the equivalent of a  diabetic coma . A health professional must attend it at all times. Other provocation tests which cause much less release of growth hormone include the use of  glucagon ,  arginine  and  clonidine ."}
{"_id": "WikiPedia_Hematology$$$corpus_3430", "text": "Side effects include sweating, palpitations, loss of consciousness and rarely convulsions due to severe hypoglycemia which may cause coma. If extreme symptoms are present, glucose should be given  intravenously . In subjects with no adrenal reserve an  Addisonian crisis  may occur.  For cortisol stimulation, the  ACTH stimulation test  has much less risk. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3431", "text": "Insulin tolerance test contraindications are: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3432", "text": "The test cannot be interpreted unless hypoglycaemia (< 2.2\u00a0mmol/L (or) < 40\u00a0mg/dL) is achieved. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3433", "text": "An adequate cortisol response is defined as a rise to greater than 550 nmol/L. Patients with impaired cortisol responses (less than 550 but greater than 400 nmol/L) may only need steroid cover for major illnesses or stresses. An adequate GH response occurs with an absolute response exceeding 20 mU/L. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3434", "text": "There will be a rise of less than 170 nmol/L above the fluctuations of basal levels of cortisol. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3435", "text": "In medicine,  intravascular volume status  refers to the volume of  blood  in a patient's  circulatory system , and is essentially the  blood plasma  component of the overall  volume status  of the body, which otherwise includes both  intracellular fluid  and  extracellular fluid . Still, the intravascular component is usually of primary interest, and  volume status  is sometimes used synonymously with  intravascular volume status ."}
{"_id": "WikiPedia_Hematology$$$corpus_3436", "text": "It is related to the patient's state of hydration, but is not identical to it. For instance, intravascular volume depletion can exist in an adequately hydrated person if there is loss of water into  interstitial tissue  (e.g. due to  hyponatremia  or  liver failure )."}
{"_id": "WikiPedia_Hematology$$$corpus_3437", "text": "Volume contraction  of intravascular fluid ( blood plasma ) is termed  hypovolemia , [ 1 ] [ 2 ]  and its signs include, in order of severity:"}
{"_id": "WikiPedia_Hematology$$$corpus_3438", "text": "Signs of  intravascular volume overload  (high blood volume) include:"}
{"_id": "WikiPedia_Hematology$$$corpus_3439", "text": "For the clinical assessment of intravascular blood volume, the BVA-100, a semi-automated blood volume analyzer device that has FDA approval, determines the status of a patient\u2019s blood volume based on the Ideal Height and Weight Method. [ 3 ] \nUsing a patient\u2019s ideal weight and actual weight, the percent deviation from the desirable weight is found using the following equation:"}
{"_id": "WikiPedia_Hematology$$$corpus_3440", "text": "\u00b1 \n % \n \n \u00a0Desirable Weight \n \n = \n \n \n \n \n Actual Weight \n \n \u2212 \n \n Desirable Weight \n \n \n Desirable Weight \n \n \n \u00d7 \n 100 \n \n \n {\\displaystyle \\pm \\%{\\text{ Desirable Weight}}={\\frac {{\\text{Actual Weight}}-{\\text{Desirable Weight}}}{\\text{Desirable Weight}}}\\times 100} \n \n \nUsing the deviation from desirable weight, the BV ratio (ml/kg), i.e. Ideal Blood Volume, can be determined.\nThe machine was tested in clinical studies for the treatment of a broad range of medical conditions related to Intravascular Volume Status, such as anemia, [ 4 ]  congestive heart failure, [ 5 ]  sepsis, [ 6 ]  CFS, [ 7 ]  Hyponatremia, [ 8 ]  Syncope [ 9 ]  and more. This tool for measuring blood volume may foster improved patient care [ 10 ]  as both a stand-alone and complementary diagnostic tool as there has been a statistically significant increase in patient survival. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3441", "text": "The most common cause of  hypovolemia  is diarrhea or vomiting. The other causes are usually divided into  renal  and  extrarenal  causes. Renal causes include overuse of diuretics, or trauma or disease of the kidney.  Extrarenal causes include bleeding, burns, and any causes of  edema  (e.g. congestive heart failure, liver failure). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3442", "text": "Intravascular volume depletion is divided into three types based on the blood sodium level:"}
{"_id": "WikiPedia_Hematology$$$corpus_3443", "text": "Intravascular volume overload  can occur during surgery, if water rather than isotonic saline is used to wash the incision. It can also occur if there is inadequate urination, e.g. with certain kidney diseases. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3444", "text": "Iron tests  are groups of  clinical chemistry  laboratory  blood tests  that are used to evaluate  body iron stores  or the  iron  level in  blood serum ."}
{"_id": "WikiPedia_Hematology$$$corpus_3445", "text": "Other terms used for the same tests are  iron panel ,  iron profile ,  iron indices ,  iron status  or  iron studies ."}
{"_id": "WikiPedia_Hematology$$$corpus_3446", "text": "*  = or normal."}
{"_id": "WikiPedia_Hematology$$$corpus_3447", "text": "Jostel's TSH index  ( TSHI  or  JTI ), also referred to as  Jostel's thyrotropin index  or  Thyroid Function index  ( TFI ), is a method for estimating the thyrotropic (i.e. thyroid stimulating) function of the anterior  pituitary  lobe in a quantitative way. [ 1 ] [ 2 ]  The equation has been derived from the logarithmic standard model of  thyroid homeostasis . [ 3 ] [ 4 ] [ 5 ] [ 6 ]  In a paper from 2014 further study was suggested to show if it is useful, [ 7 ]  but the 2018 guideline by the European Thyroid Association for the diagnosis of uncertain cases of central hypothyroidism regarded it as beneficial. [ 2 ]  It is also recommended for purposes of differential diagnosis in the  sociomedical expert assessment . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3448", "text": "Jostel's TSH index can be calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_3449", "text": "from equilibrium serum concentrations of  thyrotropin  (TSH), free  T4  (FT4) and a correction coefficient derived from the logarithmic standard model (\u03b2 = 0.1345)."}
{"_id": "WikiPedia_Hematology$$$corpus_3450", "text": "An alternative standardised form ( standardised TSH index  or  sTSHI ) is calculated with. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3451", "text": "as a  z-transformed  value incorporating  mean  (2.7) and  standard deviation  (0.676) of TSHI in a reference population [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3452", "text": "The TSH index is reduced in patients with  secondary hypothyroidism  resulting from thyrotropic insufficiency. [ 1 ] [ 9 ] [ 10 ] [ 11 ]  For this indication, it has, however, up to now only been validated in adults. [ 12 ]  JTI was also found reduced in cases of  TACITUS syndrome (non-thyroidal illness syndrome)  as an example of type 1 thyroid  allostasis . [ 13 ] [ 14 ]  Conversely, an elevated thyroid function index may serve as a biomarker for type 2 allostasis and contextual stress. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3453", "text": "Jostel's TSH index may decrease under therapy with the antidiabetic drug  metformin , [ 17 ]  especially in women under oral  contraceptives . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3454", "text": "In two large population-based cohorts included in the  Study of Health in Pomerania  differentially correlated to some markers of  body composition . Correlation was positive to  body mass index  (BMI),  waist circumference  and fat mass, but negative to body cell mass. [ 19 ]  With the exception of fat mass all correlations were age-dependent. [ 19 ]  Very similar observations have been made earlier in the  NHANES  dataset. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3455", "text": "In  Parkinson's disease , JTI is significantly elevated in early sub-types of the disease compared to an advanced group. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3456", "text": "A longitudinal study in  euthyroid  subjects with  structural heart disease  found that JTI predicts the risk of malignant  arrhythmia  including  ventricular fibrillation  and  ventricular tachycardia . [ 22 ]  This applies to both incidence and event-free survival. [ 22 ]  A second study in a different population undergoing coronary angiography arrived at similar results. [ 23 ]  It was therefore concluded that an elevated set point of thyroid homeostasis may contribute to cardiovascular risk. A positive correlation of JTI to SIQALS 2, [ 16 ]  a score for  allostatic load , suggests that thyroid hormones are among the mediators linking stress to major cardiovascular endpoints. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3457", "text": "Jostel's TSH index and the  thyroid feedback quantile-based index , another biomarker for the central thyrotropic function, were observed to be elevated in certain psychiatric diseases including schizophrenia. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3458", "text": "Another study demonstrated the TSH index to inversely correlate to  thyroid's secretory capacity  and thyroid volume. [ 26 ]  It is unclear if this finding reflects shortcomings of the index (i.e. low specificity in the setting of subclinical hypothyroidism) or plastic responses of the pituitary gland to beginning hypothyroidism. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3459", "text": "In subjects with  type 2 diabetes , treatment with  beta blockers  resulted in increased TSH index, but the mechanism is unclear. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3460", "text": "Negative correlation of Jostel's TSH index to the urinary excretion of certain  phthalates  suggests that  endocrine disruptors  may affect the central set point of thyroid homeostasis. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3461", "text": "Drugs that reduce the TSH index, probably via effects on the central set point of the feedback loop, include mirtazapine [ 29 ]  and oxcarbazepine. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3462", "text": "A reduction of Jostel's TSH index may predict the development of  hypophysitis  due to therapy with  immune checkpoint inhibitors , e. g.  ipilimumab . [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3463", "text": "Kaolin clotting time  ( KCT ) is a  sensitive  test to detect  lupus anticoagulants . [ 2 ]  There is evidence that suggests it is the most sensitive test for detecting lupus anticoagulants. [ 3 ]  It can also detect  factor VIII  inhibitors but is sensitive to  unfractionated heparin  as well. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3464", "text": "The KCT on whole blood is known as the \"Activated Clotting Time\" (ACT) and is widely used in various instruments during surgery such as cardiac bypass to monitor heparin. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3465", "text": "KCT was first described by Dr. Joel Margolis in 1958. [ 6 ]  Later on, it was found to be very sensitive to lupus anticoagulants but was only reliable when test plasmas were mixed with normal plasma in various proportions. [ 3 ]  It became the preferred method for lupus anticoagulant testing after Dr. Wilhelm Lubbe showed it to be a good marker for recurrent fetal loss. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3466", "text": "KCT is similar to the  activated partial thromboplastin time  test, except it does not use exogenous  phospholipid . [ 2 ]  Thus, a confirmatory test that uses excess phospholipid is needed to validate the presence of lupus anticoagulants. [ 2 ]  Otherwise, diluting the test plasma in normal plasma before testing provides characteristic mixing patterns. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3467", "text": "Kaolin is the surface activator, and the test also requires small amounts of cell fragments and plasma lipids to provide the phospholipid surface required for coagulation. [ 2 ] [ 4 ]  Therefore, the sample quality is important for the validity of the screening test. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3468", "text": "The test combines a test  plasma  with  kaolin , and after a brief pre-incubation and the addition of calcium chloride, the time to clot (in seconds) is measured. [ 6 ]  Mixes of patient plasma with normal plasma are recommended for testing. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3469", "text": "The KCT test/control ratio of greater than or equal to 1.2 indicates that a defect is present. [ 4 ]  If the test/control ratio is between 1.1 and 1.2, the test is equivocal. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3470", "text": "A good way of expressing the result using mixes is to calculate the Rosner index. [ 10 ]  If A is the KCT of normal plasma, B is that of the 1:1 mix and C is that of the patient plasma, then the Rosner index is 100x(B-A)/C. Values above 15 indicate a positive result but in most cases labs set their own cutoff values. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3471", "text": "If the KCT is less than 60 seconds, this suggests that the test plasma is contaminated with platelet fragments; therefore, the test is not valid. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3472", "text": "The  Kleihauer\u2013Betke (\"KB\") test ,  Kleihauer\u2013Betke (\"KB\") stain ,  Kleihauer test  or  acid elution test  is a  blood test  used to measure the amount of  fetal hemoglobin  transferred from a  fetus  to a mother's  bloodstream . [ 1 ]  It is usually performed on  Rh-negative  mothers to determine the required dose of  Rho(D) immune globulin  (RhIg) to inhibit formation of Rh  antibodies  in the mother and prevent  Rh disease  in future Rh-positive children. [ 2 ]  It is named after Enno Kleihauer and Klaus Betke who described it in 1957."}
{"_id": "WikiPedia_Hematology$$$corpus_3473", "text": "The KB test is the standard method of quantitating  fetal\u2013maternal hemorrhage  (FMH). It takes advantage of the differential resistance of fetal hemoglobin to acid. A standard  blood smear  is prepared from the mother's  blood  and exposed to an acid bath. This removes adult  hemoglobin , but not fetal hemoglobin, from the red blood cells. Subsequent staining, using Shepard's method, [ 3 ]  makes fetal cells (containing fetal hemoglobin) appear rose-pink in color, while adult red blood cells are only seen as \"ghosts\". 2,000 cells are counted under the microscope and a percentage of fetal to maternal cells is calculated. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3474", "text": "In those with positive tests, follow up testing at a  postpartum  check should be done to rule out the possibility of a  false positive . This could be caused by a  hemoglobinopathy  in the mother which causes persistent elevation of fetal hemoglobin, e.g.  sickle cell trait . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3475", "text": "Comparison with other more expensive or technologically advanced methods such as  flow cytometry  has shown that the KB stain, like the more advanced methods, is sensitive in its detection of FMH. [ 1 ]  However, publications have shown that in comparison with flow cytometry methods, the KB Test overestimates FMH due to false positive results when F-cells are present in the maternal blood sample. Background counting errors can result in estimates of as much as 5\u00a0mL fetal  blood loss  when there actually is no such blood loss, but standard methods available in most laboratories admit an extremely low probability of the return of a false positive when more severe FMH has taken place. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3476", "text": "Thin smears are prepared from capillary blood or venous blood collected into anticoagulants such as  heparin ,  oxalate ,  citrate , or  EDTA . Smears are air dried between 10 and 60 minutes, fixed in 80 vol% ethanol for 5 min at 20-22\u00a0\u00b0C, rinsed with tap water, and air dried. Films are then immersed in the citrate-phosphate buffer for 5 minutes at 37\u00a0\u00b0C and gently agitated for about 3 minutes. Slides are rinsed with tap water, dried, and stained with Ehrlich's acid hematoxylin for 3 min, rinsed with water, and dried again. They are counterstained with erythrosine for 3 min. After a final rinse, films are dried and examined under light microscopy. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3477", "text": "Hemoglobin F cells are densely stained with erythrosine, Hemoglobin A cells appear as ghost cells, while intermediate cells are stained more or less pink. Reticulocytes containing Hemoglobin A may appear as intermediate cells and/or may show intracellular granulation.  Inclusion bodies  (Heinz bodies, precipitated \u03b1-chains or \u03b2-chains) are visible in eluted cells as compact inclusions of different size. Hemoglobin A is eluted regardless of whether it is oxyhemoglobin, methemoglobin, cyanmethemoglobin, reduced hemoglobin, or carboxyhemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_3478", "text": "Methods developed by Schneider and Ludwig [ 5 ]  and Bartsch' are recommended. For determination of the intracellular distribution of Hemoglobin F, the semi-quantitative method of Shepard, Weatherall, and Conley' may be employed."}
{"_id": "WikiPedia_Hematology$$$corpus_3479", "text": "Normal values for Hemoglobin F cells in adults as published originally by Kleihauer were below 0.01%; in full-term newborns they are above 90%."}
{"_id": "WikiPedia_Hematology$$$corpus_3480", "text": "To determine if a positive test for FMH indicates the likely cause of fetal death, the percent of total fetal blood volume lost should be calculated, making appropriate adjustments based on the following known relationships:"}
{"_id": "WikiPedia_Hematology$$$corpus_3481", "text": "These  constraints  can then be applied to yield the formula"}
{"_id": "WikiPedia_Hematology$$$corpus_3482", "text": "where"}
{"_id": "WikiPedia_Hematology$$$corpus_3483", "text": "An estimate of the required number of Rho(D) immune globulin vials may assume the following equations: [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3484", "text": "Combining those two equations results in: [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3485", "text": "This is approximately equal to:"}
{"_id": "WikiPedia_Hematology$$$corpus_3486", "text": "Practically, if the number to the right of the decimal point is \u22655, it is rounded up to add one vial. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3487", "text": "Suppose that a KB stain is performed and  \n \n \n \n T \n C \n = \n 5000 \n \n \n {\\displaystyle TC=5000} \n \n  total red blood cells are observed,  \n \n \n \n F \n C \n = \n 200 \n \n \n {\\displaystyle FC=200} \n \n  of which are found to be fetal red blood cells.  Suppose further that the stillbirth weight of the fetus under consideration is  \n \n \n \n F \n W \n = \n 2.0 \n k \n g \n \n \n {\\displaystyle FW=2.0kg} \n \n .  Then we would conclude that the total percentage of fetal blood lost is approximately:"}
{"_id": "WikiPedia_Hematology$$$corpus_3488", "text": "to five  significant digits .  We would hence conclude that the fetus under consideration lost 66.667% (two-thirds) of its blood via FMH.  Generally, stillbirth is highly probable for any value of  \n \n \n \n P \n F \n B \n \u2265 \n 20 \n \n \n {\\displaystyle PFB\\geq 20} \n \n , particularly if the fetus abruptly loses this much blood; in this example, we would hence be likely to suspect FMH as the cause of the stillbirth.  It is important to note, however, that such a  diagnosis  is still not completely conclusive; fetuses losing large quantities of blood over long periods of time are able to compensate for this slower blood loss; since the KB stain tells us nothing with regard to the level of acuity of FMH.  This means that it is not possible to entirely correlate a positive KB stain and high  \n \n \n \n P \n F \n B \n \n \n {\\displaystyle PFB} \n \n  with a stillbirth, though in many cases, given other information, such as known hereditary complications of pregnancy, extremely high positive  correlation coefficients   \n \n \n \n r \n \u2248 \n + \n 1.000 \n \n \n {\\displaystyle r\\approx +1.000} \n \n  between FMH and stillbirth have been observed. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3489", "text": "Since fetal and maternal  blood cells  have the same life expectancy in the maternal bloodstream, it is possible to obtain informative results from a KB stain for a fair period of time after a stillbirth. However, if the mother and fetus are  ABO  incompatible, it is more crucial to quickly perform the KB stain following a stillbirth, as the fetal red blood cells will be eliminated from the maternal bloodstream quickly, causing the KB stain to underestimate the degree of FMH, if any. Much concern has been raised in the literature concerning false positives when sampling is done after delivery. In general this is not a problem. Delivery does result in higher frequency of detection of micro-hemorrhages but this should not confound interpretation of FMH as a possible cause of stillbirth. It is not necessary to draw the sample before induction, onset of labor, delivery, placental delivery etc. despite what some published literature purports. However, if Caesarean section is to be used, failure to draw the sample prior to that will result in a 2% false positive rate. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3490", "text": "Finally, anything which causes persistence of fetal hemoglobin in maternal blood cells will make interpretation much trickier. Certain  hemoglobinopathies , the most common of which is sickle cell trait, do this. Overall, somewhere around 1\u20133% of the time this could result in false interpretation."}
{"_id": "WikiPedia_Hematology$$$corpus_3491", "text": "An article published in 2004 concluded that a Kleihauer-Betke (KB) test is necessary in all cases of maternal trauma, as clinical evaluation is not sensitive enough for determination of risk of pre-term labour. It accurately predicts the risk of preterm labor after maternal trauma whereas the article concluded that clinical assessment does not. With a negative KB test, posttrauma electronic fetal monitoring duration may be limited safely. With a positive KB test, the significant risk of pre-term labour mandates detailed monitoring. KB testing has important advantages to all maternal trauma victims, regardless of Rh status. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3492", "text": "A  latex fixation test , also called a  latex agglutination assay  or  test  ( LA assay  or  test ), is an  assay  used clinically in the identification and  typing  of many important  microorganisms . These tests use the patient's  antigen - antibody  immune response. This response occurs when the body detects a  pathogen  and forms an antibody specific to an identified antigen (a protein configuration) present on the surface of the pathogen. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3493", "text": "Agglutination tests, specific to a variety of pathogens, can be designed and manufactured for clinicians by coating  microbeads  of  latex  with pathogen-specific antigens or antibodies.  In performing a test, laboratory clinicians will mix a patient's  cerebrospinal fluid ,  serum  or  urine  with the coated latex particles in  serial dilutions  with  normal saline  (important to avoid the  prozone effect ) and observe for  agglutination  (clumping). Agglutination of the beads in any of the dilutions is considered a positive result, confirming either that the patient's body has produced the pathogen-specific antibody (if the test supplied the antigen) or that the specimen contains the pathogen's antigen (if the test supplied the antibody). Instances of  cross-reactivity  (where the antibody sticks to another antigen besides the antigen of interest) can lead to confusing results."}
{"_id": "WikiPedia_Hematology$$$corpus_3494", "text": "Agglutination techniques are used to detect antibodies produced in response to a variety of  viruses  and  bacteria , as well as  autoantibodies , which are produced against the self in  autoimmune diseases . For example, assays exist for  rubella virus ,  rotavirus , and  rheumatoid factor , and an excellent LA test is available for  cryptococcus . [ 1 ]  Agglutination techniques are also used in definitive diagnosis of  group A streptococcal infection ."}
{"_id": "WikiPedia_Hematology$$$corpus_3495", "text": "A  lipid profile  or  lipid panel  is a  panel  of  blood tests  used to find abnormalities in  blood lipid  ( such as  cholesterol  and  triglycerides ) concentrations. [ not verified in body ]  The results of this test can identify certain  genetic diseases  and can determine approximate risks for  cardiovascular disease , certain forms of  pancreatitis , and other diseases."}
{"_id": "WikiPedia_Hematology$$$corpus_3496", "text": "Lipid panels are usually ordered as part of a  physical exam , along with other panels such as the  complete blood count  (CBC) and  basic metabolic panel  (BMP). [ not verified in body ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3497", "text": "A lipid profile report typically includes: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3498", "text": "LDL is not usually actually measured, but calculated from the other three using the  Friedewald equation . [ 1 ]  A laboratory can optionally calculate the two extra values from the report:"}
{"_id": "WikiPedia_Hematology$$$corpus_3499", "text": "Recommendations for cholesterol testing come from the Adult Treatment Panel (ATP) III guidelines, and are based on many large clinical studies, such as the  Framingham Heart Study . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3500", "text": "For healthy adults with no cardiovascular risk factors, the ATP III guidelines recommend screening once every five years. [ 2 ]  A lipid profile may also be ordered at regular intervals to evaluate the success of lipid-lowering drugs such as  statins . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3501", "text": "In the pediatric and adolescent population, lipid testing is not routinely performed. However, the  American Academy of Pediatrics  and the  National Heart, Lung, and Blood Institute  (NHLBI) recommend that children aged 9\u201311 be screened once for severe cholesterol abnormalities. [ 3 ]  This screening can be valuable to detect  genetic diseases  such as  familial hypercholesterolemia  that can be lethal if not treated early. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3502", "text": "Traditionally, most laboratories have required patients to fast for 9\u201312 hours before screening. However, studies have questioned the utility of  fasting  before lipid panels, and some diagnostic labs routinely accept non-fasting samples. [ 4 ] [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3503", "text": "Typically the laboratory measures only three quantities: total cholesterol; HDL; Triglycerides. A typical procedure used by  NHANES  2004 uses the following measurement methods: [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3504", "text": "From these three data LDL may be calculated. According to Friedewald's equation: [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3505", "text": "Other calculations of LDL from those same three data have been proposed which yield some significantly different results. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3506", "text": "VLDL can be defined as the total cholesterol that is neither HDL nor LDL. With that definition, Friedewald's equation [ 9 ]  yields:"}
{"_id": "WikiPedia_Hematology$$$corpus_3507", "text": "The alternative calculations mentioned above may yield significantly different values for VLDL."}
{"_id": "WikiPedia_Hematology$$$corpus_3508", "text": "The Friedewald method is reasonably reliable for the majority of patients, but is notably inaccurate in patients with  hypertriglyceridemia  (> 400 mg/dL or 4.5 mmol/L). It also underestimates LDL-C in patients with low LDL-C (< 25 mg/dL or 0.6 mmol/L). It does not take into account  intermediate-density lipoprotein . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3509", "text": "A \"Martin/Hopkins\" variation that takes into how triglycerides-to-VLDL ratio tends to vary with other parameters appears more reliable and accurate. [ 11 ] [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3510", "text": "Every part of the lipid panel can be measured directly using ultracentrifugation, which is the  gold standard . [ 1 ]   This type of measurement involves no errors from estimation and can also measure  IDL -C and  Lp(a) -C levels. Fully direct measurement is more costly, however. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3511", "text": "Laboratories may also use proprietrary tests for \"direct chemical LDL-C\" which require no prior separation by centrifugation. These tests are not yet standardized in US and Europe and lack validation. [ 13 ]  A specific version of the test seems popular in Japan, however. [ 15 ]  A number of other LDL-C determination methods have been used in the past or have been proposed for future use. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3512", "text": "This test is used to identify  dyslipidemia  (various disturbances of cholesterol and triglyceride levels), many forms of which are recognized risk factors for  cardiovascular disease  and rarely  pancreatitis ."}
{"_id": "WikiPedia_Hematology$$$corpus_3513", "text": "A total cholesterol reading can be used to assess an individual's risk for heart disease; however, it should not be relied upon as the only indicator. The individual components that make up total cholesterol reading\u2014 LDL ,  HDL , and  VLDL \u2014are also important in measuring risk. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3514", "text": "For instance, someone's total cholesterol may be high, but this may be due to very high HDL (\"good cholesterol\") cholesterol levels,\u2014which can help prevent heart disease (the test is mainly concerned with high LDL, or \"bad cholesterol\" levels). So, while a high total cholesterol level may help give an indication that there is a problem with cholesterol levels, the components that make up total cholesterol should also be measured. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3515", "text": "Live blood analysis  ( LBA ),  live cell analysis ,  Hemaview  or  nutritional blood analysis  is the use of high-resolution  dark field microscopy  to observe live blood cells. Live blood analysis is promoted by some  alternative medicine  practitioners, who assert that it can diagnose a range of diseases. There is no  scientific evidence  that live blood analysis is reliable or effective, and it has been described as a fraudulent means of convincing people that they are ill and should purchase  dietary supplements . [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3516", "text": "Live blood analysis is not accepted in laboratory practice and its validity as a laboratory test has not been established. [ 4 ]  There is no scientific evidence for the validity of live blood analysis, [ 4 ]  it has been described as a pseudoscientific, bogus and fraudulent medical test, [ 5 ] [ 6 ]  and its practice has been dismissed by the medical profession as  quackery . [ 7 ]  The field of live blood microscopy is  unregulated , there is no training requirement for practitioners and no recognised qualification, no recognised medical validity to the results, and proponents have made false claims about both medical  blood pathology testing  and their own services, which some have refused to amend when instructed by the  Advertising Standards Authority . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3517", "text": "It has its origins in the now-discarded theories of  pleomorphism  promoted by  G\u00fcnther Enderlein , notably in his 1925 book  Bakterien-Cyklogenie ."}
{"_id": "WikiPedia_Hematology$$$corpus_3518", "text": "In January 2014 prominent live blood proponent and teacher  Robert O. Young  was arrested and charged for practising medicine without a license, [ 9 ]  and in March 2014 Errol Denton, a former student of his, a UK live blood practitioner, was convicted on nine counts in a rare prosecution under the  Cancer Act 1939 , [ 7 ]  followed in May 2014 by another former student, Stephen Ferguson. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3519", "text": "Proponents claim that live blood analysis provides information \"about the state of the immune system, possible vitamin deficiencies, amount of toxicity, pH and mineral imbalance, areas of concern and weaknesses, fungus and yeast.\" Some even claim it can \"spot cancer and other degenerative immune system diseases up to two years before they would otherwise be detectable\" or say they can diagnose \"lack of oxygen in the blood, low trace minerals, lack of exercise, too much alcohol or yeast, weak kidneys, bladder or spleen.\" [ 1 ]  Practitioners include alternative medicine providers such as nutritionists, herbologists, naturopaths, and chiropractors. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3520", "text": "Dark field microscopy  is useful to enhance contrast in unstained samples, but live blood analysis is not proven to be useful for any of its claimed indications. Two journal articles published in the alternative medical literature found that darkfield microscopy seemed unable to detect cancer, and that live blood analysis lacked reliability,  reproducibility , and  sensitivity and specificity . [ 10 ] [ 11 ]   Edzard Ernst , professor of  complementary medicine  at the  University of Exeter  and  University of Plymouth , notes: \"No credible scientific studies have demonstrated the reliability of LBA for detecting any of the above conditions.\" Ernst describes live blood analysis as a \"fraudulent\" means of convincing patients to buy  dietary supplements . [ 1 ] \n Quackwatch  has been critical of live blood analysis, noting dishonesty in the claims brought forward by its proponents. [ 12 ]  The alternative medicine popularizer  Andrew Weil  dismissed live blood analysis as \"completely bogus\", writing: \"Dark-field microscopy combined with live blood analysis may sound like cutting-edge science, but it's old-fashioned hokum. Don't buy into it.\" [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3521", "text": "There are several common diagnoses by the LBA practitioners that are actually based on observation of artifacts normally found in microscopy, and ignorance of basic biological science: [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3522", "text": "Acid in the blood:  When the  red blood cells  stack on top of one another and appear like stacks of coins, it is called ' rouleaux ' formation.   By observation of the rouleaux, the LBA practitioners diagnose 'acid in the blood', while other practitioners suggest a weak pancreas.  Rouleaux of red blood cells under the microscope is an artifact which occurs when the blood sample at the edge of the coverslip [ 15 ]  starts to dry out; where a large number of red blood cells clump together; or when the blood starts to clot when contacted with the glass.  These artifacts are observed in only small, selected areas on the slide, while near the center of the slide the red blood cells are free floating.  Blood  acidosis  is a severe illness and can not be diagnosed by observation of blood, nor treated by dietary supplements. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3523", "text": "In 1996, the Pennsylvania Department of Laboratories informed three Pennsylvania chiropractors that Infinity2's \"Nutritional Blood Analysis\" could not be used for diagnostic purposes unless they maintain a laboratory that has both state and federal certification for complex testing. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3524", "text": "In 2001, the  Health and Human Services  Office of the Inspector General issued a report on regulation of \"unestablished laboratory tests\" that focused on live blood cell analysis and the difficulty of regulating unestablished tests and laboratories. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3525", "text": "In 2002, an Australian  naturopath  was convicted and fined for  falsely claiming  that he could diagnose illness using live blood analysis [ 17 ]  after the death of a patient. He was acquitted of  manslaughter . He subsequently changed his name and was later banned from practice for life. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3526", "text": "In 2005, the  Rhode Island  Department of Health ordered a  chiropractor  to stop performing live blood analysis. An attorney for the State Board of Examiners in Chiropractic Medicine described the test as \"useless\" and a \"money-making scheme... The point of it all is apparently to sell nutritional supplements.\" A state medical board official said that live blood analysis has no discernible value, and that the public \"should be very suspicious of any practitioner who offers this test.\" [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3527", "text": "In 2011, the UK  General Medical Council  suspended a doctor's licence to practise after he used live blood analysis to diagnose patients with  Lyme disease . The doctor accepted he had been practising \"bad medicine\". [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3528", "text": "In 2013, following several  Advertising Standards Authority  adjudications  [ 20 ]  against claims made by LBA practitioners, the  Committee of Advertising Practice  added new guidelines to their  AdviceOnline  database advising what LBA marketers may claim in their advertising material. These state that \"CAP is yet to see any evidence for the efficacy of this therapy which, without rigorous evidence to support it, should be advertised on an availability-only platform.\" [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3529", "text": "One of these practitioners, Errol Denton, who practised out of a serviced office in Harley Street, was prosecuted in December 2013 under the  Cancer Act 1939 , and chose to use a  Freeman on the Land  defence. [ 22 ]  On March 20, 2014, he was convicted on nine counts under the  Cancer Act 1939  and fined \u00a39,000 plus around \u00a310,000 in costs. [ 7 ] [ 23 ]  In April 2018, Denton was further convicted of two counts of \"engaging in unfair commercial practice\" and one of \"selling food not of the quality demanded\", for selling a bottle of  colloidal silver  drink to an undercover  trading standards  officer in February 2016, after examining a drop of her blood and from it claiming that she had dislocated her shoulder. [ 24 ] [ 25 ]  He was made the subject of a  Criminal Behaviour Order , fined \u00a32,250, and ordered pay \u00a315,000 in costs. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3530", "text": "Liver function tests  ( LFTs  or  LFs ), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's  liver . [ 1 ]  These tests include  prothrombin time  (PT/INR),  activated partial thromboplastin time  (aPTT),  albumin ,  bilirubin  (direct and indirect), and others. The liver transaminases  aspartate transaminase (AST or SGOT)  and  alanine transaminase (ALT or SGPT)  are useful biomarkers of liver injury in a patient with some degree of intact liver function. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3531", "text": "Most  liver diseases  cause only mild symptoms initially, but these diseases must be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance.  This testing is performed on a patient's blood sample. Some tests are associated with functionality (e.g., albumin), some with cellular integrity (e.g.,  transaminase ), and some with conditions linked to the biliary tract ( gamma-glutamyl transferase  and  alkaline phosphatase ). Because some of these tests do not measure function, it is more accurate to call these liver chemistries or liver tests rather than liver function tests. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3532", "text": "Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used to detect the presence of liver disease. They can help distinguish among different types of liver disorders, gauge the extent of known liver damage, and monitor the response to treatment. Some or all of these measurements are also carried out (usually about twice a year for routine cases) on individuals taking certain medications, such as anticonvulsants, to ensure that these medications are not adversely impacting the person's liver. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3533", "text": "Standard liver tests for assessing liver damage include alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Bilirubin may be used to estimate the excretory function of the liver and coagulation tests and albumin can be used to evaluate the metabolic activity of the liver. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3534", "text": "Although example reference ranges are given, these will vary depending on method of analysis used at the administering laboratory, as well as age, gender, ethnicity, and potentially unrelated health factors. Individual results should always be interpreted using the reference range provided by the laboratory that performed the test. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3535", "text": "Measurement of total  bilirubin  includes both unconjugated (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of  heme  (a part of  hemoglobin  in red blood cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it (modified to make it water-soluble) through an enzyme named  UDP-glucuronyl-transferase . When the total bilirubin level exceeds 17 \u03bcmol/L, it indicates liver disease. When total bilirubin levels exceed 40 \u03bcmol/L, bilirubin deposition at the sclera, skin, and mucous membranes will give these areas a yellow colour, thus it is called  jaundice . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3536", "text": "The increase in predominantly unconjugated bilirubin is due to overproduction, reduced hepatic uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due to the reabsorption of a  haematoma  and ineffective  erythropoiesis  leading to increased red blood cell destruction.  Gilbert's syndrome  and  Crigler\u2013Najjar syndrome  have defects in the  UDP-glucuronyl-transferase  enzyme, affecting bilirubin conjugation. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3537", "text": "The degree of rise in conjugated bilirubin is directly proportional to the degree of hepatocyte injury. Viral  hepatitis  can also cause the rise in conjugated bilirubin. In parenchymal liver disease and incomplete extrahepatic obstruction, the rise in conjugated bilirubin is less than the complete  common bile duct  obstruction due to malignant causes. In  Dubin\u2013Johnson syndrome , a mutation in  multiple drug-resistance protein 2 (MRP2)  causes a rise in conjugated bilirubin. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3538", "text": "In  acute appendicitis , total bilirubin can rise from 20.52 \u03bcmol/L to 143 \u03bcmol/L. In pregnant women, the total bilirubin level is low in all three trimesters. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3539", "text": "The measurement of bilirubin levels in the newborns is done through the use of bilimeter or transcutanoeus bilirubinometer instead of performing LFTs. When the total serum bilirubin increases over 95th percentile for age during the first week of life for high risk babies, it is known as hyperbilirubinemia of the newborn ( neonatal jaundice ) and requires  light therapy  to reduce the amount of bilirubin in the blood. Pathological jaundice in newborns should be suspected when the serum bilirubin level rises by more than 5\u00a0mg/dL per day, serum bilirubin more than the physiological range, clinical jaundice more than 2 weeks, and conjugated bilirubin (dark urine staining clothes).  Haemolytic jaundice  is the commonest cause of pathological jaundice. Those babies with Rh hemolytic disease, ABO incompatibility with the mother,  Glucose-6-phosphate dehydrogenase  (G-6-PD) deficiency and minor blood group incompatibility are at increased risk of getting haemolytic jaundice. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3540", "text": "Apart from being found in high concentrations in the liver, ALT is found in the kidneys, heart, and muscles. It catalyses the  transamination  reaction, and only exists in a cytoplasmic form. Any kind of liver injury can cause a rise in ALT. A rise of up to 300 IU/L is not specific to the liver, but can be due to the damage of other organs such as the kidneys or muscles. When ALT rises to more than 500 IU/L, causes are usually from the liver. It can be due to hepatitis, ischemic liver injury, and toxins that causes liver damage. The ALT levels in  hepatitis C  rises more than in hepatitis A and B. Persistent ALT elevation more than 6 months is known as  chronic hepatitis .  Alcoholic liver disease ,  non-alcoholic fatty liver disease  (NAFLD), fat accumulation in liver during childhood obesity,  steatohepatitis  (inflammation of fatty liver disease) are associated with a rise in ALT. Rise in ALT is also associated with reduced insulin response, reduced glucose tolerance, and increased free  fatty acids  and  triglycerides . Bright liver syndrome (bright liver on ultrasound suggestive of fatty liver) with raised ALT is suggestive of  metabolic syndrome . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3541", "text": "In pregnancy, ALT levels would rise during the second trimester. In one of the studies, measured ALT levels in pregnancy-related conditions such as  hyperemesis gravidarum  was 103.5 IU/L,  pre-eclampsia  was 115,  HELLP syndrome  was 149. ALT levels would reduce by greater than 50% in three days after child delivery. Another study also shows that  caffeine  consumption can reduce the risk of ALT elevation in those who consume alcohol, overweight people, impaired glucose metabolism, and viral hepatitis. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3542", "text": "AST exists in two  isoenzymes  namely mitochondrial form and cytoplasmic form. It is found in highest concentration in the liver, followed by heart, muscle, kidney, brain, pancreas, and lungs. [ 10 ]  This wide range of AST containing organs makes it a relatively less specific indicator of liver damage compared to ALT. An increase of mitochondrial AST in bloods is highly suggestive of tissue  necrosis  in  myocardial infarction  and chronic liver disease. More than 80% of the liver AST activity are contributed by mitochondrial form of the isoenzymes, while the circulating AST in blood are contributed by cytoplasmic form of AST. AST is especially markedly raised in those with  liver cirrhosis . [ 6 ]  AST can be released from a variety of other tissues and if the elevation is less than two times the normal AST, no further workup needs to be performed if a patient is proceeding to surgery. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3543", "text": "In certain pregnancy related conditions such as hyperemesis gravidarum, AST can reach as high as 73 IU/L, 66 IU/L in pre-eclampsia, and 81 IU/L in HELLP syndrome. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3544", "text": "The AST/ALT ratio increases in liver functional impairment. In alcoholic liver disease, the mean ratio is 1.45, and mean ratio is 1.33 in post necrotic liver cirrhosis. Ratio is greater than 1.17 in viral cirrhosis, greater than 2.0 in alcoholic hepatitis, and 0.9 in non-alcoholic hepatitis. Ratio is greater than 4.5 in  Wilson disease  or  hyperthyroidism . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3545", "text": "Alkaline phosphatase  (ALP) is an enzyme in the cells lining the  biliary ducts  of the liver.  It can also be found on the mucosal epithelium of the small intestine,  proximal convoluted tubule  of the kidneys, bone, liver, and placenta. It plays an important role in lipid transposition in small intestines and calcification of bones. 50% of all the serum ALP activities in blood are contributed by bone. Acute viral hepatitis usually has normal or increased ALP. For example, hepatitis A has increased ALP due to  cholestasis  (impaired bile formation or bile flow obstruction) and would have the feature of prolonged itching. Other causes include: infiltrative liver diseases, granulomatous liver disease, abscess,  amyloidosis  of the liver and  peripheral arterial disease . Mild elevation of ALP can be seen in liver cirrhosis, hepatitis, and  congestive cardiac failure . Transient  hyperphosphataemia  is a benign condition in  infants , and can reach normal level in 4 months. In contrast, low levels of ALP is found in  hypothyroidism ,  pernicious anemia ,  zinc deficiency , and  hypophosphatasia . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3546", "text": "ALP activity is significantly increased in the third trimester of  pregnancy . [ 11 ]  This is due to increased synthesis from the  placenta  as well as increased synthesis in the  liver  induced by large amounts of estrogens. [ 11 ] [ 12 ] [ 13 ]  Levels in the third trimester can be as much as 2-fold greater than in non-pregnant women. [ 11 ]  As a result, ALP is not a reliable marker of hepatic function in pregnant women. [ 11 ]  In contrast to ALP, levels of ALT, AST, GGT, and  lactate dehydrogenase  are only slightly changed or largely unchanged during pregnancy. [ 11 ]   Bilirubin  levels are significantly decreased in pregnancy. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3547", "text": "In pregnancy conditions such as hyperemesis gravdirum, ALP levels can reach 215 IU/L, meanwhile, in pre-eclampsia, ALP can reach 14 IU/L, and in HELLP syndrome ALP levels can reach 15 IU/L. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3548", "text": "GGT is a microsomal enzyme found in hepatocytes, biliary epithelial cells, renal tubules, pancreas, and intestines. It helps in  glutathione  metabolism by transporting peptides across the cell membrane. Much like ALP, GGT measurements are usually elevated if cholestasis is present. [ 10 ]  In acute viral hepatitis, the GGT levels can peak at 2nd and 3rd week of illness, and remained elevated at 6 weeks of illness. GGT is also elevated in 30% of the hepatitis C patients. GGT can increase by 10 times in alcoholism. GGT can increase by 2 to 3 times in 50% of the patients with non-alcoholic liver disease. When GGT levels is elevated, the  triglyceride  level is elevated also. With insulin treatment, the GGT level can reduce. Other causes of elevated GGT are: diabetes mellitus,  acute pancreatitis , myocardial infarction,  anorexia nervosa ,  Guillain\u2013Barr\u00e9 syndrome , hyperthyroidism, obesity and  myotonic dystrophy . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3549", "text": "In pregnancy conditions GGT activity is reduced in 2nd and 3rd trimesters. In hyperemesis gravidarum, GGT level value can reach 45 IU/L, 17 IU/L in pre-eclampsia, and 35 IU/L in HELPP syndrome. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3550", "text": "Albumin  is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein (the remaining constituents are primarily  globulins ). Albumin levels are decreased in chronic liver disease, such as  cirrhosis . It is also decreased in  nephrotic syndrome , where it is lost through the urine.  The consequence of low albumin can be edema since the intravascular  oncotic pressure  becomes lower than the extravascular space. An alternative to albumin measurement is prealbumin, which is better at detecting acute changes (half-life of albumin and prealbumin is about 2 weeks and about 2 days, respectively). [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3551", "text": "Other tests are requested alongside LFT to rule out specific causes."}
{"_id": "WikiPedia_Hematology$$$corpus_3552", "text": "5'  Nucleotidase  (5NT) is a  glycoprotein  found throughout the body, in the cytoplasmic membrane, catalyzing the conversion to inorganic phosphates from nucleoside-5-phosphate. Its level is raised in conditions such as obstructive jaundice, parenchymal liver disease, liver metastases, and bone disease. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3553", "text": "Serum NT levels are higher during 2nd and 3rd trimesters in pregnancy. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3554", "text": "Ceruloplasmin is an  acute phase protein  synthesized in the liver. It is the carrier of the copper ion. Its level is increased in infections,  rheumatoid arthritis , pregnancy, non-Wilson liver disease and obstructive jaundice. In Wilson disease, the ceruloplasmin level is depressed which lead to copper accumulation in body tissues. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3555", "text": "Alpha-fetoprotein (AFP) is significantly expressed in foetal liver. However, the mechanism that led to the suppression of AFP synthesis in adults is not fully known. Exposure of the liver to cancer-causing agents and arrest of liver maturation in childhood can lead to the rise in AFP. AFP can reach until 400\u2013500 \u03bcg/L in  hepatocellular carcinoma . AFP concentration of more than 400 \u03bcg/L is associated with greater tumour size, involvement of both lobes of liver, portal vein invasion and a lower median survival rate. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3556", "text": "The liver is responsible for the production of the vast majority of  coagulation  factors. In patients with liver disease,  international normalized ratio  (INR) can be used as a marker of liver synthetic function as it includes  factor VII , which has the shortest half life (2\u20136 hours) of all coagulation factors measured in INR. An elevated INR in patients with liver disease, however, does not necessarily mean the patient has a tendency to bleed, as it only measures procoagulants and not anticoagulants. In liver disease the synthesis of both are decreased and some patients are even found to be hypercoagulable (increased tendency to clot) despite an elevated INR. In liver patients, coagulation is better determined by more modern tests such as  thromboelastogram  (TEG) or thomboelastrometry (ROTEM). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3557", "text": "Prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and INR are measures of the  extrinsic pathway  of  coagulation . This test is also called \"ProTime INR\" and \"INR PT\". They are used to determine the clotting tendency of blood, in the measure of  warfarin  dosage, liver damage, and  vitamin K  status. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3558", "text": "The serum glucose test, abbreviated as \"BG\" or \"Glu\", measures the liver's ability to produce glucose ( gluconeogenesis ); it is usually the last function to be lost in the setting of  fulminant liver failure . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3559", "text": "Lactate dehydrogenase  (LDH) is found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage. [ 18 ]  LDH isotype-1 (or cardiac) is used for estimating damage to cardiac tissue, although troponin and creatine kinase tests are preferred. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3560", "text": "Macro-creatine kinase (macro-CK)  is a macroenzyme, an enzyme of high  molecular weight  and prolonged  half-life  found in human  serum . [ 1 ]  It is one of the most common macroenzymes. [ 1 ]  Macro-CK type 1 is a  complex  formed by one of the  creatine kinase   isoenzyme  types, typically CK-BB, and  antibodies ; typically  IgG , sometimes  IgA , rarely  IgM . Macro-CK type 2 is formed from  mitochondrial  CK polymer. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3561", "text": "Macro-CK type 1 has been associated with autoimmune and other chronic conditions. [ 1 ]  Macro-CK type 2 has been associated with  malignancy . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3562", "text": "Macro-CK has been implicated as a source of interference in interpretation of medical labs. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3563", "text": "Magnetic immunoassay  ( MIA ) is a type of diagnostic  immunoassay  using magnetic beads as labels in lieu of conventional enzymes ( ELISA ), radioisotopes ( RIA ) or fluorescent moieties ( fluorescent immunoassays ) [ 1 ]  to detect a specified  analyte . MIA involves the specific binding of an antibody to its antigen, where a magnetic label is conjugated to one element of the pair. The presence of magnetic beads is then detected by a magnetic reader ( magnetometer ) which measures the magnetic field change induced by the beads. The signal measured by the magnetometer is proportional to the analyte (virus, toxin, bacteria, cardiac marker, etc.) concentration in the initial sample."}
{"_id": "WikiPedia_Hematology$$$corpus_3564", "text": "Magnetic beads are made of nanometric-sized iron oxide particles encapsulated or glued together with polymers. These magnetic beads range from 35\u00a0nm up to 4.5 \u03bcm. The component  magnetic nanoparticles  range from 5 to 50\u00a0nm and exhibit a unique quality referred to as  superparamagnetism  in the presence of an externally applied magnetic field. [ 2 ]  First discovered by Frenchman  Louis N\u00e9el , Nobel Physics Prize winner in 1970, this superparamagnetic quality has already been used for medical application in Magnetic Resonance Imaging (MRI) and in biological separations, but not yet for labeling in commercial diagnostic applications.\nMagnetic labels exhibit several features very well adapted for such applications: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3565", "text": "Magnetic Immunoassay (MIA) is able to detect select molecules or pathogens through the use of a magnetically tagged antibody. Functioning in a way similar to that of an ELISA or Western Blot, a two-antibody binding process is used to determine concentrations of analytes. MIA uses antibodies that are coating a magnetic bead. These anti-bodies directly bind to the desired pathogen or molecule and the magnetic signal given off the bound beads is read using a magnetometer. The largest benefit this technology provides for immunostaining is that it can be conducted in a liquid medium, where methods such as ELISA or Western Blotting require a stationary medium for the desired target to bind to before the secondary antibody (such as HRP [Horse Radish Peroxidase]) is able to be applied. Since MIA can be conducted in a liquid medium a more accurate measurement of desired molecules can be performed in the model system. Since no isolation must occur to achieve quantifiable results users can monitor activity within a system. Getting a better idea of the behavior of their target.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3566", "text": "The manners in which this detection can occur are very numerous. The most basic form of detection is to run a sample through a gravity column that contains a polyethylene matrix with the secondary anti-body. The target compound binds to the antibody contained in the matrix, and any residual substances are washed out using a chosen buffer. The magnetic antibodies are then passed through the same column and after an incubation period, any unbound antibodies are washed out using the same method as before. The reading obtained from the magnetic beads bound to the target which is captured by the antibodies on the membrane is used to quantify the target compound in solution. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3567", "text": "Also, because it is so similar in methodology to ELISA or Western Blot the experiments for MIA can be adapted to use the same detection if the researcher wants to quantify their data in a similar manner."}
{"_id": "WikiPedia_Hematology$$$corpus_3568", "text": "A simple instrument can detect the presence and measure the total magnetic signal of a sample, however, the challenge of developing an effective MIA is to separate naturally occurring magnetic background (noise) from the weak magnetically labeled target (signal). Various approaches and devices have been employed to achieve a meaningful signal-to-noise ratio (SNR) for bio-sensing applications: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3569", "text": "But improving SNR often requires a complex instrument to provide repeated scanning and extrapolation through data processing, or precise alignment of target and sensor of miniature and matching size. Beyond this requirement, MIA that exploits the non-linear magnetic properties of magnetic labels [ citation needed ]  can effectively use the intrinsic ability of a magnetic field to pass through plastic, water,  nitrocellulose , and other materials, thus allowing for true volumetric measurements in various immunoassay formats. Unlike conventional methods that measure the susceptibility of superparamagnetic materials, a MIA-based on non-linear magnetization eliminates the impact of linear dia- or paramagnetic materials such as sample matrix, consumable plastics and/or nitrocellulose. Although the intrinsic magnetism of these materials is very weak, with typical susceptibility values of \u201310 \u22125  (dia) or +10 \u22123  (para), when one is investigating very small quantities of superparamagnetic materials, such as nanograms per test, the background signal generated by ancillary materials cannot be ignored. In MIA based on non-linear magnetic properties of magnetic labels the beads are exposed to an alternating magnetic field at two frequencies, f1 and f2. In the presence of non-linear materials such as superparamagnetic labels, a signal can be recorded at combinatorial frequencies, for example, at f = f1 \u00b1 2\u00d7f2. This signal is exactly proportional to the amount of magnetic material inside the reading coil."}
{"_id": "WikiPedia_Hematology$$$corpus_3570", "text": "This technology makes magnetic immunoassay possible in a variety of formats such as:"}
{"_id": "WikiPedia_Hematology$$$corpus_3571", "text": "It was also described for in vivo applications [ 4 ]  and for multiparametric testing."}
{"_id": "WikiPedia_Hematology$$$corpus_3572", "text": "MIA is a versatile technique that can be used for a wide variety of practices."}
{"_id": "WikiPedia_Hematology$$$corpus_3573", "text": "Currently it has been used to detect viruses in plants to catch pathogens that would normally devastate crops such as  Grapevine fanleaf virus , [ 5 ] [ full citation needed ]  and  Potato virus X . Its adaptations now include portable devices that allow the user to gather sensitive data in the field. [ 6 ] [ full citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3574", "text": "MIA can also be used to monitor therapeutic drugs. A case report of a 53-year-old [ 7 ] [ full citation needed ]  kidney transplant patient details how the doctors were able to alter the quantities of the therapeutic drug."}
{"_id": "WikiPedia_Hematology$$$corpus_3575", "text": "Malaria antigen detection tests  are a group of commercially available  rapid diagnostic tests  of the  rapid antigen test  type that allow quick  diagnosis  of  malaria  by people who are not otherwise skilled in traditional laboratory techniques for diagnosing malaria or in situations where such equipment is not available. There are currently over 20 such tests commercially available (WHO product testing 2008). The first malaria  antigen  suitable as target for such a test was a soluble  glycolytic   enzyme   Glutamate dehydrogenase . [ 1 ] [ 2 ] [ 3 ] \nNone of the rapid tests are currently as sensitive as a thick  blood film , nor as cheap. A major drawback in the use of all current  dipstick  methods is that the result is essentially qualitative. In many endemic areas of  tropical Africa , however, the quantitative assessment of parasitaemia is important, as a large percentage of the population will test positive in any qualitative assay."}
{"_id": "WikiPedia_Hematology$$$corpus_3576", "text": "Malaria is a curable  disease  if the patients have access to early diagnosis and prompt  treatment . Antigen-based  rapid diagnostic tests   (RDTs)  have an important role at the periphery of health services capability because many rural  clinics  do not have the ability to diagnose malaria on-site due to a lack of microscopes and trained  technicians  to evaluate blood films. Furthermore, in regions where the disease is not  endemic , laboratory technologists have very limited experience in detecting and identifying malaria parasites. An ever increasing numbers of travelers from temperate areas each year visit  tropical countries  and many of them return with a malaria infection. The RDT tests are still regarded as complements to conventional  microscopy  but with some improvements it may well replace the  microscope . The tests are simple and the procedure can be performed on the spot in field conditions. These tests use finger-stick or venous  blood , the completed test takes a total of 15\u201320 minutes, and a  laboratory  is not needed.  The threshold of detection by these rapid diagnostic tests is in the range of 100 parasites/\u03bcL of blood compared to 5 by thick film microscopy. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3577", "text": "An accurate diagnosis is becoming more and more important, in view of the increasing resistance of  Plasmodium falciparum  and the high price of alternatives to  chloroquine . The enzyme pGluDH does not occur in the host  red blood cell  and was recommended as a marker enzyme for  Plasmodium  species by Picard-Maureau et al. in 1975. [ 7 ]  The malaria marker enzyme test is suitable for routine work and is now a standard test in most departments dealing with malaria. Presence of pGluDH is known to represent parasite viability [ 2 ]  and a rapid diagnostic test using pGluDH as antigen would have the ability to differentiate live from dead organisms. A complete RDT with pGluDH as antigen has been developed in  China  and is now undergoing  clinical trials . [ 3 ] \nGluDHs are ubiquitous enzymes that occupy an important branch-point between carbon and nitrogen metabolism. Both  nicotinamide adenine dinucleotide  (NAD)  [EC  1.4.1.2] and  nicotinamide adenine dinucleotide phosphate  (NADP) dependent GluDH [EC 1.4.1.4] enzymes are present in  Plasmodia ; the NAD-dependent GluDH is relatively unstable and not useful for diagnostic purposes. Glutamate dehydrogenase provides an oxidizable carbon source used for the production of energy as well as a reduced electron carrier, NADH.  Glutamate  is a principal amino donor to other  amino acids  in subsequent transamination reactions. The multiple roles of glutamate in nitrogen balance make it a gateway between free ammonia and the amino groups of most amino acids. Its  crystal structure  is published. [ 8 ]  The GluDH activity in  P.vivax ,  P.ovale  and  P. malariae  has never been tested, but given the importance of GluDH as a branch point enzyme, every cell must have a high concentration of GluDH. It is well known that enzymes with a high molecular weight (like GluDH) have many  isozymes , which allows strain differentiations (given the right  monoclonal antibody ). The host produces antibodies against the parasitic enzyme indicating a low sequence identity. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3578", "text": "The histidine-rich protein II (HRP II) is a  histidine - and  alanine -rich, water-soluble protein, which is localized in several cell compartments including the parasite cytoplasm. The antigen is expressed only by  P. falciparum   trophozoites . [ 9 ] [ 10 ]  HRP II from  P. falciparum  has been implicated in the  biocrystallization  of  hemozoin , an inert, crystalline form of ferriprotoporphyrin IX (Fe(3+)-PPIX) produced by the parasite.  A substantial amount of the HRP II is secreted by the parasite into the host bloodstream and the antigen can be detected in  erythrocytes ,  serum ,  plasma ,  cerebrospinal fluid  and even  urine  as a secreted water-soluble protein. [ 11 ]  These antigens persist in the circulating blood after the parasitaemia has cleared or has been greatly reduced. It generally takes around two weeks after successful treatment for HRP2-based tests to turn negative, but may take as long as one month, which compromises their value in the detection of active infection. [ 12 ]  False positive dipstick results were reported in patients with rheumatoid-factor-positive  rheumatoid arthritis . [ 9 ]  Since HRP-2 is expressed only by  P. falciparum , these tests will give negative results with samples containing only  P. vivax ,  P. ovale , or  P. malariae ; many cases of non-falciparum malaria may therefore be misdiagnosed as malaria negative (some  P.falciparum  strains also don't have HRP II). The variability in the results of pHRP2-based RDTs is related to the variability in the target antigen. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3579", "text": "P. falciparum   lactate dehydrogenase  (PfLDH) is a 33 kDa  oxidoreductase  [EC 1.1.1.27]. [ 14 ]  It is the last enzyme of the glycolytic pathway, essential for  ATP  generation and one of the most abundant enzymes expressed by  P. falciparum . [ 15 ]   Plasmodium  LDH (pLDH) from  P. vivax ,  P. malariae , and  P. ovale ) exhibit 90-92% identity to PfLDH from  P. falciparum . [ 16 ]  pLDH levels have been seen to reduce in the blood sooner after treatment than HRP2. [ 17 ]  In this respect, pLDH is similar to pGluDH.  Nevertheless, the kinetic properties and sensitivities to inhibitors targeted to the cofactor binding site differ significantly and are identifiable by measuring dissociation constants for inhibitors which, differ by up to 21-fold. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3580", "text": "Fructose-bisphosphate aldolase  [EC 4.1.2.13] catalyzes a key reaction in  glycolysis  and energy production and is produced by all four species. [ 19 ]  The  P.falciparum  aldolase is a 41 kDa protein and has 61-68% sequence similarity to known  eukaryotic  aldolases. [ 20 ]  Its crystal structure has been published. [ 21 ]  The presence of antibodies against p41 in the sera of human adults partially immune to malaria suggest that p41 is implicated in protective immune response against the parasite. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3581", "text": "mChip  is a  portable blood test device  which is capable of  diagnosing  an  infection  of  HIV  or  Syphilis [ 1 ] [ 2 ]  within 15 minutes [ 3 ]  and could be used effectively against  HIV/AIDS  in developing countries. [ 1 ] [ 3 ] [ 4 ]  The mChip costs about  US$  1 [ 3 ]  and the entire diagnostic kit costs about  US$  100. [ 3 ] [ 5 ]  mChip was developed so that people in regions with poor health facilities can access portable diagnosis for HIV/AIDS rather than travelling long distances to go to clinics for diagnosis. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3582", "text": "Lateral flow test  is one of the blood testing methods used, in which a  blood sample  or  oral fluid  is placed on a strip of paper. In this method, a colored band indicates  infection . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3583", "text": "People in lesser developed regions like the  Sub-Saharan Africa  are adversely affected by  HIV/AIDS  and have very limited access to  clinical labs  or  hospitals . There have been estimates which have indicated that there are about 22.5 million people with HIV/AIDS in such regions and hence there is a high demand for  portable blood test devices . [ 6 ]  Hence devices like mChip will be able to diagnose HIV/AIDS in such regions [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3584", "text": "mChip was developed by scientists at  Columbia University [ 7 ]  in  New York City . Initial testing of this device was undertaken in a village in  Rwanda , [ 2 ] [ 8 ]  where, according to the  World Health Organization , approximately 3 percent of the population has  HIV/AIDS . [ 1 ]  Of the 400 volunteers who turned up for testing, 399 were correctly diagnosed with an accuracy of nearly 100 percent. [ 7 ] [ 9 ] [ 10 ] [ 11 ]  mChip was also tested for its effectiveness in diagnosing  syphilis , where, out of the 67 volunteers who turned up for testing, 63 were correctly diagnosed with an accuracy of nearly 94 percent. [ 1 ] [ 3 ]  The appearance of mChip resembles a  credit card . [ 1 ] [ 5 ]  and is estimated to cost just  US$  1. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3585", "text": "The operation of mChip is similar to that of  ELISA  (Enzyme-Linked Immunosorbent Assay). [ 2 ]  The ELISA can be performed to evaluate either the presence of antigen or the presence of antibody in a sample. It is a useful tool for determining  serum  antibody concentrations such as with the  HIV test . [ 12 ]  The mChip contains 10 zones [ 5 ]  which detect the passage of a small amount (about 1\u03bcl) of blood. [ 2 ]  The results can be obtained in a color-coded format [ 4 ]  in about 15 minutes. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3586", "text": "The  mean corpuscular hemoglobin , or \"mean cell hemoglobin\" ( MCH ), is the average mass of  hemoglobin  (Hb) per  red blood cell  (RBC) in a sample of blood. It is reported as part of a standard  complete blood count . MCH value is diminished in  hypochromic anemias . [ 1 ]  RBCs are either  normochromic  or hypochromic. They are never \"hyperchromic\". If more than the normal amount of hemoglobin is made, the cells get larger\u2014they do not become darker. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3587", "text": "It is calculated by dividing the total mass of hemoglobin by the number of red blood cells in a volume of blood."}
{"_id": "WikiPedia_Hematology$$$corpus_3588", "text": "MCH=(Hb*10)/RBC (in millions) [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3589", "text": "A normal MCH value in humans is 27 to 33  picograms  (pg)/cell. The amount of hemoglobin per RBC depends on hemoglobin synthesis and the size of the RBC. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3590", "text": "The mass of the red cell is determined by the iron (as part of the hemoglobin molecule), thus MCH in picograms is roughly the mass of one red cell. In  iron deficiency anemia  the cell mass becomes lighter, thus a MCH below 27 pg is an indication of iron deficiency."}
{"_id": "WikiPedia_Hematology$$$corpus_3591", "text": "The MCH decreases when Hb synthesis is reduced, or when RBCs are smaller than normal, such as in cases of iron-deficiency anemia. [ 1 ]  Conversion to SI-units: 1 pg of hemoglobin = 0.06207  femtomole  (fmol). [ 5 ]  Normal value converted to  SI-units : 1.68 \u2013 1.92 fmol/cell."}
{"_id": "WikiPedia_Hematology$$$corpus_3592", "text": "The  mean corpuscular hemoglobin concentration  ( MCHC ) is a measure of the concentration of  hemoglobin  in a given volume of packed red blood cell."}
{"_id": "WikiPedia_Hematology$$$corpus_3593", "text": "It is calculated by dividing the hemoglobin by the  hematocrit .  Reference ranges for blood tests  are 32 to 36 g/dL (320 to 360g/L), [ 1 ]  or between 4.81 and 5.58 mmol/L. It is thus a mass or  molar concentration . Still, many instances measure MCHC in  percentage  (%), as if it were a  mass fraction  (m Hb  / m RBC ). [ 2 ] [ 3 ]  Numerically, however, the MCHC in g/dL and the mass fraction of hemoglobin in red blood cells in\u00a0% are identical, assuming an RBC  density  of 1g/mL and negligible hemoglobin in plasma. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3594", "text": "A low MCHC can be interpreted as identifying decreased production of hemoglobin. MCHC can be normal even when hemoglobin production is decreased (such as in iron deficiency) due to a calculation artifact. MCHC can be elevated (\"hyperchromic\") in  hereditary spherocytosis ,  sickle cell disease  and  homozygous hemoglobin C disease , depending upon the hemocytometer. [ 4 ] [ 5 ]  MCHC can be elevated in some megaloblastic anemias. MCHC can be falsely elevated when there is agglutination of red cells (falsely lowering the measured RBC count) or when there is opacification of the plasma (falsely increasing the measured hemoglobin). Causes of plasma opacification that can falsely increase the MCHC include hyperbilirubinemia, hypertriglyceridemia, and free hemoglobin in the plasma (due to hemolysis). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3595", "text": "Because of the way  automated analysers  count blood cells, a very high MCHC (greater than about 370 g/L) may indicate the  blood  is from someone with a  cold agglutinin , or there may be some other problem resulting in one or more artifactual results affecting the MCHC. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3596", "text": "For example, for some patients with cold agglutinins, when their blood gets colder than 37\u00a0\u00b0C, the red cells will clump together. As a result, the analyzer may incorrectly report a low number of very dense red blood cells. This will result in an impossibly high number when the analyzer calculates the MCHC. This problem is usually picked up by the laboratory before the result is reported. The blood can be warmed until the cells separate from each other, and quickly put through the machine while still warm. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3597", "text": "There are four steps to perform when a suspect increased MCHC (>370 g/L or >37.0 g/dL) is received from the analyzer: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3598", "text": "The  mean corpuscular volume , or  mean cell volume  ( MCV ), is a measure of the average volume of a red blood corpuscle (or  red blood cell ). The measure is obtained by multiplying a volume of blood by the proportion of blood that is cellular (the  hematocrit ), and dividing that product by the number of  erythrocytes  (red blood cells) in that volume. The mean corpuscular volume is a part of a standard  complete blood count ."}
{"_id": "WikiPedia_Hematology$$$corpus_3599", "text": "In patients with  anemia , it is the MCV measurement that allows classification as either a  microcytic anemia  (MCV below normal range),  normocytic anemia  (MCV within normal range) or  macrocytic anemia  (MCV above normal range). Normocytic anemia is usually deemed so because the bone marrow has not yet responded with a change in cell volume. It occurs occasionally in acute conditions, namely blood loss and hemolysis."}
{"_id": "WikiPedia_Hematology$$$corpus_3600", "text": "If the MCV was determined by automated equipment, the result can be compared to RBC morphology on a  peripheral blood smear , where a normal RBC is about the size of a normal lymphocyte nucleus. Any deviation would usually be indicative of either faulty equipment or technician error, although there are some conditions that present with high MCV without megaloblastic cells."}
{"_id": "WikiPedia_Hematology$$$corpus_3601", "text": "For further specification, it can be used to calculate  red blood cell distribution width  (RDW).  The RDW is a statistical calculation made by automated analyzers that reflects the variability in size and shape of the RBCs."}
{"_id": "WikiPedia_Hematology$$$corpus_3602", "text": "To calculate MCV, the  hematocrit  (Hct) is divided by the concentration of RBCs ([RBC]) [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3603", "text": "MCV \n \n \n = \n \n \n \n Hct \n \n \n [ \n \n RBC \n \n ] \n \n \n \n \n \n {\\displaystyle {\\textit {MCV}}={\\frac {\\textit {Hct}}{[{\\text{RBC}}]}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_3604", "text": "Normally, MCV is expressed in femtoliters ( fL , or 10 \u221215  L), and [RBC] in millions per microliter (10 6  / \u03bcL).  The normal range for MCV is 80\u2013100 fL."}
{"_id": "WikiPedia_Hematology$$$corpus_3605", "text": "If the hematocrit is expressed as a percentage, the red blood cell concentration as millions per microliter, and the MCV in femtoliters, the formula becomes"}
{"_id": "WikiPedia_Hematology$$$corpus_3606", "text": "MCV \n \n \n \n / \n \n \n L \n \n = \n \n \n \n \n \n H \n c \n t \n % \n \n \n \n / \n \n 100 \n \n \n [ \n \n RBCmmL \n \n ] \n \u00d7 \n ( \n \n 10 \n \n 6 \n \n \n \n / \n \n \n 10 \n \n \u2212 \n 6 \n \n \n ) \n \n / \n \n \n \n L \n \n \n \u2212 \n 1 \n \n \n \n \n \n \n \n {\\displaystyle {\\textit {MCV}}/\\mathrm {L} ={\\frac {{\\mathit {Hct\\%}}/100}{[{\\text{RBCmmL}}]\\times (10^{6}/10^{-6})/\\mathrm {L} ^{-1}}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_3607", "text": "MCV \n \n \n \n / \n \n \n f \n L \n \n = \n \n \n MCV \n \n \n \n / \n \n ( \n \n 10 \n \n \u2212 \n 15 \n \n \n \n \n L \n \n ) \n = \n \n 10 \n \n 15 \n \n \n \n \n \n \n \n H \n c \n t \n % \n \n \n \n / \n \n 100 \n \n \n [ \n \n RBCmmL \n \n ] \n \u00d7 \n \n 10 \n \n 12 \n \n \n \n \n \n = \n \n \n \n \n \n H \n c \n t \n % \n \n \n \u00d7 \n 10 \n \n \n [ \n \n RBCmmL \n \n ] \n \n \n \n \n \n {\\displaystyle {\\textit {MCV}}/\\mathrm {fL} ={\\textit {MCV}}/(10^{-15}\\,\\mathrm {L} )=10^{15}{\\frac {{\\mathit {Hct\\%}}/100}{[{\\text{RBCmmL}}]\\times 10^{12}}}={\\frac {{\\mathit {Hct\\%}}\\times 10}{[{\\text{RBCmmL}}]}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_3608", "text": "For example, if the Hct = 42.5% and [RBC] = 4.58 million per microliter (4,580,000/\u03bcL), then"}
{"_id": "WikiPedia_Hematology$$$corpus_3609", "text": "MCV \n \n \n = \n \n \n 0.425 \n \n 4.58 \n \u22c5 \n \n 10 \n \n 6 \n \n \n \n / \n \n ( \n \n 10 \n \n \u2212 \n 6 \n \n \n \n \n L \n \n ) \n \n \n \n = \n 92.8 \n \u22c5 \n \n 10 \n \n \u2212 \n 15 \n \n \n \n \n L \n \n = \n 92.8 \n \n \n f \n L \n \n \n \n {\\displaystyle {\\textit {MCV}}={\\frac {0.425}{4.58\\cdot 10^{6}/(10^{-6}\\,\\mathrm {L} )}}=92.8\\cdot 10^{-15}\\,\\mathrm {L} =92.8\\,\\mathrm {fL} }"}
{"_id": "WikiPedia_Hematology$$$corpus_3610", "text": "Using implied units,"}
{"_id": "WikiPedia_Hematology$$$corpus_3611", "text": "MCV \n \n \n \n / \n \n \n \n fL \n \n \n = \n \n \n \n 42.5 \n \u00d7 \n 10 \n \n 4.58 \n \n \n = \n 92.8 \n \n \n {\\displaystyle {\\textit {MCV}}/{\\textrm {fL}}={\\frac {42.5\\times 10}{4.58}}=92.8}"}
{"_id": "WikiPedia_Hematology$$$corpus_3612", "text": "The MCV can be determined in a number of ways by automatic analyzers. In volume-sensitive automated blood cell counters, such as the  Coulter counter , the red cells pass one-by-one through a small aperture and generate a signal directly proportional to their volume.\nOther automated counters measure red blood cell volume by means of techniques that measure refracted, diffracted, or scattered light. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3613", "text": "The normal  reference range  is typically 80-100  fL . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3614", "text": "In  pernicious anemia  (macrocytic), MCV can range up to 150  femtolitres . [ 4 ]  (as are an elevated  GGT  and an  AST/ALT ratio  of 2:1).  Vitamin B12  and/or  folic acid  deficiency has also been associated with  macrocytic anemia  (high MCV numbers)."}
{"_id": "WikiPedia_Hematology$$$corpus_3615", "text": "The most common causes of  microcytic anemia  are  iron deficiency  (due to inadequate  dietary  intake,  gastrointestinal blood loss , or  menstrual blood loss ),  thalassemia ,  sideroblastic anemia  or  chronic disease . In  iron deficiency anemia  (microcytic anemia), it can be as low as 60 to 70 femtolitres. In some cases of  thalassemia , the MCV may be low even though the patient is not iron deficient. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3616", "text": "The MCV can be conceptualized as the total volume of a group of cells divided by the number of cells.  For a real world sized example, imagine you had 10 small jellybeans with a combined volume of 10 \u03bcL. The mean volume of a jellybean in this group would be 10 \u03bcL / 10 jellybeans = 1 \u03bcL / jellybean.  A similar calculation works for MCV. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3617", "text": "1.  Measure the RBC index in cells/\u03bcL. Take the reciprocal (1/RBC index) to convert it to \u03bcL/cell."}
{"_id": "WikiPedia_Hematology$$$corpus_3618", "text": "2.  The 1 \u03bcL is only made of a proportion of red cells (e.g. 40%) with the rest of the volume composed of plasma. Multiply by the hematocrit (a unitless quantity) to take this into account."}
{"_id": "WikiPedia_Hematology$$$corpus_3619", "text": "3.  Finally, convert the units of \u03bcL to fL by multiplying by  \n \n \n \n \n 10 \n \n 9 \n \n \n \n \n {\\displaystyle 10^{9}} \n \n .  The result would look like this:"}
{"_id": "WikiPedia_Hematology$$$corpus_3620", "text": "Note: the shortcut proposed above just makes the units work out:  \n \n \n \n 10 \n \u00d7 \n 40 \n \u00f7 \n 5 \n = \n 80 \n \n \n {\\displaystyle 10\\times 40\\div 5=80}"}
{"_id": "WikiPedia_Hematology$$$corpus_3621", "text": "Mean platelet volume  ( MPV ) is a machine-calculated measurement of the average size of  platelets  found in blood and is typically included in  blood tests  as part of the  CBC . Since the average platelet size is larger when the body is producing increased numbers of platelets, the MPV test results can be used to make inferences about platelet production in  bone marrow  or platelet destruction problems. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3622", "text": "An increased mean platelet volume (MPV) increases the risk to suffer a heart disease  [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3623", "text": "MPV may be higher when there is destruction of platelets. This may be seen in  immune thrombocytopenic purpura  (ITP),  myeloproliferative diseases  and  Bernard\u2013Soulier syndrome . It may also be related to  pre-eclampsia  and recovery from transient  hypoplasia . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3624", "text": "Abnormally low MPV values may correlate with  thrombocytopenia  when it is due to impaired production of  megakaryocytes  in the  bone marrow , such as in  aplastic anemia . A low MPV may indicate  inflammatory bowel disease  (IBD), such as  Crohn's disease  and  ulcerative colitis . [ 4 ]  A high MPV is also a bad prognostic marker in patients with sepsis or septic shock. [ 5 ] [ 6 ]  In addition, low MPV may correlate with abnormally small platelet size, sometimes a symptom of a spectrum referred to as  Wiskott\u2013Aldrich syndrome  (WAS), [ 7 ]  caused by a genetic mutation of the WAS gene."}
{"_id": "WikiPedia_Hematology$$$corpus_3625", "text": "Sample for MPV testing is obtained in a Lavender-Top  EDTA tube. A typical range of platelet volumes is 7.2 - 11.7\u00a0fL [ 8 ]  ( femtolitre ), equivalent to spheres 2.65 to 2.9\u00a0 \u03bcm  in diameter."}
{"_id": "WikiPedia_Hematology$$$corpus_3626", "text": "MELISA  ( Memory Lymphocyte Immunostimulation Assay ) is a blood test that detects  type IV hypersensitivity  to metals, chemicals, environmental toxins and molds. Type IV hypersensitivity reactions, particularly to nickel, are well established and may affect 20% of the population. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3627", "text": "The MELISA test measures type-IV delayed hypersensitivity reaction. Type-IV reactions are mediated by  T-lymphocytes  (or memory lymphocytes) that have had prior contact with a given allergen. [ 2 ]  This is in contrast to a type-I allergy, which is mediated by IgE  antibodies  and is often tested using an  ELISA  test. In genetically predisposed individuals, an ongoing exposure to allergens can induce type-IV hypersensitivity. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3628", "text": "The MELISA  assay  is a cell culture and requires live memory lymphocytes. Lymphocytes are isolated from a blood sample and cultured in an incubator for five days. A portion of the blood is kept intact (unexposed to allergens) to serve as a negative control. A second portion is exposed to a universal allergen,  Pokeweed , to serve as a positive control. Finally, the blood is exposed to the suspected allergen/s in several different concentrations, to ensure that the conditions in vitro are as similar as possible to those in vivo. The lymphocyte reaction to each allergen is measured by two separate technologies: one based on the uptake of a radioactive  isotope ,  3 H-thymidine, by dividing lymphocytes (proliferation); the other by cell staining and microscopy evaluation. The level of reactivity is measured as a Stimulation Index (SI), against the na\u00efve lymphocytes from the unexposed sample (negative control). Viability and reactivity are determined by cell count as well as reaction to the positive control. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3629", "text": "MELISA is an optimised, standardised version of the lymphocyte transformation test (LTT) which was developed in the early 1960s to help identify allergies to drugs, metabolites and metals. The LTT for beryllium is now accepted as the gold standard for diagnosing  berylliosis . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3630", "text": "MELISA differs from standard LTTs in several ways:"}
{"_id": "WikiPedia_Hematology$$$corpus_3631", "text": "MELISA was further developed to help to assess the impact of hypersensitivity to metals used in dentistry. Hypersensitivity to dental metals may be associated with local oral reactions including oral lichen planus, stomatitis and ulceration. [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3632", "text": "The frequency of metal-induced lymphocyte responses was examined in 3,162 dental patients in three European laboratories using the MELISA test. [ 10 ]  The patients suffered from local and systemic symptoms attributed to their dental restorations. The effect of dental metal removal was studied in 111 patients with metal hypersensitivity and symptoms resembling  chronic fatigue syndrome  ( CFS ). After consultation with a dentist, a subgroup of 111 patients who showed allergy to their dental metals replaced their restorations with non-metallic materials. Nickel was the most common sensitizer, followed by inorganic mercury, gold, phenylmercury, cadmium and palladium. As compared to lymphocyte responses in healthy subjects, the CFS group had significantly increased responses to several metals, especially to inorganic mercury, phenylmercury and gold.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3633", "text": "Following dental metal removal:"}
{"_id": "WikiPedia_Hematology$$$corpus_3634", "text": "Type IV hypersensitivity to metals is common, particularly to nickel, however hypersensitivity related complications associated with metal implants are less frequently reported. Potential hypersensitivity complications include skin rashes, chronic joint pain, swelling, aseptic loosening, and joint failure.  [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3635", "text": "Many authors conclude that LTT-based blood tests like MELISA may be a better option for detecting systemic allergies from implants, while patch testing is better suited to detecting dermal hypersensitivity. They add that LTT based testing may also be a good option in cases of indeterminate hypersensitivity or in patients with joint failure of an unknown cause since it has higher sensitivity than patch testing  [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3636", "text": "Some surgeons and researchers suggest LTT testing prior to surgery in patients with suspected/self-reported metal allergy  [ 15 ] [ 16 ] [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3637", "text": "Titanium and its main alloy (Ti6Al4V) are generally seen as hypoallergenic options for arthroplasty and for dental implants. Although uncommon, with a prevalence estimated at between 0.6-6.3%, [ 19 ] [ 20 ]  titanium hypersensitivity has been reported post-implantation with symptoms including impaired fracture healing, local eczema, pain, swelling, systemic dermatitis, implant loosening, and failure, all of which have been reported to resolve with implant removal and replacement with a non-titanium implant  [ 21 ] [ 22 ] [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3638", "text": "In spinal surgery, microscopic titanium particles are present in the tissues surrounding the implant. [ 25 ]  These particles activate macrophages that increase bone absorption and inflammatory reactions. [ 26 ]  Released nanoparticles will circulate in the body fluids, eventually accumulating in remote organs. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3639", "text": "Titanium has been shown to induce clinically relevant hypersensitivity which can be detected with MELISA testing. [ 28 ]  The accuracy of patch testing for titanium allergy, in particular, seems to be variable; the Mayo clinic failed to find any positive reactions to titanium in over a decade, [ 29 ]  despite several published cases of titanium allergy. [ 22 ] [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3640", "text": "The test is also used to determine whether metal allergy is a contributing factor in the development of chronic diseases such as  CFS  (Sterzl, et al., 1999) and  multiple sclerosis . The authors hypothesize that if the immune system is constantly displaying an allergic reaction to a metal present in the body, this will alert the  HPA axis  inducing fatigue-like symptoms. A study (Stejskal, et al., 1999)  of 930 patients with CFS-like symptoms showed 62% testing MELISA-positive to metal allergy. Of those who removed the offending metals, 76% improved, but there was no placebo control. Metal hypersensitivity is not widely recognized by researchers as an accepted cause of  CFS  or  multiple sclerosis . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3641", "text": "The MELISA test is used in  occupational medicine  and environmental health. It has been used to screen workers exposed to metals, chemicals or other allergens in their workplace. This is what the test was developed for originally, at Astra\u2019s (now Astra-Zeneca) laboratories in S\u00f6dert\u00e4lje, Sweden. In the U.S., a similar technique (BeLT) is routinely used to screen for  beryllium  allergy in asymptomatic workers exposed to beryllium dust (Mroz, et al., 1991) (Newman LS, 1996)."}
{"_id": "WikiPedia_Hematology$$$corpus_3642", "text": "Whilst two articles have concluded that the MELISA test may give false positive (Cederbrant, et al., 1999) (Cederbrant, et al., 1997) reactions, a subsequent study concluded the MELISA test is \"reproducible, sensitive, specific, and reliable for detecting metal sensitivity in metal-sensitive patients.\" (Valentine-Thon & Schiawara, 2003)"}
{"_id": "WikiPedia_Hematology$$$corpus_3643", "text": "The developers of the MELISA test argue that the critical articles calculated the sensitivity and specificity of in vitro lymphocyte proliferation tests using patch testing as its reference. It is well-known that patch testing can cause irritative local reactions. \nIt is generally agreed that LTT based tests like MELISA are better suited for diagnosing implant-related metals sensitivity than patch testing as the relationship between skin hypersensitivity and systemic hypersensitivity (St\u00e4nder, et al., 2017) is ill-defined. Performing the LTT under optimised stimulating conditions might be a useful additional tool for the diagnosis of hypersensitivity (St\u00e4nder, et al., 2017) (FDA, 2019). \nTo test whether patients with symptoms attributed to dental amalgam differed from healthy controls, a study compared 23 amalgam patients, 30 subjects who considered themselves healthy with amalgams and 10 subjects without amalgam using MELISA and other tests. The researchers found that a high frequency of positive results was obtained among healthy subjects with or without dental amalgam, and concluded that the test cannot be used as an objective test for mercury allergy (Cederbrant, et al., 1999)."}
{"_id": "WikiPedia_Hematology$$$corpus_3644", "text": "Another study by the same critical author used 34 patients to test the sensitivity and specificity if the MELISA test, and concluded that it is not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since many false-positive results will be obtained (Cederbrant, et al., 1997). \nThe clinical relevance of the test has been shown by the decrease of patient-reported metal-specific responses following the removal of the allergy-causing metals (however the trial did not have a placebo control). (Stejskal, et al., 2006) (Valentine-Thon, et al., 2006)"}
{"_id": "WikiPedia_Hematology$$$corpus_3645", "text": "The  Mentzer index,  described in 1973 by William C. Mentzer, [ 1 ]    is the MCV divided by the RBC count. It is said to be helpful in differentiating  iron deficiency anemia  from  beta thalassemia trait . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3646", "text": "The index is calculated from the results of a  complete blood count . If the  quotient  of the  mean corpuscular volume  (MCV, in fL) divided by the  red blood cell  count (RBC, in million per microliter) is less than 13, \u03b2-thalassemia trait is said to be more likely. If the result is greater than 13, then iron-deficiency anemia is said to be more likely. [ 4 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3647", "text": "The principle involved is as follows:  In iron deficiency, the marrow cannot produce as many RBCs and they are small (microcytic), so the RBC count and the MCV will both be low, and as a result, the index will be greater than 13. Conversely, in thalassemia, which is a disorder of globin synthesis, the number of RBCs produced is normal, but the cells are smaller and more fragile. Therefore, the RBC count is normal, but the MCV is low, so the index will be less than 13. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3648", "text": "Missouri v. McNeely , 569 U.S. 141 (2013), was a case decided by  United States Supreme Court , on appeal from the  Supreme Court of Missouri , regarding exceptions to the  Fourth Amendment to the United States Constitution  under  exigent circumstances . [ 1 ] [ 2 ]  The United States Supreme Court ruled that police must generally obtain a warrant before subjecting a drunken-driving suspect to a blood test, and that the natural metabolism of blood alcohol does not establish a  per se  exigency that would justify a blood draw without consent."}
{"_id": "WikiPedia_Hematology$$$corpus_3649", "text": "At approximately 2:08\u00a0a.m. on October 3, 2010, Tyler McNeely was stopped after a highway patrol officer observed him exceed the posted speed limit, and cross over the centerline. The officer reportedly noticed signs of intoxication from McNeely, including bloodshot eyes, slurred speech, and the smell of alcohol on his breath. McNeely failed field-sobriety tests administered by the officer. After refusing to blow into a handheld breathalyzer, and stating that he would refuse a breathalyzer at the police station, the officer drove McNeely directly to a medical center instead of the station. The officer did not seek a warrant to conduct the blood test, but asked McNeely for his consent. McNeely was warned by the officer that by refusing a chemical test, his license would be revoked for one year. McNeely continued to refuse, and at 2:35\u00a0a.m., the officer proceeded to instruct the lab technician to draw a specimen of blood from McNeely. The results of the blood test showed a BAC of 0.154 percent, which was above the state's legal limit of 0.08 percent. McNeely was charged with driving while intoxicated, and later moved to suppress the results of his blood test, as he argued that it was done unconstitutionally as an unreasonable search and seizure. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3650", "text": "A trial judge sided with McNeely, ruling in their favor by suppressing the results of the blood test. The judge emphasized that conducting a blood test without a warrant constituted a breach of the suspect's  Fourth Amendment  protection against unreasonable searches and seizures."}
{"_id": "WikiPedia_Hematology$$$corpus_3651", "text": "Later, state prosecutors argued that justifying the administration of the test without a warrant was valid because blood alcohol would metabolize with time, and a delay in obtaining a warrant would amount to  destruction of evidence , citing the exigent circumstances exception in the 1966 United States Supreme Court decision  Schmerber v. California . On appeal, the  state appeals court  stated an intention to reverse, but transferred the case directly to the  Missouri Supreme Court . The Missouri Supreme Court affirmed the trial court's decision that the officer had violated McNeely's Fourth Amendment rights. The United States Supreme Court granted a petition for  writ of certiorari  on 25 September 2012. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3652", "text": "A 5-4 Supreme Court affirmed the Missouri Supreme Court, agreeing that an involuntary blood draw is a \"search\" as that term is used in the Fourth Amendment. [ 5 ]  As such, a warrant is generally required. In its majority opinion, the Court found that because McNeely's \"case was unquestionably a routine  DWI  case\" in which no factors other than the natural dissipation of blood-alcohol suggested that there was an emergency, the court held that the nonconsensual warrantless blood draw violated McNeely's Fourth Amendment right to be free from unreasonable searches of his person. However, the Court left open the possibility that the \"exigent circumstances\" exception to that general requirement might apply in some drunk-driving cases. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3653", "text": "Mitchell v. Wisconsin , 588 U.S. ___ (2019), is a  United States Supreme Court  case in which the Court held that \"when a driver is unconscious and cannot be given a  breath test , the  exigent-circumstances doctrine  generally permits a  blood test  without a  warrant .\" [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3654", "text": "In May 2013, Gerald Mitchell crashed his car near a lake in  Sheboygan, Wisconsin . When police arrived, they used a breathalyzer to test his  blood alcohol content . Mitchell registered a 0.24% BAC and was subsequently arrested for OWI. As police were driving him to the police station, he fell unconscious, so the officers changed plans and drove him to a local hospital to have his blood drawn intravenously. This test registered his BAC at 0.22%, and prosecutors formally charged Mitchell with violating several Wisconsin drunk driving laws. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3655", "text": "At the trial court, Mitchell made a motion to suppress the results of the hospital blood draw on the grounds that it was a warrantless search and thus unconstitutional under the  Fourth Amendment . The prosecutor argued that Wisconsin's state laws constitute implied consent to blood draws once someone begins driving a vehicle. [ 2 ]  Sheboygan County Judge Terence Bourke sided with the prosecutor, denying Mitchell's motion to suppress. A jury then convicted Mitchell of all charges. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3656", "text": "Mitchell appealed his conviction to the state appellate court on the basis that the evidence gained from his blood draw should have been suppressed. The appellate court declined to hear the case, and instead certified two questions to the  Wisconsin Supreme Court  \u2013 whether the \"implied consent\" rule was constitutional, and whether a warrantless blood draw from an unconscious person was a violation of the Fourth Amendment. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3657", "text": "In a 5\u20132 decision written by Chief Justice  Roggensack , the  Wisconsin Supreme Court  upheld Mitchell's conviction, answering that the \"implied consent\" rule was constitutional, and thus the blood draw was permissible under the Fourth Amendment. Justice  Kelly  wrote a concurring opinion that was joined by  Justice Rebecca Bradley . In it, he argued that the \"implied consent\" rule is unconstitutional, but that the  exigent circumstances doctrine , along with United States Supreme Court precedent, allow for a warrantless blood draw from an unconscious driver who is suspected of being intoxicated. Justice  Ann Walsh Bradley  wrote a dissent joined by Justice  Abrahamson , which argued that \"implied consent\" is not the same as actual consent, and that a blood draw is such an invasive type of search that exigent circumstances do not apply. Thus, nothing the officers did was constitutional, and the blood draw should have been thrown out as evidence. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3658", "text": "Mitchell applied for certiorari before the United States Supreme Court, which accepted the case to decide \"[w]hether a statute authorizing a blood draw from an unconscious motorist provides an exception to the Fourth Amendment warrant requirement.\""}
{"_id": "WikiPedia_Hematology$$$corpus_3659", "text": "Oral argument was held on April 23, 2019. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3660", "text": "On June 27, 2019, the Court announced its decision. In a plurality opinion written by Justice  Samuel Alito  and joined by Chief Justice  Roberts  and Justices  Breyer  and  Kavanaugh , the United States Supreme Court reversed the judgement of the  Wisconsin Supreme Court . Justice  Thomas  wrote an opinion concurring in the judgement. In opposition, Justice  Sotomayor  wrote a dissenting opinion that was joined by Justices  Ginsburg  and  Kagan . Justice  Gorsuch  wrote a lone one-paragraph dissenting opinion, arguing that the Court did not properly decide the question presented. He said that he would have dismissed the case as  improvidently granted . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3661", "text": "Mixing studies  are tests performed on  blood plasma  of patients or test subjects to distinguish factor deficiencies from  factor inhibitors , such as  lupus anticoagulant , or specific factor inhibitors, such as  antibodies  directed against  factor VIII . [ 1 ]  Mixing studies are screening tests widely performed in coagulation laboratories. The basic purpose of these tests is to determine the cause of prolongation of  Prothrombin Time  (PT),  Partial Thromboplastin Time , or sometimes of  thrombin time  (TT). Mixing studies take advantage of the fact that factor levels that are 50 percent of normal should give a normal  Prothrombin time  (PT) or  Partial thromboplastin time  (PTT) result. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3662", "text": "Fresh normal plasma has all the blood coagulation factors with normal levels."}
{"_id": "WikiPedia_Hematology$$$corpus_3663", "text": "If the problem is a simple factor deficiency, mixing the patient plasma 1:1 with plasma that contains 100% of the normal factor level results in a level \u226550% in the mixture (say the patient has an activity of 0%; the average of 100% + 0% = 50%). [ 3 ]  The PT or PTT will be normal (the mixing study shows correction).  Correction with mixing indicates factor deficiency.  Failure to correct with mixing indicates an inhibitor.  Performing a thrombin time on the test plasma can provide useful additional information for the interpretation of mixing tests, such as by demonstrating the presence of anticoagulants, hypofibrinogenemia or dysfibrinogenemia. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3664", "text": "Factor deficient plasmas (Adsorbed Plasma and Aged Plasma, etc.) have been used historically in mixing studies. Plasma with known factor deficiencies are commercially available but are very expensive, so they have been prepared in the laboratory and used for mixing tests. Adsorbed plasma or plasma from patients on oral anticoagulants ( Warfarin  etc.) for a week or more is deficient in Factor II, Factor VII, Factor IX, and Factor X. Plasma from patients on oral anticoagulants ( Warfarin  etc.) for 48\u201372 hours is deficient in  Factor VII .  Aged plasma is deficient in  Factor V  &  Factor VIII C. Serum is deficient in factors I, V & VIIIC."}
{"_id": "WikiPedia_Hematology$$$corpus_3665", "text": "Prothrombin time  (PT) may be corrected as follows: [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3666", "text": "Partial thromboplastin time  (PTT) may be corrected as follows: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3667", "text": "Some inhibitors are time dependent. In other words, it takes time for the antibody to react with and inactivate the added clotting factor. The clotting test performed immediately after the specimens are mixed may show correction because the antibody has not had time to inactivate its target factor. A test performed after the mixture is incubated for 1 to 2 hours at 37\u00b0C will show significant prolongation over the clotting time obtained after immediate mixing. Nonspecific inhibitors like the lupus anticoagulant usually are not time dependent; the immediate mixture will show prolongation. Many specific factor inhibitors are time dependent, and the inhibitor will not be detected unless the test is repeated after incubation (factor VIII inhibitors are notorious for this). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3668", "text": "A common problem is an unexplained increase in the PT and/or PTT. If this is observed, the test should be repeated with a fresh sample. Another consideration is  heparin . It is possible that the blood sample was mistakenly drawn though a running line. Interference by heparin can be detected by absorbing the heparin with a resin (\u201cHeparsorb\u201d) or by using an  enzyme  to digest the heparin (\u201cHepzyme [ 8 ] \u201d). Also, the patient's  history  should be checked, especially  with regard to anticoagulant use or  liver disease . Provided that the abnormal result is reproduced on a fresh specimen and there is no obvious explanation from the history, a mixing study should be performed. If the mixing study shows correction and no prolongation with incubation, factor deficiency should be looked for, starting with VIII and IX.  Vitamin K -dependent and nonvitamin K\u2013dependent factors should be considered to rule out vitamin K deficiency, or accidental or surreptitious  warfarin  ingestion."}
{"_id": "WikiPedia_Hematology$$$corpus_3669", "text": "If the mixing study fails to correct, then an inhibitor should be suspected. [ 9 ] [ 10 ]  The most common inhibitor is a nonspecific inhibitor such as a  lupus anticoagulant . [ 9 ]  Perform a test to demonstrate a phospholipid-dependent antibody, such as a  platelet  neutralization procedure. Spontaneous specific inhibitors against clotting factors occur (i.e. not in  hemophiliacs ), most often against factor VIII. [ 11 ]  This can occur in patients with  systemic lupus erythematosus ,  monoclonal gammopathies , other  malignancies , during  pregnancy  and for no apparent reason ( idiopathic ). These patients can have devastating bleeding. The thing to do is identify the specific factor involved and find out how high the titer is. If the patient has a low titer inhibitor, try to overwhelm it with high doses of the factor. If the patient has a high titer antibody against  factor VIII , try  porcine factor VIII , activated prothrombin complex concentrate  FEIBA  (Factor Eight Inhibitor Bypassing Agent), [ 12 ]  or  NovoSeven [ 13 ]  to stop the bleeding.  Prednisone  will often lower the titer over time.  Intravenous immunoglobulin  has been reported to also help but it does not seem to work for hemophiliacs with an inhibitor.   Rituximab ,  cyclophosphamide  or other immunosuppressive therapy may be required. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3670", "text": "In order to provide specific cutoffs to distinguish an inhibitor defect from a factor deficiency, the \"Rosner index\" (index of circulating anticoagulant) [ 15 ]  and/or the \"Chang percentage\" (percent correction method) can be used: [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3671", "text": "R \n o \n s \n n \n e \n r \n \n i \n n \n d \n e \n x \n = \n \n \n \n ( \n a \n P \n T \n T \n \n o \n f \n \n 1 \n : \n 1 \n \n m \n i \n x \n ) \n \u2212 \n ( \n a \n P \n T \n T \n \n o \n f \n \n n \n o \n r \n m \n a \n l \n \n p \n o \n o \n l \n e \n d \n \n p \n l \n a \n s \n m \n a \n ) \n \n \n a \n P \n T \n T \n \n o \n f \n \n n \n o \n n \n m \n i \n x \n e \n d \n \n p \n a \n t \n i \n e \n n \n t \n \n p \n l \n a \n s \n m \n a \n \n \n \n x \n 100 \n \n \n {\\displaystyle Rosner\\;index={\\frac {(aPTT\\;of\\;1:1\\;mix)-(aPTT\\;of\\;normal\\;pooled\\;plasma)}{aPTT\\;of\\;nonmixed\\;patient\\;plasma}}x100}"}
{"_id": "WikiPedia_Hematology$$$corpus_3672", "text": "Results are: \u226410 is classified as correction, \u226515 indicates presence of an inhibitor, and 11-15 is classified as \"indeterminate\". [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3673", "text": "C \n h \n a \n n \n g \n \n p \n e \n r \n c \n e \n n \n t \n a \n g \n e \n = \n \n \n \n ( \n a \n P \n T \n T \n \n o \n f \n \n n \n o \n n \n m \n i \n x \n e \n d \n \n p \n a \n t \n i \n e \n n \n t \n \n p \n l \n a \n s \n m \n a \n ) \n \u2212 \n ( \n a \n P \n T \n T \n \n o \n f \n \n 1 \n : \n 1 \n \n m \n i \n x \n ) \n \n \n ( \n a \n P \n T \n T \n \n o \n f \n \n n \n o \n n \n m \n i \n x \n e \n d \n \n p \n a \n t \n i \n e \n n \n t \n \n p \n l \n a \n s \n m \n a \n ) \n \u2212 \n ( \n a \n P \n T \n T \n \n o \n f \n \n n \n o \n r \n m \n a \n l \n \n p \n o \n o \n l \n e \n d \n \n p \n l \n a \n s \n m \n a \n ) \n \n \n \n x \n 100 \n \n \n {\\displaystyle Chang\\;percentage={\\frac {(aPTT\\;of\\;nonmixed\\;patient\\;plasma)-(aPTT\\;of\\;1:1\\;mix)}{(aPTT\\;of\\;nonmixed\\;patient\\;plasma)-(aPTT\\;of\\;normal\\;pooled\\;plasma)}}x100}"}
{"_id": "WikiPedia_Hematology$$$corpus_3674", "text": "Results are classified as follows: <58% as inhibitor and >70% as correction. [ 18 ] >"}
{"_id": "WikiPedia_Hematology$$$corpus_3675", "text": "Alternatively, correction into the reference range can be used to define complete correction. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3676", "text": "A fourth method is known as Estimated Factor Correction (EFC). This method involves four steps.  First, determine the most likely factor suspected to be deficient, based on PT, aPTT, and clinical history.  Next, choose the appropriate curve \u2014 single factor deficiency, vitamin K-dependent factor deficient, or all factor-deficient. Use this curve to estimate the factor level in the patient sample.  Then, predict the factor level and PT or aPTT that will occur after 1:1 mix in case of deficiency.  Finally, compare the actual mix results with the predicted results for deficiency. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3677", "text": "Monocyte distribution width  ( MDW ) is a cytometry-based parameter that measures the range of variation of  monocytes . If the parameter is available, it is reported as part of the standard  complete blood count  (CBC) with differential. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3678", "text": "The parameter was FDA cleared as an early sepsis indicator for ER patients in 2019 for  Beckman Coulter . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3679", "text": "MDW serves as an indicator for early screening of sepsis in conjunction with CRP and PCT and for differentiating false positive blood cultures. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3680", "text": "The  monocyte monolayer assay  (MMA) is used to determine the clinical significance of alloantibodies produced by blood transfusion recipients. [ 1 ]  The assay is used to assess the potential for  intravascular hemolysis  when incompatible cellular blood products are transfused to the anemic patient. When donor cells possess substances that are not produced by the recipient, the recipient's immune system produces antibodies against the substance; these are called alloantibodies. Specific white blood cells, called monocytes, are tasked with ingesting foreign material and become activated during certain inflammatory events. [ 2 ] [ 3 ]  These activated  monocytes  come in contact with antibody-sensitized red blood cells (RBC) and may or may not exhibit  phagocytosis  (ingestion) and destroy the donor red blood cells. If monocytes destroy the RBC, the antibody attached to those RBC is considered clinically significant. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3681", "text": "Blood banking  is a concentration within a clinical laboratory that analyzes specimens from potential transfusion recipients and provides compatible blood products to the healthcare team in charge of that patient's care. Several routine tests are performed including blood typing (determination of  ABO / Rh  status), antibody screening, serologic  cross-matching , direct antiglobulin testing, and antibody identification. Beyond the presence of naturally occurring antibodies (isohemagglutinins) to the ABO and Rh(D) blood group antigens, additional immune-stimulated antibodies are considered unexpected alloantibodies. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3682", "text": "The identification of unexpected antibodies is a labor-intensive process, and sometimes requires the addition of special laboratory techniques to aid in the proper identification of the antibody. Among these techniques are  elutions , adsorptions, and enzyme treatment. [ 4 ] [ 5 ]  Some patients produce antibodies to high frequency antigens. That is, the red cell antigens are present in a significant portion of the human population. It may be questionable and very difficult to assess if the antibody is considered clinically significant or not. [ 6 ]  A clinically significant antibody is an antibody that is capable of causing in vitro hemolysis or a decreased survival of transfused donor red blood cells. [ 7 ]  Antibodies to high frequency antigens can be assessed for clinical significance using the monocyte monolayer assay.  [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3683", "text": "There are many different varieties of abnormal reactions to blood transfusion. Among these, a potentially life-threatening reaction is known as a  hemolytic transfusion reaction . This is an immune mediated reaction where recipient antibodies attack donor red blood cell antigen(s), causing hemolysis of donor cells. The reaction may occur during, immediately after, or up to 28 days later. An acute reaction is observed within the first 24 hours, whereas a delayed reaction will be observed between 24 hours and 28 days after transfusion. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3684", "text": "When talking about the ABO blood group system, Landsteiner's Law states that if an individual possesses the A and/or B antigen, they will not form antibodies to these antigens. [ 9 ]  However, if an individual does not have either A or B antigens, they will naturally produce anti-A and anti-B antibodies. [ 10 ]  According to the  International Society of Blood Transfusion  (ISBT), 43 blood group systems containing hundreds of different red blood cell antigens have been described.  [ 11 ]  With some exceptions, many non-ABO blood group system antigens require a sensitizing event to stimulate antibody production. In other words, the immune system must be exposed to the antigen in order to illicit antibody production. Exposure to antigens can occur through blood transfusion, stem cell/bone marrow transplant, and pregnancy. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3685", "text": "The clinical significance of an alloantibody depends on its ability to cause a decrease in donor red blood cell survival. [ 12 ]  Characteristics of clinically significant alloantibodies include:  immunoglobulin G  antibody subclass, reactivity at body temperature, and ability to cause red blood cell agglutination in the presence of anti-human globulin (AHG) in an indirect antiglobulin test. [ 4 ]  Sometimes, clinical significance of an antibody can be difficult to determine. [ 6 ]  Antibodies to high prevalence red cell antigens can sometimes mask the detection of clinically significant alloantibodies because the corresponding antigen is present on most, if not all, of the screening red blood cells used to detect these antibodies possess the antigen. This is where the monocyte monolayer assay may be useful."}
{"_id": "WikiPedia_Hematology$$$corpus_3686", "text": "The MMA is a very labor-intensive, manual laboratory testing method. The following steps are performed in this assay: [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3687", "text": "If the positive or negative controls fail, than the entire testing procedure is invalid and must be repeated. Criteria for a positive MMA will vary by laboratory, though the originally established threshold set by Sandra Nance et al., is >20% phagocytic activity observed. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3688", "text": "Clinically, a positive MMA would indicate that the patient's serum used in the assay contains clinically significant antibodies that are capable of causing  antibody-mediated phagocytosis ."}
{"_id": "WikiPedia_Hematology$$$corpus_3689", "text": "Nightscout  is a  free and open-source  project, and associated social movement, that enables accessing and working with  continuous glucose monitor  (CGM) data. [ 1 ] [ 2 ] \nNightscout software aims to give users access to their real time  blood sugar  data by putting this data in the  cloud . In addition to browser-based data visualization, Nightscout can also be used to review data from a phone or  smartwatch , or to remotely monitor CGM data for individuals with  type 1 diabetes . Associated with Nightscout software is a broader \"CGM in the Cloud\" social movement, supporting individuals seeking to access and use realtime CGM data through commercial and  DIY  (\"do it yourself\") approaches. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3690", "text": "The Nightscout Project traces its origin to February 2013, when the parents of a 4-year-old boy newly diagnosed with type 1 diabetes began using a continuous glucose monitoring system.\n [ 1 ] [ 2 ] \nThis data was inaccessible to the parents when the child was at school \u2013 there was no commercially available way to access the data in real time. The boy's father, John Costik, a software engineer, developed software to access and transfer CGM data to cloud computing infrastructure. Costik shared his accomplishment on  Twitter  and, after others expressed interest, privately shared the source code. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3691", "text": "Costik's uploader was expanded by Lane Desborough and Ross Naylor, [ 4 ]  to develop \"Nightscout\": adding a blood glucose chart display that could be viewed throughout a home. Further development to make the software accessible to the general public occurred within a private community of developers, including Ben West, [ 5 ] [ 6 ]  Ross Naylor, Kevin Lee, [ 7 ]  Jason Calabrese, Jason Adams, and Toby Canning.  Because this software was, in effect, an unlicensed medical device, the community delayed releasing the code as open source to explore and address legal concerns. Once this was done, the combined code was released in 2014 as the Nightscout Project. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3692", "text": "A website,  Facebook  group, and  Gitter channel  were also created to support new users. [ 3 ] [ 9 ]  The primary Facebook group for the movement is \"CGM in the Cloud\", broadly supporting individuals seeking to use realtime CGM data, via commercial and/or  DIY  methods. As of May 2017, this group has over 23,000 members. In addition, the related  501(c)(3) organization   Nightscout Foundation  was formed in 2014 to encourage and support open source technology projects for individuals with type 1 diabetes. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3693", "text": "The #WeAreNotWaiting hashtag used by the group was initially coined by Lane Desborough [ 11 ]  and Howard Look, in reference to a growing call for a \"diabetes data exchange\" hosted by  Tidepool  and  DiabetesMine  in November 2013. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3694", "text": "A survey of the Nightscout community indicated that the software was most highly used by parents of young children with type 1 diabetes (less than 12 years of age), but is also used by adolescents and adults.\n [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3695", "text": "Because Nightscout software displays information relevant to medical care, there are safety concerns regarding reliability, liability, and regulation. The United States  Food and Drug Administration  (FDA) expressed concern that a singular entity was needed to review code, monitor safety, and respond to issues. [ 2 ]  As of 2016, no such entity had arisen, beyond the unstructured approach of community communication channels (e.g. Facebook group and Gitter channel). [ 3 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3696", "text": "As a non-commercial open source project, Nightscout software has not been regulated by the FDA. [ 2 ] [ 14 ]  The software is released with a strong disclaimer:"}
{"_id": "WikiPedia_Hematology$$$corpus_3697", "text": "Highly experimental. Not intended for therapy. Use at your own risk. Intended only as an investigational and educational tool to learn about this technology."}
{"_id": "WikiPedia_Hematology$$$corpus_3698", "text": "On November 20, 2020,  Medical Data Networks LLC  (Ben West, CEO) met with and formally petitioned the FDA for clearance of the service product \u201c T1Pal .\u201d    T1Pal  is a hosted Nightscout platform that runs copies of the latest Nightscout software on its servers for the benefit of individual subscribers."}
{"_id": "WikiPedia_Hematology$$$corpus_3699", "text": "Nightscout, when operated as a hosted service, is expected to enable many more people to use and benefit from Nightscout.    T1Pal.com  charges a monthly fee to do this ($12.00/mo.), which includes technical support to set up and use the platform.\n Medical Data Networks LLC  has asserted with the FDA that its implementation of  T1Pal  meets all of the stated FDA requirements for code review, safety monitoring, and responding to issues.  To support this view, a complete copy of the \u201cQuality Management System\u201d currently used by  Medical Data Networks LLC  was provided to the FDA."}
{"_id": "WikiPedia_Hematology$$$corpus_3700", "text": "The FDA generally viewed each operating instance of Nightscout as a \"medical device\" subject to labeling, hazard management, and FDA reporting requirements.    Medical Data Networks LLC  asserts that its product  T1Pal  meets all of the FDA criteria for a \"Class 2\" medical device,  and embraces needed FDA oversight and data reporting requirements.\n Medical Data Networks LLC  is actively seeking to work more efficiently with firms that market CGM and other data so as to improve the quality and efficiency by which data is transferred into Nightscout.   Nightscout's features for remote monitoring, data integration, and sharing are of immense value to the Nightscout community and merit continued support by the CGM device manufacturers. [ citation needed ] .    T1Pal  service adds to the Nightscout software patent-pending sharing features and standard email and phone support capabilities needed to enable access the largest possible community of users."}
{"_id": "WikiPedia_Hematology$$$corpus_3701", "text": "In 2015, subsequent to the development of the Nightscout Project,  Dexcom  released a CGM system that included 'Share', providing software for transferring data to cell phones via  Bluetooth , and sharing CGM data with others via cell phone apps. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3702", "text": "In 2017, the Spanish company Instead Technologies launched a continuous reading system named GlucoAngel for the  FreeStyle Libre flash glucose monitor . [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3703", "text": "In 2020,  Medical Data Networks LLC  commenced commercial service operations, providing  T1Pal  as \"Nightscout in the Cloud\" for $12.00/mo.\nThe service is supported by email and phone support for paying customers.   Beginning January 2022 the company added integrated support for  T1Pal  combined with iPhone Loop services.  This positions  Medical Data Networks LLC  as the first commercial provider of IT services needed to implement and support closed Loop operations."}
{"_id": "WikiPedia_Hematology$$$corpus_3704", "text": "The  OpenAPS  project has extended Nightscout to create a do-it-yourself \"artificial pancreas\", by automating basal insulin delivery by an  insulin pump  to create a \"closed loop\" system. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3705", "text": "Noninvasive glucose monitoring  ( NIGM ), called  Noninvasive continuous glucose monitoring  when used as a  CGM  technique, is the measurement of  blood glucose  levels, required by people with  diabetes  to prevent both chronic and acute complications from the disease, without drawing blood, puncturing the skin, or causing pain or trauma. The search for a successful technique began about 1975 and has continued to the present without a clinically or commercially viable product. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3706", "text": "As of 1999 [update] , only one such product had been approved for sale by the  FDA , based on a technique for electrically pulling glucose through intact skin, and it was withdrawn after a short time owing to poor performance and occasional damage to the skin of users. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3707", "text": "Hundreds of millions of dollars have been invested in companies who have sought the solution to this long-standing problem. Approaches that have been tried include  near-infrared spectroscopy  (NIRS, measuring glucose through the skin using light of slightly longer wavelengths than the  visible region ), [ 3 ]   transdermal  measurement (attempting to pull glucose through the skin using either chemicals, electricity or ultrasound), measuring the amount that  polarized light  is rotated by glucose in the front chamber of the eye (containing the  aqueous humor ), and many others."}
{"_id": "WikiPedia_Hematology$$$corpus_3708", "text": "A 2012 study reviewed ten technologies:  bioimpedance  spectroscopy,  microwave / RF  sensing, [ 4 ] [ 5 ]  fluorescence technology, mid-infrared spectroscopy, near-infrared spectroscopy,  optical coherence tomography , optical  polarimetry ,  Raman spectroscopy , reverse  iontophoresis , and  ultrasound  technology, concluding with the observation that none of these had produced a commercially available, clinically reliable device and that therefore, much work remained to be done. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3709", "text": "As of 2014 [update] , disregarding the severe shortcomings mentioned above, at least one non-invasive glucose meter was being marketed in a number of countries. [ 7 ] [ 8 ]  Still, as the mean absolute deviation of this device was nearly 30% in clinical trials, \"further research efforts were desired to significantly improve the accuracy [...]\". [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3710", "text": "While multiple technologies have been tried, Raman spectroscopy has gained traction as one promising technology for measuring glucose in  interstitial fluid . Early attempts include C8 Medisensors [ 10 ]  and the Laser Biomedical Research Center at  Massachusetts Institute of Technology  (MIT) which have been working on a Raman spectroscopy sensor for more than 20 years and conducting clinical investigations in collaboration with the Clinical Research Center at  University of Missouri , Columbia, US. [ 11 ] \nIn 2018 a paper in PLOS ONE  showed independent validation data from a clinical investigation comprising 15 subjects with  diabetes mellitus type 1  with a mean absolute relative difference (MARD) of 25.8%. [ 12 ]  The system used, was a custom-built  confocal  Raman setup.\nIn 2019 researchers at the  Samsung Advanced Institute of Technology  (SAIT),  Samsung Electronics , in collaboration with the Laser Biomedical Research Center MIT developed a new approach based on Raman spectroscopy that allowed them to see the glucose signal directly. The researchers tested the system in pigs and could get accurate glucose readings for up to an hour after initial calibration. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3711", "text": "In 2020,  German Institute for Diabetes-Technology  published data from 15 subjects with type 1 diabetes on a new prototype GlucoBeam based on Raman spectroscopy from RSP Systems Denmark, showing a MARD of 23.6% on independent validation in out-patient setup with up till 8 days without recalibration. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3712", "text": "With accuracy on marketed BGM devices in the US between 5.6 and 20.8%. [ 15 ]   A NIGM solution would likely need to have an accuracy with a MARD below 20% to be widely accepted."}
{"_id": "WikiPedia_Hematology$$$corpus_3713", "text": "The number of clinical trials of non-invasive glucose monitors has grown throughout the 21st century. While the  National Institutes of Health  recorded only 4 clinical investigations of the technology from 2000 to 2015, there were 16 from 2016 to 2020. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3714", "text": "From approximately 2020, onwards there has been increased R&D activity in the space of new NIGM solutions (particularly CGM ones) with renewed focus on approaches that had already been explored, and new ones altogether.  [ 17 ]  This includes both large tech companies, such as  Apple  and  Samsung , and startup companies."}
{"_id": "WikiPedia_Hematology$$$corpus_3715", "text": "Optical spectroscopy methods in continuous glucose monitoring (CGM) utilize light to measure glucose levels in the interstitial fluid or blood. These methods typically involve shining a specific wavelength of light (near-infrared, mid-infrared, or Raman) onto the skin, where it interacts with the glucose molecules. The light either gets absorbed or scattered by the glucose, and the resulting changes in the light's properties are detected and analyzed. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3716", "text": "DiaMonTech AG is a  Berlin , Germany-based privately-held company developing the D-Pocket, [ 19 ]  a medical device that uses infrared laser technology to scan the tissue fluid in the skin and detect glucose molecules. Short pulses of infrared light are sent to the skin, which are absorbed by the glucose molecules. This generates heat waves that are detected using its patented IRE-PTD method. [ 20 ]  The company claims a high selectivity of its method, results of a first study have been published in the  Journal of Diabetes Science and Technology . In this study, a Median Absolute Relative Difference of 11.3% is claimed. [ 21 ]  DiaMonTech has announced that its envisioned follow-up product D-Sensor, will feature continuous measurements, making it a CGM though no release date has been given. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3717", "text": "Apple  has been working on a noninvasive CGM combining silicon photonics and optical absorption spectroscopy, [ 23 ]  that it seeks to integrate into its  Apple Watch . In March 2023 it was reported to have established proof-of-concept of a noninvasive CGM. [ 24 ]  Another company working on noninvasive CGM is  Masimo , which sued Apple for patent infringement in this area in 2020. [ 25 ]  Masimo has also filed new patents through its subsidiary Cercacor (pending as of September 2023) covering a joint continuous glucose monitoring and pump-closed loop delivery system. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3718", "text": "U.S. company Rockley Photonics is building a Near-Infrared system. This approach integrates Rockley\u2019s short-wave infrared (SWIR) spectroscopy technology into its miniaturized photonic integrated circuit (PIC) chips, with the resulting mechanism aiming to be embedded into a smartwatch-style wearable device. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3719", "text": "Lithuanian  company BROLIS is another NIR Spectroscopy emerging NIGM player. [ 28 ]  Based on news reports, it developed a fully functioning prototype in 2019. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3720", "text": "Samsung  announced that it would be incorporating glucose monitoring with its smartwatch with a targeted release year of 2025. It is not clear whether the watch will integrate readings from an external CGM such as Dexcom's or Abbott's, or work standalone. [ 30 ]  The company in 2020 published literature regarding the aforementioned (see above) non-invasive method it had developed with MIT scientists to engage in continuous glucose monitoring using spectroscopy. [ 31 ]  The company has filed patents related to this technology. [ 32 ]  In January 2024, Samsung gave an update affirming its NIGM ambitions but did not give a release date. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3721", "text": "Seoul, South Korea-based start-up Apollon commenced work on a Raman CGM and secured a partnership with MIT in 2023.  [ 34 ]  In 2024, it secured 2.3B won (approximately $1.5M) in pre-Series A funding for development of needle-free glucose monitoring. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3722", "text": "Liom (formerly called  Spiden ) is a  Swiss  startup building a multi-biomarker and drug level monitoring noninvasive smartwatch wearable (using  Raman spectroscopy ) with continuous glucose monitoring capability as its first application.  [ 36 ] [ 37 ]  It has so far not attained regulatory approval as of October 2023. In January of 2024, Liom declared it had developed a prototype, with a claimed MARD (Mean Absolute Relative Difference) value to a reference glucose measurement of approximately 9%. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3723", "text": "In 2023, RSP Systems Denmark published data from prospective measurements with at least 15 days following calibration. the study was a home-based clinical study involving 160 subjects with diabetes, the largest study of its kind to date. Data from a subset of subjects with type 2 diabetes shoved 99.8% of measurements within A + B zones in the consensus error grid and a mean absolute relative difference of 14.3%. The full clinical study involved 160 subjects, 137 with type 1 on intensive insulin therapy or insulin pumps. The measurements form the type 1 diabetes subgroup, showed 96.5% of the points in zones A + B, while the typical indices of accuracy, the mean absolute relative difference (MARD) and RMSE, over the 15 days were 19.9% and 1.9 mmol/L, respectively. With 12,374 paired data points, the size of the dataset demonstrates the robustness of the Raman spectroscopy-based approach.  [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3724", "text": "Electromagnetic sensing for non-invasive glucose monitoring utilizes the interaction between electromagnetic waves and the glucose molecules present in the body. These techniques typically involve applying a specific radio frequency or microwave signal to the skin, which then penetrates the underlying tissues. The presence of glucose alters the dielectric properties (permittivity and conductivity) of the tissue, leading to changes in the  amplitude , phase, or other characteristics of the transmitted or reflected  electromagnetic waves ."}
{"_id": "WikiPedia_Hematology$$$corpus_3725", "text": "Electrochemical  glucose monitoring is based on the  glucose oxidation reaction .  Glucose oxidase  is the enzyme that is specific to glucose. Glucose is oxidized by oxygen in the presence of glucose oxidase and water to make  gluconolactone  and  hydrogen peroxide . Hydrogen peroxide is further oxidized at the electrode, producing free electrons, resulting in an  electrical current  proportional to the glucose concentration in an area of interest. By measuring this current, the sensor can accurately determine the glucose level. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3726", "text": "Haifa , Israel-based company HAGAR completed a study of its GWave non-invasive CGM, reporting high accuracy. This sensor uses radiofrequency waves to measure glucose levels in the blood. [ 41 ]  The device had not received regulatory approval anywhere as of August 2023. One of the criticisms of radiofrequency technology as a way of measuring glucose is that studies in 2019 found that glucose can only be detected in the far infrared (nanometer wavelengths), rather than radiofrequencies even in the centimeter and millimeter wavelength range, putting into question the viability of radio frequencies for measuring glucose. [ 42 ]  A second study (performed in Israel) reported a GWave prototype showed a MARD of 6.7% though Food and Drug Administration (FDA) comparator standards were not applied (the study determined accuracy (MARD) by comparing with a regular Abbott Blood Glucose Monitoring/fingerstick device as a comparator, which measures capillary blood glucose levels, not venous ones as required for FDA CGM approval). [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3727", "text": "KnowLabs is a  Seattle , U.S-based company building a CGM called the Bio-RFID sensor, which works by sending radio waves through the skin to measure molecular signatures in the blood, which Know Labs' machine learning algorithms use to compute the user's blood sugar levels. The company reported that it had built a prototype, but had not attained regulatory approval as of August 2023. [ 44 ]  In March 2024, news outlets reported that the company's sensor had attained a MARD of 11.1%. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3728", "text": "The BioXensor developed by British company BioRX uses patented radio frequency technology, alongside a multiple sensor (also capturing blood oxygen levels,  ECG , respiration rate, heart rate and body temperature) approach. [ 46 ]  The company claims this enables the measurement of blood glucose levels every minute reliably, accurately, and non-invasively. BioXensor had not received regulatory approval as of June\u00a02023 [update] ."}
{"_id": "WikiPedia_Hematology$$$corpus_3729", "text": "Afon Technology, based in  Wales , is developing  Glucowear , a non-invasive continuous glucose monitor (CGM) using radiofrequency (RF) technology. This device, worn under a smartwatch, has the goal to monitor blood glucose in real-time. Their approach uses RF signals to detect glucose levels beneath the skin, differing from optical sensor-based methods.  [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3730", "text": "Synex Medical (based in Boston, US and Toronto, Canada) uses portable  magnetic resonance spectroscopy  (MRS) for non-invasive glucose monitoring. Their compact devices aim to measure blood metabolites like glucose in real-time by analyzing the magnetic properties of hydrogen atoms in glucose molecules. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3731", "text": "Another noninvasive system was attempted to be built by US company Movano Health. It envisioned a small ring placed on the arm. Movano said in 2021 that it was building the smallest ever custom radio frequency (RF)-enabled sensor designed for simultaneous blood pressure and glucose monitoring. [ 49 ]  Movano is listed as MOVE on NASDAQ. By August 2023 Movano had shifted to building sensor rings for other parameters, such as heart rate,  blood oxygen levels, respiration rate, skin temperature variability, and menstrual symptom tracking. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3732", "text": "SugarBeat, built by  Nemaura Medical , is a wireless non-invasive blood glucose monitoring system using a disposable  skin patch . The patch connects to a rechargeable transmitter which detects blood sugar and transfers the data to a mobile app every five minutes. The patch can be used for 24 hours. Electronic currents are used to draw  interstitial fluid  to the surface to analyse the glucose level. SugarBeat has achieved regulatory approval in Saudi Arabia [ 51 ]  and Europe, [ 52 ]  though market penetration rates remain very low. The company declared  US$ 503,906 in revenue for the fiscal year ending March 2022, [ 53 ]  which compares to Dexcom's more than $3 billion. [ 54 ]   As of August\u00a02023 [update]  it had submitted a US  FDA  premarket approval application for sugarBEAT. [ 55 ]  Nemaura was listed on  NASDAQ  since January 2018 as NMRD. [ 56 ] [ 57 ]  However, due to poor performance (a below than $35m market cap) and low trading volumes it was threatened with delisting from NASDAQ (in April 2023). [ 58 ]  It was delisted from NASDAQ January 4, 2024 and is currently trading on  OTC . [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3733", "text": "Glucomodicum is based in  Helsinki , Finland and was founded as a spin out of the  University of Helsinki .  Their attempted solution uses interstitial fluid to non-invasively measure glucose levels continuously. It does not have regulatory approval. [ 60 ]  Its device is a combination of  magnetohydrodynamic  (MHD) technology, advanced algorithms and highly-sensitive biosensors which link to a smartphone app for data collection and reporting. It works by sending a small amount of energy through the skin to the interstitial fluid between the cells, bringing the fluid to the surface of the skin for non-invasive sample capture. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3734", "text": "Occuity, a  Reading , UK-based startup is taking a different approach to noninvasive glucose monitoring, by using the eye. [ 62 ]  The company states it is developing the Occuity Indigo, [ 63 ]  which aims to measure the change in refractive index of the eye to determine the concentration of glucose in the blood. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3735", "text": "BOYDSense is a French-based startup developing a noninvasive glucose monitoring device that analyzes breath-based volatile organic compounds  (VOCs) . The company\u2019s device,  Lassie , measures specific VOCs in the breath, which are metabolic byproducts of glucose usage in the body. Early clinical trials have demonstrated that these VOCs can reliably indicate blood glucose levels in individuals with type 2 diabetes. BOYDSense\u2019s goal is to provide a compact, affordable alternative to traditional CGMs, which rely on blood samples. The technology is currently in clinical trials, with ongoing research to refine its accuracy and algorithm.  [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3736", "text": "The  overall hemostatic potential  ( OHP ) test is a  global coagulation assay  which can be used to measure  coagulation . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  The OHP assay measures total  fibrin  generation in the presence of  thrombin  or  tissue factor  and  tissue plasminogen activator  (t-PA). [ 2 ] [ 1 ] [ 3 ] [ 4 ]  It generates a fibrin time curve through the use of  optical density measurement . [ 1 ]  This curve represents the balance between fibrin formation induced by thrombin or tissue factor and  fibrinolysis  induced by t-PA. [ 1 ]  The assay provides three parameters:  overall coagulation potential  ( OCP ),  overall hemostatic potential  ( OHP ), and  overall fibrinolytic potential  ( OFP ). [ 2 ] [ 1 ] [ 4 ]  OHP is the main parameter, while OCP and OFP are supplementary parameters to assess coagulation and fibrinolysis. [ 3 ]  One further parameter, clot lysis time (CLT), can also be determined. [ 3 ]  The OHP assay measures the integrated effect of  procoagulant ,  anticoagulant , and fibrinolytic factors. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3737", "text": "The OHP is a technically simple [ 1 ] [ 3 ]  but relatively labor-intensive assay. [ 2 ]  As of 2010, it had been implemented in several laboratories, but was not available commercially. [ 3 ]  The assay is novel in terms of its combined evaluation of both fibrin generation and fibrinolysis. [ 1 ]  The test is potentially useful in the evaluation of  hypercoagulability ,  hypocoagulability , and  fibrinolytic abnormalities . [ 1 ] [ 2 ] [ 3 ]  It is able to detect hypercoagulability associated with  pregnancy  and  estrogen / progestogen   hormone therapy . [ 3 ] [ 4 ]  The test has also been used to study coagulation in  feminizing hormone therapy  in  transgender women . [ 5 ]  However, more studies are needed to validate the test as a  biomarker  of  thrombosis  and other abnormalities of coagulation. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3738", "text": "The original OHP assay was developed in  Sweden  by Blomb\u00e4ck and colleagues and was first described in 1999. [ 1 ] [ 6 ] [ 7 ]  It used thrombin to trigger coagulation. [ 1 ]  Since then, a modified version has been developed which can use either thrombin or tissue factor to trigger coagulation. [ 1 ] [ 3 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3739", "text": "Para-aminohippurate  (PAH) clearance  is a method used in  renal physiology  to measure  renal plasma flow , which is a measure of  renal function . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3740", "text": "PAH is completely removed from blood that passes through the kidneys (PAH undergoes both glomerular filtration and tubular secretion), and therefore the rate at which the kidneys can clear PAH from the blood reflects total renal plasma flow."}
{"_id": "WikiPedia_Hematology$$$corpus_3741", "text": "The concentration of PAH is measured in one  arterial blood sample  (P PAH ) and one urine sample(U PAH ). The  urine flow  (V) is also measured. Renal perfusion flow is then calculated by:"}
{"_id": "WikiPedia_Hematology$$$corpus_3742", "text": "What is calculated is the  effective renal plasma flow  (eRPF). However, since the renal  extraction ratio  of PAH almost equals 1, then eRPF almost equals RPF."}
{"_id": "WikiPedia_Hematology$$$corpus_3743", "text": "The renal  extraction ratio  of PAH in a normal individual is approximately 0.92, [ 1 ]  and thus not exactly 1.0. Thus, this method usually underestimates RPF by approximately 10%. This margin of error is generally acceptable considering the ease with which eRPF is measured. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3744", "text": "Pentagastrin  (trade name  Peptavlon ) is a synthetic  polypeptide  that has effects like  gastrin  when given  parenterally . [ 2 ]  It stimulates the  secretion  of  gastric acid ,  pepsin , and  intrinsic factor , and has been used as a  diagnostic  aid as the  pentagastrin-stimulated calcitonin test ."}
{"_id": "WikiPedia_Hematology$$$corpus_3745", "text": "Pentagastrin binds to the  cholecystokinin -B receptor, which is expressed widely in the brain.  Activation of these receptors activates the  phospholipase C  second messenger system.  When given  intravenously  it may cause  panic  attacks. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3746", "text": "Pentagastrin's  IUPAC  chemical name is \"N-((1,1-dimethylethoxy)carbonyl)-beta-alanyl-L-tryptophyl-L-methionyl-L-alpha-aspartyl-L-phenylalaninamide\"."}
{"_id": "WikiPedia_Hematology$$$corpus_3747", "text": "Pentagastrin is also used as a stimulation test to elevate of several hormones, such as  serotonin .  It provokes flushing and is useful in evaluating patients who describe flushing, but have normal or only marginally elevated biochemical markers for  carcinoid syndrome . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3748", "text": "It has been used to stimulate ectopic gastric mucosa for the detection of  Meckels diverticulum  by  nuclear medicine . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3749", "text": "The  pentagastrin-stimulated calcitonin test  is a diagnostic test for  medullary carcinoma of the thyroid  (MTC). MTC is a malignancy of the  calcitonin -secreting cells of the  thyroid gland , and thus MTC is commonly associated with an elevated calcitonin level, but an elevated level may not always be obvious. The pentagastrin-stimulated calcitonin test is useful in cases of suspected MTC that are not associated with elevated calcitonin. In these patients, injecting pentagastrin will cause calcitonin levels to rise significantly above the normal or basal range. [ 4 ]  After a total  thyroidectomy  for  medullary thyroid carcinoma , the pentagastrin-stimulated  calcitonin  release can be used to detect residual  parafollicular C-cells ."}
{"_id": "WikiPedia_Hematology$$$corpus_3750", "text": "Phadia  develops, manufactures and markets blood test systems to support the clinical diagnosis and monitoring of  allergy ,  asthma  and  autoimmune diseases . The company is headquartered in  Uppsala , Sweden. It has been owned by  Thermo Fisher Scientific  since 2011."}
{"_id": "WikiPedia_Hematology$$$corpus_3751", "text": "Originally part of the  Pharmacia  group of companies and an offshoot of the diagnostics division that developed out of  Pfizer  and Pharmacia & Upjohn (all Uppsala-based companies), Phadia was renamed in January 2006. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3752", "text": "The first steps towards the present  Phadia AB  were taken in the mid 1960s. Three scientists working at  Uppsala University Hospital , Leif Wide, Rolf Ax\u00e9n and  Jerker Porath , then presented their ideas to use Pharmacia's separation medium  Sephadex  as the solid phase in  immunodiagnostics  tests and proposed a collaboration with the company for the commercial development. Pharmacia's management decided to go for the project and established a special R&D group for diagnostics products. In 1970 Pharmacia's first product,  Phadebas  Amylase Test, a test for the enzyme  alpha-amylase , was launched. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3753", "text": "At the same time an important medical discovery was made which would be of decisive importance to Phadia. In 1967  immunoglobulin E , or  IgE , was discovered by two separate research teams, by Teruko and  Kimishige Ishizaka  in the US and by  Gunnar Johansson  and  Hans Bennich \u00a0[ sv ]  at Uppsala University Hospital. Johansson and Bennich worked together with Wide to develop a method to measure the levels of the substance in blood samples. Eventually a clear connection was demonstrated between  IgE  antibodies and  allergic  symptoms. Johansson, Bennich and Wide then suggested that Pharmacia should use the findings to develop a commercial allergy test. This led to the ground-breaking product Phadebas  RAST , which established the leading position that Phadia still maintains in the area of allergy testing. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3754", "text": "Since the discovery of  IgE  in 1967, Phadia has pioneered the development of  in vitro  test systems for  allergy  ( immunoglobulin  E). These  IgE  tests have been followed by tests for  IgG  and  IgA   antibodies , as well as other analytes with applications in  asthma ,  celiac disease  and  autoimmunity . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3755", "text": "In addition, the ImmunoCAP testing system has revolutionized the level of automation and speed which these tests are processed. Based on the high binding capacity and solid phase technology, ImmunoCAP tests are both highly sensitive and highly specific."}
{"_id": "WikiPedia_Hematology$$$corpus_3756", "text": "Phlebotomy  is the process of making a puncture in a  vein , usually in the arm, with a  cannula  for the purpose of  drawing blood . [ 1 ]  The procedure itself is known as a  venipuncture , which is also used for  intravenous therapy . A person who performs a phlebotomy is called a  phlebotomist , although most doctors, nurses, and other technicians can also carry out a phlebotomy. [ 2 ]  In contrast,  phlebectomy  is the removal of a vein."}
{"_id": "WikiPedia_Hematology$$$corpus_3757", "text": "Phlebotomies that are carried out in the treatment of some  blood disorders  are known as  therapeutic phlebotomies . [ 3 ]  The average volume of whole blood drawn in a therapeutic phlebotomy to an adult is 1 unit (450\u2013500 ml) weekly to once every several months, as needed. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3758", "text": "From  Ancient Greek :  \u03c6\u03bb\u03b5\u03b2\u03bf\u03c4\u03bf\u03bc\u03af\u03b1  ( phlebotomia  \u2013  phleb  'blood vessel, vein' +  tomia  'cutting'), via  Old French :  flebothomie  (modern French  phl\u00e9botomie ). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3759", "text": "Phlebotomies are carried out by phlebotomists \u2013 people trained to draw blood mostly from veins for clinical or medical testing, transfusions, donations, or research. Blood is collected primarily by performing  venipunctures , or by using  capillary blood sampling  with [ 5 ]   fingersticks  or a  heel stick  in infants for the collection of minute quantities of blood. [ 6 ]  The duties of a phlebotomist may include interpreting the tests requested, drawing blood into the correct tubes with the proper additives, accurately explaining the procedure to the person and preparing them accordingly, practicing the required forms of  asepsis , practicing standard and  universal precautions , restoring  hemostasis  of the puncture site, giving instructions on post-puncture care, affixing tubes with electronically printed labels, and delivering specimens to a laboratory. [ 7 ]  Some countries, states, or districts require that phlebotomists be licensed or registered. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3760", "text": "A  therapeutic phlebotomy  may be carried out in the treatment of some blood disorders (example:  Hemochromatosis ,  polycythemia vera ,  porphyria cutanea tarda ), and  chronic hives  (in research). [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3761", "text": "In  Australia , there are a number of courses in phlebotomy offered by educational institutions, but training is typically provided on the job. The minimum primary qualification for phlebotomists in Australia is a Certificate III in Pathology Collection (HLT37215) from an approved educational institution. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3762", "text": "In the  UK  there is no requirement for holding a formal qualification or certification prior to becoming a phlebotomist as training is usually provided on the job. The  NHS  offers training with formal certification upon completion. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3763", "text": "Special state certification in the  United States  is required only in four states:  California ,  Washington ,  Nevada , and  Louisiana . A phlebotomist can become nationally certified through many different organizations. However, California currently only accepts national certificates from six agencies. These include the  American Certification Agency  (ACA),  American Medical Technologists  (AMT),  American Society for Clinical Pathology  (ASCP),  National Center for Competency Testing / Multi-skilled Medical Certification Institute  (NCCT/MMCI),  National Credentialing Agency  (NCA), and  National Healthcareer Association  (NHA). [ 12 ]  These and other agencies such as the American Society of Phlebotomy Technicians also certify phlebotomists outside the state of California. To qualify to sit for an examination, candidates must complete a full phlebotomy course and provide documentation of clinical or  laboratory  experience."}
{"_id": "WikiPedia_Hematology$$$corpus_3764", "text": "In  South Africa  learnerships to qualify as a Phlebotomy Technician are offered by many public and private educational institutions as well as by private academies owned up by pathology laboratories (such as Ampath Laboratories, Lancet, PathCare) and healthcare service providers (such as  Netcare ,  South African National Blood Service ). Some of the larger retail pharmacy chains offering in-store clinical services (such as Clicks,  Dis-Chem ) also provide training for aspirant phlebotomists. Certification can be obtained from a number of examination and testing institutions. To work as a phlebotomist in South Africa, registration with the  Health Professions Council of South Africa  (HPCSA) is required."}
{"_id": "WikiPedia_Hematology$$$corpus_3765", "text": "A phlebotomy draw station is a place where blood is drawn from patients for laboratory testing, transfusions, donations, or research purposes. The blood is typically drawn via  venipuncture  or a  finger stick  by a healthcare professional such as a  phlebotomist ,  nurse , or  medical assistant . [ 21 ] \nThe draw station typically includes a padded chair or a bed for patients prone to fainting during blood draws.\nDraw stations can be found in various settings, such as hospitals, clinics, blood donation centers, and independent laboratories or as part of  patient service centers  (PSC)."}
{"_id": "WikiPedia_Hematology$$$corpus_3766", "text": "Early phlebotomists used techniques such as  leeches  and incision to extract blood from the body. Bloodletting was used as a therapeutic as well as a prophylactic process, thought to remove toxins from the body and to balance the  humors . While physicians did perform bloodletting, it was a specialty of  barber surgeons , the primary provider of health care to most people in the medieval and early modern eras."}
{"_id": "WikiPedia_Hematology$$$corpus_3767", "text": "Plasma osmolality  measures the body's  electrolyte\u2013water balance . [ 1 ]  There are several methods for arriving at this quantity through measurement or calculation."}
{"_id": "WikiPedia_Hematology$$$corpus_3768", "text": "Osmolality  and  osmolarity  are measures that are technically different, but functionally the same for normal use. Whereas osmolality (with an \"l\") is defined as the number of  osmoles  (Osm) of solute per  kilogram  of  solvent  (osmol/kg or Osm/kg), osmolarity (with an \"r\") is defined as the number of osmoles of solute per  liter  (L) of  solution  (osmol/L or Osm/L). As such, larger numbers indicate a greater concentration of solutes in the plasma."}
{"_id": "WikiPedia_Hematology$$$corpus_3769", "text": "Osmolality can be measured on an analytical instrument called an  osmometer . It works on the method of depression of  freezing point . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3770", "text": "Osmolarity is affected by changes in water content, as well as temperature and pressure. In contrast, osmolality is independent of temperature and pressure. For a given solution,  osmolarity  is slightly less than osmolality, because the total solvent weight (the  divisor  used for osmolality) excludes the weight of any solutes, whereas the total solution volume (used for osmolarity) includes solute content. Otherwise, one litre of plasma would be equivalent to one kilogram of plasma, and plasma osmolarity and plasma osmolality would be equal. However, at low concentrations (below about 500 mM), the mass of the solute is negligible compared to the mass of the solvent, and osmolarity and osmolality are very similar. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3771", "text": "Technically, the terms can be compared as follows: [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3772", "text": "Therefore, bedside calculations are actually in units of  osmolarity , whereas laboratory measurements will provide readings in units of  osmolality . In practice, there is almost negligible difference between the absolute values of the different measurements.  For this reason, both terms are often used interchangeably, even though they refer to different units of measurement."}
{"_id": "WikiPedia_Hematology$$$corpus_3773", "text": "Normal human  reference range  of osmolality in plasma is about 275-299 milli-osmoles per kilogram. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3774", "text": "Plasma osmolarity of some reptiles, especial those from a freshwater aquatic environment, may be lower than that of mammals (e.g.  < 260 mOsm/L) during favourable conditions. Consequently, solutions osmotically balanced for mammals (e.g., 0.9% normal saline) are likely to be mildly  hypertonic  for such animals.\nMany arid species of reptiles and hibernating  uricotelic  species allow major elevations of plasma osmolarity (e.g.  > 400 mOsm/L) that could be fatal to some mammals. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3775", "text": "Deep-sea fish have adapted to the extreme hydrostatic pressures of depth through a number of factors, including increasing osmolality, with one of the deepest known fish in the world, the hadal snailfish ( Notoliparis kermadecensis)  having a recorded muscle osmolality of 991 \u00b1 22 mOsmol/kg, almost four times the osmolality of mammals and three times that of shallow water fish species (typically 350 mOsmol/kg). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3776", "text": "As  cell membranes  in general are freely permeable to water, the osmolality of the  extracellular fluid  (ECF) is approximately equal to that of the  intracellular fluid  (ICF). Therefore, plasma osmolality is a guide to intracellular osmolality. This is important, as it shows that changes in ECF osmolality have a great effect on ICF osmolality \u2014 changes that can cause problems with normal cell functioning and volume. If the ECF were to become too  hypotonic , water would readily fill surrounding cells, increasing their volume and potentially  lysing  them ( cytolysis ). Many poisons, medications and diseases affect the balance between the ICF and ECF, affecting individual cells and homeostasis as a whole. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3777", "text": "Osmolality of  blood  increases with  dehydration  and decreases with overhydration. In normal people, increased osmolality in the blood will stimulate secretion of  antidiuretic hormone  (ADH). This will result in increased water reabsorption, more concentrated  urine , and less concentrated blood plasma. A low serum osmolality will suppress the release of ADH, resulting in decreased water reabsorption and more concentrated plasma."}
{"_id": "WikiPedia_Hematology$$$corpus_3778", "text": "Syndrome of inappropriate ADH secretion  occurs when excessive release of antidiuretic hormone results in inappropriately elevated urine osmolality (>100 mOsmol/L) relative to the blood plasma, leading to  hyponatraemia . This ADH secretion may occur in excessive amounts from the  posterior pituitary gland , or from ectopic sources such as  small-cell carcinoma of the lung . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3779", "text": "Elevation may be associated with stroke mortality. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3780", "text": "In medical lab reports, this quantity often appears as \"Osmo, Calc\" or \"Osmo (Calc).\" According to the international SI unit use the following equation\u00a0:"}
{"_id": "WikiPedia_Hematology$$$corpus_3781", "text": "Calculated osmolarity = 2 Na + Glucose + Urea (all in mmol/L)"}
{"_id": "WikiPedia_Hematology$$$corpus_3782", "text": "As Na+ is the major extracellular cation, the sum of osmolarity of all other anions can be assumed to be equal to natremia, hence [Na+]x2 \u2248 [Na+] + [anions]"}
{"_id": "WikiPedia_Hematology$$$corpus_3783", "text": "To calculate plasma osmolality use the following equation (typical in the US):"}
{"_id": "WikiPedia_Hematology$$$corpus_3784", "text": "If the patient has ingested  ethanol , the ethanol level should be included in the calculated osmolarity:"}
{"_id": "WikiPedia_Hematology$$$corpus_3785", "text": "Based on the molecular weight of ethanol the divisor should be 4.6 but empiric data shows that ethanol does not behave as an ideal osmole."}
{"_id": "WikiPedia_Hematology$$$corpus_3786", "text": "The  osmolar gap  is the difference between the measured osmolality and the calculated osmolarity.  The difference in units is attributed to the difference in the way that blood solutes are measured in the laboratory versus the way they are calculated.  The laboratory value measures the freezing point depression, properly called  osmolality  while the calculated value is given in units of  osmolarity .  Even though these values are presented in different units, when there is a small amount of solute compared to total volume of solution, the absolute values of osmolality vs. osmolarity are very close.  Often, this results in confusion as to which units are meant.  For practical purposes, the units are considered interchangeable.  The resulting \"osmolar gap\" can be thought of as either osmolar or osmolal, since both units have been used in its derivation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3787", "text": "Measured osmolality is abbreviated \"MO\", calculated osmolarity is abbreviated \"CO\", and the osmolality gap is abbreviated \"OG\". [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3788", "text": "Clinically, the osmolar gap is used to detect the presence of an osmotically active particle that is not normally found in plasma, usually a toxic alcohol such as ethanol, methanol or isopropyl alcohol."}
{"_id": "WikiPedia_Hematology$$$corpus_3789", "text": "Platelet swirling  is a  noninvasive  method for testing the quality of  platelet-rich plasma  (PRP). [ 1 ]   Platelet swirling is caused by  light diffraction  due to the alignment of normal disc-shaped  platelets . These discs align light that is diffracted, creating a cloud- or swirl-like appearance. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3790", "text": "Results of a platelet swirling test are recorded as positive or extensive swirl, moderate or intermediate swirl, and absent or negative swirl. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3791", "text": "A  Price-Jones curve  is a graph showing the  distribution  of diameters of  red blood cells . Higher diameter may be seen in  pernicious anaemia , while lower diameter may be seen after  haemorrhage ."}
{"_id": "WikiPedia_Hematology$$$corpus_3792", "text": "A Price-Jones curve can be used in the diagnosis of  anaemia . [ 1 ] [ 2 ]  Price-Jones curves usually vary both by average red blood cell size, and the distribution of sizes. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3793", "text": "Higher red blood cell diameter and wider variation in size are often seen in  pernicious anaemia . [ 3 ]  Lower diameter with normal variation in size are often seen after  haemorrhage . [ 3 ]  A higher variation in size is known as  anisocytosis . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3794", "text": "A  blood smear  can be used to view individual  red blood cells . The diameter of each red blood cell can be measured, which is usually analogous to volume. [ 2 ]  This is usually performed automatically by particle counters. [ 2 ] [ 4 ]  Data is then converted into a  histogram . [ 1 ]  This can be used to assess  red blood cell distribution width  (RDW). [ 1 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3795", "text": "Cecil Price-Jones first proposed using the Price-Jones curve in a 1922 paper. [ 6 ]  It has been used for assessing  red blood cells  since then. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3796", "text": "Procalcitonin  ( PCT ) is a  peptide  precursor of the hormone  calcitonin , the latter being involved with  calcium   homeostasis . It arises once preprocalcitonin is cleaved by  endopeptidase . [ 1 ]  It was first identified by Leonard J. Deftos and Bernard A. Roos in the 1970s. [ 2 ]  It is composed of 116  amino acids  and is produced by  parafollicular cells  (C cells) of the  thyroid  and by the  neuroendocrine cells  of the lung and the intestine."}
{"_id": "WikiPedia_Hematology$$$corpus_3797", "text": "The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (0.01\u00a0\u03bcg/L) of clinical assays. [ 3 ]  The level of procalcitonin rises in a response to a pro-inflammatory stimulus, especially of  bacterial  origin. It is therefore often classed as an  acute phase reactant . [ 4 ]  The induction period for procalcitonin ranges from 4\u201312 hours with a half-life spanning anywhere from 22\u201335 hours. [ 5 ]  It does not rise significantly with viral or non-infectious inflammations. In the case of viral infections this is due to the fact that one of the cellular responses to a viral infection is to produce  interferon gamma , which also inhibits the initial formation of procalcitonin. [ 6 ]  With the inflammatory cascade and systemic response that a severe  infection  brings, the blood levels of procalcitonin may rise multiple orders of magnitude with higher values correlating with more severe disease. [ 7 ]  However, the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or a decrease in serum calcium levels. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3798", "text": "PCT is a member of the  calcitonin  (CT) superfamily of  peptides . It is a peptide of 116 amino acids with an approximate molecular weight of 14.5 kDa, and its structure can be divided into three sections ( see Figure 1 ): [ 9 ]  amino terminus (represented by the ball and stick model in Figure 1), immature calcitonin (shown in Figure 1 from PDB as the crystal structure of procalcitonin is not yet available), and calcitonin carboxyl-terminus peptide 1. [ 9 ]  Under normal physiological conditions, active CT is produced and secreted in the C-cells of the  thyroid gland  after proteolytic cleavage of PCT, meaning, in a healthy individual, that PCT levels in circulation are very low (<.05\u00a0ng/mL). [ citation needed ]  The pathway for production of PCT under normal and inflammatory conditions are shown in Figure 2. [ 10 ]  During inflammation, LPS, microbial toxin, and inflammatory mediators, such as IL-6 or TNF-\u03b1, induce the CALC-1 gene in adipocytes, but PCT never gets cleaved to produce CT. [ 10 ]  In a healthy individual, PCT in endocrine cells is produced by CALC-1 by elevated calcium levels, glucocorticoids, CGRP, glucagon, or gastrin, and is cleaved to form CT, which is released to the blood. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3799", "text": "PCT is located on the CALC-1 gene on  chromosome  11. [ 9 ]  Bacterial infections induce a universal increase in the CALC-1 gene expression and a release of PCT (>1 \u03bcg/mL). [ 11 ]  Expression of this hormone occurs in a site specific manner. [ 9 ]  In healthy and non-infected individuals, transcription of PCT only occurs in  neuroendocrine  tissue, except for the C cells in the thyroid. The formed PCT then undergoes post-translational modifications, resulting in the production small peptides and mature CT by removal of the C-terminal glycine from the immature CT by peptidylglycine \u03b1-amidating monooxygenase (PAM). [ 12 ]  In a microbial infected individual, non-neuroendocrine tissue also secretes PCT by expression of CALC-1. A microbial infection induces a substantial increase in the expression of CALC-1, leading to the production of PCT in all differentiated cell types. [ 13 ]  The function of PCT synthesized in nonneuroendocrine tissue due to a microbial infection is currently unknown, but, its detection aids in the differentiation of inflammatory processes. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3800", "text": "Due to PCT\u2019s variance between microbial infections and healthy individuals, it has become a marker to improve identification of bacterial infection and guide antibiotic therapy. [ 14 ]  The table below is a summary from Schuetz, Albrich, and Mueller, [ 14 ]  summarizing the current data of selected, relevant studies investigating PCT in different types of infections."}
{"_id": "WikiPedia_Hematology$$$corpus_3801", "text": "Legend: \n\u2713 = Moderate evidence in favor of PCT \n\u2713\u2713 = Good evidence in favor of PCT \n\u2713\u2713\u2713 = Strong evidence in favor of PCT \n~ = Evidence in favor or against the use of PCT, or still undefined"}
{"_id": "WikiPedia_Hematology$$$corpus_3802", "text": "Measurement of procalcitonin can be used as a marker of severe  sepsis  caused by bacteria and generally grades well with the degree of sepsis, [ 51 ]  although levels of procalcitonin in the  blood  are very low. PCT has the greatest  sensitivity  (90%) and  specificity  (91%) for differentiating patients with  systemic inflammatory response syndrome  (SIRS) from those with sepsis, when compared with  IL-2 ,  IL-6 ,  IL-8 ,  CRP  and  TNF-alpha . [ 52 ]  Evidence is emerging that procalcitonin levels can reduce unnecessary antibiotic prescribing to people with  lower respiratory tract infections . [ 53 ]  Currently, procalcitonin assays are widely used in the clinical environment. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3803", "text": "A meta-analysis reported a  sensitivity  of 76% and  specificity  of 70% for bacteremia. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3804", "text": "A 2018 systematic review comparing PCT and  C-reactive protein (CRP)  found PCT to have a sensitivity of 80% and a specificity of 77% in identifying septic patients.  In the study, PCT outperformed CRP in diagnostic accuracy of predicting sepsis. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3805", "text": "In a 2018 meta-analysis of randomized trials of over 4400 ICU patients with sepsis, researchers concluded that PCT led therapy resulted in lower mortality and lower antibiotic administration. [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3806", "text": "Immune responses to both  organ rejection  and severe bacterial infection can lead to similar symptoms such as swelling and fever that can make initial diagnosis difficult. To differentiate between acute rejection of an organ transplant and bacterial infections, plasma procalcitonin levels have been proposed as a potential diagnostic tool. [ 58 ]  Typically the levels of procalcitonin in the blood remain below 0.5\u00a0ng/mL in cases of acute organ rejection, which has been stated previously to be well below the 1 \u03bcg/mL typically seen in bacterial infection. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3807", "text": "Given procalcitonin is a blood marker for bacterial infections, evidence shows that it is a useful tool in guiding the initiation and duration of  antibiotics  in patients with  bacterial pneumonia  and other acute respiratory infections. [ 59 ]  The use of procalcitonin guided antibiotic therapy leads to lower mortality, less antibiotic usage, decreased side effects due to antibiotics and promotes good  antibiotic stewardship . [ 59 ]   The value in these protocols are evident since a high PCT level correlates with increased mortality in critically ill pneumonia patients especially those with a low  CURB-65 pneumonia risk factor  score. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3808", "text": "In adults with acute respiratory infections, a 2017 systematic review found that PCT-guided therapy reduced mortality, reduced antibiotic use (2.4 fewer days of antibiotics) and led to decreased  adverse drug effects  across a variety of clinical settings (ED, ICU, primary care clinic). [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3809", "text": "Procalcitonin-guided treatment limits antibiotic exposure with no increased mortality in patients with acute exacerbation of  chronic obstructive pulmonary disease . [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3810", "text": "Using procalcitonin to guide protocol in  acute asthma exacerbation  led to reduction in prescriptions of antibiotics in primary care clinics, emergency departments and during hospital admission.  This was apparent without an increase in ventilator days or risk of intubation.  Be that acute  asthma  exacerbation is one condition that leads to overuse of antibiotics worldwide, researchers concluded that PCT could help curb over-prescribing. [ 62 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3811", "text": "PCT serves a marker to help differentiate acute respiratory illness such as infection from an acute cardiovascular concern.  It also has value as a prognostic lab value in patients with  atherosclerosis  or  coronary heart disease  as its levels correlate with the severity of the illness. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3812", "text": "The  European Society of Cardiology  recently released a PCT-guided algorithm for administering antibiotics in patients with  dyspnea  and suspected acute  heart failure . The guidelines use a cut off point of     .2\u00a0ng/mL and above as the point at which to give antibiotics. [ 64 ]   This coincides with a 2017 review of literature which concluded that PCT can help reduce antibiotic overuse in patients presenting with acute heart failure. [ 65 ]   In regards to mortality, a meta analysis of over 5000 patients with heart failure concluded that elevated PCT was reliable in predicting short term mortality. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3813", "text": "Blood procalcitonin levels can help confirm  bacterial meningitis  and. if negative, can effectively rule out bacterial meningitis.  This was shown in a review of over 2000 patients in which PCT had a sensitivity of 86% and a specificity of 80% for  cerebrospinal fluid  PCT.  Blood PCT measurements proved superior to cerebrospinal fluid PCT with a sensitivity of 95% and a specificity of 97% as a marker for bacterial meningitis. [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3814", "text": "In acute meningitis, serum PCT is useful as a biomarker for sepsis.  It can also be of use in determining viral meningitis versus bacterial meningitis. These findings are the result of a 2018 literature review. [ 68 ]   This followed a 2015 meta analysis that showed that PCT had a sensitivity of 90% and a specificity of 98% in judging viral versus bacterial meningitis.  PCT also outperformed other biomarkers such as C-reactive protein. [ 69 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3815", "text": "Evidence shows that an elevated PCT above .5\u00a0ng/mL could help diagnose infectious complications of  inflammatory bowel disease  such as abdominal abscesses, bacterial  enterocolitis  etc.  PCT can be effective in early recognition of infections in IBD patients and decisions on whether to prescribe antibiotics. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3816", "text": "Patients with chronic kidney disease and end-stage renal disease are at higher risk for infections, and procalcitonin has been studied in these populations, who often have higher levels. Procalcitonin can be dialyzed, and so levels are dependent upon when patients receive  hemodialysis . While there is no formally accepted cutoff value for patients undergoing HD, using a value of greater or equal to 0.5\u00a0ng/mL yielded a sensitivity of 97-98% and a specificity of 70-96%. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3817", "text": "PCT, possibly together with  CRP , is used to corroborate the  MELD  score. [ 72 ] [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3818", "text": "PCT at a cutoff  value of .5\u00a0ng/mL was effective at ruling in  septic arthritis  in an analysis of over 8000 patients across 10 prospective studies.  PCT had a sensitivity of 54% and specificity of 95%.  The study also concluded that PCT outperforms  C-reactive protein  in differentiating septic arthritis from non-septic arthritis. [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3819", "text": "A 2016 literature review showed that PCT has good value in diagnosing infections in oncologic patients. Moreso, it is especially effective in diagnosing major life threatening episodes in cancer patient such as bacteremia and sepsis. [ 75 ]  Procalcitonin is reliable to monitor recurrence of  medullary thyroid carcinoma .  In detecting cancer recurrence, PCT had a sensitivity and specificity of 96% and 96% respectively. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3820", "text": "In a meta analysis of 17 studies, PCT had a sensitivity of 85% and a specificity of 54% in diagnosing sepsis in neonates and children.  The PCT cut off used was between 2-2.5\u00a0ng/mL. [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3821", "text": "In children presenting with fever without an apparent source, a PCT level of .5\u00a0ng/mL had a sensitivity of 82% and specificity of 86%.  At a 5\u00a0ng/mL value, the sensitivity and specificity were 61% and 94%.  PCT can help the clinical decision making while identifying invasive bacterial infection in children with unexplained fever. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3822", "text": "PCT levels correlate with the degree of illness in pediatric patients with sepsis or  urinary tract infections  making it effective as a prognostic lab value in these patients. [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3823", "text": "Procalcitonin guided cessation of antibiotic use reduces duration of  antibiotic  exposure and lowers mortality in critically ill patients in the  Intensive Care Unit . [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3824", "text": "In adult emergency department patients with respiratory tract illnesses,  PCT-guided treatment groups had reduced antibiotic use. [ 81 ]  PCT references ranges are also used to determine the likelihood a patient has systemic infection (sepsis), thereby reducing incidence of unnecessary antibiotic use in cases where sepsis is unlikely. [ 82 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3825", "text": "Although some literature differs in antibiotic cessation requirements the general consensus is stopping antibiotics when procalcitonin levels fall 80% below peak or below 0.5\u00a0\u03bcg/L at day five or later during antibiotic therapy. [ 83 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3826", "text": "Excessive overdose on  amphetamine  or  its analogs  can induce systemic inflammation; in a case report of amphetamine overdose, without bacterial infection, significant elevations in procalcitonin were observed. [ 84 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3827", "text": "2ZCH ,  2ZCK ,  2ZCL ,  3QUM"}
{"_id": "WikiPedia_Hematology$$$corpus_3828", "text": "354"}
{"_id": "WikiPedia_Hematology$$$corpus_3829", "text": "18048"}
{"_id": "WikiPedia_Hematology$$$corpus_3830", "text": "ENSG00000142515"}
{"_id": "WikiPedia_Hematology$$$corpus_3831", "text": "ENSMUSG00000066513"}
{"_id": "WikiPedia_Hematology$$$corpus_3832", "text": "P07288"}
{"_id": "WikiPedia_Hematology$$$corpus_3833", "text": "P00757"}
{"_id": "WikiPedia_Hematology$$$corpus_3834", "text": "NM_145864"}
{"_id": "WikiPedia_Hematology$$$corpus_3835", "text": "NM_010915"}
{"_id": "WikiPedia_Hematology$$$corpus_3836", "text": "NP_001025218 NP_001025219 NP_001639"}
{"_id": "WikiPedia_Hematology$$$corpus_3837", "text": "NP_035045"}
{"_id": "WikiPedia_Hematology$$$corpus_3838", "text": "Prostate-specific antigen  ( PSA ), also known as  gamma-seminoprotein  or  kallikrein-3  ( KLK3 ), P-30 antigen, is a  glycoprotein   enzyme  encoded in humans by the  KLK3   gene . PSA is a member of the  kallikrein -related  peptidase  family and is secreted by the  epithelial cells  of the  prostate  gland in men and the  paraurethral glands  in women. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3839", "text": "PSA is produced for the  ejaculate , where it liquefies  semen  in the seminal coagulum and allows  sperm  to swim freely. [ 6 ]  It is also believed to be instrumental in dissolving  cervical mucus , allowing the entry of sperm into the  uterus . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3840", "text": "PSA is present in small quantities in the  serum  of men with healthy prostates, but is often elevated in the presence of  prostate cancer  or other prostate disorders. [ 8 ]  PSA is not uniquely an indicator of prostate cancer, but may also detect  prostatitis  or  benign prostatic hyperplasia . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3841", "text": "Clinical practice guidelines  for prostate cancer  screening  vary and are controversial, in part due to uncertainty as to whether the benefits of screening ultimately outweigh the risks of  overdiagnosis  and overtreatment. [ 10 ]  In the United States, the  Food and Drug Administration  (FDA) has approved the PSA test for annual screening of prostate cancer in men of age 50 and older. [ medical citation needed ]  The patient is required to be informed of the risks and benefits of PSA testing prior to performing the test. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3842", "text": "In the United Kingdom, the  National Health Service  (NHS) as of 2018 [update]  does not mandate, nor advise for PSA test, but allows patients to decide based on their doctor's advice. [ 11 ]  The NHS does not offer general PSA screening, for similar reasons. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3843", "text": "PSA levels between 4 and 10 \u00a0 ng/mL (nanograms per milliliter) are considered to be suspicious, and consideration should be given to confirming the abnormal PSA with a repeat test. If indicated,  prostate biopsy  is performed to obtain a tissue sample for histopathological analysis.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3844", "text": "While PSA testing may help 1 in 1,000 avoid death due to prostate cancer, 4 to 5 in 1,000 would die from prostate cancer after 10 years even with screening. This means that PSA screening may reduce mortality from prostate cancer by up to 25%. Expected harms include anxiety for 100\u2013120 receiving false positives, biopsy pain, and other complications from biopsy for false positive tests. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3845", "text": "Use of PSA screening tests is also controversial due to questionable test accuracy. The screening can present abnormal results even when a man does not have cancer (known as a  false-positive  result ), or normal results even when a man does have cancer (known as a  false-negative  result ). [ 13 ]  False-positive test results can cause confusion and anxiety in men, and can lead to unnecessary prostate  biopsies , a procedure which causes risk of pain, infection, and  hemorrhage . False-negative results can give men a false sense of security, though they may actually have cancer. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3846", "text": "Of those found to have prostate cancer, overtreatment is common because most cases of prostate cancer are not expected to cause any symptoms due to low rate of growth of the prostate tumor. Therefore, many will experience the side effects of treatment, such as for every 1000 men screened, 29 will experience erectile dysfunction, 18 will develop urinary incontinence, two  will have serious cardiovascular events, one will develop pulmonary embolus or deep venous thrombosis, and one perioperative death. [ failed verification ]  Since the expected harms relative to risk of death are perceived by patients as minimal, men found to have prostate cancer usually (up to 90% of cases) elect to receive treatment. [ 14 ] [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3847", "text": "Men with prostate cancer may be characterized as low, intermediate, or high risk for having/developing metastatic disease or dying of prostate cancer. PSA level is one of three variables on which the risk stratification is based; the others are the grade of prostate cancer ( Gleason grading system ) and the stage of cancer based on physical examination and imaging studies. D'Amico criteria for each risk category are: [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3848", "text": "Given the relative simplicity of the 1998 D'Amico criteria (above), other predictive models of risk stratification based on  mathematical probability  constructs exist or have been proposed to allow for better matching of treatment decisions with disease features. [ 18 ] \nStudies are being conducted into the incorporation of multiparametric  MRI  imaging results into  nomograms  that rely on PSA, Gleason grade, and tumor stage. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3849", "text": "PSA levels are monitored periodically (e.g., every 6\u201336 months) after treatment for prostate cancer \u2013 more frequently in patients with high-risk disease, less frequently in patients with lower-risk disease. If surgical therapy (i.e., radical prostatectomy) is successful at removing all prostate tissue (and prostate cancer), PSA becomes undetectable within a few weeks. A subsequent rise in PSA level above 0.2 \u00a0 ng/mL [ 20 ]  L [ disputed  \u2013  discuss ]  is generally regarded as evidence of recurrent prostate cancer after a radical prostatectomy; less commonly, it may simply indicate residual benign prostate tissue. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3850", "text": "Following radiation therapy of any type for prostate cancer, some PSA levels might be detected, even when the treatment ultimately proves to be successful. This makes  interpreting the relationship between PSA levels and recurrence/persistence of prostate cancer after radiation therapy more difficult. PSA levels may continue to decrease for several years after radiation therapy. The lowest level is referred to as the PSA nadir. A subsequent increase in PSA levels by 2.0 \u00a0 ng/mL [ disputed  \u2013  discuss ]  above the nadir is the currently accepted definition of prostate cancer recurrence after radiation therapy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3851", "text": "Recurrent prostate cancer detected by a rise in PSA levels after curative treatment is referred to as a \" biochemical recurrence \". The likelihood of developing recurrent prostate cancer after curative treatment is related to the pre-operative variables described in the preceding section (PSA level and grade/stage of cancer). Low-risk cancers are the least likely to recur, but they are also the least likely to have required treatment in the first place. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3852", "text": "PSA levels increase in the setting of prostate infection/inflammation (prostatitis), often markedly (> 100)."}
{"_id": "WikiPedia_Hematology$$$corpus_3853", "text": "PSA was first identified by researchers attempting to find a substance in seminal fluid that would aid in the investigation of rape cases. [ 21 ]  PSA is used to indicate the presence of  semen  in forensic  serology . [ 22 ]  The semen of adult males has PSA levels far in excess of those found in other tissues; therefore, a high level of PSA found in a sample is an indicator that semen may be present. Because PSA is a  biomarker  that is expressed independently of  spermatozoa , it remains useful in identifying semen from  vasectomized  and  azoospermic  males. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3854", "text": "PSA can also be found at low levels in other body fluids, such as urine and breast milk, thus setting a high minimum threshold of interpretation to rule out  false positive  results and conclusively state that semen is present. [ 24 ]  While traditional tests such as crossover  electrophoresis  have a sufficiently low sensitivity to detect only seminal PSA, newer diagnostics tests developed from clinical  prostate cancer screening  methods have lowered the threshold of detection down to 4 \u00a0 ng/mL. [ 25 ]  This level of antigen has been shown to be present in the peripheral blood of males with prostate cancer, and rarely in female urine samples and breast milk. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3855", "text": "PSA is produced in the  epithelial  cells of the prostate, and can be demonstrated in biopsy samples or other  histological  specimens using  immunohistochemistry . Disruption of this epithelium, for example in inflammation or  benign prostatic hyperplasia , may lead to some diffusion of the antigen into the tissue around the epithelium, and is the cause of elevated blood levels of PSA in these conditions. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3856", "text": "More significantly, PSA remains present in prostate cells after they become malignant. Prostate cancer cells generally have variable or weak staining for PSA, due to the disruption of their normal functioning. Thus, individual prostate cancer cells produce less PSA than healthy cells; the raised serum levels in prostate cancer patients is due to the greatly increased number of such cells, not their individual activity. In most cases of prostate cancer, though, the cells remain positive for the antigen, which can then be used to identify  metastasis . Since some high-grade prostate cancers may be entirely negative for PSA, however, histological analysis to identify such cases usually uses PSA in combination with other antibodies, such as  prostatic acid phosphatase  and  CD57 . [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3857", "text": "The physiological function of KLK3 is the dissolution of the coagulum, the sperm-entrapping gel composed of  semenogelins  and  fibronectin . Its proteolytic action is effective in liquefying the coagulum so that the sperm can be liberated. The activity of PSA is well regulated. In the prostate, it is present as an inactive pro-form, which is activated through the action of  KLK2 , another kallikrein-related peptidase. In the prostate, zinc ion concentrations are 10 times higher than in other bodily fluids. Zinc ions have a strong inhibitory effect on the activity of PSA and on that of KLK2, so that PSA is totally inactive. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3858", "text": "Further regulation is achieved through pH variations. Although its activity is increased by higher pH, the inhibitory effect of zinc also increases. The pH of semen is slightly alkaline and the concentrations of zinc are high. On ejaculation, semen is exposed to the acidic pH of the  vagina , due to the presence of  lactic acid . In fertile couples, the final vaginal pH after coitus approaches the 6-7 levels, which coincides well with reduced zinc inhibition of PSA. At these pH levels, the reduced PSA activity is countered by a decrease in zinc inhibition. Thus, the coagulum is slowly liquefied, releasing the sperm in a well-regulated manner. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3859", "text": "Prostate-specific antigen (PSA, also known as kallikrein III, seminin, semenogelase, \u03b3-seminoprotein and P-30 antigen) is a 34- kD   glycoprotein  produced almost exclusively by the  prostate gland . It is a  serine protease  ( EC   3.4.21.77 )  enzyme , the  gene  of which is located on the 19th  chromosome  (19q13) in humans. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3860", "text": "The discovery of prostate-specific antigen (PSA) is beset with controversy; as PSA is present in prostatic tissue and semen, it was independently discovered and given different names, thus adding to the controversy. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3861", "text": "Flocks was the first to experiment with antigens in the prostate [ 30 ]  and 10 years later  Ablin  reported the presence of precipitation antigens in the prostate. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3862", "text": "In 1971, Mitsuwo Hara characterized a unique protein in the semen fluid, gamma-seminoprotein. Li and Beling, in 1973, isolated a protein, E1, from human semen in an attempt to find a novel method to achieve fertility control. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3863", "text": "In 1978, Sensabaugh identified semen-specific protein p30, but proved that it was similar to E1 protein, and that prostate was the source. [ 34 ]  In 1979, Wang purified a tissue-specific antigen from the prostate ('prostate antigen'). [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3864", "text": "PSA was first measured quantitatively in the blood by Papsidero in 1980, [ 36 ]  and Stamey carried out the initial work on the clinical use of PSA as a marker of prostate cancer. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3865", "text": "PSA is normally present in the  blood  at very low levels. The  reference range  of less than 4 \u00a0 ng/mL for the first commercial PSA test, the Hybritech Tandem-R PSA test released in February 1986, was based on a study that found 99% of 472 apparently healthy men had a total PSA level below 4 \u00a0 ng/mL. [ 37 ] [ 38 ] [ 39 ] [ 40 ] [ 41 ] [ 42 ] [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3866", "text": "Increased levels of PSA may suggest the presence of prostate cancer. However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a  false negative . [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3867", "text": "Obesity  has been reported to reduce serum PSA levels. [ 46 ]  Delayed early detection may partially explain worse outcomes in obese men with early prostate cancer. [ 47 ]  After treatment, higher BMI also correlates to higher risk of recurrence. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3868", "text": "PSA levels can be also increased by  prostatitis , irritation,  benign prostatic hyperplasia  (BPH), and recent ejaculation, [ 49 ] [ 50 ]  producing a  false positive  result. Digital  rectal examination  (DRE) has been shown in several studies [ 51 ] [ 52 ] [ 53 ] [ 54 ]  to produce an increase in PSA. However, the effect is clinically insignificant, since DRE causes the most substantial increases in patients with PSA levels already elevated over 4.0 \u00a0 ng/mL. PSA levels are higher during the summer than during the rest of the year. [ 55 ] [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3869", "text": "The \"normal\"  reference ranges  for prostate-specific antigen increase with age, as do the usual ranges in cancer (per associated table). [ 57 ] [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3870", "text": "Despite earlier findings, [ 59 ]  recent research suggests that the rate of increase of PSA (e.g. >0.35 \u00a0 ng/mL/yr, the 'PSA velocity' [ 60 ] ) is not a more specific marker for prostate cancer than the serum level of PSA. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3871", "text": "However, the PSA rate of rise may have value in prostate cancer prognosis. Men with prostate cancer whose PSA level increased by more than 2.0 \u00a0 ng per milliliter during the year before the diagnosis of prostate cancer have a higher risk of death from prostate cancer despite undergoing  radical prostatectomy . [ 62 ]  PSA velocity (PSAV) was found in a 2008 study to be more useful than the PSA doubling time (PSA DT) to help identify those men with life-threatening disease before start of treatment. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3872", "text": "Men who are known to be at risk for prostate cancer, and who decide to plot their PSA values as a function of time (i.e., years), may choose to use a  semi-log plot . An exponential growth in PSA values appears as a straight line [ 64 ]  on a semi-log plot, so that a new PSA value significantly above the straight line signals a  switch  to a new and significantly higher growth rate, [ 64 ]  i.e., a higher PSA velocity."}
{"_id": "WikiPedia_Hematology$$$corpus_3873", "text": "Most PSA in the blood is bound to serum proteins. A small amount is not protein-bound and is called 'free PSA'. In men with prostate cancer, the ratio of free (unbound) PSA to total PSA is decreased. The risk of cancer increases if the free to total ratio is less than 25%. (See graph) The lower the ratio is, the greater the probability of prostate cancer. Measuring the ratio of free to total PSA appears to be particularly promising for eliminating unnecessary  biopsies  in men with PSA levels between 4 and 10 \u00a0 ng/mL. [ 66 ]  However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3874", "text": "The PSA test in 1994 failed to differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the commercial assay kits for PSA did not provide correct PSA values. [ 67 ]  Thus with the introduction of the ratio of free-to-total PSA, the reliability of the test has improved. Measuring the activity of the enzyme could add to the ratio of free-to-total PSA and further improve the diagnostic value of test. [ 68 ]  Proteolytically active PSA has been shown to have an anti-angiogenic effect  [ 69 ]  and certain inactive subforms may be associated with prostate cancer, as shown by MAb 5D3D11, an antibody able to detect forms abundantly represented in sera from cancer patients. [ 70 ] \nThe presence of inactive proenzyme forms of PSA is another potential indicator of disease. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3875", "text": "PSA exists in serum in the free (unbound) form and in a complex with  alpha 1-antichymotrypsin ; research has been conducted to see if measurements of complexed PSA are more specific and sensitive biomarkers for prostate cancer than other approaches. [ 72 ] [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3876", "text": "The term prostate-specific antigen is a  misnomer : it is an  antigen  but is not specific to the prostate. Although present in large amounts in prostatic tissue and semen, it has been detected in other body fluids and tissues. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3877", "text": "In women, PSA is found in  female ejaculate  at concentrations roughly equal to that found in male semen. [ 5 ]  Other than semen and female ejaculate, the greatest concentrations of PSA in biological fluids are detected in breast milk and amniotic fluid. Low concentrations of PSA have been identified in the urethral glands, endometrium, normal breast tissue and salivary gland tissue. PSA also is found in the serum of women with breast, lung, or uterine cancer and in some patients with renal cancer. [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3878", "text": "Tissue samples can be stained for the presence of PSA in order to determine the origin of malignant cells that have metastasized. [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3879", "text": "Prostate-specific antigen has been shown to  interact  with  protein C inhibitor . [ 76 ] [ 77 ] \nProstate-specific antigen interacts with and activates the vascular endothelial growth factors  VEGF-C  and  VEGF-D , which are involved in tumor  angiogenesis  and in the lymphatic  metastasis  of tumors. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3880", "text": "Prothrombin fragment 1+2  ( F1+2 ), also written as  prothrombin fragment 1.2  ( F1.2 ), is a  polypeptide  fragment of  prothrombin  (factor II) generated by the  in vivo   cleavage  of prothrombin into  thrombin  (factor IIa) by the  enzyme   prothrombinase  (a complex of  factor Xa  and  factor Va ). [ 1 ] [ 2 ] [ 3 ]  It is released from the  N-terminus  of prothrombin. [ 3 ]  F1+2 is a marker of  thrombin generation  and hence of  coagulation  activation. [ 4 ] [ 3 ] [ 1 ]  It is considered the best marker of  in vivo  thrombin generation. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3881", "text": "F1+2 levels can be quantified with  blood tests  and is used in the diagnosis of  hyper-  and  hypocoagulable  states and in the monitoring of  anticoagulant  therapy. [ 4 ] [ 1 ]  It was initially determined with a  radioimmunoassay , but is now measured with several  enzyme-linked immunosorbent assays . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3882", "text": "The  molecular weight  of F1+2 is around 41 to 43\u00a0kDa. [ 4 ] [ 1 ]  Its  biological half-life  is 90\u00a0minutes and it persists in blood for a few hours after formation. [ 4 ] [ 3 ] [ 1 ]  The half-life of F1+2 is relatively long, which makes it more reliable for measuring ongoing coagulation than other markers like  thrombin\u2013antithrombin complexes  and  fibrinopeptide A . [ 1 ] [ 3 ]  Concentrations of F1+2 in healthy individuals range from 0.44 to 1.11\u00a0nM. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3883", "text": "F1+2 levels increase with  age . [ 3 ]  Levels of F1+2 have been reported to be elevated in  venous thromboembolism ,  protein C deficiency ,  protein S deficiency ,  atrial fibrillation ,  unstable angina , acute  myocardial infarction , acute  stroke ,  atherosclerosis ,  peripheral arterial disease , and in  smokers . [ 3 ] [ 1 ]  Anticoagulants have been found to reduce F1+2 levels. [ 1 ]  F1+2 levels are increased with  pregnancy [ 5 ]  and by  ethinylestradiol -containing  birth control pills . [ 6 ]  Conversely, they do not appear to be increased with  estetrol - or  estradiol-containing birth control pills . [ 6 ]  However, F1+2 levels have been reported to be increased with oral  estrogen -based  menopausal hormone therapy , whereas  transdermal  estradiol-based menpausal hormone therapy appears to result in less or no consistent increase. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3884", "text": "The  prothrombin time  ( PT ) \u2013 along with its derived measures of  prothrombin ratio  ( PR ) and  international normalized ratio  ( INR ) \u2013 is an  assay  for evaluating the  extrinsic pathway  and  common pathway  of  coagulation . This  blood test  is also called  protime INR  and  PT/INR . They are used to determine the  clotting tendency  of blood, in conditions such as the measure of  warfarin  dosage, liver damage (cirrhosis), and  vitamin K  status. PT measures the following  coagulation factors :  I (fibrinogen) ,  II (prothrombin) ,  V (proaccelerin) ,  VII (proconvertin) , and  X (Stuart\u2013Prower factor) ."}
{"_id": "WikiPedia_Hematology$$$corpus_3885", "text": "PT is often used in conjunction with the  activated partial thromboplastin time  (aPTT) which measures the  intrinsic  pathway  and common pathway of coagulation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3886", "text": "The reference range for prothrombin time depends on the analytical method used, but is usually around 12\u201313 seconds (results should always be interpreted using the reference range from the laboratory that performed the test), and the INR in absence of anticoagulation therapy is 0.8\u20131.2. The target range for INR in anticoagulant use (e.g.  warfarin ) is 2 to 3. In some cases, if more intense anticoagulation is thought to be required, the target range may be as high as 2.5\u20133.5 depending on the indication for anticoagulation. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3887", "text": "Prothrombin time is typically analyzed by a laboratory technologist on an automated instrument at 37\u00a0\u00b0C (as a nominal approximation of normal human body temperature). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3888", "text": "The prothrombin time ratio is the ratio of a subject's measured prothrombin time (in seconds) to the normal laboratory reference PT. The PT ratio varies depending on the specific reagents used, and has been replaced by the INR. [ 3 ]  Elevated INR may be useful as a rapid and inexpensive  diagnostic  of infection in people with COVID-19. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3889", "text": "The result (in seconds) for a prothrombin time performed on a normal individual will vary according to the type of analytical system employed. This is due to the variations between different types and batches of manufacturer's tissue factor used in the reagent to perform the test. The INR was devised to standardize the results. Each manufacturer assigns an ISI value (International Sensitivity Index) for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares to an international reference tissue factor. The ISI is usually between 0.94 and 1.4 for more sensitive and 2.0\u20133.0 for less sensitive thromboplastins. [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3890", "text": "The INR is the ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system being used."}
{"_id": "WikiPedia_Hematology$$$corpus_3891", "text": "PT normal  is established as the geometric mean of the prothrombin times (PT) of a reference sample group. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3892", "text": "The prothrombin time is the time it takes  plasma  to clot after addition of  tissue factor  (obtained from animals such as rabbits, or recombinant tissue factor, or from brains of autopsy patients). This measures the quality of the  extrinsic pathway  (as well as the  common pathway ) of  coagulation . The speed of the  extrinsic pathway  is greatly affected by levels of functional  factor VII  in the body. Factor VII has a short  half-life  and the  carboxylation  of its  glutamate  residues requires  vitamin K . The prothrombin time can be prolonged as a result of deficiencies in vitamin K,  warfarin  therapy,  malabsorption , or lack of intestinal colonization by bacteria (such as in  newborns ). In addition, poor factor VII synthesis (due to  liver disease ) or increased consumption (in  disseminated intravascular coagulation ) may prolong the PT. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3893", "text": "The INR is typically used to monitor patients on warfarin or related oral anticoagulant therapy.  The normal range for a healthy person not using warfarin is 0.8\u20131.2, and for people on warfarin therapy an INR of 2.0\u20133.0 is usually targeted, although the target INR may be higher in particular situations, such as for those with a  mechanical heart valve . If the INR is outside the target range, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot. In patients on a vitamin K antagonist such as warfarin with supratherapeutic INR but INR less than 10 and no bleeding, it is enough to lower the dose or omit a dose, monitor the INR and resume the vitamin K antagonist at an adjusted lower dose when the target INR is reached. [ 9 ]  For people who need rapid reversal of the vitamin K antagonist \u2013 such as due to serious bleeding \u2013 or who need emergency surgery, the effects of warfarin can be reversed with vitamin K,  prothrombin complex concentrate  (PCC), or  fresh frozen plasma  (FFP). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3894", "text": "Lupus anticoagulant , a circulating inhibitor predisposing for thrombosis, may skew PT results, depending on the assay used. [ 11 ]  Variations between various thromboplastin preparations have in the past led to decreased accuracy of INR readings, and a 2005 study suggested that despite international calibration efforts (by INR) there were still statistically significant differences between various kits, [ 12 ]  casting doubt on the long-term tenability of PT/INR as a measure for anticoagulant therapy. [ 13 ]  Indeed, a new prothrombin time variant, the Fiix prothrombin time, intended solely for monitoring warfarin and other vitamin K antagonists has been invented [ 14 ]  and recently become available as a manufactured test. The Fiix prothrombin time is only affected by reductions in factor II and/or factor X and this stabilizes the anticoagulant effect and appears to improve clinical outcome according to an investigator initiated randomized blinded clinical trial, The Fiix-trial. [ 15 ]  In this trial thromboembolism was reduced by 50% during long-term treatment and despite that bleeding was not increased."}
{"_id": "WikiPedia_Hematology$$$corpus_3895", "text": "An estimated 800 million PT/INR assays are performed annually worldwide. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3896", "text": "In addition to the laboratory method outlined above, near-patient testing (NPT) or home INR monitoring is becoming increasingly common in some countries. In the United Kingdom, for example, near-patient testing is used both by patients at home and by some anticoagulation clinics (often hospital-based) as a fast and convenient alternative to the lab method. After a period of doubt about the accuracy of NPT results, a new generation of machines and reagents seems to be gaining acceptance for its ability to deliver results close in accuracy to those of the lab. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3897", "text": "In a typical NPT set up, a small table-top device is used. A drop of capillary blood is obtained with an automated finger-prick, which is almost painless. This drop is placed on a disposable test strip with which the machine has been prepared. The resulting INR comes up on the display a few seconds later. A similar form of testing is used by people with  diabetes  for monitoring  blood sugar  levels, which is easily taught and routinely practiced. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3898", "text": "Local policy determines whether the patient or a coagulation specialist (pharmacist, nurse, general practitioner or hospital doctor) interprets the result and determines the dose of medication. In Germany and Austria, patients may adjust the medication dose themselves, [ citation needed ]  while in the UK and the US this remains in the hands of a health care professional."}
{"_id": "WikiPedia_Hematology$$$corpus_3899", "text": "A significant advantage of home testing is the evidence that patient self-testing with medical support and patient self-management (where patients adjust their own anticoagulant dose) improves anticoagulant control. A meta analysis which reviewed 14 trials showed that home testing led to a reduced incidence of complications (bleeding and thrombosis) and improved the time in the therapeutic range, which is an indirect measure of anticoagulant control. [ 17 ]  In 2022, a smartphone system was introduced by researchers to perform PT/INR testing in an inexpensive and accessible manner. [ 18 ]  It uses the vibration motor and camera ubiquitous on smartphones to track micro-mechanical movements of a copper particle and compute PT/INR values."}
{"_id": "WikiPedia_Hematology$$$corpus_3900", "text": "Other advantages of the NPT approach are that it is fast and convenient, usually less painful, and offers, in home use, the ability for patients to measure their own INRs when required. Among its problems are that quite a steady hand is needed to deliver the blood to the exact spot, that some patients find the finger-pricking difficult, and that the cost of the test strips must also be taken into account. In the UK these are available on prescription so that elderly and unwaged people will not pay for them and others will pay only a standard prescription charge, which at the moment represents only about 20% of the retail price of the strips. In the US, NPT in the home is currently reimbursed by  Medicare  for patients with mechanical heart valves, while private insurers may cover for other indications. Medicare is now covering home testing for patients with chronic atrial fibrillation. Home testing requires a doctor's prescription and that the meter and supplies are obtained from a Medicare-approved Independent Diagnostic Testing Facility (IDTF). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3901", "text": "There is some evidence to suggest that NPT may be less accurate for certain patients, for example those who have the  lupus anticoagulant . [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3902", "text": "International guidelines were published in 2005 to govern home monitoring of oral anticoagulation by the International Self-Monitoring Association for Oral Anticoagulation. [ 20 ]  The international guidelines study stated, \"The consensus agrees that patient self-testing and patient self-management are effective methods of monitoring oral anticoagulation therapy, providing outcomes at least as good as, and possibly better than, those achieved with an anticoagulation clinic. All patients must be appropriately selected and trained. Currently, available self-testing/self-management devices give INR results which are comparable with those obtained in laboratory testing.\""}
{"_id": "WikiPedia_Hematology$$$corpus_3903", "text": "Medicare coverage for home testing of INR has been expanded in order to allow more people access to home testing of INR in the US. The release on 19 March 2008 said, \"[t]he Centers for Medicare & Medicaid Services (CMS) expanded Medicare coverage for home blood testing of prothrombin time (PT) International Normalized Ratio (INR) to include beneficiaries who are using the drug warfarin, an anticoagulant (blood thinner) medication, for chronic atrial fibrillation or venous thromboembolism.\" In addition, \"those Medicare beneficiaries and their physicians managing conditions related to chronic atrial fibrillation or venous thromboembolism will benefit greatly through the use of the home test.\" [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3904", "text": "The prothrombin time was developed by  Armand J. Quick  and colleagues in 1935, [ 22 ]  and a second method was published by  Paul Owren \u00a0[ no ] , [ 23 ]  also called the \"p and p\" or \"prothrombin and proconvertin\" method. It aided in the identification of the  anticoagulants   dicumarol  and  warfarin , [ 24 ]  and was used subsequently as a measure of activity for warfarin when used therapeutically."}
{"_id": "WikiPedia_Hematology$$$corpus_3905", "text": "The INR was invented in the early 1980s by Tom Kirkwood working at the UK National Institute for Biological Standards and Control (and subsequently at the UK National Institute for Medical Research) to provide a consistent way of expressing the prothrombin time ratio, which had previously suffered from a large degree of variation between centres using different reagents. The INR was coupled to Dr Kirkwood's simultaneous invention of the International Sensitivity Index (ISI), which provided the means to calibrate different batches of thromboplastins to an international standard. [ 25 ]  The INR became widely accepted worldwide, especially after endorsement by the World Health Organization. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3906", "text": "A  radioallergosorbent test  ( RAST ) is a blood test using  radioimmunoassay test  to detect specific  IgE  antibodies in order to determine the substances a subject is  allergic  to. This is different from a  skin allergy test , which determines allergy by the reaction of a person's skin to different substances. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3907", "text": "The two most commonly used methods of confirming allergen sensitization are skin testing and allergy blood testing. Both methods are recommended by the NIH guidelines and have similar diagnostic value in terms of sensitivity and specificity. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3908", "text": "Advantages of the allergy blood test range from: excellent reproducibility across the full measuring range of the calibration curve, it has very high specificity as it binds to allergen specific IgE, and extremely sensitive too, when compared with skin prick testing. In general, this method of blood testing (in-vitro, out of body) vs skin-prick testing (in-vivo, in body) has a major advantage: it is not always necessary to remove the patient from an antihistamine medication regimen, and if the skin conditions (such as  eczema ) are so widespread that allergy skin testing cannot be done. Allergy blood tests, such as ImmunoCAP, are performed without procedure variations, and the results are of excellent standardization. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3909", "text": "Adults and children of any age can take an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often more gentle than several skin tests. However, skin testing techniques have improved. Most skin testing does not involve needles and typically skin testing results in minimal patient discomfort. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3910", "text": "Drawbacks to RAST and ImmunoCAP techniques do exist. Compared to skin testing, ImmunoCAP and other RAST techniques take longer to perform and are less cost effective. [ 4 ]  Several studies have also found these tests to be less sensitive than skin testing for the detection of clinically relevant allergies. [ 5 ]   False positive results may be obtained due to  cross-reactivity  of homologous proteins or by  cross-reactive carbohydrate determinants  (CCDs). [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3911", "text": "In the NIH food guidelines issued in December 2010 it was stated that  \"The predictive values associated with clinical evidence of allergy for ImmunoCAP cannot be applied to other test methods.\" [ 7 ]  With over 4000 scientific articles using ImmunoCAP and showing its clinical value, ImmunoCAP is perceived as \"Gold standard\" for in vitro IgE testing [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3912", "text": "The RAST is a  radioimmunoassay test  to detect specific  IgE  antibodies to suspected or known  allergens  for the purpose of guiding a diagnosis about allergy. [ 10 ] [ 11 ]  IgE is the  antibody  associated with  Type I allergic response : for example, if a person exhibits a high level of IgE directed against  pollen , the test may indicate the person is allergic to pollen (or pollen-like) proteins. A person who has outgrown an allergy may still have a positive IgE years after exposure. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3913", "text": "The suspected allergen is bound to an insoluble material and the patient's serum is added. If the serum contains antibodies to the allergen, those antibodies will bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material. The unbound anti-human IgE antibodies are washed away. The amount of radioactivity is proportional to the serum IgE for the allergen. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3914", "text": "RASTs are often used to test for allergies when:"}
{"_id": "WikiPedia_Hematology$$$corpus_3915", "text": "The RAST is scored on a scale from 0 to 6:"}
{"_id": "WikiPedia_Hematology$$$corpus_3916", "text": "The market-leading RAST methodology was invented and marketed in 1974 by  Pharmacia Diagnostics AB , Uppsala, Sweden, and the acronym RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which literature may also describe as: CAP RAST, CAP FEIA ( fluorenzymeimmunoassay ), and Pharmacia CAP. A review of applicable quality assessment programs shows that this new test has replaced the original RAST in approximately 80% of the world's commercial clinical laboratories, where specific IgE testing is performed. The newest version, the ImmunoCAP Specific IgE 0\u2013100, is the only specific IgE assay to receive FDA approval to quantitatively report to its detection limit of 0.1kU/L. This clearance is based on the CLSI/NCCLS-17A Limits of Detection and Limits of Quantitation, October 2004 guideline. [ citation needed ] The guidelines for diagnosis and management of food allergy issues by the National Institute of Health state that:"}
{"_id": "WikiPedia_Hematology$$$corpus_3917", "text": "In 2010 the United States  National Institute of Allergy and Infectious Diseases  recommended that the RAST measurements of specific immunoglobulin E for the diagnosis of allergy be abandoned in favor of testing with more sensitive fluorescence enzyme-labeled assays. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3918", "text": "A  random glucose test , also known as a  random blood glucose test  ( RBG test ) or a  casual blood glucose test  ( CBG test ) is a  glucose test  (test of  blood sugar level ) on the blood of a non- fasting  person. This test assumes a recent  meal  and therefore has higher  reference values  than the fasting blood glucose (FBG) test."}
{"_id": "WikiPedia_Hematology$$$corpus_3919", "text": "Most mentions of  capillary blood glucose  (CBG) tests refer to random, nonfasting instances thereof, but the real distinction in that term is capillary blood glucose versus venous blood glucose, arterial blood glucose, or interstitial fluid glucose; any fingerstick or optical transdermal glucose test, fasting or nonfasting, measures capillary blood glucose level."}
{"_id": "WikiPedia_Hematology$$$corpus_3920", "text": "The reference values for a \"normal\" random glucose test in an average adult are 80\u2013140 mg / dl  (4.4\u20137.8  mmol /l), between 140 and 200 mg / dl  (7.8\u201311.1  mmol /l) is considered pre-diabetes [ citation needed ] , and \u2265 200  mg / dl  is considered diabetes according to ADA guidelines [ 1 ]  (you should visit your doctor or a clinic for additional tests however as a random glucose of > 160 mg / dl  does not necessarily mean you are diabetic). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3921", "text": "Red blood cell distribution width  ( RDW ), as well as various types thereof ( RDW-CV  or  RCDW  and  RDW-SD ), is a measure of the range of variation of  red blood cell  (RBC) volume that is reported as part of a standard  complete blood count . [ 1 ]  Red blood cells have an  average volume  of 80\u2013100 femtoliters, but individual cell volumes vary even in healthy blood. [ 1 ]  Certain disorders, however, cause a significantly increased variation in cell size. Higher RDW values indicate greater variation in size. Normal  reference range  of RDW-CV in human red blood cells is 11.5\u201315.4%. [ 2 ] [ 1 ]  If  anemia  is observed, RDW test results are often used together with  mean corpuscular volume  (MCV) results to determine the possible causes of the anemia. It is mainly used to differentiate an anemia of mixed causes from an anemia of a single cause."}
{"_id": "WikiPedia_Hematology$$$corpus_3922", "text": "Deficiencies of  Vitamin B 12  or  folate  produce a  macrocytic anemia  (large cell anemia) in which the RDW is elevated in roughly two-thirds of all cases. However, a varied size distribution of red blood cells is a hallmark of iron deficiency anemia, and as such shows an increased RDW in virtually all cases. In the case of both iron and B 12  deficiencies, there will normally be a mix of both large cells and small cells, causing the RDW to be elevated. An elevated RDW (red blood cells of unequal sizes) is known as  anisocytosis . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3923", "text": "An elevation in the RDW is not characteristic of all anemias.  Anemia of chronic disease ,  hereditary spherocytosis ,  acute blood loss ,  aplastic anemia  (anemia resulting from an inability of the bone marrow to produce red blood cells), and certain  hereditary hemoglobinopathies  (including some cases of  thalassemia minor ) may all present with a normal RDW. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3924", "text": "The \"width\" in RDW is sometimes thought to be \"misleading\", since it in fact is a measure of deviation of the  volume  of RBCs, and not directly the diameter. RDW-CV \"width\" refers to the width of the volume curve (distribution width), not the width of the cells. \n [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3925", "text": "RDW-SD is calculated as the width (in fL) of the RBC size distribution histogram at the 20% height level. This parameter is, therefore, not influenced by the average RBC size ( mean corpuscular volume , MCV). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3926", "text": "RDW-CV (expressed in\u00a0%) is calculated with the following formula:"}
{"_id": "WikiPedia_Hematology$$$corpus_3927", "text": "Since RDW-CV is mathematically derived from MCV, it is therefore affected by the average RBC size (MCV). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3928", "text": "Anemia in the presence of a normal RDW may suggest  thalassemia . A low  Mentzer Index , calculated from CBC data [MCV/RBC < 13], may suggest this disorder but a hemoglobin electrophoresis would be diagnostic. Anemia of chronic diseases show normal RDW. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3929", "text": "High RDW may be a result of the presence of fragments, groups of agglutination, and/or abnormal shape of red blood cells. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3930", "text": "By severity, elevated RDW can be classified as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_3931", "text": "Red blood cell indices  are  blood tests  that provide information about the  hemoglobin  content and size of  red blood cells .  Abnormal values indicate the presence of  anemia  and which type of anemia it is. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3932", "text": "Mean corpuscular volume (MCV) is the average volume of a red blood cell and is calculated by dividing the  hematocrit  (Hct) by the concentration of red blood cell count. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3933", "text": "Mean corpuscular hemoglobin (MCH) is the average amount of  hemoglobin  (Hb) per red blood cell and is calculated by dividing the hemoglobin by the red blood cell count.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3934", "text": "Mean corpuscular hemoglobin concentration (MCHC) is the average concentration of hemoglobin per unit volume of red blood cells and is calculated by dividing the hemoglobin by the hematocrit.  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3935", "text": "Red blood cell distribution width (RDW or RDW-CV or RCDW and RDW-SD) is a measure of the range of variation of red blood cell (RBC) volume, yielding clues about morphology. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3936", "text": "The reticulocyte production index (RPI) or corrected reticulocyte count (CRC) represents the true significance of the absolute reticulocyte count to provide some reflection of erythropoietic demand and supply. The immature reticulocyte fraction (IRF) goes a step further to cast more light on the same question. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3937", "text": "In:"}
{"_id": "WikiPedia_Hematology$$$corpus_3938", "text": "Reference ranges (reference intervals) for blood tests  are sets of values used by a  health professional  to interpret a set of  medical test  results from blood samples.  Reference ranges  for  blood tests  are studied within the field of  clinical chemistry  (also known as \"clinical biochemistry\", \"chemical pathology\" or \"pure blood chemistry\"), the area of  pathology  that is generally concerned with analysis of  bodily fluids . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3939", "text": "Blood test results should always be interpreted using the reference range provided by the laboratory that performed the test. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3940", "text": "A  reference range  is usually defined as the set of values 95 percent of the normal population falls within (that is, 95%  prediction interval ). [ 2 ]  It is determined by collecting data from vast numbers of laboratory tests. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3941", "text": "In this article, all values (except the ones listed below) denote  blood plasma  concentration, which is approximately 60\u2013100% larger than the actual blood concentration if the amount inside  red blood cells  (RBCs) is negligible. The precise factor depends on  hematocrit  as well as amount inside RBCs. Exceptions are mainly those values that denote total blood concentration, and in this article they are: [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3942", "text": "A few values are for inside red blood cells only:"}
{"_id": "WikiPedia_Hematology$$$corpus_3943", "text": "If not otherwise specified, a reference range for a blood test is generally the  venous  range, as the standard process of obtaining a sample is by  venipuncture . An exception is for acid\u2013base and  blood gases , which are generally given for arterial blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3944", "text": "Still, the blood values are approximately equal between the arterial and venous sides for most substances, with the exception of acid\u2013base, blood gases and drugs (used in  therapeutic drug monitoring  (TDM) assays). [ 6 ]  Arterial levels for drugs are generally higher than venous levels because of extraction while passing through tissues. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3945", "text": "Reference ranges  are usually given as what are the usual (or  normal ) values found in the population, more specifically the  prediction interval  that 95% of the population fall into. This may also be called  standard range . In contrast,  optimal (health) range  or  therapeutic target  is a reference range or limit that is based on concentrations or levels that are associated with optimal health or minimal risk of related complications and diseases. For most substances presented, the optimal levels are the ones normally found in the population as well. More specifically, optimal levels are generally close to a  central tendency  of the values found in the population. However, usual and optimal levels may differ substantially, most notably among vitamins and blood lipids, so these tables give limits on both standard and optimal (or target) ranges. In addition, some values, including  troponin I  and  brain natriuretic peptide , are given as the estimated appropriate  cutoffs  to distinguish healthy people from people with specific conditions, which here are  myocardial infarction  and  congestive heart failure , respectively, for the aforementioned substances. [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3946", "text": "References range may vary with age, sex, race, pregnancy, [ 10 ]  diet, use of prescribed or herbal drugs and stress. Reference ranges often depend on the analytical method used, for reasons such as  inaccuracy , lack of  standardisation , lack of  certified reference material  and differing  antibody reactivity . [ 11 ]  Also, reference ranges may be inaccurate when the reference groups used to establish the ranges are small. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3947", "text": "Smaller, narrower boxes indicate a more tight homeostatic regulation when measured as  standard \"usual\" reference range ."}
{"_id": "WikiPedia_Hematology$$$corpus_3948", "text": "Hormones predominate at the left part of the scale, shown with a red at ng/L or pmol/L, being in very low concentration. There appears to be the greatest cluster of substances in the yellow part (\u03bcg/L or nmol/L), becoming sparser in the green part (mg/L or \u03bcmol/L). However, there is another cluster containing many metabolic substances like cholesterol and glucose at the limit with the blue part (g/L or mmol/L). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3949", "text": "The unit conversions of substance concentrations from the molar to the mass concentration scale above are made as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_3950", "text": "where distance is the direct (not logarithmic) distance in number of  decades  or \"octaves\" to the right the mass concentration is found. To translate from mass to molar concentration, the dividend ( molar mass  and the divisor (1000) in the  division  change places, or, alternatively,  distance to right  is changed to  distance to left . Substances with a molar mass around 1000g/mol (e.g. thyroxine) are almost vertically aligned in the mass and molar images. Adrenocorticotropic hormone, on the other hand, with a molar mass of 4540, [ 13 ]  is 0.7 decades to the right in the mass image. Substances with molar mass below 1000g/mol (e.g. electrolytes and metabolites) would have \"negative\" distance, that is, masses deviating to the left.\nMany substances given in mass concentration are not given in molar amount because they haven't been added to the article."}
{"_id": "WikiPedia_Hematology$$$corpus_3951", "text": "The diagram above can also be used as an alternative way to convert any substance concentration (not only the normal or optimal ones) from molar to mass units and vice versa for those substances appearing in both scales, by measuring how much they are horizontally displaced from one another (representing the molar mass for that substance), and using the same distance from the concentration to be converted to determine the equivalent concentration in terms of the other unit. For example, on a certain monitor, the horizontal distance between the upper limits for parathyroid hormone in pmol/L and pg/mL may be 7\u00a0cm, with the mass concentration to the right. A molar concentration of, for example, 5 pmol/L would therefore correspond to a mass concentration located 7\u00a0cm to the right in the mass diagram, that is, approximately 45 pg/mL."}
{"_id": "WikiPedia_Hematology$$$corpus_3952", "text": "Units do not necessarily imply anything about molarity or mass."}
{"_id": "WikiPedia_Hematology$$$corpus_3953", "text": "A few substances are below this main interval, e.g.  thyroid stimulating hormone , being measured in  m U/L, or above, like  rheumatoid factor  and  CA19-9 , being measured in U/mL."}
{"_id": "WikiPedia_Hematology$$$corpus_3954", "text": "Included here are also related binding proteins, like  ferritin  and  transferrin  for iron, and  ceruloplasmin  for copper."}
{"_id": "WikiPedia_Hematology$$$corpus_3955", "text": "If  arterial / venous  is not specified for an acid\u2013base or blood gas value, then it generally refers to arterial, and not venous which otherwise is standard for other blood tests. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3956", "text": "Acid\u2013base and blood gases are among the few blood constituents that exhibit substantial difference between arterial and venous values. [ 6 ]  Still, pH, bicarbonate and base excess show a high level of  inter-method reliability  between arterial and venous tests, so arterial and venous values are roughly equivalent for these. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3957", "text": "(high sensitive)"}
{"_id": "WikiPedia_Hematology$$$corpus_3958", "text": "The diagrams below take inter-cycle and inter-woman variability into account in displaying reference ranges for  estradiol ,  progesterone ,  FSH  and  LH ."}
{"_id": "WikiPedia_Hematology$$$corpus_3959", "text": "Also including the vitamin B 12 )-related amino acid  homocysteine ."}
{"_id": "WikiPedia_Hematology$$$corpus_3960", "text": "These values (except  Hemoglobin in plasma ) are for total blood and not only blood plasma."}
{"_id": "WikiPedia_Hematology$$$corpus_3961", "text": "These values are for total blood and not only blood plasma."}
{"_id": "WikiPedia_Hematology$$$corpus_3962", "text": "Acute phase proteins  are markers of  inflammation ."}
{"_id": "WikiPedia_Hematology$$$corpus_3963", "text": "Autoantibodies are usually absent or very low, so instead of being given in standard reference ranges, the values usually denote where they are said to be present, or whether the test is a  positive test . There may also be an  equivocal  interval, where it is uncertain whether there is a significantly increased level."}
{"_id": "WikiPedia_Hematology$$$corpus_3964", "text": "Electrolytes  and  metabolites :\nFor iron and copper, some related proteins are also included."}
{"_id": "WikiPedia_Hematology$$$corpus_3965", "text": "Assessment of kidney function  occurs in different ways, using the presence of  symptoms  and  signs , as well as measurements using urine tests, blood tests, and medical imaging."}
{"_id": "WikiPedia_Hematology$$$corpus_3966", "text": "Functions of a healthy kidney  include maintaining a person's   fluid balance , maintaining an  acid-base balance ; regulating electrolytes  sodium ,  and other  electrolytes ;  clearing   toxins ; regulating  blood pressure ; and regulating  hormones , such as  erythropoietin ; and activation of  vitamin D . The kidney is also involved in maintaining blood pH balance."}
{"_id": "WikiPedia_Hematology$$$corpus_3967", "text": "The functions of the kidney include maintenance of  acid-base balance ; regulation of  fluid balance ; regulation of  sodium ,  potassium , and other  electrolytes ;  clearance  of  toxins ; absorption of  glucose ,  amino acids , and other small molecules; regulation of  blood pressure ; production of various  hormones , such as  erythropoietin ; and activation of  vitamin D ."}
{"_id": "WikiPedia_Hematology$$$corpus_3968", "text": "The  Glomerular filtration rate  (GFR) is regarded as the best overall measure of the kidney's ability to carry out these numerous functions. An estimate of the GFR is used clinically to determine the degree of kidney impairment and to track the progression of the disease. The GFR, however, does not reveal the source of the kidney disease. This is accomplished by urinalysis, measurement of urine protein excretion, kidney imaging, and, if necessary, kidney biopsy. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3969", "text": "Much of renal physiology is studied at the level of the  nephron  \u2013 the smallest functional unit of the kidney. Each nephron begins with a  filtration  component that filters the  blood  entering the kidney. This filtrate then flows along the length of the nephron, which is a tubular structure lined by a single layer of specialized  cells  and surrounded by  capillaries . The major functions of these lining cells are the  reabsorption  of water and small molecules from the filtrate into the blood, and the  secretion  of wastes from the blood into the  urine . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3970", "text": "Proper function of the kidney requires that it receives and adequately filters blood. This is performed at the microscopic level by many hundreds of thousands of filtration units called  renal corpuscles , each of which is composed of a  glomerulus  and a  Bowman's capsule . A global assessment of renal function is often ascertained by estimating the rate of filtration, called the  glomerular filtration rate  (GFR)."}
{"_id": "WikiPedia_Hematology$$$corpus_3971", "text": "Clinical assessment can be used to assess the function of the kidneys. This is because a person with abnormally functioning kidneys may have symptoms that develop. For example, a person with chronic kidney disease may develop  oedema  due to failure of the kidneys to regulate water balance. They may develop evidence of chronic kidney disease, that can be used to assess its severity, for example  high blood pressure ,  osteoporosis  or  anaemia . If the kidneys are unable to excrete  urea , a person may develop a widespread  itch  or  confusion . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3972", "text": "Part of the assessment of kidney function includes the measurement of urine and its contents. Abnormal kidney function may cause too much or too little urine to be produced. The ability of the kidneys to filter protein is often measured, as  urine albumin  or  urine protein  levels, [ 2 ]  measured either at a single instance or, because of variation throughout the day, as 24-hour urine tests. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3973", "text": "Blood tests are also used to assess kidney function. These include tests that are intended to directly measure the function of the kidneys, as well as tests that assess the function of the kidneys by looking for evidence of problems associated with abnormal function. One of the measures of kidney function is the glomerular filtration rate (GFR). Other tests that can assess the function of the kidneys include assessment of  electrolyte  levels such as  potassium  and  phosphate , assessment of acid-base status by the measurement of  bicarbonate  levels from a vein, and assessment of the  full blood count  for  anaemia . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3974", "text": "The glomerular filtration rate (GFR) describes the volume of fluid filtered from the  renal  (kidney)  glomerular  capillaries into the  Bowman's capsule  per unit time. [ 3 ]  Creatinine clearance (C Cr ) is the volume of  blood plasma  that is cleared of  creatinine  per unit time and is a useful measure for approximating the GFR. Creatinine clearance exceeds GFR due to creatinine secretion, [ 4 ]  which can be blocked by  cimetidine .   Both GFR and C Cr  may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result ( eGFR  and  eC Cr ) The results of these tests are used to assess the excretory function of the kidneys.  Staging  of  chronic kidney disease  is based on categories of GFR as well as  albuminuria  and cause of  kidney disease . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3975", "text": "Central to the physiologic maintenance of GFR is the differential basal tone of the afferent and efferent arterioles (see diagram). In other words, the filtration rate is dependent on the difference between the higher blood pressure created by vasoconstriction of the input or afferent arteriole versus the lower blood pressure created by lesser vasoconstriction of the output or efferent arteriole."}
{"_id": "WikiPedia_Hematology$$$corpus_3976", "text": "GFR is equal to the  renal clearance ratio  when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. Relating this principle to the below equation \u2013 for the substance used, the product of urine concentration and urine flow equals the mass of substance excreted during the time that urine has been collected. This mass equals the mass filtered at the glomerulus as nothing is added or removed in the nephron. Dividing this mass by the plasma concentration gives the volume of plasma which the mass must have originally come from, and thus the volume of plasma fluid that has entered Bowman's capsule within the aforementioned period of time. The GFR is typically recorded in units of  volume per time , e.g., milliliters per minute ( mL / min ). Compare to  filtration fraction . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3977", "text": "There are several different techniques used to calculate or estimate the glomerular filtration rate (GFR or eGFR). The above formula only applies for GFR calculation when it is equal to the clearance rate."}
{"_id": "WikiPedia_Hematology$$$corpus_3978", "text": "The normal range of GFR, adjusted for  body surface area , is 100\u2013130 average 125 (mL/min)/(1.73 m 2 ) in men and 90\u2013120 (mL/min)/(1.73 m 2 ) in women younger than the age of 40. In children, GFR measured by inulin clearance is 110 (mL/min)/(1.73 m 2 ) until 2 years of age in both sexes, and then it progressively decreases. After age 40, GFR decreases progressively with age, by 0.4\u20131.2 mL/min per year. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3979", "text": "Estimated GFR (eGFR) is now recommended by clinical practice guidelines and regulatory agencies for routine evaluation of GFR whereas measured GFR (mGFR) is recommended as a confirmatory test when more accurate assessment is required. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3980", "text": "The kidney function can also be assessed with  medical imaging . Some forms of imaging, such as  kidney ultrasound  or  CT scans , may assess kidney function by indicating chronic disease that can impact function, by showing a small or shrivelled kidney. [ citation needed ] . Other tests, such as  nuclear medicine  tests, directly assess the function of the kidney by measuring the perfusion and excretion of radioactive substances through the kidneys. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3981", "text": "A decreased renal function can be caused by many types of  kidney disease . Upon presentation of decreased renal function, it is recommended to perform a  history  and  physical examination , as well as performing a  renal ultrasound  and a  urinalysis . [ citation needed ]  The most relevant items in the history are  medications ,  edema ,  nocturia , gross  hematuria ,  family history  of kidney disease,  diabetes  and  polyuria . The most important items in a physical examination are signs of  vasculitis ,  lupus erythematosus ,  diabetes ,  endocarditis  and  hypertension . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3982", "text": "A urinalysis is helpful even when not showing any pathology, as this finding suggests an extrarenal etiology.  Proteinuria  and/or  urinary sediment  usually indicates the presence of  glomerular disease .  Hematuria  may be caused by glomerular disease or by a disease along the  urinary tract . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3983", "text": "The most relevant assessments in a  renal ultrasound  are renal sizes,  echogenicity  and any signs of  hydronephrosis . Renal enlargement usually indicates diabetic nephropathy,  focal segmental glomerular sclerosis  or  myeloma . Renal atrophy suggests longstanding chronic renal disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3984", "text": "Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic group and smoking.\nFor most patients, a GFR over 60 (mL/min)/(1.73 m 2 ) is adequate. But significant decline of the GFR from a previous test result can be an early indicator of kidney disease requiring medical intervention. The sooner kidney dysfunction is diagnosed and treated the greater odds of preserving remaining nephrons, and preventing the need for dialysis."}
{"_id": "WikiPedia_Hematology$$$corpus_3985", "text": "The  severity of chronic kidney disease  (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease (e.g.,  proteinuria ):"}
{"_id": "WikiPedia_Hematology$$$corpus_3986", "text": "Note: others add a \"T\" to patients who have had a transplant regardless of stage."}
{"_id": "WikiPedia_Hematology$$$corpus_3987", "text": "Not all clinicians agree with the above classification, suggesting that it may mislabel patients with mildly reduced kidney function, especially the elderly, as having a disease. [ 6 ] [ 7 ]  A conference was held in 2009 regarding these controversies by Kidney Disease: Improving Global Outcomes (KDIGO) on CKD: Definition, Classification and Prognosis, gathering data on CKD prognosis to refine the definition and staging of CKD. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3988", "text": "Renal functions  include maintaining an  acid\u2013base balance ; regulating  fluid balance ; regulating  sodium ,  potassium , and other  electrolytes ;  clearing   toxins ; absorption of  glucose ,  amino acids , and other small molecules;  regulation of  blood pressure ; production of various  hormones , such as  erythropoietin ; and activation of  vitamin D ."}
{"_id": "WikiPedia_Hematology$$$corpus_3989", "text": "The  kidney  has many functions, which a well-functioning kidney realizes by filtering blood in a process known as  glomerular filtration . A major measure of  kidney function  is the  glomerular filtration rate  ( GFR ).\nThe glomerular filtration rate is the flow rate of filtered fluid through the kidney. The  creatinine clearance rate  ( C Cr  or  CrCl ) is the volume of  blood plasma  that is cleared of  creatinine  per unit time and is a useful measure for approximating the GFR. Creatinine clearance exceeds GFR due to creatinine secretion, [ 1 ]  which can be blocked by  cimetidine .  Both GFR and C Cr  may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result ( eGFR  and  eC Cr ) The results of these tests are used to assess the excretory function of the kidneys.  Staging  of  chronic kidney disease  is based on categories of GFR as well as  albuminuria  and cause of  kidney disease . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3990", "text": "Estimated GFR (eGFR) is now recommended by clinical practice guidelines and regulatory agencies for routine evaluation of GFR whereas measured GFR (mGFR) is recommended as a confirmatory test when more accurate assessment is required. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3991", "text": "Glomerular filtration rate (GFR) is the volume of fluid filtered from the  renal  (kidney)  glomerular  capillaries into the  Bowman's capsule  per unit time. [ 4 ]   Central to the physiologic maintenance of GFR is the differential basal tone of the afferent (input) and efferent (output) arterioles (see diagram). In other words, the filtration rate is dependent on the difference between the higher blood pressure created by vasoconstriction of the afferent arteriole versus the lower blood pressure created by lesser vasoconstriction of the efferent arteriole. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3992", "text": "GFR is equal to the  renal clearance rate  when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. Relating this principle to the below equation \u2013 for the substance used, the product of urine concentration and urine flow equals the mass of substance excreted during the time that urine has been collected. This mass equals the mass filtered at the glomerulus as nothing is added or removed in the nephron. Dividing this mass by the plasma concentration gives the volume of plasma which the mass must have originally come from, and thus the volume of plasma fluid that has entered Bowman's capsule within the aforementioned period of time. The GFR is typically recorded in units of  volume per time , e.g., milliliters per minute (mL/min). Compare to  filtration fraction ."}
{"_id": "WikiPedia_Hematology$$$corpus_3993", "text": "There are several different techniques used to calculate or estimate the glomerular filtration rate (GFR or eGFR). The above formula only applies for GFR calculation when it is equal to the Clearance Rate."}
{"_id": "WikiPedia_Hematology$$$corpus_3994", "text": "In clinical practice, however,  creatinine clearance  or estimates of creatinine clearance based on the serum creatinine level are used to measure GFR. [ citation needed ]  Creatinine is produced naturally by the body ( creatinine   is a breakdown product of  creatine phosphate , which is found in muscle). It is freely filtered by the glomerulus, but also actively  secreted by the peritubular capillaries  in very small amounts such that creatinine clearance overestimates actual GFR by 10\u201320%. This margin of error is acceptable, considering the ease with which creatinine clearance is measured. Unlike precise GFR measurements involving constant infusions of inulin, creatinine is already at a steady-state concentration in the blood, and so measuring creatinine clearance is much less cumbersome.  However, creatinine estimates of GFR have their limitations. All of the estimating equations depend on a prediction of the 24-hour creatinine excretion rate, which is a function of muscle mass which is quite variable.  One of the equations, the Cockcroft and Gault equation (see below) does not correct for race. With a higher muscle mass, serum creatinine will be higher for any given rate of clearance."}
{"_id": "WikiPedia_Hematology$$$corpus_3995", "text": "The GFR can be determined by injecting  inulin  or the inulin-analog  sinistrin  into the blood stream.  Since both inulin and sinistrin are neither reabsorbed nor secreted by the kidney after glomerular filtration, their rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular filter. Incomplete urine collection is an important source of error in inulin clearance measurement. [ 5 ] \nUsing inulin to measure  kidney function  is the  \"gold standard\"  for comparison with other means of estimating  glomerular filtration rate . [ 6 ]  In 2018, the French  pharmacovigilance  agency withdrew  inulin  and  sinistrin -based products from the market after some patients experienced hypersensitivity reactions including a fatal outcome. [ 7 ]  Consequently, the  contrast agents   Iohexol  and  Iothalamate  have become more popular alternatives to determine GFR and are considered to show sufficient accuracy to determine GFR. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3996", "text": "GFR can be accurately measured using radioactive substances, in particular  chromium-51  and  technetium-99m . These come close to the ideal properties of inulin (undergoing only glomerular filtration) but can be measured more practically with only a few urine or blood samples. [ 9 ]  Measurement of renal or plasma clearance of  51 Cr- EDTA  is widely used in Europe but not available in the United States, where  99m Tc- DTPA  may be used instead. [ 10 ]  Renal and plasma clearance  51 Cr-EDTA has been shown to be accurate in comparison with the gold standard, inulin. [ 11 ] [ 12 ] [ 6 ]  Use of  51 Cr\u2011EDTA is considered a reference standard measure in UK guidance. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3997", "text": "Problems with creatinine (varying muscle mass, recent meat ingestion (much less dependent on the diet than urea), etc.) have led to evaluation of alternative agents for estimation of GFR.  One of these is  cystatin C , a ubiquitous protein secreted by most cells in the body (it is an inhibitor of cysteine protease). [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_3998", "text": "Cystatin C is freely filtered at the glomerulus.  After filtration, Cystatin C is reabsorbed and catabolized by the tubular epithelial cells, with only small amounts excreted in the urine.  Cystatin C levels are therefore measured not in the urine, but in the bloodstream."}
{"_id": "WikiPedia_Hematology$$$corpus_3999", "text": "Equations have been developed linking estimated GFR to serum cystatin C levels. [ 15 ]  Most recently, some proposed equations have combined sex, age, adjusted cystatin C and creatinine. In 2022, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN)'s Joint Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases recommended national efforts to facilitate increased, routine, and timely use of cystatin C. They noted that cystatin C would be useful particularly to confirm estimated GFR in adults who are at risk for or have chronic kidney disease. They suggested that combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4000", "text": "INTEGRATION"}
{"_id": "WikiPedia_Hematology$$$corpus_4001", "text": "More precisely, GFR is the fluid flow rate between the glomerular capillaries and the Bowman's capsule:"}
{"_id": "WikiPedia_Hematology$$$corpus_4002", "text": "Where:"}
{"_id": "WikiPedia_Hematology$$$corpus_4003", "text": "Because this constant is a measurement of  hydraulic conductivity  multiplied by the capillary surface area, it is almost impossible to measure physically.  However, it can be determined experimentally.  Methods of determining the GFR are listed in the above and below sections and it is clear from our equation that  \n \n \n \n \n K \n \n f \n \n \n \n \n {\\displaystyle K_{f}} \n \n  can be found by dividing the experimental GFR by the net filtration pressure: [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4004", "text": "The hydrostatic pressure within the glomerular capillaries is determined by the pressure difference between the fluid entering immediately from the  afferent arteriole  and leaving through the  efferent arteriole .  The pressure difference is approximated by the product of the total resistance of the respective arteriole and the flux of blood through it: [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4005", "text": "The pressure in the Bowman's capsule and proximal tubule can be determined by the difference between the pressure in the Bowman's capsule and the descending tubule: [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4006", "text": "Blood plasma has a good many proteins in it and they exert an inward directed force called the  osmotic pressure  on the water in hypotonic solutions across a membrane, i.e., in the Bowman's capsule.  Because plasma proteins are virtually incapable of escaping the glomerular capillaries, this oncotic pressure is defined, simply, by the ideal gas law: [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4007", "text": "This value is almost always taken to be equal to zero because in a healthy  nephron , there should be no proteins in the Bowman's capsule. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4008", "text": "The filtration fraction is the amount of plasma that is actually filtered through the kidney. This can be defined using the equation:"}
{"_id": "WikiPedia_Hematology$$$corpus_4009", "text": "FF = \u2060 GFR / RPF \u2060"}
{"_id": "WikiPedia_Hematology$$$corpus_4010", "text": "Normal human FF is 20%."}
{"_id": "WikiPedia_Hematology$$$corpus_4011", "text": "C x =( U x ) \u2060 V / P x \u2060"}
{"_id": "WikiPedia_Hematology$$$corpus_4012", "text": "In clinical practice, however,  creatinine clearance  or estimates of creatinine clearance based on the serum creatinine level are used to measure GFR. Creatinine is produced naturally by the body ( creatinine   is a breakdown product of  creatine phosphate , which is found in muscle). It is freely filtered by the glomerulus, but also actively  secreted by the peritubular capillaries  in very small amounts such that creatinine clearance overestimates actual GFR by 10\u201320%. This margin of error is acceptable, considering the ease with which creatinine clearance is measured. Unlike precise GFR measurements involving constant infusions of inulin, creatinine is already at a steady-state concentration in the blood, and so measuring creatinine clearance is much less cumbersome.  However, creatinine estimates of GFR have their limitations. All of the estimating equations depend on a prediction of the 24-hour creatinine excretion rate, which is a function of muscle mass which is quite variable.  The Cockcroft-Gault and CKD-EPI 2021 equations (see below) do not correct for race. With a higher muscle mass, serum creatinine will be higher for any given rate of clearance. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4013", "text": "A common mistake made when just looking at serum creatinine is the failure to account for muscle mass.  Hence, an older woman with a serum creatinine of 1.4\u00a0mg/dL may actually have a moderately severe  chronic kidney disease , whereas a young muscular male can have a normal level of renal function at this serum creatinine level.  Creatinine-based equations should be used with caution in  cachectic  patients and patients with  cirrhosis .  They often have very low muscle mass and a much lower creatinine excretion rate than predicted by the equations below, such that a cirrhotic patient with a serum creatinine of 0.9\u00a0mg/dL may have a moderately severe degree of chronic kidney disease."}
{"_id": "WikiPedia_Hematology$$$corpus_4014", "text": "One method of determining GFR from creatinine is to collect urine (usually for 24 h) to determine the amount of creatinine that was removed from the blood over a given time interval.  If one removes 1440\u00a0mg in 24\u00a0h, this is equivalent to removing 1\u00a0mg/min.  If the blood concentration is 0.01\u00a0mg/mL (1\u00a0mg/dL), then one can say that 100 mL/min of blood is being \"cleared\" of creatinine, since, to get 1\u00a0mg of creatinine, 100 mL of blood containing 0.01\u00a0mg/mL would need to have been cleared."}
{"_id": "WikiPedia_Hematology$$$corpus_4015", "text": "Creatinine clearance (C Cr ) is calculated from the creatinine concentration in the collected urine sample (U Cr ),  urine flow rate  (V dt ), and the plasma concentration (P Cr ). Since the product of urine concentration and urine flow rate yields creatinine excretion rate, which is the rate of removal from the blood, creatinine clearance is calculated as removal rate per min (U Cr \u00d7V dt ) divided by the plasma creatinine concentration. This is commonly represented mathematically as"}
{"_id": "WikiPedia_Hematology$$$corpus_4016", "text": "Example: A person has a plasma creatinine concentration of 0.01\u00a0mg/mL and in 1 hour produces 60 mL of urine with a creatinine concentration of 1.25\u00a0mg/mL."}
{"_id": "WikiPedia_Hematology$$$corpus_4017", "text": "The common procedure involves undertaking a 24-hour urine collection, from empty-bladder one morning to the contents of the bladder the following morning, with a comparative blood test then taken.  The urinary flow rate is still calculated per minute, hence:"}
{"_id": "WikiPedia_Hematology$$$corpus_4018", "text": "To allow comparison of results between people of different sizes, the C Cr  is often corrected for the  body surface area  (BSA) and expressed compared to the average sized man as mL/min/1.73 m 2 . While most adults have a BSA that approaches 1.7 m 2  (1.6 m 2  to 1.9 m 2 ), extremely obese or slim patients should have their C Cr  corrected for their  actual  BSA."}
{"_id": "WikiPedia_Hematology$$$corpus_4019", "text": "Twenty-four-hour urine collection to assess creatinine clearance is no longer widely performed, due to difficulty in assuring complete specimen collection.  To assess the adequacy of a complete collection, one always calculates the amount of creatinine excreted over a 24-hour period.  This amount varies with muscle mass and is higher in young people/old, and in men/women.  An unexpectedly low or high 24-hour creatinine excretion rate voids the test.  Nevertheless, in cases where estimates of creatinine clearance from serum creatinine are unreliable, creatinine clearance remains a useful test. These cases include \"estimation of GFR in individuals with variation in dietary intake (vegetarian diet, creatine supplements) or muscle mass (amputation, malnutrition, muscle wasting), since these factors are not specifically taken into account in prediction equations.\" [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4020", "text": "A number of formulae have been devised to estimate GFR or C cr  values on the basis of serum creatinine levels. Where not otherwise stated serum creatinine is assumed to be stated in mg/dL, not \u03bcmol/L\u2014divide by 88.4 to convert from \u03bcmol/Lto mg/dL."}
{"_id": "WikiPedia_Hematology$$$corpus_4021", "text": "A commonly used surrogate marker for the estimation of  creatinine clearance  is the Cockcroft\u2013Gault (CG) formula, which in turn estimates GFR in ml/min: [ 21 ]  It is named after the scientists, the asthmologist  Donald William Cockcroft \u00a0[ de ]  (b. 1946) and the nephrologist  Matthew Henry Gault \u00a0[ de ]  (1925\u20132003), who first published the formula in 1976, and it employs serum  creatinine  measurements and a patient's weight to predict the creatinine clearance. [ 22 ] [ 23 ] \nThe formula, as originally published, is:"}
{"_id": "WikiPedia_Hematology$$$corpus_4022", "text": "When serum creatinine is measured in \u03bcmol/L:"}
{"_id": "WikiPedia_Hematology$$$corpus_4023", "text": "One interesting feature of the Cockcroft and Gault equation is that it shows how dependent the estimation of CCr is based on age. The age term is (140 \u2013 age).  This means that a 20-year-old person (140 \u2013 20 = 120) will have twice the creatinine clearance as an 80-year-old (140 \u2013 80 = 60) for the same level of serum creatinine.  The C-G equation assumes that a woman will have a 15% lower creatinine clearance than a man at the same level of serum creatinine."}
{"_id": "WikiPedia_Hematology$$$corpus_4024", "text": "Another formula for calculating the GFR is the one developed by the  Modification of Diet in Renal Disease Study Group . [ 24 ]  Most laboratories in Australia, [ 25 ]  and the United Kingdom now calculate and report the estimated GFR along with creatinine measurements and this forms the basis of diagnosis of  chronic kidney disease . [ 26 ] [ 27 ]  The adoption of the automatic reporting of MDRD-eGFR has been widely criticised. [ 28 ] [ 29 ] [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4025", "text": "The most commonly used formula is the \"4-variable MDRD\", which estimates GFR using four variables: serum creatinine, age, ethnicity, and gender. [ 31 ]  The original MDRD used six variables with the additional variables being the  blood urea nitrogen  and  albumin  levels. [ 24 ]  The equations have been validated in patients with chronic kidney disease; however, both versions underestimate the GFR in healthy patients with GFRs over 60 mL/min. [ 32 ] [ 33 ]  The equations have not been validated in acute renal failure."}
{"_id": "WikiPedia_Hematology$$$corpus_4026", "text": "For creatinine in \u03bcmol/L:"}
{"_id": "WikiPedia_Hematology$$$corpus_4027", "text": "For creatinine in mg/dL:"}
{"_id": "WikiPedia_Hematology$$$corpus_4028", "text": "A more elaborate version of the MDRD equation also includes  serum albumin  and  blood urea nitrogen  (BUN) levels:"}
{"_id": "WikiPedia_Hematology$$$corpus_4029", "text": "These MDRD equations are to be used only if the laboratory has NOT calibrated its serum creatinine measurements to isotope dilution mass spectrometry (IDMS).  When IDMS-calibrated serum creatinine is used (which is about 6% lower), the above equations should be multiplied by 175/186 or by 0.94086. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4030", "text": "Since these formulae do not adjust for body size, results are given in units of mL/min per 1.73 m 2 , 1.73 m 2  being the estimated body surface area of an adult with a mass of 63\u00a0kg and a height of 1.7\u00a0m."}
{"_id": "WikiPedia_Hematology$$$corpus_4031", "text": "The CKD-EPI  (Chronic Kidney Disease Epidemiology Collaboration) formula was first published in May 2009.  It was developed in an effort to create a formula more accurate than the MDRD formula, especially when actual GFR is greater than 60\u00a0mL/min per 1.73\u00a0m 2 . This is the formula currently recommended by NICE in the UK. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4032", "text": "Researchers pooled data from multiple studies to develop and validate this new equation.  They used 10 studies that included 8254 participants, randomly using 2/3 of the data sets for development and the other 1/3 for internal validation. Sixteen additional studies, which included 3896 participants, were used for external validation."}
{"_id": "WikiPedia_Hematology$$$corpus_4033", "text": "The CKD-EPI equation performed better than the MDRD (Modification of Diet in Renal Disease Study) equation, especially at higher GFR, with less bias and greater accuracy. When looking at NHANES (National Health and Nutrition Examination Survey) data, the median estimated GFR was 94.5\u00a0mL/min per 1.73\u00a0m 2  vs. 85.0\u00a0mL/min per 1.73\u00a0m 2 , and the prevalence of chronic kidney disease was 11.5% versus 13.1%. Despite its overall superiority to the MDRD equation, the CKD-EPI equations performed poorly in certain populations, including black women, the elderly and the obese, and was less popular among clinicians than the MDRD estimate. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4034", "text": "The 2009 CKD-EPI equation is:"}
{"_id": "WikiPedia_Hematology$$$corpus_4035", "text": "where SCr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, a is \u22120.329 for females and \u22120.411 for males, min indicates the minimum of SCr/k or 1, and max indicates the maximum of SCr/k or 1."}
{"_id": "WikiPedia_Hematology$$$corpus_4036", "text": "As separate equations for different populations:\nFor creatinine (IDMS calibrated) in mg/dL:"}
{"_id": "WikiPedia_Hematology$$$corpus_4037", "text": "This formula was developed by Levey et al. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4038", "text": "The 2009 CKD-EPI formula was suggested to improve cardiovascular risk prediction over the MDRD Study formula in a middle-age population. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4039", "text": "The 2021 CKD-EPI formula [ 38 ]  does not include a race coefficient (see discussion below).\nThe 2021 CKD-EPI equation is:"}
{"_id": "WikiPedia_Hematology$$$corpus_4040", "text": "where SCr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, a is \u22120.241 for females and \u22120.302 for males, min indicates the minimum of SCr/k or 1, and max indicates the maximum of SCr/k or 1."}
{"_id": "WikiPedia_Hematology$$$corpus_4041", "text": "Another estimation tool to calculate GFR is the Mayo Quadratic formula. This formula was developed by Rule et al., [ 32 ]  in an attempt to better estimate GFR in patients with preserved kidney function.  It is well recognized that the MDRD formula tends to underestimate GFR in patients with preserved kidney function. Studies in 2008 found that the Mayo Clinic Quadratic Equation compared moderately well with radionuclide GFR, but had inferior bias and accuracy than the MDRD equation in a clinical setting. [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4042", "text": "The equation is:"}
{"_id": "WikiPedia_Hematology$$$corpus_4043", "text": "If Serum Creatinine < 0.8\u00a0mg/dL, use 0.8\u00a0mg/dL for Serum Creatinine."}
{"_id": "WikiPedia_Hematology$$$corpus_4044", "text": "In children, the Schwartz formula is used. [ 41 ] [ 42 ]  This employs the serum  creatinine  (mg/dL), the child's height (cm) and a constant to estimate the glomerular filtration rate:"}
{"_id": "WikiPedia_Hematology$$$corpus_4045", "text": "The method of selection of the constant  k  has been questioned as being dependent upon the gold-standard of renal function used (i.e. inulin clearance, creatinine clearance, etc.) and also may be dependent upon the urinary flow rate at the time of measurement. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4046", "text": "In 2009 the formula was updated to use standardized serum creatinine (recommend  k =0.413) and additional formulas that allow improved precision were derived if serum  cystatin C  is measured in addition to serum creatinine. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4047", "text": "One problem with any creatinine-based equation for GFR is that the methods used to assay creatinine in the blood differ widely in their susceptibility to non-specific chromogens, which cause the creatinine value to be overestimated.  In particular, the MDRD equation was derived using serum creatinine measurements that had this problem.  The NKDEP program in the United States has attempted to solve this problem by trying to get all laboratories to calibrate their measures of creatinine to a \"gold standard\", which in this case is  isotope dilution mass spectrometry  (IDMS).  In late 2009 not all labs in the U.S. had changed over to the new system.  There are two forms of the MDRD equation that are available, depending on whether or not creatinine was measured by an IDMS-calibrated assay.  The CKD-EPI equation is designed to be used with IDMS-calibrated serum creatinine values only. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4048", "text": "The normal range of GFR, adjusted for  body surface area , is 100\u2013130 average 125 mL/min/1.73m 2  in men and 90\u2013120 ml/min/1.73m 2  in women younger than the age of 40. In children, GFR measured by inulin clearance is 110 mL/min/1.73 m 2  until 2 years of age in both sexes, and then it progressively decreases. After age 40, GFR decreases progressively with age, by 0.4\u20131.2 mL/min per year. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4049", "text": "Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic group and smoking.\nFor most patients, a GFR over 60 mL/min/1.73\u00a0m 2  is adequate. But significant decline of the GFR from a previous test result can be an early indicator of kidney disease requiring medical intervention. The sooner kidney dysfunction is diagnosed and treated the greater odds of preserving remaining nephrons, and preventing the need for dialysis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4050", "text": "Not all clinicians agree with the above classification, suggesting that it may mislabel patients with mildly reduced kidney function, especially the elderly, as having a disease. [ 46 ] [ 47 ]  A conference was held in 2009 regarding these controversies by Kidney Disease: Improving Global Outcomes (KDIGO) on CKD: Definition, Classification and Prognosis, gathering data on CKD prognosis to refine the definition and staging of CKD. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4051", "text": "In 2017, Beth Israel Deaconess Medical Center dropped the Black race coefficient in their estimated glomerular filtration rate (eGFR) report, resulting in a steady increase in the percentage of Black patients listed before starting dialysis. Hoenig et al said on the topic \"Race is a social construct that cannot be measured, can be used imprecisely and may contribute to disparities in kidney transplant access for Black patients.\" [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4052", "text": "In 2020, Vyas et al published an article in  The New England Journal of Medicine  criticizing the use of race in eGFR calculations which resulted in higher reported eGFR values for black-identifying patients. They noted that \"The algorithm developers justified these outcomes with evidence of higher average serum creatinine concentrations among black people than among white people. Explanations that have been given for this finding include the notion that black people release more creatinine into their blood at baseline, in part because they are reportedly more muscular. Analyses have cast doubt on this claim, but the \"race-corrected\" eGFR remains the standard.\" They concluded saying \"As long as uncertainty persists about the cause of racial differences in serum creatinine levels, we should favor practices that may alleviate health inequities over those that may exacerbate them.\" [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4053", "text": "In February 2022, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN)'s Joint Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases recommended use of the 2021 CKD-EPI equation which discontinues using a race modifier. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4054", "text": "In July 2022 the  OPTN  Board eliminated race-based calculations for  transplant  candidate listing across all transplant hospitals in the US. [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4055", "text": "Reptilase time  ( RT ) is a  blood test  used to detect deficiency or abnormalities in  fibrinogen , [ 1 ] [ 2 ]  especially in cases of  heparin  contamination."}
{"_id": "WikiPedia_Hematology$$$corpus_4056", "text": "Reptilase , an enzyme found in the  venom  of  Bothrops snakes , has activity similar to  thrombin . Unlike thrombin, reptilase is resistant to inhibition by  antithrombin III . Thus, the reptilase time is not prolonged in blood samples containing heparin,  hirudin , or  direct thrombin inhibitors , whereas the  thrombin time  will be prolonged in these samples. Reptilase also differs from thrombin by releasing  fibrinopeptide A , but not  fibrinopeptide B , in its cleavage of  fibrinogen . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4057", "text": "The  reticulocyte production index  ( RPI ), also called a  corrected reticulocyte count  ( CRC ), is a calculated value used in the diagnosis of  anemia . This calculation is necessary because the raw  reticulocyte  count is misleading in anemic patients. The problem arises because the reticulocyte count is not really a  count  but rather a  percentage : it reports the number of reticulocytes as a percentage of the number of red blood cells. In anemia, the patient's red blood cells are depleted, creating an erroneously  elevated reticulocyte count ."}
{"_id": "WikiPedia_Hematology$$$corpus_4058", "text": "[ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4059", "text": "Reticulocytes  are newly produced red blood cells. They are slightly larger than totally mature red blood cells, and have some residual ribosomal  RNA . The presence of RNA allows a visible blue stain to bind or, in the case of fluorescent dye, result in a different brightness. This allows them to be detected and counted as a distinct population. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4060", "text": "The RPI is used to assess whether the  bone marrow  is producing an appropriate response to an anemic state. Reticulocyte production should increase in response to any loss of red blood cells. It should increase within 2\u20133 days of a major acute  hemorrhage , for instance, and reach its peak in 6\u201310 days. [ 3 ]  If reticulocyte production is not raised in response to anemia, then the anemia may be due to an acute cause with insufficient time to compensate, or there is a defect with red blood cell production in the bone marrow. Marrow defects include nutritional deficiencies (i.e. iron, folate, or B 12 ) or insufficient  erythropoietin , the stimulus for red blood cell production.  Reticulocytopenia , or \"aplastic crisis\", is the medical term for an abnormal decrease of reticulocytes in the body\nThe reticulocyte production index may find new use as a more reliable detector of erythropoietin-doping in athletes. The use of this method is referred to as \"biological passport.\" [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4061", "text": "Reticulocyte Production Index is calculated as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_4062", "text": "1. \n \n \n \n C \n o \n r \n r \n e \n c \n t \n e \n d \n R \n e \n t \n i \n c \n P \n e \n r \n c \n e \n n \n t \n a \n g \n e \n = \n R \n e \n t \n i \n c \n P \n e \n r \n c \n e \n n \n t \n a \n g \n e \n \u2217 \n \n \n \n H \n e \n m \n a \n t \n o \n c \n r \n i \n t \n \n \n N \n o \n r \n m \n a \n l \n H \n e \n m \n a \n t \n o \n c \n r \n i \n t \n \n \n \n \n \n {\\displaystyle CorrectedReticPercentage=ReticPercentage*{Hematocrit \\over NormalHematocrit}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4063", "text": "This calculation is to correct for the severity of the anemia.\nA value of 45% (or 0,45  L/L ) is usually used as a normal hematocrit for males. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4064", "text": "2. The next step is to correct for the longer life span of prematurely released reticulocytes in the blood\u2014a phenomenon of increased red blood cell production. This relies on a table:"}
{"_id": "WikiPedia_Hematology$$$corpus_4065", "text": "So,  in a person whose reticulocyte percentage is 5%, hemoglobin 7.5 g/dL, hematocrit 25%, the RPI would be:"}
{"_id": "WikiPedia_Hematology$$$corpus_4066", "text": "R \n P \n I \n = \n \n \n \n C \n o \n r \n r \n e \n c \n t \n e \n d \n R \n e \n t \n i \n c \n P \n e \n r \n c \n e \n n \n t \n a \n g \n e \n \n \n M \n a \n t \n u \n r \n a \n t \n i \n o \n n \n C \n o \n r \n r \n e \n c \n t \n i \n o \n n \n \n \n \n \n \n {\\displaystyle RPI={CorrectedReticPercentage \\over MaturationCorrection}} \n \n   \u2192 RPI    \n \n \n \n = \n \n \n \n 5 \n \u2217 \n \n \n 25 \n 45 \n \n \n \n 2 \n \n \n = \n \n \n {\\displaystyle ={{5*{25 \\over 45}} \\over 2}=} \n \n 1.4"}
{"_id": "WikiPedia_Hematology$$$corpus_4067", "text": "Alternatively some books provide the following formula and is called  Reticulocyte Index (RI) :"}
{"_id": "WikiPedia_Hematology$$$corpus_4068", "text": "Whereas normal reticulocytes lose their RNA within 24 hours, a severely anemic patient with a full erythropoietin response will release reticulocytes that take from 2-3 days to lose their RNA. This has the effect of raising the reticulocyte count simply because reticulocytes produced on any single\nday will spend more than 1 day in circulation as reticulocytes and, therefore, will be counted for 2 or more days. The  simplest  method for correcting the reticulocyte count, to obtain a more accurate daily production index, is to  divide the corrected count by a factor of 2  ( or multiply with \u00bd ) whenever polychromasia (the presence of immature marrow reticulocytes or \"shift\" cells) is observed on the smear or the immature fraction on the automated counter is increased. [ 5 ]   [ 6 ]   [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4069", "text": "R \n I \n = \n R \n e \n t \n i \n c \n P \n e \n r \n c \n e \n n \n t \n a \n g \n e \n \u2217 \n \n \n \n H \n e \n m \n a \n t \n o \n c \n r \n i \n t \n \n \n N \n o \n r \n m \n a \n l \n H \n e \n m \n a \n t \n o \n c \n r \n i \n t \n \n \n \n \u2217 \n 0.5 \n \n \n {\\displaystyle RI=ReticPercentage*{Hematocrit \\over NormalHematocrit}*0.5} \n \n   \u2192   \n \n \n \n R \n I \n = \n 5 \n \u2217 \n \n \n 25 \n 45 \n \n \n \u2217 \n 0.5 \n = \n \n \n {\\displaystyle RI=5*{25 \\over 45}*0.5=} \n \n 1.4"}
{"_id": "WikiPedia_Hematology$$$corpus_4070", "text": "Interpretation of these values are not standard and vary based on specific laboratory values and clinical context. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4071", "text": "The  ristocetin-induced platelet aggregation  ( RIPA ) is an ex vivo assay for live platelet function. It measures platelet aggregation with the help of  von Willebrand factor  (vWF) and exogenous antibiotic  ristocetin  added in a graded fashion. [ 1 ]  It is similar to the ristocetin cofactor assay but has the added benefit in that it helps in the diagnosis of type 2B/pseudo  von Willebrand disease  (vWD) and  Bernard\u2013Soulier syndrome  because it uses patient's live endogenous platelets, whereas ristocetin cofactor assay tests the function of only the vWF and not the platelets. Ristocetin cofactor assay uses the patient's platelet poor plasma (with vWF but no platelets) and adds ristocetin and exogenous formalin-fixed platelets which can passively agglutinate (but not actively aggregate, as they are dead). Formalin does not allow the extrinsic platelets to secrete the vWF of their \u03b1-granules, and thus only the activity of the intrinsic vWF is tested. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4072", "text": "In an unknown fashion, the antibiotic  ristocetin  causes von Willebrand factor to bind the platelet receptor  glycoprotein Ib  (GpIb), so when ristocetin is added to normal blood, it causes agglutination of fixed platelets or initiates the initial agglutination phase of aggregation of live platelets. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4073", "text": "The results of the ristocetin-induced platelet aggregation in some characteristic diseases are the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_4074", "text": "INTERPRETATION OF TEST\nRAT+ Ve= normal (gp1b & vWF present)\nRAT-ve=abnormal(gp1b & vWF absent)"}
{"_id": "WikiPedia_Hematology$$$corpus_4075", "text": "Schmerber v. California , 384 U.S. 757 (1966), was a  landmark [ 1 ]   United States Supreme Court  case in which the Court clarified the application of the  Fourth Amendment 's protection against  warrantless  searches and the  Fifth Amendment  right against  self-incrimination  for searches that intrude into the human body. Until  Schmerber , the Supreme Court had not yet clarified whether state police officers must procure a search warrant before  taking blood samples  from criminal suspects. Likewise, the Court had not yet clarified whether blood evidence taken against the wishes of a criminal suspect may be used against that suspect in the course of a criminal prosecution. [ fn 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4076", "text": "In a 5\u20134 opinion, the Court held that forced extraction and analysis of a blood sample is not compelled testimony; therefore, it does not violate the Fifth Amendment right against self-incrimination. [ 5 ]  The Court also held that intrusions into the human body ordinarily require a search warrant. [ 6 ]  However, the Court ruled that the involuntary, warrantless blood sample taken in this case was justified under the Fourth Amendment's  exigent circumstances  exception because evidence of blood alcohol would be destroyed by the body's natural  metabolic  processes if the officers were to wait for a warrant. [ 7 ]  In 2013, the Supreme Court clarified in  Missouri v. McNeely  that the natural metabolism of alcohol in the bloodstream is not a  per se  exigency that would always justify warrantless blood tests of individuals suspected of driving under the influence of alcohol. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4077", "text": "In the years following the Court's decision in  Schmerber , many legal scholars feared the ruling would be used to limit  civil liberties . [ 9 ]  Other scholars, including Nita A. Farahany, Benjamin Holley, and John G. New, have suggested courts may use the ruling in  Schmerber  to justify the use of  mind reading  devices against criminal suspects. [ 10 ]  Because the Court's ruling in  Schmerber  prohibited the use of warrantless blood tests in most circumstances, some commentators argue that the decision was responsible for the proliferation of  breathalyzers  to test for alcohol and  urine analyses  to test for controlled substances in criminal investigations. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4078", "text": "In the 1950s, the  Supreme Court of the United States  issued two key rulings clarifying the constitutionality of physical intrusions into the human body by police and other government agents. In  Rochin v. California , police officers broke into the home of an individual suspected of selling narcotics and observed him place several small objects into his mouth. [ 12 ]  Officers were unable to force his mouth open, so they transported him to a local hospital where his stomach was pumped against his will. [ 13 ]  A unanimous Supreme Court held the involuntary stomach pump was an unlawful violation of  substantive due process  because it \"shocked the conscience\", and was so \"brutal\" and \"offensive\" that it did not comport with traditional ideas of fair play and decency. [ 14 ]  In 1957, the Court held in  Breithaupt v. Abram  that involuntary blood samples \"taken by a skilled technician\" neither \"shocked the conscience\" nor violated  substantive due process . [ 15 ]  In  Breithaupt , police took a blood sample from a patient suspected of driving under the influence of alcohol while he lay unconscious in a hospital. [ 16 ]  The Court held that the blood samples were justified, in part, because \"modern community living requires modern scientific methods of crime detection.\" [ 3 ]  Additionally, the Court mentioned in  dicta  that involuntary blood samples may violate the constitution if officers do not provide \"every proper medical precaution\" to the accused. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4079", "text": "Until the twentieth century, courts would admit evidence at trial even if it was seized in violation of the Fourth Amendment. [ 18 ]  Although the Supreme Court developed an  exclusionary rule  for federal cases in  Weeks v. United States  and  Silverthorne Lumber Co. v. United States , [ 19 ]  the Court held in 1949 that the exclusionary rule did not  apply to the states . [ 20 ]  In  Rochin , the Court held that evidence obtained in a manner that \"shocks the conscience\" must be excluded in criminal prosecutions but the court declined to incorporate a broad exclusionary rule for all Fourth Amendment violations. [ 21 ]  By the middle of the twentieth century, many state courts had crafted their own exclusionary rules. [ 22 ]  In 1955, the  California Supreme Court  ruled in  People v. Cahan  that the Fourth Amendment's exclusionary rule applied in California because it was necessary to deter constitutional violations by law enforcement. [ 23 ]  In 1961, the Supreme Court of the United States relied upon  Cahan  to hold in  Mapp v. Ohio  that the exclusionary rule was incorporated to the states. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4080", "text": "On the night of November 12, 1964, Armando Schmerber and a passenger were driving home after drinking at a tavern and bowling alley in the  San Fernando Valley  region of  Los Angeles, California , when their car skidded off the road and struck a tree. [ 25 ]  Schmerber and his companion were injured in the crash and taken to a hospital for treatment. [ 26 ]  When investigating police officers arrived at the hospital, they asked Schmerber to submit a sample of his blood, but Schmerber refused. [ 27 ]  Although they did not possess a  search warrant , officers instructed attending physicians to take a blood sample from Schmerber. [ 28 ]  The blood sample indicated that Schmerber was intoxicated, and he was placed under arrest. [ 29 ]  The blood sample was ultimately admitted into evidence at trial, and Schmerber was convicted for driving under the influence of intoxicating liquors. [ 30 ]  Schmerber objected to the admissibility of the blood sample, claiming that the police violated his rights to  due process , his right against  self-incrimination , his  right to counsel , and his right not to be subjected to  unreasonable searches and seizures . [ 29 ]  The Appellate Department of the California Superior Court rejected Schmerber's arguments, and the California District Court of Appeal declined to review his case. [ fn 2 ] [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4081", "text": "\"I think it follows if this Court holds that it's proper to withdraw the blood that is certainly just as proper to inject the  Nalline  if we're looking at the welfare of society and how we want to keep  narcotic  users off the street.\""}
{"_id": "WikiPedia_Hematology$$$corpus_4082", "text": "Schmerber submitted an appeal to the Supreme Court of the United States, which granted certiorari on January 17, 1966. [ 34 ]  In his brief, Schmerber argued,  inter alia , that the warrantless blood test violated his Fourth Amendment right to be free from unlawful searches and seizures, as well as his Fifth Amendment right against self-incrimination. [ fn 3 ] [ 35 ]  The  Los Angeles City Attorney 's office represented the State of California on appeal. [ 36 ]  In their brief, the City Attorney argued that the blood test did not violate the Fourth Amendment because the seizure was conducted  incident to a lawful arrest . [ 36 ]  The City Attorney also argued that admitting the sample into evidence did not violate Schmerber's Fifth Amendment right against self-incrimination because blood is not testimonial evidence under the Fifth Amendment. [ 36 ]  Oral arguments were held on April 25, 1966, and the Court issued its opinion on June 20, 1966. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4083", "text": "In his majority opinion,  Justice   William J. Brennan, Jr.  held that Schmerber's constitutional rights were not violated when police took his blood without his consent. Relying upon the Court's holding in  Breithaupt v. Abram , he concluded that the police did not violate Schmerber's Fifth Amendment right against self-incrimination because the extraction and chemical analysis of the blood sample did not involve \"even a shadow of testimonial compulsion.\" [ 38 ]  Likewise, Justice Brennan held that the officers did not violate Schmerber's Fourth Amendment right against unreasonable seizures. Justice Brennan wrote that absent exigent circumstances, searches that involve intrusions into the human body require a search warrant. [ 6 ]  Here, the search was not justified as a search incident to arrest because weapons and contraband are not ordinarily concealed beneath the skin. [ 39 ]  However, the involuntary blood draw was justified under the Fourth Amendment's exigent circumstances exception because if the officers had waited to receive a search warrant, evidence of intoxication would have been lost through the body's natural metabolism of alcohol in the bloodstream. [ 40 ]  He wrote that the responding officer \"might reasonably have believed that he was confronted with an emergency,\" where evidence would be destroyed if he waited to receive a warrant. [ 6 ]  Additionally, Justice Brennan cautioned that the Court's ruling was limited \"only to the facts of the present record\" and that \"minor intrusions into an individual's body under stringently limited conditions in no way indicates that it permits more substantial intrusions, or intrusions under other conditions.\" [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4084", "text": "In his concurring opinion, Justice  John Marshall Harlan II  agreed that the involuntary blood sample did not implicate involuntary testimonial compulsion, but wrote separately to emphasize his opinion that the case before the Court \"in no way implicates the Fifth Amendment.\" [ 42 ]  Additionally, Justice Harlan cited to his dissent in  Miranda v. Arizona  where he argued against a broad expansion of the Fifth Amendment right against self-incrimination. Justice Harlan disagreed with the Court's ruling in  Miranda  and even stated that the case \"represents poor constitutional law and entails harmful consequences for the country at large.\" [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4085", "text": "All four dissenting Justices wrote separate dissenting opinions in  Schmerber .  Chief Justice   Earl Warren  reiterated his dissenting opinion in  Breithaupt v. Abram , where he argued that involuntary blood samples violate substantive due process. [ 45 ]  Justice  Hugo Black  authored an impassioned dissent in which he argued that the officers violated Schmerber's right against self-incrimination. [ 46 ]  He wrote, \"[b]elieving with the Framers that these constitutional safeguards broadly construed by independent tribunals of justice provide our best hope for keeping our people free from governmental oppression, I deeply regret the Court's holding.\" [ 46 ]  Justice  William O. Douglas  also reiterated his dissent in  Breithaupt v. Abram , but added that physical invasions into the human body violate the right to privacy enumerated in  Griswold v. Connecticut  and that \"[n]o clearer invasion of this right of privacy can be imagined than forcible bloodletting of the kind involved here.\" [ 44 ]  Finally, Justice  Abe Fortas  wrote that the involuntary blood sample was an act of violence that violated substantive due process and that states may not resort to acts of violence when prosecuting crimes. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4086", "text": "In the 1970s and 1980s, the Supreme Court revisited questions about the constitutionality of involuntary bodily intrusions in several key cases. In 1973, the Court ruled in  Cupp v. Murphy  that the police were permitted to extract a tissue sample from underneath a suspect's fingernails to recover \"evanescent\" physical evidence. [ 48 ]  The suspect in  Cupp  was suspected of strangling his wife and voluntarily went to a police station to answer questions. [ 49 ]  Officers noticed bloodstains under the suspect's fingernails and detained him, but did not place him under arrest. [ 49 ]  Against the suspect's wishes, the police scraped out a tissue sample from under his fingernails to retrieve the evidence. [ 49 ]  The biological material found under the suspect's fingernails was later found to have come from the victim. [ 49 ]  Citing  Schmerber , the Court held that this warrantless search was justified under the exigent circumstances exemption of the Fourth Amendment because the search was necessary to preserve the \u201chighly evanescent evidence\u201d under the defendant's fingernails. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4087", "text": "Twelve years later, the Court again revisited the topic of involuntary bodily intrusions in  Winston v. Lee , where the Court held that the State of  Virginia  could not force an individual to undergo surgery to extract a bullet that may be evidence of a crime. [ 51 ]  The Court applied its previous holding in  Schmerber  to conclude that the surgery would constitute an unreasonable search under the Fourth Amendment and that a crucial factor for evaluating any bodily intrusion \"is the extent to which the procedure may threaten the safety or health of the individual.\" [ 52 ]  Writing for the Court's majority, Justice Brennan concluded that forcing a patient to undergo major surgery intrudes too far upon individual privacy rights and that surgical intrusions \"can only be characterized as severe.\" [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4088", "text": "In 1989, the Court ruled in  Skinner v. Railway Labor Executives\u2019 Association  that warrantless blood tests of railroad employees were reasonable under the Fourth Amendment. [ 54 ]  The Court reaffirmed that the \u201ccompelled intrusio[n] into the body for blood to be analyzed for alcohol content\u201d is a search under the Fourth Amendment, [ 55 ]  but that warrantless blood tests of railroad employees were necessary to \"prevent accidents and casualties in railroad operations that result from impairment of employees by alcohol or drugs.\u201d [ 56 ]  The Court also concluded that when individuals \u201cparticipate in an industry that is regulated pervasively to ensure safety,\u201d these individuals \u201chave a reduced expectation of privacy.\u201d [ 57 ]  Because these employees had a \"diminished expectation of privacy,\" the warrantless blood tests were permissible. [ 58 ]  Justice  Thurgood Marshall  and Justice Brennan wrote a dissenting opinion in which they argued that this case was distinguishable from  Schmerber  because \"no such exigency prevents railroad officials from securing a warrant before chemically testing the samples they obtain.\" [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4089", "text": "After the Court issued its decision in  Schmerber , a split of authority emerged in lower courts with regard to whether the Fifth Amendment's right against self-incrimination prohibited the use of a suspect's refusal to submit to a blood test as evidence of guilt. [ 61 ]  The United States Supreme Court resolved this split in authority in  South Dakota v. Neville , where the Court held that prosecutors could use a suspect's refusal to submit to a blood test as evidence of guilt, and the introduction of this evidence at trial does not violate the suspect's Fifth Amendment right against self-incrimination. [ 62 ]  Writing for the Court's majority, Justice  Sandra Day O'Connor  concluded that \"the state did not directly compel respondent to refuse the test\" and that a \"simple blood-alcohol test is so safe, painless, and commonplace\" a suspect would not feel coerced to refuse the test. [ 63 ]  Justice  John Paul Stevens  wrote a dissenting opinion, joined by Justice  Thurgood Marshall , in which he argued that the Court in  Schmerber  intended to adopt a broad and liberal interpretation of the Fifth Amendment right against self-incrimination. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4090", "text": "Over time, a split of authority grew among lower courts with regard to whether the Fourth Amendment's exigent circumstances exception allowed officers to  always  conduct warrantless blood tests on individuals suspected of driving under the influence of alcohol because evidence of alcohol was being destroyed by the body's natural metabolic processes. [ 65 ]  States that recognized this  per se  exigency argued that \"[o]nce police arrest a suspect for drunk driving, each passing minute eliminates probative evidence of the crime.\" [ 66 ]  In 2012, the Court granted review in  Missouri v. McNeely  to resolve this question. [ 67 ]  In a 5\u20134 opinion, the Court rejected the theory that the natural dissipation of blood alcohol constituted a  per se  exigency. [ 68 ]  Instead, the court affirmed the basic principle from  Schmerber  that absent \"an emergency that justifie[s] acting without a warrant,\" police may not conduct warrantless blood testing on suspects. [ 69 ]  Consequently, exigency in drunk driving cases \"must be determined case by case based on the  totality of the circumstances .\" [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4091", "text": "Scholars have described  Schmerber v. California  as a  landmark case [ 71 ]  and a \"watershed moment\" in the history of Fourth Amendment jurisprudence. [ 72 ]  Likewise, John D. Castiglione described the case as \"seminal for its place in the annals of Fifth Amendment jurisprudence.\" [ 73 ]  Constitutional law scholar  Akhil Reed Amar  identified  Schmerber  as a turning point in the Fifth Amendment's \"distinction between words and physical evidence.\" [ 74 ]  Anne Marie Schubert has also argued that  Schmerber  served as the genesis for a long line of Supreme Court cases ordering the compelled production of physical evidence. [ 75 ]  Because  Schmerber  foreclosed the use of warrantless blood tests in most circumstances, some scholars, including John A. Scanlan, argue that the Court's ruling was responsible for the proliferation of  breathalyzers  to test for alcohol and  urine analysis  to test for controlled substances in criminal investigations. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4092", "text": "Soon after the Court's ruling, analysts predicted that the effects of the case would be \"far-reaching.\" [ 76 ]  Some analysts feared the ruling would be used to justify \"other intrusive searches.\" [ 77 ]  Other commentators also observed that the Court's holding in  Schmerber  seemed to \"reverse direction\" from the court's decision in  Miranda v. Arizona  one week earlier, where the Court enlarged protections against the police for criminal suspects. [ 78 ]  However, in his assessment of  Schmerber , Charles L. Berry praised the decision as a \"successful effort to find a practical solution to the problem of the drinking motorist.\" [ 79 ]  Additionally, many  law journals  also offered commentary of the case's significance. For example, a November 1966 article in the  Harvard Law Review  opined that Justice Brennan's majority opinion was \"a good exposition of his view of the interrelationship between the fourth and fifth amendments,\" [ 80 ]  and a February 1967 article in the  Texas Law Review  argued that  Schmerber  \"exemplifies the proposition that the fifth amendment is not absolute.\" [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4093", "text": "Some legal scholars have criticized the Court's ruling in Schmerber for infringing too far upon  civil liberty  and privacy. [ 82 ]  E. John Wherry, Jr., former Dean of the  University of Orlando School of Law , wrote that \"[b]lindly following  Schmerber  as authorization for all non-consensual blood seizure for forensic purposes is, in this day and age, an outrage.\" [ 83 ]  Writing for the  Notre Dame Law Review , Blake A. Bailey, Elaine M. Martin, and Jeffrey M. Thompson observed that although the Court limited the holding in  Schmerber  to the facts of the case, prior to  Winston v. Lee , many lower courts relied upon the ruling to order criminal defendants to undergo surgery to remove bullets that may have been evidence of a crime. [ 84 ]  Other scholars have expressed concern that the Court's decision to exclude physical evidence from protections against self-incrimination may one day lead to the use of  mind reading  devices when prosecuting criminal suspects. [ 85 ]  For example, the  Harvard Law Review  suggested that the Court's decision may be used to justify monitoring brain waves. [ 86 ]  Additionally, in an article in the journal  Developments in Mental Health Law , Benjamin Holley suggested that \"neurotechnological lie detection\" could be used in criminal prosecutions, as long as a suspect's words are not \"linked with the physical manifestations sought to be introduced at trial.\" [ 87 ]  Likewise, in an article in the  Journal of Legal Medicine , John G. New suggested that non-testimonial evidence gathered from  electroencephalography  or  magnetic resonance imaging  may be admissible to demonstrate a suspect's thoughts. [ 88 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4094", "text": "The citations in this Article are written in  Bluebook  style."}
{"_id": "WikiPedia_Hematology$$$corpus_4095", "text": "The  Schumm test   (shoom)  is a blood test that uses  spectroscopy  to determine significant levels of  methemalbumin  in the  blood . A positive result could indicate intravascular  hemolysis . [ 1 ] [ 2 ]  The Schumm test was named for  Otto Schumm , a German chemist who lived in the early 20th century. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4096", "text": "A positive test result occurs when the  haptoglobin  binding capacity of the blood is saturated, leading to heme released from cell free  hemoglobin  to bind to  albumin . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4097", "text": "Serology  is the scientific study of  serum  and other  body fluids . In practice, the term usually refers to the  diagnostic  identification of  antibodies  in the serum. [ 1 ]  Such antibodies are typically formed in response to an infection (against a given  microorganism ), [ 2 ]  against other foreign proteins (in response, for example, to a  mismatched   blood transfusion ), or to one's own proteins (in instances of  autoimmune disease ). In either case, the procedure is simple. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4098", "text": "Serological tests are diagnostic methods that are used to identify antibodies and  antigens  in a patient's sample. Serological tests may be performed to diagnose  infections  and  autoimmune illnesses , to check if a person has  immunity  to certain diseases, and in many other situations, such as determining an individual's  blood type . [ 1 ]  Serological tests may also be used in  forensic serology  to investigate crime scene evidence. [ 3 ]  Several methods can be used to detect antibodies and antigens, including  ELISA , [ 4 ]   agglutination ,  precipitation ,  complement-fixation , and  fluorescent antibodies  and more recently  chemiluminescence . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4099", "text": "In  microbiology ,  serologic tests  are used to determine if a person has antibodies against a specific  pathogen , or to detect antigens associated with a pathogen in a person's sample. [ 6 ]   Serologic tests are especially useful for organisms that are difficult to  culture  by routine laboratory methods, like  Treponema pallidum  (the causative agent of  syphilis ), or  viruses . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4100", "text": "The presence of antibodies against a pathogen in a person's blood indicates that they have been exposed to that pathogen. Most serologic tests measure one of two types of antibodies:  immunoglobulin M  (IgM) and  immunoglobulin G  (IgG). IgM is produced in high quantities shortly after a person is exposed to the pathogen, and production declines quickly thereafter. IgG is also produced on the first exposure, but not as quickly as IgM. On subsequent exposures, the antibodies produced are primarily IgG, and they remain in circulation for a prolonged period of time. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4101", "text": "This affects the interpretation of serology results: a positive result for IgM suggests that a person is currently or recently infected, while a positive result for IgG and negative result for IgM suggests that the person may have been infected or immunized in the past. Antibody testing for infectious diseases is often done in two phases: during the initial illness (acute phase) and after recovery (convalescent phase). The amount of antibody in each specimen ( antibody titer ) is compared, and a significantly higher amount of IgG in the convalescent specimen suggests infection as opposed to previous exposure. [ 8 ]  False negative results for antibody testing can occur in people who are  immunosuppressed , as they produce lower amounts of antibodies, and in people who receive  antimicrobial drugs  early in the course of the infection. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4102", "text": "Blood typing  is typically performed using serologic methods. The antigens on a person's red blood cells, which determine their  blood type , are identified using  reagents  that contain antibodies, called  antisera . When the antibodies bind to red blood cells that express the corresponding antigen, they cause red blood cells to clump together (agglutinate), which can be identified visually. The person's blood group antibodies can also be identified by adding plasma to cells that express the corresponding antigen and observing the agglutination reactions. [ 9 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4103", "text": "Other serologic methods used in  transfusion medicine  include  crossmatching  and the direct and indirect  antiglobulin tests . Crossmatching is performed before a  blood transfusion  to ensure that the donor blood is compatible. It involves adding the recipient's plasma to the donor blood cells and observing for agglutination reactions. [ 9 ]  The direct antiglobulin test is performed to detect if antibodies are bound to red blood cells inside the person's body, which is abnormal and can occur in conditions like  autoimmune hemolytic anemia ,  hemolytic disease of the newborn  and  transfusion reactions . [ 10 ]   The indirect antiglobulin test is used to screen for antibodies that could cause transfusion reactions and identify certain blood group antigens. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4104", "text": "Serologic tests can help to diagnose autoimmune disorders by identifying abnormal antibodies directed against a person's own tissues ( autoantibodies ). [ 12 ]  All people have different immunology graphs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4105", "text": "A 2016 research paper by Metcalf et al., amongst whom were  Neil Ferguson  and  Jeremy Farrar , stated that serological surveys are often used by  epidemiologists  to determine the prevalence of a disease in a population. Such surveys are sometimes performed by random, anonymous sampling from samples taken for other medical tests or to assess the prevalence of antibodies of a specific organism or protective titre of antibodies in a population. Serological surveys are usually used to quantify the proportion of people or animals in a population positive for a specific antibody or the titre or concentrations of an antibody. These surveys are potentially the most direct and informative technique available to infer the dynamics of a population's susceptibility and level of immunity. The authors proposed a  World Serology Bank  (or serum bank) and foresaw \"associated major methodological developments in serological testing,  study design , and  quantitative analysis , which could drive a  step change  in our understanding and  optimum control  of  infectious diseases .\" [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4106", "text": "In a helpful reply entitled \"Opportunities and challenges of a World Serum Bank\", de Lusignan and Correa observed [ 14 ]  that the"}
{"_id": "WikiPedia_Hematology$$$corpus_4107", "text": "principal  ethical  and logistical challenges that need to be overcome are the methods of obtaining specimens, how  informed consent  is acquired in busy practices, and the filling in of gaps in  patient sampling ."}
{"_id": "WikiPedia_Hematology$$$corpus_4108", "text": "In another helpful reply on the World Serum Bank, the Australian researcher  Karen Coates  declared that: [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4109", "text": "Improved serological surveillance would allow  governments ,  aid agencies , and  policy writers  to direct  public health  resources to where they are needed most. A better understanding of  infection dynamics  with respect to the  changing patterns of global weather  should inform policy measures including where to concentrate  vaccination  efforts and  insect control  measures."}
{"_id": "WikiPedia_Hematology$$$corpus_4110", "text": "In April 2020,  Justin Trudeau  formed the  COVID-19 Immunity Task Force , whose mandate is to carry out a serological survey in a scheme hatched in the midst of the  COVID-19 pandemic . [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4111", "text": "Free light chains (FLCs)  are immunoglobulin light chains that are found in the serum (blood) in an unbound (free) state. In recent decades, measuring the amount of free light chains (FLCs) in the blood has become a practical clinical test. FLC tests can be used to diagnose and monitor diseases like  multiple myeloma  and  amyloidosis ."}
{"_id": "WikiPedia_Hematology$$$corpus_4112", "text": "Each immunoglobulin light-chain molecule contains approximately 220 amino acids in a single polypeptide chain that is folded to form constant and variable region domains.\nEach domain comprises two  \u03b2-pleated sheets . The sheets are linked by a disulfide bridge and together form a roughly barrel-shaped structure known as a  \u03b2-barrel .\nThe variable (V) domain of light chains has a high degree of structural diversity, particularly the antigen-binding region. In addition, the first 23 amino acids of the 1st variable domain framework region have a number of variations known as subgroups. Four kappa (V\u03ba1\u2013V\u03ba4) and six lambda subgroups (V\u03bb1\u2013V\u03bb6) can be identified. [ 1 ]  The subgroup structures of FLCs influence their ability to polymerize (combine) and form proteins like amyloid fibrils. For example, the V\u03bb6 subgroup of FLCs is associated with a type of amyloidosis called AL amyloidosis, while the V\u03ba1 and V\u03ba4 subgroups are associated with a different type of amyloidosis called light-chain deposition disease. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4113", "text": "Kappa light-chain molecules are constructed from approximately 40 functional V\u03ba gene segments (chromosome 2), five J\u03ba gene segments and a single C\u03ba gene. Lambda molecules (chromosome 22) are constructed from about 30 V\u03bb gene segments and four pairs of functional J\u03bb gene segments and a C\u03bb gene. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4114", "text": "Light chains are incorporated into immunoglobulin molecules during  B-cell  development and are expressed initially on the surface of pre B-cells. Production of light chains occurs throughout the rest of B-cell development and in plasma cells, where secretion is highest. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4115", "text": "The production of free immunoglobulin light chains in normal individuals is approximately 500\u00a0mg/day from bone marrow and lymph node cells. [ 1 ] [ 4 ]  The production of immunoglobulin light chains is about 40% greater than the production of immunoglobulin heavy chains. This may simply be to allow for the proper structure of the intact immunoglobulin molecules, but it is also possible that free light chains have an immunological function. [ 5 ]  There are approximately twice as many kappa-producing plasma cells as lambda plasma cells. Kappa free-light chains are normally monomeric, while lambda free-light chains tend to be dimeric, joined by disulphide bonds. Polymeric forms of both types of free light chain can also occur. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4116", "text": "In normal individuals, free light chains are rapidly cleared from the blood and catabolised by the kidneys. Monomeric free light chains are cleared in 2\u20134 hours, and dimeric light chains in 3\u20136 hours. [ 7 ]  Removal may be prolonged to 2\u20133 days in people with complete renal failure. [ 1 ] [ 4 ] [ 8 ]  Human kidneys are composed of approximately half a million  nephrons . Each nephron contains a  glomerulus  with  basement membrane  pores that allow filtration of immunoglobulin light chains and other small molecules from the blood into the  proximal tubule  of the nephron. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4117", "text": "Filtered molecules are either excreted in the urine or may be specifically re-absorbed. Protein molecules that pass through the glomerular pores are either absorbed unchanged (such as  albumin ), degraded in the proximal tubular cells and absorbed (such as free light chains), or excreted as fragments. [ 9 ]  This re-absorption is mediated by a receptor complex ( megalin / cubulin ) and prevents the loss of large amounts of protein into the urine. It is very efficient and can process 10\u201330 g of low-molecular-weight proteins per day, so under normal conditions no light chains pass beyond the proximal tubules. [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4118", "text": "If immunoglobulin light chains are produced in sufficient amounts to overwhelm the proximal tubules' absorption mechanisms (usually due to the presence of a plasma cell tumour) the light chains enter the distal tubules and can appear in the urine ( Bence Jones protein ). The passage of large amounts of immunoglobulin light chains through the kidneys may cause inflammation or blockage of the kidney tubules. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4119", "text": "The  distal tubules  of the kidneys secrete large amounts of uromucoid ( Tamm\u2013Horsfall protein ). This is the dominant protein in normal urine and is thought to be important in preventing ascending urinary infections. It is a relatively small glycoprotein (80 kDa) that aggregates into  polymers  of 20\u201330 molecules. It contains a short amino-acid sequence that can specifically bind to some free light chains. [ 13 ]  Together they can form an insoluble precipitate which blocks the distal part of the nephrons. This is termed \" cast nephropathy \" or \"myeloma kidney\" and is typically found in patients with multiple myeloma. [ 14 ] [ 15 ]  This can block the flow of urine causing the death of the respective nephrons. Rising concentrations of light chains are filtered by the remaining nephrons leading to a cycle of accelerating renal damage with rising concentrations of free light chains in the blood. [ 16 ]  At the same time, the amount of free light chains entering the urine will be decreased and will be zero if the patient stops producing urine ( anuria ). Conversely, urine concentrations of free light chains could increase if renal function improved in a multiple myeloma patient receiving treatment. This could account for the poor correlation frequently seen when urine and serum free light-chain concentrations are compared. [ 17 ] [ 18 ] [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4120", "text": "The 500\u00a0mg of FLCs produced per day by the normal  lymphoid system , however, flows through the glomeruli and is completely processed by the proximal tubules. If the proximal tubules of the nephrons are damaged or stressed (such as in hard exercise), filtered FLCs may not be completely metabolised and small amounts may then appear in the urine. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4121", "text": "Serum free light-chain assays have been used in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma [ 21 ] [ 22 ] [ 23 ]  and AL amyloidosis. [ 23 ] [ 24 ] [ 25 ] [ 26 ]  This is primarily because of the re-absorption of free light chains in the kidneys, creating a threshold of light chain production which must be exceeded before measurable quantities overflow into the urine. [ 17 ] [ 18 ] [ 19 ]  While there are a number of publications indicating that serum free light chain analysis is preferable to urine analysis at diagnosis, [ 27 ] [ 28 ] [ 29 ] [ 30 ]  there is currently no consensus on whether urine tests for monitoring should be replaced. [ 18 ] [ 19 ] [ 20 ] [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4122", "text": "A series of studies, principally from the  Mayo Clinic , have indicated that patients with an abnormal free kappa to free lambda ratio have an increased risk of progression to active myeloma from precursor conditions including  monoclonal gammopathy of undetermined significance  (MGUS), [ 32 ] [ 33 ]   smouldering myeloma [ 34 ]  and solitary  plasmacytoma  of the bone. [ 35 ]  Abnormal free light chain production has also been reported to be prognostic of a worse outcome in multiple myeloma [ 36 ] [ 37 ] [ 38 ]  and  chronic lymphocytic leukaemia . [ 39 ]  An abnormal light-chain ratio has been defined as a kappa to lambda chain ratio of less than 0.26 or more than 1.65. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4123", "text": "In 2009, the International Myeloma Working Group published guidelines making recommendations of when serum free light-chain analysis should be used in the management of multiple myeloma. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4124", "text": "The serum free light-chain assay in combination with  serum protein electrophoresis  and serum  immunofixation  electrophoresis is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL amyloidosis which requires all the serum tests as well as 24 h urine immunofixation electrophoresis."}
{"_id": "WikiPedia_Hematology$$$corpus_4125", "text": "Serial serum free light-chain measurement should be routinely performed in patients with AL amyloidosis and multiple myeloma patients with oligosecretory disease.  It should also be done in all patients who have achieved a complete response to treatment to determine whether they have attained a stringent complete response. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4126", "text": "Other guidelines for the use of serum free light chain measurement in the management of AL amyloidosis, [ 42 ]  plasmacytoma [ 43 ]  and the comparison of treatment responses in clinical trials [ 44 ]  have also been published."}
{"_id": "WikiPedia_Hematology$$$corpus_4127", "text": "Technical and clinical reviews of serum free light-chain measurement have recently been written by Pratt and Jagannath. [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4128", "text": "Serum  iron  is a  medical  laboratory test that measures the amount of circulating  iron  that is bound to  transferrin  and freely circulate in the blood. Clinicians order this laboratory test when they are concerned about  iron deficiency , which can cause  anemia  and other problems. 65% of the iron in the body is bound up in  hemoglobin  molecules in  red blood cells . About 4% is bound up in  myoglobin  molecules. Around 30% of the iron in the body is stored as  ferritin  or  hemosiderin  in the  spleen , the  bone marrow  and the  liver . Small amounts of iron can be found in other molecules in cells throughout the body. None of this iron is directly accessible by testing the serum. [ citation needed ] }"}
{"_id": "WikiPedia_Hematology$$$corpus_4129", "text": "However, some iron is circulating in the serum. Transferrin is a molecule produced by the liver that binds one or two iron(III)  ions , i.e. ferric iron, Fe 3+ ; transferrin is essential if stored iron is to be moved and used. Most of the time, about 30% of the available sites on the transferrin molecule are filled. The test for serum iron uses blood drawn from  veins  to measure the iron ions that are bound to transferrin and circulating in the blood. This test should be done after 12 hours of fasting. The extent to which sites on transferrin molecules are filled by iron ions can be another helpful clinical indicator, known as  percent transferrin saturation . Another lab test saturates the sample to measure the total amount of transferrin; this test is called  total iron-binding capacity  (TIBC). These three tests are generally done at the same time, and taken together are an important part of the diagnostic process for conditions such as  anemia ,  iron deficiency anemia ,  anemia of chronic disease  and  haemochromatosis . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4130", "text": "Normal  reference ranges  are:"}
{"_id": "WikiPedia_Hematology$$$corpus_4131", "text": "\u03bcg/dL =  micrograms  per  deciliter ."}
{"_id": "WikiPedia_Hematology$$$corpus_4132", "text": "Laboratories often use different units and \"normal\" may vary by population and the lab techniques used; look at the individual laboratory  reference values  to interpret a specific test (for instance, your own)."}
{"_id": "WikiPedia_Hematology$$$corpus_4133", "text": "Serum total protein , also known as  total protein , is a  clinical chemistry   parameter  representing the concentration of  protein  in  serum . [ 1 ] \nSerum contains many proteins including  serum albumin , a variety of  globulins , and many others. While it is possible to analyze these proteins individually, total protein is a relatively quick and inexpensive analysis that does not discriminate by protein type."}
{"_id": "WikiPedia_Hematology$$$corpus_4134", "text": "The traditional method for measuring total protein uses the  biuret reagent , but other chemical methods such as dye-binding and  refractometry  are now available. The measurement is usually performed on  automated analysers  along with other  laboratory  tests. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4135", "text": "The  reference range  for total protein is typically 60-80g/L. (It is also sometimes reported as \"6.0-8.0g/dl\"), [ 2 ]  but this may vary depending on the method of analysis."}
{"_id": "WikiPedia_Hematology$$$corpus_4136", "text": "Serum vitamin B 12   is a  medical  laboratory test that measure  vitamin B 12  only in the  blood  binding to both  transcobalamins . [ 1 ]  Most of the time, 80\u201394% of vitamin B 12  in the blood binds to  haptocorrin , while only 6\u201320% is binds to transcobalamin ll. [ 2 ]  Only transcobalamin ll is \"active\" and can be used by the body. [ 1 ]  Normal total body vitamin B 12  is between 2 and 5 mg with 50% of that stored in the  liver . [ 3 ]  Total serum vitamin B 12  may not be a reliable  biomarker  for reflecting what the body stores inside cells. [ 1 ]  Vitamin B 12  levels can be falsely high or low and data for  sensitivity and specificity  vary widely. There is no gold standard human assay to confirm a  vitamin B 12  deficiency . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4137", "text": "Healthcare providers use this test when a vitamin B 12  deficiency is suspected, which can cause  anemia  and irreversible nerve damage. [ 3 ]  The cutoff between normal vitamin B 12  levels and deficiency varies by country and region. [ 3 ]  A diagnosis of vitamin B 12  deficiency is determined by blood levels lower than 200 or 250  picograms  per ml (148 or 185 picomoles per liter). [ 3 ]  Some people can have symptoms with their normal levels of the vitamin, or may have low levels despite having no symptoms. [ 5 ]  Other tests may be done to ensure individuals status. [ 3 ]  Measuring vitamin B 12  values in individuals during or after treatment, in order to measure the effectiveness of treatment, is useless. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4138", "text": "A blood test shows vitamin B 12  levels in the blood. [ 3 ]  Vitamin B 12  deficiency can be determined, but not always. [ 4 ]  This means it measures forms of vitamin B 12  that are \"active\" and can be used by the body, as well as the \"inactive\" forms, which cannot. [ 7 ]  However, also normal or supraphysiological vitamin B 12  levels should be carefully assessed in the context of the individual state of health. [ 1 ]  Elevated or normal serum vitamin B 12  levels may also be associated with a functional vitamin deficiency. [ 1 ]   Functional deficiency has been described despite high B 12  concentrations and is due to a failure of cellular uptake, intracellular processing, trafficking, or utilization. [ 1 ]  However, low vitamin B 12  levels may occur other than the true deficiency for various reasons and circumstances. [ 8 ]  High or supraphysiological serum levels are usually not of concern, although without supplementation they have been associated with many pathological conditions. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4139", "text": "Laboratories often use different units and \"normal\" may vary by population and the lab techniques used. Some researchers have suggested that current standards for vitamin B 12  levels are too low. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4140", "text": "The  ST Genesia  is a  fully automated  commercial analyzer system for performing  thrombin generation assays  (TGAs) and hence for  coagulation testing . [ 1 ]  It was developed by Diagnostica Stago and was introduced by the company in 2018. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4141", "text": "Traditionally, TGAs has been conducted using partially automated methods like the  calibrated automated thrombogram  (CAT), which was introduced in 2003. [ 1 ] [ 3 ] [ 4 ]  However, the CAT is performed in a  96-well plate  and requires specialized  technologists  to be performed. [ 1 ]  Consequently, it has seen low implementation in routine laboratories and has been more limited to research settings. [ 1 ] [ 5 ]  Lack of  standardization  with the CAT has also led to difficulties in study-to-study comparisons in research. [ 1 ] [ 6 ]  It has been said that the introduction of the ST Genesia system, which will allow TGAs to be performed more easily and also shows improved  reproducibility  compared to the CAT, should allow for more widespread adoption of TGAs in clinical laboratories. [ 1 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4142", "text": "The  Staub-Traugott Phenomenon  (or Staub-Traugott Effect) is the premise that a normal subject fed  glucose  will rapidly return to normal levels of  blood glucose  after an initial spike, and will see improved reaction to subsequent glucose feedings. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4143", "text": "A. T. B. Jacobson determined in 1913 that  carbohydrate  ingestion results in blood glucose fluctuations. [ 1 ]  Hamman and Hirschman first reported improvement of carbohydrate tolerance following repeated glucose administration in 1919. [ 2 ]  H. Staub in 1921 and K. Traugott in 1922 subsequently confirmed the improved reaction in healthy subjects and the phenomenon was named for them. [ 3 ] [ 4 ]  As this effect does not occur in  diabetic  subjects, it became the basis for the  Glucose Tolerance Test . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4144", "text": "Abraira and Lawrence describe the original discovery as being that \"when glucose loads are given in succession, orally or intravenously, significant and progressive improvement in glucose tolerance will occur in normal and nonketotic diabetic subjects. This facilitated disposal of a glucose load is known as the Staub-Traugott phenomenon.\" [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4145", "text": "This phenomenon drew considerable interest as it was demonstrated that the ingested glucose was still being processed by the gut at the same rate while being cleared much more rapidly in the bloodstream. \"It is not surprising that when a large amount of readily diffusible glucose is suddenly introduced into the alimentary tract the rate of absorption should exceed the rate at which the tissues can abstract it from the blood. But it is not so clear why the curve should again fall to normal as rapidly as it often does at a time when the rate of absorption from the gut can be scarcely diminished.\" [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4146", "text": "Various mechanisms were hypothesized involving the  liver  and  insulin . It was determined in 2009 that \"enhanced potentiation of insulin response and increased suppression of hepatic glucose production are the main mechanisms underlying the Staub-Traugott effect\", meaning that the liver slows its release of glucose into the bloodstream and the existing insulin becomes better at clearing glucose from the bloodstream with each dose of glucose administered. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4147", "text": "This effect has been observed to disappear under conditions of  starvation  and in  hypopituitary  patients. [ 5 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4148", "text": "Attempts to base dietary and nutrition advice on this effect have met with limited success. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4149", "text": "The  sum activity of peripheral deiodinases  ( G D , also referred to as  deiodination capacity ,  total deiodinase activity  or, if calculated from levels of thyroid hormones, as  SPINA-GD [ a ] ) is the maximum amount of  triiodothyronine  produced per time-unit under conditions of substrate saturation. [ 1 ]  It is assumed to reflect the activity of  deiodinases  outside the  central nervous system  and other isolated compartments. GD is therefore expected to reflect predominantly the activity of  type I deiodinase ."}
{"_id": "WikiPedia_Hematology$$$corpus_4150", "text": "G D  can be determined experimentally by exposing a  cell culture  system to saturating concentrations of  T4  and measuring the  T3  production. Whole body deiodination activity can be assessed by measuring production of radioactive iodine after loading the organism with marked thyroxine. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4151", "text": "However, both approaches are faced with draw-backs. Measuring deiodination in cell culture delivers little, if any, information on total deiodination activity. Using marked thyroxine exposes the body to  thyrotoxicosis  and radioactivity. Additionally, it is not possible to differentiate step-up reactions resulting in T3 production from the step-down reaction catalyzed by type 3 deiodination, which mediates production of  reverse T3 . Distinguishing the contribution of distinct deiodinases is possible, however, by sequential approaches using deiodinase-specific blocking agents, but this approach is cumbersome and time-consuming. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4152", "text": "In vivo , it may therefore be beneficial to estimate  G D  from equilibrium levels of T4 and T3. It is obtained with"}
{"_id": "WikiPedia_Hematology$$$corpus_4153", "text": "G \n ^ \n \n \n \n \n D \n \n \n = \n \n \n \n \n \u03b2 \n \n 31 \n \n \n ( \n \n K \n \n M \n 1 \n \n \n + \n [ \n F \n \n T \n \n 4 \n \n \n ] \n ) \n ( \n 1 \n + \n \n K \n \n 30 \n \n \n [ \n T \n B \n G \n ] \n ) \n [ \n F \n \n T \n \n 3 \n \n \n ] \n \n \n \n \u03b1 \n \n 31 \n \n \n [ \n F \n \n T \n \n 4 \n \n \n ] \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{D}={{\\beta _{31}(K_{M1}+[FT_{4}])(1+K_{30}[TBG])[FT_{3}]} \\over {\\alpha _{31}[FT_{4}]}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4154", "text": "G \n ^ \n \n \n \n \n D \n \n \n = \n \n \n \n \n \u03b2 \n \n 31 \n \n \n ( \n \n K \n \n M \n 1 \n \n \n + \n [ \n F \n \n T \n \n 4 \n \n \n ] \n ) \n [ \n T \n \n T \n \n 3 \n \n \n ] \n \n \n \n \u03b1 \n \n 31 \n \n \n [ \n F \n \n T \n \n 4 \n \n \n ] \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{D}={{\\beta _{31}(K_{M1}+[FT_{4}])[TT_{3}]} \\over {\\alpha _{31}[FT_{4}]}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4155", "text": "[ FT4 ]: Serum free T4 concentration (in pmol/L) \n[ FT3 ]: Serum free T3 concentration (in pmol/L) \n[ TT3 ]: Serum total T3 concentration (in nmol/L) \n \n \n \n \n \n \u03b1 \n \n 31 \n \n \n \n \n {\\displaystyle \\alpha _{31}} \n \n :  Dilution  factor for T3 (reciprocal of apparent volume of distribution, 0.026 L \u22121 ) \n \n \n \n \n \n \u03b2 \n \n 31 \n \n \n \n \n {\\displaystyle \\beta _{31}} \n \n :  Clearance  exponent for T3 (8e-6 sec \u22121 ) (i. e.,  reaction rate constant  for degradation) \n K M 1 :  Binding constant  of type-1-deiodinase (5e-7\u00a0mol/L) \n K 30 : Binding constant T3-TBG (2e9 L/mol) [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4156", "text": "The method is based on mathematical models of thyroid homeostasis. [ 1 ] [ 3 ]  Calculating deiodinase activity with one of these equations is an  inverse problem . Therefore, certain conditions (e.g. stationarity) have to be fulfilled to deliver a reliable result."}
{"_id": "WikiPedia_Hematology$$$corpus_4157", "text": "The product of SPINA-GD times the urinary  iodine  excretion can be used to assess iodine-independent factors affecting deiodinase activity, e.g. selenium deficiency. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4158", "text": "The equations and their parameters are calibrated for adult humans with a body mass of 70\u00a0kg and a plasma volume of ca. 2.5 L. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4159", "text": "SPINA-GD correlates to the T4-T3 conversion rate in slow tissue pools, as determined with isotope-based measurements in healthy volunteers. [ 1 ]  It was also shown that GD correlates with  resting energy expenditure , [ 5 ]   body mass index [ 3 ] [ 6 ] [ 7 ]  and thyrotropin levels in humans, [ 8 ] [ 9 ]  and that it is reduced in  nonthyroidal illness  with hypodeiodination. [ 6 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ]  Multiple studies demonstrated SPINA-GD to rise after initiation of substitution therapy with  selenium , a trace element that is essential for the synthesis of deiodinases. [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ]  Conversely, it was observed that SPINA-GD is reduced in persons positive for autoantibodies to  selenoprotein P , which is assumed to be involved in transport and storage of selenium. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4160", "text": "Compared to both healthy volunteers and subjects with  hypothyroidism  and  hyperthyroidism , SPINA-GD is reduced in  subacute thyroiditis . In this condition, it has a higher  specificity ,   positive  and  negative likelihood ratio  than serum concentrations of  thyrotropin , free T4 or free T3. [ 3 ]  These measures of diagnostic utility are also high in nodular  goitre , where SPINA-GD is elevated. [ 3 ]  Among subjects with subclinical thyrotoxicosis, calculated deiodinase activity is significantly lower in  exogenous thyrotoxicosis  (resulting from therapy with levothyroxine) than in true hyperthyroidism (ensuing from  toxic adenoma ,  toxic multinodular goitre  or  Graves' disease ). [ 19 ]  SPINA-GD may therefore be an effective  biomarker  for the differential diagnosis of thyrotoxicosis. [ 20 ] [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4161", "text": "Compared to healthy subjects, SPINA-GD is significantly reduced in  euthyroid sick syndrome . [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4162", "text": "Recent research revealed total deiodinase activity to be higher in untreated hypothyroid patients as long as thyroid tissue is still present. [ 9 ]  This effect may ensue from the existence of an effective TSH-deiodinase axis or  TSH-T3 shunt . After total  thyroidectomy  or high-dose  radioiodine  therapy (e.g. in treated  thyroid cancer ) as well as after initiation of substitution therapy with levothyroxine the activity of step-up deiodinases decreases [ 23 ] [ 24 ]  and the correlation of SPINA-GD to thyrotropin concentration is lost. [ 25 ]  In patients suffering from toxic adenoma, toxic multinodular goitre and Graves\u2019 disease low-dose  radioiodine therapy  leads to a significant reduction of SPINA-GD as well. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4163", "text": "SPINA-GD is elevated in obesity. This applies to both the metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO) phenotypes. [ 27 ]  In two large population-based cohorts within the  Study of Health in Pomerania  SPINA-GD was positively correlated to some markers of  body composition  including  body mass index  (BMI),  waist circumference , fat-free mass and body cell mass, [ 28 ]  confirming observations in the  NHANES  dataset [ 29 ]  and in a Chinese study. [ 30 ]  This positive association was age-dependent and with respect to BMI significant in young subjects only, but with respect to body cell mass stronger in elderly persons. [ 28 ]  Generally, SPINA-GD seems to be upregulated in  metabolic syndrome , as demonstrated by a significant correlation to the triglyceride-glucose index, a marker of  insulin resistance . [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4164", "text": "SPINA-GD is reduced in  low-T3 syndrome [ 32 ]  and certain chronic diseases, e.g.  chronic fatigue syndrome , [ 33 ] [ 4 ]   chronic kidney disease , [ 34 ] [ 35 ]   short bowel syndrome [ 36 ]  or geriatric  asthma . [ 37 ]  Six months after the primary infection, it correlates negatively to the FS-14 score for  fatigue  in patients affected by  Long COVID  (PASC) [ 38 ] . In  Graves' disease , SPINA-GD is initially elevated but decreases with antithyroid treatment in parallel to declining TSH receptor autoantibody titres. [ 5 ]  Although  takotsubo syndrome  (TTS) results in most cases from  psychosocial stressors , thereby reflecting type 2  allostatic load , SPINA-GD has been described to be reduced in TTS. [ 39 ]  This may result from concomitant  non-thyroidal illness syndrome , so that the clinical phenotype represents overlapping type 1 and type 2 allostatic response. In a large register-based study, reduced SPINA-GD predicted a poor outcome of Takotsubo syndrome. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4165", "text": "In certain psychiatric diseases, including major depression, bipolar disorder and schizophrenia SPINA-GD is reduced compared to healthy controls. [ 41 ]  This observation is supported by negative correlation of SPINA-GD with the depression percentiles in the  Hospital Anxiety and Depression Scale  (HADS). [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4166", "text": "In hyperthyroid [ 43 ]  men both  SPINA-GT  and SPINA-GD negatively correlate to  erectile function , intercourse satisfaction,  orgasmic function  and  sexual desire . Substitution with  selenomethionine  results in increased SPINA-GD in subjects with autoimmune thyroiditis. [ 14 ] [ 15 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4167", "text": "In subjects with  diabetes mellitus  SPINA-GD is positively correlated to several bone resorption markers including the N-mid fragment of osteocalcin and procollagen type I N-terminal propeptide (P1NP), as well as, however in men only, the \u03b2-C-terminal cross-linked telopeptides of type I collagen (\u03b2-CTX). [ 44 ]  In the general population it is, however, positively associated with the bone mineral density of the femoral neck and with reduced risk of osteoporosis. [ 45 ]  In both diabetic and non-diabetic subsjects it correlates (negatively) with age and concentrations of  c-reactive protein ,  troponin T  and  B-type natriuretic peptide , and (positively) with the concentrations of total  cholesterol ,  low-density lipoprotein  and  triglycerides . [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4168", "text": "Deiodination capacity proved to be an independent predictor of substitution dose in several trials that included persons on replacement therapy with  levothyroxine . [ 47 ] [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4169", "text": "Probably as a consequence of  non-thyroidal illness syndrome , SPINA-GD predicts  mortality  in  trauma [ 22 ]  and postoperative  atrial fibrillation  in patients undergoing cardiac surgery. [ 12 ]   The association to mortality is retained even after adjustment for other established risk factors, including age,  APACHE II  score and plasma protein binding of thyroid hormones. [ 22 ]  Correlations were also shown to age, total atrial conduction time, and concentrations of  3,5-diiodothyronine  and  B-type natriuretic peptide . [ 12 ]  SPINA-GD also correlates with several components of the  kynurenine pathway , which might mirror an assosication to a pro-inflammatory milieu. [ 49 ]  Accordingly, in a population suffering from pyogenic liver abscess SPINA-GD correlated to markers of  malnutrition ,  inflammation  and  liver failure . [ 32 ]  A study on subjects with  Parkinson's disease  found SPINA-GD to be significantly decreased in  tremor -dominant and mixed subtypes compared to the akinetic-rigid type. [ 50 ]   Euthyroid sick syndrome  may be the reason for variations of SPINA-GD in subjects treated with  immune checkpoint inhibitors  for  cancer  as well. [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4170", "text": "Endocrine disruptors  may have pronounced effects on step-up deiodinases, as suggested by positive correlation of SPINA-GD to combined exposure to polycyclic aromatic hydrocarbons (PAHs) [ 52 ]  and urine concentrations of  cadmium  and  phthalate  metabolites, [ 53 ] [ 54 ] [ 55 ]  negative correlation to  paraben ,  mercury  and  bisphenol A  concentration [ 56 ] [ 53 ] [ 54 ]  and a nonlinear association to the concentrations of  per- and polyfluoroalkyl substances . [ 57 ]  In a cohort of manganese-exposed workers, SPINA-GD responded to a tenfold increase in concentrations of titanium, nickel, selenium and strontium. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4171", "text": "In a longitudinal evaluation of a large sample of the general US population over 10 years, reduced SPINA-GD significantly predicted reduced overall survival. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4172", "text": "suPARnostic  is a simplified double monoclonal antibody sandwich enzyme-linked immunosorbent assay ( ELISA ) that measures the amount of soluble urokinase plasminogen activator receptor ( suPAR ) in blood. [ 1 ]  Elevated plasma suPAR levels have been observed in various  infectious ,  inflammatory  and  autoimmune diseases . [ 2 ]  suPAR concentration positively correlates to the activation level of the immune system. suPARnostic can be used as a prognostic tool [ 3 ]  to determine the severity of a disease within a patient, but is not used as a reliable diagnostic tool, as it can detect the severity of the immune response in a patient, but does not reveal the specific disease from which the patient may be suffering. Recently, increase suPAR levels were shown to be associated with increased risk of systemic inflammatory response syndrome ( SIRS )/ sepsis ,  cardiovascular disease ,  type 2 diabetes ,  infectious diseases ,  HIV , [ 4 ]   cancer [ 5 ]   tuberculosis , [ 3 ]   malaria , [ 6 ]  bacterial and viral  CNS infections , [ 7 ]   rheumatoid arthritis , [ 8 ]   multiple sclerosis [ 3 ]  and  mortality  in the general population."}
{"_id": "WikiPedia_Hematology$$$corpus_4173", "text": "Performing the suPARnostic  ELISA  requires two antibodies with high specificity for  suPAR .  The blood plasma sample from the patient that contains an unknown amount of suPAR is immobilized on the microwells on the clear  microtiter plate  and a detection antibody forms a complex with suPAR.\nBetween each step the plate is rinsed with a wash buffer to dispose of any proteins that do not specifically bind to any of the wells on the plate.  After the final wash step, the plate is developed by adding the  TMB  substrate to produce a visible signal, which indicates the quantity of suPAR in the sample.  The measured  absorbance  can, based on the values from the standard curve, be converted to the concentration (ng/mL) of suPAR in the sample.  This level can then suggest whether or not the patient is experiencing challenges to their immune system. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4174", "text": "The suPARnostic  ELISA  is a simplified double  monoclonal antibody  sandwich assay that measures the level of  suPAR  and suPAR II-III  in the body . The suPARnostic ELISA utilizes monoclonal mouse and rat antibodies against human  suPAR . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4175", "text": "The advantages of using  monoclonal antibodies  compared to using  polyclonal antibodies  includes: High  homogeneity , absence of nonspecific antibodies and no batch-to-batch or lot-to-lot variability.  This results in a very robust and reliable assay. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4176", "text": "A 'sandwich' is formed of solid-phase  antibody , suPAR and peroxidase-conjugated antibody. The concentration (ng/mL plasma) of suPAR in the patient sample is determined via interpolation, based on a  calibration curve  prepared from seven suPAR standards. Recombinant suPAR standards are calibrated against healthy human blood donor samples. Absorbance is measured using a  microtiter plate  reader, at 450\u00a0nm with a 650\u00a0nm reference filter. Measurement of suPAR levels from blood samples provides greater accuracy and precision than measurement from  urine  or  cerebral spinal fluid . suPAR level is not changed by transient illness such as cold. It also remains stable after a blood sample is taken despite storage. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4177", "text": "suPARnostic measurements between 0.1 and 4.0\u00a0ng/mL suggest that a patient is healthy, with no challenges to their  immune system  and no signs or symptoms of an  opportunistic infection  or  inflammation ; the average level among the population is 3.4\u00a0ng/mL. However, a patient's immune system can be considered 'negatively activated' at suPAR levels above 4.0 and up to 6.0\u00a0ng/mL, indicating a potential infection or high level of inflammation. In this case, a patient's health is likely to worsen and he or she should be referred for further testing. suPARnostic measurements from 6.0\u00a0ng/mL to double digit levels can indicate a serious illness that is progressing rapidly to a critical situation. Patients in the intensive care unit average a level of 10.0\u00a0ng/mL. There is no difference in suPAR levels intrinsic to various races; however, the scale varies for male and female. [ 9 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4178", "text": "There are two suPARnostic tests available. The suPARnostic Standard ELISA (Code No. A001) is for research use and large trials, one batch consisting of 41 samples in doublets. The suPARnostic Flex ELISA (Code No. A002) has been developed for clinical applications consisting of 93 samples, is modular and flexible, and gives fully quantitative results in 2 hours. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4179", "text": "The suPARnostic kit has a refrigerated  shelf life  of several years and when frozen, may be kept for longer.  The kit should sit at room temperature for half an hour before use but it may be held at room temperature for as long as three to four hours. [ 12 ]  The suPARnostic Flex ELISA (Code No. A002) is able to provide fully quantitative results in 2 hours. [ 13 ]  suPARnostic is run as large, batch test with up to 41 samples in doublets for research purposes or 93 samples for clinical use at one time. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4180", "text": "Although suPARnostic currently does not have FDA approval, it is CE/ IVD  marked for distribution throughout Europe. [ 11 ]  suPAR is a prognostic test to indicate general health, and it cannot be used as a diagnostic tool to suggest a particular illness. [ 9 ]  suPAR cannot be used in the detection of brain tumors because the suPAR molecule cannot migrate through the  blood brain barrier . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4181", "text": "Syndromic testing  is a process by which a healthcare provider simultaneously tests a patient for multiple pathogens with overlapping  symptomology . This allows providers to order one test to see if patients are suffering from any one of multiple causes, rather than having to order a test for each potential underlying reason for the illness. It can be used with patients that are  immunosuppressed , in hospital environments that have limited testing assets, or patients that could be suffering from any number of or combination of reasons for a specific syndrome, such as respiratory distress,  gastroenteritis , [ 1 ]  bloodstream infections, or CNS infections. [ 2 ]  The test uses multi-panel syndromic  assays  that allow the simultaneous detection of a number of agents, increasing the accuracy of tests for microbial agents. [ 3 ]  The first multiplex panel for syndromic testing to be approved by the  FDA  received approval in 2008, [ 4 ] [ 5 ]  and since, panels for several potential pathogens have been approved. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4182", "text": "A  tetramer assay  (also known as a  tetramer stain ) is a procedure that uses  tetrameric  proteins to detect and quantify  T cells  that are specific for a given  antigen  within a blood sample. [ 1 ]  The tetramers used in the assay are made up of four  major histocompatibility complex  (MHC) molecules, which are found on the surface of most cells in the body. [ 2 ]  MHC molecules present  peptides  to T-cells as a way to communicate the presence of viruses, bacteria, cancerous mutations, or other antigens in a cell. If a T-cell's receptor matches the peptide being presented by an MHC molecule, an immune response is triggered. [ 3 ]  Thus, MHC tetramers that are bioengineered to present a specific peptide can be used to find T-cells with receptors that match that peptide.\nThe tetramers are labeled with a  fluorophore , allowing tetramer-bound T-cells to be analyzed with  flow cytometry . [ 4 ]  Quantification and sorting of T-cells by flow cytometry enables researchers to investigate immune response to viral infection and vaccine administration as well as functionality of antigen-specific T-cells. [ 5 ]  Generally, if a person's  immune system  has encountered a  pathogen , the individual will possess T cells with specificity toward some peptide on that pathogen. Hence, if a tetramer stain specific for a pathogenic peptide results in a positive signal, this may indicate that the person's immune system has encountered and built a response to that pathogen. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4183", "text": "This methodology was first published in 1996 by a lab at Stanford University. [ 6 ]  Previous attempts to quantify antigen-specific T-cells involved the less accurate limiting dilution assay, which estimates numbers of T-cells at 50-500 times below their actual levels. [ 7 ] [ 8 ]  Stains using soluble MHC  monomers  were also unsuccessful due to the low binding affinity of T-cell receptors and MHC-peptide monomers. MHC tetramers can bind to more than one receptor on the target T-cell, resulting in an increased total binding strength and lower dissociation rates. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4184", "text": "Tetramer stains usually analyze  cytotoxic T lymphocyte  (CTL) populations. [ 9 ]  CTLs are also called CD8+ T-cells, because they have  CD8  co-receptors that bind to MHC class I molecules. Most cells in the body express MHC class I molecules, which are responsible for processing intracellular antigens and presenting at the cell's surface. If the peptides being presented by MHC class I molecules are foreign\u2014for example, derived from viral proteins instead of the cell's own proteins\u2014the CTL with a receptor that matches the peptide will destroy the cell. [ 2 ] [ 3 ]  Tetramer stains allow for the visualization, quantification, and sorting of these cells by flow cytometry, which is extremely useful in  immunology . T-cell populations can be tracked over the duration of a virus or after the application of a vaccine. Tetramer stains can also be paired with functional assays like  ELIspot , which detects the number of  cytokine  secreting cells in a sample. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4185", "text": "MHC tetramer molecules developed in a lab can mimic the antigen presenting complex on cells and bind to T-cells that recognize the antigen. Class I MHC molecules are made up of a polymorphic heavy \u03b1-chain associated with an invariant light chain  beta-2 microglobulin  (\u03b22m).  Escherichia coli  are used to synthesize the light chain and a shortened version of the heavy chain that includes the  biotin  15 amino acid recognition tag. These MHC chains are biotinylated with the enzyme BirA and refolded with the antigenic peptide of interest. Biotin is a small molecule that forms a strong bond with another protein called streptavidin. Fluorophore tagged streptavidin is added to the bioengineered MHC monomers, and the biotin-streptavidin interaction causes four MHC monomers to bind to the streptavidin and create a tetramer. When the tetramers are mixed with a blood sample, they will bind to T-cells expressing the appropriate antigen specific receptor. Any MHC tetramers that are not bound are washed out of the sample before it is analyzed with flow cytometry. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4186", "text": "Recent advancements within recombinant MHC molecules have democratised peptide MHC complex formulation and subsequent multimerisation. Highly active formulations of a broad range of MHC class I molecules [ 10 ]  now allows non-experts users to make their own custom peptide-MHC complexes from day-to-day in any lab without special equipment. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4187", "text": "Tetramers that bind to helper T-cells have also been developed. [ 9 ]   Helper T-cells  or CD4+ T-cells express  CD4  co-receptors. They bind to  class II MHC  molecules, which are only expressed in professional  antigen-presenting  cells like dendritic cells or  macrophages . Class II MHC molecules present extracellular antigens, allowing helper T-cells to detect bacteria, [ 11 ]  fungi, and parasites. [ 2 ]  Class II MHC tetramer use is becoming more common, but the tetramers are more difficult to create than class I tetramers and the bond between helper T-cells and MHC molecules is even weaker. [ 9 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4188", "text": "Natural killer T-cells  (NKT cells) can also be visualized with tetramer technology. NKT cells bind to proteins that present  lipid  or  glycolipid  antigens. [ 13 ]  The antigen presenting complex that NKT cells bind to involves  CD1  proteins, so tetramers made of CD1 can be used to stain for NKT cells. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4189", "text": "An early application of tetramer technology focused on the cell-mediated immune response to  HIV  infection. MHC tetramers were developed to present HIV antigens and used to find the percentage of CTLs specific to those HIV antigens in blood samples of infected patients. This was compared to results of cytotoxic assays and plasma  RNA  viral load to characterize the function of CTLs in HIV infection. The CTLs that bound to tetramers were sorted into ELIspot wells for analysis of cytokine secretion. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4190", "text": "Another study utilized MHC tetramer complexes to investigate the effectiveness of an influenza  vaccine  delivery method. Mice were given subcutaneous and intranasal vaccinations for influenza, and tetramer stains coupled with flow cytometry were used to quantify the CTLs specific to the antigen used in the vaccine. This allowed for comparison of the immune response (the number of T-cells that target a virus) in two different vaccine delivery methods. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4191", "text": "A  thrombin generation assay  ( TGA ) or  thrombin generation test  ( TGT ) is a  global coagulation assay  (GCA) and type of  coagulation test  which can be used to assess  coagulation  and  thrombotic  risk. [ 1 ] [ 2 ] [ 3 ]  It is based on the potential of a  plasma  to generate  thrombin  over time, following activation of coagulation via addition of  phospholipids ,  tissue factor , and  calcium . [ 4 ]  The results of the TGA can be output as a  thrombogram  or thrombin generation curve using computer software with calculation of thrombogram parameters. [ 5 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4192", "text": "TGAs can be performed with methods like the semi-automated  calibrated automated thrombogram  (CAT) (2003) or the fully-automated  ST Genesia  system (2018). [ 6 ] [ 1 ] [ 7 ]  TGAs were first used as manual assays in the 1950s and have since become increasingly automated. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4193", "text": "Thrombogram parameters for the TGA include: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4194", "text": "The addition of  activated protein C  (APC) to a TGA results in an inhibition of thrombin generation as measured by reduction of the endogenous thrombin potential (ETP; area under the thrombin generation curve). [ 4 ]  This can be used to assess  APC resistance  and is termed the ETP-based APC resistance test. [ 4 ]  Results may be expressed as normalized APC sensitivity ratio (nAPCsr), which corresponds to the ratio of the ETP measured in the presence and absence of APC divided by the same ratio in reference plasma. [ 4 ]  The higher the nAPCsr value, the greater the APC resistance of the person. [ 4 ]  The ETP-based APC resistance test was developed in 1997. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4195", "text": "The  thrombin time  ( TT ), also known as the  thrombin clotting time  ( TCT ), is a  blood test  that measures the time it takes for a  clot  to form in the plasma of a blood sample containing  anticoagulant , after an excess of  thrombin  has been added. [ 1 ]  It is used to diagnose blood  coagulation  disorders and to assess the effectiveness of fibrinolytic therapy.  This test is repeated with pooled plasma from normal patients. The difference in time between the test and the 'normal' indicates an abnormality in the conversion of  fibrinogen  (a soluble protein) to fibrin, an insoluble protein. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4196", "text": "The thrombin time compares the rate of clot formation to that of a sample of normal pooled plasma. Thrombin is added to the samples of plasma. If the time it takes for the plasma to clot is prolonged, a quantitative (fibrinogen deficiency) or qualitative (dysfunctional fibrinogen) defect is present. [ 3 ]  In  blood samples suspected to contain  heparin , a substance derived from snake venom called  batroxobin [ 4 ]  (formerly  reptilase ) is used for comparison to thrombin time. Batroxobin has a similar action to thrombin but unlike thrombin it is not inhibited by heparin, so  reptilase time  and thrombin time can be used concurrently to distinguish anticoagulant effect from  hypofibrinogenemia  or  dysfibrinogenemia . [ 1 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4197", "text": "Normal values for thrombin time may be 12 to 14 seconds, [ 6 ]  but the test has significant reagent variability. If batroxobin is used, the time should be between 15 and 20 seconds. Thrombin time can be prolonged by heparin, fibrin degradation products, and fibrinogen deficiency or abnormality.  Thrombin time is not affected by anti-Xa anticoagulants such as  rivaroxaban  or  apixaban , but is very sensitive to  direct thrombin inhibitors  including  dabigatran ,  argatroban , and  bivalirudin . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4198", "text": "After separating the plasma from the whole blood by  centrifugation , bovine  thrombin  is added to the sample of plasma. Clot formation is detected optically or mechanically by a coagulation instrument. The time between the addition of the thrombin and the clot formation is recorded as the thrombin clotting time. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4199", "text": "Whole blood is taken with either  citrate  or  oxalate  additive (if using the  vacutainer  system, this is a light blue top tube).  As with other coagulation assays, the tube must not be over- or under-filled in order to ensure the correct anticoagulant-to-blood ratio: one part anticoagulant per nine parts blood. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4200", "text": "The  reference ranges  of the thrombin clotting time is generally <22 seconds, [ 7 ]  and often from 14 to 16 seconds. [ 6 ]  Laboratories usually calculate their own ranges, based on the method used and the results obtained from healthy individuals from the local population.  Variability arises from differences in thrombin concentration, dilution of plasma, presence and/or concentration of calcium ions, as well as the influence of analyser type. [ 5 ]  TT may also be sensitive to citrate pH. Separate ranges are used for infants. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4201", "text": "Blood samples that are more than eight hours old can give inaccurate results when tested. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4202", "text": "Thrombodynamics test  is a method for blood  coagulation  monitoring and anticoagulant control. This test is based on imitation of coagulation processes occurring  in vivo , is sensitive both to pro- and anticoagulant changes in the hemostatic balance. Highly sensitive to thrombosis."}
{"_id": "WikiPedia_Hematology$$$corpus_4203", "text": "The method was developed in the Physical Biochemistry Laboratory under the direction of Prof. Fazly Ataullakhanov."}
{"_id": "WikiPedia_Hematology$$$corpus_4204", "text": "Thrombodynamics designed to investigate the  in vitro  spatial-temporal dynamics of blood coagulation initiated by localized coagulation activator under conditions similar to the conditions of the blood clotting  in vivo . Thrombodynamics takes into account the spatial heterogeneity trombodinamiki processes in blood coagulation. The test is performed without mixing in a thin layer of  plasma ."}
{"_id": "WikiPedia_Hematology$$$corpus_4205", "text": "The measurement cuvette with the blood plasma sample is placed inside the water thermostat. Clotting starts when activator with immobilized  TF  is immersed into the cuvette. The clot then propagates from the activating surface into the bulk of plasma. Image of growing clot is registered via the CCD camera using a time-lapse microscopy mode in scattered light and then parameters of coagulation are calculated on the computer. Thrombodynamics analyser T-2 device also supports measurement of spatial dynamics of thrombin propagation during the process of clot growth via usage of the fluorogenic substrate for thrombin. Blood plasma sample is periodically irradiated with the excitation light and the emission of the fluorophore is registered by CCD camera."}
{"_id": "WikiPedia_Hematology$$$corpus_4206", "text": "Mathematical methods are used to restore spatio-temporal distribution of the thrombin from the fluorophore signal. This experimental model worked well in research and has demonstrated good sensitivity to various disorders of the coagulation system."}
{"_id": "WikiPedia_Hematology$$$corpus_4207", "text": "[ 1 ] \n [ 2 ] \n [ 3 ] \n [ 4 ] \n [ 5 ] \n [ 6 ] \n [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4208", "text": "Thromboelastography  ( TEG ) is a method of testing the efficiency of  blood   coagulation . It is a test mainly used in  surgery  and  anesthesiology , although increasingly used in resuscitations in emergency departments, intensive care units, and labor and delivery suites. More common tests of blood coagulation include  prothrombin time  (PT) and  partial thromboplastin time  (aPTT) which measure coagulation factor function, but TEG also can assess platelet function, clot strength, and  fibrinolysis  which these other tests cannot. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4209", "text": "Thromboelastometry  (TEM), previously named rotational thromboelastography (ROTEG) or rotational thromboelastometry (ROTEM), is another version of TEG in which it is the sensor shaft, rather than the cup, that rotates."}
{"_id": "WikiPedia_Hematology$$$corpus_4210", "text": "A small sample of blood is taken from the selected person and rotated gently through 4\u00ba 45', six times a minute, to imitate sluggish  venous flow  and activate coagulation. The clot forms around a thin wire probe used for measurement. The speed and strength of clot formation is measured in various ways, typically by computer. The speed at which the sample coagulates depends on the activity of the  plasma  coagulation system,  platelet  function,  fibrinolysis  and other factors which can be affected by genetics, illness, environment, and medications. The patterns of changes in strength and elasticity in the clot provide information about how well the blood can perform  hemostasis  and how well or poorly different factors are contributing to clot formation. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4211", "text": "Four values that represent clot formation are determined by this test: the reaction time (R value), the K value, the angle and the maximum amplitude (MA). The R value represents the time until the first evidence of a clot is detected. The K value is the time from the end of R until the clot reaches 20mm and this represents the speed of clot formation. The angle is the tangent of the curve made as the K is reached and offers similar information to K. The MA is a reflection of clot strength. A mathematical formula determined by the manufacturer can be used to determine a Coagulation Index (CI) (or overall assessment of coagulability) which takes into account the relative contribution of each of these 4 values into 1 equation. The G-value is a log-derivation of the MA and is meant to also represent the clot strength using dynes/sec as its units. There are some studies which suggest that an elevated G-value is associated with a hypercoagulable state and therefore increases the risk for venous thromboembolic disease. However, there are no studies dosing of prophylactic heparin products based on the G-value. TEG also measures clot lysis which is reported as both the estimated percent lysis (EPL) and the percentage of clot which has actually lysed after 30 minutes (LY 30,%). Although a normal EPL can be as high as 15% and a normal LY 30 can be as high as 8%, some studies in the trauma population suggest that a LY30 greater than 3% is associated with risk of hemorrhage. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4212", "text": "Thromboelastometry  (TEM), previously named rotational thromboelastography (ROTEG) or rotational thromboelastometry (ROTEM), is another version of TEG in which it is the sensor shaft, rather than the cup, that rotates. Blood (300 \u03bcL, anticoagulated with  citrate ) is placed into the disposable cuvette using an electronic pipette. A disposable pin is attached to a shaft which is connected with a thin spring (the equivalent to Hartert's torsion wire in thrombelastography) and slowly  oscillates  back and forth. The signal of the pin suspended in the blood sample is transmitted via an optical detector system. The test is started by adding appropriate reagents. The instrument measures and graphically displays the changes in elasticity at all stages of the developing and resolving clot. The typical test temperature is 37\u00a0\u00b0C, but different temperatures can be selected, e.g. for patients with hypothermia. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4213", "text": "Parameters derived from thromboelastography are mainly: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4214", "text": "Following are examples of thromboelastography patterns and recommended treatments. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4215", "text": "There are several types of assays that can be run using TEG: Standard (kaolin), RapidTEG, heparinase, Functional Fibrinogen and PlateletMapping. A standard TEG is the most commonly ordered test and includes the parameters noted above. A RapidTEG uses tissue factor in addition to kaolin thereby further speeding up the reaction. In this assay, the R-value is replaced by the TEG-ACT value which is measured in seconds rather than in minutes. The remainder of the TEG parameters do not differ between a standard and RapidTEG. A heparinase TEG is used to assess for heparin-associated anticoagulation as the cause of hemorrhage. It is used most commonly following  cardiopulmonary bypass  procedures where heparin is reversed using protamine intraoperatively. In instances where a patient develops bleeding due to recurrent coagulopathy (usually shortly after arrival to the ICU), the heparinase TEG can help quickly discern patients who can be treated with additional dosing of protamine versus those who need to be taken back to the operating room for re-exploration. In this assay, a standard TEG is run twice \u2013 once using the patient's blood only and another time using the patient's blood plus added heparinase. If the two graphs are nearly the same, the cause of bleeding is not related to heparin rebound. However, if the R-time associated with the heparinase-added specimen is significantly shorter than the R-time of the patient's blood without added heparinase, the bleeding is likely due to heparin rebound and should respond to administration of protamine. Lastly, the platelet map TEG aims to determine to what degree platelet function may be inhibited due to pharmacologic inhibition of either the arachidonic acid (AA) or adenosine diphosphate (ADP) pathways. Aspirin inhibits platelet function via the AA pathway while clopidogrel inhibits platelet function via the ADP pathway; thus, this test can be used to determine the degree to which a patient is anticoagulated due to either medication. In this assay, a standard TEG is run using patient's whole blood. Then, separate assays are run using the patient's blood with added AA or ADP. The contribution of fibrin to the MA is subtracted using a mathematical formula. This allows determination of the MA (AA) and MA (ADP), respectively. The difference between the patient's whole blood result and AA/ADP added results are used to calculate the percent inhibition."}
{"_id": "WikiPedia_Hematology$$$corpus_4216", "text": "Because the R value on the TEG represents the time it takes for clot formation to start, it is a reflection of coagulation factor activity. Coagulation factors are essentially enzymes that drive clot formation. Thus, a significantly prolonged R time could be treated with frozen plasma. The alpha angle represents the thrombin burst and conversion of fibrinogen to fibrin. Thus, a depressed alpha angle could be treated with  cryoprecipitate . 80% of the MA is derived from platelet function whereas the remaining 20% is derived from fibrin. Thus, a significantly depressed MA could be treated with platelet transfusion or medications that improve platelet function, such as DDAVP. An elevated EPL or LY30 suggests fibrinolysis and may be treated with an antifibrinolytic, such as tranexamic acid or aminocaproic acid, in the appropriate clinical setting. A single, modified TEG assay with exogenous tissue plasminogen activator (tPA) demonstrated remarkable efficiency in unmasking patients' impending risk for massive transfusion in trauma patients. [ 8 ]  The iTACTIC trial showed no difference in outcomes in trauma patients with massive hemorrhage managed with conventional coagulation tests compared to viscoelastic assays.  However, the traumatic brain injury subgroup showed slightly better survival in the TEG/ROTEM group with a \u201cvery low\u201d quality assessment by the GRADE system. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4217", "text": "Clinical studies of thromboelastography during elective surgery (cardiac and liver surgery) and emergency resuscitation have shown improvements in clinical outcomes. [ 10 ]  In elective surgery there was a decreased need for blood products (platelets and plasma) and reduced operating room length of stay as well as duration of intensive care admission and bleeding rates; mortality was not affected. In emergency settings, mortality was reduced with an associated decrease in the need for platelets and plasma. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4218", "text": "Additional studies show thromboelastography may be used to characterize COVID-19-associated coagulopathy. TEG with platelet mapping may be used to guide use of anticoagulant and antiplatelet medications. When using a TEG-guided strategy hospital length of stay, intensive care unit length of stay, mortality, acute kidney injury, intensive care unit admissions and need for mechanical ventilation may be reduced.  [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4219", "text": "Thromboelastometry  ( TEM ), previously named  rotational thromboelastography  ( ROTEG ) or  rotational thromboelastometry  ( ROTEM ), is an established  viscoelastic  method for  hemostasis  testing in  whole blood . [ 1 ]  It is a modification of traditional  thromboelastography  (TEG)."}
{"_id": "WikiPedia_Hematology$$$corpus_4220", "text": "TEM investigates the interaction of  coagulation factors , their  inhibitors ,  anticoagulant drugs ,  blood cells , specifically  platelets , during clotting and subsequent  fibrinolysis . The  rheological  conditions mimic the sluggish flow of blood in  veins ."}
{"_id": "WikiPedia_Hematology$$$corpus_4221", "text": "While traditional thromboelastography is a global  assay  for  blood clotting  disorders and drug effects, TEM is primarily used in combination with appropriate differential assays. They allow testing in the presence of therapeutic  heparin  concentrations and provide differential diagnostic information to support decisions in therapy. In numerous publications, the validity of the method is shown. Application of TEM at the  point of care  (POC) or in emergency laboratories is getting more and more popular. TEM detects both hypo- and hyperfunctional stages of the clotting process and is probably the only reliable rapid test for the diagnosis of  hyperfibrinolysis . In contrast to standard clotting tests, the  fibrin -stabilizing effect of  factor XIII  contributes to the result."}
{"_id": "WikiPedia_Hematology$$$corpus_4222", "text": "The rapid availability of results helps to discriminate surgical bleeding from a true haemostasis disorder and improves the therapy with  blood products , factor concentrates,  anticoagulants  and  protamine , hemostyptic and  antifibrinolytic  drugs. [ 2 ] [ 3 ]  Several reports confirm that application of TEM is cost effective by reducing the consumption of blood products. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4223", "text": "Blood (300 \u03bcL, anticoagulated with  citrate ) is placed into the disposable cuvette using an electronic pipette.  A disposable pin is attached to a shaft which is connected with a thin spring (the equivalent to Hartert\u2019s torsion wire in thrombelastography) and slowly  oscillates  back and forth. The signal of the pin suspended in the blood sample is transmitted via an optical detector system. The test is started by adding appropriate reagents. The instrument measures and graphically displays the changes in elasticity at all stages of the developing and resolving clot. The typical test temperature is 37\u00a0\u00b0C, but different temperatures can be selected, e.g. for patients with hypothermia. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4224", "text": "In contrast to thrombelastography with its pendulum-like principle, the design of the TEM  viscoelastic  detection system (figure 1) makes it quite robust and insensitive against mechanical shocks or vibrations. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4225", "text": "The primary result of TEM is a reaction curve which shows the elasticity over time when the clot forms or dissolves. This curve is also called a TEMogram. Four key parameters describe the clotting curve for clinical routine. More than 10 additional  calculated parameters, including  derivative  curves which are useful in specific research applications, e.g. in hemophilia [ 8 ]  or thrombophilia [ 9 ]  or for the effects of recombinant FVIIa [ 10 ]  are available for research purposes."}
{"_id": "WikiPedia_Hematology$$$corpus_4226", "text": "CT  (Clotting time):\nThe CT is the latency time from adding the start reagent to blood until the clot starts to form. Prolongation of CT may be a result of coagulation deficiencies, primarily coagulation factors, or heparin (dependent on the test used).  A potential contribution of heparin can be detected by comparing INTEM- with HEPTEM CT data (see \u201creagents\u201d below). A shortening of CT indicates hypercoagulability. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4227", "text": "CFT  (Clot formation time) and  alpha-angle :\nThe alpha angle is the angle of tangent between 0\u00a0mm and the curve when the clot firmness is 20\u00a0mm, while CFT is the time from CT until a clot firmness of  20\u00a0mm point has been reached. These parameters denote the speed at which a solid clot forms and are primarily influenced by  platelet  function, but to a certain extent especially  fibrinogen  and  coagulation factors  contribute. A prolonged CFT (or a lower alpha-angle) is usually caused by poor platelet function, low platelet count, fibrin polymerization disorders or fibrinogen deficiency. Apparently also FXIII seems to be involved already in this phase. [ 11 ]  Higher concentrations of  heparin  can also prolong CFT in the INTEM assay, but not in HEPTEM, EXTEM, FIBTEM or APTEM (see under \u201creagents\u201d). A shortening of CFT (or a high alpha-angle) indicate hypercoagulability. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4228", "text": "MCF  (Maximum clot firmness):\nMCF is the greatest vertical  amplitude  of the trace. It reflects the absolute strength of the fibrin and platelet clot. A low MCF is indicative of decreased platelet number or function, decreased fibrinogen level or fibrin polymerization disorders, or low activity of factor XIII. A mechanically weak clot represents a severe bleeding risk and should initiate immediate therapeutic steps. High doses of heparin can lower MCF in the INTEM assay, but not in HEPTEM, EXTEM, FIBTEM or APTEM (see under \u201creagents\u201d)."}
{"_id": "WikiPedia_Hematology$$$corpus_4229", "text": "A5, A 10, A15 or A20 value \nThese values describe the clot firmness (or amplitude) obtained after 10, 15 or 20 minutes (beginning from CFT) and  provide a forecast on the expected MCF value at an earlier stage already. A recent investigation has validated this approach for the A15 value in more than 800 cases during  liver transplantation . [ 12 ]  The advantage of the A15-values is obvious: It allows for a more rapid decision about therapeutic interventions."}
{"_id": "WikiPedia_Hematology$$$corpus_4230", "text": "LI 30  (Lysis Index after 30 minutes) and  ML  (Maximum Lysis)\nThe LI30 value is the percentage of remaining clot stability in relation to the MCF value at 30 min after CT. A similar value can also be calculated at other time points (45 or 60 min). The ML parameter describes the percentage of lost clot stability (relative to MCF, in\u00a0%) viewed at any selected time point or when the test has been stopped.  A low LI (X) value or a high ML value indicates hyperfibrinolysis. While in normal blood fibrinolysis activity is quite low, in clinical samples a more rapid loss of clot stability by hyperfibrinolysis may lead to bleeding complications which can be treated by the administration of  antifibrinolytic  drugs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4231", "text": "Initially,  thrombelastography  was simply performed with whole blood without adding reagents (except calcium when citrate anticoagulated blood was used). This provides a global overview about all phases of clot formation, stabilization and degradation. In the case of monocausal haemostasis disorders, the resulting reaction curves may be quite typical; however, under most clinical conditions this approach has severe limitations. In reality various effects overlap, including haemodilution or application of high doses of  parenteral  anticoagulants. High doses of heparin often prevent clot formation at all. Absence of a controlled activation step leads to inferior reproducibility and very long test times which are not acceptable for POC applications.\nThe assays for ROTEM analysis help to get a rapid differentiation between various potential haemostasis defects or anticoagulant drug effects and allow for a rapid differential diagnosis. They form the base for selecting a therapeutic strategy. Several diagnostic  algorithms  have been proposed and were clinically validated. [ 12 ] [ 13 ] [ 14 ]  Application of this strategy helps to minimize the exposure of patients to  allogeneic  blood products which have certain risks; and it saves costs. [ 4 ] [ 5 ] [ 6 ]  Numerous research applications have used the technique as well. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4232", "text": "INTEM \nThis test mildly activates the contact phase of haemostasis. The result is influenced by coagulation factors, platelets, fibrinogen and heparin. Low molecular weight heparin is detected at higher concentrations. [ 15 ] [ 16 ]  In the absence of heparin, INTEM is a screening test for the haemostasis system. It is used for therapeutic decisions regarding the administration of fresh frozen plasma, coagulation factors, fibrinogen or platelets."}
{"_id": "WikiPedia_Hematology$$$corpus_4233", "text": "HEPTEM \nThis assay represents an INTEM assay performed in the presence of heparinase, a heparin (or LMWH) degrading enzyme. It allows the identification of haemostasis deficiencies even in the presence of heparin and represents an INTEM test without interference by heparin or heparin like anticoagulants. The difference between HEPTEM and INTEM CT-value comparison confirms the presence of heparin, e.g. accidental exposure. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4234", "text": "EXTEM \ntest mildly activates haemostasis via the physiological activator tissue factor. The result is influenced by extrinsic coagulation factors, platelets and fibrinogen. EXTEM is a screening test for the (extrinsic) haemostasis system. This assay is not influenced by heparin (heparin inhibitor included in the EXTEM reagent). It is used for therapeutic decisions regarding the administration of fresh frozen plasma, coagulation factors, fibrinogen or platelets. EXTEM is also the base activator for FIBTEM and APTEM."}
{"_id": "WikiPedia_Hematology$$$corpus_4235", "text": "FIBTEM \ntest is an EXTEM based assay for the fibrin part of the clot. FIBTEM eliminates the platelet contribution of clot formation by inhibiting the platelets irreversibly with  cytochalasin D , a potent  inhibitor  of  actin  polymerization which disrupts actin microfilaments, an essential part of a cytoskeleton-mediated contractibility apparatus of the platelet. The use of cytochalasin is more favorable than using  glycoprotein  IIb/ IIIa inhibitors which block platelet incompletely, especially at higher platelet counts. [ 18 ]  FIBTEM allows for the detection of fibrinogen deficiency or fibrin polymerization disorders, e.g. induced by certain plasma expanders, and may identify rapidly the need to substitute fibrinogen. FIBTEM results correlate well in many cases with the Clauss fibrinogen assay, but is additionally influenced by fibrin polymerization disorders which cannot reliably be detected with clotting tests. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4236", "text": "APTEM \ntest is an EXTEM based assay in which  fibrinolysis  is inhibited by  aprotinin  in the reagent. A significant improvement of the clot in APTEM compared to EXTEM allows to detect fulminant hyperfibrinolysis. Therefore, the test helps in identifying the necessity of administrating  antifibrinolytic  drugs. Furthermore, APTEM enables the estimation if an antifibrinolytic therapy alone normalizes coagulation or if additional measures have to be taken (e.g. administration of fibrinogen or platelets)."}
{"_id": "WikiPedia_Hematology$$$corpus_4237", "text": "Quality control is an important requirement in laboratory and POC testing. An automatic internal electronic control procedure is implemented in the ROTEM whole blood analyzer. Furthermore, biological control materials at 2 different levels are available and should be used in order to document quality and validity of results."}
{"_id": "WikiPedia_Hematology$$$corpus_4238", "text": "TEM is successfully used in the near patient assessment of haemostasis. The method allows detection of complex haemostasis disorders (available in most coagulopathies) within a few minutes and thus enables rapid therapeutic intervention. Whole blood TEM is sensitive to haemostasis affecting agents such as plasma expanders or  acidosis  while the effects of these agents are hardly identified by plasma based laboratory tests.\nTEM-guided  transfusion  of blood products or factor concentrates in  cardiac ,  hepatic  and major  orthopedic  surgery is the main application of the method. Moreover, it is successfully used in the complex situation of  (poly) trauma , or in decision making for of alternative therapy such as antifibrinolytic drug administration . \nThe clinical benefits of TEM have resulted in major savings [ 4 ] [ 5 ] [ 6 ]  and publications recommend that  viscoelastic  methods such as TEM should be used in surgical procedures where major blood loss followed by the need for transfusions can be expected. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4239", "text": "Like any other haemostasis evaluating method, TEM (and thrombelastography) have limitations which need to be considered when interpreting the results. The typical assays are not responsive for the effect of von Willebrand factor or platelet antagonists such as  aspirin  or thienopyridines (e.g.  clopidogrel ), and only supratherapeutic doses of  GPIIb/IIIa  antagonists may influence results. The sensitivity for coagulation factor deficiencies, including those induced by oral anticoagulation, is less pronounced as compared to clotting assays. Therefore, TEM is not meant to replace laboratory assays such as prothrombin time (PT) or factor assays. However, due to the rapid availability of differential diagnostic information, TEM has become an established method in surgical procedures where blood losses can be expected."}
{"_id": "WikiPedia_Hematology$$$corpus_4240", "text": "The  Thyroid Feedback Quantile-based Index  ( TFQI ) is a calculated parameter for thyrotropic  pituitary  function. It was defined to be more robust to distorted data than established markers including  Jostel's TSH index  (JTI) and the  thyrotroph thyroid hormone sensitivity index  (TTSI)."}
{"_id": "WikiPedia_Hematology$$$corpus_4241", "text": "The TFQI can be calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4242", "text": "from  quantiles  of FT4 and TSH concentration (as determined based on  cumulative distribution functions ). [ 1 ]  Per definition the TFQI has a  mean  of 0 and a  standard deviation  of 0.37 in a reference population. [ 1 ]  This explains the reference range of \u20130.74 to + 0.74."}
{"_id": "WikiPedia_Hematology$$$corpus_4243", "text": "Higher values of TFQI are associated with  obesity ,  metabolic syndrome , impaired  renal  function,  diabetes , and diabetes-related  mortality . [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ]  In a large population of community-dwelling euthyroid subjects the thyroid feedback quantile-based index predicted all-cause mortality, even after adjustment for other established risk factors and comorbidities. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4244", "text": "A cross-sectional study from Spain observed increased prevalence of type 2 diabetes, atrial fibrillation, ischemic heart disease and hypertension in persons with elevated PTFQI. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4245", "text": "Serum Concentrations of Adipocyte Fatty Acid-Binding Protein (A-FABP) are significantly correlateted to TFQI, suggesting some form of cross-talk between adipose tissue and HPT axis. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4246", "text": "TFQI results are also elevated in  takotsubo syndrome , [ 11 ]  potentially reflecting type 2  allostatic load  in the situation of  psychosocial stress . Reductions have been observed in subjects with  schizophrenia  after initiation of therapy with  oxcarbazepine [ 12 ]  and quetiapine, [ 13 ]  potentially reflecting declining allostatic load."}
{"_id": "WikiPedia_Hematology$$$corpus_4247", "text": "Despite positive association to metabolic syndrome and type 2 allostatic load a large population-based study failed to identify an association to risks of  dyslipidemia  and  non-alcoholic fatty liver disease  (NAFLD). [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4248", "text": "Thyroid function tests  ( TFTs ) is a collective term for  blood tests  used to check the function of the  thyroid . [ 1 ] \nTFTs may be requested if a patient is thought to suffer from  hyperthyroidism  (overactive thyroid) or  hypothyroidism  (underactive thyroid), or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as  atrial fibrillation  and  anxiety disorder ."}
{"_id": "WikiPedia_Hematology$$$corpus_4249", "text": "A TFT  panel  typically includes  thyroid hormones  such as  thyroid-stimulating hormone  (TSH, thyrotropin) and  thyroxine  (T4), and  triiodothyronine  (T3) depending on local laboratory policy."}
{"_id": "WikiPedia_Hematology$$$corpus_4250", "text": "Thyroid-stimulating hormone  (TSH, thyrotropin) is generally increased in hypothyroidism and decreased in hyperthyroidism, [ 2 ]  making it the most important test for early detection of both of these conditions. [ 3 ] [ 4 ]  The result of this  assay  is suggestive of the presence and cause of thyroid disease, since a measurement of elevated TSH generally indicates  hypothyroidism , while a measurement of low TSH generally indicates  hyperthyroidism . [ 2 ]  However, when TSH is measured by itself, it can yield misleading results, so additional thyroid function tests must be compared with the result of this test for accurate diagnosis. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4251", "text": "TSH is produced in the  pituitary gland . The production of TSH is controlled by  thyrotropin-releasing hormone  (TRH), which is produced in the  hypothalamus . TSH levels may be suppressed by excess free T3 (fT3) or free T4 (fT4) in the blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4252", "text": "First-generation TSH assays were done by  radioimmunoassay  and were introduced in 1965. [ 3 ]  There were variations and improvements upon TSH radioimmunoassay, but their use declined as a new immunometric assay technique became available in the middle of the 1980s. [ 3 ] [ 4 ]  The new techniques were more accurate, leading to the second, third, and even fourth generations of TSH assay, with each generation possessing ten times greater functional sensitivity than the last. [ 7 ]  Third generation immunometric assay methods are typically automated. [ 3 ]  Fourth generation TSH immunometric assay has been developed for use in research. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4253", "text": "Third generation TSH assay is the requirement for modern standards of care. TSH testing in the United States is typically carried out with automated platforms using advanced forms of immunometric assay. [ 3 ]  Nonetheless, there is no international standard for measurement of thyroid-stimulating hormone. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4254", "text": "Accurate interpretation takes a variety of factors into account, such as the thyroid hormones i.e.  thyroxine  (T 4 ) and  triiodothyronine  (T 3 ), current medical status (such as pregnancy [ 3 ] ), [ 4 ]  certain medications like  propylthiouracil , [ 4 ]  temporal effects including  circadian rhythm [ 8 ]  and  hysteresis , [ 9 ]  and other past  medical history . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4255", "text": "Total thyroxine is rarely measured, having been largely superseded by free thyroxine tests. Total  thyroxine  (Total T 4 ) is generally elevated in  hyperthyroidism  and decreased in  hypothyroidism . [ 2 ]  It is usually slightly elevated in pregnancy secondary to increased levels of  thyroid binding globulin  (TBG). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4256", "text": "Total T4 is measured to see the bound and unbound levels of T4. The total T4 is less useful in cases where there could be protein abnormalities. The total T4 is less accurate due to the large amount of T4 that is bound. The total T3 is measured in clinical practice since the T3 has decreased amount that is bound as compared to T4. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4257", "text": "Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:"}
{"_id": "WikiPedia_Hematology$$$corpus_4258", "text": "Free  thyroxine  (fT 4  or free T4) is generally elevated in  hyperthyroidism  and decreased in  hypothyroidism . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4259", "text": "Total  triiodothyronine  (Total T 3 ) is rarely measured, having been largely superseded by free T3 tests. Total T3 is generally elevated in hyperthyroidism and decreased in hypothyroidism. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4260", "text": "Free  triiodothyronine  (fT 3  or free T3) is generally elevated in hyperthyroidism and decreased in hypothyroidism. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4261", "text": "An increased  thyroxine-binding globulin  results in an increased total thyroxine and total triiodothyronine without an actual increase in hormonal activity of thyroid hormones."}
{"_id": "WikiPedia_Hematology$$$corpus_4262", "text": "Reference ranges:"}
{"_id": "WikiPedia_Hematology$$$corpus_4263", "text": "Thyroid hormone uptake (T uptake  or T 3 uptake ) is a measure of the unbound  thyroxine binding globulins  in the blood, that is, the TBG that is unsaturated with thyroid hormone. [ 2 ]  Unsaturated TBG increases with decreased levels of thyroid hormones. It is not directly related to triiodothyronine, despite the name T 3 uptake . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4264", "text": "The Free Thyroxine Index (FTI or T7) is obtained by multiplying the total T 4  with T 3  uptake. [ 2 ]  FTI is considered to be a more reliable indicator of thyroid status in the presence of abnormalities in plasma protein binding. [ 2 ]  This test is rarely used now that reliable free thyroxine and free triiodothyronine assays are routinely available."}
{"_id": "WikiPedia_Hematology$$$corpus_4265", "text": "FTI is elevated in hyperthyroidism and decreased in hypothyroidism. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4266", "text": "Derived  structure parameters  that describe constant properties of the overall  feedback control system  may add useful information for special purposes, e.g. in diagnosis of  nonthyroidal illness syndrome  or  central hypothyroidism . [ 20 ] [ 21 ] [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4267", "text": "Thyroid's secretory capacity  ( G T , also referred to as SPINA-GT) is the maximum stimulated amount of thyroxine the thyroid can produce in one second. [ 24 ]   G T  is elevated in hyperthyroidism and reduced in hypothyroidism. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4268", "text": "G T  is calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4269", "text": "G \n ^ \n \n \n \n \n T \n \n \n = \n \n \n \n \n \u03b2 \n \n T \n \n \n ( \n \n D \n \n T \n \n \n + \n [ \n T \n S \n H \n ] \n ) \n ( \n 1 \n + \n \n K \n \n 41 \n \n \n [ \n T \n B \n G \n ] \n + \n \n K \n \n 42 \n \n \n [ \n T \n B \n P \n A \n ] \n ) \n [ \n F \n \n T \n \n 4 \n \n \n ] \n \n \n \n \u03b1 \n \n T \n \n \n [ \n T \n S \n H \n ] \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{T}={{\\beta _{T}(D_{T}+[TSH])(1+K_{41}[TBG]+K_{42}[TBPA])[FT_{4}]} \\over {\\alpha _{T}[TSH]}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4270", "text": "G \n ^ \n \n \n \n \n T \n \n \n = \n \n \n \n \n \u03b2 \n \n T \n \n \n ( \n \n D \n \n T \n \n \n + \n [ \n T \n S \n H \n ] \n ) \n [ \n T \n \n T \n \n 4 \n \n \n ] \n \n \n \n \u03b1 \n \n T \n \n \n [ \n T \n S \n H \n ] \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{T}={{\\beta _{T}(D_{T}+[TSH])[TT_{4}]} \\over {\\alpha _{T}[TSH]}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4271", "text": "\u03b1 \n \n T \n \n \n \n \n {\\displaystyle \\alpha _{T}} \n \n : Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l \u22121 ) \n \n \n \n \n \n \u03b2 \n \n T \n \n \n \n \n {\\displaystyle \\beta _{T}} \n \n : Clearance exponent for T4 (1.1e-6 sec \u22121 ) \n K 41 : Dissociation constant T4-TBG (2e10 L/mol) \n K 42 : Dissociation constant T4-TBPA (2e8 L/mol) \n D T : EC 50  for TSH (2.75 mU/L) [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4272", "text": "The  sum activity of peripheral deiodinases  ( G D , also referred to as SPINA-GD) is reduced in nonthyroidal illness with hypodeiodination. [ 21 ] [ 22 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4273", "text": "G D  is obtained with"}
{"_id": "WikiPedia_Hematology$$$corpus_4274", "text": "\u03b1 \n \n 31 \n \n \n \n \n {\\displaystyle \\alpha _{31}} \n \n : Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 L \u22121 ) \n \n \n \n \n \n \u03b2 \n \n 31 \n \n \n \n \n {\\displaystyle \\beta _{31}} \n \n : Clearance exponent for T3 (8e-6 sec \u22121 ) \n K M 1 : Dissociation constant of type-1-deiodinase (5e-7\u00a0mol/L) \n K 30 : Dissociation constant T3-TBG (2e9 L/mol) [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4275", "text": "Jostel's TSH index  (JTI or TSHI) helps to determine thyrotropic function of anterior  pituitary  on a quantitative level. [ 27 ]  It is reduced in thyrotropic insufficiency [ 27 ]  and in certain cases of non-thyroidal illness syndrome. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4276", "text": "It is calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4277", "text": "T \n S \n H \n I \n = \n L \n N \n ( \n T \n S \n H \n ) \n + \n 0.1345 \n \u2217 \n F \n T \n 4 \n \n \n {\\displaystyle TSHI=LN(TSH)+0.1345*FT4} \n \n ."}
{"_id": "WikiPedia_Hematology$$$corpus_4278", "text": "Additionally, a standardized form of TSH index may be calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4279", "text": "s \n T \n S \n H \n I \n = \n ( \n T \n S \n H \n I \n \u2212 \n 2.7 \n ) \n \n / \n \n 0.676 \n \n \n {\\displaystyle sTSHI=(TSHI-2.7)/0.676} \n \n . [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4280", "text": "The  Thyrotroph Thyroid Hormone Sensitivity Index  (TTSI, also referred to as  Thyrotroph T4 Resistance Index  or TT4RI) was developed to enable fast screening for  resistance to thyroid hormone . [ 28 ] [ 29 ]  Somewhat similar to the TSH Index it is calculated from equilibrium values for TSH and FT4, however with a different equation."}
{"_id": "WikiPedia_Hematology$$$corpus_4281", "text": "The  Thyroid Feedback Quantile-based Index  (TFQI) is another parameter for thyrotropic pituitary function. It was defined to be more robust to distorted data than JTI and TTSI. It is calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4282", "text": "T \n F \n Q \n I \n = \n \n F \n \n F \n T \n 4 \n \n \n ( \n F \n T \n 4 \n ) \n \u2212 \n ( \n 1 \n \u2212 \n \n F \n \n T \n S \n H \n \n \n ( \n T \n S \n H \n ) \n ) \n \n \n {\\displaystyle TFQI=F_{FT4}(FT4)-(1-F_{TSH}(TSH))}"}
{"_id": "WikiPedia_Hematology$$$corpus_4283", "text": "from quantiles of FT4 and TSH concentration (as determined based on  cumulative distribution functions ). [ 30 ]  Per definition the TFQI has a  mean  of 0 and a  standard deviation  of 0.37 in a reference population. [ 30 ]  Higher values of TFQI are associated with  obesity ,  metabolic syndrome , impaired  renal  function,  diabetes , and diabetes-related  mortality . [ 30 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ] [ 35 ] [ 36 ]  TFQI results are also elevated in  takotsubo syndrome , [ 37 ]  potentially reflecting type 2  allostatic load  in the situation of  psychosocial stress . Reductions have been observed in subjects with  schizophrenia  after initiation of therapy with  oxcarbazepine , potentially reflecting declining allostatic load. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4284", "text": "In healthy persons, the intra-individual variation of TSH and thyroid hormones is considerably smaller than the inter-individual variation. [ 39 ] [ 40 ] [ 41 ]  This results from a personal  set point  of thyroid homeostasis. [ 42 ]  In hypothyroidism, it is impossible to directly access the set point, [ 43 ]  but it can be reconstructed with methods of systems theory. [ 44 ] [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4285", "text": "A computerised algorithm, called Thyroid-SPOT, which is based on this mathematical theory, has been implemented in software applications. [ 47 ]  In patients undergoing thyroidectomy it could be demonstrated that this algorithm can be used to reconstruct the personal set point with sufficient precision. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4286", "text": "Drugs can profoundly affect thyroid function tests. Listed below is a selection of important effects."}
{"_id": "WikiPedia_Hematology$$$corpus_4287", "text": "\u2193: reduced serum concentration or structure parameter; \u2191: increased serum concentration or structure parameter; \u2194: no change; TSH: Thyroid-stimulating hormone; T 3 : Total triiodothyronine; T 4 : Total thyroxine; fT 4 : Free thyroxine; fT 3 : Free triiodothyronine; rT 3 : Reverse triiodothyronine"}
{"_id": "WikiPedia_Hematology$$$corpus_4288", "text": "The  Centers for Disease Control and Prevention  has published the following laboratory procedure manuals for measuring thyroid-stimulating hormone:"}
{"_id": "WikiPedia_Hematology$$$corpus_4289", "text": "Thyroid hormone binding ratio (THBR)  is a  thyroid function test  that measures the \"uptake\" of  T3 or T4  tracer by  thyroid-binding globulin  (TBG) in a given serum sample. This provides an indirect and  reciprocal  estimate of the available binding sites on TBG within the sample."}
{"_id": "WikiPedia_Hematology$$$corpus_4290", "text": "The results are then reported as a ratio to normal serum."}
{"_id": "WikiPedia_Hematology$$$corpus_4291", "text": "Attempts to correct for changes in thyroid binding globulin due to liver disease, protein losing states, pregnancy or various drugs [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4292", "text": "It is used to calculate  free thyroxine index  (total T4 x T3 uptake), an estimate of free T4. Free thyroxine index may be calculated with increased diagnostic accuracy using direct TBG measurement when the total hormone concentration is abnormally elevated  [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4293", "text": "Invalid if other proteins or immunoglobulins compete with TBG, including  familial dysalbuminemic hyperthyroxinemia [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4294", "text": "Thyroid's secretory capacity  ( G T , also referred to as  thyroid's incretory capacity ,  maximum thyroid hormone output ,  T4 output  or, if calculated from serum levels of thyrotropin and thyroxine, as  SPINA-GT [ a ] ) is the maximum stimulated amount of  thyroxine  that the  thyroid  can produce in a given time-unit (e.g. one second). [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4295", "text": "Experimentally,  G T  can be determined by stimulating the thyroid with a high thyrotropin concentration (e.g. by means of  rhTSH , i.e.  recombinant  human thyrotropin) and measuring its output in terms of T4 production, or by measuring the serum concentration of protein-bound  iodine-131  after administration of  radioiodine . [ 4 ]  These approaches are, however, costly and accompanied by significant exposure to radiation. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4296", "text": "In vivo ,  G T  can also be estimated from equilibrium levels of TSH and T4 or free T4. In this case it is calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4297", "text": "[ TSH ]: Serum thyrotropin concentration (in mIU/L or   \u03bcIU/mL) \n[ FT4 ]: Serum free T4 concentration (in pmol/L) \n[ TT4 ]: Serum total T4 concentration (in nmol/L) \n \n \n \n \n \n \n \n \n G \n ^ \n \n \n \n \n T \n \n \n \n \n {\\displaystyle {\\hat {G}}_{T}} \n \n : Theoretical (apparent) secretory capacity (SPINA-GT) \n \n \n \n \n \n \u03b1 \n \n T \n \n \n \n \n {\\displaystyle \\alpha _{T}} \n \n :  Dilution  factor for T4 (reciprocal of apparent volume of distribution, 0.1 L \u22121 ) \n \n \n \n \n \n \u03b2 \n \n T \n \n \n \n \n {\\displaystyle \\beta _{T}} \n \n :  Clearance  exponent for T4 (1.1e-6 sec \u22121 ), i. e.,  reaction rate constant  for degradation \n K 41 :  Binding constant  T4-TBG (2e10 L/mol) \n K 42 : Binding constant T4-TBPA (2e8 L/mol) \n D T :  EC 50  for TSH (2.75 mU/L) [ 2 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4298", "text": "The method is based on mathematical models of thyroid homeostasis. [ 2 ] [ 3 ]  Calculating the secretory capacity with one of these equations is an  inverse problem . Therefore, certain conditions (e.g. stationarity) have to be fulfilled to deliver a reliable result."}
{"_id": "WikiPedia_Hematology$$$corpus_4299", "text": "The ratio of SPINA-GT and thyroid volume  V T  (as determined e.g. by  ultrasonography )"}
{"_id": "WikiPedia_Hematology$$$corpus_4300", "text": "G \n ^ \n \n \n \n \n T \n S \n \n \n = \n \n \n \n \n \n \n G \n ^ \n \n \n \n \n T \n \n \n \n \n V \n \n \n T \n \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{TS}={\\frac {{\\hat {G}}_{T}}{{V}_{T}}}} \n \n ,"}
{"_id": "WikiPedia_Hematology$$$corpus_4301", "text": "i.e."}
{"_id": "WikiPedia_Hematology$$$corpus_4302", "text": "G \n ^ \n \n \n \n \n T \n S \n \n \n = \n \n \n \n \n \u03b2 \n \n T \n \n \n ( \n \n D \n \n T \n \n \n + \n [ \n T \n S \n H \n ] \n ) \n ( \n 1 \n + \n \n K \n \n 41 \n \n \n [ \n T \n B \n G \n ] \n + \n \n K \n \n 42 \n \n \n [ \n T \n B \n P \n A \n ] \n ) \n [ \n F \n \n T \n \n 4 \n \n \n ] \n \n \n \n \u03b1 \n \n T \n \n \n [ \n T \n S \n H \n ] \n \n \n V \n \n \n T \n \n \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{TS}={\\frac {\\beta _{T}(D_{T}+[TSH])(1+K_{41}[TBG]+K_{42}[TBPA])[FT_{4}]}{\\alpha _{T}[TSH]{V}_{T}}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4303", "text": "G \n ^ \n \n \n \n \n T \n S \n \n \n = \n \n \n \n \n \u03b2 \n \n T \n \n \n ( \n \n D \n \n T \n \n \n + \n [ \n T \n S \n H \n ] \n ) \n [ \n T \n \n T \n \n 4 \n \n \n ] \n \n \n \n \u03b1 \n \n T \n \n \n [ \n T \n S \n H \n ] \n \n \n V \n \n \n T \n \n \n \n \n \n \n \n {\\displaystyle {\\hat {G}}_{TS}={\\frac {\\beta _{T}(D_{T}+[TSH])[TT_{4}]}{\\alpha _{T}[TSH]{V}_{T}}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_4304", "text": "is referred to as  specific thyroid capacity  (SPINA-GTs). [ 7 ]  It is a measure for how much one  millilitre  of thyroid tissue can produce under conditions of maximum stimulation. Thereby, SPINA-GTs is an estimate for the endocrine quality of thyroid tissue. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4305", "text": "The equations and their parameters are calibrated for adult humans with a body mass of 70\u00a0kg and a plasma volume of ca. 2.5 L. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4306", "text": "SPINA-GT is elevated in primary  hyperthyroidism [ 8 ] [ 9 ]  and reduced in both primary  hypothyroidism [ 10 ] [ 11 ] [ 12 ] [ 9 ]  and untreated autoimmune thyroiditis. [ 13 ]  It has been observed to correlate (with positive direction) to  resting energy expenditure , [ 14 ]   resting heart rate , [ 15 ]  the colour Doppler ultrasound pattern [ 16 ]  and thyroid volume, [ 2 ] [ 7 ]  and (with negative direction) to thyroid autoantibody titres, which reflect organ destruction due to autoimmunity. [ 17 ]  Elevated SPINA-GT in  Graves' disease  is reversible with antithyroid treatment. [ 14 ]  While SPINA-GT is significantly altered in primary thyroid disorders, it is insensitive to disorders of secondary nature (e.g. pure pituitary diseases). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4307", "text": "In silico  experiments with  Monte Carlo simulations  demonstrated that both SPINA-GT and  SPINA-GD  can be estimated with sufficient reliability, even if laboratory assays have limited accuracy. [ 3 ]  This was confirmed by longitudinal  in vivo  studies that showed that GT has lower intraindividual variation (i.e. higher reliability) than  TSH ,  FT4  or  FT3 . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4308", "text": "In clinical trials SPINA-GT was significantly elevated in patients with  Graves' disease  and  toxic adenoma  compared to normal subjects. [ 2 ] [ 8 ] [ 19 ]  It is also elevated in diffuse and nodular  goiters , and reduced in untreated autoimmune thyroiditis. [ 2 ] [ 13 ]  In patients with toxic adenoma it has higher  specificity  and  positive likelihood ratio  for diagnosis of thyrotoxicosis than serum concentrations of  thyrotropin , free T4 or free T3. [ 2 ]  GT's specificity is also high in thyroid disorders of secondary or tertiary origin. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4309", "text": "Calculating SPINA-GT has proved to be useful in challenging clinical situations, e.g. for differential diagnosis of subclinical hypothyroidism and elevated TSH concentration due to type 2 allostatic load (as it is typical for obesity and certain psychiatric diseases). For this purpose, its usage has been recommended in  sociomedical assessment . [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4310", "text": "In patients suffering from toxic adenoma, toxic multinodular goitre and Graves\u2019 disease  radioiodine therapy  leads to a significant decrease of the initially elevated SPINA-GT. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4311", "text": "Correlation of SPINA-GT with  creatinine clearance  suggests a negative influence of  uremic  toxins on thyroid biology. [ 21 ] [ 22 ]  In the initial phase of major  non-thyroidal illness syndrome  (NTIS) SPINA-GT may be temporarily elevated. [ 23 ] [ 24 ]  In chronic NTIS [ 25 ]  as well as in certain non-critical chronic diseases, e.g.  chronic fatigue syndrome [ 26 ] [ 27 ]  or  asthma [ 28 ]  SPINA-GT is slightly reduced."}
{"_id": "WikiPedia_Hematology$$$corpus_4312", "text": "According to the results of a community-based study in China it was associated to sleep duration and exercise habits. [ 29 ]  With respect to iodine supply, it showed a complex U-shaped pattern, being reduced in subjects consuming iodine-rich food, but elevated in situations of iodine excess. [ 29 ]  In two other studies from China, SPINA-GT correlated with negative direction to markers of obesity including body mass index, waist circumference and waist to hip ratio. [ 30 ] [ 31 ]  This doesn't seem to be the case, however, in Western populations. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4313", "text": "In women, therapy with  Metformin  results in increased SPINA-GT, in parallel to improved  insulin sensitivity . [ 33 ] [ 34 ]  This observation was reproducible in men with hypogonadism, but not in men with normal testosterone concentrations,. [ 35 ]  In postmenopausal women this effect was only observed in subjects on oestradiol replacement therapy. [ 36 ]  Therefore, the described phenomenon seems to depend on an interaction of metformin with sex hormones. [ 35 ] [ 37 ]  In hyperthyroid [ 8 ]  men both SPINA-GT and  SPINA-GD  negatively correlate to  erectile function , intercourse satisfaction,  orgasmic function  and  sexual desire . Likewise, in women with thyrotoxicosis elevated thyroid's secretory capacity predicts depression and sexual dysfunction. [ 38 ]  Conversely, in androgen-deficient men with concomitant  autoimmune thyroiditis , substitution therapy with  testosterone  leads to a decrease in  thyroid autoantibody  titres and an increase in SPINA-GT. [ 39 ]  In a large study from mainland China, SPINA-GT was elevated in certain psychiatric diseases including bipolar disorder and schizophrenia. [ 40 ]  In bipolar disorder with manic or mixed episodes it was higher than in cases with depressive episodes. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4314", "text": "SPINA-GT is reduced in persons suffering from  hidradenitis suppurativa  compared to healthy controls with the same sex and age distribution. [ 41 ]  This phenomenon has been ascribed to  B-cell -mediated  hypothyroidism , i.e. hypothyroid  Graves' disease  due to inhibiting TSH receptor autoantibodies (iTRAb). [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4315", "text": "In patients with autoimmune thyroiditis a  gluten-free diet  results in increased SPINA-GT (in parallel to sinking autoantibody titres). [ 42 ]   Statin  therapy has the same effect, but only if supply with  vitamin D  is sufficient. [ 43 ]  Accordingly, substitution therapy with  25-hydroxyvitamin D  leads to rising secretory capacity. [ 44 ] [ 45 ] [ 46 ] [ 47 ]  This effect is potentiated by substitution therapy with  myo-inositol [ 48 ]  and  selenomethionine [ 44 ] [ 45 ] [ 49 ]  or, in women, with  dehydroepiandrosterone , [ 50 ]  but impaired in males with early-onset androgenic alopecia. [ 51 ]  The effects of vitamin D and selenomethionine are attenuated in  hyperprolactinaemia , suggesting an inhibitory effect of  prolactin . [ 52 ]  Although both vitamin D supplementation and gluten-free diet result in increased SPINA-GT, there seems to be a complex interaction between both therapeutic measures, since vitamin D treatment is only able to elevate the thyroid's secretory capacity in subjects not following any dietary recommendation. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4316", "text": "On the other hand, men treated with  spironolactone  are faced with decreasing SPINA-GT (in addition to rising  thyroid antibody  titres). [ 54 ]  It has, therefore, been concluded that spironolactone may aggravate thyroid autoimmunity in men. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4317", "text": "In subjects with  type 2 diabetes , treatment with  beta blockers  resulted in decreased SPINA-GT, suggesting  sympathetic innervation  to contribute to the control of thyroid function. [ 55 ]  In diabetic women, but not in men, SPINA-GT shows a positive correlation to the \u03b2-C-terminal cross-linked telopeptides of type I collagen (\u03b2-CTX), a marker of bone resorption. [ 56 ]  In both diabetic and non-diabetic persons it correlates (negatively) with age and (positively) with the concentrations of  troponin T  and  HbA1c . [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4318", "text": "SPINA-GT correlates to mechanical pain sensitivity (MPS) in  quantitative sensory testing  (QST) and to measures of respiratory arrhythmia in the analysis of  heart rate variability , indicating a potential link to both  sensorimotor  and  autonomic neuropathy . [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4319", "text": "A study in  euthyroid  subjects with  structural heart disease  found that increased SPINA-GT predicts the risk of malignant  arrhythmia  including  ventricular fibrillation  and  ventricular tachycardia . [ 59 ]  This applies to both incidence and event-free survival. [ 59 ]  Likewise, SPINA-GT is elevated in a significant subgroup of patients with  takotsubo syndrome , [ 60 ]  especially in non-survivors. [ 61 ]  A stress-mediated effect on SPINA-GT is also suggested by the observation that it is increased in persons with a history of psychological trauma. [ 62 ]  On the other hand, two studies found negative correlation between SPINA-GT and markers of dispersion in cardiac repolarisation, including Tp-e interval, JT interval, Tp-e/ QT ratio and Tp-e/QTc ratio. These results suggest that reduced thyroid function may trigger cardiovascular mortality as well. [ 63 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4320", "text": "Among subjects with  Parkinson's disease , SPINA-GT is significantly elevated in  tremor -dominant and mixed subtypes compared to the akinetic-rigid type. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4321", "text": "Specific secretory capacity (SPINA-GTs) is reduced in  obesity [ 2 ]  and  autoimmune thyroiditis . [ 7 ] [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4322", "text": "Endocrine disruptors  may affect stimulated thyroid output, as demonstrated by a positive correlation of SPINA-GT with exposure to  2-hydroxynaphthalene  (2-NAP), [ 66 ]  urinary  mercury  concentration [ 67 ]  and the excretion of certain  phthalate  metabolites, [ 68 ]  and negative correlation with combined exposure to  polycyclic aromatic hydrocarbons  (PAHs) [ 66 ]  and  nickel . [ 69 ]  Additionally, SPINA-GT was altered in young people exposed to  butylparaben . [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4323", "text": "In a longitudinal evaluation of a large sample of the general US population over 10 years, reduced SPINA-GT significantly predicted all-cause mortality. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4324", "text": "The  Thyrotroph Thyroid Hormone Sensitivity Index  (abbreviated  TTSI , also referred to as  Thyrotroph T4 Resistance Index  or  TT4RI ) is a calculated structure parameter of  thyroid homeostasis . It was originally developed to deliver a method for fast  screening  for  resistance to thyroid hormone . [ 1 ] [ 2 ]  Today it is also used to get an estimate for the  set point  of thyroid homeostasis, [ 3 ]  especially to assess dynamic thyrotropic adaptation of the anterior  pituitary  gland, including  non-thyroidal illnesses . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4325", "text": "The TTSI can be calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4326", "text": "from equilibrium  serum  or  plasma  concentrations of  thyrotropin  (TSH), free  T4  (FT4) and the  assay -specific upper limit of the  reference interval  for FT4 concentration ( l u ). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4327", "text": "Some publications use a simpler form of this equation that doesn't correct for the reference range of free T4. It is calculated with"}
{"_id": "WikiPedia_Hematology$$$corpus_4328", "text": "The disadvantage of this uncorrected version is that its numeric results are highly dependent on the used  assays  and their  units of measurement . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4329", "text": "In case of resistance to thyroid hormone, the magnitude of TTSI depends on which nucleotide in the  THRB  gene is mutated, but also on the genotype of coactivators. A systematic investigation in mice demonstrated a strong association of TT4RI to the genotypes of THRB and the steroid receptor coactivator ( SRC-1 ) gene. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4330", "text": "The TTSI is used as a screening parameter for resistance to thyroid hormone due to mutations in the  THRB  gene, where it is elevated. [ 4 ]  It is also beneficial for assessing the severity of already confirmed thyroid hormone resistance, [ 6 ]  even on replacement therapy with L-T4, [ 7 ]  and for monitoring the pituitary response to substitution therapy with thyromimetics (e.g.  TRIAC ) in RTH Beta. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4331", "text": "In  autoimmune thyroiditis  the TTSI is moderately elevated. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4332", "text": "A large cohort study demonstrated TTSI to be strongly influenced by genetic factors. [ 10 ]  A variant of the TTSI that is not corrected for the upper limit of the FT4 reference range was shown to be significantly increased in offspring from long-lived siblings compared to their partners. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4333", "text": "Conversely, an elevated set point of thyroid homeostasis, as quantified by the TT4RI, is associated to higher prevalence of  metabolic syndrome [ 3 ]  and several harmonized criteria by the  International Diabetes Federation , including  triglyceride  and  HDL  concentration and  blood pressure . [ 12 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4334", "text": "In certain phenotypes of  non-thyroidal illness syndrome , especially in cases with concomitant  sepsis , the TTSI is reduced. [ 14 ]  This reflects a reduced set point of thyroid homeostasis, as also experimentally predicted in rodent models of  inflammation  and sepsis. [ 15 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4335", "text": "Negative correlation of the TTSI with the urinary excretion of certain  phthalates  suggests that  endocrine disruptors  may affect the central set point of thyroid homeostasis. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4336", "text": "Total iron-binding capacity  ( TIBC ) or sometimes  transferrin iron-binding capacity  is a medical laboratory test that measures the blood's capacity to bind  iron  with  transferrin . [ 1 ]   Transferrin  can bind two atoms of  ferric iron  (Fe 3+ ) with high affinity. It means that  transferrin  has the capacity to transport approximately from 1.40 to 1.49\u00a0mg of  iron  per gram of  transferrin  present in the blood. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4337", "text": "It is performed by  drawing blood  and measuring the maximum amount of iron that it can carry, which indirectly measures  transferrin [ 3 ]  since transferrin is the most dynamic carrier. If TIBC values are known, the transferrin concentration can be estimated with the following formulas: [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4338", "text": "To measure TIBC in the blood is less expensive than a direct measurement of  transferrin . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4339", "text": "The TIBC should not be confused with the  unsaturated iron-binding capacity  or  UIBC  ( LOINC   2501-5 ,  22753-8  &  35216-1 ). The UIBC is calculated by subtracting the serum iron from the TIBC. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4340", "text": "Taken together with  serum iron  and  percent transferrin saturation  clinicians usually perform this test when they are concerned about  anemia ,  iron deficiency  or  iron deficiency anemia . However, because the  liver  produces transferrin, alterations in function (such as  cirrhosis ,  hepatitis , or  liver failure ) must be considered when performing this test. It can also be an indirect test of liver function, but is rarely used for this purpose. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4341", "text": "The percent transferrin saturation (i.e., the result of the formula of serum iron/TIBC x 100) can also be a useful indicator. Studies also revealed that a transferrin saturation (serum iron concentration \u00f7 total iron binding capacity) over 60 percent in men and over 50 percent in women identified the presence of an abnormality in iron metabolism (hereditary hemochromatosis, heterozygotes and homozygotes) with approximately 95 percent accuracy. This finding helps in the early diagnosis of hereditary hemochromatosis, especially while serum  ferritin  still remains low. The retained iron in hereditary hemochromatosis is primarily deposited in parenchymal cells, with reticuloendothelial cell accumulation occurring very late in the disease. This is in contrast to transfusional iron overload in which iron deposition occurs first in the reticuloendothelial cells and then in parenchymal cells. This explains why ferritin levels remain relative low in hereditary hemochromatosis, while transferrin saturation is high. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4342", "text": "These examples demonstrate that to properly understand a value for TIBC, one also must know the serum iron, the percent transferrin saturation, and the individual clinical situation. In modern laboratory testings, serum ferritin levels are generally accepted as reliable single indicators of the presence of iron deficiency. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4343", "text": "Laboratories often use different units of measurement and \"normal ranges\" may vary by population and the laboratory techniques used. Look at the individual laboratory  reference values  to interpret a specific test (for instance, your own). [ citation needed ]  Example reference ranges are:"}
{"_id": "WikiPedia_Hematology$$$corpus_4344", "text": "\u03bcg/dL = micrograms per deciliter; \u03bcmol/L = micromoles per litre."}
{"_id": "WikiPedia_Hematology$$$corpus_4345", "text": "Transferrin saturation  (TS), measured as a percentage, is a  medical  laboratory value. It is the value of  serum iron  divided by the  total iron-binding capacity [ 1 ]  of the available  transferrin , the main protein that binds iron in the blood, this value tells a clinician how much serum iron is bound. For instance, a value of 15% means that 15% of iron-binding sites of transferrin are being occupied by iron. The three results are usually reported together. A low transferrin saturation is a common indicator of  iron deficiency anemia  whereas a high transferrin saturation may indicate  iron overload  or  hemochromatosis . [ 1 ] [ 2 ] \nTransferrin saturation is also called transferrin saturation index (TSI) or transferrin saturation percentage (TS%)  [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4346", "text": "Studies also reveal that a transferrin saturation (serum iron concentration \u00f7 total iron binding capacity) over 60 percent in men and over 50 percent in women identified the presence of an abnormality in iron metabolism (hereditary hemochromatosis, heterozygotes and homozygotes) with approximately 95 percent accuracy. This finding helps in the early diagnosis of hereditary hemochromatosis, especially while serum  ferritin  still remains low. The retained iron in hereditary hemochromatosis is primarily deposited in parenchymal cells, with reticuloendothelial cell accumulation occurring very late in the disease. This is in contrast to transfusional iron overload in which iron deposition occurs first in the reticuloendothelial cells and then in parenchymal cells. This explains why ferritin levels remain relative low in hereditary hemochromatosis, while transferrin saturation is high. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4347", "text": "Normal  reference ranges  are: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4348", "text": "\u03bcg/dL = micrograms per deciliter"}
{"_id": "WikiPedia_Hematology$$$corpus_4349", "text": "\u03bcmol/L = micromoles per liter"}
{"_id": "WikiPedia_Hematology$$$corpus_4350", "text": "Laboratories often use different units and \"normal\" may vary by population and the lab techniques used. To help clinicians interpret their patients' results, laboratories are generally also required to report their normal or  reference values . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4351", "text": "Prior to the availability of sensitive  TSH assays ,  thyrotropin releasing hormone  or  TRH stimulation tests  were relied upon for confirming and assessing the degree of suppression\nin suspected  hyperthyroidism . Typically, this stimulation test involves determining basal\n TSH  levels and levels 15 to 30 minutes after an intravenous  bolus  of TRH. Normally,\nTSH would rise into the concentration range measurable with less sensitive TSH assays.\nThird generation TSH assays do not have this\nlimitation and thus TRH stimulation is generally not required when third generation TSH\nassays are used to assess degree of suppression."}
{"_id": "WikiPedia_Hematology$$$corpus_4352", "text": "TRH-stimulation testing however\ncontinues to be useful for the differential diagnosis of secondary (pituitary disorder) and tertiary (hypothalamic disorder) hypothyroidism. Patients with these conditions\nappear to have physiologically inactive TSH in their circulation that is recognized by\nTSH assays to a degree such that they may yield misleading, \" euthyroid \" TSH\nresults. Use and Interpretation: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4353", "text": "\u2022 Helpful in diagnosis in patients with confusing TFTs. In primary hyperthyroidism\nTSH are low and TRH administration induces little or no change in TSH levels"}
{"_id": "WikiPedia_Hematology$$$corpus_4354", "text": "\u2022 In hypothyroidism due to end  organ failure , administration of TRH produces a\nprompt increase in TSH"}
{"_id": "WikiPedia_Hematology$$$corpus_4355", "text": "\u2022 In hypothyroidism due to  pituitary disease  (secondary hypothyroidism) administration of TRH does not produce\nan increase in TSH"}
{"_id": "WikiPedia_Hematology$$$corpus_4356", "text": "\u2022 In hypothyroidism due to  hypothalamic disease  (tertiary hypothyroidism), administration of TRH produces a\ndelayed (60\u2013120 minutes, rather than 15\u201330 minutes) increase in TSH"}
{"_id": "WikiPedia_Hematology$$$corpus_4357", "text": "The TRH test involves administration of a small amount of TRH intravenously, [ 1 ]  following which levels of TSH will be measured at several subsequent time points using samples of blood taken from a peripheral vein. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4358", "text": "The test is used in the differential diagnosis of secondary and tertiary hypothyroidism.  First, blood is drawn and a baseline TSH level is measured.  Then, TRH is administered via a vein.  After 30 minutes blood is drawn again and the levels of TSH are measured and compared to the baseline. Some authors recommend additional blood sampling at 15 minutes. In children, late blood sampling at 60 to 120 minutes is necessary.\nAn increase in the serum TSH level following TRH administration means that the cause of the hypothyroidism is in the  hypothalamus  (tertiary hypothyroidism), i.e. the hypothalamus is not producing TRH.  Therefore, when TRH is given exogenously, TSH levels increase. If the increase in serum TSH level following TRH administration is absent or very slight, then the cause of the hypothyroidism is in the  anterior pituitary gland , i.e. the pituitary is not secreting TSH.  Therefore, even when TRH is given exogenously, TSH levels do not rise as the pituitary is diseased. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4359", "text": "TRH may cause nausea, vomiting and some patients experience an urge to urinate. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4360", "text": "Rarely, TRH may cause blood vessel constriction leading to  hemorrhage  in patients with pre-existing  pituitary tumors . Accordingly, patients should be advised about the risks, albeit rare, of TRH testing. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4361", "text": "Typhidot  is a  medical test  consisting of a dot  ELISA  kit [ 1 ]  that detects  IgM  and  IgG   antibodies  against the  outer membrane protein  (OMP) of the  Salmonella typhi . The typhidot test becomes positive within 2\u20133 days of infection and separately identifies IgM and IgG antibodies. The test is based on the presence of specific IgM and IgG antibodies to a specific 50 Kd  OMP  antigen , which is impregnated on  nitrocellulose  strips. IgM shows recent infection whereas IgG signifies remote infection. The most important  limitation of this test is that it is not quantitative and result is only positive or negative hhj8b . Whereas a detailed  Widal test  can tell the titres of specific antibodies. However both tests lack sensitivity and specificity. The Widal test is losing its value as it is labor-intensive and time-consuming. It is an  immunochromatographic  test. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4362", "text": "The  vertical auto profile  ( VAP ) test is a  cholesterol ,  lipid  and  lipoprotein  test."}
{"_id": "WikiPedia_Hematology$$$corpus_4363", "text": "The name \"VAP test\" uses a technology, the vertical auto profile, to measure and report risk factors for patients who are at increased risk for cardiovascular disease that are not captured by routine cholesterol testing. Its accuracy is unaffected by triglycerides and can be performed in a non-fasting state."}
{"_id": "WikiPedia_Hematology$$$corpus_4364", "text": "The VAP test has a unique ability to identify far more areas of risk to patients than the standard lipid panel, specifically because it reports 15 separate components versus four in the standard cholesterol test. Studies report that this comprehensive test is able to identify more than twice the number of patients with lipid abnormalities than the standard lipid panel (cholesterol and triglyceride test)."}
{"_id": "WikiPedia_Hematology$$$corpus_4365", "text": "The VAP test directly measures and routinely reports all five lipoprotein classes and sub-classes, including LDL, HDL, intermediate-density lipoprotein (IDL), very low density lipoprotein (VLDL), and lipoprotein (a) [Lp(a)]. In routine cholesterol testing, LDL-cholesterol (LDL-C) is not directly measured, rather it is estimated using the  Friedewald equation , is generally inaccurate when patients are not fasting because of its dependence on triglycerides levels in the calculation. Also, estimated LDL-C is falsely low when directly measured LDL-C is < 100\u00a0mg/dL or when triglycerides are elevated. The VAP technology also measures and reports LDL particle concentration (LDL-P)."}
{"_id": "WikiPedia_Hematology$$$corpus_4366", "text": "The test meets the American Diabetes Association and American College of Cardiology (ADA-ACC) cholesterol guidelines for people at high risk of heart attack and stroke (including people with Type 2 diabetes mellitus). The ADA-ACC consensus statement establishes measurement and treatment guidelines for Apolipoprotein B|apoB in addition to LDL and non-HDL in high-risk patients.  The VAP test was the first cholesterol profile to comply with updated National Cholesterol Education Program ATP III recommendations for LDL measurement."}
{"_id": "WikiPedia_Hematology$$$corpus_4367", "text": "The VAP technology is currently owned and operated by VAP Diagnostics Lab, an international company."}
{"_id": "WikiPedia_Hematology$$$corpus_4368", "text": "Summary of studies:"}
{"_id": "WikiPedia_Hematology$$$corpus_4369", "text": "\u2022 In a Johns Hopkins study of 1.34 million patients, up to 60% of patients assessed were misclassified using the Friedewald estimated basic lipid panel, potentially leading to undertreatment of those\npatients most at risk.1"}
{"_id": "WikiPedia_Hematology$$$corpus_4370", "text": "\u2022 Fasting remnant lipoprotein cholesterol is independently associated with subclinical atherosclerosis: The ELSA-BRASIL Study.2"}
{"_id": "WikiPedia_Hematology$$$corpus_4371", "text": "\u2022 Smaller, denser HDL3-C levels are primarily responsible for the inverse association between HDL-C and incident CHD in this diverse group of primary prevention subjects: Jackson Heart Study & Framingham\nOffspring Cohort Study.3"}
{"_id": "WikiPedia_Hematology$$$corpus_4372", "text": "\u2022 Remnant Lipoprotein cholesterol (RLP-C) levels are an independent predictor of the incidents of CHD in two primary prevention cohorts: Jackson Heart Study & Framingham Offspring Cohort Study.4"}
{"_id": "WikiPedia_Hematology$$$corpus_4373", "text": "\u2022 Low HDL3-C, but not HDL2-C or HDL-C, independently increased the risk for long-term hard clinical events in secondary prevention patients: TRIUMPH.5"}
{"_id": "WikiPedia_Hematology$$$corpus_4374", "text": "\u2022 The apo A1 remnant ratio was a significant predictor of short and intermediate-term death/myocardial infarction risk among women over 50.6"}
{"_id": "WikiPedia_Hematology$$$corpus_4375", "text": "1. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol. 2013 Aug 20;62(8):732-9."}
{"_id": "WikiPedia_Hematology$$$corpus_4376", "text": "2. Fasting remnant lipoprotein cholesterol is independently associated with subclinical atherosclerosis: The ELSA-BRASIL Study. JACC 5 April 2016 Volume 67, Issue 12."}
{"_id": "WikiPedia_Hematology$$$corpus_4377", "text": "3. Association of high-density lipoprotein subclasses and incident coronary heart disease: The Jackson Heart and Framingham Offspring Cohort Studies. Eur J Prev Cardiol. 2016 Jan;23(1):41-9."}
{"_id": "WikiPedia_Hematology$$$corpus_4378", "text": "4. Remnant lipoprotein cholesterol and incident coronary heart disease: The Jackson Heart and Framingham Offspring Cohort Studies. J Am Heart Assoc. 2016 Apr 29;5(5)."}
{"_id": "WikiPedia_Hematology$$$corpus_4379", "text": "5. HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the Lipoprotein Investigators Collaborative. Eur Heart J. 2015 Jan 1;36(1):22-30."}
{"_id": "WikiPedia_Hematology$$$corpus_4380", "text": "6. A new ratio for better predicting future death/myocardial infarction than standard lipid measurements in women >50 years undergoing coronary angiography: the apolipoprotein A1 remnant ratio (Apo A1/ [VLDL\u2083+IDL]). Lipids Health Dis. 2013 Apr 26;12:55."}
{"_id": "WikiPedia_Hematology$$$corpus_4381", "text": "A  white blood cell differential  is a  medical laboratory  test that provides information about the types and amounts of  white blood cells  in a person's blood. The test, which is usually ordered as part of a  complete blood count  (CBC), measures the amounts of the five normal white blood cell types\u00a0\u2013  neutrophils ,  lymphocytes ,  monocytes ,  eosinophils  and  basophils \u00a0\u2013 as well as abnormal cell types if they are present. These results are reported as percentages and absolute values, and compared against  reference ranges  to determine whether the values are normal, low, or high. Changes in the amounts of white blood cells can aid in the diagnosis of many health conditions, including  viral ,  bacterial , and  parasitic  infections and  blood disorders  such as  leukemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_4382", "text": "White blood cell differentials may be performed by an  automated analyzer \u00a0\u2013 a machine designed to run laboratory tests \u2013 or manually, by examining  blood smears  under a microscope. The test was performed manually until white blood cell differential analyzers were introduced in the 1970s, making the  automated differential  possible. In the automated differential, a blood sample is loaded onto an analyzer, which samples a small volume of blood and measures various properties of white blood cells to produce a differential count. The  manual differential , in which white blood cells are counted on a  stained  microscope slide, is now performed to investigate abnormal results from the automated differential, or upon request by the healthcare provider. The manual differential can identify cell types that are not counted by automated methods and detect clinically significant changes in the appearance of white   blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_4383", "text": "In 1674,  Antonie van Leeuwenhoek  published the first microscopic observations of blood cells. Improvements in microscope technology throughout the 18th and 19th centuries allowed the three cellular components of blood to be identified and counted. In the 1870s,  Paul Ehrlich  invented a staining technique that could differentiate between each type of white blood cell.  Dmitri Leonidovich Romanowsky  later modified Ehrlich's stain to produce a wider range of colours, creating the  Romanowsky stain , which is still used to stain blood smears for manual differentials."}
{"_id": "WikiPedia_Hematology$$$corpus_4384", "text": "Automation of the white blood cell differential began with the invention of the  Coulter counter , the first automated  hematology analyzer , in the early 1950s. This machine used electrical impedance measurements to count cells and determine their sizes, allowing white and red blood cells to be enumerated. In the 1970s, two techniques were developed for performing automated differential counts: digital image processing of microscope slides and  flow cytometry  techniques using light scattering and cell staining. These methods remain in use on modern hematology analyzers."}
{"_id": "WikiPedia_Hematology$$$corpus_4385", "text": "The white blood cell differential is a common blood test that is often ordered alongside a  complete blood count . The test may be performed as part of a routine  medical examination ; to investigate certain symptoms, particularly those suggestive of  infection  or  hematological disorders ; [ 5 ] [ 6 ]  or to monitor existing conditions, such as blood disorders and inflammatory diseases. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4386", "text": "Five types of white blood cells are normally found in blood:  neutrophils ,  lymphocytes ,  monocytes ,  eosinophils  and  basophils . [ 8 ]   Marked shifts in the proportions of these cell types, as measured by the automated or manual differential, can indicate various health conditions. [ 9 ]  Additionally, cell types which do not normally occur in the blood, such as  blast cells , can be identified by the manual differential. These cell types may be found in blood disorders and other pathological states. [ 10 ] [ 11 ]  The manual differential can also identify changes in the appearance of white blood cells, such as   reactive lymphocytes , [ 12 ]  or features such as  toxic granulation  and  vacuolation  in neutrophils. [ 13 ]  The results of the white blood cell differential are reported as percentages and absolute values. Absolute counts are usually reported in units of cells per microliter (\u03bcL) or 10 9  cells per liter (L). [ 6 ]  The result are then compared against  reference ranges , which are defined by individual laboratories and may vary due to different patient populations and testing methods. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4387", "text": "CBC and differential testing is usually performed on  venous  or  capillary  blood. Capillary blood draws are generally used for infants and individuals whose veins are difficult to access. [ 15 ]  To prevent  clotting , the sample is drawn into a tube containing the  anticoagulant  compound  ethylenediaminetetraacetic acid  (EDTA)., [ 16 ]  meaning blood that has not been  centrifuged . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4388", "text": "In a manual differential, a stained  blood smear  is examined under a microscope and white blood cells are counted and classified based on their appearance. A manual differential is usually performed when the automated differential is flagged for review or when the healthcare provider requests it. [ 1 ] [ 9 ]  If the manual differential shows findings suggestive of certain serious conditions, such as leukemia, the blood smear is referred to a physician (generally a  hematologist  or  pathologist ) for confirmation. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4389", "text": "A blood smear is prepared by placing a drop of blood on a microscope slide and using a second slide held at an angle to spread the blood and pull it across the slide, forming a \"feathered edge\" consisting of a single layer of cells at the end of the smear. [ 18 ]  This may be done by hand or using an automated slide maker coupled to a hematology analyzer. The slide is treated with a Romanowsky stain, commonly  Wright's stain  or Wright-Giemsa, and examined under the microscope. The smear is examined in a systematic pattern, scanning from side to side within the feathered edge and counting cells consecutively. The differential is typically performed at 400x or 500x  magnification , but 1000x magnification may be used if abnormal cells are present. [ 19 ]  Cells are identified based on their  morphologic  features, such as the size and structure of their nucleus and the colour and texture of their cytoplasm. This allows abnormal cell types and changes in cellular appearance to be identified. [ 8 ]  In most cases, the microscopist counts 100 white blood cells, but 200 may be counted for better representation if the white blood cell count is high. [ 20 ]  The manual differential count produces percentages of each cell type, which can be multiplied by the total white blood cell count from the analyzer to derive the absolute values. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4390", "text": "The manual differential can be partially automated with digital microscopy software, [ 22 ]  which uses  artificial intelligence  to classify white blood cells from  photomicrographs  of the blood smear. [ 23 ]  However, this technique requires confirmation by manual review. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4391", "text": "Because relatively few cells are counted in the manual differential, the variability is higher than in automated techniques, especially when cells are present in low amounts. [ 26 ]  For example, in a sample containing 5 percent monocytes, the manual differential results could be between 1 and 10 percent due to  sampling  variation. [ 27 ]  Additionally, cell identification is subjective and the accuracy depends on the skills of the person reading the slide. [ 26 ] [ 28 ]  Poor blood smear preparation can cause an uneven distribution of white blood cells, resulting in inaccurate counting, [ 29 ]  and improper staining can impede cell identification. [ 30 ]  Overall, manual differential counts exhibit  coefficients of variation  (CVs) ranging from 5 to 10 percent, while automated differential counts of normal neutrophils and lymphocytes have CVs of about 3 percent. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4392", "text": "In  leukemias  and other hematologic  malignancies , the lineage and genetic characteristics of white blood cells have important implications for treatment and prognosis, and the microscopic appearance of the cells is often insufficient for accurate classification. [ 31 ] [ 14 ]  In these cases, other techniques such as  immunophenotyping  by flow cytometry or special staining can be used to definitively identify the cells. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4393", "text": "Most  hematology analyzers  provide a five-part differential, enumerating neutrophils, lymphocytes, monocytes, eosinophils and basophils. Some instruments can also count immature  granulocytes  and  nucleated red blood cells . [ 33 ]   If a six-part differential is provided, the IG or immature granulocyte category consists of promyelocytes, myelocytes and metamyelocytes. [ 34 ]  Hematology analyzers measure various properties of white blood cells, such as impedance,  light scattering  parameters, and staining reactions. This data is analyzed and plotted on a  scattergram , forming distinct clusters which correspond to white blood cell types. [ 35 ]  The analyzer counts many more cells than are counted in a manual differential, resulting in improved precision. [ 26 ]  If abnormal features or cell populations that the analyzer cannot identify are present, the instrument can flag the results for manual blood smear review. [ 33 ] [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4394", "text": "Common techniques used by hematology analyzers to identify cells include light scattering,  Coulter counting , and cytochemical staining techniques. Some analyzers also use  radiofrequency  analysis and  monoclonal antibody  tagging to identify cells. [ 26 ] [ 36 ]  Staining techniques used in differential analyzers include staining of  myeloperoxidase , [ 30 ]  an enzyme found in cells of  myeloid  lineage, [ 37 ]  and  nucleic acids , which are found in higher concentrations in immature cells. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4395", "text": "A small volume of blood (as low as 150 microliters) is aspirated into the analyzer, where  reagents  are applied to  lyse  red blood cells and preserve white blood cells. The sample is diluted and passed into a flow cell, which uses  hydrodynamic focusing  to isolate single cells for accurate analysis of their properties. Various cellular parameters, such as size, complexity and staining reactions, are measured and analyzed to identify cell populations. Basophils are often quantified using a reagent that lyses the cytoplasm of other white blood cells but leaves basophils intact. [ 30 ]  Samples that have abnormal results [ 1 ]  or are suspected to contain abnormal cells are flagged by the analyzer for manual blood smear review. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4396", "text": "To ensure that results from the automated analyzer are correct, quality control samples are run at least once per day. These are samples with known results that are most often provided by the instrument manufacturer. Laboratories compare their differential results to the known values to ensure the instrument is operating correctly. A moving average measurement may also be used, in which the average results for patient samples are measured at certain intervals. Assuming that the characteristics of the patient population remain roughly the same over time, the average should remain constant. Large shifts in the average value can indicate instrument problems. [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4397", "text": "When immature or abnormal white blood cells are present, automated differential results may be incorrect, necessitating a manual blood smear review. Overall, 10 to 25 percent of CBC samples are flagged for manual review by the analyzer. [ 41 ]  Although most abnormal samples are automatically flagged, some may be missed; [ 42 ]  conversely, analyzers may generate false positive flags when no abnormal cells are present. [ 41 ]  Hematology laboratories compensate for these issues by requiring a smear review when differential or CBC results fall outside certain numerical thresholds, regardless of the presence of analyzer flags. [ 1 ]  The  sensitivity and specificity  of analyzer flagging can be determined by comparing analyzer flags to manual differential results. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4398", "text": "The automated  basophil  count is notoriously unreliable, [ 11 ] [ 30 ]  often underestimating counts in  basophilia  and producing falsely elevated results in the presence of abnormal cells. [ 43 ]  The manual differential is therefore considered the reference method for these cells. [ 11 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4399", "text": "Analyzers may count nucleated red blood cells,  giant  and clumped platelets,  and red blood cells containing abnormal  hemoglobins  (such as Hemoglobin S in  sickle cell disease ) as white blood cells, leading to faulty differential results. Automated differential counts on aged specimens may be incorrect due to cellular degeneration. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4400", "text": "The neutrophil count is normally higher in newborns and pregnant women than in other groups. [ 48 ]  Outside of these conditions, increased neutrophil counts ( neutrophilia ) are associated with  bacterial infection , inflammation, and various forms of physiological stress. [ 49 ]  Neutrophil counts can become extremely high in response to some infections and inflammatory states, which is termed  leukemoid reaction  because the high  white blood cell count  mimics leukemia. [ 50 ]  Neutrophilia may also occur in  myeloproliferative disorders . [ 49 ] Neutropenia , meaning a low neutrophil count, may occur as a response to drug treatment (especially chemotherapy) [ 51 ]  or in certain infections, such as  tuberculosis  and  Gram-negative   sepsis . Neutropenia also occurs in many hematologic disorders, such as leukemia and  myelodysplastic syndrome , and in a variety of autoimmune and congenital diseases. [ 52 ]  A neutrophil count below the reference interval may be normal in individuals of certain ethnicities; this is termed  benign ethnic neutropenia . [ 53 ] [ 54 ]  Very low neutrophil counts are associated with  immunosuppression . [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4401", "text": "When stimulated by infection or inflammation, neutrophils may develop abnormal features in their cytoplasm, such as  toxic granulation ,  toxic vacuolation  and  D\u00f6hle bodies . These features, which are caused by the release of  cytokines , [ 56 ]  are collectively known as toxic changes. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4402", "text": "Increased lymphocyte counts ( lymphocytosis ) can be caused by viral infections [ 58 ]  and may also occur after  splenectomy . Children have higher lymphocyte counts than adults. [ 59 ]   Chronic lymphocytic leukemia  presents with an elevated lymphocyte count and abnormal lymphocyte morphology, in which the lymphocytes have extremely dense, clumped nuclei [ 60 ]  and some cells appear  smudged  on the blood smear. [ 61 ]    Low lymphocyte counts ( lymphopenia ) may be seen in infections such as  HIV/AIDS ,  influenza  and  viral hepatitis , as well as in  protein-energy malnutrition , [ 62 ]  acute illnesses and drug reactions. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4403", "text": "In response to viral infections (especially  infectious mononucleosis ), lymphocytes may increase greatly in size, developing unusually shaped nuclei and large amounts of dark blue cytoplasm. Such cells are referred to as  reactive or atypical lymphocytes [ 12 ]  and when present they are either commented on or counted separately from normal lymphocytes in the manual differential. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4404", "text": "Increased monocyte counts ( monocytosis ) are seen in chronic infection and inflammation. Extremely high monocyte counts, as well as immature forms of monocytes, occur in  chronic myelomonocytic leukemia  and acute leukemias of monocytic origin. [ 64 ]  Monocyte counts may be decreased ( monocytopenia ) in individuals who are receiving chemotherapy as well as those with  aplastic anemia , severe burns, and AIDS. [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4405", "text": "Elevated eosinophil counts ( eosinophilia ) are associated with  allergic reactions ,  parasitic infections , and asthma. [ 66 ] [ 67 ]  Eosinophil counts may be decreased in pregnancy and in response to physiological stress, inflammation or treatment with certain drugs, such as  steroids  and  epinephrine . [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4406", "text": "Basophilia  and eosinophilia can occur along with other white blood cell abnormalities in  chronic myeloid leukemia  and other myeloproliferative disorders. [ 68 ]  An increased basophil count may also be seen in  hypersensitivity reactions  and after splenectomy. The basophil count may decrease during  ovulation , steroid treatment, and periods of physiological stress. [ 69 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4407", "text": "A  left shift , meaning an increase in band neutrophils or immature granulocytes, can indicate infection,  inflammation  or bone marrow disorders, although it can also be a normal finding in  pregnancy . [ 70 ] [ 71 ]  Some laboratories do not separate bands from mature neutrophils in the differential count because the classification is highly subjective and unreliable. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4408", "text": "When present in significant quantities in the blood, immature granulocytes can indicate infection and inflammation, [ 11 ]   as well as  myeloproliferative disease ,  leukemia  and other conditions affecting the marrow. [ 73 ]  IGs may also be increased in steroid use and pregnancy. [ 11 ]   Chronic myeloid leukemia  often presents with a high number of immature granulocytes in the peripheral blood. [ 74 ]  Abnormal promyelocytes with multiple  Auer rods , called  faggot cells , occur in  acute promyelocytic leukemia . [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4409", "text": "When seen on the blood smear, blast cells are an abnormal finding and may be indicative of  acute leukemia  or other serious blood disorders. Rarely, they may be seen in severe cases of left shift. The presence of Auer rods inside blast cells indicates that they are of  myeloid  origin, which has important implications for leukemia treatment. [ 10 ] [ 76 ]  Other morphologic features can provide information about the lineage of blast cells: for example,  myeloblasts  tend to be large with distinct nucleoli, while  lymphoblasts  can be smaller with a denser chromatin pattern. However, these features are not diagnostic, and flow cytometry or special staining is generally used to confirm the lineage. [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4410", "text": "Before automated cell counters were introduced, cell counts were performed manually; white and red blood cells, and platelets were counted using microscopes. [ 81 ]  The first person to publish microscopic observations of blood cells was  Antonie van Leeuwenhoek , [ 82 ]  who reported on the appearance of red cells in a 1674 letter to the  Proceedings of the Royal Society of London ; [ 83 ]   Jan Swammerdam  had described red blood cells some years earlier, but had not published his findings at the time. Throughout the 18th and 19th centuries, improvements in microscope technology such as  achromatic lenses  allowed white blood cells and  platelets  to be counted in unstained samples. In the 1870s,  Paul Ehrlich  developed a staining technique that could differentiate between the five white blood cell types. Ehrlich's stain used a combination of an acidic and basic dye to stain white and red blood cells simultaneously. [ 84 ]   Dmitri Leonidovich Romanowsky  improved on this technique in the 1890s by using a mixture of  eosin  and aged  methylene blue , which produced a wide range of hues that was not present when either of the stains was used alone. This was termed the Romanowsky effect and became the basis for  Romanowsky staining , the technique that is still used to stain blood smears for manual differentials. [ 85 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4411", "text": "By the early years of the 20th century, the white blood cell differential had become a common practice in the United States, but difficulties in interpreting the results cast doubt on the test's utility. [ 86 ]  In 1906, [ 87 ]  Charles Langdon Gibson introduced the Gibson chart, which compared the total white blood cell count against the neutrophil count to distinguish between \" pyogenic \" and \"non-pyogenic\" conditions and to predict the severity of infections. Around the same time,  Josef Arneth  proposed a system of classifying neutrophils by their number of nuclear lobes \u2013 termed the \"lobe index\" or  Arneth count  \u2013 and established a set of reference ranges for neutrophil lobularity. Arneth's analysis of neutrophil segmentation was later found to have limited clinical significance, but the association of  hypersegmented neutrophils  with  vitamin B12  and  folate deficiency  remains accepted. [ 88 ] [ 89 ] [ 90 ]   Viktor Schilling \u00a0[ de ]  in 1912 proposed a different classification of neutrophils, separating them into \" myelozyten ,  jugendliche ,  stabkernige  and  segmentkernige \" \u2013 that is, myelocytes, \"juveniles\" (metamyelocytes), band neutrophils (sometimes called \"stabs\"), and mature, fully segmented neutrophils \u2013 and remarked on the clinical significance of the neutrophilic left shift in conjunction with the white blood cell count and the presence of toxic changes. Schilling's monograph,  Das Blutbild und seine klinische Verwertung  ( The Blood Picture and its Clinical Significance ), was translated into English in 1926, and his neutrophil classification system quickly found acceptance in American laboratories. [ 91 ] [ 92 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4412", "text": "The first automated hematology analyzer, the  Coulter counter , was invented in the early 1950s by  Wallace H. Coulter . [ 93 ] [ 94 ]  The analyzer worked on the Coulter principle, which states that when cells are suspended in a fluid carrying an  electric current  and passed through an aperture, they cause decreases in current proportional to their volume because of their poor  electrical conductivity . The number and magnitude of these decreases can be used to count blood cells and calculate their sizes. The Coulter counter was initially designed for counting  red blood cells , but it proved effective for counting white blood cells as well. [ 94 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4413", "text": "After basic cell counting had been automated, the white blood cell differential remained a challenge. Research into automating the differential count began in the 1970s and took two main approaches: digital image processing and flow cytometry. Using technology developed in the 1950s and 60s to automate the reading of  Pap smears , several models of image processing analyzers were produced. [ 95 ]  These instruments would scan a stained blood smear to find cell nuclei, then take a higher resolution snapshot of the cell to analyze it through  densitometry . [ 96 ]  They were expensive, slow, and did little to reduce workload in the laboratory because they still required blood smears to be prepared and stained, so flow cytometry-based systems became more popular, [ 97 ] [ 98 ]  and by 1990, no digital image analyzers were commercially available in the United States or western Europe. [ 99 ]  These techniques enjoyed a resurgence in the 2000s with the introduction of more advanced image analysis platforms using  artificial neural networks . [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4414", "text": "Early flow cytometry devices shot beams of light at cells in specific wavelengths and measured the resulting absorbance, fluorescence or light scatter, collecting information about the cells' features and allowing cellular contents such as  DNA  to be quantified. [ 100 ]  One such instrument\u2014the Rapid Cell Spectrophotometer, developed by Louis Kamentsky in 1965 to automate cervical cytology\u2014could generate blood cell scattergrams using cytochemical staining techniques. Leonard Ornstein, who had helped to develop the staining system on the Rapid Cell Spectrophotometer, and his colleagues later created the  first commercial flow cytometric white blood cell differential analyzer, the Hemalog\u00a0D. [ 101 ] [ 102 ]  Introduced in 1974, [ 103 ] [ 104 ]  this analyzer used light scattering, absorbance and cell staining to identify the five normal white blood cell types in addition to \"large unidentified cells\", a classification that usually consisted of  atypical lymphocytes  or blast cells. The Hemalog\u00a0D could count 10,000 cells in one run, a marked improvement over the manual differential. [ 102 ] [ 105 ] \nBy 1977 it was estimated that \"at least 200\" automated differential analyzers were in use throughout the world. [ 106 ]  In 1981, Technicon combined the Hemalog\u00a0D with the Hemalog-8 analyzer to produce the Technicon\u00a0H6000, the first combined complete blood count and differential analyzer. This analyzer was unpopular with hematology laboratories because it was labour-intensive to operate, but in the late 1980s to early 1990s similar systems were widely produced by other manufacturers such as  Sysmex ,  Abbott ,  Roche  and  Beckman Coulter . [ 107 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4415", "text": "The  whole blood clotting test  is a blood test used to check the coagulation mechanism in the blood following a  snake bite . [ 1 ]  If the test is positive after a bite in South East Asia it indicates the snake was a  viper  rather than an  elapid . [ 1 ] \nIt can also be used to assess the effectiveness of antivenin therapy. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4416", "text": "This test indirectly measures the severity of  defibrinogenation  in  envenomed  samples. [ 3 ]  The test is done by collecting 2 ml  of venous blood in a dry and clean glass tube. The clot and stability of the formed clot is checked after 20 minutes. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4417", "text": "The  Widal test , developed in 1896 and named after its inventor,  Georges-Fernand Widal , is an indirect  agglutination  test for  enteric fever  or  undulant fever  whereby bacteria causing typhoid fever are mixed with a serum containing specific  antibodies  obtained from an infected individual. In cases of  Salmonella  infection, the test assesses for host antibodies to the O soma antigen and the H flagellar antigen of the bacteria. [ 1 ]   False positive and false negative results may occur. Test results need to be interpreted carefully to account for any history of enteric fever,  typhoid  vaccination, and the general level of antibodies in the populations in endemic areas of the world. As with all serological tests, the rise in antibody levels needed to perform the diagnosis takes 7\u201314 days, which limits its applicability in early diagnosis. Other means of diagnosing  Salmonella typhi  (and  paratyphi ) include cultures of blood, urine and  faeces . These organisms produce H 2 S from thiosulfate and can be identified easily on differential media such as  bismuth sulfite agar . [ 2 ] [ 3 ] [ 4 ]   Typhidot  is the other test used to ascertain the diagnosis of  typhoid fever . A new serological test called the Tubex test is neither superior nor better performing than the Widal test. Therefore, Tubex test is not recommended for diagnosis of typhoid fever. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4418", "text": "2-mercaptoethanol  is often added to the Widal test. This agent more easily denatures the  IgM  class of  antibodies , so if a decrease in the titer is seen after using this agent, it means that the contribution of IgM has been removed leaving the  IgG  component. This differentiation of  antibody  classes is important as it allows for the distinction of a recent (IgM) from an old infection (IgG)."}
{"_id": "WikiPedia_Hematology$$$corpus_4419", "text": "The Widal test is positive if TO antigen  titer  is more than 1:160 in an active infection, or if TH antigen titer is more than 1:160 in past infection or in immunized persons. A single Widal test is of little clinical relevance especially in endemic areas such as Indian subcontinent, Africa and South-east Asia. This is due to recurrent exposure to the typhoid causing bacteria, immunization and high chances of cross-reaction from infections, such as malaria and non typhoidal salmonella.  [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4420", "text": "If no other tests (either bacteriologic culture or more specific serology) are available, a fourfold increase in the titer (e.g., from 1:40 to 1:640) in the course of the infection, or a conversion from an IgM reaction to an IgG reaction of at least the same titer, would be consistent with a typhoid infection. The normal widal ranges are 1:20 and 1:80, these are in the normal range anything more is a concern and you should seek medical consulation."}
{"_id": "WikiPedia_Hematology$$$corpus_4421", "text": "D-xylose absorption test  is a medical test performed to diagnose conditions that present with  malabsorption  of the proximal  small intestine [ 1 ]  due to defects in the integrity of the gastrointestinal mucosa. [ 2 ]   D-xylose  is a  monosaccharide , or simple sugar, that does not require enzymes for digestion prior to absorption. Its absorption requires an intact mucosa only. In contrast,  polysaccharides  require enzymes, such as  amylase , to break them down so that they can eventually be absorbed as monosaccharides. This test was previously in use but has been made redundant by  antibody tests . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4422", "text": "In normal individuals, a 25\u00a0g oral dose of D-xylose will be absorbed and excreted in the urine at approximately 4.5\u00a0g in 5 hours. A decreased urinary excretion of D-xylose is seen in conditions involving the gastrointestinal mucosa, such as  small intestinal bacterial overgrowth  and  Whipple's disease . In cases of bacterial overgrowth, the values of D-xylose absorption return to normal after treatment with  antibiotics . In contrast, if the D-xylose urinary excretion is not normal after a course of antibiotics, then the problem must be due to a non-infectious cause of malabsorption (i.e.,  celiac disease ). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4423", "text": "Carbaminohemoglobin  ( carbaminohaemoglobin   BrE ) ( CO 2 Hb , also known as  carbhemoglobin  and  carbohemoglobin ) is a  compound  of  hemoglobin  and  carbon dioxide , and is one of the forms in which carbon dioxide exists in the  blood . [ 1 ]   Twenty-three percent of carbon dioxide is carried in  blood  this way (70% is converted into   bicarbonate  by  carbonic anhydrase  and then carried in plasma, 7% carried as free CO 2 , dissolved in plasma). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4424", "text": "The structure of carbaminohemoglobin can be described as the binding of carbon dioxide to the amino groups of the globin chains of hemoglobin. This occurs at the N-terminals of the globin chains and at the amino sidebranches of  arginine  and  lysine  residues. [ 3 ]  The process of carbon dioxide binding to hemoglobin is generally known as carbamino formation. This is the source from where the protein gets its name, as it is a combination of carbamino and hemoglobin. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4425", "text": "One of the primary functions of carbaminohemoglobin is to enable the transport of carbon dioxide in the bloodstream. When carbon dioxide is produced as a waste product of cellular metabolism in tissues, the compound is diffused into the bloodstream and it works to react with hemoglobin. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4426", "text": "When the binding of molecules occurs to form carbaminohemoglobin, it allows for the transport of carbon dioxide from the tissues to the lungs. Once it is in the lungs, carbon dioxide is released from carbaminohemoglobin and can be let out from the body during the exhalation process. This complete process is very important for maintaining the balance of gases in the blood and to ensure that gas exchange is being transported between tissues and organs. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4427", "text": "Carbaminohemoglobin interacts with carbon dioxide in a process known as respiratory gas exchange. The interaction involves the binding of carbon dioxide to hemoglobin. Carbon dioxide binds to the protein chains of hemoglobin. The ability of hemoglobin to bind to both oxygen and carbon dioxide molecules is what makes it an important protein to the respiratory system in respiratory gas exchange."}
{"_id": "WikiPedia_Hematology$$$corpus_4428", "text": "The interactions between carbon dioxide and hemoglobin helps in the transport of carbon dioxide from the tissues to the lungs for eliminations. When carbon dioxide is transported from the tissues, it is produced as a waste product of a set of reactions known as cellular metabolism. Most importantly, the binding of carbon dioxide to hemoglobin plays a part in the buffering of blood pH by preventing the drop of pH due to the production of carbonic acid. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4429", "text": "Although, the carbaminohemoglobin protein interacts with another protein (like hemoglobin) found in red blood cells, this interaction only takes place in the bloodstream and its products can be expelled. Carbaminohemoglobin does not interact with DNA since DNA is a molecule that is found in cell nucleus and its function is to carry genetic information. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4430", "text": "The formation and dissociation of the protein carbaminohemoglobin are controlled by many factors to guarantee the transport of carbon dioxide to the blood stream. A list of regulatory factors are listed below:"}
{"_id": "WikiPedia_Hematology$$$corpus_4431", "text": "When the tissues release carbon dioxide into the bloodstream, around 10% is dissolved into the plasma. The rest of the carbon dioxide is carried either directly or indirectly by  hemoglobin . Approximately 10% of the carbon dioxide carried by hemoglobin is in the form of carbaminohemoglobin. This carbaminohemoglobin is formed by the reaction between carbon dioxide and an amino (-NH 2 ) residue from the globin molecule, resulting in the formation of a carbamino residue (-NH.COO \u2212 ). The rest of the carbon dioxide is transported in the plasma as bicarbonate anions. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4432", "text": "When carbon dioxide binds to hemoglobin, carbaminohemoglobin is formed, lowering hemoglobin's affinity for  oxygen  via the  Bohr effect . The reaction is formed between a carbon dioxide molecule and an amino residue. [ 12 ]  In the absence of oxygen, unbound hemoglobin molecules have a greater chance of becoming carbaminohemoglobin. The  Haldane effect  relates to the increased affinity of de-oxygenated hemoglobin for  H + : offloading of oxygen to the tissues thus results in increased affinity of the hemoglobin for  carbon dioxide ,  and  H + , which the body needs to get rid of, which can then be transported to the lung for removal. Because the formation of this compound generates hydrogen ions, haemoglobin is needed to buffer it. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4433", "text": "Hemoglobin can bind to four molecules of carbon dioxide. The carbon dioxide molecules form a  carbamate  with the four terminal-amine groups of the four protein chains in the deoxy form of the molecule. Thus, one hemoglobin molecule can transport four carbon dioxide molecules back to the lungs, where they are released when the molecule changes back to the oxyhemoglobin form.  [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4434", "text": "When carbon dioxide diffuses as a dissolved gas from the tissue capillaries, it binds to the \u03b1-amino terminus of the globulin chain, forming Carbaminohemoglobin. Carbaminohemoglobin is able to directly stabilise the T conformation as part of the carbon dioxide  Bohr effect . Deoxyhemoglobin in turn subsequently increases the uptake of carbon dioxide in the form of favouring the formation of Bicarbonate as well as Carbaminohemoglobin through the  Haldane effect . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4435", "text": "Dysfunctional or altered levels of carbaminohemoglobin do not generally cause disease or disorders. Carbaminohemoglobin is a part of the carbon dioxide transport process in the body. The levels of this protein can decrease and increase based on factors that regulate the protein in the body. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4436", "text": "A way that carbaminohemoglobin can be associated with disease is when there is a change in its level caused by a pre-existing condition or imbalance in the respiratory and metabolic systems of the human body."}
{"_id": "WikiPedia_Hematology$$$corpus_4437", "text": "Some of these existing medical conditions can be the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_4438", "text": "The protein carbaminohemoglobin plays an important role in the transport of carbon dioxide in the blood, and its biologically important in many functions:"}
{"_id": "WikiPedia_Hematology$$$corpus_4439", "text": "Carboxyhemoglobin  ( carboxyhaemoglobin   BrE ) (symbol  COHb  or  HbCO ) is a stable  complex  of  carbon monoxide  and  hemoglobin  (Hb) that forms in  red blood cells  upon contact with carbon monoxide. Carboxyhemoglobin is often mistaken for the compound formed by the combination of carbon dioxide ( carboxyl ) and hemoglobin, which is actually  carbaminohemoglobin . Carboxyhemoglobin terminology emerged when carbon monoxide was known by its historic name, \"carbonic oxide\", and evolved through Germanic and British English etymological influences; the preferred  IUPAC  nomenclature is  carbonylhemoglobin . [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4440", "text": "The average non-smoker maintains a systemic carboxyhemoglobin level under 3% COHb whereas smokers approach 10% COHb. [ 4 ]  The biological threshold for carboxyhemoglobin tolerance is 15% COHb, meaning toxicity is consistently observed at levels in excess of this concentration. [ 5 ]  The  FDA  has previously set a threshold of 14% COHb in certain  clinical trials  evaluating the therapeutic potential of carbon monoxide. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4441", "text": "The average  red blood cell  contains 250 million  hemoglobin  molecules. [ 7 ]  Hemoglobin contains a  globin  protein unit with four  prosthetic   heme  groups (hence the name  heme   -o-   globin ); each heme is capable of reversibly binding with one gaseous molecule (oxygen, carbon monoxide, cyanide, etc.), [ 8 ]  therefore a typical red blood cell may carry up to one billion gas molecules. As the binding of carbon monoxide with hemoglobin is reversible, certain models have estimated that 20% of the carbon monoxide carried as carboxyhemoglobin may dissociate in remote tissues. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4442", "text": "In biology, carbon monoxide is naturally produced through many enzymatic and non-enzymatic pathways. [ 7 ]  The most extensively studied pathway is the metabolism of  heme  by  heme oxygenase  which occurs throughout the body with significant activity in the spleen to facilitate  hemoglobin  breakdown during  erythrocyte  recycling. Therefore heme can both carry carbon monoxide in the case of carboxyhemoglobin, or, undergo enzymatic catabolism to generate carbon monoxide."}
{"_id": "WikiPedia_Hematology$$$corpus_4443", "text": "Carbon monoxide was characterized as a neurotransmitter in 1993 and has since been subcategorized as a  gasotransmitter . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4444", "text": "Most endogenously produced carbon monoxide is stored as carboxyhemoglobin. The gas primarily undergoes  pulmonary  excretion, however trace amounts may be oxidized to  carbon dioxide  by certain  cytochromes , metabolized by resident  microbiota , or excreted by transdermal diffusion. [ 4 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4445", "text": "Compared to oxygen, carbon monoxide binds with approximately 240 times greater affinity, [ 9 ] [ 4 ]  however the affinity of carbon monoxide for hemoglobin varies both across species and within a species. In the 1950s,  Esther Killick  was among the first to recognize a difference in carbon monoxide affinity between adult and  foetal  blood, and a difference between humans and sheep. [ 4 ] [ 10 ] [ 11 ]  In humans, the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb. [ 5 ]  Other human mutations have been described (see also:  hemoglobin variants ). [ 12 ] [ 13 ]  Structural variations and mutations across other  hemoproteins  likewise affect carbon monoxide's interaction with the heme prosthetic group as exemplified by  Cytochrome P450  where certain forms of the  CYP3A   family  is relatively less affected by the inhibitory effects of carbon monoxide. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4446", "text": "Murinae  species have a COHb half-life of 20 minutes compared to 300 minutes for a typical human (see  \u00a7\u00a0Toxicokinetics ). [ 4 ]  As a result, the metabolic kinetics, blood saturation point, and tolerance for carbon monoxide exposure vary across species, potentially leading to data inconsistencies pertaining to the  toxicology  of  carbon monoxide poisoning  and  pharmacology  of low-dose therapeutic protocols. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4447", "text": "Some deep-diving marine mammal species are known to contain concentrations of carbon monoxide in their blood that resembles levels seen in chronic cigarette smokers, which may provide benefits against hypoxia. [ 14 ]  Similarly, the elevated levels in smokers has been suggested to be a basis for the  smoker's paradox . [ 4 ]  Prolonged exposure to carbon monoxide and elevated carboxyhemoglobin, such as in smoking, results in  erythremia . [ 4 ]  Furthermore, humans can  acclimate  to toxic levels of carbon monoxide based on findings reported by  Esther Killick . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4448", "text": "A bright red skin complexion is commonly associated with elevated carboxyhemoglobin levels. Trace evidence for an endogenous presence of carbon monoxide dates back to  Marcellus Donato  circa 1570 who noted an unusually red complexion upon conducting an autopsy of victims who died from charcoal fumes in  Mantua . [ 4 ]  Similar findings pertaining to red complexion later emerged as documented by  Johann Jakob Wepfer  in the 1600s, and  M.   Antoine Portal  in the late 1700s. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4449", "text": "Phlogiston theory  is a trace origin for the first chemical explanations of endogenous carboxyhemoglobin exemplified by the work of  Joseph Priestley  in the eighteenth century who suspected phlogiston to be a cellular waste product carried by the blood of animals which was subsequently exhaled. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4450", "text": "Thomas Beddoes ,  James Watt ,  Humphry Davy ,  James Lind , and many others investigated the therapeutic potential of inhaling  factitious airs  in the late eighteenth century (see also:  Pneumatic Institution ). Among the gases experimented with,  hydrocarbonate  had received significant attention. Hydrocarbonate is  water gas  generated by passing steam over  coke , the process of which generates carbon monoxide and hydrogen, and some considered it contain  phlogiston . Beddoes and Watt recognized hydrocarbonate brightened venous blood in 1793. Watt suggested coal fumes could act as an  antidote  to the oxygen in blood, and Beddoes and Watt likewise speculated hydrocarbonate has a greater affinity for animal fiber than oxygen in 1796. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4451", "text": "After the discovery of carbon monoxide by  William Cruickshank  in 1800,  Johann D\u00f6mling  (1803) and  John Bostock  (1804) developed hypotheses suggesting blood returned to the heart loaded with carbon monoxide to subsequently be oxidized to carbon dioxide in the lung prior to exhalation. [ 4 ]  Later in 1854,  Adrien Chenot  similarly suggested carbon monoxide could remove oxygen from blood and be oxidized within the body to carbon dioxide. [ 4 ]  The mechanism for carbon monoxide poisoning in the context of carboxyhemoglobin formation is widely credited to  Claude Bernard  whose memoirs beginning in 1846 and published in 1857 notably phrased, \"prevents arterials blood from becoming venous\". [ 4 ]   Felix Hoppe-Seyler  independently published similar conclusions in the following year."}
{"_id": "WikiPedia_Hematology$$$corpus_4452", "text": "The first analytical method to detect carboxyhemoglobin emerged in 1858 with a colorimetric method developed by  Felix Hoppe-Seyler , and the first quantitative analysis method emerged in 1880 with  Josef von Fodor . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4453", "text": "Carbon  is derived from the Latin term  carbo , meaning coal, via the French  charbone , which first appeared in print in 1786. [ 15 ]  The  etymology of oxygen  is generally accepted mean 'acid' based on Lavoisier's system, which also recognized carbon as a nonmetallic element capable of oxidation, although the original degrees of oxides were based on diamond, graphite, coal and  carbonic acid (CO 2 )  as the most oxidized form; [ 15 ]  Lavoisier's system was superseded by other obsolete oxide nomenclature systems. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4454", "text": "Upon discovering carbon monoxide through a series of experiments originating from  coke  (short for coal-cake [ 15 ] ),  Cruickshank  named the new molecule \"gaseous oxide of carbon\" which evolved to \"carbonic oxide\" and was translated into German as \"kohlenoxyd\". Kohlen is the German word for coal. [ 4 ] [ 17 ]  As carbonic acid (CO 2 ) was considered to be the most highly oxidized form in Lavoisier's system, the name carbonic oxide implied an intermediate oxidized species between coal and carbonic acid (i.e. use of the word acid indicated maximum oxidation)."}
{"_id": "WikiPedia_Hematology$$$corpus_4455", "text": "Haem is derived from Greek  meaning blood, [ 18 ] [ 19 ]  and globin is Latin derived from  globus  typically accepted to mean glob/spherical/round object; the terms are conjoined with an  -o-  . Regarding haem,  the use of \"ae / \u00e6\" remains prevalent in British English  in modern day [ 20 ]  whereas the American English spelling evolved to heme from hema. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4456", "text": "Felix Hoppe-Seyler  coined the name \"h\u00e4moglobin\" in 1864. [ 21 ]  In German, an  umlaut  such as  \u00e4  is synonymous with spelling as \"ae\", therefore h\u00e4moglobin is commonly spelled as haemoglobin throughout German literature, hence haemoglobin is the term adopted by English literature."}
{"_id": "WikiPedia_Hematology$$$corpus_4457", "text": "Hoppe-Seyler likewise coined the name Kohlenoxydh\u00e4moglobin [ 22 ]  which may have similarly been directly translated back into English as \"carbonic oxide h\u00e6moglobin\". [ 23 ]  The term carboxyh\u00e6moglobin appeared as early as 1895 in works by  John Haldane  while the name for CO was still widely regarded as carbonic oxide. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4458", "text": "The term \"carbon monoxide\" was formally introduced in 1879, but the name would not become mainstream for several decades. [ 4 ]  Variations of COHb terminology, such as carbonmonoxyhemoglobin, [ 25 ] [ 11 ]  followed and eventually evolved and simplified back into \"carboxyhemoglobin\"."}
{"_id": "WikiPedia_Hematology$$$corpus_4459", "text": "As carboxy is now firmly associated with the CO 2   carboxyl  group, and carbon monoxide is generally regarded as a  carbonyl , IUPAC has recommended \"carbonylhemoglobin\" as the preferred COHb nomenclature. [ 4 ]  Despite the IUPAC guidance, carboxyhemoglobin remains the most widely used term (akin to the  survival  of  bicarbonate  nomenclature)."}
{"_id": "WikiPedia_Hematology$$$corpus_4460", "text": "Historically, carboxyhemoglobin detection has been achieved by  colorimetric analysis , chemical reactivity,  spectrophotometry , gasometric and  thermoelectric  detection methods. [ 4 ]   Gas chromatography  analysis emerged in 1961 and remains a commonly used method. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4461", "text": "Modern methods include  pulse oximetry  with a  CO-oximeter , and a variety of other analytical techniques. [ 26 ] [ 27 ]  Most methods require laboratory equipment, skilled technicians, or expensive electronics therefore rapid and economical detection technologies remain in development."}
{"_id": "WikiPedia_Hematology$$$corpus_4462", "text": "Breath carbon monoxide  is another detection method that may correlate with carboxyhemoglobin levels. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4463", "text": "Carbon monoxide poisoning, also known as carboxyhemoglobinemia, [ 29 ] [ 30 ]  has plagued humankind since primitive ancestors first harnessed fire. In modern times, carboxyhemoglobin data assist physicians in making a poisoning diagnosis. However, carboxyhemoglobin levels do not necessarily correlate with the symptoms of carbon monoxide poisoning. [ 31 ]  In general, 30% COHb is considered severe carbon monoxide poisoning. [ 4 ]  The highest reported non-fatal carboxyhemoglobin level was 73% COHb. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4464", "text": "Gas exchange  is an essential process for many organisms to maintain homeostasis. Oxygen accounts for about 20% of Earth's atmospheric  air . While inhaling air is critical to supply cells with oxygen for  aerobic respiration  via the  Bohr effect  and  Haldane effect  (and perhaps local low oxygen partial pressure e.g. active muscles), [ 32 ]  exhaling the cellular waste product  carbon dioxide  is arguably the more critical aspect of respiration. Whereas the body can tolerate brief periods of  hypoxia  (as commonly occurs in  anaerobic exercise , although the brain, heart, liver and kidney are significantly less tolerant than skeletal muscle), failure to expel carbon dioxide may cause  respiratory acidosis  (meaning bodily fluids and blood become too acidic thereby affecting homeostasis). [ 33 ]  In absence of oxygen, cells switch to  anaerobic respiration  which if prolonged may significantly increase  lactic acid  leading to  metabolic acidosis . [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4465", "text": "To provide a simplified synopsis of the molecular mechanism of systemic gas exchange, upon inhalation of air it was widely thought oxygen binding to any of the heme sites triggers a  conformational change  in the protein unit of hemoglobin which then enables the binding of additional oxygen to each of the other heme sites. Upon arrival to the cellular region, oxygen is released at the tissue due to a conformational change in hemoglobin as caused by ionization of hemoglobin's surface due to the \"acidification\" of the tissue's local pH (meaning a relatively higher concentration of 'acidic' protons / hydrogen  ions  annotated as H + ; an acidic pH is commonly referenced to as either low pH based on the acidity of pH 1-7 having a  low  number, or, referred to as a high pH due to the  high  concentration of H +  ions as the scale approaches pH 1); the local acidity is caused by an increase in the biotransformation of carbon dioxide waste into  carbonic acid  via  carbonic anhydrase . In other words, oxygenated arterial blood arrives to cells in the \" hemoglobin R-state \" which has deprotonated/unionized amino acid  residues  (regarding hemoglobin's  amines  transitioning between the deprotonated/unionized Hb-NH2 to the protonated/ionized Hb-NH3 +  state) based on the less-acidic pH (arterial blood averages pH 7.407 whereas venous blood is slightly more acidic at pH 7.371 [ 35 ] ). The \"T-state\" of hemoglobin is deoxygenated in venous blood partially due to protonation/ionization as caused by the acidic environment hence causing a conformation unsuited for oxygen-binding [ 36 ]  (i.e. oxygen is 'ejected' upon arrival at the cell due to H +  ions bombarding the hemoglobin surface residues to convert Hb from \"R-state\" to \"T-state\"). Furthermore, the mechanism for formation of  carbaminohemoglobin  generates additional H +  ions that may further stabilize the protonated/ionized deoxygenated hemoglobin. Upon return of venous blood into the lung and subsequent exhalation of carbon dioxide, the blood is \"de-acidified\" (see also:  hyperventilation ) for the deprotonation/unionization of hemoglobin to re-enable oxygen binding as part of the transition to arterial blood (note this process is complex due to involvement of  chemoreceptors , pH buffers and other physiochemical functionalities). Carbon monoxide poisoning disturbs this physiological process hence the venous blood of poisoning patients is bright red akin to arterial blood since the carbonyl/carbon monoxide is retained, whereas deoxygenated hemoglobin is dark red and carbaminohemoglobin has a blue hue. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4466", "text": "At toxic concentrations, carbon monoxide as carboxyhemoglobin significantly interferes with respiration and gas exchange by simultaneously inhibiting acquisition and delivery of oxygen to cells, and preventing formation of  carbaminohemoglobin  which accounts for approximately 30% of carbon dioxide exportation. [ 37 ]  Therefore a patient suffering from carbon monoxide poisoning may experience severe  hypoxia  and  acidosis  in addition to the toxicities of excess carbon monoxide binding to numerous hemoproteins, metallic and non-metallic targets which affect cellular machinery (such as inhibition of  cytochrome c oxidase ). [ 7 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4467", "text": "In common air under normal atmospheric conditions, a typical patient's carboxyhemoglobin has a half-life around 300 minutes. [ 4 ]  This time can be reduced to 90 minutes upon administration of high-flow pure oxygen, and the time is further reduced when oxygen is administered with 5% carbon dioxide as first identified by  Esther Killick . [ 4 ]  Additionally, treatment in a  hyperbaric chamber  is a more effective manner of reducing the half-life of carboxyhemoglobin to 30 minutes [ 4 ]  and allows oxygen to dissolve in biological fluids for delivery to tissues. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4468", "text": "Supplemental oxygen takes advantage of  Le Chatelier's principle  to quicken the decomposition of carboxyhemoglobin back to hemoglobin: [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4469", "text": "As carbon monoxide is now understood to have a therapeutic potential, pharmaceutical efforts have focused on development of  carbon monoxide-releasing molecules  and selective  heme oxygenase  inducers. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4470", "text": "An alternative method for drug delivery consists of carbon monoxide immobilized on  polyethylene glycol  (PEG)-lyated  bovine  carboxyhemoglobin which is currently in late clinical development. Similarly,  maleimide  PEG conjugated human carboxyhemoglobin had previously been the subject of pharmaceutical development. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4471", "text": "The human embryonic haemoglobins were discovered in 1961. [ 1 ] [ 2 ]  These include Hb-Gower 1, consisting of 2 zeta chains and 2 epsilon chains, and Hb-Gower 2, which consists of 2 \u03b1lpha-chains and 2 epsilon-chains, the zeta and epsilon chains being the embryonic haemoglobin chains."}
{"_id": "WikiPedia_Hematology$$$corpus_4472", "text": "Embryonic hemoglobin  is a  tetramer  produced in the  blood islands  in the embryonic  yolk sac  during the  mesoblastic stage  (from 3rd week of pregnancy until 3 months). The protein is commonly referred to as  hemoglobin \u03b5 ."}
{"_id": "WikiPedia_Hematology$$$corpus_4473", "text": "Chromosomal abnormalities  can lead to a delay in switching from embryonic hemoglobin. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4474", "text": "Hemoglobin Gower 1  (also referred to as  \u03b6 2 \u03b5 2  or  HbE Gower-1 ) is a form of hemoglobin existing only during embryonic life, and is the primary embryonic hemoglobin.  It is composed of two  zeta chains  and two  epsilon chains , and is relatively unstable, breaking down easily. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4475", "text": "Hemoglobin Gower 2  (also referred to as  \u03b1 2 \u03b5 2  or  HbE Gower-2 ) is a form of hemoglobin existing at low levels during embryonic and fetal life.  It is composed of two alpha chains and two epsilon chains, and is somewhat unstable, though not as much as hemoglobin Gower 1. [ 4 ]   Due to its relative stability compared to hemoglobin Gower 1 and  hemoglobin S , it has been proposed as a subject for reactivation in the adult in cases of severe  \u03b2 thalassemia  and  hemoglobinopathies  in subjects for which the reactivation of  hemoglobin F  is contraindicated due to toxicity concerns. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4476", "text": "Hemoglobin Portland I  (also referred to as  \u03b6 2 \u03b3 2  or  HbE Portland-1 ) is a form of hemoglobin existing at low levels during embryonic and fetal life, composed of two zeta chains and two gamma chains. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4477", "text": "Hemoglobin Portland II  (also referred to as  \u03b6 2 \u03b2 2  or  HbE Portland-2 ) is a form of hemoglobin existing at low levels during embryonic and fetal life, composed of two zeta chains and two beta chains.  It is quite unstable, more so than even hemoglobin Gower 1, and breaks down very rapidly under stress. [ 4 ]   Despite this, it has been proposed as a candidate for reactivation in cases of severe  \u03b1 thalassemia  or hemoglobinopathies afflicting the alpha chain. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4478", "text": "[ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4479", "text": "Fetal hemoglobin , or  foetal haemoglobin  (also  hemoglobin F ,  HbF , or  \u03b1 2 \u03b3 2 ) is the main  oxygen   carrier protein  in the human  fetus . Hemoglobin \u00a0 F is found in fetal  red blood cells , and is involved in transporting oxygen from the mother's  bloodstream  to organs and tissues in the fetus. It is produced at around 6 \u00a0 weeks of pregnancy  [ 1 ]  and the levels remain high after birth until the baby is roughly 2\u20134 \u00a0 months old. [ 2 ]  Hemoglobin \u00a0 F has a different composition than adult forms of  hemoglobin , allowing it to bind (or attach to) oxygen more strongly; this in turn enables the developing fetus to retrieve oxygen from the mother's bloodstream, which occurs through the  placenta  found in the mother's  uterus . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4480", "text": "In the newborn, levels of hemoglobin F gradually decrease and reach adult levels (less than 1% of total hemoglobin) usually within the first year, as adult forms of hemoglobin begin to be produced. [ 4 ]  Diseases such as  beta thalassemias , which affect components of the  adult hemoglobin , can delay this process, and cause hemoglobin F levels to be higher than normal. [ 5 ]  In  sickle cell anemia , increasing the production of hemoglobin F has been used as a treatment to relieve some of the symptoms. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4481", "text": "Hemoglobin F, like adult hemoglobin ( hemoglobin A  and  hemoglobin A2 ), has four  subunits  or chains. Each subunit contains a  heme  group with an iron element which is key in allowing the binding and unbinding of oxygen. As such, hemoglobin F can adopt two states:  oxyhemoglobin  (bound to oxygen) and  deoxyhemoglobin  (without oxygen). As hemoglobin F has 4 heme groups, it can bind to up to four oxygen molecules. [ 7 ]  It is composed of  two \u03b1 (alpha)  subunits and  two \u03b3 (gamma)  subunits, whereas hemoglobin A (97% of total hemoglobin in adults) is composed of two \u03b1 and two \u03b2 (beta) subunits."}
{"_id": "WikiPedia_Hematology$$$corpus_4482", "text": "In humans, the \u03b1 subunit is encoded on  chromosome 16  and the \u03b3 subunit is encoded on  chromosome 11 . There are two very similar  genes  that code for the \u03b1 subunit,  HBA1  and  HBA2 . The protein that they produce is identical, but they differ in gene regulatory regions that determine when or how much of the protein is produced. This leads to HBA1 and HBA2 contributing 40% and 60%, respectively, of the total \u03b1 subunits produced. As a consequence, mutations on the  HBA2  gene are expected to have a stronger effect than mutations on the  HBA1  gene. [ 8 ]  \nThere are also two similar copies of the gene coding for the \u03b3 subunit,  HBG1  and  HBG2 , but the protein produced is slightly different, just in one  protein unit :  HBG1  codes for the protein form with an  alanine  at position 136, whereas  HBG2  codes for a  glycine [ 9 ] \nBCL11A and ZBTB7A are major repressor proteins of hemoglobin F production, by binding to the gene coding for the \u03b3 subunit at their promoter region. [ 10 ]  This happens naturally as the newborn baby starts to switch from producing hemoglobin F to producing hemoglobin A.\nSome genetic diseases can take place due to mutations to genes coding for components of hemoglobin F. Mutations to  HBA1  and  HBA2  genes can cause  alpha-thalassemia [ 11 ]  and mutations to the promoter regions of  HBG1  and  HBG2  can cause hemoglobin F to still be produced after the switch to hemoglobin A should have occurred, which is called  hereditary persistence of fetal hemoglobin . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4483", "text": "During the first 3 months of pregnancy, the main form of hemoglobin in the embryo/fetus is  embryonic hemoglobin , which has 3 variants depending on the types of subunits it contains. The production of hemoglobin F starts from week 6, but it's only from 3 months onwards that it becomes the main type found in fetal red blood cells. [ 4 ] \nThe switch to produce adult forms of hemoglobin (essentially hemoglobin A) starts at around 40 weeks of gestation, which is close to the expected time of birth. [ 1 ]  At birth, hemoglobin F accounts for 50-95% of the infant's hemoglobin and at around 6 months after birth, hemoglobin A becomes the predominant type. By the time the baby is one year old, the proportions of different types of hemoglobin are expected to approximate the adult levels, with hemoglobin F reduced to very low levels. [ 4 ]  The small proportion of red blood cells containing hemoglobin F are called F-cells, which also contain other types of hemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_4484", "text": "In healthy adults, the composition of hemoglobin is hemoglobin A (~97%), hemoglobin A2 (2.2 - 3.5%) and hemoglobin F (<1%). [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4485", "text": "Certain genetic abnormalities can cause the switch to adult hemoglobin synthesis to fail, resulting in a condition known as  hereditary persistence of fetal hemoglobin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4486", "text": "The four hemes, which are the oxygen-binding parts of hemoglobin, are similar between hemoglobin F and other types of hemoglobin, including hemoglobin A. Thus, the key feature that allows hemoglobin F to bind more strongly to oxygen is by having \u03b3 subunits (instead of \u03b2, for example). In fact, some naturally existing molecules in our body can bind to hemoglobin and change its binding affinity for oxygen. One of the molecules is  2,3-bisphosphoglycerate (2,3-BPG)  and it enhances hemoglobin's ability to release oxygen. [ 13 ]  2,3-BPG interacts much more with hemoglobin A than hemoglobin F. This is because the adult \u03b2 subunit has more positive charges than the fetal \u03b3 subunit, which attract the negative charges from 2,3-BPG. Due to the preference of 2,3-BPG for hemoglobin A, hemoglobin F binds to oxygen with more affinity, in average. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4487", "text": "Hemoglobin Barts  is an abnormal form of hemoglobin produced in hemoglobin Barts syndrome or alpha-thalassemia major, the most severe form of  alpha-thalassemia . Alpha-thalassemia is a genetic blood disorder and one of the most common hemoglobin-related diseases, affecting the production of \u03b1 subunits from hemoglobin. [ 15 ]  Depending on how many genes coding for the \u03b1 subunit are impacted (between one and four), patients with this disease can have reduced to no production of the \u03b1 subunit of the hemoglobin. As a consequence, less hemoglobin is available and this affects oxygen supply to the tissues. \nHemoglobin Barts syndrome manifests when all four genes coding for \u03b1 subunit are deleted. This is often fatal for the fetus carrying the disorder, as in the absence of \u03b1 subunits, a form of hemoglobin with four \u03b3 subunits, hemoglobin Barts, is produced. This form of hemoglobin isn't fit for oxygen exchange precisely due to its very high affinity for oxygen.  While hemoglobin Barts is very efficient at binding oxygen, it doesn't release oxygen to the organs and tissues. [ 16 ]  The disease is fatal for the fetus or newborn unless early diagnosis and intervention is carried out during pregnancy, and the child will be dependent on lifelong blood transfusions."}
{"_id": "WikiPedia_Hematology$$$corpus_4488", "text": "To quantify how strongly a certain type of hemoglobin binds to oxygen (or its affinity for oxygen), a parameter called P50 is often used. In a given situation, P50 can be understood as the partial pressure of oxygen at which Hb is 50% saturated. [ 17 ]  For example, Hemoglobin F has a lower P50 than hemoglobin A. This means that if we have the same amount of hemoglobin F and hemoglobin A in the blood and add oxygen to it, half of hemoglobin F will bind to oxygen before half of hemoglobin A manages to do so. Therefore, a lower P50 means stronger binding or higher affinity for oxygen."}
{"_id": "WikiPedia_Hematology$$$corpus_4489", "text": "For reference, the P50 of fetal hemoglobin is roughly 19 mmHg (a measure of pressure), whereas adult hemoglobin is approximately 26.8 mmHg (see  Blood gas tension ). [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4490", "text": "During pregnancy, the mother's circulatory system delivers oxygen and nutrients to the fetus and carries away nutrient-depleted blood enriched with carbon dioxide. The maternal and fetal blood circulations are separate and the exchange of molecules occurs through the placenta, in a region called  intervillous space  which is located in between maternal and fetal blood vessels. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4491", "text": "Focusing on oxygen exchange, there are three important aspects that allow oxygen to pass from the maternal circulation into the fetal circulation. Firstly, the presence of hemoglobin F in the fetus allows a stronger binding to oxygen than maternal hemoglobin (see  Factors affecting oxygen affinity ). Secondly, the mother's bloodstream is richer in oxygen than that of the fetus, so oxygen naturally flows towards the fetal circulation by diffusion. [ 19 ]  The final factor is related to the effects of pH on maternal and fetal hemoglobin. As the maternal blood acquires more carbon dioxide, it becomes more acidic and this favors the release of oxygen by the maternal hemoglobin. At the same time, the decrease in carbon dioxide in fetal blood makes it more alkaline and favors the uptake of oxygen. This is called the Bohr effect or  Haldane effect , which also happens in the air exchange in the lungs. [ 20 ]  All of these three factors are present simultaneously and cooperate to improve the fetus\u2019 access to oxygen from the mother."}
{"_id": "WikiPedia_Hematology$$$corpus_4492", "text": "F-cells are the subpopulation of red blood cells that contain hemoglobin F, in amongst other types of hemoglobin. While common in fetuses, in normal adults, only around 3-7% of red blood cells contain hemoglobin F. [ 21 ]  The low percentage of F-cells in adults owes to two factors: very low levels of hemoglobin F being present and its tendency to be produced only in a subset of cells rather than evenly distributed amongst all red blood cells. In fact, there is a positive correlation between the levels of hemoglobin F and number of F-cells, with patients with higher percentages of hemoglobin F also having a higher proportion of F-cells. [ 22 ]   Despite the correlations between hemoglobin F levels and F-cell numbers, usually they are determined by direct measurements. While the amount of hemoglobin F is calculated using cell lysates, which are fluids with contents of cells that were broken open, F-cell numbers are done by counting intact red blood cells. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4493", "text": "Due to the correlation between the amount of hemoglobin F and F-cells, F-cell numbers are higher in some inherited hemoglobin disorders, including  beta-thalassemia ,  sickle cell anemia  and  hereditary persistence of fetal hemoglobin . Additionally, some acquired conditions can also have higher F-cell numbers, such as acute erythropoietic stress (response to poor oxygenation which includes very rapid synthesis of new red blood cells) [ 23 ]  and pregnancy. [ 21 ] \nF-cells have similar mass of haemoglobin per cell compared to red blood cells without haemoglobin F, which is measured  mean cell haemoglobin  values (MCH). [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4494", "text": "There is a significant increase in hemoglobin F levels during early pregnancy. However, it's not clear whether these levels are stable or decrease as the pregnancy goes on, as different sources reported different results. [ 25 ] [ 26 ] \nThe increase in hemoglobin F then induces a 3 to 7 fold increase in the number of F-cells in pregnant women, which was observed between the 23rd to 31st week of gestation. [ 27 ] \nHowever, as to the reason of the increase in hemoglobin F levels in pregnant women, there doesn't seem to be conclusive evidence. While an early study suggested that maternal red blood cells switch on hemoglobin F production during pregnancy, [ 27 ]  more recent literature suggested that the increase in haemoglobin F could be, at least in part, due to fetal red blood cells being transferred to the maternal circulation. [ 28 ] [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4495", "text": "Presence of high levels of hemoglobin F in pregnant women can impact the growth of the fetus, as fetal red blood cells struggle to compete for the oxygen from the mother's circulation. This is because instead of competing with hemoglobin A, which has a weaker association to oxygen than hemoglobin F, it becomes a competition between fetal and maternal hemoglobin F which have similar affinities for oxygen. As a result, women with hemoglobin F as >70% of total hemoglobin are much more likely to have fetuses that are small for their gestational age compared women with <70% hemoglobin F (at a rate of 100% compared to 8%, respectively). [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4496", "text": "This is a rare benign genetic disease where production of hemoglobin F persists after twelve months of life and into the adulthood. As a result, hemoglobin F is present in a higher number of adult red blood cells than normal. [ 30 ] \nIt doesn't present symptoms and is usually discovered when screening for other blood-related diseases. \nIn this condition, the genes coding for the \u03b3 subunit (HBG1 and HBG2) are not suppressed shortly before birth. This can happen when a mutation occurs in the promoter region of HBG1 and HBG2, preventing the binding of BCL11A and ZBTB7A proteins. These proteins would normally bind and suppress the production of \u03b3 subunits and as they can't bind due to the mutation, \u03b3 subunits continue to be produced. [ 10 ]  There are two types of patients with HPFH: either with one normal copy of the gene and one disease form or with two disease copies. Whereas normal adults have less than 1% of hemoglobin F, patients with only one disease gene have 5-30%. Patients with two disease copies can have hemoglobin F in up to 100% of red blood cells. [ 31 ]  \nAs other diseases such as sickle cell disease could also cause a higher level of hemoglobin F to be present, it can sometimes be misdiagnosed. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4497", "text": "Delta beta-thalassemia is a rare genetic blood disorder in which the production of both \u03b4 and \u03b2 subunits are reduced or absent. In these cases, the production of the \u03b3 subunit increases to compensate for the loss of \u03b4 and \u03b2 subunits, resulting in a higher amount of hemoglobin F present in the blood. Normally,  people have two sets of genes for producing \u03b4 and \u03b2 subunits. People with only one set of working genes don't get any symptoms and in the rarely reported cases where both sets of genes are affected, the patients only experienced mild symptoms. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4498", "text": "The discovery that hemoglobin F alleviated the symptoms of sickle cell disease occurred in 1948. Janet Watson observed that red blood cells from infants with the disease took longer to sickle and did not deform as much compared to their mother's cells, which carried the disease trait. Later, it was noted that patients with sickle cell trait as well as hereditary persistence of hemoglobin F (HPFH) didn't have symptoms. [ 34 ]  Additionally, in sickle cell patients, F-cells were found to be more long living than non-F cells as they contain hemoglobin F."}
{"_id": "WikiPedia_Hematology$$$corpus_4499", "text": "When fetal hemoglobin production is switched off after birth, normal children begin producing adult hemoglobin (HbA). Children with  sickle-cell disease  begin producing a defective form of hemoglobin called  hemoglobin S  instead, which form chains that cause  red blood cells  to change their shape from round to  sickle -shaped. [ 35 ] \nThese defective red blood cells have a much shorter life span than normal red blood cells (10\u201320 days compared to up to 120 days). [ 36 ]  They also have a greater tendency to clump together and block small  blood vessels , preventing blood supply to tissues and organs. This leads to the so-called  vaso-occlusive crisis , which is a hallmark of the disease. [ 37 ] \nIf fetal hemoglobin remains relatively high after birth, the number of painful episodes decreases in patients with sickle-cell disease and they have a better prognosis. [ 38 ] \nFetal hemoglobin's role in reducing disease severity comes from its ability to disrupt the formation of hemoglobin S chains within red blood cells. [ 39 ]  \nInterestingly, while higher levels of hemoglobin F were associated with improvement of some symptoms, including the frequency of painful episodes, leg ulcers and the general severity of the disease, it had no correlation to others. A few examples are  priapism , stroke and systemic blood pressure. [ 34 ]   As hemoglobin F are only produced by some red blood cells, in different quantities, only a subpopulation of cells are protected against sickling. It could be that the symptoms that high hemoglobin F doesn't prevent are quite sensitive to the rupture of the sickled non-F cells. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4500", "text": "Hydroxyurea  is a chemical that promotes the production of fetal hemoglobin and reduces the premature rupturing of red blood cells. [ 6 ] [ 40 ]  Combination therapy with hydroxyurea and recombinant  erythropoietin  \u2014 rather than treatment with hydroxyurea alone \u2014 has been shown to further elevate hemoglobin F levels and to promote the development of HbF-containing F-cells. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4501", "text": "There have been some studies evaluating the possibility of using hemoglobin F as an indicator of the prognosis for cancer. It has been suggested that elevated concentrations of haemoglobin F can be found in main kinds of solid tumours and blood cancers. [ 42 ] \nExamples include acute lymphoblastic leukemia and myeloid leukemia in children, where higher concentrations of hemoglobin F were associated with a worse outcome, including a higher risk of relapse or death. [ 43 ] \nOther cancer types where higher hemoglobin F levels have been observed are transitional cell cancer, [ 44 ]  colorectal carcinoma [ 45 ] \nand various types of blastomas. [ 46 ]  In fact, in several types of blastomas, including neuroblastoma and retinoblastoma (affecting the nerve cells and the eyes, respectively), F-cells were found in newly formed blood vessels and spaces in between tumour cells. Clusters of F-cells were also present in the  bone marrow  of some of these patients. [ 46 ] \nInterestingly, hemoglobin F is not directly produced by tumour cells, but seems to be induced by the biological environment of the cancer in nearby blood cells. A reason suggested for this increase in hemoglobin F is that it may favor cancer growth by providing better oxygen supply to the developing cancerous cells. [ 44 ]  In adults, increased hemoglobin F production is thought to be caused by factors leading to the activation of the gene coding for the \u03b3 subunit, such as  DNA demethylation  (which can activate normally silent genes and is a hallmark of cancer). [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4502", "text": "1SHR ,  1SI4"}
{"_id": "WikiPedia_Hematology$$$corpus_4503", "text": "3045"}
{"_id": "WikiPedia_Hematology$$$corpus_4504", "text": "n/a"}
{"_id": "WikiPedia_Hematology$$$corpus_4505", "text": "ENSG00000223609"}
{"_id": "WikiPedia_Hematology$$$corpus_4506", "text": "P02042"}
{"_id": "WikiPedia_Hematology$$$corpus_4507", "text": "NM_000519"}
{"_id": "WikiPedia_Hematology$$$corpus_4508", "text": "NP_000510"}
{"_id": "WikiPedia_Hematology$$$corpus_4509", "text": "Hemoglobin subunit delta  is a  protein  that in  humans  is encoded by the  HBD   gene . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4510", "text": "The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute  HbA , which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute  HbA2 , which with  HbF  comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5' -  epsilon  \u2013  gamma-G  \u2013  gamma-A  \u2013  delta  \u2013  beta  - 3'. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4511", "text": "Mutations in the delta-globin gene are associated with  Delta-thalassemia . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4512", "text": "1A9W"}
{"_id": "WikiPedia_Hematology$$$corpus_4513", "text": "3046"}
{"_id": "WikiPedia_Hematology$$$corpus_4514", "text": "15132"}
{"_id": "WikiPedia_Hematology$$$corpus_4515", "text": "ENSG00000213931"}
{"_id": "WikiPedia_Hematology$$$corpus_4516", "text": "ENSMUSG00000052217"}
{"_id": "WikiPedia_Hematology$$$corpus_4517", "text": "P02100"}
{"_id": "WikiPedia_Hematology$$$corpus_4518", "text": "P04444"}
{"_id": "WikiPedia_Hematology$$$corpus_4519", "text": "NM_005330"}
{"_id": "WikiPedia_Hematology$$$corpus_4520", "text": "NM_008219"}
{"_id": "WikiPedia_Hematology$$$corpus_4521", "text": "NP_005321 NP_005321.1"}
{"_id": "WikiPedia_Hematology$$$corpus_4522", "text": "NP_032245"}
{"_id": "WikiPedia_Hematology$$$corpus_4523", "text": "Hemoglobin subunit epsilon  is a  protein  that in humans is encoded by the  HBE1   gene . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4524", "text": "The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two  zeta chains  (an alpha-like globin) constitute the embryonic hemoglobin  Hb Gower I ; two epsilon chains together with two alpha chains form the embryonic  Hb Gower II . Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order:  5' -  epsilon  \u2013  gamma-G  \u2013  gamma-A  \u2013  delta  \u2013  beta  - 3'. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4525", "text": "This article incorporates text from the  United States National Library of Medicine , which is in the  public domain ."}
{"_id": "WikiPedia_Hematology$$$corpus_4526", "text": "1I3D ,  1I3E"}
{"_id": "WikiPedia_Hematology$$$corpus_4527", "text": "3047"}
{"_id": "WikiPedia_Hematology$$$corpus_4528", "text": "ENSG00000213934"}
{"_id": "WikiPedia_Hematology$$$corpus_4529", "text": "P69891"}
{"_id": "WikiPedia_Hematology$$$corpus_4530", "text": "NM_000559"}
{"_id": "WikiPedia_Hematology$$$corpus_4531", "text": "NP_000550"}
{"_id": "WikiPedia_Hematology$$$corpus_4532", "text": "Hemoglobin subunit gamma-1  is a  protein  that in humans is encoded by the  HBG1   gene . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4533", "text": "The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) in the year following birth. In the non-pathological condition known as hereditary persistence of fetal hemoglobin (HPFH), gamma globin expression is continued into adulthood. Also, in cases of beta-thalassemia and related conditions, gamma chain production may be maintained, possibly as a mechanism to compensate for the mutated beta-globin. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5' -  epsilon  \u2013  gamma-G  \u2013  gamma-A  \u2013  delta  \u2013  beta  - 3'. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4534", "text": "1FDH ,  4MQJ ,  4MQK"}
{"_id": "WikiPedia_Hematology$$$corpus_4535", "text": "3048"}
{"_id": "WikiPedia_Hematology$$$corpus_4536", "text": "15135"}
{"_id": "WikiPedia_Hematology$$$corpus_4537", "text": "ENSG00000196565"}
{"_id": "WikiPedia_Hematology$$$corpus_4538", "text": "ENSMUSG00000052187"}
{"_id": "WikiPedia_Hematology$$$corpus_4539", "text": "P69892"}
{"_id": "WikiPedia_Hematology$$$corpus_4540", "text": "P02104"}
{"_id": "WikiPedia_Hematology$$$corpus_4541", "text": "NM_000184"}
{"_id": "WikiPedia_Hematology$$$corpus_4542", "text": "NM_008221"}
{"_id": "WikiPedia_Hematology$$$corpus_4543", "text": "NP_000175"}
{"_id": "WikiPedia_Hematology$$$corpus_4544", "text": "NP_032247"}
{"_id": "WikiPedia_Hematology$$$corpus_4545", "text": "Hemoglobin subunit gamma-2  is a  protein  that in humans is encoded by the  HBG2   gene . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4546", "text": "The gamma globin genes ( HBG1  and HBG2, this gene) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some  beta-thalassemias  and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where  glycine  is found in the G-gamma product (HBG2) and  alanine  is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5' -  epsilon  \u2013  gamma-G  \u2013  gamma-A  \u2013  delta  \u2013  beta  - 3'. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4547", "text": "3049"}
{"_id": "WikiPedia_Hematology$$$corpus_4548", "text": "544763"}
{"_id": "WikiPedia_Hematology$$$corpus_4549", "text": "ENSG00000086506"}
{"_id": "WikiPedia_Hematology$$$corpus_4550", "text": "ENSMUSG00000073063"}
{"_id": "WikiPedia_Hematology$$$corpus_4551", "text": "P09105"}
{"_id": "WikiPedia_Hematology$$$corpus_4552", "text": "Q3U0A6"}
{"_id": "WikiPedia_Hematology$$$corpus_4553", "text": "NM_005331"}
{"_id": "WikiPedia_Hematology$$$corpus_4554", "text": "NM_001033981"}
{"_id": "WikiPedia_Hematology$$$corpus_4555", "text": "NP_005322"}
{"_id": "WikiPedia_Hematology$$$corpus_4556", "text": "NP_001029153"}
{"_id": "WikiPedia_Hematology$$$corpus_4557", "text": "Hemoglobin subunit theta-1  is a  protein  that in humans is encoded by the  HBQ1   gene . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4558", "text": "Theta-globin mRNA is found in human  fetal  erythroid tissue but not in adult  erythroid  or other nonerythroid tissue. The theta-1 gene may be expressed very early in embryonic life, perhaps sometime before 5 weeks. Theta-1 is a member of the human alpha-globin gene cluster that involves five functional genes and two pseudogenes. The order of genes is: 5' -  zeta  - pseudozeta -  mu  - pseudoalpha-1 -  alpha-2  -  alpha-1  -  theta-1  - 3'. Research supports a transcriptionally active role for the gene and a functional role for the peptide in specific cells, possibly those of early erythroid tissue. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4559", "text": "This article on a  gene  on human  chromosome 16  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4560", "text": "Hemoglobin  ( haemoglobin , [ a ]   Hb  or  Hgb ) is a  protein  containing  iron  that facilitates the transportation of  oxygen  in  red blood cells . Almost all  vertebrates  contain hemoglobin, [ 3 ]  with the sole exception of the fish family  Channichthyidae . [ 4 ]  Hemoglobin in the  blood  carries oxygen from the respiratory organs ( lungs  or  gills ) to the other tissues of the body, where it releases the oxygen to enable  aerobic respiration  which powers an animal's  metabolism . A healthy human has 12 \u00a0 to 20 \u00a0 grams of hemoglobin in every 100 \u00a0 mL of blood. Hemoglobin is a  metalloprotein , a  chromoprotein , and  globulin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4561", "text": "In  mammals , hemoglobin makes up about 96% of a red blood cell's  dry weight  (excluding water), and around 35% of the total weight (including water). [ 5 ]  Hemoglobin has an oxygen-binding capacity of 1.34 \u00a0 mL of O 2  per gram, [ 6 ]  which increases the total  blood oxygen capacity  seventy-fold compared to dissolved oxygen in blood plasma alone. [ 7 ]  The mammalian hemoglobin molecule can bind and transport up to four oxygen molecules. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4562", "text": "Hemoglobin also transports other gases. It carries off some of the body's respiratory  carbon dioxide  (about 20\u201325% of the total) [ 9 ]  as  carbaminohemoglobin , in which CO 2  binds to the  heme protein . The molecule also carries the important regulatory molecule  nitric oxide  bound to a  thiol  group in the globin protein, releasing it at the same time as oxygen. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4563", "text": "Hemoglobin is also found in other cells, including in the  A9 dopaminergic neurons  of the  substantia nigra ,  macrophages ,  alveolar cells , lungs, retinal pigment epithelium, hepatocytes,  mesangial cells  of the kidney, endometrial cells, cervical cells, and vaginal epithelial cells. [ 11 ]  In these tissues, hemoglobin absorbs unneeded oxygen as an  antioxidant , and regulates  iron metabolism . [ 12 ]  Excessive glucose in the blood can attach to hemoglobin and raise the level of hemoglobin A1c. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4564", "text": "Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. [ 14 ]  In these organisms, hemoglobins may carry oxygen, or they may transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant called  leghemoglobin  serves to scavenge oxygen away from  anaerobic  systems such as the nitrogen-fixing nodules of  leguminous  plants, preventing oxygen poisoning."}
{"_id": "WikiPedia_Hematology$$$corpus_4565", "text": "The medical condition  hemoglobinemia , a form of  anemia , is caused by  intravascular hemolysis , in which hemoglobin leaks from red blood cells into the  blood plasma ."}
{"_id": "WikiPedia_Hematology$$$corpus_4566", "text": "In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. [ 16 ] [ 17 ]  From the known atomic mass of iron, he calculated the molecular mass of hemoglobin to  n  \u00d7 16000 ( n =number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a protein's molecular mass. This \"hasty conclusion\" drew ridicule from colleagues who could not believe that any molecule could be so large. However,  Gilbert Smithson Adair  confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4567", "text": "Although blood had been known to carry oxygen since at least 1794, [ 19 ] [ 20 ]  the oxygen-carrying property of hemoglobin was described by H\u00fcnefeld in 1840. [ 21 ]  In 1851, German physiologist  Otto Funke  published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. [ 22 ] [ 23 ]  Hemoglobin's reversible oxygenation was described a few years later by  Felix Hoppe-Seyler . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4568", "text": "With the development of  X-ray crystallography , it became possible to sequence protein structures. [ 25 ]  In 1959,  Max Perutz  determined the molecular structure of hemoglobin. [ 26 ] [ 27 ]  For this work he shared the 1962  Nobel Prize in Chemistry  with  John Kendrew , who sequenced the globular protein  myoglobin . [ 25 ] [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4569", "text": "The role of hemoglobin in the blood was elucidated by French  physiologist   Claude Bernard ."}
{"_id": "WikiPedia_Hematology$$$corpus_4570", "text": "The name  hemoglobin  (or  haemoglobin ) is derived from the words  heme  (or  haem ) and  globin , reflecting the fact that each  subunit  of hemoglobin is a  globular protein  with an embedded  heme  group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4571", "text": "Hemoglobin consists of  protein subunits  ( globin  molecules), which are  polypeptides , long folded chains of specific  amino acids  which determine the protein's chemical properties and function. The amino acid sequence of any polypeptide is  translated  from a segment of DNA, the corresponding  gene ."}
{"_id": "WikiPedia_Hematology$$$corpus_4572", "text": "There is more than one hemoglobin gene. In humans,  hemoglobin A  (the main form of hemoglobin in adults) is coded by genes  HBA1 ,  HBA2 , and  HBB . [ 30 ]  Alpha 1 and alpha 2 subunits are respectively coded by genes  HBA1  and  HBA2  close together on chromosome 16, while the beta subunit is coded by gene  HBB  on chromosome 11. The amino acid sequences of the globin subunits usually differ between species, with the difference growing with evolutionary distance. For example, the most common hemoglobin sequences in humans, bonobos and chimpanzees are completely identical, with exactly the same alpha and beta globin protein chains. [ 31 ] [ 32 ] [ 33 ]  Human and gorilla hemoglobin differ in one amino acid in both alpha and beta chains, and these differences grow larger between less closely related species. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4573", "text": "Mutations  in the genes for hemoglobin can result in  variants of hemoglobin  within a single species, although one sequence is usually \"most common\" in each species. [ 34 ] [ 35 ]  Many of these mutations cause no disease, but some cause a group of  hereditary diseases  called  hemoglobinopathies . The best known hemoglobinopathy is  sickle-cell disease , which was the first human disease whose  mechanism  was understood at the molecular level. A mostly separate set of diseases called  thalassemias  involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin  gene regulation . All these diseases produce  anemia . [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4574", "text": "Variations in hemoglobin sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to the thin air at high altitudes, where lower partial pressure of oxygen diminishes its binding to hemoglobin compared to the higher pressures at sea level. Recent studies of deer mice found mutations in four genes that can account for differences between high- and low-elevation populations. It was found that the genes of the two breeds are \"virtually identical\u2014except for those that govern the oxygen-carrying capacity of their hemoglobin. . . . The genetic difference enables highland mice to make more efficient use of their oxygen.\" [ 37 ]   Mammoth  hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during the  Pleistocene . [ 38 ]  This was also found in hummingbirds that inhabit the Andes. Hummingbirds already expend a lot of energy and thus have high oxygen demands and yet Andean hummingbirds have been found to thrive in high altitudes. Non-synonymous mutations in the hemoglobin gene of multiple species living at high elevations ( Oreotrochilus, A. castelnaudii, C. violifer, P. gigas,  and  A. viridicuada ) have caused the protein to have less of an affinity for  inositol hexaphosphate  (IHP), a molecule found in birds that has a similar role as 2,3-BPG in humans; this results in the ability to bind oxygen in lower partial pressures. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4575", "text": "Birds' unique  circulatory lungs  also promote efficient use of oxygen at low partial pressures of O 2 . These two adaptations reinforce each other and account for birds' remarkable high-altitude performance. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4576", "text": "Hemoglobin adaptation extends to humans, as well. There is a higher offspring survival rate among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. [ 40 ]  Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower for women with higher hemoglobin-oxygen affinity when compared to the mortality rate of offspring from women with low hemoglobin-oxygen affinity. While the exact genotype and mechanism by which this occurs is not yet clear, selection is acting on these women's ability to bind oxygen in low partial pressures, which overall allows them to better sustain crucial metabolic processes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4577", "text": "Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the  mitochondria  and the  cytosol  of immature red blood cells, while the  globin  protein parts are synthesized by  ribosomes  in the cytosol. [ 41 ]  Production of Hb continues in the cell throughout its early development from the  proerythroblast  to the  reticulocyte  in the  bone marrow . At this point, the  nucleus  is lost in mammalian red blood cells, but not in  birds  and many other species. Even after the loss of the nucleus in mammals, residual  ribosomal RNA  allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering the  vasculature  (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4578", "text": "Hemoglobin has a  quaternary structure  characteristic of many multi-subunit globular proteins. [ 43 ]  Most of the amino acids in hemoglobin form  alpha helices , and these helices are connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within the molecule, which then causes each polypeptide chain to fold into a specific shape. [ 44 ]  Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4579", "text": "In most vertebrates, the hemoglobin  molecule  is an assembly of four  globular protein  subunits. Each subunit is composed of a protein chain tightly associated with a non-protein  prosthetic   heme  group. Each protein chain arranges into a set of  alpha-helix  structural segments connected together in a  globin fold  arrangement. Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as  myoglobin . [ 45 ] [ 46 ]  This folding pattern contains a pocket that strongly binds the heme group. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4580", "text": "A heme group consists of an iron (Fe)  ion  held in a  heterocyclic  ring, known as a  porphyrin . This porphyrin ring consists of four  pyrrole  molecules cyclically linked together (by  methine  bridges) with the iron ion bound in the center. [ 47 ]  The iron ion, which is the site of oxygen binding, coordinates with the four  nitrogen  atoms in the center of the ring, which all lie in one plane. The heme is bound strongly (covalently) to the globular protein via the N atoms of the  imidazole  ring of F8  histidine  residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by a  coordinate covalent bond , [ 48 ]  completing the octahedral group of six ligands. This reversible bonding with oxygen is why hemoglobin is so useful for transporting oxygen around the body. [ 49 ]  Oxygen binds in an \"end-on bent\" geometry where one oxygen atom binds to Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted  octahedron ."}
{"_id": "WikiPedia_Hematology$$$corpus_4581", "text": "Even though carbon dioxide is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the amine groups of the protein chains attached to the heme groups."}
{"_id": "WikiPedia_Hematology$$$corpus_4582", "text": "The iron ion may be either in the  ferrous Fe 2+  or in the  ferric Fe 3+  state, but ferrihemoglobin ( methemoglobin ) (Fe 3+ ) cannot bind oxygen. [ 50 ]  In binding, oxygen temporarily and reversibly oxidizes (Fe 2+ ) to (Fe 3+ ) while oxygen temporarily turns into the  superoxide  ion, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe 3+  is protonated, the hemoglobin iron will remain oxidized and incapable of binding oxygen. In such cases, the enzyme  methemoglobin reductase  will be able to eventually reactivate methemoglobin by reducing the iron center."}
{"_id": "WikiPedia_Hematology$$$corpus_4583", "text": "In adult humans, the most common hemoglobin type is a  tetramer  (which contains four subunit proteins) called  hemoglobin A , consisting of two \u03b1 and two \u03b2 subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This is denoted as \u03b1 2 \u03b2 2 . The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 16,000\u00a0 daltons , [ 51 ]  for a total  molecular weight  of the tetramer of about 64,000\u00a0daltons (64,458 g/mol). [ 52 ]  Thus, 1 g/dL=0.1551\u00a0mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4584", "text": "In human infants, the  fetal hemoglobin  molecule is made up of 2 \u03b1 chains and 2 \u03b3 chains. The \u03b3 chains are gradually replaced by \u03b2 chains as the infant grows. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4585", "text": "The four  polypeptide chains  are bound to each other by  salt bridges ,  hydrogen bonds , and the  hydrophobic effect ."}
{"_id": "WikiPedia_Hematology$$$corpus_4586", "text": "In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin). [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4587", "text": "Oxyhemoglobin  is formed during  physiological respiration  when oxygen binds to the heme component of the protein hemoglobin in red blood cells. This process occurs in the  pulmonary capillaries  adjacent to the  alveoli  of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized as a terminal electron acceptor in the production of  ATP  by the process of  oxidative phosphorylation . It does not, however, help to counteract a decrease in blood pH.  Ventilation , or breathing, may reverse this condition by removal of  carbon dioxide , thus causing a shift up in pH. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4588", "text": "Hemoglobin exists in two forms, a  taut (tense) form  (T) and a  relaxed form  (R). Various factors such as low pH, high CO 2  and high  2,3 BPG  at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely, a high pH, low CO 2 , or low 2,3 BPG favors the relaxed form, which can better bind oxygen. [ 56 ]  The partial pressure of the system also affects O 2  affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state is favoured. [ 57 ]  Additionally, the binding of oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4589", "text": "Classically, the iron in oxyhemoglobin is seen as existing in the iron(II) oxidation state. However, the complex of oxygen with heme iron is  diamagnetic , whereas both oxygen and high-spin iron(II) are  paramagnetic . Experimental evidence strongly suggests heme iron is in the iron(III) oxidation state in oxyhemoglobin, with the oxygen existing as  superoxide anion  (O 2 \u2022\u2212 ) or in a covalent charge-transfer complex. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4590", "text": "Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The  absorption spectra  of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of the 660\u00a0nm  wavelength  than deoxyhemoglobin, while at 940\u00a0nm its absorption is slightly higher. This difference is used for the measurement of the amount of oxygen in a patient's blood by an instrument called a  pulse oximeter . This difference also accounts for the presentation of  cyanosis , the blue to purplish color that tissues develop during  hypoxia . [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4591", "text": "Deoxygenated hemoglobin is  paramagnetic ; it is weakly attracted to  magnetic fields . [ 60 ] [ 61 ]  In contrast, oxygenated hemoglobin exhibits  diamagnetism , a weak repulsion from a magnetic field. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4592", "text": "Scientists agree that the event that separated myoglobin from hemoglobin occurred after  lampreys  diverged from  jawed vertebrates . [ 62 ]  This separation of myoglobin and hemoglobin allowed for the different functions of the two molecules to arise and develop: myoglobin has more to do with oxygen storage while hemoglobin is tasked with oxygen transport. [ 63 ]  The \u03b1- and \u03b2-like globin genes encode the individual subunits of the protein. [ 30 ]  The predecessors of these genes arose through another duplication event also after the gnathosome common ancestor derived from jawless fish, approximately 450\u2013500\u00a0million years ago. [ 62 ]  Ancestral reconstruction studies suggest that the preduplication ancestor of the \u03b1 and \u03b2 genes was a dimer made up of identical globin subunits, which then evolved to assemble into a tetrameric architecture after the duplication. [ 64 ]  The development of \u03b1 and \u03b2 genes created the potential for hemoglobin to be composed of multiple distinct subunits, a physical composition central to hemoglobin's ability to transport oxygen. Having multiple subunits contributes to hemoglobin's ability to bind oxygen cooperatively as well as be regulated allosterically. [ 63 ] [ 64 ]  Subsequently, the \u03b1 gene also underwent a duplication event to form the  HBA1  and  HBA2  genes. [ 65 ]  These further duplications and divergences have created a diverse range of \u03b1- and \u03b2-like globin genes that are regulated so that certain forms occur at different stages of development. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4593", "text": "Most ice fish of the family  Channichthyidae  have lost their hemoglobin genes as an adaptation to cold water. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4594", "text": "When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the  porphyrin  ring (see moving diagram). At the same time, the  imidazole  side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier."}
{"_id": "WikiPedia_Hematology$$$corpus_4595", "text": "As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes the binding of oxygen to the remaining three monomers' heme groups, thus saturating the hemoglobin molecule with oxygen. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4596", "text": "In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a  cooperative process . The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for the next ones, in a way favorable for binding. This positive cooperative binding is achieved through  steric  conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is  sigmoidal , or  S -shaped, as opposed to the normal  hyperbolic  curve associated with noncooperative binding."}
{"_id": "WikiPedia_Hematology$$$corpus_4597", "text": "The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency  resonance  has been discussed. [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4598", "text": "Besides the oxygen  ligand , which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include  competitive inhibitors  such as  carbon monoxide  (CO) and  allosteric ligands  such as carbon dioxide (CO 2 ) and  nitric oxide  (NO). The carbon dioxide is bound to amino groups of the globin proteins to form  carbaminohemoglobin ; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals.  Nitric oxide  can also be transported by hemoglobin; it is bound to specific  thiol  groups in the globin protein to form an S-nitrosothiol, which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues is hypothesized to assist oxygen transport in tissues, by releasing  vasodilatory  nitric oxide to tissues in which oxygen levels are low. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4599", "text": "The binding of oxygen is affected by molecules such as carbon monoxide (for example, from  tobacco smoking ,  exhaust gas , and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin's binding affinity for CO is 250 times greater than its affinity for oxygen, [ 69 ] [ 70 ]  Since carbon monoxide is a colorless, odorless and tasteless gas, and poses a potentially fatal threat,  carbon monoxide detectors  have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called  carboxyhemoglobin , which may cause the skin of  CO poisoning  victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%,  headache  and  nausea  occur; if the CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO."}
{"_id": "WikiPedia_Hematology$$$corpus_4600", "text": "In similar fashion, hemoglobin also has competitive binding affinity for  cyanide  (CN \u2212 ),  sulfur monoxide  (SO), and  sulfide  (S 2\u2212 ), including  hydrogen sulfide  (H 2 S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity."}
{"_id": "WikiPedia_Hematology$$$corpus_4601", "text": "The iron atom in the heme group must initially be in the  ferrous  (Fe 2+ ) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the  ferric  (Fe 3+ ) state without oxygen converts hemoglobin into \"hem i globin\" or  methemoglobin , which cannot bind oxygen. Hemoglobin in normal red blood cells is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient  nitric oxide dioxygenase  function of globins."}
{"_id": "WikiPedia_Hematology$$$corpus_4602", "text": "Carbon  di oxide occupies a different binding site on the hemoglobin. At tissues, where carbon dioxide concentration is higher, carbon dioxide binds to allosteric site of hemoglobin, facilitating unloading of oxygen from hemoglobin and ultimately its removal from the body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the  Bohr effect . Through the enzyme  carbonic anhydrase , carbon dioxide reacts with water to give  carbonic acid , which decomposes into  bicarbonate  and  protons :"}
{"_id": "WikiPedia_Hematology$$$corpus_4603", "text": "Hence, blood with high carbon dioxide levels is also lower in  pH  (more  acidic ). Hemoglobin can bind protons and carbon dioxide, which causes a conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the \u03b1-amino group. [ 71 ]  Carbon dioxide binds to hemoglobin and forms  carbaminohemoglobin . [ 72 ]  This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the  Bohr effect . The Bohr effect favors the T state rather than the R state. (shifts the O 2 -saturation curve to the  right ). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the  root effect . This is seen in bony fish."}
{"_id": "WikiPedia_Hematology$$$corpus_4604", "text": "It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O 2  in lungs), and efficient in unloading (unloading O 2  in tissues). [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4605", "text": "In people acclimated to high altitudes, the concentration of  2,3-Bisphosphoglycerate  (2,3-BPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower  oxygen tension . This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a  heterotropic  allosteric effect. Hemoglobin in organisms at high altitudes has also adapted such that it has less of an affinity for 2,3-BPG and so the protein will be shifted more towards its R state. In its R state, hemoglobin will bind oxygen more readily, thus allowing organisms to perform the necessary metabolic processes when oxygen is present at low partial pressures. [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4606", "text": "Animals other than humans use different molecules to bind to hemoglobin and change its O 2  affinity under unfavorable conditions. Fish use both  ATP  and  GTP . These bind to a phosphate \"pocket\" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity. [ 75 ]  GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra  hydrogen bond  formed that further stabilizes the tense state. [ 76 ]  Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity. [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4607", "text": "A variant hemoglobin, called  fetal hemoglobin  (HbF, \u03b1 2 \u03b3 2 ), is found in the developing  fetus , and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the  placenta  is able to take oxygen from maternal blood."}
{"_id": "WikiPedia_Hematology$$$corpus_4608", "text": "Hemoglobin also carries  nitric oxide  (NO) in the globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting S-nitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO is not released in the cytoplasm of red blood cells but transported out of them by an anion exchanger called  AE1 . [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4609", "text": "Hemoglobin variants  are a part of the normal  embryonic  and  fetal  development. They may also be pathologic mutant forms of hemoglobin in a  population , caused by variations in genetics. Some well-known hemoglobin variants, such as  sickle-cell anemia , are responsible for diseases and are considered  hemoglobinopathies . Other variants cause no detectable  pathology , and are thus considered non-pathological variants. [ 34 ] [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4610", "text": "In  embryos :"}
{"_id": "WikiPedia_Hematology$$$corpus_4611", "text": "In fetuses:"}
{"_id": "WikiPedia_Hematology$$$corpus_4612", "text": "In  neonates  (newborns inmmediately after birth):"}
{"_id": "WikiPedia_Hematology$$$corpus_4613", "text": "Abnormal forms that occur in diseases:"}
{"_id": "WikiPedia_Hematology$$$corpus_4614", "text": "When  red blood cells  reach the end of their life due to aging or defects, they are removed from the circulation by the phagocytic activity of macrophages in the spleen or the liver or hemolyze within the circulation.  Free hemoglobin  is then cleared from the circulation via the hemoglobin transporter  CD163 , which is exclusively expressed on monocytes or macrophages. Within these cells the hemoglobin molecule is broken up, and the iron gets recycled. This process also produces one molecule of carbon monoxide for every molecule of heme degraded. [ 80 ]  Heme degradation is the only natural source of carbon monoxide in the human body, and is responsible for the normal blood levels of carbon monoxide in people breathing normal air. [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4615", "text": "The other major final product of heme degradation is  bilirubin . Increased levels of this chemical are detected in the blood if red blood cells are being destroyed more rapidly than usual. Improperly degraded hemoglobin protein or hemoglobin that has been released from the blood cells too rapidly can clog small blood vessels, especially the delicate blood filtering vessels of the  kidneys , causing kidney damage. Iron is removed from heme and salvaged for later use, it is stored as hemosiderin or  ferritin  in tissues and transported in plasma by beta globulins as  transferrins . When the porphyrin ring is broken up, the fragments are normally secreted as a yellow pigment called bilirubin, which is secreted into the intestines as bile. Intestines metabolize bilirubin into urobilinogen. Urobilinogen leaves the body in faeces, in a pigment called stercobilin. Globulin is metabolized into amino acids that are then released into circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_4616", "text": "Hemoglobin deficiency can be caused either by a decreased amount of hemoglobin molecules, as in  anemia , or by decreased ability of each molecule to bind oxygen at the same partial pressure of oxygen.  Hemoglobinopathies  (genetic defects resulting in abnormal structure of the hemoglobin molecule) [ 82 ]  may cause both. In any case, hemoglobin deficiency decreases  blood oxygen-carrying capacity . Hemoglobin deficiency is, in general, strictly distinguished from  hypoxemia , defined as decreased  partial pressure  of oxygen in blood, [ 83 ] [ 84 ] [ 85 ] [ 86 ]  although both are causes of  hypoxia  (insufficient oxygen supply to tissues)."}
{"_id": "WikiPedia_Hematology$$$corpus_4617", "text": "Other common causes of low hemoglobin include loss of blood, nutritional deficiency, bone marrow problems, chemotherapy, kidney failure, or abnormal hemoglobin (such as that of sickle-cell disease)."}
{"_id": "WikiPedia_Hematology$$$corpus_4618", "text": "The ability of each hemoglobin molecule to carry oxygen is normally modified by altered blood pH or CO 2 , causing an altered  oxygen\u2013hemoglobin dissociation curve . However, it can also be pathologically altered in, e.g.,  carbon monoxide poisoning ."}
{"_id": "WikiPedia_Hematology$$$corpus_4619", "text": "Decrease of hemoglobin, with or without an absolute decrease of red blood cells, leads to symptoms of anemia. Anemia has many different causes, although  iron deficiency  and its resultant  iron deficiency anemia  are the most common causes in the Western world. As absence of iron decreases heme synthesis, red blood cells in iron deficiency anemia are  hypochromic  (lacking the red hemoglobin pigment) and  microcytic  (smaller than normal). Other anemias are rarer. In  hemolysis  (accelerated breakdown of red blood cells), associated  jaundice  is caused by the hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause  kidney failure ."}
{"_id": "WikiPedia_Hematology$$$corpus_4620", "text": "Some mutations in the globin chain are associated with the  hemoglobinopathies , such as sickle-cell disease and  thalassemia . Other mutations, as discussed at the beginning of the article, are benign and are referred to merely as  hemoglobin variants ."}
{"_id": "WikiPedia_Hematology$$$corpus_4621", "text": "There is a group of genetic disorders, known as the  porphyrias  that are characterized by errors in metabolic pathways of heme synthesis. King  George III of the United Kingdom  was probably the most famous porphyria sufferer."}
{"_id": "WikiPedia_Hematology$$$corpus_4622", "text": "To a small extent, hemoglobin A slowly combines with  glucose  at the terminal valine (an alpha aminoacid) of each \u03b2 chain. The resulting molecule is often referred to as  Hb A 1c , a  glycated hemoglobin . The binding of glucose to amino acids in the hemoglobin takes place spontaneously (without the help of an enzyme) in many proteins, and is not known to serve a useful purpose. However, as the concentration of glucose in the blood increases, the percentage of Hb A that turns into Hb A 1c  increases. In  diabetics  whose glucose usually runs high, the percent Hb A 1c  also runs high. Because of the slow rate of Hb A combination with glucose, the Hb A 1c  percentage reflects a weighted average of blood glucose levels over the lifetime of red cells, which is approximately 120 days. [ 87 ]  The levels of glycated hemoglobin are therefore measured in order to monitor the long-term control of the chronic disease of type 2 diabetes mellitus (T2DM). Poor control of T2DM results in high levels of glycated hemoglobin in the red blood cells. The normal reference range is approximately 4.0\u20135.9%. Though difficult to obtain, values less than 7% are recommended for people with T2DM. Levels greater than 9% are associated with poor control of the glycated hemoglobin, and levels greater than 12% are associated with very poor control. Diabetics who keep their glycated hemoglobin levels close to 7% have a much better chance of avoiding the complications that may accompany diabetes (than those whose levels are 8% or higher). [ 88 ]  In addition, increased glycated of hemoglobin increases its affinity for oxygen, therefore preventing its release at the tissue and inducing a level of hypoxia in extreme cases. [ 89 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4623", "text": "Elevated levels of hemoglobin are associated with increased numbers or sizes of red blood cells, called  polycythemia . This elevation may be caused by  congenital heart disease ,  cor pulmonale ,  pulmonary fibrosis , too much  erythropoietin , or  polycythemia vera . [ 90 ]  High hemoglobin levels may also be caused by exposure to high altitudes, smoking, dehydration (artificially by concentrating Hb), advanced lung disease and certain tumors. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4624", "text": "Hemoglobin concentration measurement is among the most commonly performed  blood tests , usually as part of a  complete blood count . For example, it is typically tested before or after  blood donation . Results are reported in  g / L , g/ dL  or  mol /L. 1 g/dL equals about 0.6206\u00a0mmol/L, although the latter units are not used as often due to uncertainty regarding the polymeric state of the molecule. [ 91 ]  This conversion factor, using the single globin unit molecular weight of 16,000  Da , is more common for hemoglobin concentration in blood. For MCHC (mean corpuscular hemoglobin concentration) the conversion factor 0.155, which uses the tetramer weight of 64,500 Da, is more common. [ 92 ]  Normal levels are:"}
{"_id": "WikiPedia_Hematology$$$corpus_4625", "text": "Normal values of hemoglobin in the 1st and 3rd trimesters of pregnant women must be at least 11 g/dL and at least 10.5 g/dL during the 2nd trimester. [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4626", "text": "Dehydration or hyperhydration can greatly influence measured hemoglobin levels. Albumin can indicate hydration status."}
{"_id": "WikiPedia_Hematology$$$corpus_4627", "text": "If the concentration is below normal, this is called anemia. Anemias are classified by the size of red blood cells, the cells that contain hemoglobin in vertebrates. The anemia is called \"microcytic\" if red cells are small, \"macrocytic\" if they are large, and \"normocytic\" otherwise."}
{"_id": "WikiPedia_Hematology$$$corpus_4628", "text": "Hematocrit , the proportion of blood volume occupied by red blood cells, is typically about three times the hemoglobin concentration measured in g/dL. For example, if the hemoglobin is measured at 17 g/dL, that compares with a hematocrit of 51%. [ 96 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4629", "text": "Laboratory hemoglobin test methods require a blood sample (arterial, venous, or capillary) and analysis on hematology analyzer and CO-oximeter. Additionally, a new noninvasive hemoglobin (SpHb) test method called Pulse CO-Oximetry is also available with comparable accuracy to invasive methods. [ 97 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4630", "text": "Concentrations of oxy- and deoxyhemoglobin can be measured continuously, regionally and noninvasively using  NIRS . [ 98 ] [ 99 ] [ 100 ] [ 101 ] [ 102 ]  NIRS can be used both on the head and on muscles. This technique is often used for research in e.g. elite sports training, ergonomics, rehabilitation, patient monitoring, neonatal research, functional brain monitoring,  brain\u2013computer interface , urology (bladder contraction), neurology (Neurovascular coupling) and more."}
{"_id": "WikiPedia_Hematology$$$corpus_4631", "text": "Hemoglobin mass can be measured in humans using the non-radioactive, carbon monoxide (CO) rebreathing technique that has been used for more than 100 years. With this technique, a small volume of pure CO gas is inhaled and rebreathed for a few minutes. During rebreathing, CO binds to hemoglobin present in red blood cells. Based on the increase in blood CO after the rebreathing period, the hemoglobin mass can be determined through the dilution principle. [ 103 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4632", "text": "Long-term control of  blood sugar  concentration can be measured by the concentration of Hb A 1c . Measuring it directly would require many samples because blood sugar levels vary widely through the day. Hb A 1c  is the product of the  irreversible reaction  of hemoglobin A with glucose. A higher glucose  concentration  results in more Hb A 1c . Because the reaction is slow, the Hb A 1c  proportion represents glucose level in blood averaged over the half-life of red blood cells, is typically ~120 days. An Hb A 1c  proportion of 6.0% or less show good long-term glucose control, while values above 7.0% are elevated. This test is especially useful for diabetics. [ c ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4633", "text": "The  functional magnetic resonance imaging  (fMRI) machine uses the signal from deoxyhemoglobin, which is sensitive to magnetic fields since it is paramagnetic. Combined measurement with  NIRS  shows good correlation with both the oxy- and deoxyhemoglobin signal compared to the  BOLD signal . [ 104 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4634", "text": "Hemoglobin can be tracked noninvasively, to build an individual data set tracking the hemoconcentration and hemodilution effects of daily activities for better understanding of sports performance and training. Athletes are often concerned about endurance and intensity of exercise. The sensor uses light-emitting diodes that emit red and infrared light through the tissue to a light detector, which then sends a signal to a processor to calculate the absorption of light by the hemoglobin protein. [ 105 ]  This sensor is similar to a  pulse oximeter , which consists of a small sensing device that clips to the finger."}
{"_id": "WikiPedia_Hematology$$$corpus_4635", "text": "A variety of oxygen-transport and -binding proteins exist in organisms throughout the animal and plant kingdoms. Organisms including  bacteria ,  protozoans , and  fungi  all have hemoglobin-like proteins whose known and predicted roles include the reversible binding of gaseous  ligands . Since many of these proteins contain  globins  and the heme  moiety  (iron in a flat porphyrin support), they are often called hemoglobins, even if their overall tertiary structure is very different from that of vertebrate hemoglobin. In particular, the distinction of \"myoglobin\" and hemoglobin in lower animals is often impossible, because some of these organisms do not contain  muscles . Or, they may have a recognizable separate  circulatory system  but not one that deals with oxygen transport (for example, many  insects  and other  arthropods ). In all these groups, heme/globin-containing molecules (even monomeric globin ones) that deal with gas-binding are referred to as oxyhemoglobins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO, CO 2 , sulfide compounds, and even O 2  scavenging in environments that must be anaerobic. [ 106 ]  They may even deal with detoxification of chlorinated materials in a way analogous to heme-containing P450 enzymes and peroxidases."}
{"_id": "WikiPedia_Hematology$$$corpus_4636", "text": "The structure of hemoglobins varies across species. Hemoglobin occurs in all kingdoms of organisms, but not in all organisms. Primitive species such as bacteria, protozoa,  algae , and  plants  often have single-globin hemoglobins. Many  nematode  worms,  molluscs , and  crustaceans  contain very large multisubunit molecules, much larger than those in vertebrates. In particular, chimeric hemoglobins found in  fungi  and giant  annelids  may contain both globin and other types of proteins. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4637", "text": "One of the most striking occurrences and uses of hemoglobin in organisms is in the  giant tube worm  ( Riftia pachyptila , also called Vestimentifera), which can reach 2.4 meters length and populates ocean  volcanic vents . Instead of a  digestive tract , these worms contain a population of bacteria constituting half the organism's weight. The bacteria oxidize H 2 S from the vent with O 2  from the water to produce energy to make food from H 2 O and CO 2 . The worms' upper end is a deep-red fan-like structure (\"plume\"), which extends into the water and absorbs H 2 S and O 2  for the bacteria, and CO 2  for use as synthetic raw material similar to photosynthetic plants. The structures are bright red due to their content of several extraordinarily complex hemoglobins that have up to 144 globin chains, each including associated heme structures. These hemoglobins are remarkable for being able to carry oxygen in the presence of sulfide, and even to carry sulfide, without being completely \"poisoned\" or inhibited by it as hemoglobins in most other species are. [ 107 ] [ 108 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4638", "text": "Some nonerythroid cells (i.e., cells other than the red blood cell line) contain hemoglobin. In the brain, these include the A9  dopaminergic  neurons in the  substantia nigra ,  astrocytes  in the  cerebral cortex  and  hippocampus , and in all mature  oligodendrocytes . [ 12 ]  It has been suggested that brain hemoglobin in these cells may enable the \"storage of oxygen to provide a homeostatic mechanism in anoxic conditions, which is especially important for A9 DA neurons that have an elevated metabolism with a high requirement for energy production\". [ 12 ]  It has been noted further that \"A9  dopaminergic  neurons may be at particular risk of anoxic degeneration since in addition to their high mitochondrial activity they are under intense oxidative stress caused by the production of hydrogen peroxide via autoxidation and/or monoamine oxidase (MAO)-mediated deamination of dopamine and the subsequent reaction of accessible ferrous iron to generate highly toxic hydroxyl radicals\". [ 12 ]  This may explain the risk of degeneration of these cells in  Parkinson's disease . [ 12 ]  The hemoglobin-derived iron in these cells is not the cause of the post-mortem darkness of these cells (origin of the Latin name, substantia  nigra ), but rather is due to  neuromelanin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4639", "text": "Outside the brain, hemoglobin has non-oxygen-carrying functions as an  antioxidant  and a regulator of  iron metabolism  in  macrophages , [ 109 ]   alveolar cells , [ 110 ]  and  mesangial cells  in the kidney. [ 111 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4640", "text": "Historically, an association between the color of blood and rust occurs in the association of the planet  Mars , with the Roman god of war, since the planet is an orange-red, which reminded the ancients of blood. Although the color of the planet is due to iron compounds in combination with oxygen in the Martian soil, it is a common misconception that the iron in hemoglobin and its oxides gives blood its red color. The color is actually due to the  porphyrin   moiety  of hemoglobin to which the iron is bound, not the iron itself, [ 112 ]  although the ligation and redox state of the iron can influence the pi to pi* or n to pi* electronic transitions of the porphyrin and hence its optical characteristics."}
{"_id": "WikiPedia_Hematology$$$corpus_4641", "text": "Artist  Julian Voss-Andreae  created a  sculpture  called  Heart of Steel (Hemoglobin)  in 2005, based on the protein's backbone. The sculpture was made from glass and  weathering steel . The intentional rusting of the initially shiny work of art mirrors hemoglobin's fundamental chemical reaction of oxygen binding to iron. [ 113 ] [ 114 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4642", "text": "Montreal artist Nicolas Baier created  Lustre (H\u00e9moglobine) , a sculpture in stainless steel that shows the structure of the hemoglobin molecule. It is displayed in the atrium of  McGill University Health Centre 's research centre in Montreal. The sculpture measures about 10 metres \u00d7 10 metres \u00d7 10 metres. [ 115 ] [ 116 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4643", "text": "Hemoglobin A  (HbA), also known as  adult hemoglobin, hemoglobin A1  or  \u03b1 2 \u03b2 2 , is the most common human  hemoglobin  tetramer, accounting for over 97% of the total  red blood cell  hemoglobin. [ 1 ]   Hemoglobin  is an oxygen-binding protein, found in  erythrocytes , which transports oxygen from the lungs to the tissues. [ 2 ]   Hemoglobin A is the most common adult form of hemoglobin and exists as a tetramer containing two alpha subunits and two beta subunits (\u03b12\u03b22). [ 3 ]   Hemoglobin A2  (HbA2) is a less common adult form of hemoglobin and is composed of two alpha and two delta-globin subunits. This hemoglobin makes up 1-3% of hemoglobin in adults. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4644", "text": "Hemoglobin A (HbA) is the most common adult form of hemoglobin and exists as a tetramer containing two alpha subunits and two beta subunits (\u03b12\u03b22). [ 3 ]   Each subunit contains a  heme  group that diatomic oxygen (O 2 ) molecules can bind to. [ 5 ]   In addition to oxygen, subunit assembly and quaternary structure are known to play important roles in Hb affinity. When hemoglobin binds to O2 ( oxyhemoglobin ), it will attach to the Iron II (Fe2+) of heme and it is this iron ion that can bind and unbind oxygen to transport oxygen throughout the body. [ 2 ]   All subunits must be present for hemoglobin to pick up and release oxygen under normal conditions. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4645", "text": "Heme  synthesis involves a series of  enzymatic  steps that take place within the  mitochondrion  and  cytosol  of the cell. First, in the mitochondrion, the condensation of  succinyl CoA  and  glycine  by ALA synthase takes place to produce  5-aminolevulinic acid  (ALA). ALA then moves to the cytosol and after a series of reactions creates  coproporphyringen III . This molecule moves back into the mitochondrion where it reacts with protoporphyrin-III oxidase to produce  protoporphyrin IX . Iron is then enzymatically inserted into protoporphyrin via  ferrochelatase  to produce heme. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4646", "text": "Globin synthesis takes place in the  ribosomes  which are located within the cytosol. Two globin chains that have heme groups combine to form hemoglobin. One of the chains is an alpha chain and the other is a non-alpha chain. Non-alpha chain nature in hemoglobin molecules varies due to different variables. Fetuses have a non-alpha chain called gamma and after birth it is then called beta. The beta chain will pair with the alpha chain. It is the combining of two alpha and non-alpha chains which create a hemoglobin molecule. Two alpha and two gamma chains form fetal hemoglobin or  hemoglobin F  (HbF). After the first five to six months after birth, the combining of two alpha chains and two beta chains form adult hemoglobin (HbA). The genes that encode for the alpha chains are located on  chromosome 16 , while the genes that encode for non-alpha chains are located on  chromosome 11 . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4647", "text": "Due to the numerous steps and processes during hemoglobin synthesis, there are many places in which errors can occur. Heme synthesis involves multiple  enzymes  and when these enzymes are deficient or do not function properly consequences such as  mutations  or deletions in genes coding for the globin chain can occur. [ 2 ]  This results in globin gene disorders ( hemoglobinopathies ) which can be either abnormal globin chain variants ( sickle cell anemia ) or reduced chain synthesis in erythroid cells ( thalassemia ) during the cellular process of  hematopoiesis . [ 8 ]  These hemoglobinopathies are often inherited as  autosomal recessive  traits. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4648", "text": "Alpha-thalassemia  (\u03b1-thalassemia) is defined by a lack of \u03b1-globin chain production in hemoglobin, and those who carry a mutation impacting the \u03b1-globin chain on only one  chromosome  are considered to have a \u201csilent\u201d \u03b1-thalassemia whereas, if the mutation is on both then it is considered an \u03b1-thalassemia trait. [ 9 ]   \u03b1-thalassemia is mostly found in sub-tropical and tropical areas, where individuals who carry the gene is 80-90% of the population. [ 10 ]   Like other hemoglobin related disorders (sickle cell and \u03b2-thalassemia), it is hypothesized that \u03b1-thalassemia is selected for within populations due to carriers being better protected against  malaria falciparum . [ 9 ]   Most carriers of \u03b1-thalassemia are  asymptomatic  and are diagnosed if it is found after routine hematological analyses or before birth screenings. [ 11 ]   Single \u03b1-globin gene carriers usually have no profound fatigue or  anemia  because they have a compensating increase in the number of  microcytic  red blood cells. [ 9 ] [ 11 ]  In contrast, mild \u03b1-thalassemia carriers could have symptoms of anemia due to other factors not related specifically to the disorder: poor diet, drop in hemoglobin levels due to blood loss, or other diseases. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4649", "text": "The most severe form of \u03b1 -thalassemia is a condition that begins at infancy in which there is no expression of \u03b1-genes and results in a large production of hemoglobin Bart's  (Hb Bart's) . [ 11 ]   The most common cause of Hb Bart\u2019s is the inheritance of a deletion  allele  in that lacks functional \u03b1-globin genes from both parents. [ 9 ]   Hb Bart\u2019s is a tetramer of four gamma-globulin subunits and is ineffective at transporting oxygen to the tissues due to its very high oxygen affinity. [ 12 ]  This usually results in fatal hydrops fetalis and associated symptoms include intra-uterine anemia, slowing of brain growth,  oedema ,  deformities  of the skeleton, and cardiovascular deformities that could lead to  cardiac failure . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4650", "text": "Beta-thalassemia  (\u03b2-thalassemia) is an inherited mutation of the \u03b2-globulin gene which causes the reduced synthesis of the \u03b2-globin chain of hemoglobin. [ 14 ]   The majority of the mutations are point mutations that affect  translation , transcriptional control, and  splicing  of the hemoglobin \u03b2 gene and gene product. [ 15 ]   Individuals with one gene mutation ( heterozygocity ) are considered to have \u03b2-thalassemia minor (carrier or trait \u03b2-thalassemia), while those who have two gene mutations ( homozygosity  or compound heterozygosity) are diagnosed with \u03b2-thalassemia or intermedia. [ 14 ] [ 2 ]   Due to the lack of  beta-globin , accumulation of alpha-globin subunits and alpha tetramers begin to accumulate leading to damage of erythrocytes. [ 2 ]  People of Asian, Middle Eastern, and Mediterranean descent have a much higher incidences of \u03b2-thalassemia. [ 14 ]   It has been determined that there is a wide variation in  phenotypes  and  genotypes  of the disease due to more than 200 different thalassemia-associated mutations have being found in the beta-globin gene. [ 15 ]   Individuals with \u03b2-thalassemia major usually require medical attention within the first 2 years of life and require regular  blood transfusions  to survive. Patients who present the disorder later usually do not require  transfusions  and are diagnosed with thalassemia intermedia. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4651", "text": "health/health-topics/topics/sca/"}
{"_id": "WikiPedia_Hematology$$$corpus_4652", "text": "Sickle hemoglobin (HbS) is the most common variant of hemoglobin and arises due to an  amino acid  substitution in the beta-globin subunit at the sixth residue from  glutamic acid  to  valine . There are different forms of  sickle cell disease . HB SS which is the most common and severe form of sickle cell. Hb SC is due to inheriting Hb S from one parent and Hb C ( hemoglobin C ) from the other parent. Hb S beta thalassemia is the least common and is experienced in patients who have inherited beta thalassemia hemoglobin from one parent and HbS from the other. [ 17 ]   In addition, there is sickle cell trait (HbAS) which is defined by having HbA and HbS. This makes the individual heterozygous for sickle cell. Of the world population, it is estimated that there are about 300 million individuals with the sickle cell trait and about 100 million of those are in sub-Saharan Africa. [ 18 ]   There is also a higher prevalence of sickle cell trait in areas that malaria is commonly found, with the prevalence in some parts of Africa and Saudi Arabia being as high as 25% and 60%, respectively. [ 19 ]  Individuals who have HbAS have about 40%HbS, 56% HBA, and are usually asymptomatic unless there is a severe lack of oxygen to the body (hypoxia) which can lead to symptoms of sickle cell disease. [ 12 ]   However, HbAS does not cause vaso-occlusive crisis, which is known to be associated with sickle cell disease. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4653", "text": "Patients that are homozygous for HbS have multi-stranded fibers that induce a change in shape of  red blood cells  from  biconcave disks  to elongated crescents. The sickling reaction is reversible after re-oxygenating the hemoglobin, therefore, red blood cells can go through cycles of sickling and unsickling depending on the concentration of oxygen present in the bloodstream. [ 12 ]  Red blood cells that are sickle-shaped lack flexibility and stick to the walls of blood vessels decreasing or stopping the flow of oxygen to nearby tissues. This decrease in oxygen to the tissues cause  vaso-occlusive crisis  which presents itself in muscle pain and injury to tissues. Some symptoms of sickle cell anemia include fever, fatigue from  anemia , swelling of the hands and feet,  stroke , and organ failure. [ 20 ]  Current treatments include  blood transfusions  which aid with increasing the number of normal red blood cells,  bone marrow transplants  to help the patients body produce healthy red blood cells, and medications to help alleviate the symptoms listed previously. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4654", "text": "Hemoglobin"}
{"_id": "WikiPedia_Hematology$$$corpus_4655", "text": "Hemoglobin variants:"}
{"_id": "WikiPedia_Hematology$$$corpus_4656", "text": "Hemoglobin protein subunits (genes):"}
{"_id": "WikiPedia_Hematology$$$corpus_4657", "text": "Hemoglobin A2  ( HbA 2 ) is a normal variant of  hemoglobin A  that consists of two alpha and two  delta chains  (\u03b1 2 \u03b4 2 ) and is found at low levels in normal human  blood .  Hemoglobin A2 may be increased in  beta thalassemia  or in people who are  heterozygous  for the beta thalassemia gene."}
{"_id": "WikiPedia_Hematology$$$corpus_4658", "text": "HbA2 exists in small amounts in all adult humans (1.5\u20133.1% of all hemoglobin molecules) and is approximately normal in people with  sickle-cell disease . [ 1 ]  Its biological importance is not yet known."}
{"_id": "WikiPedia_Hematology$$$corpus_4659", "text": "HbA2 may seem physiologically minor, but it plays a very crucial role in identifying the beta-thalassemia traits, also known as BTT, and identifying other hemoglobin disorders. [ 2 ]  Human hemoglobin is made up of two different chains, this includes alpha-globin and beta-globin. In the blood, there are two different variants, HbA and HbA2, and these variants only differ by 10 amino acids. These two variants have distinctions with the alpha and beta-globin chains. HbA2 is a vital component for screening programs targeting beta-thalassemia and hemoglobin pathogens. Typically the normal HbA2 levels range from 2.1% to 3.2%, but these values may change based on individual factors and different hemoglobin or hematological patterns. [ 3 ]  Testing HbA2 levels can be challenging because different disorders can cause it to have higher or lower values. Testing for the beta-thalassemia trait is usually identified when the value of HbA2 is higher than 3.5%. [ 3 ]  HbA2 is also important for diagnosing sickle cell disease, which is one of the most prevalent genetic conditions. Sickle cell disease exhibits characteristics of either homozygous hemoglobin S, also known as Hb S, or Hb S paired with another hemoglobin variant. In diagnosing patients with sickle cell, HbA2 is taken into account alongside a complete blood count, family history, and clinical data. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4660", "text": "Elevated HbA2 levels that surpass 3.5%, indicate a potential mutation in the beta-globin genes. This potential mutation typically occurs in the -87 and -88 promoter region, which affects the proximal CACCC box. Another factor leading to increased HbA2 levels involves the deletion of bases that are placed adjacent to the beta-globin genes. This deletion results in a heightened HbA2 levels due to removing the locus control regions in the beta promoter. This specific promoter is crucial for gene interactions with both gamma and beta globin genes, which also enables both genes to be expressed. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4661", "text": "Low values of HbA2, defined as 2.1% and below, can stem from various factors. The different reasons for reduced HbA2 levels depend on the factors such as hematological indices, hemoglobin patterns, red blood cells, and iron status. Reports suggest that individuals with low iron levels often exhibit low levels of HbA2. Additionally, low levels of HbA2 may be caused from decreased transcription or translation of the globin chains, which would affect how they bind. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4662", "text": "Hemoglobin pathogens are disorders caused by inherited autosomal recessive genes or hemoglobin structures that have been altered and changed. Autosomal recessive inheritance means acquiring two changed genes from each parent. If both parents are carriers for the autosomal recessive gene, there is a 75% chance the child will be normal and a 25% chance of having and expressing the disorder. There are various autosomal recessive disorders and hemoglobin pathogens, among these, beta-thalassemia is associated with changes in HbA2 levels in our blood. Thalassemia is a disorder involving both alpha and beta globin chains, is characterized by a deficiency in the globin chains within the hemoglobin, not characterized by the structural change to these chains. This deficiency leads to two disorders: beta-thalassemia and alpha-thalassemia. Beta-thalassemia has beta globin chains that are reduced and alpha-thalassemia has alpha globin chains that are also reduced. [ 5 ]  This disorder is the most common autosomal recessive disorder in some countries. [ 6 ]  Hemoglobin A2 is employed to diagnose thalassemia disorders, encompassing both beta and alpha types. In beta-thalassemia, affected individuals express elevated HbA2 levels, which can be a potential indicator of the heterozygous gene marker for the disorder. Normal levels range from 2.1-3.2%, but in the beta-thalassemia disorder, the levels increase to 3.5-6.0%. Additionally, individuals with beta-thalassemia exhibit a high red cell count and low hemoglobin levels. [ 3 ]  Individuals that express lower levels of hemoglobin A2, have the a 0 -thalassemia trait or homozygous gene for a + -thalassemia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4663", "text": "Hemoglobin A2 is a crucial role for screening and measuring for the beta-thalassemia trait. Various laboratory methods exist, each providing different outcomes of accuracy. The different quantification methods of HbA2 relies on how effective it can be separated from other hemoglobin variants. [ 3 ]  Various laboratory methods are employed, such as cation exchange high-performance liquid chromatography (HPLC), microcolumn chromatography, and cellulose acetate electrophoresis with elution. At first, cellulose acetate electrophoresis was utilized to measure HbA2, but this process proved to be too time-consuming and labor-intensive, making it impractical for large examinations or samples. Similar efficiency issues were encountered with other methods like IEF and scanning densitometry. These two methods separate proteins based on their isoelectric point. Chromatography, another commonly used method, demonstrated reliability in diagnosing individuals with the beta carrier gene. However, this method was also time-consuming and inefficient when dealing with large sample numbers. [ 3 ]  Out of the various methods, the one that accurately measures HbA2 is HPLC. [ 2 ]  It is a reliable technique because it's able to accurately determine HbA2, HbF, and Hb variants. The various different Hb variants include: HbS, HbE, Hb Lepore, HbC,  HbD  and HbO-Arab. [ 3 ]  There are several different factors that can contribute to the quantification of HbA2 to be inaccurately measured. These factors include column defects, batch variations, sample concentrations, dilution, calibration discrepancies, and the overall conditions of the samples. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4664", "text": "Hemoglobin A3  is a predominantly historic term for a fraction of normal hemoglobin molecules that is seen when hemoglobin is separated out using starch block electrophoresis. These Hemoglobin molecules are non-enzymatic modifications of the hemoglobin molecules and they encompass  hemoglobin A1c , Hb 1a  (both the subtypes Hb 1a1  and Hb 1a2 ) and Hb 1b . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4665", "text": "As these Hemoglobin subtypes are formed over time, they are found more prevalent in older red cells."}
{"_id": "WikiPedia_Hematology$$$corpus_4666", "text": "This  cell biology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4667", "text": "Hemoglobin Barts , abbreviated  Hb Barts , is an abnormal type of  hemoglobin  that consists of four  gamma globins . It is moderately insoluble, and therefore accumulates in the  red blood cells . Hb Barts has an extremely  high affinity for oxygen , so it cannot release oxygen to the tissue. Therefore, this makes it an inefficient oxygen carrier. As an  embryo  develops, it begins to produce alpha-globins at  weeks 5\u20136 of development . When both of the  HBA1  and  HBA2  genes which code for alpha globins becomes dysfunctional, the affected fetuses will have difficulty in synthesizing a functional hemoglobin. As a result, gamma chains will accumulate and form four gamma globins. These gamma globins bind to form hemoglobin Barts. [ 1 ]  It is produced in the disease  alpha-thalassemia  and in the most severe of cases, it is the only form of hemoglobin in circulation. In this situation, a fetus will develop  hydrops fetalis  and normally die before or shortly after birth, unless intrauterine  blood transfusion  is performed. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4668", "text": "Since hemoglobin Barts is elevated in alpha thalassemia, it can be measured, providing a useful screening test for this disease in some populations. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4669", "text": "The ability to measure hemoglobin Barts makes it useful in newborn screening tests.  If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or  hemoglobin H disease  (three alpha globin gene deletions).  Deletion of four alpha globin genes was previously felt to be  incompatible with life , but there are currently 69 patients who have survived past infancy. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4670", "text": "Table 1: \u03b1 represents the presence of \u03b1-globin gene and- represents the deletion of \u03b1-globin gene. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4671", "text": "The chance of a fetus developing Hemoglobin Bart's hydrops fetalis is dependent upon if one or both parent carries the alpha-thalassemia trait. Due to this disease being incompatible with life, diagnosis for it is done prenatally. [ 7 ]  Early detection of Hemoglobin (Hb) Bart's disease before the development of hydrops fetalis is crucial because fetuses that develop hydrops fetalis will either be stillborn or may die shortly after birth. There can be early pregnancy termination to prevent serious complications for the baby or mother. Studies shows that in 11 to 14\u2009weeks of gestation, sonographic markers can associate affected from unaffected pregnancies. It was found that the most sensitive marker was CT ratio and MCA\u2010PSV. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4672", "text": "Parents at risk of having a child with Fetal Hydrops can continue their pregnancy with regular ultrasounds and intrauterine blood transfusion. Babies of such parents are born with no edema or major neurological defects, and eventually, this disease can be cured with  Haematopoietic Stem Cell Transplantation . A newly developed diagnostic test, called Immunochromatography (IC) Strip Tests, uses monoclonal antibodies to detect Hemoglobin Barts in red blood cells' lysate. This diagnostic test is validated for positive and negative predictive values. It is also cheap and easy, making regular screening for alpha-thalassemia a plausible possibility. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4673", "text": "Anemia is a factor in fetuses with Hemoglobin Bart's disease as there is an \"increased cardiac output\" and hypovolemia as the tissues of the fetus require oxygen because of the gamma globulin's high affinity for oxygen. This deprives the tissues of receiving oxygen to function well. The symptoms of anemia occur within the first trimester. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4674", "text": "This variant of hemoglobin is so called as it was discovered at  St Bartholomew's Hospital  in London, often abbreviated to Barts. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4675", "text": "Hemoglobin Constant Spring  is a  variant  of  hemoglobin  in which a  mutation  in the  alpha globin   gene  produces an alpha globin chain that is abnormally long. It is the most common nondeletional  alpha-thalassemia  mutation associated with  hemoglobin H  disease. [ 1 ]  The quantity of hemoglobin in the cells is low because the  messenger RNA  is unstable and some is degraded prior to protein synthesis. Another reason is that the Constant Spring alpha chain protein is itself unstable. The result is a thalassemic phenotype. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4676", "text": "Hemoglobin Constant Spring is renamed after  Constant Spring district  in  Jamaica . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4677", "text": "Within the medical specialty of  hematology ,  Hemoglobin D-Punjab , also known as  hemoglobin D-Los Angeles , [ 1 ]   D-North Carolina ,  D-Portugal ,  D-Oak Ridge , and  D-Chicago , [ 2 ]  is a  hemoglobin variant . It originates from a  point mutation  in the  human \u03b2-globin locus  and is one of the most common hemoglobin variants worldwide. [ 1 ]  It is so named because of its higher prevalence in the  Punjab region  of  India  and  Pakistan , along with northern China, and North America. It is also the most frequent hemoglobin variant in  Xinjiang Uyghur Autonomous Region  of  China , with a 1997 study indicating that Hemoglobin D-Punjab accounts for 55.6% of the total hemoglobin variants. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4678", "text": "Hemoglobin D is a result of a mutation in the one or both of the Beta-chains that make up hemoglobin molecules.  Having one gene effected is referred to as trait; having two is referred to as homozygous \"disease\" although the symptoms of this disease are mild."}
{"_id": "WikiPedia_Hematology$$$corpus_4679", "text": "Until the early 1950s,  hemoglobin A  and some of its variants had been identified, such as  hemoglobin S  and  hemoglobin C . Hemoglobin D was discovered in 1951 with one source stating it was the third variant discovered, [ 2 ]  and another source claiming it was the fourth. [ 1 ]  Later in 1962, it was found that five other regional variants of hemoglobin D all had the same chemical structure termed hemoglobin D-Punjab. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4680", "text": "Hemoglobin is the main ingredient in red blood cells. Hemoglobin helps red blood cells carry oxygen from the lungs to other parts of the body. Normal red blood cells have hemoglobin A. People with hemoglobin D trait have red blood cells that have normal hemoglobin A (made up of normal alpha and beta chains) and abnormal hemoglobin D (made up of normal alpha chains and variant beta chains). People with hemoglobin D trait have slightly more hemoglobin A than hemoglobin D. The abnormal hemoglobin is called hemoglobin D. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4681", "text": "People with Hemoglobin D trait do not have health problems related to having the trait. People with hemoglobin D trait do not have Hemoglobin D  disease  or  sickle cell disease . They cannot develop these diseases later in life. While Hemoglobin D can be detected without a DNA test, one is needed to ascertain that a person who carries Hemoglobin D carries hemoglobin D-Punjab. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4682", "text": "There is no clinical disease detected, however children of affected individuals have increased risk of having Hemoglobin D Disease, Hemoglobin SD disease or  Beta-thalassemia  Disease. [ citation needed ]  Among the seven known types of Hemoglobin D, only Hemoglobin D Punjab can cause a serious hemoglobin disorder."}
{"_id": "WikiPedia_Hematology$$$corpus_4683", "text": "usually present with mild hemolytic anemia and mild to moderate splenomegaly."}
{"_id": "WikiPedia_Hematology$$$corpus_4684", "text": "Even homozygous Hemoglobin D disease does not typically cause clinically significant symptoms. It is usually present with mild haemolytic  anaemia  and moderate  splenomegaly . [ 4 ]  The anemia usually occurs in the first few months of life, as fetal hemoglobin decreases and hemoglobin D increases. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4685", "text": "Hb D-Punjab becomes significant when it is co-inherited with Hb S or B thalassemia."}
{"_id": "WikiPedia_Hematology$$$corpus_4686", "text": "1. Tyagi S, Marwaha N, Parmar V, Basu S. Sickle cell hemoglobin-D Punjab disease (Compound Heterozygous state). Ind J Hematol Blood Transf 2000;18:31-2.\n2.  Zeng YT, Huang SZ, Ren ZR, Li HJ (1989).  \"Identification of Hb D-Punjab gene: application of DNA amplification in the study of abnormal hemoglobins\" .  Am. J. Hum. Genet .  44  (6):  886\u2013 9.  PMC \u00a0 1715661 .  PMID \u00a0 2729278 . \n3.  http://www.idph.state.il.us/HealthWellness/fs/hemoglobin_d.htm \n4.  http://health.utah.gov/newbornscreening/Disorders/HB/Hb_D_Disease_DD/FactSheet_Provider_HbDD_En.pdf \n5. www.chime.ucl.ac.uk/APoGI/data/rtf/hb/carriers/b/dp/carbook.rtf"}
{"_id": "WikiPedia_Hematology$$$corpus_4687", "text": "Hemoglobin E  ( HbE ) is an abnormal  hemoglobin  with a single point  mutation  in the \u03b2 chain. At position 26 there is a change in the  amino acid , from  glutamic acid  to  lysine  (E26K). Hemoglobin E is very common among people of  Southeast Asian ,  Northeast Indian ,  Sri Lankan  and  Bangladeshi  descent. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4688", "text": "The \u03b2E mutation affects \u03b2-gene expression creating an alternate splicing site in the mRNA at codons 25-27 of the \u03b2-globin gene. Through this mechanism, there is a mild deficiency in normal \u03b2 mRNA and production of small amounts of anomalous \u03b2 mRNA. The reduced synthesis of \u03b2 chain may cause  \u03b2-thalassemia . Also, this hemoglobin variant has a weak union between \u03b1- and \u03b2-globin, causing instability when there is a high amount of oxidant. [ 3 ]  HbE can be detected on  electrophoresis ."}
{"_id": "WikiPedia_Hematology$$$corpus_4689", "text": "Hemoglobin E disease results when the offspring inherits the gene for HbE from both parents. At birth, babies  homozygous  for the hemoglobin E allele do not present symptoms because they still have HbF ( fetal hemoglobin ). In the first months of life, fetal hemoglobin disappears and the amount of hemoglobin E increases, so the subjects start to have a mild \u03b2-thalassemia.\nSubjects homozygous for the hemoglobin E allele (two abnormal alleles) have a mild hemolytic anemia and mild  enlargement of the spleen ."}
{"_id": "WikiPedia_Hematology$$$corpus_4690", "text": "Heterozygous  AE occurs when the gene for hemoglobin E is inherited from one parent and the gene for hemoglobin A from the other. This is called hemoglobin E trait, and it is not a disease. People who have hemoglobin E trait (heterozygous) are asymptomatic and their state does not usually result in health problems. They may have a low  mean corpuscular volume  (MCV) and very abnormal red blood cells ( target cells ), but clinical relevance is mainly due to the potential for transmitting E or \u03b2-thalassemia. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4691", "text": "Compound heterozygotes with sickle-hemoglobin E disease result when the gene of hemoglobin E is inherited from one parent and the gene for hemoglobin S from the other. As the amount of fetal hemoglobin decreases and hemoglobin S increases, a mild hemolytic anemia appears in the early stage of development. Patients with this disease experience some of the symptoms of  sickle cell anemia , including mild-moderate anemia, increased risk of infection, and painful sickling crises. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4692", "text": "People who have hemoglobin E/\u03b2-thalassemia have inherited one gene for hemoglobin E from one parent and one gene for \u03b2-thalassemia from the other parent. Hemoglobin E/\u03b2-thalassemia is a severe disease, and it still has no universal cure. However, the mutation is amenable to genome editing at high efficiency in preclinical studies. [ 6 ]  It affects more than a million people in the world. [ 7 ]  Symptoms of hemoglobin E/\u03b2-thalassemia vary but can include growth retardation, enlargement of the spleen ( splenomegaly ) and liver ( hepatomegaly ),  jaundice , bone abnormalities, and cardiovascular problems. [ 8 ]  Recommended course of treatment depends on the nature and severity of the symptoms and may involve close monitoring of hemoglobin levels, folic acid supplements, and potentially regular blood transfusions. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4693", "text": "There is a variety of phenotypes depending on the interaction of HbE and \u03b1-thalassemia. The presence of the \u03b1-thalassemia reduces the amount of HbE usually found in HbE heterozygotes. In other cases, in combination with certain thalassemia mutations, it provides an increased resistance to  malaria  ( P. falciparum ). [ 4 ]  This disease was first described by  Virginia Minnich  in 1954, who discovered a high prevalence of it in Thailand and initially referred to it as \"Mediterranean Anaemia.\" [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4694", "text": "Hemoglobin E is most prevalent in  mainland Southeast Asia  (Thailand, Myanmar, Cambodia, Laos, Vietnam [ 9 ] ),  Sri Lanka ,  Northeast India  and  Bangladesh . In mainland Southeast Asia, its prevalence can reach 30 or 40%, and  Northeast India , in certain areas it has carrier rates that reach 60% of the population. In Thailand the mutation can reach 50 or 70%, and it is higher in the northeast of the country. In Sri Lanka, it can reach up to 40% and affects those of  Sinhalese  and  Vedda  descent. [ 10 ] [ 11 ]  It is also found at high frequencies in Bangladesh and Indonesia. [ 12 ] [ 13 ]  The trait can also appear in people of Turkish, Chinese and Filipino descent. [ 1 ]  The mutation is estimated to have arisen within the last 5,000 years. [ 14 ]  In Europe, there have been found cases of families with hemoglobin E, but in these cases, the mutation differs from the one found in South-East Asia. This means that there may be different origins of the \u03b2E mutation. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4695", "text": "Hemoglobin Hopkins-2  (Hb Hop-2) is a mutation of the protein  hemoglobin , which is responsible for the transportation of oxygen through the blood from the lungs to the musculature of the body in vertebrates.  The specific mutation in Hemoglobin Hopkins-2 results in two abnormal \u03b1 chains (human hemoglobin consist of 2 \u03b1 and 2 \u03b2 polypeptides usually termed chains). [ 1 ]   The mutation is the result of  histidine  112 being replaced with  aspartic acid  in the protein's polypeptide sequence. [ 1 ]  Additionally, within one of the mutated alpha chains, there are substitutes at 114 and 118, two points on the amino acid chain. [ 2 ]  This mutation can cause  sickle cell anemia . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4696", "text": "Following the initial discovery of hemoglobin, two researchers working at  Johns Hopkins Hospital  in the mid-twentieth century, Ernest W. Smith and J.V. Torbert, discovered the Hopkins-2 mutation of hemoglobin. [ 4 ]   Work by  Harvey A. Itano  and Elizabeth A. Robinson in 1960 confirmed Smith's and Torbert's finding and emphasized the importance of the alpha loci in the mutation. [ 5 ]   Later in the twentieth century, Samuel Charache, another Hopkins affiliated scientist and doctor, studied the physiological impacts of the variant on health. [ 6 ]   His findings suggest that the variant plays no effect clinically. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4697", "text": "In the mid-1900s, many factors prompted hemoglobin research in  Baltimore, Maryland  and ultimately led to the discovery of Hemoglobin Hopkins-2.  First, the development of new technology, including  x-ray crystallography  and protein chemistry, that could be utilized in molecular biology studies catalyzed research. [ 8 ]   Furthermore, the large presence of  thalassemia  (Hb H), a disorder in which the alpha gene is dysfunctional, in Southeast Asia and southern China further concerned researchers as, if left untreated, the mutation could result in bone deformities,  swelling of the spleen , slowed growth rate, or  cardiac dysfunction . [ 9 ] [ 10 ]   Additionally,  Max Perutz 's, a Cambridge researcher, discovery of hemoglobin's basic  tertiary structure  in 1962 catalyzed research in hematology. [ 11 ]   Vernon Ingram's  research surrounding  sickle cell anemia  in 1956 revealed that variants, or mutations, in hemoglobin's RNA resulted in the  sickle cell disease . [ 8 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4698", "text": "Ernest W. Smith and J.V. Norbert examined Ingram's discovery and, in 1958, they discovered the hemoglobin Hopkins-2 mutation.  Smith and Torbert, research fellows working in Lockard Conley's  Hematology  Research Department at Johns Hopkins University, proved that recombination of  non-allelic genes  resulted in two variants of the gene that produced hemoglobin.  Variants of the \"normal\" hemoglobin gene result in mutation in the hemoglobins produced. [ 4 ]    In other words, the researchers discovered two versions of  hemoglobin :  the [Hb-Hop2] and  S variants . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4699", "text": "Smith's and Torbert's findings were confirmed and built upon by  Harvey A. Itano  and Elizabeth A. Robinson in 1960.   In their paper,  Genetic Control of the a- and B-Chains of Hemoglobin ,  Itano  and Robinson explained that both the alpha and beta  loci  are involved in the regulation of hemoglobin.  The recombination of the alpha loci on the gene coding for hemoglobin results in a mutation of the hemoglobin protein.  Researchers refer to this mutated protein as a Hopkins-2 variation of hemoglobin. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4700", "text": "Further research surrounding the Hopkins-2 genetic mutation was conducted by Johns Hopkins doctors, who remained engaged in research in the hematologic field despite a general change in focus away from hematology in the medical community.  Prominent Hopkins researcher Samuel Charache was one of many scientists at Hopkins who investigated  blood  and its components during the late twentieth century. [ 8 ]  Specifically, Charache is well known for his work with George Dover, another Hopkins researcher; together, they discovered a treatment option for  sickle cell anemia .  However, Charache was also engaged in hemoglobin Hopkins-2 research.  In his  Nature  article, titled  Clinical Studies and Physiological Properties of Hopkins Hemoglobin-2,  Charache announced his discoveries surrounding the hemoglobin variant.  Charache focused on physical implications of the variant, rather than on genetics themselves. Ultimately, Charache asserts in his paper that the variant is not prominent  phenotypically  and plays an unnoticeable or no effect on human health. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4701", "text": "Hematologic studies were prominent at Johns Hopkins Hospital prior to the discovery of the hemoglobin Hopkins-2 variant. After observing the cells under a  microscope , Sir William Osler connected the concept of dysfunctional platelets to the development of ulcerative endocarditis and  thrombosis .  Osler's initial observations of platelets catalyzed the study of blood and hematology at Hopkins and in other research environments. [ 12 ]  Platelets were discovered independently by Max Schultze in 1865 [ 13 ]  and G. Bizzozero in 1882. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4702", "text": "Beginning in 1920, doctors at Johns Hopkins Hospital conducted research on  sickle cell anemia , or sickle cell disease.  Although their conclusions surrounding the disease are outdated, Doctors Taliaferro and Huck discovered a  latent  form of sickle cell anemia.  Their study on sickle cell anemia was the first of many to occur at Hopkins.  In 1940, Irving Sherman, a medical student at Johns Hopkins, correctly identified the  deoxygenation  of hemoglobin in sickle cell patients after he noted  refraction  patterns characteristic of deoxygenation when light was passed through the protein. [ 15 ]   The deoxygenation of hemoglobin in sickle cell patients has severe implications on those who carry the mutation.  The hemoglobin proteins, present in those with sickle cell disease, cannot carry oxygen to the organs and other tissues of the human body.  This results in  pain crises  and the disease results in an abbreviated  life expectancy  of 40\u201360 years. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4703", "text": "Ernest W. Smith and Torbert were integral in the discovery of Hopkins Hemoglobin-2, in addition to many other hematologic mutations and conditions. [ 4 ]   The two scientists worked together at Hopkins to identify the N-Baltimore mutation of Hemoglobin in 1958. [ 17 ]   Also referred to as the Hopkins-I, Jenkins, N-Memphis, or Kenwood mutation, the N-Baltimore mutation is a point mutation in which a  glycine  codon is replaced with an  adenosine  codon.  The N-Baltimore mutation is associated with the C and S mutations of hemoglobin. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4704", "text": "Smith conducted extensive research in conjunction with Locklard Conley, one of Smith's bosses at the time of the Hopkins Hemoglobin-2 variant discovery.  Lockard Conley, commonly referred to as \"Lock,\" was a  Johns Hopkins  undergraduate and  Columbia  trained doctor.  In 1947, Conley became the first director of the Hematology Department at Hopkins and remained in the position for 33 years.  While there, he studied blood-related diseases, such as  blood coagulation  and  sickle cell anemia , and invented machinery to analyze molecular species. [ 19 ]   Specifically, he and Smith created a device that allowed for the separation of hemoglobin variants from standard hemoglobin molecules.  Conley's impact on hematology, therefore, was not only scientific discovery; but, also, technological discovery that allowed the hematologic field to expand. [ 20 ]   Conley remained a doctor and professor at  Johns Hopkins Hospital  until his death in 2010. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4705", "text": "Although a significant amount of hematologic research was completed during the 1950s and 1960s, scientists questioned whether more research could be completed without the development of more advanced technology. Ultimately, this doubt resulted in fewer scientists pursuing research in hematology in the mid twentieth century. [ 8 ]   Despite the scarcity of researchers, new discoveries surrounding genetics and hemoglobin were made.  However, research continued in major medical laboratories, like Hopkins. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4706", "text": "In the mid and late twentieth century, both doctors George J. Dover and Samuel Charache studied sickle cell anemia's pathology at Johns Hopkins Hospital. [ 7 ]   Together, they implemented treatment of the disease through the use of a cancer drug,  hydroxyurea ; the drug was successful in alleviating some of the painful spurts associated with  sickle cell anemia , in addition to  pulmonary  symptoms associated with the disease.  Dover, a pediatric hematologist and expert on  fetal hemoglobin , initiated the use of the protein as a way to treat sickle cell anemia in adults. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4707", "text": "The Hopkins-2 variant of hemoglobin has an oxygen affinity within the body, meaning that there is an increase of oxygen spreading through the body due to the fact that Ho-2 carries a higher amount of oxygen. [ 22 ]  There is no red cell effect with Ho-2 compared to  Hemoglobin S , which changes the shape of the cell to become sickled. The Hopkins-2 variant of hemoglobin is not involved in forming  sickle cells . There is a lack of phenotypic expression of Ho-2 in terms of sickle cell, so a person with sickle cell and hemoglobin Hopkins-2 would be asymptomatic. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4708", "text": "The Hopkins 2 variant of  hemoglobin  is the result of a mutation.  Specifically, the mutated protein is composed of two alpha chains.  The mutation for the Hopkins-2 variant of hemoglobin is located on the surface of the molecule.  Within the Ho-2 variant,  aspartic acid  replaces  histidine  at position 112 on the alpha chain. [ 2 ]  Dr.  Max Perutz  examined the aspartic acid in alpha 112 claiming that the carboxyl group of the amino acid forms a hydrogen bond with phenolix hydroxyl, which in turn stabilizes the structure of the molecule and increases oxygen affinity.  Ho-2 hemoglobin has high levels of oxygen, which replaces the lack of oxygen within red blood cells.  Ho-2 is similar to  Hemoglobin A , which is normal hemoglobin and also contains two \u03b1-chains.  This provides an explanation as to how the Hopkins-2 variant of hemoglobin is related to the symptoms of  sickle cell . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4709", "text": "Hopkins-2 can also interact specifically with Hemoglobin S.   Hemoglobin S  is the most common abnormal hemoglobin variant.  Hemoglobin S is the variant that causes  sickle cell , which is a disorder in which red blood cells break down and become abnormally shaped.  Hemoglobin S has two beta chains, whereas hemoglobin Hopkins-2 has two alpha chains.  Hopkins-2 makes up 22% of hemolysates in single heterozygotes; therefore, there is the normal version of the gene in these patients.  Hemolysates are the products of the destruction of red blood cells.  Ho-2 also comprises 11% of hemolysates in \u2018double\u2019 heterozygotes, which are when the gene contains both Hopkins-2 and Hemoglobin S. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4710", "text": "There are currently multiple possible explanations as to how the Hemoglobin variant Hopkins-2 works. One explanation that scientists have come up with is that Ho-2 is created due to a point mutation causing the substitution of histidine by aspartic acid. [ 23 ]  The other explanation is that there is an unequal crossing over between two \u03b1 genes which explains the replacement of histidine by aspartic acid. [ 23 ]  This then led a deletion occurring within the chromosome housing Ho-2. This deletion removes the region where the N-terminus is located in the major \u03b1-chain and where the c-terminus is located on the minor \u03b1-chain. [ 23 ]  Deletion of the N-terminus inactivates enzymes and halting their ability to cut chains at certain areas, which inevitably damages the chain. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4711", "text": "Case studies were completed on some patients who carried the Hemoglobin Hopkins-2 genetic mutation by Samuel Charache and others. Researchers concluded after completing the studies that many of carriers of the mutation were asymptomatic to sickle cell and were overall quite healthy.  Any medical issues that occurred had no correlation to sickle cell.  These studies occurred in the 1970s. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4712", "text": "There were five carriers of Hemoglobin Hopkins 2 in the Fuller-Carr family and ten double heterozygotes of Ho-2 and Hemoglobin S. [ 24 ]  All the carriers were in good health and had normal hematology test results. Out of those carrying  hemoglobin S  and Ho-2, none were  anemic ; but, a few of those studied displayed elevated reticulocyte counts. [ 24 ]  This is measured through a blood test that analyzes the speed of production of red blood cells by bone marrow and its release into the blood. There was no suggestion of symptomatic sickle cell anemia in the family. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4713", "text": "There was a study on a three-year-old that was a carrier of the hemoglobin variant of Hopkins-2. The child had mild anemia and reticulocytosis, which is commonly seen in anemia. [ 25 ]  There were, however, no sickled cells found in the blood and they had no symptoms relating to sickle cell. There was also a reduced mean corpuscular volume (MCV), which is the average volume of  red blood cell  count. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4714", "text": "Hemoglobin Lepore syndrome   is typically an  asymptomatic   hemoglobinopathy , which is caused by an  autosomal recessive   genetic mutation . The Hb Lepore variant, consisting of two normal  alpha globin  chains (HBA) and two delta-beta globin fusion chains which occurs due to a \"crossover\" between the  delta  (HBD) and  beta globin  (HBB) gene  loci  during  meiosis  and was first identified in the Lepore family, an Italian-American family, in 1958. [ 1 ]  There are three varieties of Hb Lepore, Washington (Hb Lepore Washington, AKA Hb Lepore Boston or Hb Lepore Washington-Boston), Baltimore (Hb Lepore Baltimore) and  Hollandia  (Hb Hollandia). All three varieties show similar  electrophoretic  and  chromatographic  properties and hematological findings bear close resemblance to those of the  beta-thalassemia   trait ; a blood disorder that reduces the production of the iron-containing  protein   hemoglobin  which carries oxygen to cells and which may cause  anemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_4715", "text": "The  homozygous  state for Hb Lepore is rare. Patients of  Balkan  descent tend to have the most severe presentation of symptoms including severe  anemia  during the first five years of life. They also presented with significant  splenomegaly ,  hepatomegaly , and skeletal abnormalities identical to those of homozygous  beta-thalassemia . The amount of Hb Lepore in the patients  blood  ranged from 8 to 30%, the remainder being  fetal hemoglobin  (Hb F) which is present in minute quantities (typically<1 percent) in the  red blood cells  of adults. Known as F- cells they are present in a small proportion of overall RBCs. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4716", "text": "Homozygous  Hb Lepore is similar to beta-thalassemia major; however, the clinical course is variable. Patients with this condition typically present with severe anemia during the first two years of life. The heterozygote form is mildly anemic (Hb 11\u201313 g/dl) but presents with a significant  hypochromia  (deficiency of hemoglobin in the  red blood cells ) and  microcytosis . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4717", "text": "A potential complication that may occur in children that suffer acute anemia with a hemoglobin count below 5.5 g/dl is  silent stroke [ 5 ] [ unreliable medical source? ]  A silent stroke is a type of  stroke  that does not have any outward symptoms ( asymptomatic ), and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms a silent stroke still causes damage to the brain, and places the patient at increased risk for both  transient ischemic attack  and major stroke in the future. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4718", "text": "Sickle cell-Hb Lepore Boston syndrome is a type of sickle cell disease (HbS) that differs from homozygous sickle cell disease where both parents carry sickle hemoglobin. In this variant one parent has the sickle cell hemoglobin the second parent has Hb Lepore Boston, the only one of the three variants described in association with HbS. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4719", "text": "The diagnosis of Hb Lepore syndrome may be performed antenatally or postnatally via the use of a variety of tests"}
{"_id": "WikiPedia_Hematology$$$corpus_4720", "text": "Those homozygous (Hb LeporeLepore; a very rare situation) or compound heterozygous (Hb Lepore-\u0392-thalassaemia) might suffer from a severe anaemia. They should be managed in a comprehensive multi-disciplinary program of care. [ 10 ]  Management includes a regular course of  blood transfusions , although the clinical severity in compound (double) heterozygotes can range from minor to major, depending on the combination of genes that have caused the condition. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4721", "text": "Individuals heterozygous for the Hb Lepore require no particular treatment. There is no anemia or, if there is, it is very mild. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4722", "text": "The Hb Lepore trait has a worldwide distribution and may affect individuals of various ethnicities however the three main varieties which been defined tend to be more prevalent among specific ethnic groups, typically  Caucasians  of the Southern regions  Central  and  Eastern Europe . The three main varieties are named for the geographical areas they were first identified in with various subtypes, the three main varieties are: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4723", "text": "Hemoglobin O-Arab  (American English) or Haemoglobin O-Arab (British English) is a rare alternation of Hemoglobin (American English) or Haemoglobin (British English), characterised with the presence of \u03b2^121Glu \u2192 Lys (Hb O-Arab). Mutations of  heterozygotes  for Hb O-Arab have been reported in Saudi Arabia, North Africa, Sudan, the Mediterranean and the United States. Diagnosis of Hb O-Arab requires  liquid chromatography  on both  cellulose acetate  and  citrate agar , due to  co-migrating  with Hb C at alkaline pH. When combined with Hemoglobin S (\u03b2^6Glu \u2192 Val) it causes a severe form of  Sickle cell disease  known as Hemoglobin S/O-Arab. Detection of Hb O-Arab can be carried out with a blood test, identifying the carries of hemoglobinopathies, so as to inform patients their chances of producing an affected child and ensure appropriate guidance is given."}
{"_id": "WikiPedia_Hematology$$$corpus_4724", "text": "Although the molecular structure of hemoglobin itself has been determined by molecular biologist,  Max Perutz , by X-Ray Crystallography, earning his work with partner, John Kendrew the 1962 Nobel Prize in Chemistry, the molecular structure of hemoglobin O-Arab has not been obtained yet. The first sighted case of Hb O-Arab in combination with sickle hemoglobin was described in 1960 in an Arabic boy with severe hemolytic anaemia and recurrent painful episodes. Following cases of patients inheriting hetereozygotes for Hb O-Arab have been evident in the Middle Eastern descent, having clinical and laboratory manifestations characteristic of a sickling disease with hemolytic anaemia."}
{"_id": "WikiPedia_Hematology$$$corpus_4725", "text": "The most commonly used method for Hemoglobin analysis used is alkaline cellulose acetate electrophoresis at pH 8.6, due to its ability to split hemoglobin into its common variants, however a review of the College of American Pathologists (CAP) Hemoglobinopahty Survey Reports has provided the number of laboratories that utilise high-performance liquid chromatography (HPLC) technology for identification of hemoglobin variants, increasing approximately 12.5 fold in over the past decade. It is of clinical significance to be able to differentiate accurately between hemoglobin variants because of their reactions with Hemoglobin S to clinically different diseases, allowing data to be displayed through chromatograms to represent a visual insight of elution of Hb O-Arab using retention time.  to By using HPLC, it can accurately and reliable differentiate between Hemoglobin C and Hemoglobin O-Arab without any requirements for further confirmatory tests as stated by current CAP standards."}
{"_id": "WikiPedia_Hematology$$$corpus_4726", "text": "When Hemoglobin O-Arab co-inherits with Hemoglobin S, it produces a syndrome with similarities in severity to sickle cell anaemia, [ 1 ]  having severe haemolytic anaemia and red cells denser than normal with occurrences of some cells as dense as if contract with sickle cell anaemia. A description with the presence of two variations of \u03b2-globin chains, \u03b2^6Glu \u2192 Val (HbS) and \u03b2^121Glu \u2192 Lys (Hb O-Arab), patients heterozygous for Hemoglobin O-Arab had denser red cells, having similar traits to sickle cell disease, with few outliers of cells of normal density. From a study formulated at Harvard Medical School, the authors have concluded that \"The erythrocytic pathogenesis of Hemoglobin O-Arab involves the dehydration of red cells due to the K:Cl cotransport system.\" The abnormality thus explains the severe pathology of the double heterozygote for Hemoglobin S and Hemoglobin O-Arab, leading to the conclusion of a correlation of these hemoglobins present to additional haemolytic risk factor."}
{"_id": "WikiPedia_Hematology$$$corpus_4727", "text": "Case reports analysed by Doctor Sayar Dror, [ 2 ]  PhD, at the Paediatric Hemato-Oncology Unit, \u201cDana\u201d Children Hospital in Israel, feature three patients; a 12 month-old female of consanguineous parents, a 35 month-old female born to parents known to have the Hemoglobin O-Arab trait, and a 9 month-old male who was asymptomatic and was referred because of contracting mild anaemia. The origins of all three offspring were from South Sudan, with all three suffering from microcytic anaemia, with an average of 67.2-79% of their Hemoglobin, being Hemoglobin-O Arab. The peripheral blood smears of the tested patients displayed target cells, microcytosis, polychromasia and nucleated red blood cells. The basis drawn from these case reports is that Hemoglobin O-Arab is a rare, alternation of Hemoglobin, demonstrating effects similar to those diagnosed with mild to moderate microcytic anemia."}
{"_id": "WikiPedia_Hematology$$$corpus_4728", "text": "Another case study with data collection apparent for over 1,000 adults and paediatric patients followed by the Duke University Comprehensive Sickle Cell Center was used to identify patients, reviewing age. Gender and race to record similarities in complications in each patient such as painful vaso-occlusive events, acute chest syndrome and leg ulcers. Out of the cohort tested, with Hemoglobin O-Arab present, all patients shown a median Hemoglobin concentration of 8.7gm/dL, which is higher than the average concentration in a healthy being."}
{"_id": "WikiPedia_Hematology$$$corpus_4729", "text": "Treatment and counselling offered, depending on different ages of contraction of Hb O-Arab and severity of inheritance of the alternation. \nGeneralised, evolution of Hb O-Arab has long survival with no visual symptoms, but act as carriers of haemoglobin disorder. Thus, treatment can include screening and blood tests before coitus can detect any affected offspring, with provided genetic counselling and chances of producing affect offspring. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4730", "text": "[ 4 ] \n [ 5 ] \n [ 6 ] \n [ 7 ] \n [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4731", "text": "6HBW ,  1A00 ,  1A01 ,  1A0U ,  1A0Z ,  1A3N ,  1A3O ,  1ABW ,  1ABY ,  1AJ9 ,  1B86 ,  1BAB ,  1BBB ,  1BIJ ,  1BUW ,  1BZ0 ,  1BZ1 ,  1BZZ ,  1C7B ,  1C7C ,  1C7D ,  1CBL ,  1CBM ,  1CH4 ,  1CLS ,  1CMY ,  1COH ,  1DKE ,  1DXT ,  1DXU ,  1DXV ,  1FN3 ,  1G9V ,  1GBU ,  1GBV ,  1GLI ,  1GZX ,  1HAB ,  1HAC ,  1HBA ,  1HBB ,  1HBS ,  1HCO ,  1HDB ,  1HGA ,  1HGB ,  1HGC ,  1HHO ,  1IRD ,  1J3Y ,  1J3Z ,  1J40 ,  1J41 ,  1J7S ,  1J7W ,  1J7Y ,  1JY7 ,  1K0Y ,  1K1K ,  1KD2 ,  1LFL ,  1LFQ ,  1LFT ,  1LFV ,  1LFY ,  1LFZ ,  1LJW ,  1M9P ,  1MKO ,  1NEJ ,  1NIH ,  1NQP ,  1O1I ,  1O1J ,  1O1K ,  1O1L ,  1O1M ,  1O1N ,  1O1O ,  1O1P ,  1QI8 ,  1QSH ,  1QSI ,  1QXD ,  1QXE ,  1R1X ,  1R1Y ,  1RPS ,  1RQ3 ,  1RQ4 ,  1RQA ,  1RVW ,  1SDK ,  1SDL ,  1THB ,  1UIW ,  1VWT ,  1XXT ,  1XY0 ,  1XYE ,  1XZ2 ,  1XZ4 ,  1XZ5 ,  1XZ7 ,  1XZU ,  1XZV ,  1Y09 ,  1Y0A ,  1Y0C ,  1Y0D ,  1Y0T ,  1Y0W ,  1Y22 ,  1Y2Z ,  1Y31 ,  1Y35 ,  1Y45 ,  1Y46 ,  1Y4B ,  1Y4F ,  1Y4G ,  1Y4P ,  1Y4Q ,  1Y4R ,  1Y4V ,  1Y5F ,  1Y5J ,  1Y5K ,  1Y7C ,  1Y7D ,  1Y7G ,  1Y7Z ,  1Y83 ,  1Y85 ,  1Y8W ,  1YDZ ,  1YE0 ,  1YE1 ,  1YE2 ,  1YEN ,  1YEO ,  1YEQ ,  1YEU ,  1YEV ,  1YFF ,  1YG5 ,  1YGD ,  1YGF ,  1YH9 ,  1YHE ,  1YHR ,  1YIE ,  1YIH ,  1YVQ ,  1YVT ,  1YZI ,  2D5Z ,  2D60 ,  2DN1 ,  2DN2 ,  2DN3 ,  2DXM ,  2H35 ,  2HBC ,  2HBD ,  2HBE ,  2HBF ,  2HBS ,  2HCO ,  2HHD ,  2HHE ,  2M6Z ,  2W6V ,  2W72 ,  2YRS ,  3B75 ,  3D17 ,  3D7O ,  3DUT ,  3HXN ,  3IC0 ,  3IC2 ,  3KMF ,  3NL7 ,  3NMM ,  3ODQ ,  3ONZ ,  3OO4 ,  3OO5 ,  3P5Q ,  3QJB ,  3QJC ,  3QJD ,  3QJE ,  3R5I ,  3S65 ,  3S66 ,  3SZK ,  3W4U ,  3WCP ,  3WHM ,  4FC3 ,  4HHB ,  4IJ2 ,  4L7Y ,  4M4A ,  4M4B ,  4MQC ,  4MQG ,  4MQH ,  4MQI ,  4N7N ,  4N7O ,  4N7P ,  4N8T ,  4NI0 ,  4NI1 ,  4ROL ,  4ROM ,  4WJG ,  4X0L ,  4XS0 ,  5E29 ,  5E6E ,  5EE4 ,  5HU6 ,  5JDO ,  5KDQ ,  5E83"}
{"_id": "WikiPedia_Hematology$$$corpus_4732", "text": "3043"}
{"_id": "WikiPedia_Hematology$$$corpus_4733", "text": "101488143"}
{"_id": "WikiPedia_Hematology$$$corpus_4734", "text": "ENSG00000244734"}
{"_id": "WikiPedia_Hematology$$$corpus_4735", "text": "ENSMUSG00000073940"}
{"_id": "WikiPedia_Hematology$$$corpus_4736", "text": "P68871"}
{"_id": "WikiPedia_Hematology$$$corpus_4737", "text": "P02088"}
{"_id": "WikiPedia_Hematology$$$corpus_4738", "text": "NM_000518"}
{"_id": "WikiPedia_Hematology$$$corpus_4739", "text": "NM_008220"}
{"_id": "WikiPedia_Hematology$$$corpus_4740", "text": "NP_000509"}
{"_id": "WikiPedia_Hematology$$$corpus_4741", "text": "NP_032246 NP_001188320 NP_001265090"}
{"_id": "WikiPedia_Hematology$$$corpus_4742", "text": "Hemoglobin subunit beta  ( beta globin ,  \u03b2-globin ,  haemoglobin beta ,  hemoglobin beta ) is a  globin   protein , coded for by the  HBB  gene, which along with alpha globin ( HBA ), makes up the most common form of  haemoglobin  in adult humans,  hemoglobin A  (HbA). [ 5 ]  It is 147 amino acids long and has a molecular weight of 15,867  Da . Normal adult human HbA is a  heterotetramer  consisting of two alpha chains and two beta chains."}
{"_id": "WikiPedia_Hematology$$$corpus_4743", "text": "\u03b2-globin is encoded by the  HBB  gene on  human chromosome 11 . Mutations in the gene produce several variants of the proteins which are implicated with genetic disorders such as  sickle-cell disease  and  beta thalassemia , as well as beneficial traits such as  genetic resistance to malaria . [ 6 ] [ 7 ]  At least 50 disease-causing mutations in this gene have been discovered. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4744", "text": "HBB protein is produced by the gene  HBB  which is located in the multigene locus of  \u03b2-globin locus  on  chromosome 11 , specifically on the short arm position 15.4.  Expression  of beta globin and the neighbouring globins in the \u03b2-globin locus is controlled by single  locus control region  (LCR), the most important regulatory element in the locus located upstream of the globin genes. [ 9 ]  The normal allelic variant is 1600  base pairs  (bp) long and contains three  exons . The order of the genes in the beta-globin cluster is 5' -  epsilon  \u2013  gamma-G  \u2013  gamma-A  \u2013  delta  \u2013 beta - 3'. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4745", "text": "HBB  interacts  with  Haemoglobin, alpha 1  (HBA1) to form haemoglobin A, the major haemoglobin in adult humans. [ 10 ] [ 11 ]  The interaction is two-fold. First, one HBB and one HBA1 combine, non-covalently, to form a dimer. Secondly, two dimers combine to form the four-chain tetramer, and this becomes the functional haemoglobin. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4746", "text": "Beta thalassemia  is an inherited genetic mutation in one (Beta thalassemia minor) or both (Beta thalassemia major) of the Beta globin alleles on chromosome 11. The mutant alleles are subdivided into two groups: \u03b20, in which no functional \u03b2-globin is made, and \u03b2+, in which a small amount of normal \u03b2-globin protein is produced. Beta thalassemia minor occurs when an individual inherits one normal Beta allele and one abnormal Beta allele (either \u03b20, or \u03b2+). Beta thalassemia minor results in a mild microcytic anemia that is often asymptomatic or may cause fatigue and or pale skin. Beta thalassemia major occurs when a person inherits two abnormal alleles. This can be either two \u03b2+ alleles, two \u03b20 alleles, or one of each. Beta thalassemia major is a severe medical condition. A severe anemia is seen starting at 6 months of age. Without medical treatment death often occurs before age 12.  [ 13 ]  Beta thalassemia major can be treated by lifelong  blood transfusions  or  bone marrow transplantation . [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4747", "text": "According to a recent study, the stop gain mutation  Gln40stop  in  HBB  gene is a common cause of  autosomal recessive   Beta- thalassemia  in  Sardinian people  (almost exclusive in Sardinia). Carriers of this mutation show an enhanced red blood cell count. As a curiosity, the same mutation was also associated to a decrease in serum  LDL  levels in carriers, so the authors suggest that is due to the need of  cholesterol  to regenerate cell membranes. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4748", "text": "More than a thousand naturally occurring  HBB  variants have been discovered. The most common is HbS, which causes  sickle cell disease . HbS is produced by a  point mutation  in  HBB  in which the  codon  GAG is replaced by GTG. This results in the replacement of hydrophilic amino acid  glutamic acid  with the hydrophobic amino acid  valine  at the seventh position (\u03b26Glu\u2192Val). This substitution creates a hydrophobic spot on the outside of the protein that sticks to the hydrophobic region of an adjacent hemoglobin molecule's beta chain. This further causes clumping of HbS molecules into rigid fibers, causing \"sickling\" of the entire  red blood cells  in the  homozygous  ( HbS/HbS ) condition. [ 17 ]  The homozygous allele has become one of the deadliest genetic factors, [ 18 ]  whereas people heterozygous for the mutant allele ( HbS/HbA ) are resistant to  malaria  and develop minimal effects of the anaemia. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4749", "text": "Sickle cell disease is closely related to another mutant haemoglobin called  haemoglobin C  (HbC), because they can be inherited together. [ 20 ]  HbC mutation is at the same position in HbS, but glutamic acid is replaced by  lysine  (\u03b26Glu\u2192Lys). The mutation is particularly prevalent in West African populations. HbC provides near full protection against  Plasmodium falciparum   in homozygous (CC) individuals and intermediate protection in heterozygous (AC) individuals. [ 21 ]  This indicates that HbC has stronger influence than HbS, and is predicted to replace HbS in malaria-endemic regions. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4750", "text": "Another point mutation in HBB, in which glutamic acid is replaced with lysine at position 26 (\u03b226Glu\u2192Lys), leads to the formation of  haemoglobin E  (HbE). [ 23 ]  HbE has a very unstable \u03b1- and \u03b2-globin association. Even though the unstable protein itself has mild effect, inherited with HbS and thalassemia traits, it turns into a life-threatening form of \u03b2-thalassemia. The mutation is of relatively recent origin suggesting that it resulted from selective pressure against severe falciparum malaria, as heterozygous allele prevents the development of malaria. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4751", "text": "Malaria due to  Plasmodium falciparum  is a major selective factor in  human evolution . [ 7 ] [ 25 ]  It has influenced mutations in  HBB  in various degrees resulting in the existence of numerous HBB variants. Some of these mutations are not directly lethal and instead confer resistance to malaria, particularly in Africa where malaria is epidemic. [ 26 ]  People of African descent have evolved to have higher rates of the mutant HBB because the heterozygous individuals have a misshaped red blood cell that prevent attacks from malarial parasites. Thus, HBB mutants are the sources of positive selection in these regions and are important for their long-term survival. [ 6 ] [ 27 ]  Such selection markers are important for tracing human ancestry and  diversification from Africa . [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4752", "text": "1JEB ,  3W4U"}
{"_id": "WikiPedia_Hematology$$$corpus_4753", "text": "3050"}
{"_id": "WikiPedia_Hematology$$$corpus_4754", "text": "15126"}
{"_id": "WikiPedia_Hematology$$$corpus_4755", "text": "ENSG00000130656"}
{"_id": "WikiPedia_Hematology$$$corpus_4756", "text": "ENSMUSG00000055609"}
{"_id": "WikiPedia_Hematology$$$corpus_4757", "text": "P02008"}
{"_id": "WikiPedia_Hematology$$$corpus_4758", "text": "P06467"}
{"_id": "WikiPedia_Hematology$$$corpus_4759", "text": "NM_005332"}
{"_id": "WikiPedia_Hematology$$$corpus_4760", "text": "NM_010405"}
{"_id": "WikiPedia_Hematology$$$corpus_4761", "text": "NP_005323"}
{"_id": "WikiPedia_Hematology$$$corpus_4762", "text": "NP_034535"}
{"_id": "WikiPedia_Hematology$$$corpus_4763", "text": "Hemoglobin subunit zeta  is a  protein  that in humans is encoded by the  HBZ   gene . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4764", "text": "Zeta-globin is an alpha-like hemoglobin. The zeta-globin polypeptide is synthesized in the yolk sac of the early embryo, while alpha-globin is produced throughout fetal and adult life. The zeta-globin gene is a member of the human alpha-globin gene cluster that includes five functional genes and two pseudogenes. The order of genes is: 5' -  zeta  - pseudozeta -  mu  - pseudoalpha-1 -  alpha-2  -  alpha-1  -  theta1  - 3'. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4765", "text": "Hemoglobin  is a protein that transports oxygen in the blood. Genetic differences lead to structural variants in the hemoglobin protein structure. Some variants can cause disease while others have little to no effect."}
{"_id": "WikiPedia_Hematology$$$corpus_4766", "text": "The normal hemoglobin types are Hemoglobin A (HbA), which makes up 95\u201398% of total hemoglobin in adults, Hemoglobin A2 (HbA2), which constitutes 2\u20133% of total hemoglobin in adults, and Hemoglobin F (HbF), which is the predominant hemoglobin in the fetus during pregnancy, and may persist in small amounts in adults. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4767", "text": "Hemoglobin variants occur when there are mutations in specific genes that code for the protein chains, known as globins, which make up the hemoglobin molecule. This leads to  amino acid   substitutions  in the hemoglobin molecule that could affect the structure, properties, and/or the stability of the hemoglobin molecule. There are over 1,000 naturally occurring structural variants of  hemoglobin  in humans. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4768", "text": "The physiological effects of these variants can range from minor to severe. [ 3 ]  Mutations can caused impaired production of hemoglobin ( thalassemia ) or produce structurally altered hemoglobins. Some hemoglobin variants, such as HbS which causes  sickle-cell anemia , are responsible for severe diseases and are considered  hemoglobinopathies . Other variants cause no detectable  pathology , and are thus considered non-pathological variants. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4769", "text": "Hemoglobin variants can be discovered through examination, routine laboratory testing, or evaluation of patients with severe anemia. [ 3 ]  In some countries, all newborns are tested for hemoglobinopathies, thalassemias, and HbS.  Isoelectric focusing  or  high-performance liquid chromatography  are used to identify structural abnormalities in hemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_4770", "text": "There are in excess of 1,000 known hemoglobin variants. [ 2 ]  A research database of hemoglobin variants is maintained by  Penn State University . [ 6 ]  A few of these variants are listed below."}
{"_id": "WikiPedia_Hematology$$$corpus_4771", "text": "Hemoglobin G ,  Hemoglobin G-Philadelphia , or  hbG , is a  mutation  of the cells that  oxygenate   blood . The G-Philadelphia variant is most commonly found in African Americans, with carriers being every 1 in 5,000. [ 1 ] \nThe trait is normal-functioning and has no known negative effects. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4772", "text": "The mutation was first discovered in 1971, during the boom of research in to  hemoglobin . [ 3 ]  The push was backed by the desire to research the causes and possibly fight  sickle cell anemia  and other types of Anemia. Because the strict laws of clinical testing had not existed in the 1970s, clinical trials were conducted almost immediately upon the granting of the National Sickle Cell Act of 1971. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4773", "text": "Schwartz et al confirmed that Hemoglobin G is a normal mutation of the combination of S and A  alleles , which is reflected in the chart below. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4774", "text": "Over time the variant has been shown more commonly in people of African and of Asian descent. [ citation needed ]  The clinical presentations of the gene mutation are regarded as either  Microcytic  or  Hypochromic  if they are detectable at all. [ 5 ]  While the trait is not known to be abnormal on its own, the mutation of the gene can have an effect on the absorption of  alcohol . [ 6 ]  As well as physical difficulties with alcohol and other blood-altering substances, the hemoglobin has also been shown to effect the way the brain handles sleep disorders, like  insomnia . [ 6 ]  People with the G mutation are typically more likely to have issues oxygenating blood and because of this,  Anemia  was thought to be a side-effect of the mutation. [ 7 ] \n  The overall consensus among clinicians is that the \"G-Philadelphia\" mutation is harmless and has no clinical consequences. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4775", "text": "1A00 ,  1A01 ,  1A0U ,  1A0Z ,  1A3N ,  1A3O ,  1A9W ,  1ABW ,  1ABY ,  1AJ9 ,  1B86 ,  1BAB ,  1BBB ,  1BIJ ,  1BUW ,  1BZ0 ,  1BZ1 ,  1BZZ ,  1C7B ,  1C7C ,  1C7D ,  1CLS ,  1CMY ,  1COH ,  1DKE ,  1DXT ,  1DXU ,  1DXV ,  1FDH ,  1FN3 ,  1G9V ,  1GBU ,  1GBV ,  1GLI ,  1GZX ,  1HAB ,  1HAC ,  1HBA ,  1HBB ,  1HBS ,  1HCO ,  1HDB ,  1HGA ,  1HGB ,  1HGC ,  1HHO ,  1IRD ,  1J3Y ,  1J3Z ,  1J40 ,  1J41 ,  1J7S ,  1J7W ,  1J7Y ,  1JY7 ,  1K0Y ,  1K1K ,  1KD2 ,  1LFL ,  1LFQ ,  1LFT ,  1LFV ,  1LFY ,  1LFZ ,  1LJW ,  1M9P ,  1MKO ,  1NEJ ,  1NIH ,  1NQP ,  1O1I ,  1O1J ,  1O1K ,  1O1L ,  1O1M ,  1O1N ,  1O1O ,  1O1P ,  1QI8 ,  1QSH ,  1QSI ,  1QXD ,  1QXE ,  1R1X ,  1R1Y ,  1RPS ,  1RQ3 ,  1RQ4 ,  1RQA ,  1RVW ,  1SDK ,  1SDL ,  1SHR ,  1SI4 ,  1THB ,  1UIW ,  1VWT ,  1XXT ,  1XY0 ,  1XYE ,  1XZ2 ,  1XZ4 ,  1XZ5 ,  1XZ7 ,  1XZU ,  1XZV ,  1Y01 ,  1Y09 ,  1Y0A ,  1Y0C ,  1Y0D ,  1Y0T ,  1Y0W ,  1Y22 ,  1Y2Z ,  1Y31 ,  1Y35 ,  1Y45 ,  1Y46 ,  1Y4B ,  1Y4F ,  1Y4G ,  1Y4P ,  1Y4Q ,  1Y4R ,  1Y4V ,  1Y5F ,  1Y5J ,  1Y5K ,  1Y7C ,  1Y7D ,  1Y7G ,  1Y7Z ,  1Y83 ,  1Y85 ,  1Y8W ,  1YDZ ,  1YE0 ,  1YE1 ,  1YE2 ,  1YEN ,  1YEO ,  1YEQ ,  1YEU ,  1YEV ,  1YFF ,  1YG5 ,  1YGD ,  1YGF ,  1YH9 ,  1YHE ,  1YHR ,  1YIE ,  1YIH ,  1YVQ ,  1YVT ,  1YZI ,  1Z8U ,  2D5Z ,  2D60 ,  2DN1 ,  2DN2 ,  2DN3 ,  2DXM ,  2H35 ,  2HBC ,  2HBD ,  2HBE ,  2HBF ,  2HBS ,  2HCO ,  2HHD ,  2HHE ,  2M6Z ,  2W6V ,  2W72 ,  2YRS ,  3B75 ,  3D17 ,  3D7O ,  3DUT ,  3HXN ,  3IA3 ,  3IC0 ,  3IC2 ,  3KMF ,  3NL7 ,  3NMM ,  3ODQ ,  3ONZ ,  3OO4 ,  3OO5 ,  3OVU ,  3P5Q ,  3QJB ,  3QJC ,  3QJD ,  3QJE ,  3R5I ,  3S48 ,  3S65 ,  3S66 ,  3SZK ,  3WCP ,  3WHM ,  4FC3 ,  4HHB ,  4IJ2 ,  4L7Y ,  4M4A ,  4M4B ,  4MQC ,  4MQG ,  4MQH ,  4MQI ,  4MQJ ,  4MQK ,  4N7N ,  4N7O ,  4N7P ,  4N8T ,  4NI0 ,  4NI1 ,  4ROL ,  4ROM ,  4WJG ,  4X0L ,  4XS0 ,  6HBW ,  5E29 ,  5E6E ,  5EE4 ,  5HU6 ,  5JDO ,  5KDQ ,  5E83 ,%%s 1Y01 ,  1Z8U ,  1BZ1"}
{"_id": "WikiPedia_Hematology$$$corpus_4776", "text": "3039"}
{"_id": "WikiPedia_Hematology$$$corpus_4777", "text": "15122"}
{"_id": "WikiPedia_Hematology$$$corpus_4778", "text": "ENSG00000206172"}
{"_id": "WikiPedia_Hematology$$$corpus_4779", "text": "ENSMUSG00000069919"}
{"_id": "WikiPedia_Hematology$$$corpus_4780", "text": "P69905"}
{"_id": "WikiPedia_Hematology$$$corpus_4781", "text": "Q91VB8"}
{"_id": "WikiPedia_Hematology$$$corpus_4782", "text": "NM_000558"}
{"_id": "WikiPedia_Hematology$$$corpus_4783", "text": "NM_008218"}
{"_id": "WikiPedia_Hematology$$$corpus_4784", "text": "NP_000508 NP_000508.1 NP_000549.1"}
{"_id": "WikiPedia_Hematology$$$corpus_4785", "text": "NP_001077424"}
{"_id": "WikiPedia_Hematology$$$corpus_4786", "text": "Hemoglobin subunit alpha , Hemoglobin, alpha 1, [ 5 ]  is a  hemoglobin   protein  that in humans is encoded by the  HBA1   gene . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4787", "text": "The human alpha globin  gene cluster  located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. The alpha-2 ( HBA2 ) and alpha-1 (HBA1; this gene) coding sequences are identical. These genes differ slightly over the  5' untranslated regions  and the  introns , but they differ significantly over the  3' untranslated regions . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4788", "text": "Two alpha chains plus two beta chains constitute  HbA , which in normal adult life accounts for about 97% of the total  hemoglobin ; alpha chains combine with delta chains to constitute  HbA-2 , which with  fetal hemoglobin  (HbF), composed of alpha and gamma chains, make up the remaining 3% of adult hemoglobin. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4789", "text": "Alpha  thalassemias  result from deletions of each of the alpha genes as well as deletions of both  HBA2  and  HBA1 ; some nondeletion alpha thalassemias have also been reported. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4790", "text": "Hemoglobin subunit alpha has been shown to  interact  with  hemoglobin subunit beta  (HBB). [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4791", "text": "3040"}
{"_id": "WikiPedia_Hematology$$$corpus_4792", "text": "ENSG00000188536"}
{"_id": "WikiPedia_Hematology$$$corpus_4793", "text": "NM_000517"}
{"_id": "WikiPedia_Hematology$$$corpus_4794", "text": "Hemoglobin, alpha 2 [ 5 ]  also known as  HBA2  is a  gene  that in humans codes for the alpha globin chain of  hemoglobin . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4795", "text": "The human alpha globin gene cluster is located on chromosome 16 and spans about 30 kb, including seven alpha like globin genes and pseudogenes: 5'-  HBZ  - HBZP1 -  HBM  - HBAP1 - HBA2 -  HBA1  -  HBQ1  -3'. The HBA2 (\u03b1 2 )  and   HBA1  (\u03b1 1 ) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions."}
{"_id": "WikiPedia_Hematology$$$corpus_4796", "text": "Two alpha chains plus two beta chains constitute  HbA , which in normal adult life accounts for about 97% of the total  hemoglobin ; alpha chains combine with delta chains to constitute  HbA-2 , which with  HbF  (fetal hemoglobin), composed of alpha and gamma chains, make up the remaining 3% of adult hemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_4797", "text": "Alpha-thalassemias  most commonly result from deletions of any of the four alpha alleles, although some alpha thalassemias have been reported that are due to mutations other than deletion. Deletion of 1 or 2 alleles is clinically silent.  Deletion of 3 alleles causes HbH disease, resulting in anemia and hepatosplenomegaly.  Deletion of all 4 alleles is lethal because it renders the body unable to make fetal hemoglobin (HbF), adult hemoglobin (HbA) or adult variant hemoglobin (HbA2), and results in  hydrops fetalis . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4798", "text": "The  human \u03b2-globin  locus is composed of five  genes  located on a short region of  chromosome 11 , responsible for the creation of the beta parts (roughly half) of the oxygen transport protein  Haemoglobin . This locus contains not only the  beta globin gene  but also  delta ,  gamma-A ,  gamma-G , and  epsilon  globin.  Expression of all of these genes is controlled by single  locus control region  (LCR), and the genes are differentially expressed throughout development. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4799", "text": "The order of the genes in the beta-globin cluster is: 5' -  epsilon  \u2013  gamma-G  \u2013  gamma-A  \u2013  delta  \u2013  beta  - 3'. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4800", "text": "The arrangement of the genes directly reflects the temporal differentiation of their expression during development, with the early-embryonic stage version of the gene located closest to the LCR. If the genes are rearranged, the gene products are expressed at improper stages of development. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4801", "text": "Expression of these genes is regulated in embryonic  erythropoiesis  by many  transcription factors , including  KLF1 , [ 2 ]  which is associated with the upregulation of  adult hemoglobin  in adult definitive  erythrocytes , and  KLF2 , [ 3 ]  which is vital to the expression of  embryonic hemoglobin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4802", "text": "Many  CRMs  have been mapped within the cluster of genes encoding \u03b2-like globins expressed in embryonic (HBE1), fetal (HBG1 and HBG2), and adult (HBB and HBD) erythroid cells. All are marked by  DNase I hypersensitive sites  and  footprints , and many are bound by  GATA1  in  peripheral blood derived erythroblasts  (PBDEs). A DNA segment located between the HBG1 and HBD genes is one of the DNA segments bound by  BCL11A  and several other proteins to negatively regulate HBG1 and HBG2. It is sensitive to  DNase I  but is not conserved across  mammals . An  enhancer  located 3\u2032 of the HBG1 gene is bound by several proteins in PBDEs and  K562 cells  and is sensitive to DNase I, but shows almost no signal for mammalian constraint. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4803", "text": "Methemoglobin  (British:  methaemoglobin , shortened  MetHb ) (pronounced \"met-hemoglobin\") is a  hemoglobin   in the form of  metalloprotein , in which the  iron  in the  heme  group is in the Fe 3+  ( ferric ) state, not the Fe 2+  ( ferrous ) of normal hemoglobin. Sometimes, it is also referred to as ferrihemoglobin. [ 2 ]  Methemoglobin cannot bind  oxygen , which means it cannot carry oxygen to tissues. It is bluish chocolate-brown in color. In human  blood  a trace amount of methemoglobin is normally produced spontaneously, but when present in excess the blood becomes abnormally dark bluish brown. The  NADH -dependent enzyme  methemoglobin reductase  ( a type of diaphorase ) is responsible for converting methemoglobin back to  hemoglobin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4804", "text": "Normally one to two percent of a person's hemoglobin is methemoglobin; a higher percentage than this can be genetic or caused by exposure to various chemicals and depending on the level can cause health problems known as  methemoglobinemia . A higher level of methemoglobin will tend to cause a  pulse oximeter  to read closer to 85% regardless of the true level of  oxygen saturation ."}
{"_id": "WikiPedia_Hematology$$$corpus_4805", "text": "The word methemoglobin derives from the  Ancient Greek  prefix  \u03bc\u03b5\u03c4\u03b1-  (meta-: behind, later, subsequent) and the word  hemoglobin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4806", "text": "The name  hemoglobin  is itself derived from the words  heme  and  globin , each  subunit  of hemoglobin being a  globular protein  with an embedded  heme  group."}
{"_id": "WikiPedia_Hematology$$$corpus_4807", "text": "Amyl nitrite  is administered to treat  cyanide poisoning . It works by converting  hemoglobin  to methemoglobin, which allows for the binding of  cyanide  (CN \u2013 )  anions  by  ferric  (Fe 3+ )  cations  and the formation of  cyanomethemoglobin . The immediate goal of forming this cyanide adduct is to prevent the binding of free cyanide to the  cytochrome  a 3  group in  cytochrome c oxidase . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4808", "text": "Methemoglobin is expressed as a concentration or a percentage. Percentage of methemoglobin is calculated by dividing the concentration of methemoglobin by the concentration of total hemoglobin. Percentage of methemoglobin is likely a better indicator of illness severity than overall concentration, as underlying medical conditions play an important role. For example, a methemoglobin concentration of 1.5 g/dL may represent a percentage of 10% in an otherwise healthy patient with a baseline hemoglobin of 15\u00a0mg/dL, whereas the presence of the same concentration of 1.5 g/dL of methemoglobin in an anemic patient with a baseline hemoglobin of 8 g/dL would represent a percentage of 18.75%. The former patient will be left with a functional hemoglobin concentration of 13.5 g/dL and potentially remain asymptomatic while the latter patient with a functional hemoglobin concentration 6.5 g/dL may be severely symptomatic with a methemoglobin of less than 20%. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4809", "text": "This may be further compounded by the \"functional hemoglobin's\" decreased ability to release oxygen in the presence of methemoglobin.  Anemia ,  congestive heart failure ,  chronic obstructive pulmonary disease , and essentially any pathology that impairs the ability to deliver oxygen may worsen the symptoms of methemoglobinemia. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4810", "text": "Increased levels of methemoglobin are found in blood stains. Upon exiting the body,  bloodstains  transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO 2 ) to methemoglobin (met-Hb) and  hemichrome  (HC). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4811", "text": "Mu hemoglobin  is a  predicted  protein encoded in the  HBM   gene . The mRNA is expressed at moderate levels, but the protein has not been detected by mass spectrometry. [ 1 ] [ 2 ] [ 3 ]  The order of genes is: 5' -  zeta  - pseudozeta -  mu  - pseudoalpha-1 -  alpha-2  -  alpha-1  -  theta1  - 3'."}
{"_id": "WikiPedia_Hematology$$$corpus_4812", "text": "This  genetics  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4813", "text": "Sulfhemoglobinemia   is a rare condition in which there is excess sulfhemoglobin (SulfHb) in the  blood . The pigment is a greenish derivative of  hemoglobin  which cannot be converted back to normal, functional hemoglobin. It causes  cyanosis  even at low blood levels."}
{"_id": "WikiPedia_Hematology$$$corpus_4814", "text": "It is a rare blood condition in which the \u03b2-pyrrole ring of the  hemoglobin  molecule has the ability to bind irreversibly to any substance containing a  sulfur   atom . [ 1 ] [ 2 ]  When  hydrogen sulfide  (H 2 S) (or  sulfide   ions ) and  ferrous  ions combine in the  heme  of hemoglobin, the  blood  is thus incapable of transporting  oxygen  to the tissues."}
{"_id": "WikiPedia_Hematology$$$corpus_4815", "text": "Symptoms  include a blueish or greenish coloration of the blood (cyanosis),  skin , and  mucous membranes , even though a blood count test may not show any abnormalities in the blood.\nThis discoloration is caused by greater than 5 grams per cent of deoxyhemoglobin, or 1.5 grams per cent of methemoglobin, or 0.5 grams per cent of sulfhemoglobin, all serious medical abnormalities. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4816", "text": "Sulfhemoglobinemia is usually drug induced, with drugs associated with it including  sulphonamides , such as  sulfasalazine  or  sumatriptan . Another possible cause is occupational exposure to sulfur compounds. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4817", "text": "It can also be caused by  phenazopyridine . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4818", "text": "The condition generally resolves itself with erythrocyte (red blood cell) turnover, although  blood transfusions  can be necessary in extreme cases. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4819", "text": "Vitreoscilla  haemoglobin  ( VHb ) is a type of  haemoglobin  found in the  Gram-negative aerobic bacterium ,  Vitreoscilla . It is the first  haemoglobin  discovered from bacteria, but unlike classic haemoglobin it is composed only of a single  globin  molecule. [ 1 ]  Like typical haemoglobin, its primary role is binding oxygen, but it also performs other functions including delivery of oxygen to  oxygenases ,  detoxification  of  nitric oxide , sensing and relaying oxygen concentrations,  peroxidase -like activity by eliminating autoxidation-derived  H 2 O 2  that prevents  haeme  degradation and iron release. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4820", "text": "In 1986, a bacterial ( Vitreoscilla ) heme protein that had been studied by Webster and his colleagues, was sequenced and this amino acid sequence exhibited the globin folds of a haemoglobin. [ 3 ] [ 4 ]  It consists of a single domain which normally occurs as a dimer. The solution of its crystal structure confirmed that its 3-dimensional structure is remarkably similar to the classic globin fold. [ 5 ]  When the gene ( vgb ) for this haemoglobin was cloned into  E. coli [ 6 ]  it was found that it increased the growth of these cells under low oxygen conditions compared to control bacteria. [ 7 ]  The concentration of VHb drastically increased in  Vitreoscilla , a strict aerobe, grown under  hypoxic conditions , [ 8 ]  and it was proposed that it acted as an \"oxygen storage trap\" to feed oxygen to the terminal oxidase  (cytochrome bo ) under these conditions. [ 9 ]  Further evidence for this is that VHb is concentrated  in vivo  near the membrane of  Vitreoscilla  cells. [ 10 ]  It was also shown that VHb binds to subunit I of the cytochrome bo terminal oxidase, [ 11 ]  the heme-containing subunit that is also responsible for the unique sodium pumping function of this unique terminal oxidase. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4821", "text": "VHb is the best understood of all the bacterial haemoglobins, and is attributed to play a number of functions. Its main role is likely the binding of  oxygen  at low concentrations and its direct delivery to the terminal respiratory oxidase(s) such as cytochrome o. It is also involved in the delivery of oxygen to  oxygenases , [ 13 ]   detoxification  of  nitric oxide  by converting it to  nitrate , [ 14 ]  and sensing oxygen concentrations and passing this signal to  transcription factors . [ 15 ] [ 16 ]  It has a  peroxidase -like activity and effectively eliminates autoxidation-derived  H 2 O 2 , which is a cause of  haeme  degradation and iron release. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4822", "text": "The VHb gene,  vgb , exists as a single copy in  Vitreoscilla  and exhibits complete agreement with the primary sequence of VHb. [ 6 ] [ 17 ]  The downstream region adjacent to  vgb  carries a gene in the opposite direction having close similarity with the  uvrA  gene of  E. coli , indicating that  vgb  is not part of a multigene  operon . [ 18 ]  Biosynthesis of VHb is regulated at the transcriptional level and is induced under hypoxia in its native host. [ 19 ]   vgb  is expressed strongly in  E. coli  through its native promoter and a similar increase in its transcript level occurs under hypoxia; this suggests a close similarity in the transcriptional machinery of  Vitreoscilla  and  E. coli . [ 20 ]  The promoter region of vgb is crowded with overlapping binding sites for several redox-sensitive transcriptional regulators, involving the fumarate and nitrate reduction (Fnr) system as primary regulator. [ 15 ]  The catabolite repression (Crp) system is an additional control [ 21 ]  along with the aerobic respiration control (Arc) system as a third oxygen-dependent controller. [ 22 ]  Another binding site for the oxidative stress response regulator (OxyR) is also present within the vgb promoter; all these transcriptional regulators appear to work in coordination with each other to control the biosynthesis of VHb in a redox dependent manner. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4823", "text": "Since it was shown that VHb stimulated the growth of  E. coli  under hypoxic conditions,  vgb  was cloned into a variety of organisms, including various bacteria, yeast, fungi, and even higher plants and animals to test its effects on growth and production of products of potential commercial importance, the degradation of toxic compounds, the enhancement of nitrification in wastewater treatment, and other environmental applications. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4824", "text": "Examples of increased productivity include increased yield of a variety of biochemicals including antibiotics, an insecticide, a surfactant, and potential plastic feedstocks. They also include enzymes [ 24 ]  (including one which might have anti-leukemic properties), and fuels (including ethanol, [ 25 ]  butanediol, [ 26 ] [ 27 ]  and biodiesel [ 28 ] ). The toxic compounds studied have been aromatics including 2-chlorobenzoic acid and 2,4-dinitrotolene. [ 29 ] [ 30 ]  In these cases, increases in degradation are thought to be due both to the effects of VHb enhancing respiration to provide cells with additional ATP for growth and production of degrading enzymes, and delivery of oxygen directly to the oxygenases required for early steps in the degradative pathways."}
{"_id": "WikiPedia_Hematology$$$corpus_4825", "text": "Other environmental investigations include those related to heavy metal remediation and provision of soil phosphate to plants. [ 28 ]  Expression of  vgb  in  Nitrosomonas europaea , a bacterium involved of  conversion of ammonia to nitrite  in wastewater, enhanced, to some degree, its ability in this conversion. [ 31 ]  Furthermore, it was shown that the mechanism of haeme protein expression to enhance oxygen supply to the monooxygenase in nitrification under hypoxic conditions is similar to VHb function seen in other applications. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4826", "text": "Amino acid residues in several sections of VHb in proximity to the haeme were altered using genetic engineering to change VHb\u2019s affinity for oxygen and to examine the effects on the biotechnological properties of some of the systems studied. [ 23 ]  Many of the mutations did not have large effects on the ligand binding properties of VHb, or provided at best a modest increase in cell growth compared with cells harboring wild type VHb. [ 23 ] [ 33 ]  Two of the mutant VHb\u2019s, however, provided substantial increases in growth and aromatic compound degradation compared to wild type VHb in  Pseudomonas  and  Burkholderia  bacteria transformed to contain  vgb . [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4827", "text": "American Journal of Hematology  is an  academic journal  devoted to the coverage of  blood diseases . It has been published since 1976. The editor-in-chief is Carlo Brugnara ( Harvard Medical School ). [ 1 ]  According to the  Journal Citation Reports , the journal has a 2022  impact factor  of 12.8, ranking it 7th out of 76 journals in the category \"Hematology\". [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4828", "text": "This article about a  medical journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4829", "text": "See tips for writing articles about academic journals . Further suggestions might be found on the article's  talk page ."}
{"_id": "WikiPedia_Hematology$$$corpus_4830", "text": "The  Asian Journal of Transfusion Science  is a  peer-reviewed   open-access   medical journal  published on behalf of the Indian Society of Blood Transfusion and Immunohematology. The journal publishes articles on the subjects of  blood transfusion  and  immunohematology ."}
{"_id": "WikiPedia_Hematology$$$corpus_4831", "text": "The journal is indexed with Abstracts on Hygiene and Communicable Diseases, CAB Abstracts, Caspur, CINAHL,  DOAJ ,  Scopus ,  EBSCO , EMCARE, Expanded Academic ASAP,  JournalSeek , Global Health,  Google Scholar , Health & Wellness Research Center, Health Reference Center Academic,  Hinari , Index Copernicus, OpenJGate,  PubMed , SCOLOAR, SIIC databases, Tropical Diseases Bulletin, and  Ulrich's Periodicals Directory ."}
{"_id": "WikiPedia_Hematology$$$corpus_4832", "text": "Blood  is a  peer-reviewed   medical journal  published by the  American Society of Hematology . It was established by  William Dameshek  in 1946. The journal changed from semimonthly (24 times annually) to weekly publication at the start of 2009. It covers clinical and basic research in all areas of  hematology , including disorders of  leukocytes , both benign and malignant,  erythrocytes ,  platelets ,  hemostatic mechanisms ,  vascular biology ,  immunology , and  hematologic oncology ."}
{"_id": "WikiPedia_Hematology$$$corpus_4833", "text": "Blood  is indexed and abstracted by:"}
{"_id": "WikiPedia_Hematology$$$corpus_4834", "text": "According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 25.476, and has a Journal Impact Factor rank of 1/76 in the Hematology category. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4835", "text": "Blood Cells, Molecules and Diseases  is a  peer-reviewed   medical journal  covering  hematology . It was established in 1975 as  Blood Cells  and obtained its current title in 1995. The  editor-in-chief  is  Mohandus Narla . It is published eight times per year by  Elsevier ."}
{"_id": "WikiPedia_Hematology$$$corpus_4836", "text": "The journal is abstracted and indexed in:"}
{"_id": "WikiPedia_Hematology$$$corpus_4837", "text": "According to the  Journal Citation Reports , the journal had a 2013  impact factor  of 2.331, ranking it 39th out of 68 journals in the category \"Hematology\". [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4838", "text": "Blood Reviews  is a quarterly  peer-reviewed   medical journal  that publishes  review articles  in the field of  hematology . It was established in 1987 and is published by  Elsevier . The  editors-in-chief  are Hillard Lazarus ( University Hospitals Case Medical Center ) and Drew Provan ( Royal London Hospital ). According to the  Journal Citation Reports , the journal has a 2017  impact factor  of 6.600. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4839", "text": "Blood Transfusion  is an English-language, bimonthly  peer-reviewed   academic journal . It is published by the Italian Society of Transfusion Medicine and Immunohematology ( Societ\u00e0 Italiana di Medicina Trasfusionale e Immunoematologia , SIMTI). [ 1 ]  As of 2024, the editor-in-chief is Serelina Coluzzi. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4840", "text": "As an online open-access [ 4 ]  publication,  Blood Transfusion  covers a range of topics including  blood donation  and donor recruitment;  immunohematology ;  transfusion medicine ,  patient blood management , collection, production and storage of blood components, transfusion transmitted diseases, hemovigilance, therapeutic apheresis,  cellular therapy  and  regenerative medicine ,  hematopoietic stem cell transplantation  and  cord blood banking ,  immunogenetics , hemostasis and thrombosis,  hematology , organization and quality systems in transfusion medicine, legal and ethical aspects of transfusion medicine."}
{"_id": "WikiPedia_Hematology$$$corpus_4841", "text": "The journal is indexed and abstracted in:"}
{"_id": "WikiPedia_Hematology$$$corpus_4842", "text": "According to the  Journal Citation Reports , the journal's  impact factor  for 2023 is 2.4. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4843", "text": "Blood Transfusion  was founded in 1956 with Lorenzo Lapponi as its founding editor-in-chief. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4844", "text": "Bone Marrow Transplantation  is a  peer-reviewed   medical journal  covering  transplantation  of  bone marrow  in humans. It is published monthly by  Nature Research . The scope of the journal includes  stem cell biology ,  transplantation immunology ,  translational research , and clinical results of specific transplant protocols. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4845", "text": "According to the  Journal Citation Reports ,  Bone Marrow Transplantation  has a 2020  impact factor  of 5.483. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4846", "text": "Bone Marrow Transplantation  is abstracted and indexed in  BIOBASE /Current Awareness in Biological Sciences,   BIOSIS ,  Current Contents /Clinical Medicine, Current Contents/Life Sciences,  EMBASE/Excerpta Medica ,  MEDLINE / Index Medicus , and  Science Citation Index ."}
{"_id": "WikiPedia_Hematology$$$corpus_4847", "text": "This article about an  oncology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4848", "text": "This article about a  surgery   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4849", "text": "This article about an  immunology   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4850", "text": "The  British Journal of Haematology  is a  peer-reviewed   medical journal  focusing on  hematology  and other  blood -related topics, such as  blood diseases  and their treatment.  It is published by [Wiley] on behalf of the  British Society for Haematology ."}
{"_id": "WikiPedia_Hematology$$$corpus_4851", "text": "According to the  Journal Citation Reports , the  British Journal of Haematology  had a 2016  impact factor  of 5.67, ranking it 10th out of 70 in the category \"Hematology\". [ 1 ]  In addition, the journal is indexed in:"}
{"_id": "WikiPedia_Hematology$$$corpus_4852", "text": "Clinical and Applied Thrombosis/Hemostasis  is a  peer-reviewed   medical journal  covering research in the field of  hematology . The  editor-in-chief  is Charles A. Carter. It was established in 1995 and is published by  SAGE Publications ."}
{"_id": "WikiPedia_Hematology$$$corpus_4853", "text": "Clinical and Applied Thrombosis/Hemostasis  is abstracted and indexed in  Scopus  and the  Social Sciences Citation Index . According to the  Journal Citation Reports , its 2022  impact factor  is 2.9. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4854", "text": "Clinical Lymphoma, Myeloma & Leukemia  is a  peer-reviewed   medical journal  published by  Elsevier  (previously by  CIG Media Group ). It was established as  Clinical Lymphoma  in 2000, renamed to  Clinical Lymphoma & Myeloma  in 2005 and obtained its current name in 2010. The journal covers research on detection, diagnosis, prevention, and treatment of  lymphoma ,  myeloma ,  leukemia , and related disorders, including  macroglobulinemia ,  amyloidosis , and plasma-cell  dyscrasias ."}
{"_id": "WikiPedia_Hematology$$$corpus_4855", "text": "The journal is abstracted and indexed in  Index Medicus / MEDLINE / PubMed ,  EMBASE ,  Excerpta Medica ,  Current Contents /Clinical Medicine,  CINAHL ,  Chemical Abstracts ,  Scopus , and the  Science Citation Index Expanded . According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 2.02. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4856", "text": "Experimental Hematology  is a  peer-reviewed   medical journal  of  hematology , which publishes  original research  articles and reviews, as well as the abstracts of the annual proceedings of the  Society for Hematology and Stem Cells  (formerly known as the International Society for Experimental Hematology). The journal is published monthly by  Elsevier , and the annual proceedings are published in a supplement issue. The journal is  edited  by  Connie J. Eaves ."}
{"_id": "WikiPedia_Hematology$$$corpus_4857", "text": "Expert Review of Hematology  is a  MEDLINE -indexed,  peer-reviewed , international  medical journal  publishing review articles and original papers on all aspects of  hematology . It is part of the  Expert Review  series, published by  Informa ."}
{"_id": "WikiPedia_Hematology$$$corpus_4858", "text": "The journal provides commentary and analysis to elucidate best clinical practice in hematology and to translate advances in research \u2013 in areas such as  immunology ,  stem cell  research, and cell and gene therapy \u2013 into the clinical context. Each review includes an \u2018expert commentary\u2019 and a 'five-year view' section, in which authors are asked to provide their personal view on the current status and future direction of the research discussed."}
{"_id": "WikiPedia_Hematology$$$corpus_4859", "text": "The journal is aided by an international editorial advisory board of experts practicing within the field."}
{"_id": "WikiPedia_Hematology$$$corpus_4860", "text": "Expert Review of Hematology  is currently in its 7th year of publication, has an  Impact Factor [ 1 ]  of 2.07, and is available online or is published in paper format 12 times a year."}
{"_id": "WikiPedia_Hematology$$$corpus_4861", "text": "Haematologica  is a monthly  peer-reviewed   open access   medical journal  published by the Ferrata Storti Foundation. The  editor-in-chief  is Jacob M. Rowe (Rambam Medical Center, Haifa, Israel). The journal covers all topics related to  experimental and clinical hematology . It was established in 1920 by  Adolfo Ferrata ."}
{"_id": "WikiPedia_Hematology$$$corpus_4862", "text": "The journal is abstracted and indexed in  Biological Abstracts , [ 1 ]   BIOSIS Previews , [ 1 ]   Current Contents /Clinical Medicine, [ 1 ]  Current Contents/Life Sciences, [ 1 ]   Embase , [ 2 ]   Science Citation Index Expanded , [ 1 ]  and  Scopus . [ 3 ]  According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 11.049. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4863", "text": "International Journal of Hematology  is the official  journal  of the  Japanese Society of Hematology . [ 1 ]  Since 2008, it has been published by  Springer Japan , but used to be published by  Carden Jennings . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4864", "text": "International Journal of Hematology  is indexed in the following databases:"}
{"_id": "WikiPedia_Hematology$$$corpus_4865", "text": "The  Journal of Thrombosis and Haemostasis  is a monthly  peer-reviewed   medical journal  covering research on  thrombosis  and  hematology  in general. It is published by  Wiley-Blackwell  and the  editors-in-chief  are David Lillicrap and James Morrissey. Former editors-in-chief include Frits Rosendaal, Pieter Reitsma, Mike Greaves, David Lane, Pier Mannucci, Jos Vermylen, Jan Sixma, Francois Duckert, and  Rosemary Biggs . It is an official journal of the  International Society on Thrombosis and Haemostasis ."}
{"_id": "WikiPedia_Hematology$$$corpus_4866", "text": "According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 16.036. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4867", "text": "Leukemia  is a  peer-reviewed   medical journal  published by the  Nature Publishing Group . It was established in 1987 by  Nicole Muller-B\u00e9rat Killman  and  Sven-Aage Killman , and is currently edited by Professors Andreas Hochhaus and Robert Peter Gale. The journal covers research on all aspects of  leukemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_4868", "text": "According to the  Journal Citation Reports , the journal had a 2020  impact factor  of 11.528. [ 1 ]  In the past, the journal has been accused of practicing  coercive citation . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4869", "text": "Leukemia & Lymphoma  is a  peer-reviewed   medical journal  published by  Informa Healthcare . It covers basic and clinical aspects of hematologic malignancies ( leukemias  and  lymphomas ). The  editors-in-chief  are Aaron Polliack ( Hadassah University Hospital ), Koen Van Besien ( Weill Cornell Medical Center ), and John Seymour ( Peter MacCallum Cancer Centre )."}
{"_id": "WikiPedia_Hematology$$$corpus_4870", "text": "According to the  Journal Citation Reports , the journal has a 2014  impact factor  of 2.891. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4871", "text": "Leukemia Research  is a monthly  peer-reviewed   medical journal  covering research on  hematologic malignancies . It was established in 1977 and is published by  Elsevier . The  editor-in-chief  is Clive S. Zent ( James P. Wilmot Cancer Center )."}
{"_id": "WikiPedia_Hematology$$$corpus_4872", "text": "The journal is abstracted and indexed by: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4873", "text": "According to the  Journal Citation Reports , the journal has a 2017  impact factor  of 2.319. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4874", "text": "memo - Magazine of European Medical Oncology   is a  peer-reviewed   medical journal  published by  Springer  and covering the fields of  hematology  and  oncology .  memo  is the official journal of the  Central European Cooperative Oncology Group . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4875", "text": "memo  includes editorials and comments, peer-reviewed original reports, short reviews, case reports and controversies, articles explaining the  biology  of  neoplasia , and congress reports."}
{"_id": "WikiPedia_Hematology$$$corpus_4876", "text": "The journal is abstracted and indexed by  EMBASE , Expanded Academic,  Google Scholar , and Summon by Serial Solutions."}
{"_id": "WikiPedia_Hematology$$$corpus_4877", "text": "The Central European Cooperative Oncology Group groups centers of clinical oncology from Central and Southeastern Europe as well as  Israel  that conduct of clinical trials. It also provides postgraduate education in oncology."}
{"_id": "WikiPedia_Hematology$$$corpus_4878", "text": "Pediatric Blood & Cancer  is a  peer-review  online-only  medical journal  covering  pediatric oncology  and  hematology . It was established in 1975 as  Medical and Pediatric Oncology , obtaining its current name in 2004. [ 1 ] [ 2 ]  Starting in January 2014, it stopped publishing its print edition and moved to an exclusively online format. [ 3 ]  The  editor-in-chief  is Peter E. Newburger ( University of Massachusetts Medical School ). According to the  Journal Citation Reports , the journal has a 2021  impact factor  of 3.838, ranking it 30th out of 130 journals in the category \"Pediatrics\", [ 4 ]  39th out of 78 journals in the category \"Hematology\", [ 5 ]  and 141st out of 245 journals in the category \"Oncology\". [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4879", "text": "This article about a  pediatrics   journal  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_4880", "text": "Platelets  is a  peer-reviewed   medical journal  covering all aspects of  platelet -related research. The  editors-in-chief  are Steve Watson and Paul Harrison ( University of Birmingham ). It was established in 1990 and is published by  Taylor & Francis ."}
{"_id": "WikiPedia_Hematology$$$corpus_4881", "text": "Official website"}
{"_id": "WikiPedia_Hematology$$$corpus_4882", "text": "Seminars in Thrombosis and Hemostasis  is a  peer-reviewed   medical   review journal  covering  hematology , with a specific focus on disorders related to  thrombosis  and  hemostasis . It was established in 1974 and is published eight times per year by  Thieme Medical Publishers . The  editor-in-chief  is Emmanuel J. Favaloro. According to the  Journal Citation Reports , the journal has a 2018  impact factor  of 3.401. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4883", "text": "Thrombosis and Haemostasis  is a  peer-review   scientific journal  of  medicine . It is published by  Thieme Medical Publishers . It is the official journal of several groups and societies:  European Society of Cardiology  (Thrombosis working group, Atherosclerosis and Vascular Biology working group),  Sociedad Espa\u00f1ola de Trombosis y Hemostasia ,  Australian Vascular Biology Society , and  Gesellschaft f\u00fcr Thrombose- und H\u00e4mostaseforschung e.V .  A related publication is  TH Open . The journal was established in 1957 and is published monthly. The current  editors-in-chief  are Christian Weber and Gregory Y. H. Lip."}
{"_id": "WikiPedia_Hematology$$$corpus_4884", "text": "The journal is  abstracted and indexing  in the following bibliographic databases: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4885", "text": "According to the  Journal Citation Reports , the journal has a 2017  impact factor  of 4.952. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4886", "text": "Transfusion  is a monthly  peer-reviewed   medical journal  covering  transfusion medicine  that is published by  Wiley  on behalf of the  Association for the Advancement of Blood and Biotherapies . According to the  Journal Citation Reports , it had a 2021  impact factor  of 3.337. [ 1 ]  The journal was established in 1960 with  Tibor J. Greenwalt  as its founding  editor-in-chief . [ 2 ] [ 3 ]  As of 2021, the editor-in-chief is Richard Kaufman. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4887", "text": "The journal is abstracted and indexed in  Scopus , [ 5 ]   Index Medicus / MEDLINE / PubMed , [ 6 ]   EMBASE ,  CINAHL ,  BIOSIS Previews ,  CAB Abstracts , [ 7 ]   Current Contents /Clinical Medicine and Life Sciences,  Biological Abstracts , and the  Science Citation Index Expanded . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4888", "text": "Vox Sanguinis , formerly known as the  Bulletin of the Central Laboratory of the Blood Transfusion Service of the Dutch Red Cross , is a  peer-reviewed   medical journal  covering  hematology . It was established in 1953 and published 8 times per year by  Wiley-Blackwell  on behalf of the International Society of Blood Transfusion. The  editor-in-chief  is Miquel Lozano ( Clinic Barcelona  Secci\u00f3n de Hemotherapia). According to the  Journal Citation Reports , the journal has a 2019 impact factor of 2.347, ranking it 46th out of 76 journals in the category \"Hematology\". [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4889", "text": "An  anti-CD22 immunotoxin  is a  monoclonal antibody  targeting  CD22  linked to a  cytotoxic agent . As of August 2009, it was studied in the treatment of some types of  B-cell  cancer.\nIt binds to CD22, a receptor  protein  on the surface of normal B cells and B-cell  tumors , and, upon internalization, kills the cells, acting as  immunotoxin ."}
{"_id": "WikiPedia_Hematology$$$corpus_4890", "text": "As of August 2009, several anti-CD22 immunotoxins are undergoing clinical trials."}
{"_id": "WikiPedia_Hematology$$$corpus_4891", "text": "CAT-3888 or BL22 is an anti-CD22  immunotoxin  and in 2015 completed a  Phase I  clinical (human) trial for the treatment of  hairy cell leukemia [ 1 ]  at the  NIH  in the U.S."}
{"_id": "WikiPedia_Hematology$$$corpus_4892", "text": "Technically, CAT-3888 is an anti-CD22 immunotoxin fusion protein between a murine anti-CD22 disulfide-linked Fv (dsFv)  antibody fragment  and an edited copy of bacterial Pseudomonas exotoxin PE38.  The toxin is activated intracellularly, by the low  pH  of the  lysosome  into which the entire protein was internalized via the CD22 receptor.  The toxin kills the targeted cell through  ribosome  inactivation. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4893", "text": "CAT-3888 was initially designed and produced at the U.S.  National Cancer Institute , one of the agencies which make up the  NIH .  As of 2005, early development of BL22 was funded by California biotech  Genencor . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4894", "text": "In 2001, results  of remissions in a phase I trial for  leukemia  were reported. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4895", "text": "CAT-3888 was succeeded by  moxetumomab pasudotox  (CAT-8015, HA22), an anti-CD22 immunotoxin comprising a modified  Pseudomonas exotoxin  and an anti- CD22  antibody fragment. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4896", "text": "Like CAT-3888, CAT-8015 changes three amino acids in the antibody fragment to increase the binding affinity for the target molecule.  Both of these proteins are designed to bind to the same part of the CD22 receptor on the surface of B cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4897", "text": "Research is being carried on directly by Dr. Robert J. Kreitman at the National Cancer Institute. [ 6 ]  The patent holder is MedImmune, a subsidiary of AstraZeneca. [ 7 ]  MedImmune discontinued development of CAT-3888 in 2008 and continues to develop CAT-8015. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4898", "text": "Early Phase I results find that CAT-8015 exhibits a greater affinity for CD22 than  CAT-3888. [ 9 ]  It may be useful against any B cell  leukemia  or  lymphoma , and indeed is currently in a Phase I clinical trial, also at NIH, in patients with non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL). [ 10 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4899", "text": "Cambridge Antibody Technology  acquired CAT-3888 and CAT-8015 in 2005 from  Genencor , a subsidiary of  Danisco [ 3 ]  (where they were known as GCR-3888 and GCR-8015). [ 13 ]  CAT was then purchased in 2007 by British pharmaceutical company  AstraZeneca  for $15.2 billion. [ 14 ] [ 15 ]  AstraZeneca consolidated its biologics portfolio in MedImmune and Cambridge Antibody Technology which was rebranded to create a dedicated biologics division known as 'MedImmune'. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4900", "text": "CAT-5001  (formerly SS1P) is a  Pseudomonas exotoxin   immunotoxin  that targets  mesothelin , which is a cell surface  glycoprotein  present on normal mesothelial cells that is overexpressed in numerous cancers including  pleural  and  peritoneal mesothelioma ,  ovarian cancer  and  pancreatic cancer . [ 5 ]   Cambridge Antibody Technology  acquired CAT-5001 from Enzon Pharmaceuticals in May 2006. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4901", "text": "Avatrombopag , sold under the brand name  Doptelet ,  is a  medication  that used for certain conditions that lead to  thrombocytopenia  (low  platelets ) such as thrombocytopenia associated with  chronic liver disease  in adults who are to undergo a planned medical or dental procedure. [ 8 ] [ 9 ]  It was approved for medical use in the United States in May 2018, [ 10 ] [ 11 ]  the European Union in June 2019, [ 7 ]  and Australia in January 2023. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4902", "text": "It acts as a  thrombopoietin receptor  agonist. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4903", "text": "Benzestrol  ( INN Tooltip International Nonproprietary Name ,  BAN Tooltip British Approved Name ) (brand names  Chemestrogen ,  Ocestrol ,  Octestrol ,  Octoestrol ,  Octofollin ) is a  synthetic   nonsteroidal estrogen  of the  stilbestrol  group which was formerly used medically but has since been discontinued. [ 1 ] [ 2 ] [ 3 ]  The stilbestrol estrogens, the best-known of which is  diethylstilbestrol  (DES) were used extensively in the mid-1900s and were finally banned by the FDA due to them causing tumors in the children of women who used them. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4904", "text": "Benzestrol and other stilbestrol were used as synthetic estrogens in order to prevent premature births. [ 4 ]  Based on the idea that premature births happened because the mother did not produce enough estrogen on her own, doctors prescribed benzestrol to mothers in order to increase their estrogen levels."}
{"_id": "WikiPedia_Hematology$$$corpus_4905", "text": "Studies have been done in the past on normal, mature and castrate female rats. Benzestrol produced the same type of estrus in the castrate rat when injected at 0.8 to 1.0 micrograms as when the rat was injected with 2.0 to 2.5 micrograms of estrone. [ 5 ]  This is significant because less benzestrol could be used to produce the same effect as estrone in increasing estrogen production. It has been used in the past as a nonsteroidal estrogen antagonist."}
{"_id": "WikiPedia_Hematology$$$corpus_4906", "text": "Benzestrol is described as a very potent estrogen. [ 6 ]  It is reported to have about 130% of the  relative binding affinity  of  estradiol  for the  estrogen receptors . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4907", "text": "Benzestrol is usually grouped with the stilbestrol estrogens. However, benzestrol is technically not a stilbestrol derivative because its central chain is elongated by one carbon. In any case, it is a very close analogue of the stilbestrol estrogens. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4908", "text": "Benzestrol is a drug in the stilbestrol family of estrogens. These drugs were first produced in the late 1930s. Benzestrol itself was reported in 1946. [ 1 ]  In 1953, experiments began on benzestrol and other stilbestrols to see if they actually helped stop premature births. This study in 1953 found that benzestrol did not in fact help stop premature births. [ 4 ]  A study in 1971 found that benzestrol was the cause of a rare vaginal cancer in girls and women whose mothers had been on benzestrol while pregnant. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4909", "text": "Centhaquine  (brand name  Lyfaquin ) is a cardiovascular drug. [ 1 ]   In India, it is approved for the treatment of  hypovolemic shock . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4910", "text": "Centhaquine is a  vasopressor  that activates  \u03b1 2A -  and  \u03b1 2B -adrenoreceptors . [ 3 ]  It increases  venous return  and improves  tissue perfusion ."}
{"_id": "WikiPedia_Hematology$$$corpus_4911", "text": "Efbemalenograstim alfa , sold under the brand name  Ryzneuta , is a  medication  used to decrease the incidence of infection in  chemotherapy -induced  neutropenia . [ 1 ]  It is a leukocyte growth factor. [ 1 ]  It is given by  subcutaneous  injection. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4912", "text": "The most common side effects of efbemalenograstim alfa are nausea, anemia, and thrombocytopenia. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4913", "text": "Efbemalenograstim alfa is an immunostimulant/colony stimulating factor that belongs to the class of  hematopoietic  growth factors (granulocyte colony stimulating factor; G CSF) which increase the production and differentiation of mature and functionally active neutrophils from bone marrow precursor cells. [ 2 ]  It was approved for medical use in China in May 2023, [ 4 ]  in the United States in November 2023, [ 5 ] [ 6 ]  and in the European Union in March 2024. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4914", "text": "In the US, efbemalenograstim alfa is  indicated  to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. [ 1 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4915", "text": "In the EU, efbemalenograstim alfa is indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in adults treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4916", "text": "Efbemalenograstim alfa can cause fatal splenic rupture, acute respiratory distress syndrome, serious allergic reactions including anaphylaxis, sickle cell crises in patients with sickle cell disorders, glomerulonephritis, thrombocytopenia, capillary leak syndrome, and myelodysplastic syndrome and acute myeloid leukemia in people with breast and lung cancer. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4917", "text": "The US  Food and Drug Administration  approved efbemalenograstim alfa based on evidence from two main clinical trials, GC-627-04 and GC-627-05, in 515 participants with breast cancer receiving chemotherapy. [ 5 ]  There was one participant included in the trial from the United States, and 514 participants were included from sites outside of the United States. [ 5 ]  The trials were conducted at 52 sites in five countries including Hungary, Russia, Ukraine, Bulgaria, and the United States. [ 5 ]  The same trials (GC-627-04 and GC-627-05) were used to assess efficacy and safety. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4918", "text": "Efbemalenograstim alfa was evaluated in two main clinical trials that were randomized and controlled. [ 5 ]  A total of 515 participants were randomized to receive efbemalenograstim alfa or placebo, or Neulasta, after receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia to treat metastatic breast cancer. [ 5 ]  Both trials evaluated the benefit and side effects of efbemalenograstim alfa in participants. [ 5 ]  The benefit of efbemalenograstim alfa was based on the mean duration of severe neutropenia seen in participants after receiving either efbemalenograstim alfa or control (placebo or Neulasta). [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4919", "text": "It was approved for medical use in China in May 2023, [ 4 ]  in the United States in November 2023, [ 1 ] [ 5 ]  and in the European Union in March 2024. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4920", "text": "In January 2024, the  Committee for Medicinal Products for Human Use  of the  European Medicines Agency  adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ryzneuta, intended to reduce the duration of neutropenia and the incidence of febrile neutropenia due to chemotherapy. [ 2 ]  The applicant for this medicinal product is Evive Biotechnology Ireland Limited. [ 2 ]  Efbemalenograstim alfa was approved for medical use in the European Union in March 2024. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4921", "text": "Eltrombopag , sold under the brand name  Promacta  among others, is a medication used to treat  thrombocytopenia  (abnormally low  platelet  counts) and severe aplastic anemia. [ 3 ] [ 4 ]  Eltrombopag is sold under the brand name  Revolade  outside the US and is marketed by  Novartis . [ 6 ]  It is a thrombopoietin receptor agonist. [ 3 ]  It is taken  by mouth . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4922", "text": "Eltrombopag was discovered as a result of research collaboration between  GlaxoSmithKline  and  Ligand Pharmaceuticals  and is transferred to Novartis Pharmaceuticals. [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4923", "text": "Eltrombopag was approved by the US  Food and Drug Administration  (FDA) in November 2008, for the treatment of thrombocytopenia in people with chronic  immune (idiopathic) thrombocytopenic purpura  who have had an insufficient response to  corticosteroids ,  immunoglobulin therapy , or  splenectomy . [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4924", "text": "In August 2015, the FDA approved eltrombopag (Promacta for oral suspension) for the treatment of thrombocytopenia in children one year of age and older with idiopathic thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4925", "text": "In  preclinical studies , the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the  JAK-STAT signaling pathway  and increased proliferation and differentiation of  megakaryocytes . Animal studies confirmed that it increased platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4926", "text": "Eltrombopag has been shown to be effective in two major clinical syndromes:  idiopathic thrombocytopenic purpura  (ITP) [ 14 ]  and  cirrhosis  due to  hepatitis C  (in which low platelet counts may be a contraindication for  interferon  treatment). [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4927", "text": "After six weeks of therapy in a  phase III trial , eltrombopag 50\u00a0mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic  idiopathic thrombocytopenic purpura  (ITP). [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4928", "text": "Eltrombopag received  breakthrough therapy  designation from the US  Food and Drug Administration  (FDA) in February 2014, for people with  aplastic anemia  for which immunosuppression has not been successful. [ 17 ]   In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4929", "text": "In October 2024, the  Committee for Medicinal Products for Human Use  of the  European Medicines Agency  adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Eltrombopag Viatris, intended for the treatment of people with primary immune thrombocytopenia (ITP) and thrombocytopenia associated with chronic hepatitis C. [ 19 ]  The applicant for this medicinal product is Viatris Limited. [ 19 ]  Eltrombopag Viatris was authorized in December 2024. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4930", "text": "It has been shown to produce a trilineage hematopoiesis in some people with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4931", "text": "Enarodustat  (development code  JTZ-951 ; brand name  Enaroy ) is a drug used for the treatment of  anemia , especially when associated with  chronic kidney disease  (CKD).  Enarodustat functions as a  inhibitor of hypoxia inducible factor-proly hydroxylase  (HIF-PH). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4932", "text": "The drug was approved in September 2020 in Japan for anemia associated with CKD [ 2 ]  and is currently in  clinical development  in the United States and South Korea. [ 3 ]   The drug is being developed by  Japan Tobacco  and JW Pharmaceutical. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4933", "text": "Exagamglogene autotemcel , sold under the brand name  Casgevy , is a  gene therapy  used for the treatment of  sickle cell disease [ 3 ] [ 5 ]  and transfusion-dependent  beta thalassemia . [ 3 ]  It was developed by  Vertex Pharmaceuticals  and  CRISPR Therapeutics . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4934", "text": "The treatment was approved in the United Kingdom for the treatment of sickle cell disease and transfusion-dependent beta thalassemia in November 2023. [ 10 ] [ 11 ] [ 12 ]  It was approved in the United States for the treatment of sickle cell disease in December 2023 and for the treatment of transfusion-dependent beta thalassemia in January 2024. [ 13 ] [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4935", "text": "Exagamglogene autotemcel is the first cell-based gene therapy treatment utilizing  CRISPR/Cas9 gene editing  technology to be approved by the US  Food and Drug Administration  (FDA). [ 13 ]  The most common side effects include low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache, and itching. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4936", "text": "In the UK, exagamglogene autotemcel is  indicated  for the treatment of transfusion-dependent beta thalassemia and sickle cell disease in patients aged 12 years and older who should be treated with  hematopoietic stem cell transplantation  but for whom a suitable stem cell donor is not available. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4937", "text": "In the US, exagamglogene autotemcel is indicated for the treatment of sickle cell disease in people aged 12 years and older with recurrent  vaso-occlusive crises , [ 6 ]  and for the treatment of people with transfusion-dependent beta-thalassemia. [ 6 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4938", "text": "The gene therapy is made from the recipient's own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. [ 13 ]  Prior to treatment, the recipient's own stem cells are collected, and then the recipient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in exagamglogene autotemcel. [ 13 ]  The modified blood stem cells are transplanted back into the recipient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4939", "text": "The most common side effects observed in clinical studies included low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4940", "text": "The safety and effectiveness of exagamglogene autotemcel were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent participants with sickle cell disease. [ 13 ]  Participants had a history of at least two protocol-defined severe vaso-occlusive crises during each of the two years prior to screening. [ 13 ]  The primary efficacy outcome was freedom from severe vaso-occlusive crisis episodes for at least twelve consecutive months during the 24-month follow-up period. [ 13 ]  A total of 44 participants were treated with exagamglogene autotemcel. [ 13 ]  Of the 31 participants with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. [ 13 ]  All treated participants achieved successful engraftment with no participants experiencing graft failure or  graft rejection . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4941", "text": "The US  Food and Drug Administration  (FDA) granted the application for exagamglogene autotemcel  priority review ,  orphan drug ,  fast track , and regenerative medicine advanced therapy designations. [ 13 ]  The FDA granted approval of Casgevy to Vertex Pharmaceuticals. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4942", "text": "In December 2023, the  Committee for Medicinal Products for Human Use  (CHMP) of the  European Medicines Agency  (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Casgevy, intended for the treatment of transfusion\u2011dependent \u03b2\u2011thalassemia and sickle cell disease. [ 7 ] [ 17 ]  As Casgevy is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies. [ 7 ]  The applicant for this medicinal product is Vertex Pharmaceuticals (Ireland) Limited. [ 7 ]  Exagamglogene autotemcel was approved for medical use in the European Union in February 2024. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4943", "text": "The therapy has a US list price of  US$2.2 million . [ 18 ]  The cost effectiveness threshold of the therapy in the US is estimated to be between $1.35 million and $2.05 million [ 19 ]  depending on perspective (healthcare vs limited societal) and assuming the  willingness to pay  for 1  quality-adjusted life year  (QALY) at $100,000\u2013$150,000. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4944", "text": "The UK price is estimated to be  \u00a31 million . [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4945", "text": "Ferric derisomaltose , sold under the brand name  Monoferric  among others, is a  medication  for the treatment of  iron deficiency anemia  in adults who have intolerance to  oral iron  or have had unsatisfactory response to oral iron or who have non-hemodialysis dependent  chronic kidney disease  ( NDD-CKD ). [ 4 ]  It was approved for use in the United States in January 2020. [ 4 ] [ 5 ] [ 6 ]  It is given intravenously. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4946", "text": "Filgrastim , sold under the brand name  Neupogen  among others, is a  medication  used to treat  low neutrophil count . [ 19 ]  Low neutrophil counts may occur with  HIV/AIDS , following  chemotherapy  or  radiation poisoning , or be of an unknown cause. [ 19 ]  It may also be used to increase white blood cells for gathering during  leukapheresis . [ 19 ]  It is given either by  injection into a vein  or  under the skin . [ 19 ]  Filgrastim is a leukocyte growth factor. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4947", "text": "Common side effects include fever, cough, chest pain, joint pain, vomiting, and hair loss. [ 19 ]  Severe side effects include  splenic rupture  and  allergic reactions . [ 19 ]  It is unclear if use in  pregnancy  is safe for the baby. [ 19 ]  Filgrastim is a recombinant form of the naturally occurring  granulocyte colony-stimulating factor  (G-CSF). [ 19 ]  It works by stimulating the body to increase  neutrophil  production. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4948", "text": "Filgrastim was approved for medical use in the United States in 1991. [ 19 ]  It is on the  World Health Organization's List of Essential Medicines . [ 20 ] [ 21 ]  Filgrastim  biosimilar  medications are available. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4949", "text": "Filgrastim is used to treat neutropenia; [ 18 ]  acute myeloid leukemia; [ 18 ]  nonmyeloid malignancies; [ 18 ]  leukapheresis; [ 18 ]  congenital neutropenia\u201a cyclic neutropenia\u201a or idiopathic neutropenia; [ 18 ]  and myelosuppressive doses of radiation. [ 18 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4950", "text": "Tbo-filgrastim (Granix) is  indicated  for reduction in the duration of severe neutropenia in people with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4951", "text": "The most commonly observed adverse effect is mild bone pain after repeated administration, [ 24 ]  and local skin reactions at the site of injection. [ 18 ]  Other observed adverse effects include serious allergic reactions (including a rash over the whole body, [ 25 ]  shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating),  ruptured spleen  (sometimes resulting in death), [ 26 ]   alveolar   hemorrhage ,  acute respiratory distress syndrome , and  hemoptysis . [ 18 ]  Severe  sickle cell crises , in some cases resulting in death, have been associated with the use of filgrastim in people with sickle cell disorders. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4952", "text": "Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes; this should be considered when interpreting bone-imaging results. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4953", "text": "G-CSF is a colony stimulating factor which has been shown to have minimal direct in vivo or in vitro effects on the production of other haematopoietic cell types. Neupogen (filgrastim) is the name for recombinant methionyl human granulocyte colony stimulating factor (r-metHuG-CSF). [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4954", "text": "In 2015, Sandoz's filgrastim-sndz (Zarxio), obtained the approval of the US  Food and Drug Administration  (FDA) as a biosimilar. [ 11 ] [ 27 ] [ 28 ]  This was the first product to be passed under the  Biologics Price Competition and Innovation Act of 2009  (BPCI Act), as part of the  Affordable Care Act . [ 11 ]  Zarxio was approved as a biosimilar, not as an interchangeable product, the FDA notes. And under the BPCI Act, only a biologic that has been approved as an \"interchangeable\" may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. The FDA said its approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4955", "text": "In 2018, filgrastim-aafi (Nivestym) was approved for use in the United States. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4956", "text": "In September 2008, Ratiograstim, Tevagrastim, Biograstim, and Filgrastim ratiopharm were approved for use in the European Union. [ 10 ] [ 29 ] [ 5 ] [ 30 ]  Filgrastim ratiopharm was withdrawn in July 2011 and Biograstim was withdrawn in December 2016."}
{"_id": "WikiPedia_Hematology$$$corpus_4957", "text": "In February 2009, Filgrastim Hexal and Zarzio were approved for use in the European Union. [ 31 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4958", "text": "In June 2010, Nivestim was approved for use in the European Union. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4959", "text": "In October 2013, Grastofil was approved for use in the European Union. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4960", "text": "In September 2014, Accofil was approved for use in the European Union. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4961", "text": "In 2016, Fraven was approved for use by Republic of Turkey ministry of health. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4962", "text": "Nivestym was approved for medical use in Canada in April 2020. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4963", "text": "In October 2021, Nypozi was approved for medical use in Canada. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4964", "text": "In February 2022, filgrastim-ayow (Releuko) was approved for medical use in the United States. [ 2 ] [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4965", "text": "In June 2024, filgrastim-txid (Nypozi) was approved for medical use in the United States. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4966", "text": "In December 2024, the  Committee for Medicinal Products for Human Use  of the  European Medicines Agency  adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zefylti, intended for the treatment of neutropenia and the mobilization of peripheral blood progenitor cells. [ 35 ]  The applicant for this medicinal product is CuraTeQ Biologics s.r.o. [ 35 ]  Zefylti is a biosimilar medicinal product. [ 35 ]  It is highly similar to the reference product Neupogen (filgrastim), which has been authorized in various EU countries. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4967", "text": "Shortly after it was introduced, analyses of whether filgrastim is a cost-effective way of preventing  febrile neutropenia  depended upon the clinical situation and the financial model used to pay for treatment. [ 36 ]  The longer-acting  pegfilgrastim  may in some cases be more cost-effective. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4968", "text": "2D9Q ,  1CD9 ,  1GNC ,  1PGR ,  1RHG"}
{"_id": "WikiPedia_Hematology$$$corpus_4969", "text": "1440"}
{"_id": "WikiPedia_Hematology$$$corpus_4970", "text": "12985"}
{"_id": "WikiPedia_Hematology$$$corpus_4971", "text": "ENSG00000108342"}
{"_id": "WikiPedia_Hematology$$$corpus_4972", "text": "ENSMUSG00000038067"}
{"_id": "WikiPedia_Hematology$$$corpus_4973", "text": "P09919"}
{"_id": "WikiPedia_Hematology$$$corpus_4974", "text": "P09920"}
{"_id": "WikiPedia_Hematology$$$corpus_4975", "text": "NM_000759 NM_001178147 NM_172219 NM_172220"}
{"_id": "WikiPedia_Hematology$$$corpus_4976", "text": "NM_009971"}
{"_id": "WikiPedia_Hematology$$$corpus_4977", "text": "NP_000750 NP_001171618 NP_757373 NP_757374"}
{"_id": "WikiPedia_Hematology$$$corpus_4978", "text": "NP_034101"}
{"_id": "WikiPedia_Hematology$$$corpus_4979", "text": "Granulocyte colony-stimulating factor  ( G-CSF  or  GCSF ), also known as  colony-stimulating factor 3  ( CSF 3 ), is a  glycoprotein  that stimulates the  bone marrow  to produce  granulocytes  and  stem cells  and release them into the  bloodstream . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4980", "text": "Functionally, it is a  cytokine  and  hormone , a type of  colony-stimulating factor , and is produced by a number of different  tissues . The  pharmaceutical  analogs of naturally occurring G-CSF are called  filgrastim  and  lenograstim ."}
{"_id": "WikiPedia_Hematology$$$corpus_4981", "text": "G-CSF also stimulates the survival, proliferation, differentiation, and function of  neutrophil precursors  and mature  neutrophils ."}
{"_id": "WikiPedia_Hematology$$$corpus_4982", "text": "G-CSF is produced by  endothelium ,  macrophages , and a number of other  immune  cells. The natural human glycoprotein exists in two forms, a 174- and 177- amino-acid -long  protein  of molecular weight 19,600\u00a0grams per  mole . The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by  recombinant DNA  (rDNA) technology. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4983", "text": "The gene for G-CSF is located on  chromosome 17 , locus q11.2-q12. Nagata et al. found that the GCSF gene has four  introns , and that two different  polypeptides  are synthesized from the same gene by differential splicing of mRNA. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4984", "text": "The two polypeptides differ by the presence or absence of three amino acids. Expression studies indicate that both have authentic GCSF activity. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4985", "text": "It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the  G-CSF factor stem-loop destabilising element . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4986", "text": "Chemotherapy can cause  myelosuppression  and unacceptably low levels of  white blood cells  ( leukopenia ), making patients susceptible to  infections  and  sepsis . G-CSF stimulates the production of  granulocytes , a type of white blood cell. In  oncology  and  hematology , a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality from  neutropenia  after  chemotherapy , allowing higher-intensity treatment regimens. [ 13 ]  It is administered to oncology patients via subcutaneous or intravenous routes. [ 14 ]  A QSP model of neutrophil production and a PK/PD model of a cytotoxic chemotherapeutic drug (Zalypsis) have been developed to optimize the use of G-CSF in chemotherapy regimens with the aim to prevent mild-neutropenia. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4987", "text": "G-CSF was first trialled as a therapy for neutropenia induced by chemotherapy in 1988. The treatment was well tolerated and a dose-dependent rise in circulating neutrophils was noted. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4988", "text": "A study in mice has shown that G-CSF may decrease  bone mineral density . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4989", "text": "G-CSF administration has been shown to attenuate the  telomere  loss associated with chemotherapy. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4990", "text": "Neutropenia  can be a severe side effect of  clozapine , an  antipsychotic  medication in the treatment of  schizophrenia . G-CSF can restore neutrophil count. Following a return to baseline after stopping the drug, it may sometimes be safely  rechallenged  with the added use of G-CSF. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4991", "text": "G-CSF is also used to increase the number of  hematopoietic stem cells  in the blood of the donor before collection by  leukapheresis  for use in  hematopoietic stem cell transplantation . For this purpose, G-CSF appears to be safe in  pregnancy  during  implantation  as well as during the  second and third trimesters . [ 21 ]   Breastfeeding  should be withheld for three days after CSF administration to allow for  clearance  of it from the milk. [ 21 ]  People who have been administered colony-stimulating factors do not have a higher risk of  leukemia  than people who have not. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4992", "text": "G-CSF may also be given to the receiver in  hematopoietic stem cell transplantation , to compensate for  conditioning regimens . [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4993", "text": "The skin disease  Sweet's syndrome  is a known side effect of using this drug. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4994", "text": "Two research teams independently identified mouse granulocyte-colony stimulating factor (G-CSF) in the 1960s: Ray Bradley at  Universtiy of Melbourne  and  Donald Metcalf  at  Walter and Eliza Hall Institute , from  Australia , and Yasuo Ichikawa, Dov Pluznik and  Leo Sachs  at the  Weizmann Institute of Science ,  Israel . [ 23 ] [ 24 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4995", "text": "In 1983, Donald Metcalf's research team, led by  Nicos Nicola , isolated the murine cytokine from medium conditioned with lung tissue obtained from endotoxin-treated mice. [ 25 ] [ 26 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4996", "text": "In 1985,  Karl Welte ,  Erich Platzer ,  Janice Gabrilove ,  Roland Mertelsmann  and  Malcolm Moore  at the  Memorial Sloan Kettering Cancer Center  (MSK) purified human G-CSF produced by bladder cancer cell line 5637 from conditioned medium. [ 27 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4997", "text": "In 1986, Karl Welte's team at MSK patented the method of producing and using human G-CSF under the name \"human hematopoietic pluripotent colony stimulating factor\" or \"human pluripotent colony stimulating factor\" (P-CSF). [ 28 ]  Also in 1986, two independent research groups working with pharmaceutical companies cloned the G-CSF gene that made possible large-scale production and its clinical use:  Shigekazu Nagata 's team in collaboration with  Chugai Pharmaceutical Co . from  Japan , and  Lawrence Souza 's team at  Amgen  in collaboration with Karl Welte's research team members from  Germany  and the  USA . [ 12 ] [ 29 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4998", "text": "The  recombinant  human G-CSF (rhG-CSF) synthesised in an  E. coli  expression system is called  filgrastim . The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_4999", "text": "The  Food and Drugs Administration  (FDA) first approved filgrastim on February 20, 1991 marketed by  Amgen  with the brand name  Neupogen . [ 30 ]  It was innitially approved to reduce the risk of infection in patients with non-myeloid malignancies who are taking myelosuppressive anti-cancer drugs associated with  febrile neutropenia  with fever. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5000", "text": "Several bio-generic versions are now also available in markets such as Europe and Australia. Filgrastim (Neupogen) and  PEG-filgrastim  (Neulasta), or  pegylated  form of filgratim, are two commercially available forms of rhG-CSF. The pegylated form of filgratim form has a much longer  half-life , reducing the necessity of daily injections."}
{"_id": "WikiPedia_Hematology$$$corpus_5001", "text": "The FDA approved the first  biosimilar  of Neulasta in June 2018. It is made by  Mylan  and sold as Fulphila. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5002", "text": "Another form of rhG-CSF called  lenograstim  is synthesised in  Chinese hamster ovary cells  (CHO cells). As this is a mammalian cell expression system, lenograstim is indistinguishable from the 174-amino acid natural human G-CSF. No clinical or therapeutic consequences of the differences between filgrastim and lenograstim have yet been identified, but there are no formal comparative studies."}
{"_id": "WikiPedia_Hematology$$$corpus_5003", "text": "In 2015, filgrastim was included on the  WHO Model List of Essential Medicines , a list containing the medications considered to be most effective and safe to meet the most important needs in a  health system . [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5004", "text": "G-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents. [ 34 ] [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5005", "text": "Mesoblast  planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus  SDF  (stromal cell-derived factor) directly to the heart. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5006", "text": "G-CSF has been shown to reduce  inflammation , reduce  amyloid beta  burden, and reverse cognitive impairment in a mouse model of  Alzheimer's disease . [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5007", "text": "Due to its neuroprotective properties, G-CSF is currently under investigation for  cerebral ischemia  in a clinical phase IIb  [ 38 ]  and several clinical pilot studies are published for other neurological disease such as  amyotrophic lateral sclerosis [ 39 ]  A combination of human G-CSF and  cord blood  cells has been shown to reduce impairment from chronic traumatic brain injury in rats. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5008", "text": "1CSG ,  2GMF ,  4NKQ ,  5C7X ,  5D70 ,  5D71 ,  5D72 ,  4RS1"}
{"_id": "WikiPedia_Hematology$$$corpus_5009", "text": "1437"}
{"_id": "WikiPedia_Hematology$$$corpus_5010", "text": "12981"}
{"_id": "WikiPedia_Hematology$$$corpus_5011", "text": "ENSG00000164400"}
{"_id": "WikiPedia_Hematology$$$corpus_5012", "text": "ENSMUSG00000018916"}
{"_id": "WikiPedia_Hematology$$$corpus_5013", "text": "P04141"}
{"_id": "WikiPedia_Hematology$$$corpus_5014", "text": "P01587"}
{"_id": "WikiPedia_Hematology$$$corpus_5015", "text": "NM_000758"}
{"_id": "WikiPedia_Hematology$$$corpus_5016", "text": "NM_009969"}
{"_id": "WikiPedia_Hematology$$$corpus_5017", "text": "NP_000749"}
{"_id": "WikiPedia_Hematology$$$corpus_5018", "text": "NP_034099"}
{"_id": "WikiPedia_Hematology$$$corpus_5019", "text": "Granulocyte-macrophage colony-stimulating factor  ( GM-CSF ), also known as  colony-stimulating factor 2 (CSF2) , is a  monomeric   glycoprotein  secreted by  macrophages ,  T cells ,  mast cells ,  natural killer cells ,  endothelial cells  and  fibroblasts  that functions as a  cytokine . The  pharmaceutical  analogs of naturally occurring GM-CSF are called  sargramostim  and  molgramostim ."}
{"_id": "WikiPedia_Hematology$$$corpus_5020", "text": "Unlike  granulocyte colony-stimulating factor , which specifically promotes  neutrophil  proliferation and maturation, GM-CSF affects more cell types, especially macrophages and  eosinophils . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5021", "text": "GM-CSF is a  monomeric   glycoprotein  that functions as a  cytokine \u2014it is a  white blood cell   growth factor . [ 6 ]  GM-CSF stimulates  stem cells  to produce  granulocytes  ( neutrophils ,  eosinophils , and  basophils ) and  monocytes . Monocytes exit the circulation and migrate into tissue, whereupon they mature into  macrophages  and  dendritic cells . Thus, it is part of the  immune / inflammatory   cascade , by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting  infection . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5022", "text": "GM-CSF also has some effects on mature cells of the immune system. These include, for example, enhancing neutrophil migration and causing an alteration of the receptors expressed on the cells surface. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5023", "text": "GM-CSF signals via signal transducer and activator of transcription,  STAT5 . [ 8 ]  In macrophages, it has also been shown to signal via  STAT3 . The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of  reactive oxygen species  that culminate in fungal zinc starvation and toxicity. [ 9 ]  Thus, GM-CSF facilitates development of the immune system and promotes defense against infections. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5024", "text": "GM-CSF also plays a role in embryonic development by functioning as an  embryokine  produced by reproductive tract. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5025", "text": "The human gene has been localized in close proximity to the  interleukin 3  gene within a  T helper  type 2-associated cytokine gene cluster at chromosome region 5q31, which is known to be associated with interstitial deletions in the  5q- syndrome  and  acute myelogenous leukemia . GM-CSF and IL-3 are separated by an insulator element and thus independently regulated. [ 11 ]  Other genes in the cluster include those encoding  interleukins 4 ,  5 , and  13 . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5026", "text": "Human granulocyte-macrophage colony-stimulating factor is glycosylated in its mature form. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5027", "text": "GM-CSF was first cloned in 1985, and soon afterwards three potential drug products were being made using  recombinant DNA  technology:  molgramostim  was made in  Escherichia coli  and is not glycosylated,  sargramostim  was made in yeast, has a leucine instead of proline at position 23 and is somewhat glycosylated, and  regramostim  was made in Chinese hamster ovary cells (CHO) and has more glycosylation than sargramostim.  The amount of glycosylation affects how the body interacts with the drug and how the drug interacts with the body. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5028", "text": "At that time,  Genetics Institute, Inc.  was working on molgramostim, [ 14 ]   Immunex  was working on  sargramostim  (Leukine), [ 15 ]  and  Sandoz  was working on regramostim. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5029", "text": "Molgramostim was eventually co-developed and co-marketed by Novartis and Schering-Plough under the trade name Leucomax for use in helping white blood cell levels recover following chemotherapy, and in 2002 Novartis sold its rights to Schering-Plough. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5030", "text": "Sargramostim was approved by the US FDA in 1991 to accelerate white blood cell recovery following autologous  bone marrow transplantation  under the trade name Leukine, and passed through several hands, ending up with  Genzyme , [ 19 ]  which was subsequently acquired by  Sanofi . Leukine is now owned by Partner Therapeutics (PTx)."}
{"_id": "WikiPedia_Hematology$$$corpus_5031", "text": "Imlygic was approved by the US FDA in October 2015, [ 20 ]  and in December 2015 by the EMA, as an oncolytic virotherapy, commercialized by Amgen Inc. This  oncolytic herpes virus , named  Talimogene laherparepvec , has been genetically engineered to express human GM-CSF using the tumor cells machinery. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5032", "text": "GM-CSF is found in high levels in joints with  rheumatoid arthritis  and blocking GM-CSF as a  biological target  may reduce the inflammation or damage. Some drugs (e.g.  otilimab ) are being developed to  block  GM-CSF. [ 22 ]  In critically ill patients GM-CSF has been trialled as a therapy for the immunosuppression of critical illness, and has shown promise restoring  monocyte [ 23 ]  and  neutrophil [ 24 ]  function, although the impact on patient outcomes is currently unclear and awaits larger studies."}
{"_id": "WikiPedia_Hematology$$$corpus_5033", "text": "GM-CSF stimulates  monocytes  and  macrophages  to produce pro-inflammatory cytokines, including  CCL17 . [ 25 ]  Elevated GM-CSF has been shown to contribute to inflammation in  inflammatory arthritis ,  osteoarthritis ,  colitis   asthma ,  obesity , and  COVID-19 . [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5034", "text": "Monoclonal antibodies  against GM-CSF are being used as treatment in clinical trials against  rheumatoid arthritis ,  ankylosing spondylitis , and COVID-19. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5035", "text": "A  hematinic  is a  nutrient  required for the formation of  blood cells  in the process of  hematopoiesis . [ 1 ]  The main hematinics are  iron ,  Vitamin B 12 , and  folate . [ 2 ]  Deficiency in hematinics can lead to  anaemia . In cases of hematinic deficiency, hematinics can be administered as medicines, in order to increase the  hemoglobin  content of the  blood ."}
{"_id": "WikiPedia_Hematology$$$corpus_5036", "text": "Erythropoietin  (EPO) is a  hormone  that stimulates  erythropoiesis , which can also be given as a medicine to increase the hemoglobin content of the blood, but EPO is not classified as a hematinic as it is not considered a nutrient, but a hormone."}
{"_id": "WikiPedia_Hematology$$$corpus_5037", "text": "Iron(III)-hydroxide polymaltose complex   is a medication used to treat iron deficiency / iron deficiency anemia and belongs to the group of oral  iron preparations . The preparation is a macromolecular complex, consisting of  iron(III) hydroxide  (trivalent iron, Fe 3+ , Fe(OH) 3 \u00b7H 2 O) and the carrier polymaltose and is available in solid form as a film-coated or chewable tablet and in liquid form as a syrup, drinkable solution, or drops.  It is used for treating  iron deficiency  without anemia (latent iron deficiency) or with  anemia  (apparent iron deficiency). Prior to administration, the iron deficiency should be diagnostically established and verified via laboratory tests (e.g., low  ferritin  concentration, low  transferrin saturation )."}
{"_id": "WikiPedia_Hematology$$$corpus_5038", "text": "The drug has been on the market since 1978 and is approved in over 85 countries. In many countries it is known with brand name Maltofer."}
{"_id": "WikiPedia_Hematology$$$corpus_5039", "text": "The drug is absorbed in the small intestine, primarily in the  duodenum  and  jejunum . Absorption occurs via a controlled, active mechanism. No passive diffusion takes place, which ensures that practically no unbound (to  transferrin ) iron reaches the blood. [ 1 ]  The absorbed iron is primarily stored in the  liver  as ferritin (protein used for iron storage) and subsequently made available to the body for various functions, primarily for incorporation into the red blood cells'  hemoglobin , thereby transporting oxygen in the blood."}
{"_id": "WikiPedia_Hematology$$$corpus_5040", "text": "The utilization and absorption by the erythrocytes of the iron administered orally in the form of iron polymaltose complex is correlated with the absorption in the intestines, whereby the relative absorption decreases with increased dosage and the more severe the iron deficiency, the greater the Absorption. [ 2 ]  As with ascorbate and sulfate oral iron preparations, only about 10-15% of the iron is absorbed. [ 3 ]  A dose of 100\u00a0mg of iron is thus necessary in order for 10\u00a0mg to be absorbed."}
{"_id": "WikiPedia_Hematology$$$corpus_5041", "text": "After administration, the maximum absorption capacity is reached already after 30 minutes and continuously increasing absorption can be observed over 24 hours. [ 2 ]  The non-absorbed iron is excreted via the stool."}
{"_id": "WikiPedia_Hematology$$$corpus_5042", "text": "The effectiveness and safety have been investigated and documented in numerous clinical studies and in various patient populations. [ 4 ]  This has included children, young people, adults, and the elderly, in addition to pregnant women and breastfeeding mothers."}
{"_id": "WikiPedia_Hematology$$$corpus_5043", "text": "Randomized , open, multicenter, controlled study in pregnant women affected by iron deficiency anemia. INTERVENTION: Iron polymaltose 100\u00a0mg 2x a day in comparison to iron sulfate 100\u00a0mg 2x a day.  STUDY DURATION: 90 days. RESULTS: hemoglobin improvement after 90 days by 2.16g/dL (iron polymaltose) and 1.93g/dL (iron sulfate). Ferritin levels after 90 days: 17.9\u00a0ng/mL (iron polymaltose), 15.7\u00a0ng/mL (iron sulfate). Side-effects observed in 29.3% of patients receiving iron polymaltose and 56.4% of those receiving iron sulfate. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5044", "text": "Randomized, open study in children affected by iron deficiency anemia. INTERVENTION: Iron polymaltose 5\u00a0mg/kg body weight in one administration a day, compared to iron sulfate 5\u00a0mg/kg body weight, divided up over 2 administrations a day. STUDY DURATION: 4 months. RESULTS: hemoglobin improvement after 4 months by 2.3g/dL (iron polymaltose) and 3g/dL (iron sulfate). Fewer gastrointestinal side-effects with iron polymaltose. The mean acceptance value after 4 months was higher with iron polymaltose than with iron sulfate. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5045", "text": "Randomized, multicenter, double-blind study in adults affected by iron deficiency anemia. INTERVENTION: Iron polymaltose 100\u00a0mg 2x a day in comparison to iron sulfate 60\u00a0mg 3x a day.  STUDY DURATION: 9 weeks. RESULTS: hemoglobin improvement in both groups after 3, 6, and 9 weeks, whereby after 3 and 6 weeks, a significant improvement was observed in the iron sulfate group. After 9 weeks, comparable improvement in both groups. Side-effects occurred in 22% of patients receiving iron polymaltose and 25% of those receiving iron sulfate. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5046", "text": "Iron polymaltose must not be used in the event of known  hypersensitivity  or intolerance to the active ingredient or one of the excipients. Iron preparations are not administered to treat anemia that is not associated with iron deficiency. Furthermore, iron preparations must not be used in the event of known iron overload or iron utilization disorders."}
{"_id": "WikiPedia_Hematology$$$corpus_5047", "text": "Iron polymaltose must not be administered at the same time as parenteral iron preparations. No interactions with other medications or foods are known."}
{"_id": "WikiPedia_Hematology$$$corpus_5048", "text": "Commonly observed side-effects, occurring in 1 to 10% of cases, include stool discoloration,  diarrhea ,  nausea , and  dyspepsia . Uncommon side-effects, occurring in 0.1 to 1% of cases, include  constipation ,  vomiting ,  stomachache ,  tooth discoloration ,  itchiness , and  headache . As very rare side-effects, occurring in 0.1 to 0.01% of cases,  allergic  reactions have been observed."}
{"_id": "WikiPedia_Hematology$$$corpus_5049", "text": "The preparation is available in various galenic formulations: syrup, drops, drinkable solution, film-coated tablets, and chewable tables. The syrup, drops, or drinkable solution are preferable for children. The preparation is dosed according to age. The following general dosage guidelines apply (for iron deficiency with anemia):"}
{"_id": "WikiPedia_Hematology$$$corpus_5050", "text": "The quantity of active ingredient per unit is 100\u00a0mg of iron per chewable or film-coated tablet, 50\u00a0mg of iron per 1mL of drops, 10\u00a0mg of iron per 1mL of syrup, 100\u00a0mg of iron per 1 drinkable solution (5mL)."}
{"_id": "WikiPedia_Hematology$$$corpus_5051", "text": "Iron polymaltose should be taken with food, as this improves absorption. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5052", "text": "The preparation contains different excipients depending upon the galenic formulation."}
{"_id": "WikiPedia_Hematology$$$corpus_5053", "text": "The preparation should be stored in its original packaging at room temperature (15-25\u00a0\u00b0C) and consumed by the date printed on the packaging."}
{"_id": "WikiPedia_Hematology$$$corpus_5054", "text": "Iron supplements , also known as  iron salts  and  iron pills , are a number of  iron  formulations used to treat and prevent  iron deficiency  including  iron deficiency anemia . [ 11 ] [ 12 ]  For prevention they are only recommended in those with  poor absorption ,  heavy menstrual periods ,  pregnancy ,  hemodialysis , or a diet low in iron. [ 12 ] [ 13 ]  Prevention may also be used in  low birth weight  babies. [ 12 ]  They are taken by mouth,  injection into a vein , or  injection into a muscle . [ 12 ]  While benefits may be seen in days, up to two months may be required until iron levels return to normal. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5055", "text": "Common side effects include  constipation , abdominal pain, dark stools, and  diarrhea . [ 14 ]  Other side effects, which may occur with excessive use, include  iron overload  and  iron toxicity . [ 11 ] [ 13 ]  Ferrous salts used as supplements by mouth include  ferrous fumarate ,  ferrous gluconate ,  ferrous succinate , and  ferrous sulfate . [ 13 ]  Injectable forms include  iron dextran  and  iron sucrose . [ 13 ]  They work by providing the iron needed for  making red blood cells . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5056", "text": "Iron pills have been used medically since at least 1681, with an easy-to-use formulation being created in 1832 using Chicken  Liver  extracts and majority from plants. [ 15 ]  Ferrous salt is on the  World Health Organization's List of Essential Medicines . [ 16 ]  Ferrous salts are available as a  generic medication  and  over the counter . [ 11 ]   Slow release  formulations, while available, are not recommended. [ 12 ]  In 2021, ferrous sulfate was the 105th most commonly prescribed medication in the United States, with more than 6 \u00a0 million prescriptions. [ 17 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5057", "text": "Iron supplements are used to treat or prevent  iron deficiency  and  iron-deficiency anemia ; [ 8 ]  parenteral irons can also be used to treat functional iron deficiency, where requirements for iron are greater than the body's ability to supply iron such as in inflammatory states. The main criterion is that other causes of anemia have also been investigated, such as  vitamin B 12  or  folate deficiency , drug induced or due to other poisons such as lead, as often the anemia has more than one underlying cause. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5058", "text": "Iron deficiency anemia is classically a microcytic, hypochromic anemia. Generally, in the UK oral preparations are trialled before using parenteral delivery, [ 20 ]  unless there is the requirement for a rapid response, previous intolerance to oral iron or likely failure to respond. Intravenous iron may decrease the need for  blood transfusions  however it increases the risk of infections when compared to oral iron. [ 21 ]  Daily oral supplementation of iron during pregnancy reduces the risk of maternal anemia and that effects on infant and on other maternal outcomes are not clear. [ 22 ]  Another review found tentative evidence that intermittent iron supplements by mouth for mothers and babies is similar to daily supplementation with fewer side effects. [ 23 ]  Supplements by mouth should be taken on an empty stomach, optionally with a small amount of food to reduce discomfort. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5059", "text": "Athletes may be at elevated risk of iron deficiency and so benefit from supplementation, but the circumstances vary between individuals and dosage should be based on tested  ferritin  levels, since in some cases supplementation may be harmful. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5060", "text": "Frequent blood donors may be advised to take iron supplements.  Canadian Blood Services  recommends discussing \"taking iron supplements with your doctor or pharmacist\" as \"the amount of iron in most multivitamins may not meet your needs and iron supplements may be necessary\". [ 26 ]  The  American Red Cross  recommends \"taking a multivitamin with 18 mg of iron or an iron supplement with 18-38 mg of elemental iron for 60 days after each blood donation, for 120 days after each power red donation or after frequent platelet donations\". [ 27 ]  A 2014  Cochrane Review  found that blood donors were less likely to be deferred for low hemoglobin levels if they were taking oral iron supplements, although 29% of those who took them experienced side effects in contrast to the 17% that took a placebo. It is unknown what the long-term effects of iron supplementation for blood donors may be. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5061", "text": "Side effects of therapy with oral iron are most often  diarrhea  or  constipation  and  epigastric  abdominal discomfort. Taken after a meal, side effects decrease, but there is an increased risk of interaction with other substances. Side effects are  dose-dependent , and the dose may be adjusted."}
{"_id": "WikiPedia_Hematology$$$corpus_5062", "text": "The patient may notice that their stools become black. This is completely harmless, but patients must be warned about this to avoid unnecessary concern. When iron supplements are given in a liquid form, teeth may reversibly discolor (this can be avoided through the use of a straw). Intramuscular injection can be painful, and brown discoloration may be noticed."}
{"_id": "WikiPedia_Hematology$$$corpus_5063", "text": "Treatments with  iron(II) sulfate  have higher incidence of adverse events than  iron(III)-hydroxide polymaltose complex  (IPC) [ 29 ] [ 30 ] [ 31 ]  or iron bis-glycinate chelate. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5064", "text": "Iron overdose has been one of the leading causes of death caused by toxicological agents in children younger than six years. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5065", "text": "Iron poisoning may result in mortality or short-term and long-term morbidity. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5066", "text": "Because one of the functions of elevated  ferritin  (an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency situation that it cannot wait for any such acute infection to be treated."}
{"_id": "WikiPedia_Hematology$$$corpus_5067", "text": "Some studies have found that iron supplementation can lead to an increase in  infectious disease  morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in  diarrhea  overall and enteropathogen shedding. Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as  Salmonella typhimurium  or  Entamoeba histolytica . Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5068", "text": "Children living in areas prone for malarial infections are also at risk of developing anemia. It was thought that iron supplementation given to such children could increase the risk of malarial infection in them. A Cochrane systematic review published in 2016 found high quality evidence that iron supplementation does not increase the risk of clinical malaria in children. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5069", "text": "Contraindications often depend on the substance in question. Documented  hypersensitivity  to any ingredients and anemias without proper work-up (i.e., documentation of iron deficiency) is true of all preparations. Some can be used in iron deficiency, others require iron deficiency anaemia to be present. Some are also contraindicated in  rheumatoid arthritis . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5070", "text": "Individuals may be genetically predisposed to excessive iron absorption, as is the case with those with  HFE hereditary hemochromatosis . Within the general population, 1 out of 400 people has the homozygous form of this genetic trait, and 1 out of every 10 people has its heterozygous form. [ 38 ]  Neither individuals with the homozygous or heterozygous form should take iron supplements. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5071", "text": "Non- heme  iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and the other drug. Examples include  tetracycline ,  penicillamine ,  methyldopa ,  levodopa ,  bisphosphonates  and  quinolones . The same can occur with elements in food, such as  calcium , which impacts both heme and non-heme iron absorption. [ 39 ]  Absorption of iron is better at a low pH (i.e. an acidic environment), and absorption is decreased if there is a simultaneous intake of antacids."}
{"_id": "WikiPedia_Hematology$$$corpus_5072", "text": "Many other substances decrease the rate of non-heme iron absorption. One example is  tannins  from foods such as  tea [ 40 ]  and  phytic acid . [ 41 ]  Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources,  vegetarians  and  vegans  should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry. [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5073", "text": "Taken after a meal, there are fewer side effects but there is also less absorption because of interaction and pH alteration. Generally, an interval of 2\u20133 hours between the iron intake and that of other drugs seems advisable, but is less convenient for patients and can impact on compliance."}
{"_id": "WikiPedia_Hematology$$$corpus_5074", "text": "The first pills were commonly known as Blaud's pills, [ 44 ]  which were named after  P. Blaud of Beaucaire , the French physician who introduced and started the use of these medications as a treatment for patients with  anemia . [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5075", "text": "Iron can be supplemented  by mouth  using various forms, such as  iron(II) sulfate . This is the most common and well studied soluble iron  salt  sold under brand names such as Feratab, Fer-Iron, and Slow-FE. It is in complex with  gluconate ,  dextran ,  carbonyl iron , and other salts.  Ascorbic acid , vitamin C, increases the absorption of non-heme sources of iron. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5076", "text": "Heme iron polypeptide (HIP) (e.g. Proferrin ES and Proferrin Forte) can be used when regular iron supplements such as ferrous sulfate or ferrous fumarate are not tolerated or absorbed. A clinical study demonstrated that HIP increased serum iron levels 23 times greater than ferrous fumarate on a milligram-per-milligram basis. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5077", "text": "Another alternative is ferrous  glycine   sulfate  or ferroglycine sulfate, has less gastrointestinal side-effects than standard preparations such as iron fumarate. [ 48 ]   [ better\u00a0source\u00a0needed ]  It is unusual among oral preparations of iron supplements in that the iron in this preparation has very high oral bioavailability, especially in the liquid formulation. This option should be evaluated before resorting to parenteral therapy. It is especially useful in iron deficiency anemia associated with  autoimmune gastritis  and  Helicobacter pylori  gastritis, where it generally has satisfactory effect. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5078", "text": "Since iron stores in the body are generally depleted, and there is a limit to what the body can process (about 2\u20136\u00a0mg/kg of body mass per day; i.e. for a 100\u00a0kg/220\u00a0lb man this is equal to a maximum dose of 200\u2013600\u00a0mg/per day) without  iron poisoning , this is a chronic therapy which may take 3\u20136 months. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5079", "text": "Due to the frequent intolerance of oral iron and the slow improvement, parenteral iron is recommended in many indications. [ 51 ] [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5080", "text": "Iron therapy (intravenously or intramuscular) is given when therapy by mouth has failed (not tolerated), oral absorption is seriously compromised (by illnesses, or when the person cannot swallow), benefit from oral therapy cannot be expected, or fast improvement is required (for example, prior to elective surgery). [ 53 ]   Parenteral therapy  is more expensive than oral iron preparations and is not suitable during the first trimester of  pregnancy . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5081", "text": "There are cases where parenteral iron is preferable over oral iron. These are cases where oral iron is not tolerated, where the  haemoglobin  needs to be increased quickly (e.g. post partum, post operatively, post transfusion), where there is an underlying inflammatory condition (e.g. inflammatory bowel disease) or renal patients, the benefits of parenteral iron far outweigh the risks."}
{"_id": "WikiPedia_Hematology$$$corpus_5082", "text": "Low-certainty evidence suggests that IBD-related anemia treatment with  Intravenous (IV) iron infusion  may be more effective than  oral iron therapy , with fewer people needing to stop treatment early due to adverse effects. [ 54 ]  The type of iron preparation may be an important determinant of clinical benefit. Moderate-certainty evidence suggests response to treatment may be higher when IV  ferric carboxymaltose , rather than IV  iron sucrose  preparation is used, despite very-low certainty evidence of increased adverse effects, including bleeding, in those receiving ferric carboxymaltose treatment. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5083", "text": "In many cases, use of intravenous iron such as ferric carboxymaltose has lower risks of adverse events than a blood transfusion and as long as the person is stable is a better alternative. [ 55 ]  Ultimately this always remains a clinical decision based on local guidelines, although National Guidelines are increasingly stipulating IV iron in certain groups of patients. [ 56 ] [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5084", "text": "A Cochrane review of controlled trials comparing  intravenous (IV) iron therapy  with oral iron supplements in people with  chronic kidney disease , found low-certainty evidence that people receiving IV-iron treatment were 1.71 times as likely to reach their target  hemoglobin  levels. [ 58 ]  Overall, hemoglobin was 0.71g/dl higher than those treated with oral iron supplements. Iron stores in the liver, estimated by serum  ferritin , were also 224.84\u00a0\u03bcg/L higher in those receiving IV-iron. [ 58 ]  However, there was also low-certainty evidence that allergic reactions were more likely following IV-iron therapy. It was unclear whether type of iron therapy administration affects the risk of death from any cause, including cardiovascular, nor whether it may alter the number of people who may require a blood transfusion or dialysis. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5085", "text": "Soluble iron salts have a significant risk of adverse effects and can cause toxicity due to damage to cellular macromolecules. Delivering iron parenterally has utilised various different molecules to limit this. This has included  dextrans ,  sucrose , carboxymaltose, and Isomaltoside 1000. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5086", "text": "One formulation of parenteral iron is iron dextran which covers the old high molecular weight (brand name Dexferrum) and the much safer low molecular iron dextrans (brand names including Cosmofer and Infed). [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5087", "text": "Iron  sucrose  has an occurrence of allergic reactions of less than 1 in 1000. [ 60 ]  A common side effect is taste changes, especially a  metallic taste , occurring in between 1 in 10 and 1 in 100 treated patients. [ 60 ]  It has a maximum dose of 200\u00a0mg on each occasion according to the SPC, but it has been given in doses of 500\u00a0mg. Doses can be given up to 3 times a week. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5088", "text": "Iron carboxymaltose is marketed as Ferinject, [ 8 ]  Injectafer, [ 9 ] [ 62 ]  and Iroprem in various countries. [ 63 ]  The most common side effects are  headaches  which occur in 3.3%, and hypophosphatemia, which occurs in more than 35%. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5089", "text": "Iron isomaltoside 1000 (brand name Monofer) is a formulation of parenteral iron that has a matrix structure that results in very low levels of free iron and labile iron. It can be given at high doses \u2013 20\u00a0mg/kg in a single visit \u2013 no upper dose limit. This formulation has the benefit of giving a full iron correction in a single visit. [ 64 ] [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5090", "text": "Ferric maltol , marketed as Accrufer [ 10 ]  and Ferracru, is available in oral and intravenous preparations. When used as a treatment for IBD-related anemia, very low certainty evidence suggests a marked benefit with oral ferric maltol compared with placebo. However it was unclear whether the IV preparation was more effective than oral ferric maltol. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5091", "text": "Lipegfilgrastim , sold under the  brand name   Lonquex , is a medication used to reduce the duration of  neutropenia  and the incidence of  febrile neutropenia  in adults. [ 1 ]  It is given by  injection  under the skin in the abdomen, upper arm or thigh. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5092", "text": "The most common side effects include  nausea  as well as  bone  and  muscle pain . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5093", "text": "Lipegfilgrastim is similar to  granulocyte colony stimulating factor  ( G\u2011CSF ), a naturally occurring  protein  in the body that stimulates the production of  white blood cells  including  neutrophils  in the  bone marrow . [ 1 ]  Lipegfilgrastim acts in the same way as G\u2011CSF, increasing the production of neutrophils and thereby helping to reduce the duration of neutropenia and the occurrence of  febrile neutropenia  (a sign of infection) in people receiving  chemotherapy . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5094", "text": "Lipegfilgrastim is a  filgrastim  biosimilar. [ 1 ]  In lipegfilgrastim, the filgrastim has been ' pegylated ' (attached to  polyethylene glycol ). [ 1 ]  This slows down the medicine's removal from the body and allows the medicine to be given less often. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5095", "text": "Lipegfilgrastim was authorized for medical use in the  European Union  in July 2013. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5096", "text": "Lipegfilgrastim is indicated for the reduction in the duration of  neutropenia  and the incidence of  febrile neutropenia  in adults treated with  cytotoxic  chemotherapy for  malignancy  (with the exception of  chronic myeloid leukaemia  and  myelodysplastic syndromes ). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5097", "text": "Lovotibeglogene autotemcel , sold under the brand name  Lyfgenia , is a  lentiviral   gene therapy  used for the treatment of  sickle cell disease . [ 1 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5098", "text": "The most common side effects include stomatitis (mouth sores of the lips, mouth, and throat), low levels of platelets, white blood cells, and red blood cells, and febrile neutropenia (fever and low white blood cell count), consistent with chemotherapy and underlying disease. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5099", "text": "The US  Food and Drug Administration  (FDA) approved lovotibeglogene autotemcel in December 2023. [ 3 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5100", "text": "Lovotibeglogene autotemcel is  indicated  for the treatment of people aged twelve years of age and older with sickle cell disease and a history of  vaso-occlusive events . [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5101", "text": "The recipient's blood stem cells are genetically modified to produce HbA (T87Q), a gene-therapy derived  hemoglobin A , which is similar to the normal adult  hemoglobin  produced in persons not affected by sickle cell disease. [ 3 ]  Red blood cells containing HbA (T87Q) have a lower risk of sickling and occluding blood flow. [ 3 ]  These modified stem cells are then delivered to the recipient. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5102", "text": "The gene therapy is made from the recipient's own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. [ 3 ]  Prior to treatment, the recipient's own stem cells are collected, and then the recipient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in lovotibeglogene autotemcel. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5103", "text": "The US FDA label contains a black box warning about hematologic malignancy (blood cancer). [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5104", "text": "The safety and effectiveness of lovotibeglogene autotemcel is based on the analysis of data from a single-arm, 24-month multicenter study in participants with sickle cell disease and history of Vaso-occlusive episodes (VOEs) between the ages of twelve and fifty years. [ 3 ]  Effectiveness was evaluated based on complete resolution of VOEs (VOE-CR) between six and eighteen months after infusion with lovotibeglogene autotemcel. [ 3 ]  Twenty-eight (88%) of 32 participants achieved VOE-CR during this time period. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5105", "text": "The FDA granted the application for lovotibeglogene autotemcel  priority review ,  orphan drug ,  fast track , and regenerative medicine advanced therapy designations. [ 3 ]  The FDA granted approval of Lyfgenia to Bluebird Bio Inc. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5106", "text": "The cost effectiveness threshold of the therapy is estimated to be between  US$1.35 million  to $2.05 million. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5107", "text": "Lovotibeglogene autotemcel is the  international nonproprietary name . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5108", "text": "Lovotibeglogene autotemcel is sold under the brand name Lyfgenia. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5109", "text": "Lusutrombopag , sold under the brand name  Mulpleta  among others, is a  medication  that has been developed for certain conditions that lead to  thrombocytopenia  (abnormally low  platelet  counts) such as thrombocytopenia associated with  chronic liver disease  in patients prior to elective invasive procedures. [ 1 ]  It is being manufactured and marketed in Japan by  Shionogi . [ 2 ] [ 3 ] [ 4 ]  It was approved by the U.S.  Food and Drug Administration  (FDA) in July 2018, and NICE in January 2020. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5110", "text": "It was approved for medical use in the European Union in February 2019. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5111", "text": "Miltefosine , sold under the trade name  Impavido  among others, is a medication mainly used to treat  leishmaniasis  and free-living  amoeba infections  such as  Naegleria fowleri  and  Balamuthia mandrillaris . [ 4 ]  This includes the three forms of leishmaniasis:  cutaneous ,  visceral  and mucosal. [ 5 ]  It may be used with  liposomal amphotericin B  or  paromomycin . [ 6 ]  It is taken by mouth. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5112", "text": "Common side effects include  vomiting , abdominal pain,  fever ,  headaches , and decreased kidney function. [ 4 ]  More severe side effects may include  Stevens\u2013Johnson syndrome  or  low blood platelets . [ 4 ]  Use during  pregnancy  appears to cause harm to the baby and use during  breastfeeding  is not recommended. [ 4 ]  How it works is not entirely clear. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5113", "text": "Miltefosine was first made in the early 1980s and studied as a treatment for  cancer . [ 7 ]  A few years later it was found to be useful for leishmaniasis and was approved for this use in 2002 in India. [ 8 ]  It is on the  World Health Organization's List of Essential Medicines . [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5114", "text": "Miltefosine is primarily used for the treatment of  visceral  and  New World cutaneous leishmaniasis , and is undergoing  clinical trials  for this use in several countries. [ 11 ] [ 12 ]  This drug is now listed as a core medication for the treatment of leishmaniasis under the WHO Model List of Essential Medicines. [ 13 ]  Several medical agents have some efficacy against visceral or cutaneous leishmaniasis, however, a 2005 survey concluded that miltefosine is the only effective oral treatment for both forms of leishmaniasis. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5115", "text": "Miltefosine has been used successfully in some cases of the very rare, but highly lethal, brain infection by the amoeba,  Naegleria fowleri , acquired through water entering the nose during a plunge in contaminated water. [ 15 ]  It has orphan drug status in the United States for  acanthamoeba keratitis  and  primary amebic meningoencephalitis  (PAM). [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5116", "text": "Miltefosine is listed as pregnancy category D by the FDA. This means there is evidence-based adverse reaction data from investigational or marketing experience or studies in humans of harm to the human fetus. [ 18 ]   Despite this evidence, the potential benefits of miltefosine may warrant use of the drug in pregnant women despite potential risks.  A pregnancy test should be done prior to starting treatment. Effective  birth control  should be used while on miltefosine and 5 months after discontinuation of treatment. Its use during breast feeding is most likely unsafe. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5117", "text": "Miltefosine is contraindicated in individuals who have a  hypersensitivity  to this medication, pregnant women, and people who have the  Sj\u00f6gren-Larsson syndrome . [ 19 ]  It is embryotoxic and fetotoxic in rats and rabbits, and  teratogenic  in rats but not in rabbits. It is therefore contraindicated for use during pregnancy, and  contraception  is required beyond the end of treatment in women of child-bearing age. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5118", "text": "Common  side effects  from miltefosine treatment are  nausea  and  vomiting , which occur in 60% of people. Other common side effects are dizziness, headache, and daytime sleepiness. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5119", "text": "Serious side effects include rash, diarrhea, and arthritis. [ 21 ]  The side effects are more severe in women and young children. The overall effects are quite mild and easily reversed. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5120", "text": "Miltefosine primarily acts on  Leishmania  by affecting the species's promastigote and amastigote stages. [ 23 ]  Miltefosine exerts its activity by interacting with lipids, inhibiting  cytochrome c oxidase  and causing apoptosis-like cell death. [ 24 ]  This may affect membrane integrity and mitochondrial function of the parasite. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5121", "text": "While initially studied as a cancer medication, due to side effects it was never used for this purpose. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5122", "text": "Phospholipid  group  alkylphosphocholine  were known since the early 1980s, particularly in terms of their binding affinity with  cobra  venom. [ 26 ]  In 1987 the phospholipids were found to be potent toxins on  leukemic cell culture . [ 27 ]  Initial  in vivo  investigation on the  antineoplastic  activity showed positive result, but then only at high dosage and at high toxicity. [ 28 ]  At the same time in Germany, Hansj\u00f6rg Eibl, at the  Max Planck Institute for Biophysical Chemistry , and Clemens Unger, at the  University of G\u00f6ttingen , demonstrated that the  antineoplastic activity  of the phospholipid analogue miltefosine (at the time known as hexadecylphosphocholine) was indeed tumour-specific. It was highly effective against  methylnitrosourea -induced  mammary carcinoma , but less so on  transplantable   mammary carcinomas  and  autochthonous   benzo(a)pyrene -induced  sarcomas , and relatively inactive on Walker 256  carcinosarcoma  and autochthonous acetoxymethylmethylnitrosamine-induced  colonic tumors  of rats. [ 29 ] [ 30 ]  It was subsequently found that miltefosine was structurally unique among lipids having anticancer property in that it lacks the  glycerol  group, is highly selective on cell types and acts through different mechanism. [ 31 ] [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5123", "text": "In the same year as the discovery of the anticancer property, miltefosine was reported by S. L. Croft and his team at the  London School of Hygiene and Tropical Medicine  as having antileishmanial effect as well. The compound was effective against  Leishmania donovani   amastigotes  in cultured mouse peritoneal  macrophages  at a dose of 12.8\u00a0mg/kg/day in a five-day course. [ 33 ]  However, priority was given to the development of the compound for cutaneous  metastases  of  breast cancer . In 1992 a new research was reported in which the compound was highly effective in mouse against different  life cycle stages  of different  Leishmania  species, and in fact, more potent than the conventional  sodium stibogluconate  therapy by a factor of more than 600. [ 34 ]  Results of the first clinical trial in humans were reported from Indian patients with chronic leishmaniasis with high degree of success and safety. [ 35 ]  This promising development promulgated a unique public\u2013private partnership collaboration between  ASTA Medica  (later Zentaris GmbH), the  World Health Organization  (WHO) Special Programme for Research and Training in Tropical Diseases, and the  Government of India . Eventually, several successful Phase II and III trials led to the approval of miltefosine in 2002 as the first and only oral drug for leishmaniasis. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5124", "text": "In 2013, the US  Centers for Disease Control and Prevention  recommended miltefosine for the treatment of free-living amoeba infections such as  granulomatous amoebic encephalitis  and  primary amoebic meningoencephalitis , two fatal protozoal diseases. [ 36 ]  Historically, only four survivors have been recorded out of 138 confirmed infections in North America. One American survived the infection in 1978 and one individual from Mexico in 2003. In 2013, two children survived and recovered from primary amoebic meningoencephalitis after treatment with miltefosine. [ 37 ] [ 38 ]  In 2016 after treatment that included miltefosine, another child became the fourth person in the United States to survive  Naegleria fowleri  infection. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5125", "text": "Since 2017 Miltefosine is commercially available in the United States through Profounda. [ 40 ]  Previously one could only get it from the  CDC  for emergency use under an expanded access  IND  protocol for treatment of free-living amoeba (FLA) infections:  primary amoebic meningoencephalitis  caused by  Naegleria fowleri  and granulomatous amoebic encephalitis caused by  Balamuthia mandrillaris  and  Acanthamoeba  species. [ 37 ]  Miltefosine is almost exclusively produced by Profounda, a private pharmaceutical company. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5126", "text": "In the  developing world  a course of treatment costs US$65 to $150. [ 6 ]  In the  developed world  treatment may be 10 to 50 times greater. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5127", "text": "It is active against some  bacteria  and  fungi , [ 3 ] [ 42 ]  as well as human  trematode   Schistosoma mansoni  and the snail that spreads it  Biomphalaria alexandrina . [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5128", "text": "Miltefosine is being investigated by researchers interested in finding treatments for infections which have become resistant to existing drugs.  Animal and  in vitro  studies suggest it may have broad anti-protozoal and anti-fungal properties:"}
{"_id": "WikiPedia_Hematology$$$corpus_5129", "text": "Miltefosine targets HIV infected  macrophages , which play a role  in vivo  as long-lived HIV-1 reservoirs. The HIV protein  Tat  activates pro-survival  PI3K / Akt  pathway in primary human macrophages.  Miltefosine acts by inhibiting the  PI3K/Akt pathway , thus removing the infected macrophages from circulation, without affecting healthy cells. [ 56 ] [ 57 ]  It significantly reduces replication of HIV-1 in cocultures of human  dendritic cells  (DCs) and  CD4 +  T cells , which is due to a rapid secretion of soluble factors and is associated with induction of type-I  interferon  (IFN) in the human cells. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5130", "text": "Pentavalent antimonials  ( Meglumine antimoniate # ,  Sodium stibogluconate )"}
{"_id": "WikiPedia_Hematology$$$corpus_5131", "text": "Piperaquine/dihydroartemisinin  ( DHA/PPQ ), sold under the brand name  Eurartesim  among others, is a  fixed dose combination  medication used in the treatment of  malaria . [ 2 ]  It is a combination of  piperaquine  and  dihydroartemisinin . [ 2 ]  Specifically it is used for malaria of the  P. falciparum  and  P. vivax  types. [ 3 ] [ 4 ]  It is taken by mouth. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5132", "text": "Side effects are uncommon. [ 4 ]  Concerns include the possibility of  QT prolongation . [ 4 ]  Versions are available for use in children. [ 3 ]  Use in early  pregnancy  is not recommended. [ 4 ]  The two medications work by different mechanisms. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5133", "text": "Piperaquine/dihydroartemisinin was approved for medical use in Europe in 2011. [ 3 ]  The combination is on the  World Health Organization's List of Essential Medicines . [ 2 ] [ 5 ]  It is commercially available in Africa and Asia. [ 3 ]  It has been used to treat more than 4.5 \u00a0 million people as of 2017. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5134", "text": "Dihydroartemisinin  (also known as dihydroqinghaosu, artenimol or DHA) is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs."}
{"_id": "WikiPedia_Hematology$$$corpus_5135", "text": "Piperaquine  is an antimalarial drug, a bisquinoline first made in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. Usage declined in the 1980s as piperaquine-resistant strains of P. falciparum arose and artemisinin-based antimalarials became available. The combination dihydroartemisinin-piperaquine is an effective antimalarial that is used widely around the world. In South-East Asia, where resistance has emerged towards both artemisinin and piperaquine, the combination is being trialed with a third drug, namely  mefloquine . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5136", "text": "Piperaquine is characterized by slow absorption and a long biological half-life, making it a good partner drug with artemisinin derivatives which are fast acting but have a short biological half-life."}
{"_id": "WikiPedia_Hematology$$$corpus_5137", "text": "This product is available in the market of several countries:"}
{"_id": "WikiPedia_Hematology$$$corpus_5138", "text": "Rh o (D) immune globulin  ( RhIG ) is a medication used to prevent  RhD isoimmunization  in mothers who are  RhD negative  and to treat  idiopathic thrombocytopenic purpura  (ITP) in people who are  Rh positive . [ 2 ]  It is often given both during and following  pregnancy . [ 2 ]  It may also be used when RhD-negative people are given RhD-positive blood. [ 2 ]  It is given by  injection into muscle  or a  vein . [ 2 ]  A single dose lasts 12 weeks. [ 2 ]  It is made from  human blood plasma . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5139", "text": "Common side effects include  fever , headache, pain at the site of injection, and  red blood cell breakdown . [ 2 ]  Other side effects include  allergic reactions ,  kidney problems , and a very small risk of viral infections. [ 2 ]  In those with ITP, the amount of red blood cell breakdown may be significant. [ 2 ]  Use is safe with  breastfeeding . [ 2 ]  Rho(D) immune globulin is made up of  antibodies  to the  antigen  Rh o (D) present on some  red blood cells . [ 2 ]  It is believed to work by blocking a person's immune system from recognizing this antigen. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5140", "text": "Rh o (D) immune globulin came into medical use in the 1960s, [ 4 ]  following the pioneering work of  John G. Gorman . In 1980, Gorman shared the  Lasker-DeBakey Clinical Medical Research Award  for pioneering work on the  rhesus blood group system . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5141", "text": "RhIG is on the  World Health Organization's List of Essential Medicines . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5142", "text": "Even in normal pregnancies, a small number of fetal blood cells enters the maternal bloodstream (fetomaternal hemorrhage). If a mother is RhD negative, but the fetus is RhD positive, the mother's immune system may develop an immune response (develops  antibodies ) to the unfamiliar RhD antigens from the fetus. This process is called  RhD alloimmunization . Alloimmunization usually has minimal effect on the first such pregnancy; but, in a second such pregnancy, pre-existing maternal RhD IgG antibodies can cross the placenta in enough amounts to damage fetal red blood cells. This condition is called  erythroblastosis fetalis  and can be fatal to the fetus. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5143", "text": "The RhD status of the fetus is determined by genetic inheritance. In a pregnancy where the mother is RhD negative and the father is RhD positive, the probability of the fetus having RhD positive blood is dependent on whether the father is  homozygous  for RhD (i.e., both RhD alleles are present) or  heterozygous  (i.e., only one RhD allele is present). If the father is homozygous, the fetus will necessarily be RhD positive, as the father will necessarily pass on a RhD positive allele. If the father is heterozygous, there is a 50% chance that the fetus will be RhD positive, as he will randomly pass on either the RhD positive allele or not. [ 9 ] :\u200a130\u200a . Not all Rh-negative patients are capable of being immunized to the RhD antigen, and mothers may only become immunized after many repeated pregnancies. The risk of  hemolytic disease  (including due to RhD) significantly increases if the mother has had a past transfusion of Rh-positive blood.  [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5144", "text": "Exposure to fetal blood cells that can cause RhD alloimmunization can happen during normal pregnancy and delivery, miscarriage, amniocentesis, cordocentesis, chorionic villus sampling, external cephalic version, or trauma. [ 3 ] [ 8 ]  92% of women who develop an anti-D during pregnancy do so at or after 28 weeks gestation. [ 11 ] [ 9 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5145", "text": "In an RhD negative mother, RhIG can temporarily prevent sensitization of the maternal immune system to RhD  antigens , with each 100 \u03bcg of anti-D being able to neutralize about 4 mL of fetal blood. [ 13 ]  With the widespread use of RhIG,  Rh disease  of the  fetus  and  newborn  has almost disappeared in the developed world. The risk that an RhD negative mother can be  alloimmunized  by a RhD positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG. [ 11 ] [ 9 ] [ 14 ]  In data collected from communities in Canada, without treatment as many as 14% of affected fetuses are stillborn, 30% of affected live births almost certainly fatal without treatment, and 30% with severe  jaundice  that untreated risks brain damage from  kernicterus . [ 8 ] \n [ 15 ] . Prior to effective transfusion therapy, the mortality rate of hemolytic disease was 70-80%, dropping to 30-50% with small transfusions and 13-33% for more aggressive transfusions before RhIg treatments were introduced.  [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5146", "text": "The  American College of Obstetricians and Gynecologists  (ACOG) recommends that all RhD negative mothers, regardless of fetal blood type, receive RhIG at about 28 weeks gestation, and again shortly after delivery in the case of an RhD positive or RhD unknown baby. [ 16 ]  It should be given within 3 days of a potential exposure to Rh positive blood from the baby such as may occur during second and third trimester miscarriage, amniocentesis, cordocentesis, chorionic villus sampling, external cephalic version, trauma, or delivery (amounts detailed in the next section). [ 8 ]  It is given by intramuscular injection as part of modern routine  antenatal  care. Despite excellent results, the medication retains an FDA  Pregnancy Category  C. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5147", "text": "RhIG is recommended in the UK after antenatal pathological events that are likely to cause a feto\u2013maternal hemorrhage. Applicable 'pathologic events' include accidents that may induce fetomaternal hemorrhage (motor vehicle accidents, falls, abdominal trauma), following obstetric/gynecologic procedures during pregnancy, and at the time of threatened- or spontaneous-/elective  abortions , regardless of gestational age. RhIG is also recommended after normal delivery, with amounts detailed in the next section. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5148", "text": "There is insufficient evidence that the use of Rho(D) immune globulin after a spontaneous miscarriage is needed and a  Cochrane review  recommends that local practices be followed. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5149", "text": "Rh immune globulin is composed of IgG antibodies and therefore is able to cross the placenta. In rare cases this can cause a baby to have a weakly positive  direct antiglobulin test  (DAT) due to sensitization of fetal cells from mothers who have received multiple doses of RhIG. However, no treatment is necessary as the clinical course is benign. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5150", "text": "Widespread use of RhIG started with postpartum administration, as delivery is the main source of significant fetomaternal hemorrhage. \nA D-negative mother who is not alloimmunized to D should also receive an appropriate dose of RhIG after delivery of a D-positive infant. (In older recommendations, the Rh status of the infant is only known at delivery from testing of  cord blood .) [ 9 ]  If the infant is D-positive, the mother should have a postpartum blood sample screened for fetomaternal hemorrhage in order to determine the appropriate dosage of RhIG to be administered.  (The presence of residual anti-D from antepartum RhIG administration does not indicate ongoing protection from alloimmunization \u2013 repeat administration of RhIG is necessary.) [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5151", "text": "The  rosette test  is a sensitive method to detect fetomaternal hemorrhage of 10 cc or more.  This qualitative (not quantitative) test will be positive if fetal D-positive cells are present in the maternal sample, indicating a significantly large fetomaternal hemorrhage has occurred.  A rosette test may be falsely positive if the mother is positive for the  weak D  phenotype and falsely negative if the neonate is weak D.  If the mother is positive for the weak D phenotype, the rosette test should not be used; instead, a quantitative test such as the  Kleihauer\u2013Betke test  or flow cytometry should be utilized. If the rosette test is negative, then a dose of 300 micrograms of RhIG is given (sufficient to prevent alloimmunization after delivery in 99% of cases). [ 11 ] [ 19 ]   The RhIG dose suppresses the immune response to up to 30 cc of whole fetal blood (15 cc of red blood cells). If a fetomaternal hemorrhage in excess of 30 cc has occurred, additional testing is mandatory in order to determine the appropriate dosage of RhIG to prevent alloimmunization.  A positive rosette test should be followed by a quantitative test such as the Kleihauer\u2013Betke test or an alternative approach such as  flow cytometry .  See the article on Kleihauer\u2013Betke test for details on how the volume of fetomaternal hemorrhage is calculated. The dosage of RhIG is calculated from the volume of fetal hemorrhage (in mL).  Ex: 50 mL fetal hemorrhage / 30 mL = 1.667 (round up to 2) then add 1 = 3 vials of RhIG. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5152", "text": "Postpartum RhIG should be administered within 72 hours of delivery.  If prophylaxis is delayed, the likelihood that alloimmunization will be prevented is decreased.  However, ACOG still recommends that RhIG be administered because partial protection still occurs. [ 11 ] [ 12 ]   If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered."}
{"_id": "WikiPedia_Hematology$$$corpus_5153", "text": "Primary  immune thrombocytopenia  (ITP) is an acquired immune-mediated disorder characterized by isolated  thrombocytopenia , defined as a peripheral blood platelet count less than 100 x 10 9 /L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia.  Symptoms of ITP include abnormal bleeding and bruising due to the reduction in  platelet count . [ 20 ]   Rh o (D) Immune Globulin Intravenous [Human; Anti-D] is indicated for use in non-splenectomized, Rh o (D)-positive children with chronic or acute ITP, adults with chronic ITP, and children and adults with ITP secondary to HIV infection. Anti-D must be administered via the intravenous route when used in clinical situations requiring an increase in platelet count. The mechanism of action of anti-D is not fully understood; however, after administration the anti-D coated red blood cell complexes saturate  Fc\u03b3 receptors  sites on  macrophages , resulting in preferential destruction of  red blood cells  (RBCs), therefore sparing antibody-coated  platelets . [ 21 ]  Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG). [ 20 ] [ 22 ]   [WinRho SDF is an anti-D manufactured, distributed and marketed by  Cangene  in the US. There is a black box warning on WinRho SDF due to the risk of potentially fatal intravascular hemolysis when used in the treatment of ITP. [ 21 ]  Life-threatening  anemia ,  kidney  failure, and  disseminated intravascular coagulation  (DIC) have occurred in people treated with WinRho SDF for ITP. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5154", "text": "The following females are not candidates for RhIG:"}
{"_id": "WikiPedia_Hematology$$$corpus_5155", "text": "The first Rho(D) immune globulin treatment \"skymed\" was introduced by  Ortho Clinical Diagnostics , a subsidiary holding of  Jskymed , and was first administered on May 29, 1968, to Marianne Cummins in  Teaneck ,  New Jersey . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5156", "text": "In 1996, ZLB Bioplasma (part of  CSL Behring ) was given approval to sell Rhophylac in Europe. Effectiveness was demonstrated in a clinical trial in 2003 and in 2004 Rhophylac was approved in the United States. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5157", "text": "Conventional Rho(D) immune globulin is extracted from human  blood plasma . Excluding  autoimmunity , only people who are themselves Rho(D) negative can make the anti-D antibody. As a result, there is a limited pool of people from which to draw plasma that can contain the desired IgG. Special anti-D donation programs are set up to account for this rarity. [ 26 ]  Volunteers are given an injection containing the D antigen in order to make their immune system start producing the antibody (alloimmunization) or to boost the amounts. Only those who have no ability to become pregnant may apply. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5158", "text": "The most common way anti-D products are manufactured is by a form of the  Cohn cold ethanol fractionation process  developed in the 1950s.  Variations of the Cohn method developed in the 1950s may not completely clear aggregates of immunoglobulins, which can cause problems for patients if administered intravenously, and is a primary reason why most anti-Ds are for intramuscular use only.  A non-Cohn manufacturing variation is ChromaPlus process approved by the  U.S. Food and Drug Administration  (FDA) that is used to make Rhophylac. [ 28 ]   Rho(D) immune globulin may trigger an allergic reaction. Steps are taken in the plasma-donor screening process and the manufacturing process to eliminate bacterial and viral contamination, although a small, residual risk may remain for contamination with small viruses. There is also a theoretical possibility of transmission of the  prion  responsible for  Creutzfeldt\u2013Jakob disease , or of other, unknown infectious agents. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5159", "text": "There has been continual attempts to produce a  monoclonal  anti-D IgG formulation suitable for replacing the current polyclonal formulation. [ 30 ]  A monoclonal antibody can be produced without requiring human donors (and associated supply and disease risks) and would be more consistent from batch to batch. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5160", "text": "India has approved a monoclonal formulation called  Rhoclone  (Bharat Serums and Vaccines Ltd.), [ 31 ]  made from  hybridoma cultures . The country has also tested and recently marketed a  recombinant  version of Rhoclone expressed in  CHO cells . [ 32 ]  This recombinant formulation, Trinbelimab, marketed as AntiD, is also being evaluated in a large Real-world Prospective Study that aims to enroll 20,000 Rh-negative mothers. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5161", "text": "Roledumab  and  Rozrolimupab  are two other formulations that have undergone some clinical trials. The former is a monoclonal IgG. The latter is a recombinant mixture of 25 IgGs. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5162", "text": "RhIG can be administered by either intramuscular (IM) or intravenous (IV) injection, depending on the preparation. [ 34 ]   The IM-only preparation should never be administered IV due to the risk of complement system activation.  Multiple IM doses should be given at different sites or at different times within the 72-hour window.  Or, multiple IV doses can be administered according to the instructions in the package insert. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5163", "text": "Rh o (D) immune globulin is also spelled Rh 0 (D) immune globulin (letter  o  and digit  zero  are both widely attested; more at  Rh blood group system - Rh nomenclature )."}
{"_id": "WikiPedia_Hematology$$$corpus_5164", "text": "AntiD (Recombinant) and Rhoclone are the only Rh0(D) immune globulin marketed in the world. both manufactured by BSV Ltd. Rhophylac is manufactured by CSL Limited. RhoGAM and MICRhoGam are brand names of Kedrion Biopharma. Other brand names are BayRHo-D, Gamulin Rh, HypRho-D Mini-Dose, Mini-Gamulin Rh, Partobulin SDF ( Baxter ), Rhesonativ (Octapharma), and RhesuGam (NBI).  KamRho-D I.M. is a brand name of Kamada Ltd."}
{"_id": "WikiPedia_Hematology$$$corpus_5165", "text": "The United States  distribution  rights for WinRho SDF (another brand name) were transferred from Baxter to the manufacturer,  Cangene , in 2010; they had been held by Baxter since 2005. [ 35 ]   Sales of WinRho fell every year under the agreement with Baxter, the supposition being that Baxter was favoring the sale of its own product over WinRho; according to one analyst, \"WinRho was always an afterthought for a big company like Baxter.\" [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5166", "text": "Taurolidine  is an  antimicrobial  that is used to prevent infections in  catheters . [ 1 ]  Side effects and the induction of  bacterial resistance  is uncommon. [ 1 ]  It is also being studied as a treatment for  cancer . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5167", "text": "It is derived from the endogenous  amino acid  derivative  taurine . The putative method of action involves the metabolism of taurolidine to taurinamide and ultimately taurine and water, liberating formaldehyde that chemically reacts with the mureins in the bacterial cell wall and with the amino and hydroxyl groups of endotoxins and exotoxins. This reaction denatures the endotoxins and complex polysaccharide and lipopolysaccharide components of the bacterial cell wall and inactivates susceptible exotoxins. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5168", "text": "Taurolidine is an antimicrobial agent used as part of a  catheter lock solution  in an effort to prevent catheter infections. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5169", "text": "No systemic side effects have been identified. The safety of taurolidine has also been confirmed in clinical studies with long-term intravenous administration of high doses (up to 20 grams daily). In the body, taurolidine is metabolized rapidly via the metabolites taurultam and methylol taurinamide, which also have a bactericidal action, to taurine, an endogenous aminosulphonic acid, carbon dioxide and water. Therefore, no toxic effects are known or expected in the event of accidental injection. Burning sensation while instilling, numbness,  erythema , facial flushing, headache,  epistaxis , and nausea have been reported. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5170", "text": "Taurolidine has a relatively low acute and subacute toxicity. [ 1 ]  Intravenous injection of 5 grams taurolidine into humans over 0.5\u20132 hours produce only burning sensation while instilling, numbness, and erythema at the injection sites. [ 12 ]  For treatment of  peritonitis , taurolidine was administered by  peritoneal lavage , intraperitoneal instillation or intravenous infusion, or by a combination thereof. The total daily dose ranged widely from 0.5 to 50 g. The total cumulative dose ranged from 0.5 to 721 g. In those patients who received intravenous taurolidine, the daily intravenous dose was usually 15 to 30 g but several patients received up to 40 g/day. Total daily doses of up to 40 g and total cumulative doses exceeding 300 g were safe and well tolerated. [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5171", "text": "Following administration of taurolidine, the antimicrobial and antiendotoxin activity of the taurolidine molecule is conferred by the release of three active methylol (hydroxymethyl) groups as taurolidine is rapidly metabolized by hydrolysis via methylol taurultam to methylol taurinamide and taurine. These labile N-methylol derivatives of taurultam and taurinamide react with the bacterial cell-wall resulting in lysis of the bacteria, and by inter- and intramolecular cross-linking of the lipopolysaccharide-protein complex, neutralization of the bacterial endotoxins which is enhanced by enzymatic activation. This mechanism of action is accelerated and maximised when taurolidine is pre-warmed to 37\u00a0\u00b0C (99\u00a0\u00b0F). Microbes are killed and the resulting toxins are inactivated; the destruction time  in vitro  is 30 minutes. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5172", "text": "The chemical mode of action of taurolidine via its reactive methylol groups confers greater potency  in vivo  than indicated by  in vitro   minimum inhibitory concentration  (MIC) values, and also appears to preclude susceptibility to resistance mechanisms. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5173", "text": "Taurolidine binding to  lipopolysaccharides  (LPS) prevents microbial adherence to host epithelial cells, thereby prevents microbial invasion of uninfected host cells. Although the mechanism underlying its antineoplastic activity has not been fully elucidated, it may be related to this agent's anti-adherence property. [ 6 ] [ 7 ]  Taurolidine has been shown to block  interleukin 1  (IL-1) and  tumour necrosis factor  (TNF) in human peripheral blood  mononuclear cells  (PBMC). [ 20 ]  In addition, taurolidine also promotes  apoptosis  by inducing various apoptotic factors and suppresses the production of  vascular endothelial growth factor  (VEGF), a protein that plays an important role in  angiogenesis . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5174", "text": "Taurolidine is highly active against the common infecting pathogens associated with peritonitis and catheter sepsis, this activity extends across a wide-spectrum of aerobic and anaerobic bacteria and fungi (with no diminution of effect in the presence of biological fluids, e.g. blood, serum, pus). [ 15 ] [ 16 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5175", "text": "The chemical name for taurolidine is 4,4'-Methylene-bis(1,2,4-thiadiazinane)-1,1,1\u2019,1'-tetraoxide."}
{"_id": "WikiPedia_Hematology$$$corpus_5176", "text": "It is a white to off white odourless crystalline powder. It is practically insoluble in chloroform, slightly soluble in boiling acetone, ethanol, methanol, and ethyl acetate, sparingly soluble in water 8 at 20\u00b0 and ethyl alcohol, soluble in dilute  hydrochloric acid , and dilute sodium hydroxide, and freely soluble in N,N-dimethylformamide (at 60\u00a0\u00b0C)."}
{"_id": "WikiPedia_Hematology$$$corpus_5177", "text": "Taurolidine was first synthesized in the laboratories of Geistlich Pharma AG, Switzerland in 1972. Clinical trials begun in 1975 in patients with severe peritonitis."}
{"_id": "WikiPedia_Hematology$$$corpus_5178", "text": "Taurolidine demonstrates some anti-tumor properties, with positive results seen in early-stage clinical investigations using the drug to treat gastrointestinal malignancies and tumors of the central nervous system. [ 23 ]  More recently, it has been found to exert antineoplastic activity. Taurolidine induces cancer cell death through a variety of mechanisms. Even now, all the antineoplastic pathways it employs are not completely elucidated. It has been shown to enhance apoptosis, inhibit angiogenesis, reduce tumor adherence, downregulate pro-inflammatory cytokine release, and stimulate anticancer immune regulation following surgical trauma. Apoptosis is activated through both a mitochondrial cytochrome-c-dependent mechanism and an extrinsic direct pathway. A lot of in vitro and animal data support taurolidine's tumoricidal action. [ 24 ] [ 25 ] [ 26 ]  Taurolidine has been used as an antimicrobial agent in the clinical setting since the 1970s and thus far appears nontoxic. The nontoxic nature of taurolidine makes it a favorable option compared with current chemotherapeutic regimens. Few published clinical studies exist evaluating the role of taurolidine as a chemotherapeutic agent. The literature lacks a gold-standard level 1 randomized clinical trial to evaluate taurolidine's potential antineoplastic benefits. However, these trials are currently underway. Such randomized control studies are vital to clarify the role of taurolidine in modern cancer treatment. [ 21 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5179", "text": "Taurolidine/heparin , sold under the brand name  Defencath , is a  fixed-dose combination   catheter lock solution  used for central venous catheter instillation. [ 1 ] [ 2 ]  It contains  taurolidine , a  thiadiazinane  antimicrobial; and  heparin , an  anti-coagulant . Its use is limited to people with  kidney failure  receiving chronic  hemodialysis  through a  central venous catheter . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5180", "text": "The most frequently reported adverse reactions include hemodialysis catheter malfunction, hemorrhage/bleeding, nausea, vomiting, dizziness, musculoskeletal chest pain, and thrombocytopenia. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5181", "text": "Taurolidine/heparin was approved for medical use in the United States in November 2023. [ 2 ] [ 3 ]  The US  Food and Drug Administration  (FDA) considers it to be a  first-in-class medication . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5182", "text": "Taurolidine/heparin is  indicated  to reduce catheter-related bloodstream infections in adults with kidney failure who are receiving chronic hemodialysis through a central venous catheter. [ 1 ] [ 2 ] [ 5 ]  It is indicated in this limited and specific patient population. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5183", "text": "Taurolidine/heparin was studied in a single, randomized, active-controlled phase III clinical trial. [ 2 ]  In this trial, taurolidine/heparin delayed the time it took to acquire a catheter related bloodstream infection. [ 2 ]  Taurolidine/heparin demonstrated a 71% risk reduction in catheter related bloodstream infections versus the heparin comparator arm (95% confidence interval for risk reduction: 38% to 86%; p value = 0.0006). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5184", "text": "Athar Blood Bank  is an initiative by  Athar Minorities Social and Welfare Association  and is based in Solapur, Maharashtra. [ 2 ]  The Athar Blood Bank was inaugurated on 2 June 2012 by  Sushil Kumar Shinde  (then  Minister of Power (India)) .  Service to Humanity  was the slogan chosen by the founder as a motto for Athar Blood Bank. Construction of new Maternity Home is on cards of the Athar Minorities Social and Welfare Association in near future. It is running successfully and conducts blood donation camps across the state and helping humanity. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5185", "text": "Athar Blood Bank was established in 2012 by group of individuals mainly  Maulana Syed Shahabuddin Salfi Firdausi , Qayyum Inamdar, Dr. Nilofer Bohri, Mushtaq Chaudhary, Abdul Razzaq Kamble, Azam Shaikh,  Usman Mansoori, Mukhtar Humnabadi and few others. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5186", "text": "The blood collection center at 1st Floor, Jamiya complex, Near Samachar Chowk,  Solapur ,  Maharashtra  is equipped with all the latest equipment and can host multiple blood donations simultaneously. [ 4 ]  Eighteen staff, including three doctors, work at the center and has the capacity to store 700 units. It is operational 24*7 and supplies blood to Government Civil Hospital and Private Hospitals across Solapur district. The bank provides free blood to  thalassemia  and HIV patients. Also, financially weak sections are given discounted rate and sometimes they are not charged at all. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5187", "text": "Athar Blood Bank collects blood from different groups e.g.  colleges  and public or private organizations, where any person can donate blood. Bank organizes an average of seven blood donation camps in a month.  Blood is transported through an ambulance which also provides mobile  medical facility ."}
{"_id": "WikiPedia_Hematology$$$corpus_5188", "text": "Recently 200 people have donated the blood in a camp organized by Jamiat-e-Ahle Hadeeths in Social School, Solapur. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5189", "text": "The blood is processed in the lab having a state-of-art facility after the collection either from the center or camps. After initial screening blood is separated in major three components e.g. red cells, plasma and platelets. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5190", "text": "This article about an organisation in India is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5191", "text": "This article about a medical organization or association is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5192", "text": "Australian Red Cross Lifeblood , simply known as  Lifeblood , is a branch of the  Australian Red Cross  responsible for the  collection  and distribution of blood and biological products in Australia. Lifeblood employs around 3,700 employees across scientific, clinical and support services, processing over one and a half a million blood donations each year. Lifeblood is primarily funded by the  Australian Government  and  state and territory governments ."}
{"_id": "WikiPedia_Hematology$$$corpus_5193", "text": "On 15 November 2019, the Australian Red Cross Blood Service changed its name and branding to Australian Red Cross Lifeblood, citing its increasing responsibility for non-blood products such as  microbiota ,  tissue and organs  and  breast milk . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5194", "text": "As with other blood transfusion services, the Red Cross has had to strike a balance between protecting blood recipients against infection, and accepting enough donors to maintain an adequate supply of blood. This has led to debate over which categories of potential donors should be excluded."}
{"_id": "WikiPedia_Hematology$$$corpus_5195", "text": "In 2003, a federal government report found that despite the introduction of hepatitis C screening from February 1990, infected donors were told to keep donating until July of that same year; a total of 20,000 people were estimated to have been infected with hepatitis C via blood products. Some infected blood was given to CSL and may have been used in thousands of CSL products, although it has not been shown that any of these products caused infection in the recipients. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5196", "text": "The service has a policy of barring  men who have had sex with men  (MSM) during the previous twelve months from donating blood (an earlier policy had excluded any men who had had sex with other men since 1980, regardless of time elapsed). This has been the source of ongoing controversy, with a case (in 2008) referred to the Tasmanian Anti-Discrimination Commission. [ 4 ]  People who have engaged in heterosexual or female-to-female sex during the past 12 months are allowed to give blood. Female-to-female transmission is considered by the  Centers for Disease Control  to be rare. [ 5 ]  As well as deferring blood donations from MSM, other categories of sexual activity can also result in a 12-month deferral, such as sex with a  prostitute  or having a partner who has tested positive to hepatitis B or C. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5197", "text": "In 2014, several gay men again requested that the Australian Red Cross Blood Service permit them to donate blood. [ 7 ] [ 8 ]   The Red Cross, in noting their concern, said they were receptive to a reduction in the current deferral period from 12 to 6 months. However, the Australian  Therapeutic Goods Administration  rejected their submission, arguing that there would be a greater risk of HIV without a significant increase in blood supply. [ 9 ]  The Red Cross say they do not defer based on sexuality or relationships, but rather on sexual activity, and for this reason it is not possible to deal with MSM on an individual basis. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5198", "text": "In April 2020 the Therapeutic Goods Administration revised the deferral period for MSM down to three months. The revision required approval of the federal, state and territory governments before it could go into effect. [ 11 ]  The revised policy came into effect on 31 January 2021. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5199", "text": "In April 2022, the Therapeutic Goods Administration accepted the submission of Lifeblood and the  University of New South Wales  and removed the rule that made people who had lived in the United Kingdom for more than six months between 1980 and 1996 ineligible. Before the change came into effect in July 2022, these donors were unable to donate due to the risk of  human variant Creutzfeldt\u2013Jakob disease  (vCJD, or \"mad cow disease\") exposure. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5200", "text": "The  B Positive Choir  is a British choir. It contains 60 singers who suffer with the  sickle cell  disease or who have close friends or family suffering from it. The choir is led by Colin Anderson and  Lurine Cato  and features members from across the UK. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5201", "text": "The choir was formed by  NHS Blood and Transplant  as an initiative to help raise the awareness of the disease as well as attract new donors to give blood, which is essential to treating the disease, particularly amongst black and Asian communities who the NHS feel are under-represented. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5202", "text": "The choir performed at the  Boisdale of Canary Wharf  restaurant as a warm-up show for the 2017  MOBO Awards . [ 4 ]  They then performed at the awards show proper in  Leeds , with gospel artist  Lurine Cato  on 29 November. [ 5 ]  MOBO founder  Kanya King  later said she was happy to support and work with the B Positive Choir and was pleased that their televised performance was popular. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5203", "text": "Following the performance, they were invited to perform Christmas songs at  St Pancras railway station . [ 6 ]  They also released a charity single, \"Rise Up\" in late 2017. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5204", "text": "The B Positive Choir starred in the 12th season of  Britain's Got Talent . They were selected to appear in the live show, and came in the top three of the second semi-final.  Amanda Holden  and  Alesha Dixon  voted for the choir, but  Simon Cowell  and  David Walliams  did not. The tie left it up to the audience, and the B Positive Choir were eliminated. However, they were later chosen as the judges' wildcard act, reinstating them into the final. The choir finished in 11th place."}
{"_id": "WikiPedia_Hematology$$$corpus_5205", "text": "In 2019 the choir performed before members of the  royal family  at the annual Commonwealth Service at  Westminster Abbey . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5206", "text": "This article on a United Kingdom band or other musical ensemble is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5207", "text": "The  Blood Donation Badge of Honor  ( German :  Blutspendeehrennadel ) is a German award presented by the  German Red Cross  and by the Blood donation service of the  Bundeswehr  for voluntary unpaid  blood donations ."}
{"_id": "WikiPedia_Hematology$$$corpus_5208", "text": "The badge depicts a golden cross with a red dot in the center, symbolizing a drop of blood on red background. The awards of 25 or more donations feature a  laurel wreath  around the cross. The awards of 50 or more donations also feature diamonds around the center. The number of donations is also shown at the bottom of the laurel wreath.  If worn as a ribbon bar, a miniature version of the badge is attached to a red ribbon bar. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5209", "text": "Blood donation service of the German armed forces :"}
{"_id": "WikiPedia_Hematology$$$corpus_5210", "text": "For 3; 6; 10; 15; 25; 40; 50; 75; 100; 125; 150; 175; 200; 225; 250; 275 and 300 donations."}
{"_id": "WikiPedia_Hematology$$$corpus_5211", "text": "Donors with three or ten blood donations receive their certificate of honor directly on site. Donors with 25 donations will receive their badge of honor on site and will be sent their certificate. In the local associations, donors are honored from the 50th donation. From the 75th donation, the design of the badge of honor differs in the form of a medal with the inscription \"Donate blood save lives\", a cross in a stylized drop of blood and a garnet in a double wreath. In addition, donors who donate more than 75 blood receive an invitation to a major cross-district donor honor. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5212", "text": "German Red Cross"}
{"_id": "WikiPedia_Hematology$$$corpus_5213", "text": "For 10; 25; 50; 75; 100; 125; 150; 175; 200; 250; 275 and 300 donations."}
{"_id": "WikiPedia_Hematology$$$corpus_5214", "text": "Bavarian Red Cross"}
{"_id": "WikiPedia_Hematology$$$corpus_5215", "text": "For 3; 10; 25; 50; 75; 100; 125; 150; 175; 200; 225; 250; 275 and 300 donations."}
{"_id": "WikiPedia_Hematology$$$corpus_5216", "text": "The ribbon is an official German medal according to the  Law regarding Titles, Medals and Decorations . It is usually awarded by the local Red Cross chapter, the local mayor, or for military service members the ribbon is awarded by the commanding officer."}
{"_id": "WikiPedia_Hematology$$$corpus_5217", "text": "Members of the German fire departments, the  Federal Agency for Technical Relief  and other rescue services may wear the ribbon bar for the badge on their  uniform  or  service dress ."}
{"_id": "WikiPedia_Hematology$$$corpus_5218", "text": "The Blood Transfusion Service of the Bundeswehr awards a lapel pin to those soldiers who make voluntary donations of blood.  The ribbon is currently not permitted to be worn on uniforms of the Bundeswehr."}
{"_id": "WikiPedia_Hematology$$$corpus_5219", "text": "A  blood bank  is a center where  blood  gathered as a result of  blood donation  is stored and preserved for later use in  blood transfusion . The term \"blood bank\" typically refers to a department of a hospital usually within a  clinical pathology   laboratory  where the storage of blood product occurs and where pre-transfusion and  blood compatibility testing  is performed. However, it sometimes refers to a collection center, and some hospitals also perform collection. Blood banking includes tasks related to blood collection, processing, testing, separation, and storage. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5220", "text": "For blood donation agencies in various countries, see  list of blood donation agencies  and  list of blood donation agencies in the United States ."}
{"_id": "WikiPedia_Hematology$$$corpus_5221", "text": "Several types of blood transfusion exist: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5222", "text": "While the first  blood transfusions  were made directly from donor to receiver before  coagulation , it was discovered that by adding  anticoagulant  and  refrigerating  the blood it was possible to store it for some days, thus opening the way for the development of blood banks.  John Braxton Hicks  was the first to experiment with chemical methods to prevent the coagulation of blood at  St Mary's Hospital, London , in the late 19th century. His attempts, using  phosphate of soda , however, were unsuccessful. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5223", "text": "The first non-direct transfusion was performed on March\u00a027, 1914, by the  Belgian  doctor  Albert Hustin , though this was a diluted solution of blood. The  Argentine  doctor  Luis Agote  used a much less diluted solution in November of the same year. Both used  sodium citrate  as an anticoagulant. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5224", "text": "The  First World War  acted as a catalyst for the rapid development of blood banks and transfusion techniques. Inspired by the need to give blood to wounded soldiers in the absence of a donor,  [ 2 ]   Francis Peyton Rous  at the  Rockefeller University  (then The Rockefeller Institute for Medical Research) wanted to solve the problems of blood transfusion. [ 2 ]  With a colleague, Joseph R. Turner, he made two critical discoveries: blood typing was necessary to avoid blood clumping (coagulation) and blood samples could be preserved using chemical treatment. [ 3 ]  Their report in March 1915 to identify possible blood preservative was of a failure. The experiments with gelatine, agar, blood serum extracts, starch and beef albumin proved useless. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5225", "text": "In June 1915, they made the first important report in the  Journal of the American Medical Association  that agglutination could be avoided if the blood samples of the donor and recipient were tested before. They developed a rapid and simple method for testing blood compatibility in which coagulation and the suitability of the blood for transfusion could be easily determined. They used  sodium citrate  to dilute the blood samples, and after mixing the recipient's and donor's blood in 9:1 and 1:1 parts, blood would either clump or remain watery after 15 minutes. Their result with a medical advice was clear:"}
{"_id": "WikiPedia_Hematology$$$corpus_5226", "text": "[If] clumping is present in the 9:1 mixture and to a less degree or not at all in the 1:1 mixture, it is certain that the blood of the patient agglutinates that of the donor and may perhaps hemolyze it. Transfusion in such cases is dangerous. Clumping in the 1:1 mixture with little or none in the 9:1 indicates that the plasma of the prospective donor agglutinates the cells of the prospective recipient. The risk from transfusing is much less under such circumstances, but it may be doubted whether the blood is as useful as one which does not and is not agglutinated. A blood of the latter kind should always be chosen if possible. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5227", "text": "Rous was well aware that Austrian physician  Karl Landsteiner  had discovered blood types a decade earlier, but the practical usage was not yet developed, as he described: \"The fate of Landsteiner's effort to call attention to the practical bearing of the group differences in human bloods provides an exquisite instance of knowledge marking time on technique. Transfusion was still not done because (until at least 1915), the risk of clotting was too great.\" [ 6 ]  In February 1916, they reported in the  Journal of Experimental Medicine  the key method for blood preservation. They replaced the additive, gelatine, with a mixture sodium citrate and glucose ( dextrose ) solution and found: \"in a mixture of 3 parts of human blood, 2 parts of  isotonic  citrate solution (3.8 per cent sodium citrate in water), and 5 parts of isotonic dextrose solution (5.4 per cent dextrose in water), the cells remain intact for about 4 weeks.\" [ 7 ]  A separate report indicates the use of citrate-saccharose (sucrose) could maintain blood cells for two weeks. [ 8 ]  They noticed that the preserved bloods were just like fresh bloods and that they \"function excellently when reintroduced into the body.\" [ 7 ]  The use of sodium citrate with sugar, sometimes known as Rous-Turner solution, was the main discovery that paved the way for the development of various blood preservation methods and blood bank. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5228", "text": "Canadian Lieutenant  Lawrence Bruce Robertson  was instrumental in persuading the  Royal Army Medical Corps  (RAMC) to adopt the use of blood transfusion at the  Casualty Clearing Stations  for the wounded. In October 1915, Robertson performed his first wartime transfusion with a syringe to a patient who had multiple shrapnel wounds. He followed this up with four subsequent transfusions in the following months, and his success was reported to Sir  Walter Morley Fletcher , director of the  Medical Research Committee . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5229", "text": "Robertson published his findings in the  British Medical Journal  in 1916, and\u2014with the help of a few like minded individuals (including the eminent physician  Edward William Archibald )\u2014was able to persuade the British authorities of the merits of blood transfusion. Robertson went on to establish the first blood transfusion apparatus at a Casualty Clearing Station on the  Western Front  in the spring of 1917. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5230", "text": "Oswald Hope Robertson , a medical researcher and  U.S. Army  officer, worked with Rous at the Rockefeller between 1915 and 1917, and learned the blood matching and preservation methods. [ 12 ]  He was attached to the RAMC in 1917, where he was instrumental in establishing the first blood banks, with soldiers as donors, in preparation for the anticipated  Third Battle of Ypres . [ 13 ]  He used  sodium citrate  as the anticoagulant, and the blood was extracted from punctures in the vein, and was stored in bottles at British and American Casualty Clearing Stations along the Front. He also experimented with preserving separated  red blood cells  in iced bottles. [ 11 ]   Geoffrey Keynes , a British surgeon, developed a portable machine that could store blood to enable transfusions to be carried out more easily."}
{"_id": "WikiPedia_Hematology$$$corpus_5231", "text": "The world's first blood donor service was established in 1921 by the secretary of the  British Red Cross ,  Percy Lane Oliver . [ 14 ]  Volunteers were subjected to a series of physical tests to establish their  blood group . The  London Blood Transfusion Service  was free of charge and expanded rapidly. By 1925, it was providing services for almost 500 patients and it was incorporated into the structure of the British Red Cross in 1926. Similar systems were established in other cities including  Sheffield ,  Manchester  and  Norwich , and the service's work began to attract international attention. Similar services were established in France, Germany, Austria, Belgium, Australia and Japan. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5232", "text": "Vladimir Shamov and  Sergei Yudin  in the  Soviet Union  pioneered the  transfusion of cadaveric blood  from recently deceased donors. Yudin performed such a transfusion successfully for the first time on March 23, 1930, and reported his first seven  clinical   transfusions  with cadaveric blood at the Fourth Congress of  Ukrainian  Surgeons at Kharkiv in September. Also in 1930, Yudin organized the world's first blood bank at the Nikolay Sklifosovsky Institute, which set an example for the establishment of further blood banks in different regions of the Soviet Union and in other countries. By the mid-1930s the Soviet Union had set up a system of at least 65 large blood centers and more than 500 subsidiary ones, all storing \"canned\" blood and shipping it to all corners of the country."}
{"_id": "WikiPedia_Hematology$$$corpus_5233", "text": "One of the earliest blood banks was established by  Frederic Dur\u00e1n-Jord\u00e0  during the  Spanish Civil War  in 1936. Duran joined the Transfusion Service at the  Barcelona Hospital  at the start of the conflict, but the hospital was soon overwhelmed by the demand for blood and the paucity of available donors. With support from the Department of Health of the  Spanish Republican Army , Duran established a blood bank for the use of wounded soldiers and civilians. The 300\u2013400 ml of extracted blood was mixed with 10% citrate solution in a modified Duran Erlenmeyer flask. The blood was stored in a sterile glass enclosed under pressure at 2\u00a0\u00b0C. During 30 months of work, the Transfusion Service of Barcelona registered almost 30,000 donors, and processed 9,000 liters of blood. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5234", "text": "In 1937  Bernard Fantus , director of therapeutics at the  Cook County Hospital  in  Chicago , established one of the first hospital blood banks in the  United States . [ 17 ]  In creating a hospital laboratory that preserved, refrigerated and stored donor blood, Fantus originated the term \"blood bank\". Within a few years, hospital and community blood banks were established across the United States. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5235", "text": "Frederic Dur\u00e1n-Jord\u00e0  fled to Britain in 1938, and worked with  Janet Vaughan  at the  Royal Postgraduate Medical School  at Hammersmith Hospital to create a system of national blood banks in London. [ 19 ]  With the outbreak of  war  looking imminent in 1938, the  War Office  created the Army Blood Supply Depot (ABSD) in Bristol headed by  Lionel Whitby  and in control of four large blood depots around the country. British policy through the war was to supply military personnel with blood from centralized depots, in contrast to the approach taken by the Americans and Germans where troops at the front were bled to provide required blood. The British method proved to be more successful at adequately meeting all requirements and over 700,000 donors were bled over the course of the war. This system evolved into the  National Blood Transfusion Service  established in 1946, the first national service to be implemented. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5236", "text": "A blood collection program was initiated in the US in 1940 and  Edwin Cohn  pioneered the process of  blood fractionation . He worked out the techniques for isolating the  serum albumin  fraction of  blood plasma , which is essential for maintaining the  osmotic pressure  in the  blood vessels , preventing their collapse."}
{"_id": "WikiPedia_Hematology$$$corpus_5237", "text": "The use of blood plasma as a substitute for whole blood and for transfusion purposes was proposed as early as 1918, in the correspondence columns of the  British Medical Journal , by Gordon R. Ward. At the onset of  World War II , liquid plasma was used in Britain. A large project, known as 'Blood for Britain' began in August 1940 to collect blood in  New York City  hospitals for the export of plasma to  Britain . A dried plasma package was developed, which reduced breakage and made the transportation, packaging, and storage much simpler. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5238", "text": "The resulting dried plasma package came in two tin cans containing 400\u00a0cc bottles. One bottle contained enough  distilled water  to reconstitute the dried plasma contained within the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours. [ 22 ]   Charles R. Drew  was appointed medical supervisor, and he was able to transform the  test tube  methods into the first successful mass production technique."}
{"_id": "WikiPedia_Hematology$$$corpus_5239", "text": "Another important breakthrough came in 1939\u201340 when  Karl Landsteiner , Alex Wiener, Philip Levine, and R.E. Stetson discovered the  Rh blood group system , which was found to be the cause of the majority of  transfusion reactions  up to that time. Three years later, the introduction by  J.F. Loutit  and Patrick L. Mollison of  acid-citrate-dextrose  (ACD) solution, which reduced the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer-term storage."}
{"_id": "WikiPedia_Hematology$$$corpus_5240", "text": "Carl Walter and W.P. Murphy Jr. introduced the  plastic bag  for blood collection in 1950. Replacing breakable  glass  bottles with durable plastic bags allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood."}
{"_id": "WikiPedia_Hematology$$$corpus_5241", "text": "Further extending the shelf life of stored blood up to 42 days was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks. [ 23 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5242", "text": "In the U.S., certain standards are set for the collection and processing of each blood product.  \"Whole blood\" (WB) is the proper name for one defined product, specifically unseparated venous blood with an approved preservative added.  Most blood for transfusion is collected as whole blood.   Autologous  donations are sometimes transfused without further modification, however whole blood is typically separated (via centrifugation) into its components, with  red blood cells  (RBC) in solution being the most commonly used product.  Units of WB and RBC are both kept refrigerated at 33.8 to 42.8\u00a0\u00b0F (1.0 to 6.0\u00a0\u00b0C), with maximum permitted storage periods ( shelf lives ) of 35 and 42 days respectively. RBC units can also be frozen when buffered with glycerol, but this is an expensive and time-consuming process, and is rarely done.  Frozen red cells are given an expiration date of up to ten years and are stored at \u221285\u00a0\u00b0F (\u221265\u00a0\u00b0C)."}
{"_id": "WikiPedia_Hematology$$$corpus_5243", "text": "The less-dense  blood plasma  is made into a variety of frozen components, and is labeled differently based on when it was frozen and what the intended use of the product is.  If the plasma is frozen promptly and is intended for transfusion, it is typically labeled as  fresh frozen plasma . If it is intended to be made into other products, it is typically labeled as recovered plasma or plasma for  fractionation .   Cryoprecipitate  can be made from other plasma components.  These components must be stored at 0\u00a0\u00b0F (\u221218\u00a0\u00b0C) or colder, but are typically stored at \u221222\u00a0\u00b0F (\u221230\u00a0\u00b0C). The layer between the red cells and the plasma is referred to as the  buffy coat  and is sometimes removed to make  platelets  for transfusion.  Platelets are typically pooled before transfusion and have a shelf life of 5 to 7 days, or 3 days once the facility that collected them has completed their tests.  Platelets are stored at room temperature (72\u00a0\u00b0F or 22\u00a0\u00b0C) and must be rocked/agitated.  Since they are stored at room temperature in nutritive solutions, they are at relatively high risk for growing  bacteria ."}
{"_id": "WikiPedia_Hematology$$$corpus_5244", "text": "Some blood banks also collect products by  apheresis . The most common component collected is plasma via  plasmapheresis , but red blood cells and platelets can be collected by similar methods.  These products generally have the same shelf life and storage conditions as their conventionally-produced counterparts."}
{"_id": "WikiPedia_Hematology$$$corpus_5245", "text": "Donors are sometimes paid; in the U.S. and Europe, most blood  for transfusion  is collected from volunteers while plasma for other purposes may be from paid donors."}
{"_id": "WikiPedia_Hematology$$$corpus_5246", "text": "Most collection facilities as well as hospital blood banks also perform testing to determine the  blood type  of patients and to identify compatible blood products, along with a battery of tests (e.g. disease) and treatments (e.g. leukocyte filtration) to ensure or enhance quality. The increasingly recognized problem of inadequate efficacy of transfusion [ 25 ]  is also raising the profile of RBC viability and quality. Notably, U.S. hospitals spend more on dealing with the consequences of transfusion-related complications than on the combined costs of buying, testing/treating, and transfusing their blood. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5247", "text": "Routine blood storage is 42 days or 6 weeks for stored packed  red blood cells  (also called \"StRBC\" or \"pRBC\"), by far the most commonly transfused blood product, and involves refrigeration but usually not freezing. There has been increasing controversy about whether a given product unit's age is a factor in transfusion efficacy, specifically on whether \"older\" blood directly or indirectly increases risks of complications. [ 27 ] [ 28 ]  Studies have not been consistent on answering this question, [ 29 ]  with some showing that older blood is indeed less effective but with others showing no such difference; nevertheless, as storage time remains the only available way to estimate quality status or loss, a  first-in-first-out  inventory management approach is standard presently. [ 30 ]  It is also important to consider that there is large  variability  in storage results for different donors, which combined with limited available quality testing, poses challenges to clinicians and regulators seeking reliable indicators of quality for blood products and storage systems. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5248", "text": "Transfusions of  platelets  are comparatively far less numerous, but they present unique storage/management issues. Platelets may only be stored for 7 days, [ 32 ]  due largely to their greater potential for contamination, which is in turn due largely to a higher storage temperature."}
{"_id": "WikiPedia_Hematology$$$corpus_5249", "text": "Insufficient transfusion efficacy can result from red blood cell (RBC) blood product units damaged by so-called  storage lesion \u2014a set of biochemical and biomechanical changes which occur during storage. With red cells, this can decrease viability and ability for tissue oxygenation. [ 33 ]   Although some of the biochemical changes are reversible after the blood is transfused, [ 34 ]  the biomechanical changes are less so, [ 35 ]  and rejuvenation products are not yet able to adequately reverse this phenomenon. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5250", "text": "Current regulatory measures are in place to minimize RBC storage lesion\u2014including a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold (currently 1% in the US), and a minimum level of post-transfusion RBC survival  in vivo  (currently 75% after 24 hours). [ 37 ]  However, all of these criteria are applied in a universal manner that does not account for differences among units of product; [ 31 ]  for example, testing for the post-transfusion RBC survival  in vivo  is done on a sample of healthy volunteers, and then compliance is presumed for all RBC units based on universal (GMP) processing standards. RBC survival does not guarantee efficacy, but it is a necessary prerequisite for cell function, and hence serves as a regulatory proxy. Opinions vary as to the best way to determine transfusion efficacy in a patient  in vivo . [ 38 ]  In general, there are not yet any  in vitro  tests to assess quality deterioration or preservation for specific units of RBC blood product prior to their transfusion, though there is exploration of potentially relevant tests based on RBC membrane properties such as  erythrocyte deformability [ 39 ]  and  erythrocyte fragility  (mechanical). [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5251", "text": "Many physicians have adopted a so-called \"restrictive protocol\"\u2014whereby transfusion is held to a minimum\u2014due in part to the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions, [ 26 ]  along with the increasing view that many transfusions are inappropriate or use too many RBC units. [ 41 ] [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5252", "text": "Platelet storage lesion is a very different phenomenon from RBC storage lesion, due largely to the different functions of the products and purposes of the respective transfusions, along with different processing issues and inventory management considerations. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5253", "text": "Although as noted the primary inventory-management approach is first in, first out (FIFO) to minimize product expiration, there are some deviations from this policy\u2014both in current practice as well as under research. For example, exchange transfusion of RBC in neonates calls for use of blood product that is five days old or less, to \"ensure\" optimal cell function. [ 44 ]   Also, some hospital blood banks will attempt to accommodate physicians' requests to provide low-aged RBC product for certain kinds of patients (e.g. cardiac surgery). [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5254", "text": "More recently, novel approaches are being explored to complement or replace FIFO. One is to balance the desire to reduce average product age (at transfusion) with the need to maintain sufficient availability of non-outdated product, leading to a strategic blend of FIFO with last in, first out (LIFO). [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5255", "text": "\"Long-term\" storage for all blood products is relatively uncommon, compared to routine/short-term storage.  Cryopreservation  of red blood cells is done to store rare units for up to ten years. [ 47 ]  The cells are incubated in a  glycerol  solution which acts as a  cryoprotectant  (\"antifreeze\") within the cells. The units are then placed in special sterile containers in a freezer at very low temperatures.  The exact temperature depends on the glycerol concentration."}
{"_id": "WikiPedia_Hematology$$$corpus_5256", "text": "Blood Centers of the Pacific  was a community-based,  nonprofit   blood center  collecting blood  donations  and provides safe  blood  and  blood components  for  transfusion  and also related services to more than 40 hospitals [ 1 ]  in the  Bay Area  and  Northern California . Its predecessors included the first blood bank in the United States, which through expansions grew in the San Francisco and Sacramento areas. The Blood Centers of the Pacific name was retired in 2018 when parent Blood Systems, Inc., unified all of its regional operations under the  Vitalant  name."}
{"_id": "WikiPedia_Hematology$$$corpus_5257", "text": "On June 17, 1941, [ 2 ]  the Irwin Memorial Blood Bank opened its doors in response to the lack of a sufficient method of obtaining and storing  blood  for later use \u2013 by both the military and community hospitals in the  San Francisco  area. The aim was to ensure that patients in the  Bay Area  would never again be without an adequate supply of blood. Irwin Memorial Blood Bank is credited as the first community  blood bank  in the United States. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5258", "text": "The San Francisco County Medical Society granted the fledgling blood bank permission to operate out of the basement floor of an old San Francisco home, the Irwin Mansion. However, after years of growth, the blood bank had expanded its blood collection operations throughout  Northern California , and it soon became clear that a bigger facility was needed for its headquarters. In April 1955, Irwin opened its new doors at Masonic and Turk Streets in San Francisco. [ 4 ]  The Blood Centers of the Pacific headquarters still exist at this location today. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5259", "text": "In 1997, the Irwin Memorial Blood Bank merged with the Peninsula Memorial Blood Bank to become Blood Centers of the Pacific, reflecting its larger service area. [ 4 ]  In 1999, Blood Centers of the Pacific affiliated with United Blood Services, the nation\u2019s largest blood collection organization. [ 4 ]  Blood Centers of the Pacific merged with the Sacramento area's BloodSource blood center in 2015; [ 5 ]  United Blood Services changed its corporate brand name in 2018 to  Vitalant  and retired all of its regional brand names. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5260", "text": "The Blood Systems Research Institute was housed at Blood Centers of the Pacific. It changed its name to Vitalant Research Institute as part of the rebranding. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5261", "text": "This is a  list of blood donation agencies  in different countries."}
{"_id": "WikiPedia_Hematology$$$corpus_5262", "text": "There are more than 500 blood banks in Mexico, about 60% of which collect less than 2,000 units per year. [ 1 ]   Most are government agencies, and many are private. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5263", "text": "The United States does not have a centralized blood donation service.  The  American Red Cross  collects approximately 35% of the blood used, while the rest is collected by independent nonprofit blood centers, most of which are members of  America's Blood Centers .  The US military collects blood from service members for its own use, but also draws blood from the civilian supply. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5264", "text": "A social organization, which has active involvement in blood donation in India.\nIt has been involved in blood donation through major camps since 2010."}
{"_id": "WikiPedia_Hematology$$$corpus_5265", "text": "Detail of the Major Blood units collection through voluntary blood donation camps are:-"}
{"_id": "WikiPedia_Hematology$$$corpus_5266", "text": "Blood donation in Bangladesh  is an activity conducted by several different organisations. As of 2011 [update] , about 25% of the nation's blood supply came from voluntary donation, 20\u201325% from paid donors, and 50\u201355% from one-time donation for a specific patient."}
{"_id": "WikiPedia_Hematology$$$corpus_5267", "text": "Blood transfusion  service became available in  Bangladesh  at the  Dhaka Medical College Hospital  in 1950. [ 1 ]  Professional blood donors were the mainstay of blood donation in Bangladesh, with 47% of donated blood coming from professional donors as late as the year 2000. [ 1 ]  The potential for contamination in the supply, and the need for volunteer donors was well recognised. [ 1 ]  An estimate from 2011 is that of the 500,000 units of blood required annually, only 25% come from voluntary donation, 20\u201325% from paid donors, and 50\u201355% from one-time donation for a specific patient. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5268", "text": "Medicine Club is a non-profit humanitarian organization in Bangladesh volunteered by medical and dental students. [ 3 ]  The organization was founded on 31 January 1981, at  Mymensingh Medical College [ 3 ]  with the intention of helping the helpless and serving humanity. Now it has 21 units in different medical & dental colleges. [ 3 ]  It has since broadened its scope to include voluntary blood donating, prevent Thalassaemia  [ 4 ]  throughout Bangladesh & rise awareness about this. It contributes a large amount of donated blood throughout Bangladesh. [ 5 ]  It also helps poor patients by donating money and drugs. [ 6 ]  This organization also distributes vaccines. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5269", "text": "The first  voluntary blood donation program in Bangladesh was begun in 1977 at  Dhaka Medical College , and was organized by  SANDHANI . [ 8 ] \nSANDHANI has now 25 units in different medical and dental colleges. [ 9 ] \nSANDHANI is a voluntary institution run by the medical and dental students of BANGLADESH. It is mainly working on motivation on voluntary blood donation and posthumous eye donation in Bangladesh.\nSANDHANI is also working for the helpless patient in the community by serving them with drug from the drug bank, donating blood to the thalassaemia patient, giving relief to the flooded and disaster affected people etc. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5270", "text": "The  International Red Cross and Red Crescent Movement  began a blood program in Bangladesh in 1981. [ 11 ]  Today they operate several centres, using both whole blood and fractionated blood components. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5271", "text": "A 1997 survey of students at the  University of Dhaka  had found a generally favourable attitude towards voluntary blood donation, and an overwhelmingly unfavourable attitude to paid blood donation, and recommended that a campaign should be started immediately to increase awareness and participation in voluntary blood donation among the student population. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5272", "text": "Badhan is a non-political voluntary  blood donors'  organisation in Bangladesh that was established in 1997. [ 13 ]  Badhan's first activity was a free blood-group testing program that took place on 24 October 1997 at  Shahidullah Hall  of the University of Dhaka. [ 13 ]  Shahidullah Hall is very close to Dhaka Medical College and Hospital, and before that time people needing blood for patients would gather regularly in or near the hall gate, seeking help. [ 13 ]  Mohammad Shahidul Islam Ripon was the principal originator of the program, along with other students. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5273", "text": "The blood provided is fresh rather than stored, [ 14 ]  using a database of people whose blood type has been previously established. The graduate- and postgraduate-level students of Bangladeshi universities and postgraduate colleges are the main participants of the organisation. [ 13 ]  The organisation is active in 14 universities and 29 university colleges. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5274", "text": "Other activities include raising awareness about donating fresh blood, donating blood voluntarily for patients and helping poor people in time of natural disasters. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5275", "text": "Financing comes primarily from individual members and ex-members, as well as from the universities and colleges administration, from donations. [ 14 ]  The California non-profit organisation SpaandanB has been a significant contributor from outside Bangladesh. [ 16 ] \nBadhan wants to make blood donation as a social movement. Its ultimate goals are (a) none should die from lack of blood, (b) every person knows his/her blood group. The head office of Badhan is located on the ground floor of TSC, Dhaka University. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5276", "text": "Charpoka Blood Bank is an initiative by Project Charpoka. It is a voluntary blood donating project in  Bangladesh . The Charpoka Blood Bank was inaugurated in 2016. It has the largest database of blood donors and it aimed to build 2 million blood donors database by 2020. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5277", "text": "Blood donations  in  India  are conducted by organisations and hospitals through blood donation camps. Donors can also visit  blood banks  in hospitals to donate blood. Efforts by the government and advocacy groups over the years have helped bridge the gap between demand and supply. The regulatory framework for blood donation and blood bank management rests with the  Central Drugs Standard Control Organisation , while technical bodies like the National Blood Transfusion Council and  National AIDS Control Organisation  formulate guidelines and recommendations for transfusion medicine and blood bank management. [ 1 ]  Challenges persist with regards to regulation of blood banks and transfusion practices as the sector is largely fragmented with uneven distribution of blood banks and supply of blood in parts of the country. Donors are usually provided with refreshments after the procedure, which include  glucose  drinks, biscuits and fruits. Some organisations offer transportation facilities, as well as certificates or badges as gratitude. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5278", "text": "The history of voluntary blood donation in  India  dates back to 1942 during the  Second World War  when blood donors were required to help the wounded soldiers. The first blood bank was established in  Kolkata ,  West Bengal  in March 1949 at the  All India Institute of Hygiene and Public Health  and was managed by the  Red Cross . The donors were mostly government employees and people from the Anglo-Indian community who donated blood for a humanitarian cause. The number of voluntary donors declined after the war and donors had to be paid for the blood.  Leela Moolgaonkar , a social reformer, initiated voluntary blood donation camps in  Mumbai  from 1954. [ 3 ]  The 1960s saw many blood banks open in different cities. In 1975, the Indian Society of Blood Transfusion and Immunohaematology headed by  J. G. Jolly  declared 1 October as the National Voluntary Blood Donation Day. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5279", "text": "The HIV pandemic in the 1980s led to the government setting up the National AIDS Control Organisation (NACO) in 1992 to oversee the policies in preventing the spread of AIDS. Subsequently, the National AIDS Control Programme was launched which led to improvements in patient screening and hygienic transfusion procedures. A  public interest litigation  was filed in the Supreme Court in 1996 to abolish the practice of selling blood which became effective on 1 January 1998. [ 2 ]  This led to a temporary shortage of blood as voluntary donations were still relatively low. [ 5 ]  The NACO in 2002 adopted the WHO Guidelines on the Clinical Use of Blood. [ 6 ]  Selling or donating blood in exchange for money is illegal under the  National Blood Transfusion Services Act 2007  and those found convicted may face a prison sentence of up to three months with fine. [ 7 ]  A petition was filed in the Supreme Court in March 2021 challenging the blood donation guidelines that prohibits transgender people, members of the gay community and sex workers from donating blood. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5280", "text": "There are several parameters that determine the eligibility of an individual to donate blood. Guidelines laid down by the  Ministry of Health ,  Government of India  have to be followed by blood banks for donor screening. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5281", "text": "Overall health and vital signs: [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5282", "text": "Individuals under certain conditions are deemed ineligible to donate blood: [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5283", "text": "The number of voluntary blood donors increased from 54.4% in 2006\u20132007 to 83.1% in 2011\u20132012, with the number of blood units increasing from 4.4 million units in 2006\u20132007 to 9.3 million units in 2012\u20132013. [ 3 ]  In 2016, the  Ministry of Health and Family Welfare  reported a donation of 10.9 million units against a requirement of 12 million units. [ 10 ]  In 2018 the Ministry of Health and Family Welfare with support from its various institutions published a detailed report on the blood requirement in India. [ 11 ]  12.7 million units were donated in 2020, lower than projected due to the  COVID-19 pandemic . [ 12 ]  A study in 2022 extrapolated the eligible donor population in India at 402 million. The supply was estimated at 33.8 donations against the demand of 36.3 per thousand donations, translating to a shortage of one million units annually. Medical specialty had the highest demand for blood at 6.0 million units (41.2%), followed by surgery 4.1 million (27.9%), obstetrics and gynecology 3.3 million (22.4%) and pediatrics 1.2 million (8.5%). [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5284", "text": "Human blood is covered under the definition of  drug  under the  Drugs and Cosmetics Act, 1940 . Blood bank activities are regulated under this act and they are required to obtain timely renewal of the license from  Drug Controller General  for operation and have to comply with the terms presented in the license. It specifies accommodation, manpower, equipment, supplies and reagents, good manufacturing practices, and process control to be followed in Indian blood transfusion services. [ 14 ]  Dual licensing of blood banks by federal and state regulatory bodies was made mandatory in 1993, with a renewal required every 5 years. [ 1 ]   NABH  is the main accreditation body for hospitals and blood banks in the country. [ 15 ] [ 16 ]  The National Haemovigilance Programme was launched in 2012 to monitor adverse transfusion reactions, and subsequently in 2015 the National Blood Donor Vigilance Programme was initiated. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5285", "text": "The National AIDS Control Organisation (NACO) was formed in 1992 following the outbreak of AIDS. Following public interest litigation, a verdict by the supreme court in the case of  Common Cause vs. the Union of India  in January 1992 led to the establishment of the National Blood Transfusion Council (NBTC) at the federal level and State Blood Transfusion Councils (SBTC) for all the states to review the status of blood transfusion services in the country and conduct annual monitoring visits to blood banks. [ 18 ]  While the regulatory authority is entrusted with the task of drug regulation, NACO and NBTC are the technical bodies that frame guidelines for the practice of transfusion medicine. In 2018, an expert working group of the NBTC proposed recommendations on manpower requirements for blood banks, which outlined the minimum number of staff at blood banks and their qualifications. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5286", "text": "The Government of India in 2002 published the National Blood Policy to reiterate the commitment to safe blood and blood components. [ 21 ]  It documents the strategies for making available adequate resources, technology, and training for improving transfusion services apart from outlining methods for donor motivation and appropriate clinical use of blood by clinicians. It has also taken steps for research and development in transfusion medicine. [ 18 ]  There have been recommendations to include blood under the National List of Essential Medicines to control pricing transparency and affordability of blood. [ 22 ]  The fragmented nature of organisational types that conduct blood donations, along with advancements in transfusion science and new practices in blood bank management technology have prompted calls from academics to review and amend the  Drugs and Cosmetics Act  from time to time. [ 1 ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5287", "text": "India has government-funded and private blood donation organisations. Some major organisations operate in many regions throughout the country while others are regional and operate with local support. Along with conducting blood donation camps, they also raise awareness on voluntary blood donation and public health. Most organisations maintain online portals or physical registry where donors can enter their details and receive updates when blood donation drives are conducted; this also facilitates a network between blood donors and organisations/hospitals. [ 24 ]  Apart from such organisations, major hospitals in the country have their own blood banks where blood donation is conducted within the facility. As of 2015, there were 2.2 blood banks per million population in the country. [ 25 ]  As per a 2016 study, around 51% of the 2493 blood banks surveyed across the country had component separation facility. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5288", "text": "Despite a huge population, the demand-supply gap for blood units persists in many healthcare facilities in the country. As of 2022 the annual shortage of blood is estimated at one million units. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5289", "text": "A study conducted between 2009 and 2013 concluded a high rate of non-compliance on the part of blood banks on the quality and safety of transfusion services. [ 27 ]  Cases of transmission of infective diseases like  AIDS  due to substandard medical facilities and practices in blood banks continue to be relatively high. [ 28 ]  The  National Blood Policy  outlines the requirement for primary healthcare centres to have 24/7 service for blood transfusion, but over 80% of them lack blood storage facility. [ 29 ]  With the sector being largely unorganized and fragmented, and lack of communication between hospitals with no real-time centralized data on availability of blood units between them, there have been instances of shortage of blood at hospitals being a major factor in deaths caused by time-critical events such as accidents. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5290", "text": "Disparities in access of donors in regions have led to wastage of blood stock in some parts of the country, while at the same time creating a shortage of blood in some other parts. [ 32 ]   Voluntary blood donation comprises about 70% of the blood demand, with the rest coming from replacement donors, whereas 62 nations in the world fulfill their blood demands through voluntary donations. [ 33 ] [ 34 ]  A 2011 study reported that a mere 6% of women donated blood, mostly due to physiological problems and low hemoglobin count. [ 35 ]  Anaemia is also reported as a major cause of deferral in blood donation, accounting for up to 77.9% of female and up to 37% of male deferrals. [ 22 ]  Other hurdles in increasing voluntary blood donation include the fear of pain and weakness after the procedure, and illiteracy. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5291", "text": "Documented instances of  forced blood extraction  have occurred in India, among other countries, owing to its disproportionate ratio of available supply of blood and high poverty rate. One such ring gained national attention in 2008 when an emaciated man escaped from his captors near the city of  Gorakhpur , in  Uttar Pradesh . [ 37 ] [ 38 ]  Blood donations reduced during the COVID-19 pandemic, primarily due to restrictions on travel and fear of contracting the disease at healthcare centres. [ 39 ] [ 40 ] [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5292", "text": "1 October is celebrated as the national voluntary blood donation day. [ 42 ]  Blood donation agencies often organize workshops to educate people about the benefits of donating blood. [ 43 ]  With a huge population of youth, blood donation drives are conducted by hospitals and organisations at college campuses. [ 44 ] [ 45 ]  Blood donors and their family members are often given priority in case of emergency or accidents. 32 mobile blood banks were introduced in 2010 to facilitate donation in remote regions. [ 46 ] [ 47 ]  In 2016, the government launched an initiative called  E- RaktKosh  ( Rakt : blood,  Kosh : repository), a web-based mechanism that integrates all blood banks in the state into a single network, providing information about blood camps and the availability of blood in hospitals throughout the country. [ 48 ]  A mobile application for the  E- RaktKosh  portal was launched in 2020 to improve accessibility. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5293", "text": "Many countries have laws, regulations, or recommendations that effectively prohibit donations of  blood  or tissue for  organ  and  corneal transplants  from  men who have sex with men  (MSM), a classification irrespective of their  sexual activities with same-sex partners  and of whether they  identify themselves  as  bisexual  or  gay . Temporary restrictions are sometimes called \"deferrals\", since blood donors who are found ineligible may be found eligible at a later date. However, many deferrals are indefinite meaning that donations are not accepted at any point in the future, constituting a  de facto  ban. Even men who have monogamous relations with their same-sex partners are found ineligible."}
{"_id": "WikiPedia_Hematology$$$corpus_5294", "text": "Since 1982, the risk for HIV infection transmitted via transfusion has been almost eliminated by the use of questionnaires to exclude donors at higher risk for HIV infection and performing screening tests with highly sensitive equipment to identify infected blood donations. According to the 2015 surveillance report by Canadian Blood Services, the risk of HIV transfusion-transmitted infection was fairly low: in 1 in 21.4 million donations. [ 1 ]   Contaminated blood  put  haemophiliacs  at massive risk and severe mortality, increasing the risk of common surgical procedures. People who contracted HIV from a contaminated  blood transfusion  include  Isaac Asimov , who received a blood transfusion following cardiac surgery."}
{"_id": "WikiPedia_Hematology$$$corpus_5295", "text": "In many high-income countries HIV is more prevalent among  men who have sex with men  (MSM) than among the general population. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5296", "text": "In the United States the population most affected by HIV includes gay, bisexual, and other MSM. [ 3 ]  Of the 38,739 new HIV diagnoses in the US and dependent areas in 2017, 70% consisted of adult and adolescent gay and bisexual men. [ 3 ]  Although approximately 492,000 sexually active gay and bisexual men are at high risk for HIV, there are more tools to prevent HIV than ever before. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5297", "text": "Proponents of the lifetime restriction defend it because of the asserted risk of false negative test results [ 4 ]  and because the MSM population in developed countries tends to have a higher prevalence of HIV/AIDS infection. [ 2 ]  The UK government advisory committee, SABTO, stated in 2013 that \"the risk of transfusion of HIV infected blood would increase if MSM were allowed to donate blood\". [ 5 ]  In July 2017 however, the UK government reduced the one year deferral window to three months, to take effect in the following months, resulting from SABTO's updated conclusions that \"new testing systems were accurate and donors were good at complying with the rules\". Furthermore,  NHS Blood and Transplant  are in the process of investigating how possible it is for MSM, depending on the degree of risk, to donate without even the three-month deferral. [ 6 ]  NHS has said that there is currently a limited amount of data on effective ways of conducting such risk assessments and that the initial steps of scoping, evidence gathering and testing will potentially take up to two years to complete. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5298", "text": "Restrictions vary from country to country, and in some countries, the practice of protected sex or periods of abstinence are not considered. The restrictions affect these men and, in some cases, any female sex partners. They do not otherwise affect other women, including  women who have sex with women . With regard to blood donation, the  United States Food & Drug Administration  (FDA) enforces a three-month deferral period for MSM and women who have sex with MSM. [ 8 ]  In Canada, the deferral period for MSM blood donors was decreased to 3 months in June 2019. [ 9 ]  Meanwhile, for tissues such as  corneas , the MSM deferral period is five years in the United States and 12 months in Canada. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5299", "text": "This list shows countries that had restrictions on blood donors. [ 11 ] [ 12 ]  Most national standards require direct questioning regarding a man's sexual history, but the length of deferral varies."}
{"_id": "WikiPedia_Hematology$$$corpus_5300", "text": "Since September 2022, the ban was lifted completely. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5301", "text": "Several European countries do not have deferral policies for  men who have sex with men  (MSM). The donation is allowed if the donor has not had a risky sexual encounter, but not depending on the sexual orientation of the donor. [ 162 ] [ 163 ] [ 95 ]  For example, in Italy, the questionnaire item for sexual behaviour is symmetrical with respect to homosexual, heterosexual and bisexual intercourses and mentions them explicitly, as well as all points of sexual contact (oral, genital, anal), and does not mention usage of protection. [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5302", "text": "The UK since November 2017 has  implemented a 3-month deferral policy  on all gay/bi men who want to donate their blood. [ 164 ] [ 165 ] [ 166 ]  However, this did not apply to Northern Ireland until 2020. [ 167 ]  The Advisory Committee on the Safety of Blood, Tissues and Organs recommended the policy change after a study concluded that a total ban may breach equality legislation and that the risk of HIV reaching the blood supply would only increase by approximately 2%. [ 168 ]  In December 2020, it was announced that the UK would move to a personalised sexual behaviour risk assessment and scrap the deferral period specific to MSM. [ 169 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5303", "text": "In Ireland, MSM could historically donate blood if they had not engaged in oral or anal sex with another man at least 12 months prior to a donation. This policy had come into effect on 16 January 2017. On 27 July 2015, Tom\u00e1s Heneghan, a 23-year-old University of Limerick student, and journalist from Galway began a legal challenge in the High Court against the permanent deferral imposed on MSM donors. [ 170 ] [ 171 ]  He argued that the questionnaire and interview process used by the IBTS does not adequately assess the risk of disease transmission posed by his donation. He claims this is in breach of EU law. He said that both failed to consider the length of time between a donor's last sexual experience and the end of a \"window period\" in which infections are sometimes not detected. Heneghan's previous sexual activity posed no risk of infection, according to HSE-approved advice and he said the service had no evidence upon which it could legitimately impose a life-long ban on him donating blood. Following several adjournments of the case to allow the blood service and Department of Health to examine and develop the donation policies, in late June 2016 the Irish Blood Transfusion Service recommended that the lifetime ban on MSM be reduced to a 12-month ban. Later that week the Minister for Health Simon Harris agreed to the recommendations and announced the reduction would take place. However, no timeline was reported for the implementation of the new policies. [ 172 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5304", "text": "On 26 July 2016, Tom\u00e1s Heneghan dropped his High Court challenge against the service as an end to the lifetime deferral on MSM blood donors had been announced in the interim. [ 173 ]  Heneghan then wrote about his experiences of challenging the ban in a number of national media outlets. [ 174 ] [ 175 ]  On 2 October 2016, it was reported that Minister Harris would implement the new policy from 16 January 2017, almost seven months after he announced the policy change. [ 82 ]  On 16 January 2017, Heneghan (now 25) attended a blood donation clinic in D'Olier Street, Dublin, and became the first man who has had sex with another man to donate blood openly in the Republic of Ireland since the lifetime deferral policy was first introduced in the 1980s. However, he also criticized the new 12-month deferral policy on MSM and called on Ireland's Health Minister to initiate a review of the IBTS and replace the 12-month deferral period for MSM with no deferral or a 3-month deferral on all donors following sexual intercourse. [ 176 ] [ 177 ] [ 178 ] [ 179 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5305", "text": "On 20 May 2019, Heneghan (27) initiated a fresh legal challenge in the High Court against the blanket deferral on men who had had oral or anal sex with another man in the previous 12-month period. [ 180 ] [ 181 ] [ 182 ] [ 183 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5306", "text": "Heneghan claims he cannot understand the reasoning behind the IBTS policy and argues that the questionnaire does not enable the IBTS to make a full evaluation of the level of risk presented by an individual donor due to their sexual behaviour. He also states that according to the IBTS's own website, there is a window period following infection during which HIV and hepatitis may not be detected in the blood and that this window is seven days for HIV and 16 days for hepatitis. He claims that a far less onerous restriction could be imposed rather than the 12-month deferral, which would protect blood recipients. He claims the decision to place an \"automatic deferral\" on him is unlawful and in breach of EU law and European communities regulations on the quality and safety of human blood products and that the policy is disproportionate, discriminates against homosexual and bisexual men, and breaches his constitutional rights and rights under the European Convention on Human Rights. The case is due to return to the court in July 2019."}
{"_id": "WikiPedia_Hematology$$$corpus_5307", "text": "In July 2019, a gay man in Ireland filed two formal complaints with the European Commission against the Department of Health and the Irish Blood Transfusion Service, and the Northern Ireland Blood Transfusion Service (the only part of the United Kingdom to maintain a 12-month deferral policy for MSM) over the MSM one-year deferral policy. The man, who has chosen to have his complaints examined by the Commission anonymously, is alleging the ban in both jurisdictions violates a number of European Union laws, including two European Union Directives covering the standards of quality and safety for the collection of blood by EU member states, as well as provisions contained in both the EU Charter of Fundamental Rights and the European Convention on Human Rights. The commission has informed the man his complaints will now be considered in light of EU law. [ 184 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5308", "text": "A similar policy exists in the rest of the European Union and is the prevailing interpretation of the European Union Directive 2004\u201333/EC article 2.1 on donor deferrals. [ 185 ]  The policy, however, is not very specific and refers to \"high-risk sexual contact\". The UK interprets the directive to include all forms of homosexual sex as falling within 2.2.2 of Annex III to the directive \"Persons whose behaviour or activity places them at risk of acquiring infectious diseases that may be transmitted by blood\", requiring a deferral based on the window period for the diseases involved, and sets this at 12 months, despite the Annex suggesting 6 months for risk of exposure to hepatitis B. H\u00e9lder Trindade, President of the Portuguese Institute of Blood and Transplantation (IPST), stated in 2015 that sexually abstinent homosexuals may give blood, but that MSM is definitely seen as a risk factor. [ 186 ]  On the 28th of November 2022, the Irish Blood Transfusion Service introduced Individual Donor Risk Assessments and removed sexuality from the eligibility criteria. All potential donors including MSM are now asked about new sexual partners, of any gender, and are eligible to donate if they have had no new partners in the previous 4 months."}
{"_id": "WikiPedia_Hematology$$$corpus_5309", "text": "In Finland, the parliamentary ombudsman launched an investigation on the possible unconstitutionality of the lifetime ban in January 2006. In June 2008, it was concluded that the ban was not unlawful in Finland as it is based on \"appropriately reasoned epidemiological information\" and because it is related to sexual behaviour rather than sexual orientation. The ombudsman added that people over the age of 65 and people who lived in Britain during the  bovine spongiform encephalopathy  (mad cow disease) outbreak are also screened out during blood donor interviews. In December 2013, the Finnish Red Cross blood service announced it was lifting the ban and introducing a one-year deferral instead. In 2021, the deferral period in Finland was reduced to 4 months."}
{"_id": "WikiPedia_Hematology$$$corpus_5310", "text": "In July 2016, France implemented a 1-year deferral period policy on all gay and bisexual men donating blood. [ 187 ]  Then the blood MSM deferral policy implemented in France was lowered to 4 months effective on 1 February 2020. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5311", "text": "At the formation of the  New Zealand Blood Service  (NZBS) in 1998, the deferral period had been 10 years but was reduced to 5 years in 2009. This was following an independent review of blood donation criteria in 2007\u20132008 which found no significant difference in risk of the blood supply for a deferral period of 5 years compared to 10 years. [ 188 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5312", "text": "In 2014, the NZBS dropped the ban period from 5 years to 1 year following the recommendation of  Medsafe . [ 189 ]  Their decision was mainly caused by new information about HIV transmission in Australia [ 190 ]  which already had a one-year deferral period. The 1-year deferral commenced 15 December 2014. [ 191 ]  On 14 December 2020 the NZBS reduced the deferral to 3 months. [ 192 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5313", "text": "The 3 month deferral period for MSM is on par with the 3-month deferral period for several other behavioural categories carrying a higher probability of unrecognized HIV infection, such as persons engaging in sex work and people who have resided in a country that has a high (1% or more) HIV prevalence. [ 193 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5314", "text": "In the United States, the  Food and Drug Administration  (FDA) issues non-binding guidance for deferral of blood donations, though they are universally followed. [ 194 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5315", "text": "In May 2023, the restrictions were updated to focus on behavior rather than sexual orientation or gender. People are ineligible to donate blood if they have: [ 195 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5316", "text": "UNOS  policies for  organ donation  allow for solid organs from MSM donors such as hearts, lungs, and kidneys to be used in transplant surgeries, though they require the hospital receiving the organ to be notified if the donor was an MSM within the past 5 years. [ 196 ]  The organs are generally used unless there is a clear positive test for a disease."}
{"_id": "WikiPedia_Hematology$$$corpus_5317", "text": "Donors of human cells and tissues other than organs, such as  corneas  or reproductive tissue like semen, are ineligible for five years after the most recent contact. [ 197 ]  With regard to  corneal donations , the five-year deferral policy in the United States and the similar 12-month deferral policy in Canada have the effect of preventing thousands of corneal donations annually. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5318", "text": "Australia implemented a 12-month deferral in 1999; a comparison of confirmed HIV positive blood donations before and after the change did not see a statistically significant difference. [ 11 ]  The  Australian Red Cross Blood Service  pushed to have the deferral period lowered from twelve to six months, however it was rejected by the  Therapeutic Goods Administration  (TGA) in 2014. In April 2020 the TGA revised the deferral period for MSM down to three months. The revision requires approval of the federal, state and territory governments before it can go into effect. [ 215 ] [ 216 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5319", "text": "Lifeblood's new 3-month deferral period rules went into effect on 31 January 2021. [ 217 ]  The spokesperson said they empathise with those who cannot give blood. [ 218 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5320", "text": "Blood services first and foremost must ensure that all blood received for donation is safe for transfusion purposes. This is achieved by screening potential donors for high risk behaviours through questionnaires and interviews before blood is taken, and subsequent laboratory testing on samples of donated blood."}
{"_id": "WikiPedia_Hematology$$$corpus_5321", "text": "Blood services commonly justify their bans against MSM due to the marginal increase in the risk for transfusion-transmitted HIV. [ 219 ]  Other groups with similar restrictions, or complete prohibition to donate blood, due to increased or possible risk for certain infectious diseases include intravenous drug users, recipients of animal organs or tissues, and those who have traveled or lived abroad in certain countries. [ 220 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5322", "text": "In the 1980s, when the HIV/AIDS epidemic outbreak occurred, there was a high prevalence of the disease in MSM and no reliable tests for the virus, which justified blanket bans on blood donations from high-risk groups. [ 221 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5323", "text": "These restrictions are similar to current restrictions on people with certain residence in the United Kingdom, France, or Saudi Arabia during the height of the  BSE  (\"mad cow disease\") epidemic of 1980 through 1996, due to the absence of a test for its human form,  variant Creutzfeldt\u2013Jakob disease  (vCJD). [ 222 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5324", "text": "In 1985, early tests using the  ELISA  method looked for antibodies, which are the immune system's response to the virus. [ 223 ]  However, there is a  window period  when using this method in which a person who has been infected with HIV is able to spread the disease but may test negative for the virus. [ 224 ] [ 225 ]  This window period can be as long as three to six months, [ 226 ]  with an average of 22 days. [ 227 ]  Tests using the ELISA methods are often still used in developed countries because of their ease-of-use, as well as their fairly high  sensitivity , which boasts 100% sensitivity. [ 228 ] [ 229 ]  To cover the window period resultant from the use of these tests, donors are also screened for high risk behaviours, one of which is a history of same-sex sexual activity among male potential donors. [ 230 ]  Newer tests look for the virus itself, such as the  p24 antigen  test, which looks for a part of the virus on the surface of infected cells, and  nucleic acid tests  (NAT), which look for the genetic material of the virus in HIV-infected cells. [ 231 ]  With these tests, the window period is shorter, with an average duration of 12 days. [ 227 ]  Fourth generation, or combination, HIV tests can detect HIV infection in 99% of individuals by one and a half months after infection. [ 232 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5325", "text": "Risks are also associated with a non-MSM donors testing positive for HIV, which can have major implications as the donor's last donation could have been given within the window period for testing and could have entered the blood supply, potentially infecting blood product recipients. An incident in 2003 in New Zealand saw a non-MSM donor testing positive for HIV and subsequently all blood products made with the donor's last blood donation had to be recalled. This included NZ$4 million worth of  Factor VIII , a blood clotting factor used to treat hemophiliacs which is manufactured from large pools of donated plasma, and subsequently led to a nationwide shortage of Factor VIII and the deferral of non-emergency surgery on hemophiliac patients, costing the health sector millions of dollars more. [ 188 ]  Screening out those at high risk of blood borne diseases, including MSM, reduces the potential frequency and impact of such incidents."}
{"_id": "WikiPedia_Hematology$$$corpus_5326", "text": "Objections to the restrictions, including those from the American Medical Association [ 233 ]  and the American Red Cross, are generally based on the idea that improvements in testing and other safeguards have reduced the risk from transfusion transmitted HIV to an acceptable level. Blood shortages are common, and advocates for change to the policies point out that excluding healthy donors only makes the problem worse. In 2018, approximately 10,000 donations were still urgently needed by 10 March to continue to meet patients' needs. However, Canadian Blood Services noted that the national inventory and days on hand of several blood groups remain at critically low levels. Less than four per cent of eligible donors give blood each year. [ 234 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5327", "text": "Corneal transplant surgery  can cure blindness caused by corneal disease. However, there is a global shortage of corneal donations, severely limiting the availability of corneal transplants across most of the world. A 2016 study found that 12.7 million visually impaired people were in need of a corneal transplant, with only 1 cornea available for every 70 needed. [ 235 ]  Many countries have years-long waitlists for corneal transplant surgery due to the shortage of donated corneas. [ 236 ] [ 237 ]  Even though there has never been a reported case of HIV transmission through corneal transplant surgery, and even though all donated corneas are screened for the presence of HIV through antibody or nucleic acid testing, many countries continue to ban MSM corneal donors. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5328", "text": "In  some European countries , high-risk sexual intercourses lead to a temporary ban, regardless of the sex of the partner. In fact, advocates for change in other countries note that the ban encompasses all same-sex sexual contact, even if the partner's HIV status is shown beyond doubt to be negative. Advocates for change point out that a promiscuous straight male is a higher-risk donor than a gay or bisexual man in a monogamous relationship, but the former will usually be allowed to donate blood. Furthermore, in some countries, other high-risk activities determine a temporary ban, such as sexual contact with anyone who has used needles to take drugs not prescribed by their doctor, whereas MSM donors are deferred indefinitely. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5329", "text": "Many  LGBTQ  organizations view the restrictions on donation as based on  homophobia  and not based on valid medical concern since donations are rigorously  tested  to rule out donors that are infected with known viruses such as  HIV ,  hepatitis B , and  hepatitis C . They state the deferrals are based on stereotypes. [ 238 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5330", "text": "Advocates worldwide for change to MSM prohibitions point out that screening of donors should focus on sexual behaviour as well as  safe sex  practices since many MSM may always have protected sex, be  monogamous , or be in other low risk categories. [ 238 ] [ 5 ]  Some groups in favor of lifting the restrictions support a waiting period after the blood is donated when the donor is considered to have had behaviour considered higher risk, and before it is used, to match the blood bank's window of testing methods. [ 238 ]  While HIV is reliably detected in 10 to 14 days with RNA testing, older testing methods provide accuracy for only up to 98% of positive cases after three months. [ 239 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5331", "text": "In Canada"}
{"_id": "WikiPedia_Hematology$$$corpus_5332", "text": "In the United States [ 198 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5333", "text": "In the United Kingdom"}
{"_id": "WikiPedia_Hematology$$$corpus_5334", "text": "In 2015, Welsh writer and poet  RJ Arkhipov  exhibited a poetry series written with his own blood as ink in protest of the MSM blood donor restrictions. His poem Inkwell discusses the shame and stigma surrounding \"gay blood\". An abecedarian poem, each line of Inkwell's five quatrains begins with letters from each of the blood groups, alternating between A, B, AB and O. [ 264 ] [ 265 ] [ 266 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5335", "text": "In 2018, the European Court of Human Rights took up a case of a French citizen who was prevented from donating blood. [ 267 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5336", "text": "\" The Blood Donor \" is an episode from the television  comedy  series  Hancock , the final BBC series featuring British comedian  Tony Hancock . First transmitted on 23 June 1961, the show was written by  Ray Galton and Alan Simpson , and was produced by  Duncan Wood . Supporting Hancock were  Patrick Cargill ,  Hugh Lloyd ,  Frank Thornton ,  James Ottaway  and  June Whitfield . It remains one of the best known  situation comedy  episodes ever broadcast in the United Kingdom."}
{"_id": "WikiPedia_Hematology$$$corpus_5337", "text": "Hancock arrives at his local  hospital  to  give blood . \"It was either that or join the  Young Conservatives \", he tells the Blood Donor Department's reception nurse (Whitfield), before getting into an argument with her about whether British blood is superior to other types. After managing to offend two other waiting donors, Hancock amuses himself by reading the waiting room's wall posters out loud, finally singing \" Coughs and sneezes spread diseases \" to the tune of the  Deutschlandlied  before being shown in to see Dr MacTaggart (Cargill), greeting him in a broad Scottish accent and taken aback when the doctor responds in an educated English accent \u2013 saying \"We're not all Rob Roys.\""}
{"_id": "WikiPedia_Hematology$$$corpus_5338", "text": "After Dr. MacTaggart has taken a blood sample Hancock blithely assumes that that is all that is needed and prepares to depart. When the doctor tells him it was just a smear (\"It may be just a smear to you mate, but that\u2019s life and death to some poor wretch!\") and that he must donate a pint of blood, he protests, \"I don't mind giving a reasonable amount, but a pint! That's very nearly an armful\" Dr. MacTaggart finally persuades Hancock to donate the full pint by telling him he has a rare  blood type , which appeals to Hancock's snobbery. Having boasted of his lack of squeamishness, he faints while giving blood."}
{"_id": "WikiPedia_Hematology$$$corpus_5339", "text": "Recuperating afterwards in a hospital room with other patients (including the two Hancock spoke to earlier), Hancock has a chat about blood with a fellow patient (Lloyd), but since neither of them knows very much about blood, the conversation is not very informative. After the patient has left, Hancock is horrified to discover that the man has walked off with his [Hancock's]  wine gums . (\"If you can't trust a blood donor, who can you trust?\")"}
{"_id": "WikiPedia_Hematology$$$corpus_5340", "text": "After returning home, Hancock cuts himself on a bread knife and is rushed to the Casualty Ward of the same hospital, where he receives a  transfusion  of his own blood \u2014 the only pint the hospital has of his rare blood type."}
{"_id": "WikiPedia_Hematology$$$corpus_5341", "text": "While returning from recording  The Bowmans  a week earlier, Hancock was involved in a car accident, and rather than cancel the studio booking it was decided to place  teleprompters  around the set in order to save the  comedian  the problems of learning his lines after a delay in rehearsals. In the passage where he is alone looking at the posters, Hancock was obliged to learn his lines. While it is not true Hancock never learned a line from a script again, he increasingly relied on the device mostly thereafter in his TV career. Many Hancock devotees reckon this is one of his poorest TV performances, and it is indeed quite noticeable to see Hancock's eye movements towards the teleprompters when addressing the other performers. Others, though, see no real difference between this and other classic Hancock performances, and lines from the episode have become a part of British comic folklore (\"A pint? That's very nearly an armful!\" \"Rhesus? They're  monkeys  aren't they?\"), giving it now-legendary status."}
{"_id": "WikiPedia_Hematology$$$corpus_5342", "text": "In October 1961,  Pye Records  produced an audio remake of \"The Blood Donor\" (duration: 28'10\") starring most of the original cast, together with a remake of \" The Radio Ham \" (duration: 27'40\") from the same series. These were produced in the style of the  radio  shows, complete with an (invited) studio audience, and released as an  LP  in 1961. [ 1 ]  These recordings have been available more or less continuously ever since, and are also found on several British comedy compilation sets."}
{"_id": "WikiPedia_Hematology$$$corpus_5343", "text": "The original episode survives in the BBC Archive as a  16mm   telerecording  with a separate magnetic soundtrack, and has been released on  Laser Disc  (BBCL 7004),  VHS  (BBCV 7034),  Betamax  (BBCB 7034) in 1985 and  DVD  (2000) compilations of Hancock episodes. The original soundtrack from the episode was also subsequently released on  CD  and audio cassette."}
{"_id": "WikiPedia_Hematology$$$corpus_5344", "text": "The script was re-recorded in 2009 for a  BBC Radio 2  series of remakes of Galton and Simpson works. \"The Blood Donor\" starred  Paul Merton , with  Suzy Aitchison  as the nurse, the role played by her mother 48 years earlier. It was first transmitted in March 2009. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5345", "text": "The  Blood Emergency Readiness Corps  (known as \"BERC\" or the \"BERC Program\") consists of 38 U.S.-based community blood centers that work together to provide an emergency reserve of  blood products  to respond to a mass shooting or mass casualty event. The program is administered by the  Alliance for Community Transfusion Services (ACTS) . To date, the BERC reserve has responded to supply blood products needed as a result of the  Collierville Kroger shooting  ( Collierville , TN), the  2021 Oxford High School shooting  ( Oxford Township , MI), the  Tornado outbreak in the Mississippi Valley of December 10\u201311, 2021 , the  Robb Elementary School Shooting  ( Uvalde , TX) on May 14, 2022, the tornado outbreak sequence primarily impacting  Perrytown , TX in the  Texas Panhandle  on June 15, 2023, the  tornado outbreak in North Texas  on May 26, 2024, the  ransomware attack  impacting the blood supply in the southeast U.S. on July 30, 2024, the flooding in southwest Florida as a result of  Hurricane Debby  on August 5, 2024, the blood needs as a result of  Hurricane Milton  making landfall in southwest Florida on October 9, 2024, and the  New Orleans Terrorist Attack  of January 1, 2025.. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5346", "text": "The following blood centers are participants in the program:"}
{"_id": "WikiPedia_Hematology$$$corpus_5347", "text": "Blood transfusion  was first performed in  Sri Lanka  in late 1950. [ 1 ]  It became more widely known to the public in 1959 after the assassination of  Prime Minister   S.W.R.D. Bandaranaike , when an appeal was made to the public to  donate blood . [ 1 ]  The country's  blood bank  system has since expanded from a single initial site to multiple blood donation centres and laboratories nationwide, operating under the auspices of the National Blood Transfusion Service (NBTS). [ 1 ]  As of 2014, the NBTS collects over 350,000 voluntary blood donations every year. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5348", "text": "Initially, there was only one blood bank in Sri Lanka, confined to a room close to the surgical unit of the  National Hospital of Sri Lanka  (NHSL). [ 1 ]  In 1960, the NHSL blood bank was shifted to its current building, near the hospital's main entrance. In 1967, a \"red donor booklet\" was introduced as a certificate for free blood donors. Other donors were paid a minimum of 10  rupees  for each donation. [ 1 ]  In 1968, the blood bank was semi-decentralized under the Sri Lankan Ministry of Health and placed under the direction of a superintendent blood transfusion service. It had a staff of 124 at that time. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5349", "text": "In 1979, paid donation was discontinued and voluntary donation was encouraged to ensure the safety of collected blood. In 1980, the number of hospital-based blood banks reached 20, and 12 emergency bleeding centres were also established. Mobile blood donation programs were initiated with two mobile blood collection teams. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5350", "text": "By 1982, volunteer non-remunerated blood donations accounted for 97% of all transfusions, and the \"Anti A1\"  reagent  was manufactured for the first time in Sri Lanka using  kollu seeds . [ 1 ]  In 1985, disposable plastic bags were introduced to all Sri Lankan blood banks. Screening of blood for  hepatitis B  was initiated. In 1987, the emergence of  AIDS  led to the introduction of screening of all collected blood for  HIV  1 and 2 antibodies. In 1988, the Central Blood Bank's component laboratory facility was extended to some of the larger blood banks ( Colombo  North and  Kandy ). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5351", "text": "In 1990, the component laboratory facility was further extended to blood banks at  Karapitiya ,  Kurunegala , CI  Maharagama ,  Peradeniya ,  Anuradhapura ,  Matara  and  Badulla . By this time there were 32 blood banks and 10 emergency bleeding centres. [ 1 ]  The Central Blood Bank functioned as the training centre for medical and paramedical personnel of the National Blood Transfusion Service (NBTS). In 1999, the headquarters of the NBTS were established at the National Blood Centre, absorbing most of the vital laboratories and the majority of the staff from the Central Blood Bank. The NBTS thus became a fully  decentralized  unit. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5352", "text": "In 2009, a distributed network of cluster centres was established, and more authority was given to these cluster centres for effective delivery of blood collection and transfusion services to various parts of the country. [ 1 ]  In 2012, the  Anura Bandaranaike  Memorial Blood Bank was opened in Wathupitiwela. [ 3 ]  In June 2014, Sri Lanka hosted the  World Blood Donor Day , with the theme \"Safe Blood for Saving Mothers\". [ 2 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5353", "text": "A  bloodmobile  is a mobile  blood donation  center. It is a vehicle (usually a bus or a large van) equipped with everything necessary for a blood donation procedure. Blood drives involving bloodmobiles usually happen in public places such as colleges and churches. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5354", "text": "Often large employers will sponsor mobile blood drives and allow employees a few hours off of work to donate blood. In addition, many  high schools  hold annual blood drives which allow students aged 16 and over to donate blood with a signed permission form. Typically students are offered snacks,  T-shirts , or time out of class as an incentive, as well as positive  peer pressure ."}
{"_id": "WikiPedia_Hematology$$$corpus_5355", "text": "The first bloodmobiles were created by  Dr. Charles Drew , an African-American leader in the field, in 1941, making it particularly ironic that African-American blood was first rejected and then accepted only when kept separate from White blood. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5356", "text": "By the 1950s the  American Red Cross  ran mobile blood units that gave people a community-based location at which to donate. These mobile units were very efficient, with a large Red Cross truck staffed by two men arriving at an empty location and setting up for the first donation, which would be taken two hours later. The truck would be loaded with at least ten beds, mattresses, dozens of screens and chairs, waste receptacles, tables, stools, huge refrigerated boxes, canvas bags of ice, coffee urns, orange juice, canteen equipment, hundreds of blood bottles, boxes of sterile supplies, bottles of solution, literature and record forms, oxygen tanks, and sheets. The men would have this unloaded and set up on site in less than an hour. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5357", "text": "Once setup was complete, nurses, volunteers and doctors arrived. There were normally six nurses and 15 volunteers. The nurses did their preliminary tasks while the volunteers split off into groups. One group unpacked and set up the reception area. Another group set up the canteen and prepared food for after donations. The third group set up the blood bottle table where the blood would be tagged, numbered, and recorded. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5358", "text": "When the site opened, donors would enter via the reception area to answer questionnaires which determined whether they were eligible to donate. Once accepted, a donor was taken through to the nurse, who would take blood pressure and perform other tests. The donor then went to the next nurse, who took the blood. If the donor had a reaction while donating, they went to the recovery room where they went under the care of the doctor until they had fully recovered. If the donor did not have a reaction, they would go to the canteen for refreshments."}
{"_id": "WikiPedia_Hematology$$$corpus_5359", "text": "In the 1950s, mobile blood units like this would collect from 200 donors in six hours. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5360", "text": "Erythrocytapheresis  is an  apheresis  procedure by which  erythrocytes  ( red blood cells ) are separated from whole blood.  It is an extracorporeal blood separation method whereby whole blood is extracted from a donor or patient, the red blood cells are separated, and the remaining blood is returned to circulation."}
{"_id": "WikiPedia_Hematology$$$corpus_5361", "text": "For the separation of erythrocytes, whole blood is passed through an apparatus that isolates the red blood cells from the remaining components.  In erythrocytapheresis,  centrifugation  is the most commonly used red blood cell fractionation method.  This is because the  hematocrit , or the percentage of blood volume taken up by red blood cells, is present in the highest percentage of all blood cell components in the solid portion of blood.  Therefore, since erythrocytes have the highest specific weight in comparison to other solids in blood, they can easily be separated using centrifugation.  Whole blood is spun down in a spinning bowl centrifuge and the bottom layer, concentrated with erythrocytes, sediments to the bottom.  These are separated and the rest of the blood can be retransfused."}
{"_id": "WikiPedia_Hematology$$$corpus_5362", "text": "Centrifugal sedimentation is the most used process by which erythrocytapheresis occurs.  In this method, patient or donor blood is collected and processed into an erythrocyte concentrate with a high hematocrit content.  This exhausted, pre-filtered blood is collected in a suitable reservoir and pumped into a rotating centrifuge.  The centrifugal force will separate the red blood cells from other cells due to their high specific weight.  These cells can then be collected.  A separate washing step will lead to the removal of plasma parts which will further purify and concentrate erythrocytes.  The remaining blood, consisting of blood plasma, leukocytes, platelets, stem cells, lipids, and other solids will then be retransfused into the patient or donor."}
{"_id": "WikiPedia_Hematology$$$corpus_5363", "text": "The advancement of centrifugation and membrane filtration methods is essential to the development of erythrocytapheresis.  In addition, blood separation on microdevices containing capillary channels has been identified as a potential blood cell fractionation method. [ citation needed ]   Other plasma and blood cell separation techniques are being explored based on  magnetophoresis ,  electrophoresis , microchannel bends, and ultrasound standing waves. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5364", "text": "Therapeutic erythrocytapheresis is commonly used to remove red blood cells in patients experiencing sickle cell crisis.  The affected erythrocytes are removed while the rest of the blood is retransfused.  This blood separation is also used in patients with severe malaria.  After removal of the affected cells, the patient can then be transfused with a dose of normal red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_5365", "text": "Erythrocytapheresis can also be used for blood donations.  The procedure is commonly done using automated red blood cell collection which involves the removal of two units of red blood cells.  This includes either two standard units of red blood cells or one unit plus of red blood cells and another of either plasma or platelets.  The advantage to the donor is the use of smaller needles and saline compensation, as well as more convenient donating schedules (the no-donation period following apheresis is twice as long as that for a single unit). The advantage to the blood bankers is the on-line separation into standardized RBC masses with the subsequent reduction in testing, data entry and staffing. This process is commonly referred to as 'power reds', 'double reds' or 'double red cell apheresis'. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5366", "text": "Greater Manchester Blood Bikes  \u2013 a UK charity providing courier services for the transportation of urgent and emergency medical items such as  blood ,  human milk ,  platelets , samples,  vaccines , operating in  Greater Manchester . [ 3 ] [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5367", "text": "The group, originally set up in 2011, [ 4 ]  closed operations and transferred their assets along with the \"on call\" phone number to a new charity, registered as a  charitable incorporated organisation  in November 2022. [ 1 ]  Having started operations on 1 January 2023, the new group covers the same geographical area and is composed of experienced volunteers from Blood Bikes Manchester (also known as NorthWest Blood Bikes Manchester). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5368", "text": "In 2019, the charity estimated to had saved the  NHS  and hospices \u00a3341,350 in six years and was recognised by the government as an emergency service who alleviated high night-time costs of couriers and taxis. [ 5 ]  In October 2021, the charity was covering 1700+ miles per week on 4 motorcycles and a car which was used in inclement weather conditions. [ 3 ]  In December 2021, with 57 volunteers, the annual costs were \u00a337,029. [ 4 ]  GMBB raise funds from donors, [ 6 ]  at charity events, [ 7 ]  from bucket collections, [ 8 ]  and online through  PayPal ,  Just Giving , Buy Me a Coffee and Easy Fundraising. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5369", "text": "The motorcycle and car rides are provided by volunteers at night, daytime weekends and bank holidays. [ 10 ]  The vehicles are marked with the word BLOOD in front and covered in yellow and orange liveries allowing them to stand out despite missing blue lights. The riders are not allowed to exceed speed limits or go through red lights but hold advanced driving qualifications. [ 11 ]  Riders operate from home, working with a duty controller who acts as a dispatcher taking calls and dispatching the riders. They aim for a 90-minute service from receiving a call to delivering the cargo. On each shift, there are at least two riders and one car. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5370", "text": "GMBB work with several hospitals in the area, including  Salford Royal ,  Wythenshawe Hospital ,  Tameside General Hospital  and  Stepping Hill , [ 11 ]  and deliver blood to  North West Air Ambulance  helicopters based at  Barton Aerodrome  and  Blackpool Airport . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5371", "text": "James Christopher Harrison   OAM  (born 27 December 1936), also known as the  Man with the Golden Arm , is a  blood plasma  donor [ 2 ]  from Australia whose plasma contains antibodies against RhD which are used in making a treatment for  Rhesus disease . One of the founding donors of  New South Wales ' (NSW) Rh Program, he regularly donated until, on 11 May 2018, he made his 1,173rd donation [ 3 ] [ 4 ] \u00a0\u2013 his last, as Australian policy then prohibited blood donations from those past age 81. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5372", "text": "James Harrison was born on 27 December 1936. [ 6 ]  In 1951, at the age of 14, he underwent major chest surgery, requiring a large amount of blood. Realizing that the blood had saved his life, he made a pledge to start donating blood himself as soon as he turned 18, the then-required age. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5373", "text": "Harrison started donating in 1954. After the first few donations, it was discovered that his blood contained unusually strong and persistent antibodies against the  D Rh group antigen . Blood which contains a high level of anti-D antibodies can be processed to create immunoglobulin-based products used to prevent  haemolytic disease of the newborn  (HDN). These products are given to Rh(D) negative mothers of unknown or Rh(D) positive babies during and after pregnancy to prevent the creation of antibodies to the blood of the Rh(D) positive child. This antigen sensitization and subsequent incompatibility phenomenon causes  Rhesus disease , the most common form of HDN. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5374", "text": "Harrison was one of the founding donors in NSW's Rh Program, one of the first in the world in 1969, and he had continuously donated from then onwards. As blood plasma, in contrast with blood, can be donated as often as once every two weeks, he was able to reach his 1,000th donation in May 2011. This resulted in an average of one donation every three weeks across 57 years. Commenting on his record, he said: \"I could say it's the only record that I hope is broken, because if they do, they have donated a thousand donations\". [ 2 ]  On 11 May 2018, he made his 1,173rd and last donation in compliance with Australian policy prohibiting blood donations from those past age 81. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5375", "text": "Through their donations, the members of NSW's Rh Program have provided millions of doses of anti-D and helped prevent thousands of deaths and stillbirths, as well as many more instances of sickness and disability caused by HDN. Over his lifetime, Harrison's donations amounted to tens of thousands of doses worth of antibodies and had contributed to every batch of anti-D produced in NSW. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5376", "text": "Research is also being done on creating a mixture of  monoclonal antibodies , antibodies made by immortalised B cells in bioreactors, that matches what is naturally produced in the bodies of donors such as Harrison. The project has been colloquially called \"James in a Jar\". [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5377", "text": "In 2007, Harrison was critical of plans to open up Australia's plasma donation to foreign corporations. He believes that opening up the trade will discourage volunteer donations. This opening of trade stemmed from a review of the country's free trade agreement with the  United States . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5378", "text": "Harrison was awarded the  Medal of the Order of Australia  (OAM) on 7 June 1999. [ 11 ]  In 2011, he was nominated in the New South Wales Local Hero division of the Australian of the Year awards. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5379", "text": "The  Imam Hussain AS  Blood Donation Campaign  (IHBDC) is a voluntary campaign."}
{"_id": "WikiPedia_Hematology$$$corpus_5380", "text": "It aims to encourage more Muslims to give blood with the mission statement \"create a world where every able Muslim saves lives by donating blood regularly\" [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5381", "text": "It is the first national campaign in the UK which specifically aims to motivate Muslims to join the Blood Register by holding bespoke blood donation sessions throughout the year. Since its inception, it has grown to involve 26 cities across the UK with 3,408 successful donations and has run popular sessions at the  Islamic Centre of England  and KSIMC. [ 1 ] [ 2 ]  It has also expanded to feature 16 cities outside of the UK."}
{"_id": "WikiPedia_Hematology$$$corpus_5382", "text": "The campaign is one of several projects organised by the  Islamic Unity Society , a UK registered charity run by volunteers. The IHBDC works in conjunction with  NHS Blood and Transplant  to arrange sessions for people to donate. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5383", "text": "The Campaign was first launched in January 2006 in Manchester. 23 people were successful in donating blood. The campaign was well received by both the Muslim community and the NHS Blood and Transplant, which was then the National Blood Service (NBS). The following year the campaign took place in  London ,  Glasgow ,  Birmingham  and its hometown of  Manchester  with 50 successful blood donations. The donor sessions are held throughout the year and the busiest time is during the time of Muharram when the death of  Husayn ibn Ali , grandson of the  Prophet Muhammed  is commemorated. The campaign was inspired by the sacrifice of  Husayn ibn Ali  and tries to use his stance as motivation for others to make their own significant sacrifice by donating blood. During the last 10 years, the campaign has saved many lives by providing blood packs to the patients. [ 4 ]   In July 2016 British Muslims across London celebrated the 10th anniversary of the IHDBC by donating blood. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5384", "text": "The campaign's success has been covered by various media outlets over the years. This includes local BBC News and radio, [ 3 ]  television, [ 6 ]  local newspapers such as the  Telegraph & Argus [ 7 ]  and many others. [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 2 ] \nIn December 2011, Rugby League star  Ikram Butt  showed his support by giving blood at the Campaign's blood drive in Leeds. [ 12 ] \nIn January 2018, First Minister  Nicola Sturgeon  visited the Edinburgh donor centre expressing her support for the IHBDC. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5385", "text": "IUS IHBDC received significant exposure and praise in the first report from the  All-Party Parliamentary Group  (APPG) on British Muslims on the role Muslim charities often play during the festive season of Christmas and throughout the year. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5386", "text": "The campaign is a branch of the Islamic Unity Society, a registered charity set up in 1995 to promote and develop the wellbeing of Britain's youth on the basis of Islamic principles. They work closely with NHS Blood and Transplant who host and staff the donation sessions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5387", "text": "The campaign has clarified that donating blood is a permitted and, in fact, a recommended act in  Islam .  Some eminent religious scholars  have issued information regarding the donating of blood and shown support for the campaign. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5388", "text": "SGPGIMS Lucknow"}
{"_id": "WikiPedia_Hematology$$$corpus_5389", "text": "Jai Gopal Jolly  (born 1 October 1926) was an Indian physician and professor of the Department of Transfusion Medicine at the  Post Graduate Institute of Medical Education and Research , Chandigarh, India. He is an internationally known expert in the field of blood transfusion, who pioneered the voluntary blood donation movement in India, [ 1 ]  and is regarded as the \"Father of Transfusion Medicine in India\". [ 2 ] [ 3 ] [ 4 ]  He spearheaded the campaign to prohibit sale and purchase of blood from professional donors in India, [ 5 ] [ 6 ]  which was later incorporated into the National Blood Policy of India [ 7 ] [ 8 ] [ 9 ] [ 10 ]  by the  Government of India . He has generated awareness among the masses about the significance of blood donation programmes by observing \"Blood Donation Day\" on 1 October. This has helped in obtaining adequate quantity of quality blood from voluntary donors. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5390", "text": "He was the founder of the Blood Bank Society, Chandigarh, founder President of Indian Society of Blood Transfusion and Immunohaematology [ 12 ]  and made significant contributions to the development of Blood programme in India. As a result of his contributions, he represented India in numerous International Delegations as well as scientific conferences. During the course of these visits he got the opportunity of studying the blood transfusion programme in different parts of the world for revamping the organisational set up in India."}
{"_id": "WikiPedia_Hematology$$$corpus_5391", "text": "On the completion of his assignment at the  PGI , Chandigarh he joined  SGPGI   Lucknow  to establish a department of excellence where he introduced postgraduate degrees in  Transfusion Medicine  for the first time in India. He then provided consultation to the Government Medical College, Chandiagrh. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5392", "text": "During the recent years, he has been concentrating his activities primarily towards the academic development of transfusion medicine and to provide free factors to haemophiliacs. [ 14 ] [ 15 ] [ 16 ]  He has also advocated \"screening of parents and unborn babies for thalassaemia in India\". [ 17 ] [ 18 ] [ 19 ] [ 20 ]  He has emphasised the need for the provision of more and advanced facilities for the preparation of blood components in India. [ 21 ] [ 22 ]  He has worked to meeting blood requirement during disasters. [ 23 ] \nBeing associated with the National and State Blood Transfusion Councils of Punjab, Haryana and Chandigarh he has continued his efforts in the development of Transfusion services in the region. [ 24 ] [ 25 ] [ 26 ] [ 27 ] [ 28 ]  He was also instrumental in setting up a department of Transfusion Medicine, having well established units for blood components at the newly established  Government Medical College , Chandigarh. As an international expert on Blood Transfusion Medicine, he has reviewed  Strategies for Safe Blood Transfusion  for the  World Health Organization , [ 29 ]  and has written over 100 scientific articles in international journals. [ 30 ] [ 31 ] [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5393", "text": "As a result of his innumerable contributions in this field Jolly is recognised as the leader of blood banking in India. [ 34 ] [ 35 ] [ 36 ] [ 37 ]  Among the numerous distinctions conferred on Jolly are the J. G. Mukherjee gold medal by the  Lucknow University  for distinguished research contribution (1958),  Dr. B. C. Roy Award  for the development of the speciality of Blood Transfusion in India (1981), Philip Levine Memorial Award for national contributions in Transfusion Medicine (1993) and IDPL Diamond Jubilee IMA Oration Award (1996). He was also awarded by The Chandigarh Administration on the Republic Day of India for social service and illustrious achievements in the field of blood donation. [ 38 ]  The fact that the speciality of blood transfusion has begun to be recognised in India can be attributed to the sustained effort of Jolly. He has been accorded recognition by the  World Health Organization ,  International Society of Blood Transfusion  and  World Federation of Hemophilia ."}
{"_id": "WikiPedia_Hematology$$$corpus_5394", "text": "Daya Bir Singh Kansakar  ( Nepali :  \u0926\u092f\u093e\u0935\u0940\u0930\u0938\u093f\u0902\u0939 \u0915\u0902\u0938\u0915\u093e\u0930 ; 1911 \u2013 5 February 2001, Kathmandu, Nepal) was a Nepalese social worker and the first blood donor in  Nepal .  also the chief founder of Paropakar Organization, the country's earliest social service organization. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5395", "text": "Kansakar  was born in  Kathmandu . His father, Bhawani Bir Singh Kansakar, was a trader. His mother was named Laxmi Devi. Kansakar studied up to Class 8 at  Durbar High School  in Kathmandu, and then took up self-study at home. He went to Chandra Laxmi  Tuladhar  of Nhyokha in 1927. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5396", "text": "In 1944, Kansakar donated blood at  Bir Hospital  in Kathmandu for a patient who was in a critical state, and became Nepal's first blood donor. [ 5 ]  He continued to engage in social work, distributing free medicines to the needy. On 26 September 1947, Paropakar was formed under his leadership with the aim of providing service in an institutional manner. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5397", "text": "After the revolution of 1951 and the advent of democracy in Nepal, the Paropakar Organization expanded its sphere of activities. On 23 June 1952, Paropakar Orphanage was established. That same year, Paropakar Orphanage Middle School opened. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5398", "text": "Kansakar worked to set up Paropakar Indra Rajya Laxmi Devi Prasuti Griha maternity hospital in Kathmandu. Popularly known as Prasuti Griha, it is Nepal's first maternity hospital and opened on 26 September 1959. [ 9 ]  Kansakar was an advocate of homespun, and set up Karuna Kapa Factory to produce traditional Nepalese cloth. He was also a writer and has produced a number of literary works in  Nepal Bhasa . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5399", "text": "Kansakar was recognised as a Role Model Volunteer at the celebration of the International Volunteer Day (IVD) and closing ceremony of International Year of Volunteers 2001 (IYV) in Kathmandu. [ 11 ]  The Postal Service Department of the government of Nepal issued a commemorative postage stamp depicting Kansakar's portrait in 2002. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5400", "text": "He has also been decorated with the  Order of Gorkha Dakshina Bahu , Second Class (previously Fourth Class), and the  Order of Tri Shakti Patta  by the  king of Nepal . [ 13 ]  In 1963, he was named a member of the  Privy Council  (Raj Sabha). [ 14 ]  President of Nepal  Ram Baran Yadav  issued a message on the occasion of the centenary of his birth saying that Kansakar's philanthropic services would always be remembered. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5401", "text": "The  Karl Landsteiner Memorial Award  is a scientific award given by the  American Association of Blood Banks  (AABB) to scientists with \"an international reputation in transfusion medicine or cellular therapies\" \"whose original research resulted in an important contribution to the body of scientific knowledge\". Recipients give a lecture at the AABB Annual Meeting and receive a $7,500 honorarium. The prize was initiated in 1954 to honor  Karl Landsteiner , whose research laid the foundation for modern  blood transfusion  therapy. [ 1 ]  In 2023, the AABB renamed the Karl Landsteiner Memorial Award as the  Landsteiner-Alter Award  in honor of both Karl Landsteiner and  Harvey J. Alter . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5402", "text": "Kanta Saroop Krishen  (n\u00e9e  Bhagwan ; 7 February 1929 \u2013 30 November 2024) was an Indian social worker and one of the founders of the Blood Bank Society,  Chandigarh  and the Indian Society of  Blood transfusion  and Immunohaematology. [ citation needed ]  She is known to have worked for spreading the message of voluntary  blood donation in India [ 1 ]  and is a recipient of the fourth highest Indian civilian award of  Padma Shri  for the year 1972 from the  Government of India . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5403", "text": "Kanta Bhagwan was born on 7 February 1929, [ 3 ]  in  Punjab Province ,  British India  (now in Pakistan), into a rich family to R. B. Vishan Bhagwan, one-time chairman of the  Union Public Service Commission . She is reported to have been studious in her studies and passed the matriculation examination with scholarship. She got married at the age of 16 to Sarup Krishen, an Indian Administrative Service officer who would later become the first chief secretary of the state of  Haryana . [ 4 ] [ 5 ]  In Chandigarh, she met  J. G. Jolly , then professor and head of the department of transfusion medicine at the  Post Graduate Institute of Medical Education and Research  and started associating with Jolly's efforts in combating commercial blood donations which posed the danger of unsafe blood. She assisted Jolly in the establishment of the Blood Bank Society, Chandigarh (BBS) and the Indian Society of Blood Transfusion and Immunohaematology (ISBTI) and became the founder secretary general of ISBTI, [ citation needed ]  a post she held for 45 years. She served BBS as its secretary for 25 years and the Blood Centre of the organisation is housed in a building constructed with a donation of  \u20b9  5 million from her brother, Sudhir Bhagwan. She has also been associated with the  Indian Red Cross Society , Women's Defence Council,  Bharat Scouts and Guides  and Child Welfare Council (CWC) [ citation needed ]  and has served as the secretary of CWS."}
{"_id": "WikiPedia_Hematology$$$corpus_5404", "text": "Kanta Krishen was one of the associates of  H. D. Shourie  when he gathered information and filed a civil writ petition at the  Supreme Court of India  against the commercial practices in blood donation on which the apex court of India returned a judgment banning commercial blood donation. Later, she organised several awareness campaigns and presented papers at various conferences in India and abroad. She also participated in the activities of  Sant Nirankari Mission , a spiritual organisation based in Delhi. Her efforts were also reported behind the formulation of the National Blood Donation Policy by the  Government of India ."}
{"_id": "WikiPedia_Hematology$$$corpus_5405", "text": "Sarup Krishen, her husband died in 2006, [ 6 ]  leaving behind their son, Sanjiv Krishen and two daughters, Niti Sarin and Anu Ganju. The  Government of India  awarded her the civilian honour of  Padma Shri  in 1972. [ 2 ]  She was also a recipient of  Red Cross  Gold Medal, H. D. Shourie Award,  Mother Teresa  Award and  Rajiv Gandhi  Award."}
{"_id": "WikiPedia_Hematology$$$corpus_5406", "text": "Kanta Krishen died on 30 November 2024, at the age of 95. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5407", "text": "Richard Lewisohn  (July 12, 1875 in Hamburg \u2013 August 11, 1961 in New York [ 1 ] ) was a German-American surgeon. At  Mount Sinai Hospital  in Manhattan, he developed procedures that made  blood transfusion  practical."}
{"_id": "WikiPedia_Hematology$$$corpus_5408", "text": "Lewisohn was born to  German-Jewish [ 2 ]  parents in  Hamburg  and was educated at the local  Gymnasium  from where he entered medical school in  Kiel  in 1893. [ 3 ]  As was typical for German medical students, he attended several different medical schools, before receiving his doctorate from the  University of Freiburg  in 1899 with a thesis on malignant kidney tumors. [ 3 ]  He then served for two years as an assistant to  Karl Weigert  at the  Senckenberg Institute  in  Frankfurt . In 1904 he became an assistant to  Geheimrat Czerny  in  Heidelberg . [ 3 ]  In 1906 he emigrated to New York, where he became a gastroenterologist and surgeon; [ 4 ]  from 1928 to 1936 he was chief of the general surgical service at Mount Sinai. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5409", "text": "Following early speculation and its use in animal  transfusion , [ 6 ]  in April 1914 Belgian physician  Albert Hustin  used  sodium citrate  to prevent donated blood from clotting during transfusion. [ 1 ]   Luis Agote  had also used a citrate method at Buenos Aires on 14 November 1914. [ 1 ]  Working independently, Lewisohn's contribution, in 1915, was to determine the optimal concentration of sodium citrate for preserving blood products without inducing toxicity (0.2% for transfusions not exceeding 5g). [ 7 ]  Correct use of sodium citrate made it possible to preserve blood products for longer and longer periods of time allowing donor and donee to be geographically separate. His research was put into use during the  First World War [ 7 ]  though it was only introduced to British medical services in 1917 (by  Oswald Robertson ). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5410", "text": "In 1922, he convinced his colleague  Albert Berg  to perform the first subtotal  gastrectomy  for  peptic ulcer  in the United States. [ 5 ]  He had traveled previously to  Hans von Haberer  in Innsbruck, Austria, where the method had already been applied and where he became familiar with the surgical techniques. [ 5 ]  Following the successful application at Mount Sinai, the technique spread to the rest of the United States for ulcers resistant to other treatment. [ 3 ]  Lewisohn was also a contemporary of Alexis Moschcowitz and his successor as chief of the general surgical service at Mount Sinai. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5411", "text": "In 1937, Lewisohn retired from active surgery and became a consulting surgeon. He focused his time on cancer research, [ 3 ]  and was \"the first to define the significance of  folic acid  in the biology of cancer\" and was \"among the first to use folic acid antagonists clinically\". [ 5 ]  He spent approximately ten years thus engaged, before retiring more completely, only to re-enter the world of medical research in 1954, to oversee and the creation of a new cell research laboratory at Mount Sinai, made possible by a large donation. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5412", "text": "In 1955 he received the  American Association of Blood Banks '  Karl Landsteiner Memorial Award . [ 1 ]  In January 1959 he became an honorary fellow of the  Royal College of Surgeons of England , having been a fellow of the  American College of Surgeons  since 1916. [ 7 ]  Lewisohn was also a Fellow of the  American Gastroenterological Association , and served on the  American Board of Surgery . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5413", "text": "In 1911, Lewisohn married Constance Strauss. They had  three children, two of whom survived to adulthood.  [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5414", "text": "The  Little Yellow Duck Project  is a UK-based international project started in 2014 to raise consciousness of the need for  organ ,  stem cell  and  blood donors  and to encourage small  random acts of kindness . Participants are invited to knit, crochet or otherwise create small yellow ducks and then leave them in public places to be found by strangers. Each duck has a tag introducing the project, often naming the duck, and encouraging the finder to log on to the project website. There they can record the finding of the duck and learn more about the need for organ, stem cell and blood donors and how to become one. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5415", "text": "The project was started by British woman Emma Harris in memory of her friend Clare Cruickshank, who died from  cystic fibrosis  aged 26 on 15 April 2013 while waiting for a  double lung transplant . Cruickshank had collected  rubber ducks  during her life, and this inspired the project. [ 2 ]  It has received international media coverage including crafting blogs and websites, [ 3 ] [ 4 ]  knitting magazines, [ 2 ]  and an Australian radio show. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5416", "text": "The project was launched on 15 April 2014, the first anniversary of Cruickshank's death, [ 6 ]  and as of 24 April 2023 14,042 ducks had been recorded in 96 countries. [ 7 ]  Earlier records had shown up to 107 countries, [ 8 ]  but  the system was revised in March 2022 to include only sovereign countries, excluding, for example, the  Isle of Man . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5417", "text": "This  textile arts  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5418", "text": "This article about an organisation in the  United Kingdom  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5419", "text": "Medal of Merit for Blood Donation  ( French :  M\u00e9daille du M\u00e9rite pour le don du sang ) is a civil state  decoration  of  Luxembourg  established in 1979."}
{"_id": "WikiPedia_Hematology$$$corpus_5420", "text": "Three-grade medal was established by  Grand Duke Jean  with decree of 22 October 1979. [ 2 ]  The Medal is awarded to voluntary blood donors only, by Grand Duke of Luxembourg, at the request of Minister of Health, who is advised by of the Council of Order. The Council of Order originally consisted of five people. It was changed by decree of 4 February 1985 [ 3 ]  and presently the council consists of seven members, of which minimum six is required to make advice. Members of the council are appointed for a four-year term and can be appointed for next one. Current council was appointed 17 February 2016. Foreigners may also be awarded, if they donated blood to recognized Luxembourg organization. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5421", "text": "The Medal has three grades: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5422", "text": "According to information of Luxembourg Red Cross, Bronze Medal is awarded for donating blood twenty times, Silver Medal for forty times and  Gold Medal for eighty times, [ 1 ]  but such requirements are not included in decree. From the establishment of the medal in 1979 to 11 June 2016 (the day on which more people were awarded) it was awarded: 17,629 Bronze Medals, 10,097 Silver Medals and 3,085 Gold Medals. [ 1 ]  New decorations are awarded every year. Approx. 400 people were awarded on 21 October 2017. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5423", "text": "The badge of medal is a  cross  of  Red Cross , enameled in red, crowned, with diamond-shape plaques. On plaque on  obverse  is  coat of arms  of Grand Duchess of Luxembourg, which are three combined coats of arms with lions. In upper left quarter is lion, coat of arm of  Nassau , in lower left quarter is lion, coat of arm of  Luxembourg  and in right half is lion, coat of arm of  Belgium . On plaque on  reverse  is profile of Grand Duchess  Jos\u00e9phine Charlotte , facing left, surrounded by an inscription  S.A.R Jos\u00e9phine Charlotte Grande-Duchesse de Luxembourg  ( H.R.H. Jos\u00e9phine Charlotte Grand Duchess of Luxembourg ). Plaques, edges of cross and crown are, according to grade, gilded, silver or bronze. The ribbon of the medal is white with red stripe in the middle and thin three-colour (blue-white-red) stripes at edges."}
{"_id": "WikiPedia_Hematology$$$corpus_5424", "text": "National Blood Centre  of Malaysia ( Malay language :  Pusat Darah Negara ; or its acronym,  PDN ) is a  Malaysia \u2019s premier blood centre for transfusion medicine and transplant. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5425", "text": "Blood Bank Services in Malaysia has been initiated by a group of women volunteers of British Red Cross in 1955. Initially, the service was open on Wednesdays from 5:00 pm to 5:30 pm at the Kuala Lumpur General Hospital. On this initiative, a total of 25 to 44 donors were collected every month. Donors at that time consisted of members of the police, military, and government personnel. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5426", "text": "After 15 years of the start of the service, as much as 5,830 units of blood and no less than 13,860 successful compatibility tests were done. Due to the increasing need of the service, the blood centre was moved to another building at Hospital Kuala Lumpur in 1971. The building is known as \"National Blood Service Center\" and was inaugurated in April 1972 by the Director General of Health, Ministry of Health. The National Blood Service Centre was put under the Ministry of Health and chaired by a Director. The director was responsible for all the blood services that include donor recruitment, blood collection, processing, testing, inventory management, and clinical transfusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5427", "text": "Starting in 1975, the Blood Services Center has played an important role in the standardization of work procedures, methodology, reagent and blood bank equipment in all new buildings negara. In 2002, National Blood Centre was built in Jalan Tun Razak and it was inaugurated by the Prime Minister  Mahathir Mohamad 's wife  Siti Hasmah Mohamad Ali . The building is stately and magnificent to date in ensuring the collection of blood and ensure a safe, clean and quality."}
{"_id": "WikiPedia_Hematology$$$corpus_5428", "text": "Creating and maintaining a safe blood donors. Provides blood, blood components that are safe, adequate and appropriate screening procedures in practice and storage in accordance with international standards. Ensure optimal patient care through the use of blood and blood products as appropriate. Establish and maintain cooperative relations through training, research and development in line with the needs of the practice and the latest technology in the medical field to date."}
{"_id": "WikiPedia_Hematology$$$corpus_5429", "text": "National Blood Donation Day  comes each year on September 4.  It is an observance during  National Blood Donation Week  and  campaign  that highlights the need for  blood .  Multiple states throughout the United States have their state  blood donation  day on this same day uniting the country in its effort to keep  blood banks  and hospitals stocked. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5430", "text": "In 2015, syndicated radio host and family physician  Daliah Wachs  asked  Nevada  Governor  Brian Sandoval  to create a Nevada Blood Donation Day to help the state raise blood and awareness. [ 4 ]  Uniting with  United Blood Services  and the  American Red Cross , Nevada Blood Donation Day held blood drives across the state, and its success prompted the campaign to continue in 2016.  During this year, blood shortages were being reported nationally. [ 5 ]   Daliah approached  Governors  in all 50 states to help proclaim state blood donation days, and United Blood Services, the American Red Cross and blood banks across the US joined forces to help bring this national campaign to light.  By September 2016, the majority of states had proclaimed state blood donation days.   Indiana  and  Arizona  proclaimed a  blood donation week  during this time and  Alaska  proclaimed the entire month of September Alaska Blood Drive Donor Challenge Month. [ 6 ] [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5431", "text": "States with proclaimed Blood Donation Days on September 10 include: Oklahoma, Mississippi, New Mexico, Connecticut, North Dakota, North Carolina, Rhode Island, Indiana, Arkansas, Vermont, Utah, Montana, Louisiana, Alabama, Missouri, Massachusetts, Maryland, Maine, Oregon, Iowa, Florida, New Hampshire, Pennsylvania,  Minnesota , South Dakota, Washington, Georgia, West Virginia, Wisconsin, Illinois, Nebraska. [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5432", "text": "The First Tuesday in September has been designated Michigan Blood Donation Day."}
{"_id": "WikiPedia_Hematology$$$corpus_5433", "text": "In 2017, National Blood Donation Day was September 8.  NBDD was able to raise blood needed for recovery efforts from Hurricanes  Harvey  and  Irma ."}
{"_id": "WikiPedia_Hematology$$$corpus_5434", "text": "States who have already declared this date their Blood Donation Day include Alabama, Arkansas, Colorado, Delaware, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Louisiana, Maine, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, North Carolina, Ohio, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, Virginia, Washington, Wisconsin, Wyoming.  Arizona declared Arizona Blood Donation Week September 4-10th. Maryland declared their blood donation day September 7."}
{"_id": "WikiPedia_Hematology$$$corpus_5435", "text": "In 2018, National Blood Donation Day was September 5."}
{"_id": "WikiPedia_Hematology$$$corpus_5436", "text": "States who have already declared this date their Blood Donation Day include Alabama, Arkansas, Colorado, Delaware, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, North Carolina, Ohio, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, Virginia, Washington, West Virginia and Wisconsin."}
{"_id": "WikiPedia_Hematology$$$corpus_5437", "text": "Arizona has proclaimed September 3\u201310 Arizona Blood Donation Week.\nOklahoma proclaimed the month of September Blood Donation Month.\nAlaska proclaimed the month of July Blood Donation Month."}
{"_id": "WikiPedia_Hematology$$$corpus_5438", "text": "In 2019, National Blood Donation Day was September 5."}
{"_id": "WikiPedia_Hematology$$$corpus_5439", "text": "States who have already declared this date their Blood Donation Day include Alabama, Arkansas, Connecticut, Delaware, Georgia, Florida, Idaho, Indiana, Iowa, Kansas, Maine, Maryland, Michigan, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, North Carolina, North Dakota, Ohio, Oklahoma, Pennsylvania, Rhode Island, South Carolina, Tennessee, Utah, Vermont, Washington, West Virginia, Wisconsin and Wyoming."}
{"_id": "WikiPedia_Hematology$$$corpus_5440", "text": "Arizona declared 9/2-9/9/19 Arizona Blood Donation Week"}
{"_id": "WikiPedia_Hematology$$$corpus_5441", "text": "For 2020, National Blood Donation Week fell on 9/1/20-9/7/20, with National Blood Donation Day to be September 4. Despite many governor's offices dealing with limited staff and resources, with many \"suspending proclamations,\" Governors in the following states proclaimed September 4 to be their state Blood Donation Day: Alabama, Colorado, Delaware, Florida, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland (September 5), Massachusetts, Michigan, Missouri, Montana, New Hampshire, New Jersey (September 5), New Mexico, North Dakota, Oklahoma, Pennsylvania, Rhode Island, South Carolina, Tennessee, Utah, Vermont, Wisconsin and Wyoming, with Arizona proclaiming September 1-7 Arizona Blood Donation Week. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5442", "text": "In 2021, National Blood Donation Week is September 1\u20137, with National Blood Donation Day September 4 or 5th.\nStates who have declared this date as their State Blood Donation Day include: Alabama, Arkansas, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, Virginia, West Virginia, Wisconsin, Wyoming."}
{"_id": "WikiPedia_Hematology$$$corpus_5443", "text": "Arizona has declared September 1\u20137 Arizona Blood Donation Week."}
{"_id": "WikiPedia_Hematology$$$corpus_5444", "text": "In 2022, National Blood Donation Week is September 1\u20137, with National Blood Donation Day on September 4. Governors in the following states are proclaiming September 4 to be their state Blood Donation Day: Arkansas, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, Virginia, Washington, West Virginia, Wisconsin and Wyoming."}
{"_id": "WikiPedia_Hematology$$$corpus_5445", "text": "Alaska has proclaimed Alaska Blood Donation Week during 9/1-9/7.\nArizona has proclaimed Arizona Blood Donation Week during 9/1-9/7."}
{"_id": "WikiPedia_Hematology$$$corpus_5446", "text": "In 2023, National Blood Donation Week is September 1\u20137, with National Blood Donation Day on September 4. Governors in the following states are proclaiming September 4 to be their state Blood Donation Day:\nAlabama, Arkansas, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Kentucky, Louisiana, Maine, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Nebraska, Nevada, New Hampshire, New Jersey, North Dakota, Ohio, Oklahoma, South Carolina, South Dakota, Utah, Vermont, Virginia, Washington, West Virginia, Wisconsin, Wyoming"}
{"_id": "WikiPedia_Hematology$$$corpus_5447", "text": "Arizona has proclaimed Arizona Blood Donation Week during 9/1-9/7."}
{"_id": "WikiPedia_Hematology$$$corpus_5448", "text": "Alaska declared September 4-10th Alaska Blood Donation Week."}
{"_id": "WikiPedia_Hematology$$$corpus_5449", "text": "In 2024, Governors in the following states are proclaiming September 4 to be their state Blood Donation Day:  Alabama, Arkansas, Connecticut, Delaware, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Minnesota, Mississippi, Massachusetts, Michigan, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, North Carolina, North Dakota, Ohio, Oregon, Pennsylvania, South Carolina, South Dakota, Utah, Virginia, West Virginia, Wisconsin and Wyoming."}
{"_id": "WikiPedia_Hematology$$$corpus_5450", "text": "Alaska has declared September 1-7 Alaska Blood Donation Week. \nArizona has declared September 1\u20137 Arizona Blood Donation Week.\nColorado has declared September 1-7 Colorado Blood Donation Week."}
{"_id": "WikiPedia_Hematology$$$corpus_5451", "text": ","}
{"_id": "WikiPedia_Hematology$$$corpus_5452", "text": "The  National Donor Deferral Registry , also known as the (NDDR) is a database of individuals who have tested \"reactive\" for viral agents like  human immunodeficiency viruses (HIV) ,  Hepatitis B virus (HBV) , and  hepatitis C virus (HCV)  and are permanently prohibited from donating plasma. [ 1 ]  NDDR is a registered trademark of the Plasma Protein Therapeutics Association. U.S. regulations require organizations that collect plasma screens for viruses and flag donors and keep a list.  The NDDR was established in 1993.  This is to help plasma donation centers notify other centers of a donor who has tested positive for one of the listed viruses."}
{"_id": "WikiPedia_Hematology$$$corpus_5453", "text": "The NDDR is a confidential database that is used in North America and the United States to help provide the collection of safe plasma donation through  plasmapheresis .  When identifying information is matched in the registry, the donation center should not accept a person donation. The U.S. Food and Drug Administration lists the requirements for donor federal in 21 CFR \u00a7 610.41"}
{"_id": "WikiPedia_Hematology$$$corpus_5454", "text": "In November 2020, the U.S. Food and Drug Administration reviewed a Section 510(k) premarket notification of a cloud-based version of the NDDR by Headspring Healthcare, Inc. [ 2 ]  \nThe new web-based systems would allow"}
{"_id": "WikiPedia_Hematology$$$corpus_5455", "text": "Each donation center is responsible for checking the NDDR prior to donation and uploading any positive or reactive tests for each donor. An International Quality Plasma Program (IQPP) facility is a lab that has agreed to the voluntary standards program of the PPTA. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5456", "text": "The  personally identifiable information  (PII) that is collected is \"individual's donor ID, first and last name, middle initial birthdate and gender. The donor's social security number or INDS number.\""}
{"_id": "WikiPedia_Hematology$$$corpus_5457", "text": "The FDA has established rules under how a previously deferred donor may be able to requalify.  There are two methods which the FDA has adopted."}
{"_id": "WikiPedia_Hematology$$$corpus_5458", "text": "It was not until May 2010 when the FDA published a way for individuals to be requalified due to repeatedly reactive test for anti-HBC.  The FDA admitted that up to 21,500 people in the late 1980s and 1990s because of \" false positive \" tests results. The FDA estimated that almost 200,000 donors could be eligible for reentry. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5459", "text": "There is no central agency responsible for reviewing or correcting errors. Each company that inputs data into the NDDR must have a written procedure to correct errors."}
{"_id": "WikiPedia_Hematology$$$corpus_5460", "text": "A Woman in Des Moines, Iowa, was listed on the NDDR after having a 'reactive' test for HIV however, after additional testing was found to be negative for HIV. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5461", "text": "The  New Zealand Blood Service  (in  te reo M\u0101ori :  Te Ratonga Toto O Aotearoa ) is the provider of blood services for  New Zealand . The service is a Crown entity responsible to  New Zealand's Parliament  and is governed by a Board appointed by the Minister of Health. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5462", "text": "The New Zealand Blood Service (NZBS) was formed on 1 July 1998, when the Health Amendment Act 1998 was passed by Parliament. NZBS was created to provide the people of New Zealand with safe, appropriate and timely access to blood and tissue products and related services to meet their health needs. NZBS is responsible for the development of an integrated national  blood transfusion  process from the collection of blood from volunteer donors to the transfusion of  blood products  within the hospital environment \u2013 a 'vein to vein' transfusion service. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5463", "text": "Approximately 29,000 New Zealanders need blood or blood products every year [ 5 ]  and less than 4% of New Zealanders donate."}
{"_id": "WikiPedia_Hematology$$$corpus_5464", "text": "In November 2020, Organ Donation New Zealand became part of the NZBS. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5465", "text": "On 14 December 2020, the NZBS amended its donation policies to reduce the blood deferral period for gay and bisexual men as well as male sex workers from 12 to 3 months. [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5466", "text": "On 4 October 2021, the New Zealand Heart Valve Bank became part of NZBS. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5467", "text": "In mid February 2024, the NZBS confirmed that it would lift the  mad cow disease  blood donation restriction from 29 February. This restriction had been in place since 2000 and had excluded people who had lived in the  United Kingdom ,  France  and  Ireland  between 1980 and 1996 for at least six months from donating blood and plasma in New Zealand. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5468", "text": "New Zealand Blood Service has three groups of key responsibilities and activities: [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5469", "text": "New Zealand Blood Service plans and forecasts demand from hospitals and uses this to calculate the number of appointments and donations required for the week, based on blood type. Blood type is key, as donations are matched to the blood types of the patients being treated in hospitals."}
{"_id": "WikiPedia_Hematology$$$corpus_5470", "text": "Each year NZBS collects approximately 106,000 whole blood donations, 110,000 plasma donations and 18,000 units of platelets. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5471", "text": "NZBS has nine Donor Centres around New Zealand and runs over 300 mobile blood drives each year. The Donor Centres are in  Auckland  (Epsom, Manukau and North Shore),  Hamilton ,  Tauranga ,  Palmerston North ,  Wellington ,  Christchurch  and  Dunedin . Mobile blood drives take place in community halls, education centres and workplaces.  Whole blood  donors can donate at a mobile blood drive or any of the nine Donor Centres.  Plasma  and  platelet  donations require an  apheresis  machine and so can only be made at nine Donor Centres with these facilities."}
{"_id": "WikiPedia_Hematology$$$corpus_5472", "text": "In order to minimise risk for recipients of blood and blood products, NZBS has detailed eligibility criteria in place for potential donors. These include a donor's age, weight, health and travel history."}
{"_id": "WikiPedia_Hematology$$$corpus_5473", "text": "Blood donations are processed at  sites: Auckland, Wellington and Christchurch. These sites collectively process around 106,000 donations each year. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5474", "text": "Processing involves the separation of blood donations into blood components: red cells, platelets and plasma. Other types of donations such as stem cells and tissues are also processed and stored at these sites."}
{"_id": "WikiPedia_Hematology$$$corpus_5475", "text": "Accreditation testing is centralised in Auckland and Christchurch. Accreditation testing of all blood donations involves two distinct processes:  blood grouping  and screening for infectious markers."}
{"_id": "WikiPedia_Hematology$$$corpus_5476", "text": "Blood banks are the pre-transfusion testing laboratories where blood products are matched to suit each individual patient. This includes determining the patient's  blood type  and matching this with appropriate products. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5477", "text": "Blood banks are always located at hospitals and are often staffed after hours to meet any urgent need for blood. NZBS operates six blood banks within hospitals across New Zealand. Within the 20  District Health Board  (DHB) Blood Bank laboratories also perform pre-transfusion testing in line with defined quality standards."}
{"_id": "WikiPedia_Hematology$$$corpus_5478", "text": "Percy Lane Oliver   OBE  (11 April 1878 \u2013 16 April 1944) was a British civil servant, who is credited with founding the first volunteer  blood donation  service. [ 1 ] [ 2 ]  A layman, Oliver was working for the  Camberwell  division of the  Red Cross  in 1921 when he responded to a call from a local hospital requesting an urgent blood donation. This experience led him to organise a panel of donors whose blood types were known and who were available to donate on request. The donors, unusually for the time, were not paid. Oliver's blood donation service, which he ran out of his London home, would grow from 20 volunteers at its inception to approximately 2700 in 1938. His model of voluntary blood donation was adopted throughout Britain and in other countries."}
{"_id": "WikiPedia_Hematology$$$corpus_5479", "text": "Oliver, the son of two teachers, was born in  St. Ives, Cornwall  on 11 April 1878. [ 1 ]  His family moved to London five years later. At 14, he applied to join the  Civil Service , but despite placing first in the exam, he was denied admission on the basis of his \"weak heart\". [ 3 ] :\u200a151\u200a  He then worked as a librarian for the  Camberwell Borough Council  and in 1901 took up a position with the  Camberwell Town Hall . He married Ethel Grace in 1905 and would go on to have three children with her. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5480", "text": "Oliver was one of the founding members of the Camberwell  Red Cross  division, and in 1910 was named its honorary secretary. [ 3 ] :\u200a151\u200a  During the  First World War , the organisation helped rescue explosion victims. Oliver and Ethel also aided in rehoming  war refugees , and in 1918, the couple were appointed to the  Order of the British Empire . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5481", "text": "While Oliver had recognised the need for an organised network of blood donors as early as 1920, the beginnings of his transfusion service are generally dated to 1921. [ 1 ] [ 3 ] :\u200a151\u200a [ 4 ] :\u200aS97\u200a  In October of that year, [ 3 ] :\u200a151\u200a  the Red Cross received a call from  King's College Hospital  in nearby  Denmark Hill  for an emergency blood transfusion. Oliver, along with three of his colleagues, volunteered to donate blood; one person's blood type was compatible with the patient's, and the transfusion was successful. This inspired Oliver to establish a panel of individuals with known blood types who were available to donate upon request. The panel, which initially consisted of 20 of Oliver's colleagues and operated out of his home, [ 5 ] :\u200a53\u20134\u200a  grew to encompass 450 donors by 1926. [ 4 ] :\u200aS97\u200a  As demand for blood increased, many London  Rover Scouts  were enlisted as donors. [ 3 ] :\u200a153"}
{"_id": "WikiPedia_Hematology$$$corpus_5482", "text": "Internal struggles led Oliver to resign from his position with the Camberwell Red Cross at the end of 1925. The Camberwell transfusion service\u2014which had previously been operating unofficially\u2014was incorporated as the British Red Cross Blood Transfusion Service in 1926.  Geoffrey Keynes  was appointed as the organisation's medical advisor. [ 3 ] :\u200a153\u20134\u200a  The transfusion service continued to operate out of Oliver's home; in 1928 its demands led the family to move to a larger property at 5 Colyton Road,  Peckham Rye , London. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5483", "text": "Prospective donors underwent physical health screening and testing for  syphilis , and\u2014contrary to the practices of the time in the United States and much of England\u2014were not paid. While paid donations carried a reputation of attracting a sometimes unsavoury clientele, Oliver emphasised that his donors were \"drawn from all classes of the community \u2013 independent and professional men and women, barristers, journalists, shopmen and girls, labourers, apprentices, roadmen, maid servants and charwomen\". [ 3 ] :\u200a155\u20136\u200a [ 5 ] :\u200a54\u20136"}
{"_id": "WikiPedia_Hematology$$$corpus_5484", "text": "The removal of payment from the equation also encouraged Oliver to institute more humane practices for the treatment of donors. The Red Cross Blood Transfusion Service banned the common, but painful and dangerous technique of \"cutting down\"\u2014making a large incision in the arm to access the vein\u2014and required that the donor be lying down during the blood collection. Oliver eschewed the perception of blood donors as heroes subjecting themselves to a dangerous ordeal, [ 3 ] :\u200a155\u20136\u200a  and forbade contact between donors and patients, as he believed that \"every donor should realise that he or she is a unit of an organisation created and functioning for the benefit of humanity generally, at the direction of surgeons, and not at the behest of a single individual\". [ 4 ] :\u200aS97\u20138\u200a  In 1932, the Red Cross Blood Transfusion Service founded the Voluntary Blood Donors Association, which provided insurance for its donors, [ 3 ] :\u200a157\u200a  organised social events and published a newsletter. [ 6 ]  By 1938, the service counted approximately 2700 donors among its ranks. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5485", "text": "Despite his lay origins, Oliver gained recognition as an authority on transfusion, [ 3 ] :\u200a157\u200a  and his system of voluntary blood donation was adopted throughout Britain and in other countries. During the  Second World War  he was involved in the creation of a service for emergency blood transfusions, which, after the war (and Oliver's death), developed into a government-run national transfusion service. [ 1 ] [ 4 ] :\u200aS114"}
{"_id": "WikiPedia_Hematology$$$corpus_5486", "text": "Oliver died of a heart attack at  St George's Hospital ,  Westminster  on 16 April 1944. [ 1 ]  The Oliver Memorial Fund, established upon his death, granted the Oliver Memorial Award to individuals\u2014including laypeople\u2014who have contributed to the field of  transfusion medicine . [ 2 ]  The  Royal College of Pathologists  also issues an \"Oliver Memorial Trainee Bursary\" each year since 1948."}
{"_id": "WikiPedia_Hematology$$$corpus_5487", "text": "English Heritage  commemorated Oliver's former home at 5 Colyton Road with a  plaque  in 1979. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5488", "text": "Order for the International Merit of Blood  is awarded by the  International Federation of Blood Donor Organizations  (IFBDO or FIODS) to personalities who made a special contribution to promote the regular, anonymous, voluntary, non-remunerated gift of blood in the world."}
{"_id": "WikiPedia_Hematology$$$corpus_5489", "text": "Proposals for award are sent to President who studies them and submits them to the Executive Council. According to IFBDO Rules of Procedure in force, except under exceptional circumstances, no more than four proposals per country can be submitted per meeting of the Executive Council. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5490", "text": "Plateletpheresis  (more accurately called  thrombocytapheresis  or  thrombapheresis , though these names are rarely used) is the process of collecting  thrombocytes , more commonly called platelets, a component of blood involved in  blood clotting .  The term specifically refers to the method of collecting the platelets, which is performed by a device used in  blood donation  that separates the platelets and returns other portions of the blood to the donor.   Platelet transfusion  can be a life-saving procedure in preventing or treating serious complications from bleeding and hemorrhage in patients who have disorders manifesting as  thrombocytopenia  (low platelet count) or platelet dysfunction.  This process may also be used therapeutically to treat disorders resulting in extraordinarily high platelet counts such as  essential thrombocytosis ."}
{"_id": "WikiPedia_Hematology$$$corpus_5491", "text": "Platelet transfusions  are traditionally given to patients undergoing  chemotherapy  for  leukemia ,  multiple myeloma , those with  aplastic anemia ,  AIDS , hypersplenism,  idiopathic thrombocytopenic purpura  (ITP),  sepsis , bone marrow transplant,  radiation treatment ,  organ transplant  or surgeries such as  cardiopulmonary bypass . Platelet transfusions should be avoided in those with  thrombotic thrombocytopenic purpura  (TTP) because it can worsen neurologic symptoms and  acute renal failure , presumably due to creation of new thrombi as the platelets are consumed. It should also be avoided in patients with  heparin-induced thrombocytopenia  (HIT) or  disseminated intravascular coagulation  (DIC). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5492", "text": "In adults, platelets are recommended in those who have levels less than 10,000/\u03bcL, or less than 20,000/\u03bcL if a  central venous catheter  is being placed, or less than 50,000/\u03bcL if a  lumbar puncture  or major surgery is required. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5493", "text": "Not all platelet transfusions use platelets collected by automated apheresis.  The platelets can also be separated from donations of  whole blood  collected in a traditional  blood donation , but there are several advantages to separating the platelets at the time of collection.  The first advantage is that the whole-blood platelets, sometimes called \"random\" platelets, from a single donation are not numerous enough for a dose to give to an adult patient.  They must be pooled from several donors to create a single transfusion, and this complicates processing and increases the risk of  diseases  that can be spread in transfused blood, such as  human immunodeficiency virus . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5494", "text": "Collecting the platelets from a single donor also simplifies  human leukocyte antigen  (HLA) matching, which improves the chance of a successful transfusion.  Since it is time-consuming to find compatible donors for HLA-matched transfusions, collecting a full dose from a single donor is more practical than finding multiple compatible donors. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5495", "text": "Plateletpheresis products are also easier to test for bacterial contamination, a leading cause of transfusion-associated deaths. [ citation needed ]   Pooling of whole blood platelets is often done in an \"open\" system where the platelet containers are connected in a way that could expose the platelets to air, and pooled platelets must be transfused promptly so that any contamination does not have time to grow. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5496", "text": "Problems with apheresis include the expense of the equipment used for collection. Whole blood platelets also do not require any additional donor recruitment, as they can be made from blood donations that are also used for  packed red blood cells  and  plasma  components. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5497", "text": "Recipients in this category include those undergoing chemotherapy, those with  myelophthisic anemia ,  AIDS , or with  aplastic anemia . If indicated, transfusions (one thrombapheresis concentrate) should be given until recovery of platelet function, generally approximately twice weekly. Surgical bleeding due solely to thrombocytopenia occurs when platelets < 50,000/\u03bcL while spontaneous bleeding occurs when platelets < 10,000/\u03bcL. Thrombocytopenic patients can develop \"dry\" bleeding, that is,  petechiae  and  ecchymoses  only. They will not suffer fatal hemorrhagic events unless they first have extensive mucosal bleeding, or \"wet\" bleeding. Therefore, in those with no bleeding or only \"dry\" bleeding, the threshold for transfusion should be between 5,000 and 10,000/\u03bcL. A more conservative threshold of 20,000/\u03bcL should be used in those with a fever or other risk factors for bleeding. Those with active bleeding or prior to surgery should have a threshold of 50,000/\u03bcL. An unconfirmed, but helpful, way to determine whether a patient is recovering from chemotherapy-induced thrombocytopenia is to measure \"reticulated\" platelets, or young RNA-containing platelets, which signifies that the patient is starting to make new platelets. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5498", "text": "Recipients in this category include those with idiopathic thrombocytopenic purpura or drug-induced thrombocytopenia. Platelet transfusions are generally not recommended for this group of patients because the underlying cause involves antibodies that destroy platelets, therefore any newly transfused platelets will also be destroyed. Platelet transfusion may be used in emergency bleeding situations where the platelets could be used by the body before the immune system destroys them."}
{"_id": "WikiPedia_Hematology$$$corpus_5499", "text": "Disorders of platelet function can be congenital or acquired. Most of these disorders are mild and may respond to therapy with  desmopressin  (dDAVP). Transfusion is not necessarily required. However, with some more severe disorders such as  Glanzmann thrombasthenia , transfusions with large amount of platelets may be needed. The number of transfusions may be reduced if these patients are given  recombinant human factor VIIa [ medical citation needed ]  since the underlying cause are antibodies to platelet  glycoproteins IIb/IIIa ."}
{"_id": "WikiPedia_Hematology$$$corpus_5500", "text": "Cardiopulmonary bypass surgery  can result in destruction of a large proportion of the patient's platelets and may render the remaining viable platelets dysfunctional. The indications for transfusion in such patients is controversial. General guidelines recommend not transfusing patients prophylactically but only when they are bleeding excessively, while also giving desmopressin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5501", "text": "The most common of these is  aspirin , and its similar drug class, the  NSAIDs . Other anti-platelet drugs are commonly prescribed for patients with acute coronary syndromes such as  clopidogrel  and  ticlopidine . When surgery is undertaken following the administration of these drugs, bleeding can be serious. Transfusion under these circumstances is not clear-cut and one has to use clinical judgment."}
{"_id": "WikiPedia_Hematology$$$corpus_5502", "text": "Platelet count increase as well as platelet survival after transfusion is related to the dose of platelets infused and to the patient's body surface area (BSA). Usually these values are less than what would be expected."}
{"_id": "WikiPedia_Hematology$$$corpus_5503", "text": "The theoretical value of the CCI is 20,000/\u03bcL but clinically, the value is closer to 10,000/\u03bcL. If the CCI is less than 5,000/\u03bcL, patients are said to have \"refractoriness\" to platelet transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_5504", "text": "The separation of individual  blood components  is done with a specialized  centrifuge  (see  apheresis ). The earliest manual forms of thrombapheresis are done by the separation of platelets from multiple bags of  whole blood  collected from donors or blood sellers. Since each blood bag (usually 250 mL or 500 mL) contains a relatively small number of platelets, it can take as many as a dozen blood bags (usually from five to ten bags, depending on the size of the blood bags and each donor's platelet count) to accumulate a single unit of platelets (enough for one patient). This greatly increases the risks of the transfusion. Each unit of platelets separated from donated whole blood is called a \"platelet concentrate\". [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5505", "text": "Modern automatic thrombapheresis allows blood donors to give a portion of their platelets, while keeping their  red blood cells  and at least a portion of  blood plasma . Therefore, no more than three units of platelets are generally harvested in any one sitting from a donor.  Most donors will donate a \"single\" or \"double\" unit, however the occurrence of \"triples\" has been increasing as more suitable donors are recruited. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5506", "text": "Because platelets have a shelf life of just five days, more platelet donors are always needed.  Some centers are experimenting with seven-day platelets, but this requires additional testing and the lack of any preservative solutions means that the product is far more effective when fresh."}
{"_id": "WikiPedia_Hematology$$$corpus_5507", "text": "Even though red blood cells can also be collected in the process, many blood donation organizations do not do so because it takes much longer for the human body to replenish their loss. In addition, some (though not all) centers defer further platelet donations until the red blood cells can be replenished."}
{"_id": "WikiPedia_Hematology$$$corpus_5508", "text": "In most cases, blood plasma is returned to the donor as well. However, in locations that have plasma processing facilities, a part of the donor's plasma can also be collected in a separate blood bag (see  plasmapheresis ). For example, in Australia around 5.9\u00d710 11  platelets and 580 mL of plasma might be collected from an 88 kg donor."}
{"_id": "WikiPedia_Hematology$$$corpus_5509", "text": "Due to their higher  relative density , white blood cells are collected as an unwanted component with the platelets. Since it takes up to 3 liters of whole blood (the amount of a dozen blood bags) to generate a dose of platelets, white blood cells from one or several donors will also be collected along with the platelets. A 70\u00a0kg (154\u00a0lb) man has only about 6 liters of blood. If all of the incidentally collected white blood cells are transfused with the platelets, substantial rejection problems can occur. Therefore, it is standard practice to filter out white blood cells before transfusion by the process of  leukoreduction ."}
{"_id": "WikiPedia_Hematology$$$corpus_5510", "text": "Early platelet transfusions used a filter to remove white blood cells at the time of transfusion. It takes a trained person about 10 minutes to assemble the equipment, and this is not the safest or most efficient means of filtration because living white blood cells can release  cytokines  during storage and dead white blood cells can break up into smaller fragments that can still stimulate a dangerous response from the immune system. In addition, simple filtration can lead to increased risks of infection and loss of valuable platelets. Newer, more advanced thrombapheresis machines can filter white blood cells during separation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5511", "text": "For example, with marginally acceptable whole blood (white blood cells: < 10,000/mm\u00b3; platelets: > 150,000/mm\u00b3), a dose (3\u00d710 11 ) of platelets comes with about 2\u00d710 10  white blood cells. This can seriously damage the patient's health. A dose of single-donor platelets prepared using latest filters can contain as little as 5\u00d710 6  white blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_5512", "text": "There are two types of manual platelet apheresis.  Platelet-rich plasma  (PRP) is widely used in North America and  buffy coat  (BC) is more widely used in Europe."}
{"_id": "WikiPedia_Hematology$$$corpus_5513", "text": "Platelets  are the clotting cells of the blood. Platelet donation therapy is frequently needed by cancer patients, because  chemotherapy  for such patients can render them unable to generate platelets of their own."}
{"_id": "WikiPedia_Hematology$$$corpus_5514", "text": "The basic principles of automatic platelet  apheresis  are the same as in the manual procedure, but the whole procedure is performed by a computer-controlled machine. Since the donor's blood is processed in a sterile single-use centrifuge, the unwanted components can be returned to the donor safely. This allows the apheresis machine to repeat the draw-centrifuge-return cycle to obtain more platelets. The bulk of the machine and the length of the donation process means most platelet donations are done in blood centers instead of mobile blood drives."}
{"_id": "WikiPedia_Hematology$$$corpus_5515", "text": "Each country has its own rules to protect the safety of both donor and recipient. In a typical set of rules, a platelet donor must weigh at least 50\u00a0kg (110\u00a0lb) and have a platelet count of at least 150 x 10 9 /L (150,000 platelets per mm\u00b3). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5516", "text": "One unit has greater than 3\u00d710 11  platelets. Therefore, it takes 2 liters of blood having a platelet count of 150,000/mm\u00b3 to produce one unit of platelets. Some regular donors have higher platelet counts (over 300,000/mm\u00b3); for those donors, it only takes about one liter of their blood to produce a unit. Since the machine used to perform the procedure uses suction to draw blood out of a donor's body, some people who can give whole blood may have veins too small for platelet donation."}
{"_id": "WikiPedia_Hematology$$$corpus_5517", "text": "Blood accounts for about 8% of body weight, so a 50\u00a0kg (110\u00a0lb) donor has about four liters of blood. No more than 50% of a donor's platelets are ever extracted in one sitting, and they can be replenished by the body in about three days."}
{"_id": "WikiPedia_Hematology$$$corpus_5518", "text": "Most newer apheresis machines can separate a maximum donation of platelets in about 60 to 120 minutes depending on the donor's health condition."}
{"_id": "WikiPedia_Hematology$$$corpus_5519", "text": "After a short  physical examination  which usually involves checking the donor's height, weight,  body temperature ,  blood pressure ,  pulse rate ,  haemoglobin concentration , etc., the donor is taken into the donation room and sits in a reclining chair next to the machine. The technician cleans one or both arms with  iodine ,  chlorhexidine  or other disinfectant, and inserts the  catheter  into a  vein  in the arm. With some procedures both arms are used, one to draw blood and the other to return it. The process takes about one to two hours while blood is pulled into the machine, mixed with an anticoagulant such as  sodium citrate , spun around, and returned to the donor. \"Double needle\" procedures using both arms tend to be shorter since the blood is drawn and returned through different catheters; with \"single needle\" procedures a set volume is drawn and processed in the first part of the cycle and returned in the second part. The donor's blood undergoes repeated cycles of draw and return."}
{"_id": "WikiPedia_Hematology$$$corpus_5520", "text": "Side effects of the donation of platelets generally fall into three categories: blood pressure changes, problems with vein access, and effects of the anticoagulant on the donor's calcium level. Blood pressure changes can sometimes cause nausea, fatigue, and dizziness. Venous access problems can cause bruising, referred to as a  hematoma . While donating, a supply of calcium  antacid  tablets is usually kept close by to replenish the calcium lost. Because the anticoagulant works by binding to the  calcium  in the blood, a donor's levels of calcium \u2013 and especially of active calcium ions \u2013 drop during the donation process. The lips may begin to tingle or there may be a metallic taste; since calcium enables the function of the nervous system, nerve-ending-dense areas (such as the lips) are susceptible, at least during the donation process. Unusually low calcium can cause more serious problems such as fainting, nerve irritation [ citation needed ]  and short-duration  tetany . Such an acute  hypocalcaemia  is usually due to low calcium levels prior to donation, aggravated by the anticoagulant. Hypocalcaemia can be curtailed by modestly increasing dietary calcium intake in the days prior to donation. Serious problems are extremely rare, but apheresis donors are typically not allowed to sleep during the long donation process so that they can be monitored. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5521", "text": "Aside from the procedure, donating platelets is different from donating blood in a few ways."}
{"_id": "WikiPedia_Hematology$$$corpus_5522", "text": "Firstly, the donor must not take  aspirin  or other anti- platelet  medications such as  clopidogrel  (Plavix) for anywhere from 36 to 72 hours prior to donation (guidelines vary by blood center). (Aspirin can prevent platelets from adhering to clot bleeding.) Some blood centers also prohibit the taking of any  non-steroidal anti-inflammatory drug  (NSAID) for 36 hours prior."}
{"_id": "WikiPedia_Hematology$$$corpus_5523", "text": "Secondly, platelet donations are allowed anywhere from every 3 to 28 days. This is in contrast to whole-blood donation, which has an eight-week (or longer) waiting period. Along those lines, since platelet donation temporarily removes whole blood from the body, it may be necessary to wait eight weeks after a whole blood donation to donate platelets, although two weeks is more common. In the US, a donor is allowed to donate platelets every seven days, but not more than 24 times during any 365-day period and may not lose more red blood cells or plasma during that period than they would from the maximum allowable number of whole blood donations. [ 3 ]  In India, as per Ministry of Health, the blood donation interval criteria for apheresis requires at least 48\u00a0hours interval after platelet- or plasma-apheresis. Any donation should not be done more than two times a week and should be limited to 24 times in one year. [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5524", "text": "Thirdly, additional tests may be required before becoming a donor for the first time. These tests may establish a platelet count. Newer automated platelet pheresis machines do that as the donation begins, and adjust accordingly the quantity of platelets to be drawn. Tests may also determine the donor's compatibility with particular recipients through a  human leukocyte antigen  (HLA) test.  Multiparous  women may be excluded from becoming donors due to heightened  TRALI  risk. These tests usually involve nothing more involved than the drawing of several tubes of blood."}
{"_id": "WikiPedia_Hematology$$$corpus_5525", "text": "Adverse conditions that can happen during a plateletpheresis donation are  hypocalcemia ,  hematoma  formation, and  vasovagal  reactions.  The risk of these conditions is normally reduced by pre-donation education of the donors and change of apheresis machine configuration. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5526", "text": "Repeated platelet donations at short intervals will cause the venipuncture site to scar. While cosmetically it is virtually invisible, the scarring also occurs on the vein itself, making it harder to insert a needle on future occasions. Anecdotal reports have said that rubbing  vitamin E  oil (or the insides of a vitamin E capsule) on the venipuncture site may reduce scarring. [ citation needed ]  However, a study conducted by the  University of Miami  Department of Dermatology and Cutaneous Surgery in 1999 demonstrated no positive effect from the application of topical vitamin E. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5527", "text": "Rotary Blood Bank  is India's largest  blood bank , located in the Tughlakabad Institutional Area,  New Delhi ,  India . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5528", "text": "Rotary Blood Bank was established in 2002 and is under the supervision of the Central Government. [ 2 ]  In September 2021, Rotary revealed its plan to extend its services to other parts of the country. It has blood banks in cities including  Kakinada ,  Hyderabad , and  Visakhapatnam . [ 3 ] \nThe blood bank signed an MoU with  Shri Vishwakarma Skill University  for providing certificate programme in phlebotomy technician and OJT in medical lab technology programmes. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5529", "text": "At the 56-57 Tughlakabad Institutional Area facility are available collection stations for 5-50 people giving  blood donations  at a time."}
{"_id": "WikiPedia_Hematology$$$corpus_5530", "text": "Rotary collects blood from organized groups e.g.  Colleges  and  Organizations , where any person can donate blood. Blood collections are collected by two Mini Buses which provide a mobile  medical facility . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5531", "text": "After collection of blood from in-house/camp, it is processed in the lab; where an erst while state-of-art facility is available after initial screening. Here blood separated in major three components e.g.  Red cells ,  Plasma  and  Platelets . In last few years there is a large demand for Platelets from September to December to treat  Dengue fever .  [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5532", "text": "Sankalp India Foundations  is a Bangalore-based  non-government organisation . [ 1 ]  It is a youth organisation working for blood donation,  thalassemia ,  bone marrow transplantation  and disaster relief. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5533", "text": "Since 2003, [ 2 ]  it has been working for voluntary blood donation in Karnataka. A blood helpline is run by the organisation. [ 3 ]  It also organizes several  blood donation  camps. It is one of the pioneer organisations which helps patients worldwide with a rare blood group \"Bombay Blood Group\" (also known as  hh blood group ). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5534", "text": "Sankalp India Foundation has done extensive work in the areas of quality and safety of blood donation camps, studying the extent of non-compliance [ 5 ]  and adverse donor events [ 6 ]  blood banks in voluntary blood donation camps."}
{"_id": "WikiPedia_Hematology$$$corpus_5535", "text": "Sankalp India Foundation runs several day care centers across South and West India for patients suffering from  Thalassemia  and related blood disorders ."}
{"_id": "WikiPedia_Hematology$$$corpus_5536", "text": "The StopThalassemia campaign is an initiative of Sankalp India Foundation to strengthen Thalassemia prevention by focusing on antenatal screening. The campaign provides screening services to pregnant women and their husbands in the first trimester of their pregnancy. The following maternity centres are part of the StopThalassemia Campaign:"}
{"_id": "WikiPedia_Hematology$$$corpus_5537", "text": "Sankalp also participates in disaster relief activities. A few of the disasters in which it participated for relief are the  Tsunami on the Indian sub continent , [ 10 ]  Karnataka floods, Sikkim earthquake, J&K earthquake, and the Assam floods. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5538", "text": "Sankalp India Foundation has been offering bone marrow transplantation for patients suffering from thalassemia. The organisation started the first bone marrow transplantation center In collaboration with People Tree Hospitals and Cure2Children Foundation, Italy in Bangalore in August 2015. [ 12 ]  In May 2017, the organisation has started a new bone marrow transplantation center in collaboration with  Care Institute of Medical Science , Ahmedabad.\nIn November 2017 Sankalp got into an understanding with MY Hospital, Indore for the new Bone Marrow Transplantation Program which started in March 2018. [ 13 ]   a new centre was started in Bangalore in June 2021 at Bhagwan Mahaveer Jain Hospital, Bangalore. The organisation has done more than 500 transplants for patients with thalassemia until December 2022."}
{"_id": "WikiPedia_Hematology$$$corpus_5539", "text": "Simply Blood  is an online blood donation platform which connects blood donors using its  Android  mobile applications and website. Simply Blood is world's first virtual blood donation platform having more than 10,000 registered users from more than 180 countries. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5540", "text": "Founded by  Kiran Verma , Delhi, India in 2016 along with five college passouts from Ambala District, Haryana launched Simply Blood app on January 29, 2017, in Delhi. [ citation needed ]  The founder of the platform is a school dropout and other were all software engineers passed out from the same college. Simply Blood was founded to solve the blood donation problem and curb black marketing of blood in India."}
{"_id": "WikiPedia_Hematology$$$corpus_5541", "text": "Simply Blood has launched an Android mobile app (applications) only. The second version of the app was released by  Vijay Goel , former Minister of Youth Affairs and Sports in  India  on September 23, 2017. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5542", "text": "They have launched a realtime GPS enabled application which allows a person to raise a blood request without sharing the contact details in public and blood donors can see all the nearby blood requests near his/her current location to accept the blood request. After accepting the blood request the donor and requester will get each other's number in less than few seconds. Blood donors who wanted to donate blood on some specific date can register themselves and select a suitable date from the \"Apps\" to donate blood and save a life."}
{"_id": "WikiPedia_Hematology$$$corpus_5543", "text": "Tara Devi Tuladhar  ( Nepali :  \u0924\u093e\u0930\u093e\u0926\u0947\u0935\u0940 \u0924\u0941\u0932\u093e\u0927\u0930 ) (21 August 1931 \u2013 27 November 2012) was Nepal's first female blood donor and a social worker who dedicated her life to serving society. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5544", "text": "Tara Devi was born to an old merchant family at Tanl\u0101chhi (\u0924\u0902\u0932\u093e\u091b\u093f),  Kathmandu . Her father  Triratna Man Tuladhar  was a  Lhasa Newar  trader. Her grandfather  Dharma Man Tuladhar  was a philanthropist best known for renovating the  Swayambhu stupa  in 1918. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5545", "text": "There were only a few schools in the 1930s as the  Rana  regime did not want ordinary citizens to get an education. For girls, it was even more difficult to join school. So Tara Devi received informal tuition at home. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5546", "text": "In 1948, her family sent her to study at St. Josephs's Convent in  Kalimpong ,  India . Returning to Kathmandu, she joined Kanya High School and finished 10th grade. In 1953, she went to  Allahabad , India and enrolled at  Kamla Nehru Memorial Hospital  to pursue her long cherished goal to become a nurse. Two years later, she received her Diploma in Midwifery."}
{"_id": "WikiPedia_Hematology$$$corpus_5547", "text": "She had been inspired to become a nurse by the tales she had heard as a child about how nurse  Vidyabati Kansakar  had cared for the injured during the  great earthquake of 1934  in Kathmandu. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5548", "text": "In 1960, Tara Devi began service at Prasuti Griha Maternity Hospital, Kathmandu. After doing her Post Graduate in Nursing from the College of Nursing,  New Delhi  in 1964, she became a senior tutor at Nursing School in Kathmandu. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5549", "text": "In 1961, she became the first female blood donor in Nepal by donating blood to a patient who was due for surgery and required blood urgently. [ 6 ]  She was the supervisor at  Tribhuvan University  Teaching Hospital before she retired in 1990. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5550", "text": "After her retirement, Tara Devi worked as a volunteer at Dharmakirti Vihar, a  Theravada Buddhist   nunnery  in Kathmandu, and used her skills as a trained nurse in the service of the resident nuns and the needy people who came there seeking help. As the coordinator of its health service, she organized free health care every week besides providing training on the care of patients and the elderly. She was also a life member of the Dharmakirti Vihar Conservation Trust. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5551", "text": "Tara Devi volunteered at Jana Chikitsalaya, a community clinic in Kathmandu. Besides serving as an executive board member of Paropakar Organisation, the first modern charitable organization in Nepal which was established in 1952, [ 9 ]  she was an adviser to Udaaya Samaj, a social organization of the  Uray  community. Tara Devi remained unmarried to be free to pursue her profession."}
{"_id": "WikiPedia_Hematology$$$corpus_5552", "text": "Tara Devi has authored two books, one in  Nepali  and the other in  Nepal Bhasa ."}
{"_id": "WikiPedia_Hematology$$$corpus_5553", "text": "The  Welsh Blood Service  is a division of  Velindre University NHS Trust  responsible for the collection of  blood  in  Wales , and of the distribution of blood products to hospitals within the country, as well as other related functions. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5554", "text": "The service was established in 1946. At that time the only test carried out was for syphilis. Since then more than 10 million units of blood have been donated in Wales. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5555", "text": "The Welsh Blood Service's roles include [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5556", "text": "On 2 May 2016 the Welsh Blood Service became a national service and began collecting and distributing blood in North Wales. [ 3 ]  Previously to this, the service covered Mid, South and West Wales, with  NHS Blood and Transplant , covering North Wales. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5557", "text": "The  research and development  activity within the  Welsh Blood Service   Archived  9 July 2017 at the  Wayback Machine  supports a broad range of healthcare topics. [ 5 ]  Its four research themes,  Transplantation ,  Donor Care and Public Health ,  Products  and  Therapies  reflect the spectrum of this work. In 2017 the Welsh Blood Service published its  Research and Development Strategy , which details its planned expansion of activity into collaborative work and engaging in regenerative and personalised medicine fields. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5558", "text": "World Blood Donor Day  ( WBDD ) is  held  on  June 14  each year. The event was organised for the first time in 2004, by four core international organizations: the  World Health Organization , the  International Federation of Red Cross and Red Crescent Societies ; the  International Federation of Blood Donor Organizations  (IFBDO) and the  International Society of Blood Transfusion  (ISBT) to  raise awareness  of the need for safe  blood  and  blood products , and to thank  blood donors  for their  voluntary , life-saving gifts of blood. [ 1 ]  World Blood Donor Day is one of 11 official  global public health  campaigns marked by the  World Health Organization  (WHO), along with  World Health Day ,  World Chagas Disease Day ,  World Tuberculosis Day ,  World Immunization Week ,  World Patient Safety Day ,  World Malaria Day ,  World No Tobacco Day ,  World Hepatitis Day , World Antimicrobial Awareness Week and  World AIDS Day . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5559", "text": "Transfusion of blood  and blood products helps and save millions of lives every year. It can help patients who are suffering from life-threatening conditions live longer and with higher  quality of life , and supports complex medical and surgical procedures. It also has an essential, life-saving role in maternal and  perinatal care . Access to safe and sufficient blood and blood products can help reduce rates of death and disability due to severe bleeding during delivery and after childbirth. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5560", "text": "In many countries, there is not an adequate supply of safe blood, and blood services face the challenge of making sufficient blood available, while also ensuring its quality and safety. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5561", "text": "An adequate supply can only be assured through regular donations by voluntary unpaid blood donors. The WHO's goal is for all countries to obtain all their blood supplies from voluntary unpaid donors by 2020. In 2014, 60 countries have their national blood supplies based on 99-100% voluntary unpaid blood donations, with 73 countries still largely dependent on family and paid donors. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5562", "text": "World Blood Donor Day is celebrated every year by people around the world on June 14. It is celebrated on the birthday anniversary of  Karl Landsteiner  on June 14, 1868. [ 6 ]  Landsteiner was awarded the  Nobel Prize  for his discovery of the ABO blood group system. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5563", "text": "Blood is a necessary resource for the planned treatments and the urgent interventions. It is helpful for patients who are suffering from life-threatening conditions for living longer and with a higher quality of life. It supports complex medical and surgical procedures. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5564", "text": "The theme for World Blood Donor Day 2024 is \"20 years of celebrating giving: thank you blood donors!\"."}
{"_id": "WikiPedia_Hematology$$$corpus_5565", "text": "The theme for World Blood Donor Day 2023 was \u201cGive Blood, Give  Plasma , Share Life, Share Often\u201d. This theme reflects the important role blood donors play in maintaining the health and well-being of communities around the world."}
{"_id": "WikiPedia_Hematology$$$corpus_5566", "text": "The theme for Blood Donor Day 2022 was 'Blood donation is an act of  solidarity . Join the effort and save lives'. This year, the global event on blood donor day was hosted by Mexico on June 14, 2022. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5567", "text": "The theme for Blood Donation Day 2021 was 'Give Blood and keep the world beating'. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5568", "text": "The theme for Blood Donation Day 2020 was 'Safe Blood Saves Lives'. The Slogan of \"Blood Donation Day 2020\" was 'Give Blood And Make The World A Healthier Place'. [ 12 ]  This year WHO announced a virtual rally for COVID-19 pandemic. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5569", "text": "The theme for Blood Donation Day in 2019 was 'Safe Blood For All'. [ 14 ] [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5570", "text": "The theme for Blood Donation Day in 2018 was \"Be there for someone else. Give blood. Share life.\" [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5571", "text": "The theme for Blood Donation Day in 2017 focused on blood donation in emergency situations.  The first response when an emergency happens is \"What Can You Do?\" and the answer is \"Give Blood. Give Now. Give Often\" which is taken by World Health Organization. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5572", "text": "The theme of the World Blood Donor Day, blood connects us all, highlights the notions of \"sharing\" and \"connection\" amongst blood donors and patients. The WBDD 2016 focused on thanking blood donors while emphasizing the role of the voluntary donation. The 2016 campaign brought to light the stories of the different people saved through blood donation to promote awareness and inspire people to donate. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5573", "text": "The host country of WBDD 2016 was The Netherlands. [ 19 ]   Williem-Alexander , the king of the Netherlands, opened the ceremony by thanking donors. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5574", "text": "It emphasizes thanking of blood donors who save lives every day through their blood donations and inspires more people all over the world to donate blood voluntarily and regularly with the slogan \u201cGive freely, give often\". Blood donation matters. This year campaign pays attention to stories from people whose lives have been saved through blood donation. Activities include memorable events, meetings, publication of relevant stories on media, scientific conferences, publication of articles on national, regional and international scientific journals, and other activities that would help in encouraging the title of this year's World Blood Donor Day. [ 21 ] \nThe host country for World Blood Donor Day 2015 is China through its blood center in Shanghai, [ 22 ]  Shanghai Blood Centre, also the  WHO  Collaborating Center for Blood Transfusion Services. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5575", "text": "The focus of the WBDD 2014 campaign was \u201cSafe blood for saving mothers\u201d. The goal of the campaign was to increase awareness about why timely access to safe blood and blood products is essential for all countries, as part of a comprehensive approach to prevent maternal deaths. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5576", "text": "According to the World Health Organization, 800 women die every day from pregnancy and childbirth-related complications. [ 23 ]  Severe bleeding is the cause of 34% of maternal deaths in Africa, 31% in Asia and 21% in Latin America and the Caribbean."}
{"_id": "WikiPedia_Hematology$$$corpus_5577", "text": "The global host for the WBDD 2014 event was  Sri Lanka . [ 24 ]  Through its  national blood transfusion service , Sri Lanka promotes voluntary unpaid donation to increase access to safe and sufficient blood and blood products."}
{"_id": "WikiPedia_Hematology$$$corpus_5578", "text": "The focus for the WBDD 2013 campaign \u2013 which marked the 10th anniversary of World Blood Donor Day \u2013 was blood donation as a gift that saves lives. The WHO encouraged all countries to highlight stories from people whose lives have been saved through blood donation, as a way of motivating regular blood donors to continue giving blood and people in good health who have never given blood, particularly young people, to begin doing so."}
{"_id": "WikiPedia_Hematology$$$corpus_5579", "text": "The host country for World Blood Donor Day 2013 was  France . Through its national blood service, the Etablissement Fran\u00e7ais du Sang (EFS), France has been promoting voluntary non-remunerated blood donation since the 1950s. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5580", "text": "The 2012 campaign focused on the idea that any person can become a hero [ 26 ]  by giving blood. Blood cannot yet be  manufactured artificially , so voluntary blood donation remains vital for healthcare worldwide. Many anonymous blood donors save lives every day through their blood donations. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5581", "text": "Youth For Blood  (YFB) is a youth-led, non-profit, and service motivated circle of youths devoted to the welfare of blood donors and seekers in Nepal. Established in 2011 in Biratnagar, it has extended its network to 13 different cities and is still growing. One of the main objective of the organization is to manage fresh blood for people in need for free: YFB has saved over 4500 lives by managing over 6000 pints of blood and 3000 standby donors. Currently, YFB has a network of more than 50,000 blood donors throughout Nepal, 15,000 of which are registered blood donors while the remaining are people who can be reached through social networks. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5582", "text": "Youth For Blood was established after a real event that took place with two college students named Saroj Karki and his friend Jogendra Urau. On the night of 27 May 2011, Jogendra Urau was in need of blood for his maternal uncle, who was suffering from  tuberculosis . He tried his best to manage blood for his uncle but could not succeed alone. He then made a call to his colleague Saroj Karki and asked for some help. Karki made many attempts to manage blood or a blood donor but he too was unsuccessful. After so many efforts, on next day, while Karki was travelling to his office, he met one of his colleagues named Dashrath Shah. Karki asked him about his blood group. In reply, Shah said he belongs to the same group that Urau's uncle needed. Next day while Shah was on his way to office, Karki met him. Karki described the entire situation to him. Shah, considering the sensitivity of the situation agreed to donate blood. Soon Shah donated blood. This was the first successful coordination of Youth For Blood but yet YFB was not officially registered. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5583", "text": "After managing blood for his friend\u2019s uncle, Saroj Karki felt a need an organization that hel. He realized that this could be one of the ways to serve the society and felt this must be made a campaign. Karki launched a Facebook page named  Youth For Blood  and started to facilitate blood for other needy people with the help of social media. The page helped conduct online facilitation of blood till the registration of Youth For Blood. After one month of solitary efforts, Karki shared this campaign in a group of 60 colleagues and asked to join him but only four colleagues in the group positively responded. After that, they actively continued the campaign. They started meeting regularly and also tried to persuade and influence others to come and join them. A young energetic service motive team full of determination, dedication formed. Due to the lack of resources, they held their meetings at different public places of Biratnagar like Aarohan Gurukul (a Theatre), Paropakar Ghat (a Graveyard), Shahid Rangasala (a Stadium), etc. Finally, at last they succeed to register themselves as a legal social organization with ad hoc President Nirmal Sharma. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5584", "text": "The  American Society of Hematology  ( ASH ) is a professional organization representing  hematologists , founded in 1958. Its annual meeting is held in December of every year and has attracted more than 30,000 attendees. [ 1 ]  The society publishes the  medical journal   Blood , the most cited peer-reviewed publication in the field, [ 2 ]  and  Blood Advances , an online, peer-reviewed open-access journal. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5585", "text": "The first official ASH meeting was held in  Atlantic City, New Jersey , in April 1958. More than 300 hematologists met together to discuss the key research and clinical issues related to blood and  blood diseases . Since the first gathering, ASH has been an important member in the development of hematology as a discipline. For more than six decades, ASH has sponsored its annual meeting. Today, ASH has more than 17,000 members, [ 4 ]  many of whom have made major advancements in understanding and treating blood diseases."}
{"_id": "WikiPedia_Hematology$$$corpus_5586", "text": "Held each year in December, the annual meeting brings together hematologists from around the world to discuss hematology. During the four-day meeting, several educational programs and scientific sessions are held. The annual meeting also features oral and poster presentations that are chosen by peer-reviewers from abstracts submitted prior to the meeting and contain developments in scientific research. Plenary symposia and named lectures on specialized areas of hematology are also presented throughout the meeting program. More than 21,000 clinicians, scientists, and others attend. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5587", "text": "ASH receives financial support from, and collaborates with, a number of  pharmaceutical companies . Notable corporate partners include  AbbVie ,  Amgen ,  AstraZeneca ,  Bayer ,  Bristol Myers Squibb ,  Eli Lilly and Company ,  Genentech ,  GlaxoSmithKline ,  Janssen Pharmaceuticals ,  Merck ,  Novo Nordisk ,  Pfizer ,  Regeneron Pharmaceuticals ,  Sanofi ,  Takeda Pharmaceuticals  and  Vertex Pharmaceuticals . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5588", "text": "The  American Society of Pediatric Hematology/Oncology  (abbreviated  ASPHO ) is an American multidisciplinary professional organization dedicated to improving care in the medical disciplines of  pediatric   hematology  and  oncology . [ 1 ]  As of 2018, it had 2,000 members. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5589", "text": "The American Society of Pediatric Hematology/Oncology was founded in 1981, largely because of the efforts of physician Carl Pochedly, who served as its secretary-treasurer for fourteen years. After holding meetings jointly with the  American Pediatric Society  and the  Society for Pediatric Research , the ASPHO held its first independent meeting in  Chicago ,  Illinois , in 1988. [ 3 ]  The society was incorporated in the state of Illinois in 1989. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5590", "text": "Since 2004, the official journal of ASPHO has been  Pediatric Blood & Cancer . Its official journal was originally the  Journal of Pediatric Hematology/Oncology , which was established by Pochedly in 1979 as the  American Journal of Pediatric Hematology/Oncology . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5591", "text": "The  British Society for Haematology  is a  registered charity  founded in 1960 for professionals specialising in  haematology , the medical specialism covering blood disorders including cancers. [ 1 ]  Apart from representing the interests of its members, it publishes the  British Journal of Haematology  and the  open-access journal   EJHaem , and issues guidelines on  haematological conditions . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5592", "text": "Full membership to the society is open to all but usually consists of senior haematology professionals, including consultants, senior lecturers, senior scientists and  Allied Health Professionals  at band 8b and above. Full membership also requires payment of an annual membership fee."}
{"_id": "WikiPedia_Hematology$$$corpus_5593", "text": "A reduced fee full membership is also available for established haematology professionals, including Specialty Trainees, Academic Clinical Fellows, residents of Low-and-Middle-Income Countries, Specialty Doctors, Post-doctoral researchers and scientists and Allied Health Professionals of bands 8a."}
{"_id": "WikiPedia_Hematology$$$corpus_5594", "text": "Associate membership is available for undergraduate and full-time post-graduate students,  foundation doctors , core trainees, IM trainees, STP trainees, nurses and allied health professionals up to and including Band 7. It is also available for retired professionals that wish to access the  British Journal of Haematology  or vote in Society elections. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5595", "text": "The  British Journal of Haematology  ( BJH ) is the official journal of the British Society for Haematology. The  BJH  is a  peer-reviewed medical journal  that has been in publication since 1955. The Journal publishes original  research papers  in clinical, laboratory and experimental haematology, helping clinicians and staff in the field keep up to date with the latest recommendations, developments, and protocols."}
{"_id": "WikiPedia_Hematology$$$corpus_5596", "text": "The BSH has launched an  open access journal ,  EJHaem , with Professor Andrew M Evens appointed as Editor-in-chief. This is the society's second official journal and is co-owned and published by  Wiley . This Gold Open Access journal aims to provide an additional home for those wishing to publish haematology research on an Open Access basis. The EJHaem accepts direct submissions, as well as content cascaded from the  British Journal of Haematology ."}
{"_id": "WikiPedia_Hematology$$$corpus_5597", "text": "The British Society for Haematology produces its  guidelines . These guidelines are written by expert consultants and clinical scientists currently practising in the UK. The guidelines provide up-to-date  evidence-based  guidance on the diagnosis and treatment of haematological diseases."}
{"_id": "WikiPedia_Hematology$$$corpus_5598", "text": "They provide three different styles of guidelines:"}
{"_id": "WikiPedia_Hematology$$$corpus_5599", "text": "BSH Guideline:  Evidence-based guidelines developed following a professional literature search and a review of the evidence by the writing group."}
{"_id": "WikiPedia_Hematology$$$corpus_5600", "text": "BSH Good Practice Paper:   Used to recommend good practice in areas where there is a less robust evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care."}
{"_id": "WikiPedia_Hematology$$$corpus_5601", "text": "BSH Position Paper:  The adoption and adaptation of a non-UK evidence-based guideline for use in the UK."}
{"_id": "WikiPedia_Hematology$$$corpus_5602", "text": "Annual Scientific Meeting"}
{"_id": "WikiPedia_Hematology$$$corpus_5603", "text": "Every year the BSH holds an annual scientific meeting (ASM) at different locations within the United Kingdom. The 2019 ASM was held at the  Scottish Event Campus  in Glasgow. The meetings usually host internationally renowned expert speakers, a range of sessions discussing specialist topics, and innovative debates. In addition to this, there is a call for abstracts from haematology professionals in which they apply to present their research at the meeting."}
{"_id": "WikiPedia_Hematology$$$corpus_5604", "text": "Other Events"}
{"_id": "WikiPedia_Hematology$$$corpus_5605", "text": "The BSH also frequently hosts a variety of courses and events. These courses and events are organized for  special interest groups  and trainee haematology students and professionals.  They permit the professional development of attendees and also provide a platform for discussion and networking opportunities."}
{"_id": "WikiPedia_Hematology$$$corpus_5606", "text": "BSH Grants"}
{"_id": "WikiPedia_Hematology$$$corpus_5607", "text": "The BSH provides grants to support hundreds of haematology professionals to attend international conferences, undertake research and advance haematology education.  There are grants provided for members only \u2013 open to members after one year of membership.\nThese grants include meeting support grants,  cohort study  grants (open to members with three years of membership), early-stage research start-up grants and  visiting fellow  grants. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5608", "text": "Other grants are open to all. These grants include Undergraduate support, ASM Travel Scholarships, and some Global Haematology Scholarships."}
{"_id": "WikiPedia_Hematology$$$corpus_5609", "text": "The  Canadian Hemophilia Society  ( CHS ) is a non-profit organization founded in 1953 whose mission is to lead the fight against inherited  bleeding disorders  by helping people affected live healthy lives while searching for a cure. [ 1 ]  The organization consists of chapters in every province in Canada, and a national organization direction to the provincial chapters. It is named for the blood disease  hemophilia ."}
{"_id": "WikiPedia_Hematology$$$corpus_5610", "text": "This article related to a non-profit organization is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5611", "text": "The  Department of Defense Serum Repository  (also referred to as the  DoD Serum Repository  or simply  DoDSR ) is a biological  repository  operated by the  United States   Department of Defense  containing over 50,000,000 human  serum  specimens, collected primarily from applicants to and members of the United States  Uniformed Services ."}
{"_id": "WikiPedia_Hematology$$$corpus_5612", "text": "The DoDSR is located in  Silver Spring ,  Maryland  and is operated by the\n Armed Forces Health Surveillance Center [ permanent dead link \u200d ]  (AFHSC), a subordinate of the  United States Army Center for Health Promotion and Preventive Medicine  ( USACHPPM ), itself evolved from the   Johns Hopkins School of Hygiene and Public Health . The DoDSR traces its origins to 1985 and the beginnings of the  United States Armed Forces   HIV  screening program (originally referred to as the  HTLV-III  screening program), when serum remaining after periodic laboratory testing of service members was retained first by the  Walter Reed Army Institute of Research  (WRAIR), then later systematically archived in the Army/Navy Serum Repository, the precursor to the DoDSR."}
{"_id": "WikiPedia_Hematology$$$corpus_5613", "text": "Today the DoDSR is among the largest serum repositories in the world, in terms of numbers of individuals represented, number of longitudinal specimens stored per individual, and total quantity of serum. The majority of specimens are linked to detailed medical and personnel data, creating a valuable resource for retrospective research and public health surveillance. The DoDSR's longitudinal serum, collected systematically from a large population, has enabled major contributions to understanding the etiology of many health conditions not otherwise amenable to prospective study, including  multiple sclerosis ,  schizophrenia ,  autoimmune diseases  and  cancer ."}
{"_id": "WikiPedia_Hematology$$$corpus_5614", "text": "The earliest serum housed in the DoDSR was collected through the Armed Forces' HLTV-III screening program, implemented in 1985 in response to the emergence of a new human  virus , subsequently known as  Human Immunodeficiency Virus  (HIV). Early laboratory testing was performed via contracted private laboratories. Screening soon expanded to all civilian applicants processed at  Military Entrance Processing Stations . A condition of some early laboratory testing contracts specified that remnant serum were to remain in frozen storage. In 1989, the  Army 's  Walter Reed Army Institute of Research  (WRAIR) awarded a contract to  McKesson  to consolidate and store accumulated residual serum specimens at a single facility, established in proximity to WRAIR in  Rockville ,  Maryland . The HIV Research Program (established by Congressional Direction in 1986), [ 1 ]  under the  WRAIR  Division of  Retrovirology , established the  Walter Reed  Army Serum Repository, which would evolve to become the Army/Navy Serum Repository in 1989. In 2001, the repository inventory was moved to its current location, a 25,000-square-foot (2,300\u00a0m 2 ) facility in  Silver Spring ,  Maryland . In recent years, the DoDSR has grown by approximately 1.9 [ 2 ] -2.3 [ 3 ]  million specimens annually. By 2007, the DoDSR inventory had grown to over 44 million specimens, [ 2 ]  and by the end of 2009, over 50,000,000 specimens. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5615", "text": "The DoDSR, along with its precursor repositories, were designated as the ultimate storage facility for all serologically negative HIV specimens obtained through military HIV testing programs. Growing initially through the routine screening of all civilian applicants, and then through the continued screening of retained military personnel (at approximate two year intervals), by 1990 the DoDSR inventory had grown to contain over six million serum specimens, and by 1996 over 17 million specimens. Standardized processes in place at the contracted military HIV testing laboratories ensured efficient management of the growing inventory, permitting the DoDSR to enforce standards in specimen labelling, configuration, and shipment of specimens which facilitated their physical integration into the DoDSR inventory. Contracts for HIV testing, negotiated by the individual military services, covered all specimens shipped from Military Treatment Facilities for HIV testing within the United States; for this reason unless specifically removed, serum from military beneficiaries (i.e. spouses and children) would also find their way into the DoDSR inventory."}
{"_id": "WikiPedia_Hematology$$$corpus_5616", "text": "Prompted by experiences in the aftermath of the  Persian Gulf War , including claims by many service members of  adverse health outcomes , the December, 1995 deployment of U.S. service members to  Bosnia  was accompanied by increased emphasis on health surveillance. [ 4 ]  A 1996  Assistant Secretary of Defense for Health Affairs  memorandum  [ 5 ]  mandated the collection of pre- and post-deployment serum specimens from deploying service members, and their integration into the DoDSR. The policy also directed that specimens collected for HIV surveillance could suffice. Although a small number of specimens were collected directly for health surveillance outside of existing HIV testing channels, specimens collected in this manner suffered from lack of standardization. By 1999, the Assistant Secretary of Defense issued modified instructions, [ 6 ]  which directed that the requirement for pre- and post-deployment specimens be satisfied by HIV testing. Initially, an HIV specimen was required to be collected prior to deployment if none had been collected in the year prior."}
{"_id": "WikiPedia_Hematology$$$corpus_5617", "text": "Concerns over the adequacy of specimens collected for this purpose, [ 7 ]  including findings of the Rhode Island Gulf War Commission, contributed to public concern over the adequacy of existing serum collection practices.  The FY2005 Defense Authorization Act [ 8 ]  called on the Department of Defense to perform"}
{"_id": "WikiPedia_Hematology$$$corpus_5618", "text": "[a]n assessment of whether there is a need for changes to regulations and standards for drawing blood samples for effective tracking and health surveillance of the medical conditions of personnel before deployment, upon the end of a deployment, and for a followup period of appropriate length."}
{"_id": "WikiPedia_Hematology$$$corpus_5619", "text": "Additionally, this legislation required DoD to change its policies to require collection of an HIV specimen within 120 days pre-deployment and 30 days post-deployment. This change was later rescinded in conjunction with the later recommendations of the  Armed Forces Epidemiological Board , to permit a sample collected within the year prior to deployment to meet requirements. [ 9 ]  Despite the many changes in policies, the large numbers of service members deploying in support of Operations  Iraqi Freedom  and  Enduring Freedom  have led to a moderate increase in the rate of specimen acquisition and growth of the DoDSR inventory."}
{"_id": "WikiPedia_Hematology$$$corpus_5620", "text": "The DoDSR has evolved from a research-affiliated repository limited to storing HIV seronegative specimens, to a repository serving a broad health surveillance mission for which it was not originally intended."}
{"_id": "WikiPedia_Hematology$$$corpus_5621", "text": "The first officially articulated purpose of the DoDSR is found in a 1991  WRAIR  solicitation for the management of the precursor to the DoDSR:"}
{"_id": "WikiPedia_Hematology$$$corpus_5622", "text": "Sera repository operations are required for retrospective studies in support of current and future retroviral research efforts ... Analysis of these sera will be very important."}
{"_id": "WikiPedia_Hematology$$$corpus_5623", "text": "The  WRAIR  solicitation anticipated as-needed specimen retrieval of up to 5,000 specimens per year."}
{"_id": "WikiPedia_Hematology$$$corpus_5624", "text": "In 1995, responsibility and custody of the DoDSR inventory and its associated database was transferred from  WRAIR  to a newly formed subordinate command of the  United States Army Medical Command , the  United States Army Center for Health Promotion and Preventive Medicine  (USACHPPM). USACHPPM, or simply CHPPM, itself evolved from the U.S. Army Industrial Hygiene Laboratory, which was initially established in 1942 at the beginning of  World War II  at the Johns Hopkins School of Hygiene, now the  Johns Hopkins Bloomberg School of Public Health . [ 10 ]  The change in custody was accompanied by an increased emphasis on the  epidemiologic ,  public health  and  health surveillance  utility of DoDSR specimens."}
{"_id": "WikiPedia_Hematology$$$corpus_5625", "text": "A DoD Instruction issued in 1997, since rescinded, described the purpose of the DoDSR as being for"}
{"_id": "WikiPedia_Hematology$$$corpus_5626", "text": "medical surveillance for clinical diagnosis and epidemiological studies. The repository shall be used exclusively for the identification, prevention, and control of diseases associated with operational deployments of military personnel."}
{"_id": "WikiPedia_Hematology$$$corpus_5627", "text": "A subsequent DoD Directive,  DoDD 6490.02E , expanded authorized uses of the DoDSR slightly:"}
{"_id": "WikiPedia_Hematology$$$corpus_5628", "text": "There shall be a Department of Defense Serum Repository for medical surveillance for clinical diagnosis and epidemiological studies. The repository shall be used for the identification, prevention, and control of diseases associated with military service."}
{"_id": "WikiPedia_Hematology$$$corpus_5629", "text": "Responding to concerns outlined in the  FY2005 Defense Authorization Act   Archived  2009-01-10 at the  Wayback Machine , the  Assistant Secretary of Defense for Health Affairs  requested the  Armed Forces Epidemiological Board  (AFEB) address three questions related to the mission and operation of the DoDSR:"}
{"_id": "WikiPedia_Hematology$$$corpus_5630", "text": "The AFEB study determined that there was sound basis for the continued collection of serum, but recommending the additional collection of  white blood cells  in addition to serum. The AFEB study also recommended that the DoD establish an oversight panel be created to govern access to the specimens. Neither recommendation has yet been acted on."}
{"_id": "WikiPedia_Hematology$$$corpus_5631", "text": "The DoDSR facility is located in 25,283 square feet (2,348.9\u00a0m 2 ) of leased commercial space in a 90,000-square-foot (8,400\u00a0m 2 ) building [ 11 ]  located at 11800 Tech Road, Silver Spring, Maryland. The leased space was acquired through a ten-year lease managed by the General Services Administration (GSA) which expires October 1, 2010. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5632", "text": "The commercial facility is shared with two other major tenants:  Holy Cross Hospital , [ 13 ]  and  Comcast , [ 11 ]  whose continued occupancy precludes contiguous expansion of the DoDSR inventory. Due to space constraints at the existing facility, relocation of the DoDSR inventory to another location in the  Baltimore  -  National Capital  region (including  Ft. Meade ,  Maryland ) was considered as early as 2005. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5633", "text": "Although AFHCS maintains technical and computing facilities supporting the DoDSR at the  Walter Reed Army Medical Center  (WRAMC),  Washington, D.C.   and is subject to realignment under the recommendations of the  Base Realignment and Closure  (BRAC) Commission, published BRAC recommendations do not specify a location to which the facilities must relocate. Relocation of the WRAMC AFHSC facilities are necessary by September 15, 2011. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5634", "text": "The DoDSR is operated by  Thermo Fisher Scientific  under a  no-bid  or \"sole-source\" contract [ 16 ]  awarded in 2006. An earlier no-bid contract was awarded to Cryonix in 2005, although Cryonix was later incorporated under Thermo Electron Corporation's Biorepository Services division [ 17 ]   Thermo Electron subsequently merged with  Fisher Scientific  in 2006.  Thermo Fisher's  Fisher BioServices  business currently holds the contract."}
{"_id": "WikiPedia_Hematology$$$corpus_5635", "text": "The DoDSR consists of 15 large walk-in freezers, each approximately 30 feet (9.1\u00a0m) x 30 feet x 10 high, [ 14 ]  whose interiors are maintained at -30\u00a0\u00b0C by pairs of compressors."}
{"_id": "WikiPedia_Hematology$$$corpus_5636", "text": "The majority of serum specimens are stored inside the walk-in freezers in cardboard boxes, approximately 6 x 18 x 3.5 inches (89\u00a0mm) in size, each containing 308 specimens, and each consisting of approximately 2.5 mL of frozen serum  [ 16 ]  The cardboard boxes are sequentially numbered and labeled, and stored on metal shelving units within the walk-in freezers for ready accessibility and retrieval."}
{"_id": "WikiPedia_Hematology$$$corpus_5637", "text": "Due to storage constraints, approximately 5.5 million specimens from two walk-in freezers were placed into \"high-density\" configuration in 2006, and additional reconfiguration may be required. The current operations contract calls for the contractor to\n \"adjust the storage configurations of specimens in one or more freezers to accommodate high-density, boxed specimen storage\" [ 16 ]  as required."}
{"_id": "WikiPedia_Hematology$$$corpus_5638", "text": "The majority of specimens are received quarterly in frozen form, following completion of all HIV testing. [ 18 ]  Shipments arrive in pallets transported in a freezer truck from the major contracted testing laboratory,  ViroMed , which is located in  Minnetonka ,  Minnesota ."}
{"_id": "WikiPedia_Hematology$$$corpus_5639", "text": "In 2008, the DoDSR procured a specialized freezer truck to transport specimens to the DoDSR, and solicited a bid for more frequent transport of specimens to the repository\n. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5640", "text": "DoDSR inventory data and related information are stored in an  Oracle  database referred to as the  Defense Medical Surveillance System  (DMSS), [ 20 ]  which serves as the \"sole link\" to the DoDSR inventory. [ 21 ]  Serum specimens are identified by a unique  specimen identification number , [ 22 ]  which for the majority of specimens are linked to the  Social Security Number  of the donor, [ 21 ]  and the date the specimen was obtained."}
{"_id": "WikiPedia_Hematology$$$corpus_5641", "text": "In addition to inventory data, DMSS also integrates select medical outcomes data available through the  Military Health System  (MHS), including  International Classification of Diseases, 9th Edition, Clinical Modification  (ICD-9CM)  diagnosis  codes,  Current Procedural Terminology  (CPT) codes, and other pertinent administrating data from inpatient and outpatient encountered provided directly by the MHS or through   Tricare   managed care  services."}
{"_id": "WikiPedia_Hematology$$$corpus_5642", "text": "Active duty  component service members (unlike service members in the  Reserve components ), are entitled to free (or nearly free) health care for the duration of their military service, the details of which are captured electronically in DMSS.  The active duty component thus constitutes a cohort where health events can be assessed longitudinally with minimal  ascertainment bias . Over half of the specimens in the DoDSR are traceable to service members who have been on active duty, and 75% of active duty service members have provided three or more longitudinal specimens."}
{"_id": "WikiPedia_Hematology$$$corpus_5643", "text": "Limited additional health and personnel data linked to DoDSR specimens include records of  immunizations , overseas  deployments , military assignment data, and records from pre- and post-deployment health assessments."}
{"_id": "WikiPedia_Hematology$$$corpus_5644", "text": "Significant additional  MHS  administrative and clinical data exist which are not integrated into DMSS. These include:"}
{"_id": "WikiPedia_Hematology$$$corpus_5645", "text": "Recent AFHSC solicitations have requested additional staff to address these data shortfalls. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5646", "text": "The Department of Defense, through the  Armed Forces Institute of Pathology  operates the AFIP Tissue Repository, which contains approximately 3 million case files and associated paraffin blocks, microscopic glass slides, and formalin-fixed tissue specimens from pathologic examinations occurring throughout the Military Health System. Thousands of cases are added to the repository each year. With the disestablishment of the AFIP under  Base Realignment and Closure , management of the Tissue Repository was to have been transferred to the  Uniformed Services University of the Health Sciences . [ 23 ]  However, Public Law 110-181 Section 722 [ 24 ]  directed the President to establish a Joint Pathology Center, which would subsume responsibility for the AFIP Tissue Repository. A Joint Pathology Center Working Group Concept of Operations stated that:"}
{"_id": "WikiPedia_Hematology$$$corpus_5647", "text": "The JPC ... will provide maintenance/modernization of the Tissue Repository in support of the mission of the DoD and other federal agencies."}
{"_id": "WikiPedia_Hematology$$$corpus_5648", "text": "In its review of the JPC Working Group Concept of Operations, the  Defense Health Board  emphasized that:"}
{"_id": "WikiPedia_Hematology$$$corpus_5649", "text": "Every effort must be pursued to guarantee that the Tissue Repository is preserved, implements world-class modernization, and is utilized appropriately. A recent independent report by  Asterand  (Detroit, MI) submitted to  Uniformed Services University of the Health Sciences  found the repository to have a commercial value of $3.0-$3.6 Billion ..."}
{"_id": "WikiPedia_Hematology$$$corpus_5650", "text": "Despite the utility of linking AFIP Tissue Repository specimens to longitudinal pre-diagnostic serum available in the DoDSR, no formal linkage of the AFIP Tissue Repository inventory has yet been made to DMSS or to the DoDSR. No estimate is yet available on the potential commercial value of such a formal linkage."}
{"_id": "WikiPedia_Hematology$$$corpus_5651", "text": "Requests for access to DoDSR specimens are governed by  guidelines  developed by the Armed Forces Health Surveillance Center. According to guidelines,  \" [t]he Director of the repository is solely responsible for authorizing releases of specimens from the repository.\" [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5652", "text": "DoDSR specimens may only be released to principal investigators outside the Department of Defense for purposes of medical research if the proposed study has  \"a coinvestigator who is assigned to the Department of Defense and is knowledgeable, responsible, and accountable for all aspects of the study's design and execution (including data management, analysis, interpretation, and reporting of results). \" [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5653", "text": "Serum from the DoDSR may be requested by clinicians within the Military Health System to aid diagnosis and guide clinical management. Serum may also be released to clinicians outside the Military Health System provided a physician in the Military Health System in the same specialty as the requestor validates the clinical relevance of the requested use prior to the release of any serum. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5654", "text": "Serum specimens from the DoDSR may be used for criminal investigations and prosecutions if directed by the  Assistant Secretary of Defense for Health Affairs . [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5655", "text": "DoDSR specimens are collected without informed consent, and specimen donors are not informed of the use of their specimens in subsequent studies. Specimens retrieved by the DoDSR for use in external research studies are, with rare exceptions,  deidentified  prior to being sent to outside investigators."}
{"_id": "WikiPedia_Hematology$$$corpus_5656", "text": "A 1996  memorandum [ permanent dead link \u200d ]  specifically stated that DoDSR specimens collected for pre- and post-deployment health surveillance  \"will not be used for any genetics related testing\" . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5657", "text": "As a result of clinically indicated HIV testing performed on civilians and family beneficiaries at Military Treatment Facilities (eligible for health care within the Military Health System), approximately 900,000 serum specimens from individuals not directly affiliated with the Uniformed Services through application or service are also stored in the DoDSR. [ 29 ]  In Privacy Act documentation, DoD acknowledges that the AFHSC maintains \"... \u00a0 specimen collections (remaining serum from blood samples) from which serologic tests can be performed \u00a0 ...\" from categories of individuals which include \"Department of Defense military personnel (active and reserve) and their family members \u00a0 ...\". [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5658", "text": "DoDSR guidelines are silent as to whether a mechanism exists for specimen donors to request destruction or removal of their specimens from the repository. [ 31 ]   In Privacy Act documentation, DoD states that \"[r]ecords are destroyed when no longer needed for reference and for conducting business\", but no formal mechanism is articulated for the destruction or specimens. [ 30 ]  This is in contrast to the  Armed Forces Institute of Pathology   DNA  Repository (also known as the Repository of Specimen Samples for the Identification of Remains) which articulates a  mechanism  for donors to request the destruction of their specimens following separation from service. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5659", "text": "On May 1, 2009, during the early stages of the  2009 H1N1 flu outbreak , an unpublished  RAND  study, originally commissioned in 2006 by  USACHPPM  was published in its entirety on  WikiLeaks . The leaked documents [ 33 ]  included a justification for the $500,000 contract cost, directly authorized by former  Surgeon General of the United States Army   Kevin C. Kiley  on August 4, 2006, which stated the study and its 12-month timetable for delivery was necessary"}
{"_id": "WikiPedia_Hematology$$$corpus_5660", "text": "... to describe the current and future capabilities of the Department of Defense Serum Repository to assist with the early identification and response to an influenza pandemic. Adequate resources are not available in-house to perform these analyses in sufficient time to prepare for a pandemic ..."}
{"_id": "WikiPedia_Hematology$$$corpus_5661", "text": "Despite the leaked study draft's publication date of May 2008, at the time of the leak and outbreak in May 2009, RAND listed the study as a \"current project\", noting in its description that \"the threat of an emerging human pandemic [has] highlighted the importance of a comprehensive U.S. Armed Forces health surveillance architecture\". [ 34 ]  Around the time of the leaked documents' appearance on WikiLeaks, the lead author of the unpublished  RAND  study published an op-ed piece [ 35 ]  in  The Baltimore Sun  describing the control of the outbreak a concern of \"national security\", and highlighting the need to \"marshal the best ... institutional strengths ... to prevent, detect and respond effectively to this latest infectious disease\"."}
{"_id": "WikiPedia_Hematology$$$corpus_5662", "text": "The  European Hematology Association  ( EHA ) is a non-governmental and not-for-profit membership organization that is guided by its mission to promote excellence in patient care, research, and education in hematology."}
{"_id": "WikiPedia_Hematology$$$corpus_5663", "text": "The European Hematology Association (EHA) was officially established in 1992. [ 1 ]  EHA is a global platform for excellence in hematology, focusing on blood, blood cells, and blood disorders such as leukemia, lymphoma, hemophilia, anemia and thrombosis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5664", "text": "HemaSphere  ( ISSN \u00a0 2572-9241 ) is the official open access journal of the European Hematology Association. [ 2 ]  The journal publishes basic, translational and clinical research as well as review articles with recommendations for future research and clinical applications. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5665", "text": "The  International Council for Standardization of Hematology  (ICSH) was originally known as the International Committee for Standardization in Hematology and was initiated by the  European Society of Hematology  (ESH) in 1963, as a standardization committee [1]. In 1964 it was formally ratified as an organization during a meeting of the International Society of Hematology (ISH), in Stockholm. The ICSH is a  non-governmental organization  recognized as having formal relations with the  World Health Organization  (WHO) and is a  non-profit organization . The underlying goal of ICSH is to obtain reliable and repeatable results in the laboratory, mainly involving diagnostic haematology. All guidelines and recommendations now include the appropriate level of evidence. ICSH Working Groups review laboratory methods and tools for blood analysis, consider standardization issues, and promote and coordinate scientific work in the development of international standardized materials and guidelines."}
{"_id": "WikiPedia_Hematology$$$corpus_5666", "text": "1. McFadden S, Briggs C, Davis B, Jou J, Machin S. The reformed International Council for Standardization in Hematology (ICSH). Int Jnl Lab Hem 2008; 30: 89-90."}
{"_id": "WikiPedia_Hematology$$$corpus_5667", "text": "2. Lewis SM. International Council for Standardization in Haematology \u2013 The first 40 years. Int Jnl Lab Hem 2009; 31: 253-67."}
{"_id": "WikiPedia_Hematology$$$corpus_5668", "text": "3. Lee SH, Machin SJ. Years of the ICSH: 1964 to 2014. Int Jnl Lab Hem 2014; 36: 589-90."}
{"_id": "WikiPedia_Hematology$$$corpus_5669", "text": "4. Lewis, S. M. (24 April 2009). \"Standardization and harmonization of the blood count: The role of International Committee for Standardization in Haematology (ICSH)\". European Journal of Haematology. 45 (S53): 9\u201313. doi:10.1111/j.1600-0609.1990.tb01520.x."}
{"_id": "WikiPedia_Hematology$$$corpus_5670", "text": "5. Davis, Bruce H.; Jungerius, Bart (April 2010). \"International Council for Standardization in Haematology technical report 1-2009: new reference material for haemiglobincyanide for use in standardization of blood haemoglobin measurements\". International Journal of Laboratory Hematology. 32 (2): 139\u2013141. doi:10.1111/j.1751-553x.2009.01196.x."}
{"_id": "WikiPedia_Hematology$$$corpus_5671", "text": "6. Zini G, Kern W, Brereton M, Stephens AD. ICSH: on board for new projects. Int Jnl Lab Hem 2014; 36: 306-12"}
{"_id": "WikiPedia_Hematology$$$corpus_5672", "text": "7.Mackie I, Erber WN. The International Council for Standardization in Haematology: 1964-2021. Int Jnl Lab Hematol 2021; 43: 884-5."}
{"_id": "WikiPedia_Hematology$$$corpus_5673", "text": "The  International Society for Laboratory Hematology  (ISLH) is a  non-profit organization  founded in 1992. Its purpose is to provide a forum for the  dissemination  of new ideas and information related to the field of laboratory  hematology . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5674", "text": "In 1984, Dr. Berend Houwen began to organize meetings that brought together  scientists ,  manufacturers ,  clinicians , and  regulatory  representatives to exchange ideas on technical innovations in laboratory  hematology . The first meeting was held in  Banff, Alberta , Canada."}
{"_id": "WikiPedia_Hematology$$$corpus_5675", "text": "At the time of incorporation, the founding members agreed to start a new journal for the publication of research and review articles in the broadening arena of laboratory hematology. In 2003, this journal,  Laboratory Hematology , began to be officially indexed by the  National Center for Biotechnology Information . [ 2 ]  The current journal,  The International Journal of Laboratory Hematology , is the official journal of the ISLH. [ 3 ]  It provides an international forum for new developments in the practice and research of laboratory hematology and includes invited  reviews , original articles, research results, [ 4 ]  and correspondence. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5676", "text": "In 2001, the organization published the first flow-based reference method for  platelet  counting. [ 6 ]  In 2005, it published a document titled  The International Consensus Group for Hematology Review: Suggested Criteria for Action Following Automated CBC and White Blood Cell Differential Analysis . [ 3 ] [ 7 ]  This publication gathered 20 hematology laboratorians from around the globe to share their views on the slide review. After its publication, ISLH also maintains affiliation with the International Committee for Standardization in Hematology (ICSH), and sponsors review studies in its field. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5677", "text": "ISLH has also expanded its focus to include a number of sub-disciplines related to laboratory hematology, including cellular analysis,  flow cytometry ,  hemostasis  and  thrombosis ,  molecular diagnostics , hematology informatics,  hemoglobinopathies ,  hemolytic anemias ,  point-of-care testing , [ 9 ]  and standards and guidelines. ISLH addresses these with symposia, research, and journal reviews. As of 2015, the ISLH has about 900 members from more than 50 countries. [ 10 ] The society organizes annual international  scientific meetings  held in the  United States ,  Europe  or  Asia . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5678", "text": "The meeting, held annually in the spring, brings together laboratory  hematologists  from around the world to discuss critical issues in laboratory hematology. The symposium features a combination of invited speakers, oral and  poster presentations , and commercial exhibits/workshops."}
{"_id": "WikiPedia_Hematology$$$corpus_5679", "text": "The  Society for Hematology and Stem Cells  (formerly the  International Society for Experimental Hematology ) is a  learned society  which deals with  hematology , the study of the blood system and its diseases, including those caused by exposure to nuclear radiation. It was founded in 1950, and held its first official meeting in  Milwaukee  in 1972. [ 1 ]  Its mission statement is:  \"To promote the scientific knowledge and clinical application of basic hematology, immunology, stem cell research, cell and gene therapy and related aspects of research through publications, discussions, scientific meetings and the support of young investigators.\" [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5680", "text": "Dr.  Margaret Goodell  of the Baylor College of Medicine's Center for Cell and Gene Therapy is the current president. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5681", "text": "At the opening ceremony of the 30th annual meeting of ISEH, Emperor  Akihito  of  Japan  praised the \"remarkable results obtained by the ISEH today in the treatment of radiation-related disorders\", by contrast to the lack of any effective treatment for such disorders in 1945 when atomic bombs were dropped on  Hiroshima  and  Nagasaki . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5682", "text": "The society has an official journal,  Experimental Hematology , which has an  impact factor  of 2.907."}
{"_id": "WikiPedia_Hematology$$$corpus_5683", "text": "This template is used to identify a  hematology  stub. It uses {{ asbox }}, which is a meta-template designed to ease the process of creating and maintaining stub templates."}
{"_id": "WikiPedia_Hematology$$$corpus_5684", "text": "Typing  {{Hematology-stub}}  produces the message shown at the beginning, and adds the article to the following category:"}
{"_id": "WikiPedia_Hematology$$$corpus_5685", "text": "This is a  stub template . A brief explanation of these templates follows; for full details please consult  Wikipedia:Stub ."}
{"_id": "WikiPedia_Hematology$$$corpus_5686", "text": "A stub is an article containing only a few sentences of text which is too short to provide encyclopedic coverage of a subject."}
{"_id": "WikiPedia_Hematology$$$corpus_5687", "text": "Further information can be found at:"}
{"_id": "WikiPedia_Hematology$$$corpus_5688", "text": "New stub templates and categories (collectively \"stub types\") should not be created without prior proposal at  Wikipedia:WikiProject Stub sorting/Proposals . This allows for the proper coordination of all stub types across Wikipedia, and for the checking of any new stub type for possible problems prior to its creation."}
{"_id": "WikiPedia_Hematology$$$corpus_5689", "text": "Activated protein C\u2013protein C inhibitor  ( APC-PCI ) is a complex of  activated protein C  (APC) and  protein C inhibitor  (PCI). [ 1 ] [ 2 ] [ 3 ]  It has been measured in  coagulation testing  to evaluate  coagulation ,  thrombosis , and other  cardiovascular complications . [ 2 ] [ 3 ] [ 4 ]  It is a  marker  of  thrombin generation  and indicates  hypercoagulability . [ 1 ] [ 5 ]  The  half-life  of APC-PCI is either 40 minutes or 140 \u00a0 minutes. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5690", "text": "Ethinylestradiol -containing  birth control pills  have been found to increase levels of APC-PCI to a similar degree as  thrombin\u2013antithrombin complex  (TAT) and to a greater extent than  D-dimer . [ 5 ]  However, only APC-PCI was able to differentiate between a second- and third-generation birth control pill. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5691", "text": "Another complex related to APC-PCI is the  activated protein C\u2013\u03b1 1 -antitrypsin  (APCAT) complex. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5692", "text": "Acute posthemorrhagic anemia  or  acute blood loss anemia  is a condition in which a person quickly loses a large volume of circulating hemoglobin. Acute blood loss is usually associated with an incident of trauma or a severe injury resulting in a large loss of blood. It can also occur during or after a surgical procedure. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5693", "text": "Bisalbuminemia  is the, sometimes inherited, condition of having two types of  serum albumin  that differ in mobility during  electrophoresis . It can be seen in  densitometry  as a bifid mountain where albumin has 2 heads. Inherited bisalbuminemia has no pathologic effects, but is of interest to researchers who study the evolution and functional changes in the protein. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5694", "text": "Jeannie Callum  is a  transfusion medicine  specialist and  hematologist  in Ontario, Canada. [ 1 ]  She is also a professor at the  University of Toronto  and  Queen's University . [ 2 ]  She was the co-principal investigator of the CONCOR [ 3 ]  trial, an international  randomized controlled trial  evaluating the use of  convalescent plasma  for the treatment of  COVID-19 infection . [ 2 ] [ 4 ]  She was lead editor for  Bloody Easy 4: Blood Transfusions, Blood Alternatives and Transfusion Reactions, fourth edition  a handbook in transfusion medicine for the province of Ontario. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5695", "text": "This biography related to medicine in Canada is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5696", "text": "Clotting time  is a general term for the time required for a sample of  blood  to form a clot, or, in medical terms,  coagulate . The term \"clotting time\" is often used when referring to tests such as the  prothrombin time (PT) , activated  partial thromboplastin time  (aPTT or PTT),  activated clotting time  (ACT),  thrombin time  (TT), or  Reptilase time . These tests are coagulation studies performed to assess the natural clotting ability of a sample of blood. In a clinical setting, healthcare providers will order one of these tests to evaluate a patient's blood for any abnormalities in the time it takes for their blood to clot. [ 1 ]  Each test involves adding a specific substance to the blood and measuring the time until the blood forms fibrin which is one of the first signs of clotted blood. [ 2 ]  Each test points to a different component of the clotting sequence which is made up of coagulation factors that help form clots. Abnormal results could be due to a number of reasons including, but, not limited to, deficiency in clotting factors, dysfunction of clotting factors, blood-thinning medications, medication side-effects, platelet deficiency, inherited bleeding or clotting disorders, liver disease, or advanced illness resulting in a medical emergency known as  disseminated intravascular coagulation  (DIC). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5697", "text": "There are various methods for determining the  clotting  time, the prototype historical method being the  capillary  tube method. [ 4 ]  It is affected by calcium ion levels and many diseases. The normal range of clotting times is 2-8 minutes."}
{"_id": "WikiPedia_Hematology$$$corpus_5698", "text": "For the measurement of clotting time by the test tube method, blood is placed in a glass test tube and kept at 37\u00b0C. The required time for the blood to clot is measured. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5699", "text": "There are several other methods, including testing for those on  blood thinners , such as  heparin  or  warfarin . Activated  partial thromboplastin time  (aPTT) is used for heparin studies and the  normal range  is 20\u201336 seconds, depending upon which type of activator is used in the study. [ 6 ]   Prothrombin time  (PT) is used for warfarin studies and the normal values differ for men and women. Adult male PT normal range is 9.6\u201311.8 seconds, while adult females' normal range is 9.5\u201311.3 seconds. [ 6 ]  Internationalized normalized ratio (INR) is also a warfarin study, with therapeutic ranges of 2\u20133 for standard warfarin and 3\u20134.5 for high-dose warfarin. [ 6 ]  In a  veterinary  study of  bovine animals , the mean ACT was 145 seconds with a range of 120\u2013180 seconds. Standard deviations were 18 and 13 for the first and second sampling, respectively. Repeatability of the ACT was acceptable. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5700", "text": "Coagulation activation markers  are  biomarkers  of net activation of  coagulation  and  fibrinolysis . [ 1 ] [ 2 ]  Examples include  prothrombin fragment 1+2  (F1+2),  thrombin\u2013antithrombin complex  (TAT),  fibrinopeptide A  (FpA),  fibrin monomers  (FMs),  plasmin-\u03b1 2 -antiplasmin complex  (PAP),  activated protein C\u2013protein C inhibitor  (APC-PCI), and  D-dimer  (DD). [ 1 ] [ 2 ]  These compounds are markers of  thrombin generation  (F1+2, TAT, APC-PCI),  fibrin generation  (FpA, FMs), and fibrinolysis (DD, PAP). [ 1 ] [ 2 ]  Coagulation activation markers, particularly D-dimer, are useful in the  diagnosis  of acute  venous thromboembolism . [ 1 ] [ 3 ]  They may also be useful in the assessment of  hypercoagulability  and venous thromboembolism risk. [ 4 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5701", "text": "Levels of coagulation activation markers are increased with  pregnancy , [ 7 ]  with  estrogen -containing  birth control pills , [ 8 ]  with  menopausal hormone therapy , [ 9 ] [ 6 ]  and with high-dose  parenteral   estradiol  therapy for  prostate cancer . [ 10 ] [ 11 ] [ 12 ]   Transdermal  estradiol appears to have less influence on coagulation activation markers than  oral  estrogens in menopausal hormone therapy. [ 9 ]   Birth control pills containing estradiol  or  estetrol  also appear to have less influence on coagulation activation markers than  ethinylestradiol -containing birth control pills. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5702", "text": "Markers of  platelet activation  ( primary hemostasis ) include  platelet factor 4  (PF4),  \u03b2-thromboglobulin  (\u03b2-TG), and  P-selectin . [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5703", "text": "The  Defense Blood Standard System  ( DBSS ) is a  FDA -regulated,  Class II Medical Device  designed to handle  blood collection , processing and tracking procedures, and automation of standards and safeguards for the  Military Health System  (MHS) blood supply. [ 1 ]  It is identified by the FDA as a Blood Establishment Software item."}
{"_id": "WikiPedia_Hematology$$$corpus_5704", "text": "The DBSS supports the Armed Services Blood Program Office, which manages the blood program for the  Department of Defense , and services more than 8.7 million MHS beneficiaries."}
{"_id": "WikiPedia_Hematology$$$corpus_5705", "text": "Hal Downey  (1877\u20131959) [ 1 ]  was an American  hematologist . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5706", "text": "In 1923, he contributed to the characterization of  reactive lymphocytes , which are sometimes called \"Downey cells\". [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5707", "text": "This biographical article related to medicine in the United States is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5708", "text": "Gene therapy for blood diseases  is a novel field of  research  investigating ways in which components of  blood  can be  genetically modified  to treat  hematologic diseases . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5709", "text": "Source: [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5710", "text": "CAR T-cell therapy is a type of personalized  cancer immunotherapy  designed to strengthen the patient\u2019s own  immune system  to better fight cancer. The process begins by extracting  T-cells , a type of immune cell, from an individual patient\u2019s blood. The surface of cancer cells contains unique markers called  antigens . The patient\u2019s T-cells are genetically modified in laboratories to include chimeric antigen receptors (CARs). The CARs are designed to recognize the specific cancer antigens and bind to them, allowing T-cells to target and attack the cancer cells. The genetically modified T-cells are administered back to the patients as a treatment."}
{"_id": "WikiPedia_Hematology$$$corpus_5711", "text": "Leukemia is a group of blood cancers commonly found in children younger than 15 and elders older than 55. [ 3 ]  In 2017,  tisagenlecleucel (Kymriah\u2122) , [ 2 ]  the first CAR-T cell therapy approved by the  FDA , became available to anyone up to the age of 25 with  acute lymphoblastic leukemia  (ALL). Until 2022, a total of six CAR-T therapies have been approved by the FDA, all of which target blood cancers. [ 4 ]  These CAR-T therapies have been shown to have high efficacy in eradicating leukemia cancer, including in patients with advanced-stage, treatment-resistant ( refractory ) or returned ( relapsed ) leukemia. [ 5 ]  They also have a high  remission  rate in comparison to other traditional  cancer treatments . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5712", "text": "Patients in the U.S. suffering from sickle cell disease can now receive targeted  gene therapies  using  hematopoietic stem cells . [ 6 ]  Hematopoietic stem cells are stem cells which differentiate and give rise to  red blood cells ,  white blood cells  and  platelets . [ 7 ]  These therapies involve removing hematopoietic stem cells from the patient and making specific edits to the genome of the hematopoietic stem cells. These edits in the genome of the hematopoietic stem cells are to reverse the effects of sickle cell disease. The cells are then re-administered into the patient. The hematopoietic stem cells are then able to produce red blood cells with the factors which promote proper red blood cell shape reducing the effects of sickle cell disease."}
{"_id": "WikiPedia_Hematology$$$corpus_5713", "text": "Beta thalassemia is a heritable disorder, characterized by the inability to make  beta globin protein , and in turn reduced functioning of  hemoglobin  (which beta globin is a part of). [ 8 ]  In December 2023, the  European Medicines Agency  recommended approval for a cell based gene therapy that works through the  CRISPR/Cas9  system. The therapy known as Casgevy [ 9 ]  works through editing a dysfunctional protein that interferes with creation of  adult hemoglobin . This gene is known as the  BCL11A , and when people have Beta thalassemia, their bodies do not make enough adult hemoglobin. Casgevy uses precise gene editing of stem cells, and reduces the activity of  BCL11A . With the subsequent reduction of adult hemoglobin,  fetal hemoglobin  (HbF) genes are turned back on, allowing the cells to produce enough hemoglobin. Typically, the body stops making fetal hemoglobin around 6 months of age, and starts making adult hemoglobin. [ 10 ]  These serve similar functions, however fetal hemoglobin has a higher binding affinity for  oxygen  than adult hemoglobin, but both are functional at transporting oxygen in the body. [ 10 ]  Stem cells edited by Casgevy are then  transfused  back into the body where they can create more HbF and therefore make more functional red blood cells that have this edit. With this therapy, patients who would regularly need  blood transfusions  can now produce enough hemoglobin for themselves. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5714", "text": "Human immunodeficiency virus  (HIV) is a disease that, once contacted, attacks cells that are necessary to fight off  infections . It can be transmitted in many different ways, including through sexual contact, blood contamination, the sharing of needles, or from mother to infant. [ 12 ]  If left untreated, HIV can result in  acquired immunodeficiency syndrome  (AIDS). [ 13 ]  HIV weakens an individual\u2019s  immune system , leading to increased risk of fatal infections and cancers. [ 14 ]  In 2023, around 40 million people globally were living with HIV. [ 15 ]  Despite options available for the treatment and management of HIV (e.g.,  highly active antiretroviral therapy ; HAART), they come with limitations including the need for indefinite daily treatment. [ 16 ]  Attempts to generate a long-term HIV-resistant immune system have been promising with results from a case report of a patient who developed  acute myeloid leukemia  after HIV infection. [ 17 ]  Previously, researchers had found a version of a  gene  (an  allele ) that was resistant to HIV. These researchers therefore found a donor who had two copies of this allele ( homozygous ) and extracted their stem cells in an attempt to produce HIV resistance in the patient with acute myeloid leukemia. After stem cell transplantation from this donor, the patient tested and remained HIV-negative at 20 months post-transplantation and was able to discontinue use of antiviral therapies. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5715", "text": "This article about  biological engineering  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5716", "text": "Monocytopoiesis  is the process which leads to the production of  monocytes  (and, subsequently,  macrophages )."}
{"_id": "WikiPedia_Hematology$$$corpus_5717", "text": "It can be induced by  macrophage colony-stimulating factor . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5718", "text": "It is a component of  myelopoiesis . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5719", "text": "In  hematology ,  myelopoiesis  in the broadest  sense  of the term is the production of  bone marrow  and of all  cells  that arise from it, namely, all  blood cells . [ 1 ]  In a narrower sense, myelopoiesis also refers specifically to the regulated formation of  myeloid  leukocytes ( myelocytes ), including  eosinophilic granulocytes ,  basophilic granulocytes ,  neutrophilic granulocytes , and  monocytes . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5720", "text": "The  common myeloid progenitor  can  differentiate  in the bone marrow into  red blood cells  and  megakaryocytes  (leading to  platelets ) as well as  mast cells  and  myeloblasts , the latter leading to the  myelocytic  line ( granulocytes ) and to  monocytes ,  macrophages , and  dendritic cells  of the  innate immune system . The granulocytes, also called polymorphonuclear leukocytes because of their multilobed nuclei, are three short lived cell types including  eosinophils ,  basophils , and  neutrophils . A granulocyte differentiates into a distinct cell type by a process called  granulopoiesis . In this process it first transforms from a common  myeloblast  (myeloid progenitor) to a common promyelocyte. This promyelocyte gives rise to a unique myelocyte that for the first time can be classified as an eosinophil, basophil, or neutrophil progenitor based on the histological staining affinity (eosinophilic, basophilic, or neutral granules). [ 3 ]  The unique myelocyte next differentiates into a metamyelocyte and then a  band cell , with a C-shaped nucleus, before becoming a mature eosinophil, basophil, or neutrophil. Macrophages come from monoblast progenitors that differentiate into  promonocytes , which mature into  monocytes . Monocytes eventually enter the tissues and become  macrophages . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5721", "text": "Plasmin-\u03b12-antiplasmin complex  ( PAP ) is a 1:1 irreversibly formed inactive complex of the  enzyme   plasmin  and its inhibitor  \u03b1 2 -antiplasmin . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  It is a marker of the activity of the  fibrinolytic  system and a marker of net activation of  fibrinolysis . [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5722", "text": "PAP levels are increased with  pregnancy [ 7 ]  and by  ethinylestradiol -containing  combined birth control pills . [ 5 ]  Conversely, levels of PAP do not appear to be affected with  menopausal hormone therapy . [ 6 ]  PAP levels have been reported to be elevated in men with  prostate cancer . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5723", "text": "Bone marrow  is a semi-solid  tissue  found within the  spongy  (also known as cancellous) portions of  bones . [ 2 ]  In birds and mammals, bone marrow is the primary site of new  blood cell  production (or  haematopoiesis ). [ 3 ]  It is composed of  hematopoietic cells ,  marrow adipose tissue , and supportive  stromal cells . In adult humans, bone marrow is primarily located in the  ribs ,  vertebrae ,  sternum , and  bones of the pelvis . [ 4 ]  Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73\u00a0kg (161\u00a0lbs) will have around 3.7\u00a0kg (8\u00a0lbs) of bone marrow. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5724", "text": "Human marrow produces approximately 500 billion blood cells per day, which join the  systemic circulation  via permeable  vasculature   sinusoids  within the  medullary cavity . [ 6 ]  All types of  hematopoietic cells , including both  myeloid  and  lymphoid lineages , are created in bone marrow; however, lymphoid cells must migrate to other  lymphoid organs  (e.g.  thymus ) in order to complete maturation."}
{"_id": "WikiPedia_Hematology$$$corpus_5725", "text": "Bone marrow transplants  can be conducted to treat severe diseases of the bone marrow, including certain forms of  cancer  such as  leukemia . Several types of stem cells are related to bone marrow.  Hematopoietic stem cells  in the bone marrow can give rise to hematopoietic lineage cells, and  mesenchymal stem cells , which can be isolated from the primary culture of bone marrow stroma, can give rise to bone,  adipose , and  cartilage  tissue. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5726", "text": "The composition of marrow is dynamic, as the mixture of cellular and non-cellular components (connective tissue) shifts with age and in response to systemic factors. In humans, marrow is colloquially characterized as \"red\" or \"yellow\" marrow ( Latin :  medulla ossium rubra ,  Latin :  medulla ossium flava , respectively) depending on the prevalence of hematopoietic cells vs  fat cells .  While the precise mechanisms underlying marrow regulation are not understood, [ 6 ]  compositional changes occur according to stereotypical patterns. [ 8 ]  For example, a newborn baby's bones exclusively contain hematopoietically active \"red\" marrow, and there is a progressive conversion towards \"yellow\" marrow with age. In adults, red marrow is found mainly in the  central skeleton , such as the  pelvis ,  sternum ,  cranium ,  ribs ,  vertebrae  and  scapulae , and variably found in the proximal  epiphyseal  ends of  long bones  such as the  femur  and  humerus . In circumstances of chronic hypoxia, the body can convert yellow marrow back to red marrow to increase blood cell production. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5727", "text": "At the cellular level, the main functional component of bone marrow includes the progenitor cells which are destined to mature into blood and lymphoid cells. Human marrow produces approximately 500 billion blood cells per day. [ 10 ]  Marrow contains  hematopoietic stem cells  which give rise to the three classes of blood cells that are found in circulation:  white blood cells  (leukocytes),  red blood cells  (erythrocytes), and  platelets  (thrombocytes). [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5728", "text": "The  stroma  of the bone marrow includes all tissue not directly involved in the marrow's primary function of  hematopoiesis . [ 6 ]  Stromal cells may be indirectly involved in hematopoiesis, providing a microenvironment that influences the function and differentiation of hematopoietic cells. For instance, they generate  colony stimulating factors , which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include:"}
{"_id": "WikiPedia_Hematology$$$corpus_5729", "text": "That bone marrow is a priming site for  T-cell  responses to blood-borne  antigens  was first described in 2003. [ 13 ]  Mature circulating na\u00efve T cells home to bone marrow sinuses after they have passed through arteries and arterioles. [ 14 ]  They transmigrate sinus endothelium and enter the parenchyma which contains  dendritic cells  (DCs). These have a capacity of antigen uptake, processing, and presentation. [ 13 ]  Cognate interactions between antigen-specific T cells and antigen-presenting DCs (APCs) in parenchyma lead to rapid T-APC cluster formation followed by T cell activation, T cell proliferation and T cell re-circulation to blood. [ 13 ]  These findings were corroborated and extended in 2013 by in situ two-photon dynamic imaging of mice skulls. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5730", "text": "Bone marrow is a nest for migratory memory T cells [ 16 ]  and a sanctuary for plasma cells. [ 17 ]  This has implications for adaptive immunity and vaccinology. [ 17 ]  Memory B and T cells persist in the parenchyma in dedicated survival niches organized by stromal cells. [ 18 ]  This memory can be maintained over long time periods in the form of quiescent cells [ 18 ]  or by repeated antigenic restimulation. [ 19 ]  Bone marrow protects and optimizes immunological memory during dietary restriction. [ 20 ]  In cancer patients, cancer-reactive memory T cells can arise in bone marrow spontaneously or after specific vaccination. [ 21 ]  Bone marrow is a center of a variety of immune activities: i) hematopoiesis, ii) osteogenesis, iii) immune responses, iv) distinction between self and non-self antigens, v) central immune regulatory function, vi) storage of memory cells, vii) immune surveillance of the central nervous system, viii) adaptation to energy crisis, ix) provision of mesenchymal stem cells for tissue repair. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5731", "text": "The bone marrow stroma contains  mesenchymal stem cells  (MSCs), [ 11 ]  which are also known as marrow stromal cells. These are  multipotent   stem cells  that can  differentiate  into a variety of cell types. MSCs have been shown to differentiate,  in vitro  or  in vivo , into  osteoblasts ,  chondrocytes ,  myocytes ,  marrow adipocytes  and  beta-pancreatic islets cells . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5732", "text": "The  blood vessels  of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the marrow. Only mature blood cells contain the  membrane proteins , such as  aquaporin  and  glycophorin , that are required to attach to and pass the blood vessel  endothelium . [ 23 ]   Hematopoietic stem cells  may also cross the bone marrow barrier, and may thus be harvested from blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5733", "text": "The red bone marrow is a key element of the  lymphatic system , being one of the  primary lymphoid organs  that generate  lymphocytes  from immature hematopoietic  progenitor cells . [ 24 ]  The bone marrow and  thymus  constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. Furthermore, bone marrow performs a  valve -like function to prevent the backflow of  lymphatic fluid  in the lymphatic system. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5734", "text": "Biological compartmentalization  is evident within the bone marrow, in that certain cell types tend to aggregate in specific areas. For instance,  erythrocytes ,  macrophages , and their  precursors  tend to gather around  blood vessels , while  granulocytes  gather at the borders of the bone marrow. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5735", "text": "People have used animal bone-marrow in cuisine worldwide for millennia, as in the famed  Milanese   Ossobuco . [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5736", "text": "The normal bone marrow architecture can be damaged or displaced by  aplastic anemia ,  malignancies  such as  multiple myeloma , or infections such as  tuberculosis , leading to a decrease in the production of blood cells and blood platelets. The bone marrow can also be affected by various forms of  leukemia , which attacks its hematologic progenitor cells. [ 26 ]  Furthermore, exposure to  radiation  or  chemotherapy  will kill many of the rapidly dividing cells of the bone marrow, and will therefore result in a depressed  immune system . Many of the symptoms of  radiation poisoning  are due to damage sustained by the bone marrow cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5737", "text": "To diagnose diseases involving the bone marrow, a  bone marrow aspiration  is sometimes performed. This typically involves using a hollow needle to acquire a sample of red bone marrow from the  crest of the ilium  under general or  local anesthesia . [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5738", "text": "Medical imaging may provide a limited amount of information regarding bone marrow.  Plain film x-rays  pass through soft tissues such as marrow and do not provide visualization, although any changes in the structure of the associated bone may be detected. [ 28 ]   CT  imaging has somewhat better capacity for assessing the marrow cavity of bones, although with low sensitivity and specificity. For example, normal fatty \"yellow\" marrow in adult long bones is of low density (-30 to -100 Hounsfield units), between subcutaneous fat and soft tissue. Tissue with increased cellular composition, such as normal \"red\" marrow or cancer cells within the medullary cavity will measure variably higher in density. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5739", "text": "MRI  is more sensitive and specific for assessing bone composition. MRI enables assessment of the average molecular composition of soft tissues and thus provides information regarding the relative fat content of marrow. In adult humans, \"yellow\" fatty marrow is the dominant tissue in bones, particularly in the (peripheral)  appendicular skeleton . Because fat molecules have a high  T1-relaxivity , T1-weighted imaging sequences show \"yellow\" fatty marrow as bright (hyperintense). Furthermore, normal fatty marrow loses signal on fat-saturation sequences, in a similar pattern to subcutaneous fat. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5740", "text": "When \"yellow\" fatty marrow becomes replaced by tissue with more cellular composition, this change is apparent as decreased brightness on T1-weighted sequences. Both normal \"red\" marrow and pathologic marrow lesions (such as cancer) are darker than \"yellow\" marrow on T1-weight sequences, although can often be distinguished by comparison with the MR signal intensity of adjacent soft tissues. Normal \"red\" marrow is typically equivalent or brighter than skeletal muscle or intervertebral disc on T1-weighted sequences. [ 8 ] [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5741", "text": "Fatty marrow change, the inverse of red marrow  hyperplasia , can occur with normal aging, [ 31 ]  though it can also be seen with certain treatments such as  radiation therapy . Diffuse marrow T1 hypointensity without contrast enhancement or cortical discontinuity suggests red marrow conversion or  myelofibrosis . Falsely normal marrow on T1 can be seen with diffuse  multiple myeloma  or  leukemic  infiltration when the water to fat ratio is not sufficiently altered, as may be seen with lower grade tumors or earlier in the disease process. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5742", "text": "Bone marrow examination is the pathologic analysis of samples of bone marrow obtained via  biopsy  and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma,  anemia , and  pancytopenia . The bone marrow produces the cellular elements of the blood, including  platelets ,  red blood cells  and  white blood cells . While much information can be gleaned by testing the blood itself (drawn from a vein by  phlebotomy ), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow aspiration and biopsy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5743", "text": "The ratio between  myeloid series  and  erythroid  cells is relevant to bone marrow function, and also to diseases of the bone marrow and  peripheral blood , such as leukemia and anemia. The normal myeloid-to-erythroid ratio is around 3:1; this ratio may increase in  myelogenous leukemias , decrease in  polycythemias , and reverse in cases of  thalassemia . [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5744", "text": "In a  bone marrow transplant , hematopoietic stem cells are removed from a person and infused into another person ( allogenic ) or into the same person at a later time ( autologous ). If the donor and recipient are compatible, these infused cells will then travel to the bone marrow and initiate blood cell production. Transplantation from one person to another is conducted for the treatment of severe bone marrow diseases, such as congenital defects, autoimmune diseases or malignancies. The patient's own marrow is first killed off with drugs or  radiation , and then the new stem cells are introduced. Before radiation therapy or  chemotherapy  in cases of  cancer , some of the patient's hematopoietic stem cells are sometimes harvested and later infused back when the therapy is finished to restore the immune system. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5745", "text": "Bone marrow stem cells can be induced to become neural cells to treat neurological illnesses, [ 35 ]  and can also potentially be used for the treatment of other illnesses, such as  inflammatory bowel disease . [ 36 ]  In 2013, following a clinical trial, scientists proposed that bone marrow transplantation could be used to treat  HIV  in conjunction with  antiretroviral  drugs; [ 37 ] [ 38 ]  however, it was later found that HIV remained in the bodies of the test subjects. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5746", "text": "The stem cells are typically harvested directly from the red marrow in the  iliac crest , often under  general anesthesia . The procedure is minimally invasive and does not require stitches afterwards. Depending on the donor's health and reaction to the procedure, the actual harvesting can be an  outpatient procedure , or can require 1\u20132 days of recovery in the hospital. [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5747", "text": "Another option is to administer certain drugs that stimulate the release of stem cells from the bone marrow into circulating blood. [ 41 ]  An  intravenous   catheter  is inserted into the donor's arm, and the stem cells are then filtered out of the blood. This procedure is similar to that used in blood or platelet donation. In adults, bone marrow may also be taken from the  sternum , while the  tibia  is often used when taking samples from infants. [ 27 ]  In newborns, stem cells may be retrieved from the  umbilical cord . [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5748", "text": "One of the most damaged areas of the body following chemotherapy is typically the uterus. Following uterine damage due to cancer treatment, follicle damage makes it difficult for individuals to get pregnant even if viable ova are present. With bone marrow stem cell transplants, chemotherapy patients have been able to increase their fertility as follicle damage is repaired. [ 43 ]  As follicles are necessary for ovum attachment to the  endometrium , it is important for these areas to be repaired in order to increase fertility. For individuals who have sustained egg and follicle damage, IVF has been found to be more effective following bone marrow stem cell transplantation. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5749", "text": "One human clinical case has shown improvements of uterine lining thickness and overall endometrium repair following bone marrow stem cell transplantation. [ 45 ]  This repair allowed for the patient to successfully become pregnant and carry to term."}
{"_id": "WikiPedia_Hematology$$$corpus_5750", "text": "Additional repairs following bone marrow stem cell transplant to the endometrium include increased vascularity and iron levels, with egg implantation clustering around areas with high blood flow. [ 44 ] [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5751", "text": "Using quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS) a maximum of five DNA viruses per individual have been identified. Included were several herpesviruses, hepatitis B virus, Merkel cell polyomavirus, and human papillomavirus 31. Given the reactivation and/or oncogenic potential of these viruses, their repercussion on hematopoietic and malignant disorders calls for further studies. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5752", "text": "The earliest fossilised evidence of bone marrow was discovered in 2014 in  Eusthenopteron , a  lobe-finned fish  which lived during the  Devonian  period approximately 370 million years ago. [ 48 ]  Scientists from  Uppsala University  and the  European Synchrotron Radiation Facility  used  X-ray synchrotron microtomography  to study the fossilised interior of the skeleton's  humerus , finding organised tubular structures akin to modern vertebrate bone marrow. [ 48 ]   Eusthenopteron  is closely related to the early  tetrapods , which ultimately evolved into the land-dwelling  mammals  and  lizards  of the present day. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5753", "text": "Erythropoiesis  (from Greek 'erythro' meaning \"red\" and 'poiesis' \"to make\") is the process which produces  red blood cells  (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5754", "text": "It is stimulated by decreased O 2  in circulation, which is detected by the  kidneys , which then secrete the hormone  erythropoietin . [ 2 ]  This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the  hemopoietic  tissues, ultimately producing  red blood cells  (erythrocytes). [ 2 ]  In  postnatal   birds  and  mammals  (including  humans ), this usually occurs within the  red bone marrow . [ 2 ]  In the early  fetus , erythropoiesis takes place in the mesodermal cells of the  yolk sac . By the third or fourth month, erythropoiesis moves to the liver. [ 3 ]  After seven months, erythropoiesis occurs in the bone marrow. Increased levels of physical activity can cause an increase in erythropoiesis. [ 4 ]  However, in  humans  with certain  diseases  and in some  animals , erythropoiesis also occurs outside the  bone marrow , within the  spleen  or  liver . This is termed  extramedullary erythropoiesis ."}
{"_id": "WikiPedia_Hematology$$$corpus_5755", "text": "The  bone marrow  of essentially all the  bones  produces red blood cells until a person is around five  years  old. The  tibia  and  femur  cease to be important sites of  hematopoiesis  by about age 25; the  vertebrae ,  sternum ,  pelvis  and  ribs , and  cranial bones  continue to produce red blood cells throughout life. Up to the age of 20 years, RBCs are produced from red bone marrow of all the bones (long bones and all the flat bones). After the age of 20 years, RBCs are produced from membranous bones such as vertebrae, the sternum, ribs, scapulas, and the iliac bones. After 20 years of age, the shaft of the long bones becomes yellow bone marrow because of fat deposition and loses the erythropoietic function. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5756", "text": "Comparison of erythrocyte production by marrow stem cell lines from old and young adult donors shows no significant differences. [ 6 ]  This finding implies that little or none of the proliferative capacity of the erythropoietic stem cells is exhausted by a lifetime of normal functioning. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5757", "text": "In the process of red blood corpuscle maturation, a cell undergoes a series of  differentiations . The following stages of development all occur within the  bone marrow :"}
{"_id": "WikiPedia_Hematology$$$corpus_5758", "text": "The cell is released from the bone marrow after Stage 7, and so in newly circulating red blood cells there are about 1% reticulocytes. After one to two days, these ultimately become \"erythrocytes\" or mature red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_5759", "text": "These stages correspond to specific appearances of the cell when stained with  Wright's stain  and examined by light microscopy, and correspond to other biochemical changes."}
{"_id": "WikiPedia_Hematology$$$corpus_5760", "text": "In the process of maturation, a basophilic pronormoblast is converted from a cell with a large  nucleus  and a volume of 900  fL  to an  enucleated  disc with a volume of 95 fL. By the reticulocyte stage, the cell has extruded its nucleus, but is still capable of producing hemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_5761", "text": "Essential for the maturation of red blood cells are  Vitamin B 12  (cobalamin) and  Vitamin B 9  (folate). Lack of either causes maturation failure in the process of erythropoiesis, which manifests clinically as  reticulocytopenia , an abnormally low amount of reticulocytes."}
{"_id": "WikiPedia_Hematology$$$corpus_5762", "text": "As they mature, a number of erythrocyte characteristics change:"}
{"_id": "WikiPedia_Hematology$$$corpus_5763", "text": "The production of all blood cells begins with the haemocytoblast, a multipotent haematopoietic stem cell. Haemocytoblasts have the greatest powers of self-renewal of any adult cell. They are found in the bone marrow and can be mobilised into the circulating blood when needed.\nSome haemocytoblasts differentiate into common myeloid progenitor cells, which go on to produce erythrocytes, as well as mast cells, megakaryocytes and myeloblasts.\nThe process by which common myeloid progenitor cells become fully mature red blood cells involves several stages. First, they become normoblasts (aka eryhthroblasts), which are normally present in the bone marrow only.\nThen, they lose their nucleus as they mature into reticulocytes, which can be thought of as immature red blood cells. Some of these are released into the peripheral circulation.\nFinally, reticulocytes lose their remaining organelles as they mature into erythrocytes-which are fully mature red blood cells. The average lifespan of a red blood cell is approximately 120 days.\nDuring this maturation process, there is nuclear extrusion \u2013 i.e. mature erythrocytes have no nucleus. Nucleated red blood cells present in a sample of bone marrow can indicate the release of incompletely developed cells. This can occur in pathology such as thalassaemia, severe anaemia or haematological malignancy."}
{"_id": "WikiPedia_Hematology$$$corpus_5764", "text": "A feedback loop involving  erythropoietin  helps regulate the process of erythropoiesis so that, in non-disease states, the production of red blood cells is equal to the destruction of red blood cells and the red blood cell number is sufficient to sustain adequate tissue oxygen levels but not so high as to cause sludging,  thrombosis , or  stroke . Erythropoietin is produced in the kidney and liver in response to low oxygen levels. In addition, erythropoietin is bound by circulating red blood cells; low circulating numbers lead to a relatively high level of unbound erythropoietin, which stimulates production in the bone marrow."}
{"_id": "WikiPedia_Hematology$$$corpus_5765", "text": "Recent studies have also shown that the peptide hormone  hepcidin  may play a role in the regulation of hemoglobin production, and thus affect erythropoiesis. The liver produces hepcidin. Hepcidin controls iron absorption in the gastrointestinal tract and iron release from reticuloendothelial tissue. Iron must be released from  macrophages  in the bone marrow to be incorporated into the heme group of  hemoglobin  in erythrocytes. There are colony forming units that the cells follow during their formation. These cells are referred to as the committed cells including the granulocyte monocyte colony forming units."}
{"_id": "WikiPedia_Hematology$$$corpus_5766", "text": "The secretion of hepcidin is inhibited by another hormone,  erythroferrone , produced by erythroblasts in response to erythropoietin, and identified in 2014. [ 8 ] [ 9 ]   It appears that this links erythropoietin-driven eyrthropoiesis with the iron mobilization needed for hemoglobin synthesis."}
{"_id": "WikiPedia_Hematology$$$corpus_5767", "text": "Loss of function of the erythropoietin receptor or JAK2 in mice cells causes failure in erythropoiesis, so production of red blood cells in embryos and growth is disrupted. If there is no systemic feedback inhibition, for example, the diminishment or absence of suppressors of cytokine signaling proteins,  giantism  may result as shown in  mice  models. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5768", "text": "In addition to the steady state erythropoiesis, acute anemia probably stimulates another response which results in rapid development of new red blood cells. This has been studied in rats and happens in the liver through the activation of the BMP4-dependent stress erythropoiesis pathway. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5769", "text": "Extramedullary hematopoiesis  ( EMH  or sometimes  EH [ 1 ] ) refers to  hematopoiesis  occurring outside of the medulla of the bone ( bone marrow ). [ 2 ]  It can be physiologic or pathologic."}
{"_id": "WikiPedia_Hematology$$$corpus_5770", "text": "Physiologic EMH occurs during  embryonic  and  fetal  development; during this time the main site of fetal hematopoiesis are liver and the spleen."}
{"_id": "WikiPedia_Hematology$$$corpus_5771", "text": "Pathologic EMH can occur during adulthood when physiologic hematopoiesis can't work properly in the bone marrow and the  hematopoietic stem cells (HSC)  have to migrate to other tissues in order to continue with the formation of  blood cellular components . Pathologic EMH can be caused by  myelofibrosis , [ 3 ]   thalassemias  or disorders caused in the hematopoietic system."}
{"_id": "WikiPedia_Hematology$$$corpus_5772", "text": "During fetal development, hematopoiesis occurs mainly in the  fetal liver  and in the  spleen  followed by localization to the bone marrow. [ 4 ]  Hematopoiesis also takes place in many other tissues or organs such as the  yolk sac , the  aorta-gonad mesonephros (AGM)  region, and  lymph nodes . During development, vertebrates go through a primitive and a definitive phase of hematopoiesis. The lungs also play a role in platelet production in adults. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5773", "text": "Primitive hematopoiesis  occurs in the yolk sac during early embryonic development. It is characterized by the production of primitive nucleated erythroid cells, which is thought to originate from endothelial cells or hemangioblasts, which are capable of forming both endothelium and primitive blood cells. The main objective of the production of these cells will be the facilitation of tissue oxygenation to support rapid embryonic growth. This primitive phase is transitory and the cells that are produced express embryonic hemoglobins (HBZ and HBE1 genes produce the alpha and beta chains, respectively) aren't  pluripotent , and aren't capable of self-renewal. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5774", "text": "Definitive hematopoiesis  differs from the primitive phase through the production of  hematopoietic stem cells . [ 8 ]  The formation of these cells occurs in the AGM (aorta-gonad-mesonephros) later in development. This occurs by conversion of endothelial cells to hematopoietic stem and progenitor cells (HPSCs) - a process called endothelial-to-hematopoietic transition or EHT. These hematopoietic stem cells are further closely associated with endothelial cells throughout human life. Later, they migrate to the fetal liver where the majority of physiologic EMH (extra-medullary hematopoiesis) takes place. They can also migrate to the spleen and lymph nodes where hematopoiesis can occur, but to a lesser degree. Finally, once the bone marrow has developed, they migrate there. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5775", "text": "Pulmonary hematopoiesis  also appears to play an important role in adults. [ 5 ]  In comparison to the bone marrow, where trilineage hematopoiesis occurs, the lungs preferentially contribute to the production of platelets through a resident population of  megakaryocytes . This is supported by studies showing that blood leaving the lungs has more platelets and fewer progenitor cells than blood entering the lungs. It has been seen that in cases of severe  thrombocytopenia , pulmonary megakaryocytes migrate out of lungs into the bone marrow, where they help to replenish the depleted bone marrow population. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5776", "text": "In adults, the majority of hematopoiesis occurs in the bone marrow. Significant production in any other organ is usually the result of a pathological process. When  red blood cell (RBC)  numbers are low, the body induces a homeostatic mechanism aimed to increase the synthesis of RBCs, typically via the production of erythropoietin. If the loss of RBCs becomes severe, hematopoiesis will occur in the extramedullary spaces outside the bone. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5777", "text": "The cause of pathologic EMH can be one of many hematological diseases, such as  myelofibrosis , or as a result of bone marrow irradiation.  Thalassemia  and its resultant  hemolytic anemia  is another important cause of pathologic EMH. EMH has been observed in numerous other benign hematological disorders such as sickle cell anemia, hereditary spherocytosis, congenital dyserythroblastic anemia and idiopathic thrombocytopenic purpura. [ 10 ]  EMH can also be seen as part of the response to  systemic inflammation  or  infection ."}
{"_id": "WikiPedia_Hematology$$$corpus_5778", "text": "Sites of EMH can be widespread however, most common localizations are in the spleen, liver, and lymph nodes. Other manifestations occur in the thymus, heart, breast, prostate, broad ligaments, kidneys, adrenal glands, pleura, retroperitoneal tissue, skin, peripheral and cranial nerves, and the spinal canal. [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5779", "text": "During the postnatal period, the spleen becomes a frequent site of EMH whereas, during the embryonic stages of hematopoiesis, it is only a minor factor. Despite the hypoxic/acidic conditions of the splenic microenvironment, supplied with a legion of macrophages making it inhospitable for HSCs, EMH usually occurs within the red pulp. Among the various organs associated with EMH, the spleen offers a unique site for evaluation of hematopoietic stem cell (HSC)/niche interactions. [ 12 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5780", "text": "It is normal for infants have hepatic EMH as they are developing up until roughly 5 weeks of age. [ 13 ]  On the other hand, hepatic EMH in adults can indicate a pathological state. This includes transplantation, hepatic tumors, hepatic disorders, or sepsis. Hepatoblastoma, adenomas and hepatocellular carcinomas can also lead to EMH in adults. [ 14 ] [ 15 ]  Additionally, EMH is often observed within the hepatic sinusoids."}
{"_id": "WikiPedia_Hematology$$$corpus_5781", "text": "EMH in the lymph nodes is usually associated with underlying hematopoietic neoplasms. Myeloproliferative neoplasms (MPNs) tend to result in EMH. [ 16 ]  If EMH is identified in the lymph nodes of an adult or infant, a hematologic evaluation, including blood cell counts, peripheral blood smear and potentially a bone marrow biopsy should be performed. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5782", "text": "The following tissues may also be associated with EMH:  thymus ,  heart ,  breast ,  prostate ,  fatty tissue ,  adrenal glands ,  kidney ,  periosteum ,  pleural cavity , para-vertebral regions, intra-spinal tissue, retroperitoneal tissue, skin, peripheral and cranial nerves, the spinal canal, pre-sacral region, nasopharyngeal region, para-nasal sinuses and numerous types of benign/malignant neoplasms. The most common sites of EMH associated with neoplastic disorder are the spleen, lymph nodes, skin, bone, small intestine, orbit, breast, cervix, nasal sinus, mediastinum and brain. [ 11 ] [ 17 ] [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5783", "text": "Of the various organs associated with EMH, the spleen offers a unique site for evaluating HSC/niche interactions as it is one of the most common sites of EMH, however it does not play a major role in embryonic/developmental hematopoiesis. [ 11 ]  High expression levels of  CXCL12  were found in the human spleens of EMH-positive patients compared to those who were EMH-negative. The high expression of CXCL12, a candidate marker of bone marrow niche-constituting in cells, indicates HSC/niche interactions in the spleen. [ 20 ]  Studies have shown that CXCL12 localizes in the sinus endothelial cells of the red pulp in EMH-positive spleens; whereas, CXCL12 was expressed throughout the vascular endothelial cells of the white pulp in spleens of EMH-negative and -positive cases. [ 20 ]  The fact that EMH frequently occurs in the red pulp, is supported by current data that suggests that splenic sinus endothelial cells expressing CXCL12 may contribute to the attachment and recruitment of circulating hematopoietic precursor cells, forming bone marrow niche-like regions of EMH in the human spleen. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5784", "text": "Granulopoiesis  (or  granulocytopoiesis ) is a part of  haematopoiesis , that leads to the production of  granulocytes . A  granulocyte , also referred to as a polymorphonuclear leukocyte (PMN), is a type of  white blood cell  that has multi lobed  nuclei , usually containing three lobes, and has a significant amount of cytoplasmic  granules  within the cell. [ 1 ]  Granulopoiesis takes place in the  bone marrow . [ 2 ]  It leads to the production of three types of mature  granulocytes :  neutrophils  (most abundant, making up to 60% of all  white blood cells ),  eosinophils  (up to 4%) and  basophils  (up to 1%). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5785", "text": "Granulopoiesis is often divided into two parts;"}
{"_id": "WikiPedia_Hematology$$$corpus_5786", "text": "1) Granulocyte lineage determination and"}
{"_id": "WikiPedia_Hematology$$$corpus_5787", "text": "2) Committed granulopoiesis."}
{"_id": "WikiPedia_Hematology$$$corpus_5788", "text": "Granulopoiesis, as well as the rest of  haematopoiesis , begins from a  haematopoietic stem cells . These are  multipotent  cells that reside in the  bone marrow niche  and have the ability to give rise to all haematopoietic cells, as well as the ability of self renewal. [ 4 ]  They give rise to either a  common lymphoid progenitor  (CLP, a progenitor for all  lymphoid cells ) or a  common myeloid progenitor , CMP, an  oligopotent  progenitor cell, that gives rise to the myeloid part of the haematopoietic tree. [ 1 ]  The first stage of the myeloid lineage is a granulocyte - monocyte progenitor (GMP), still an oligopotent progenitor, which then develops into  unipotent  cells that will later on form a population of  granulocytes , as well as a population of  monocytes . The first unipotent cell in granulopoiesis is a  myeloblast . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5789", "text": "Committed granulopoiesis consists of maturation stages of unipotent cells. The first cell that starts to resemble a granulocyte is a  myeloblast . It is characterized by large oval nucleus that takes up most of the space in the cell and very little cytoplasm. The next developmental stage, a  promyelocyte , still has a large oval nucleus, but there is more cytoplasm in the cell at this point, also cytoplasmic granules are beginning to form. The development of granules continues with the next stage, a  myelocyte . At this point, the nucleus is starting to shrink. At the stage of a  metamyelocyte  the cell nucleus is becoming kidney-shaped and it becomes even more bent in the stage of a  band cell . The maturation is finished with the emergence of a segmented nucleus that is specific for a  mature granulocyte . [ 1 ] [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5790", "text": "The maturation of granulocytic precursors is tightly regulated at transcriptional level. Granulocyte lineage determination is regulated by expression of  C/EBP\u03b1 , which is necessary for the transition from  CMPs  to GMPs and levels of PU.1, that drive the differentation from GMPs to  monocytes  (high PU.1 levels) or to  granulocytes  (low PU.1 levels). [ 1 ] [ 7 ]  Committed granulopoiesis is regulated by  C/EBP\u03b5  and GFI-1, these two transcriptional factors are important for terminal granulocyte differentiation. Other transcriptional factors that regulate granulopoiesis are:  CBF ,  MYB ,  SMAD4  and  HOX genes . [ 1 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5791", "text": "Granulopoiesis is also regulated by  cytokines  to a certain extent. The main cytokines driving granulopoiesis are:  GM-CSF  (formation of GMPs from CMPs),  G-CSF  (commitment to the granulocyte lineage, formation of myeloblasts from GMPs),  IL-3  (enhances the production of  GM-CSF  and  G-CSF ) and  SCF . [ 10 ] [ 11 ]  These are secreted by other haematopoietic cells in the bone marrow or at the site of  inflammation  as well as  epithelial  and  endothelial cells . [ 2 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5792", "text": "Steady state granulopoiesis is a term used to describe the normal daily production of granulocytes. Granulocytes are short lived cells (their lifespan is between 6 and 8 hours) with a high cell turnover. The number of granulocytes produced every day is between 5 and 10 x 10 10 . [ 13 ]  The master regulator of steady state granulopoiesis is C/EBP\u03b1. It restricts the cell cycle of immature cells by inhibition of  CDK2  and  CDK4  and promotes granulocytic differentiation. [ 14 ]  Steady state production of granulocytes is activated after the engulfment of apoptotic granulocytes by  tissue macrophages . [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5793", "text": "Emergency granulopoiesis is a fundamental hematopoietic mechanism activated during acute infections or inflammatory conditions, leading to a swift increase in granulocyte production, especially neutrophils, in the bone marrow. This process is essential for enhancing the innate immune system's capability to confront pathogen invasions effectively. [ 16 ] [ 17 ] [ 18 ]  Hematopoietic stem cells (HSCs) undergo significant transcriptional reprogramming in response to emergency conditions, transitioning from a lymphoid-biased state towards a myeloid-biased identity, thereby aligning the hematopoietic system's output with the urgent demand for granulocytes. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5794", "text": "Under normal conditions, steady-state granulopoiesis maintains granulocyte levels to meet physiological needs. However, after a major insult, typically a bacterial infection, the hematopoietic program switches from steady-state to emergency granulopoiesis. This switch is mediated by a transition from C/EBP\u03b1 to C/EBP\u03b2, the primary transcriptional regulator of emergency granulopoiesis. C/EBP\u03b2 enhances the production of granulocytes by promoting the progression of the cell cycle of myeloid progenitors at an accelerated rate, thereby generating a sufficient amount of new granulocytes to combat the insult. [ 20 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5795", "text": "The transcription factor CCAAT/enhancer binding protein \u03b2 (C/EBP\u03b2) is a critical regulator in this context, significantly influencing granulocyte lineage commitment and proliferation, especially noted during candidemia-induced scenarios. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5796", "text": "The genetic backdrop plays a crucial role in the dynamics of emergency granulopoiesis, as demonstrated by studies in TP53 haploinsufficient models, particularly in FANCC\u2212/\u2212 mice, highlighting the intricate interplay between genetic predispositions and the granulopoietic response. [ 22 ]  Additionally, recent advances have highlighted the importance of both direct and indirect pathogen sensing mechanisms. HSPCs are equipped with pathogen recognition receptors (PRRs) like Toll-like receptors (TLRs), enabling them to initiate myeloid differentiation and proliferation upon detecting pathogen-associated molecular patterns (PAMPs). [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5797", "text": "Neutrophils, as primary effector cells of the innate immune defense, originate from HSCs through a series of differentiation stages. The emergency granulopoiesis significantly accelerates this differentiation process, ensuring a rapid replenishment of neutrophil populations in response to systemic inflammatory stimuli, thus maintaining immune homeostasis. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5798", "text": "The clinical significance of understanding emergency granulopoiesis extends beyond basic science, influencing therapeutic strategies against infectious diseases and immune deficiencies. Balancing rapid neutrophil mobilization against the risk of immune dysregulation is critical, as imbalances can lead to severe conditions like acute respiratory distress syndrome and sepsis-induced organ dysfunctions. [ 23 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5799", "text": "Haematopoiesis  ( / h \u026a \u02cc m \u00e6 t \u0259 p \u0254\u026a \u02c8 i\u02d0 s \u026a s ,   \u02cc h i\u02d0 m \u0259 t o\u028a -,   \u02cc h \u025b m \u0259 -/ ; [ 1 ] [ 2 ]  from  Ancient Greek     \u03b1\u1f37\u03bc\u03b1  ( ha\u00eema ) \u00a0'blood' and    \u03c0\u03bf\u03b9\u03b5\u1fd6\u03bd  ( poie\u00een ) \u00a0'to make'; also  hematopoiesis  in  American English , sometimes  h(a)emopoiesis ) is the formation of  blood  cellular components. All cellular blood components are derived from  haematopoietic stem cells . [ 3 ]  In a healthy adult human, roughly ten billion (10 10 ) to a hundred billion (10 11 ) new blood cells are produced per day, in order to maintain steady state levels in the peripheral circulation. [ 4 ] [ 5 ] [ page\u00a0needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5800", "text": "Haematopoietic stem cells  (HSCs) reside in the medulla of the bone ( bone marrow ) and have the unique ability to give rise to all of the different mature blood cell types and tissues. [ 3 ]  HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted. [ 6 ]  This phenomenon is called  asymmetric division. [ 7 ]  The other daughters of HSCs ( myeloid  and  lymphoid  progenitor cells) can follow any of the other differentiation pathways that lead to the production of one or more specific types of blood cell, but cannot renew themselves. The pool of progenitors is  heterogeneous  and can be divided into two groups; long-term self-renewing HSC and only transiently self-renewing HSC, also called short-terms. [ 8 ]  This is one of the main vital processes in the body. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5801", "text": "All blood cells are divided into three lineages. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5802", "text": "Granulopoiesis  (or granulocytopoiesis) is haematopoiesis of granulocytes, except  mast cells  which are granulocytes but with an extramedullar maturation. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5803", "text": "Thrombopoiesis  is haematopoiesis of  thrombocytes (platelets) ."}
{"_id": "WikiPedia_Hematology$$$corpus_5804", "text": "Between 1948 and 1950, the Committee for Clarification of the Nomenclature of Cells and Diseases of the Blood and Blood-forming Organs issued reports on the nomenclature of blood cells. [ 11 ] [ 12 ]  An overview of the terminology is shown below, from earliest to final stage of development: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5805", "text": "The root for erythrocyte colony-forming units (CFU-E) is \"rubri\", for granulocyte-monocyte colony-forming units (CFU-GM) is \"granulo\" or \"myelo\" and \"mono\", for lymphocyte colony-forming units (CFU-L) is \"lympho\" and for megakaryocyte colony-forming units (CFU-Meg) is \"megakaryo\". According to this terminology, the stages of red blood cell formation would be: rubriblast, prorubricyte, rubricyte, metarubricyte, and erythrocyte. However, the following nomenclature seems to be, at present, the most prevalent:"}
{"_id": "WikiPedia_Hematology$$$corpus_5806", "text": "Osteoclasts  also arise from hemopoietic cells of the monocyte/neutrophil lineage, specifically CFU-GM."}
{"_id": "WikiPedia_Hematology$$$corpus_5807", "text": "In developing embryos, blood formation occurs in aggregates of blood cells in the yolk sac, called  blood islands . As development progresses, blood formation occurs in the  spleen ,  liver  and  lymph nodes . [ 13 ]  When  bone marrow  develops, it eventually assumes the task of forming most of the blood cells for the entire organism. [ 3 ]  However, maturation, activation, and some proliferation of lymphoid cells occurs in the spleen,  thymus , and lymph nodes. In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5808", "text": "In some cases, the liver, thymus, and spleen may resume their haematopoietic function, if necessary. This is called  extramedullary haematopoiesis . It may cause these organs to increase in size substantially. During fetal development, since bones and thus the bone marrow develop later, the liver functions as the main haematopoietic organ. Therefore, the liver is enlarged during development. [ 15 ]  Extramedullary haematopoiesis and myelopoiesis may supply  leukocytes  in  cardiovascular disease  and inflammation during adulthood. [ 16 ] [ 17 ]  Splenic  macrophages  and  adhesion molecules  may be involved in regulation of extramedullary myeloid cell generation in  cardiovascular disease . [ 18 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5809", "text": "As a stem cell matures it undergoes changes in  gene expression  that limit the cell types that it can become and moves it closer to a specific cell type ( cellular differentiation ). These changes can often be tracked by monitoring the presence of proteins on the surface of the cell. Each successive change moves the cell closer to the final cell type and further limits its potential to become a different cell type. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5810", "text": "Two models for haematopoiesis have been proposed: determinism and stochastic theory. [ 20 ]  For the stem cells and other undifferentiated blood cells in the bone marrow, the determination is generally explained by the  determinism  theory of haematopoiesis, saying that colony stimulating factors and other factors of the haematopoietic microenvironment determine the cells to follow a certain path of cell differentiation. [ 3 ]  This is the classical way of describing haematopoiesis. In  stochastic   theory,  undifferentiated blood cells differentiate to specific cell types by randomness. This theory has been supported by experiments showing that within a population of mouse haematopoietic progenitor cells, underlying stochastic variability in the distribution of  Sca-1 , a  stem cell  factor, subdivides the population into groups exhibiting variable rates of  cellular differentiation . For example, under the influence of  erythropoietin  (an erythrocyte-differentiation factor), a subpopulation of cells (as defined by the levels of Sca-1) differentiated into  erythrocytes  at a sevenfold higher rate than the rest of the population. [ 21 ]  Furthermore, it was shown that if allowed to grow, this subpopulation re-established the original subpopulation of cells, supporting the theory that this is a stochastic, reversible process. Another level at which stochasticity may be important is in the process of apoptosis and self-renewal. In this case, the haematopoietic microenvironment prevails upon some of the cells to survive and some, on the other hand, to perform  apoptosis  and die. [ 3 ]  By regulating this balance between different cell types, the bone marrow can alter the quantity of different cells to ultimately be produced. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5811", "text": "Red and white blood cell production is regulated with great precision in healthy humans, and the production of leukocytes is rapidly increased during infection. The proliferation and self-renewal of these cells depend on growth factors. One of the key players in self-renewal and development of haematopoietic cells is  stem cell factor  (SCF), [ 25 ]  which binds to the c-kit receptor on the HSC. Absence of SCF is lethal. There are other important  glycoprotein  growth factors which regulate the proliferation and maturation, such as  interleukins   IL-2 ,  IL-3 ,  IL-6 ,  IL-7 . Other factors, termed  colony-stimulating factors  (CSFs), specifically stimulate the production of committed cells. Three CSFs are  granulocyte-macrophage CSF  (GM-CSF),  granulocyte CSF  (G-CSF) and  macrophage CSF  (M-CSF). [ 26 ]  These stimulate  granulocyte  formation and are active on either  progenitor cells  or end product cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5812", "text": "Erythropoietin  is required for a myeloid progenitor cell to become an erythrocyte. [ 23 ]  On the other hand,  thrombopoietin  makes myeloid progenitor cells differentiate to  megakaryocytes  ( thrombocyte -forming cells). [ 23 ]  The diagram to the right provides examples of cytokines and the differentiated blood cells they give rise to. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5813", "text": "Growth factors initiate  signal transduction  pathways, which lead to activation of  transcription factors . Growth factors elicit different outcomes depending on the combination of factors and the cell's stage of differentiation. For example, long-term expression of  PU.1  results in myeloid commitment, and short-term induction of PU.1 activity leads to the formation of immature eosinophils. [ 28 ]  Recently, it was reported that transcription factors such as  NF-\u03baB  can be regulated by  microRNAs  (e.g., miR-125b) in haematopoiesis. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5814", "text": "The first key player of differentiation from HSC to a multipotent progenitor (MPP) is transcription factor CCAAT-enhancer binding protein \u03b1 ( C/EBP \u03b1). Mutations in C/EBP\u03b1 are associated with  acute myeloid leukaemia . [ 30 ]  From this point, cells can either differentiate along the Erythroid-megakaryocyte lineage or lymphoid and myeloid lineage, which have common progenitor, called lymphoid-primed multipotent progenitor. There are two main transcription factors. PU.1 for Erythroid-megakaryocyte lineage and  GATA-1 , which leads to a lymphoid-primed multipotent progenitor. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5815", "text": "Other transcription factors include Ikaros [ 32 ]  ( B cell  development), and  Gfi1 [ 33 ]  (promotes  Th2  development and inhibits Th1) or  IRF8 [ 34 ]  ( basophils  and  mast cells ). Significantly, certain factors elicit different responses at different stages in the haematopoiesis. For example, CEBP\u03b1 in neutrophil development or  PU.1  in monocytes and dendritic cell development. It is important to note that processes are not unidirectional: differentiated cells may regain attributes of progenitor cells. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5816", "text": "An example is  PAX5  factor, which is important in B cell development and associated with lymphomas. [ 35 ]  Surprisingly, pax5 conditional knock out mice allowed peripheral mature B cells to de-differentiate to early bone marrow progenitors. These findings show that transcription factors act as caretakers of differentiation level and not only as initiators. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5817", "text": "Mutations  in transcription factors are tightly connected to blood cancers, as  acute myeloid leukemia  (AML) or  acute lymphoblastic leukemia  (ALL). For example, Ikaros is known to be regulator of numerous biological events. Mice with no Ikaros lack  B cells ,  Natural killer  and  T cells . [ 37 ]  Ikaros has six  zinc fingers  domains, four are conserved  DNA-binding domain  and two are for  dimerization . [ 38 ]  Very important finding is, that different zinc fingers are involved in binding to different place in DNA and this is the reason for pleiotropic effect of Ikaros and different involvement in cancer, but mainly are mutations associated with  BCR-Abl  patients and it is bad prognostic marker. [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5818", "text": "In some  vertebrates , haematopoiesis can occur wherever there is a loose  stroma  of connective tissue and slow blood supply, such as the  gut ,  spleen  or  kidney . [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5819", "text": "Unlike eutherian mammals, the liver of newborn marsupials is actively haematopoietic. [ 41 ] [ 42 ] [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5820", "text": "Hemogenic endothelium  or   haemogenic endothelium [ 1 ]  is a special subset of endothelial cells scattered within blood vessels that can differentiate into  haematopoietic  cells. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5821", "text": "The development of hematopoietic cells in the embryo proceeds sequentially from  mesoderm  through the  hemangioblast  to the hemogenic endothelium and hematopoietic progenitors. [ 3 ]  The relationship between the hemogenic endothelium and the hemangioblast is not clearly understood. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5822", "text": "This  molecular  or  cell biology  article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_5823", "text": "Hemopoietic growth factors  regulate the differentiation and proliferation of particular  progenitor cells . Made available through recombinant  DNA  technology, they hold tremendous potential for medical uses when a person's natural ability to form  blood cells  is diminished or defective.  Recombinant  erythropoietin  (EPO) is very effective in treating the diminished red blood cell production that accompanies end-stage kidney disease.   Erythropoietin is a sialoglycoprotein hormone produced by peritubular cells of kidney."}
{"_id": "WikiPedia_Hematology$$$corpus_5824", "text": "Granulocyte -macrophage colony-stimulating factor and granulocyte CSF are given to stimulate white blood cell formation in cancer patients who are receiving  chemotherapy , which tends to kill their red bone marrow cells as well as the cancer cells.   Thrombopoietin  shows great promise for preventing  platelet  depletion during chemotherapy.  CSFs and thrombopoietin also improve the outcome of patients who receive bone marrow transplants."}
{"_id": "WikiPedia_Hematology$$$corpus_5825", "text": "Leukopoiesis  is a form of  hematopoiesis  in which white blood cells (WBC, or  leukocytes ) are formed in  bone marrow  located in bones in adults and hematopoietic organs in the fetus. White blood cells, indeed all blood cells, are formed from the differentiation of pluripotent hematopoietic  stem cells  which give rise to several cell lines with unlimited differentiation potential. These immediate cell lines, or colonies, are progenitors of red blood cells ( erythrocytes ), platelets ( megakaryocytes ), and the two main groups of WBCs,  myelocytes  and  lymphocytes ."}
{"_id": "WikiPedia_Hematology$$$corpus_5826", "text": "Lymphopoiesis  (l\u012dm'f\u014d-poi-\u0113's\u012ds) (or  lymphocytopoiesis ) is the generation of  lymphocytes , one of the five types of  white blood cells  (WBCs). [ 1 ] [ page\u00a0needed ]  It is more formally known as  lymphoid   hematopoiesis ."}
{"_id": "WikiPedia_Hematology$$$corpus_5827", "text": "Disruption in lymphopoiesis can lead to a number of  lymphoproliferative disorders , such as  lymphomas  and  lymphoid leukemias ."}
{"_id": "WikiPedia_Hematology$$$corpus_5828", "text": "Lymphocytes  are blood cells of  lymphoid  (rather than the  myeloid  or  erythroid ) lineage."}
{"_id": "WikiPedia_Hematology$$$corpus_5829", "text": "Lymphocytes are found in the  bloodstream  and originate in the  bone marrow , however, they principally belong to the separate  lymphatic system , which interacts with the blood circulation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5830", "text": "Lymphopoiesis is now usually used interchangeably with the term \"lymphocytopoiesis\" \u2013 the making of lymphocytes, but some sources distinguish between the two, stating that \"lymphopoiesis\" additionally refers to creating  lymphatic tissue , while \"lymphocytopoiesis\" refers only to the creation of cells in that tissue. It is rare now for lymphopoiesis to refer to the creation of lymphatic tissues. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5831", "text": "Myelopoiesis  refers to the \"generation of cells of the myeloid lineage\" and  erythropoiesis  refers to the \"generation of cells of the erythroid lineage\", so parallel usage has evolved in which lymphopoiesis refers to the \"generation of cells of the lymphoid lineage\". [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5832", "text": "The two classes of WBCs in mice originate from cells with strong  stem cell  properties \u2013  myeloids  from the  common myeloid progenitor  (CMP), and  lymphoids  from the common lymphoid progenitor (CLP). [ 1 ] [ page\u00a0needed ]  It was eventually found these  progenitors  were not unique, and that the myeloid and lymphoid classes were not disjoint, but rather two partially interwoven family trees. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5833", "text": "Mature lymphocytes are a critical part of the immune system that, with the exception of  memory B  and  T cells , have short lives measured in days or weeks and must be continuously generated throughout life by cell division and  differentiation  from cells such as common lymphoid  progenitors  (CLPs) in mice. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5834", "text": "The set comprising CLP cells and similar progenitors are themselves descendants of the  pluripotential hemopoietic stem cell  (pHSC), which is capable of generating all of the cell types of the complete blood cell system. [ 2 ]  Despite their ability to generate the complete suite of  lymphocytes , most progenitors are not true stem cells, and must be continually renewed by differentiation from the pHSC stem cell. [ 1 ] [ page\u00a0needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5835", "text": "Many progenitor cells are also referred to as  transit cells , [ 3 ]  sometimes also called  transit amplifying cells , the meaning of this term being that the transit cell may find a new sub-lineage but the number of resultant cells is strictly limited (although possibly very large, even trillions yet finite) and the lineage is terminated by cells that die off (by  apoptosis ) or remain as  cells that can no longer divide . Examples of such cells are CFUs (Colony-forming units \u2013 referred to as such because of their ability to form colonies in vitro in artificial media) such as CFU-T. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5836", "text": "Transplantation of a single pHSC cell can reconstitute a sub-lethally irradiated host (i.e. a mouse that has been irradiated so that all leukocytes are killed) with all these lineages of cells, including all types of lymphocytes via CLPs."}
{"_id": "WikiPedia_Hematology$$$corpus_5837", "text": "Lymphopoiesis continues throughout life and so progenitor cells and their parent  stem cells  must always be present. [ 1 ] [ page\u00a0needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5838", "text": "In the case of  mammals  such as humans ( Homo sapiens ), lymphopoiesis begins with limited passive provision from the mother.  This includes lymphocytes and  immunoglobulin G  that cross the  placenta  and enter the fetus to provide some protection against  pathogens , as well as leukocytes that come from breast milk and enter circulation via the digestive tract. [ 5 ]  It is often not effective in preventing  infections  in the newborn. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5839", "text": "However, early in  gestation , the developing embryo has begun its own lymphopoiesis from the  fetal liver . Lymphopoiesis also arises from the  yolk sac . [ 7 ]  This is in contrast to the adult where all  lymphocytes  originate in the bone marrow. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5840", "text": "There are four major types of lymphocytes, along with many sub-types. Scientists have identified hundreds or thousands of  lymphocyte  cell types, all of which are generated by normal or abnormal lymphopoiesis, except for certain artificial strains created in laboratories through the development of existing strains. Although lymphocytes are usually considered mature, as seen in blood tests, they are certainly not inert. Lymphocytes can travel around the body wherever there is a need. When such needs arise, new rounds of downstream lymphopoiesis, such as cell multiplication and differentiation, may occur, accompanied by intense  mitotic  and  metabolic activity ."}
{"_id": "WikiPedia_Hematology$$$corpus_5841", "text": "This is hardly a simple topic. In his 1976 text  Immunology, Aging and Cancer  immunologist and Nobel Prize winner Sir Frank Macfarlane Burnet speculated that the immune system might one day be found to be as complex as the  nervous system . As the production of lymphocytes is so close to the central role of the  immune response  it is wise to approach the study of it with some humility in the face of the task. However, there are general principles that help in understanding."}
{"_id": "WikiPedia_Hematology$$$corpus_5842", "text": "Lymphopoiesis can be viewed in a  mathematical  sense as a recursive process of cell division and also as a process of differentiation, measured by changes to the properties of cells."}
{"_id": "WikiPedia_Hematology$$$corpus_5843", "text": "Considering the P as the \u2018mother\u2019 cell, but not a true stem cell, it may divide into two new cells, which are themselves identical, but differ to some degree from the mother. Or the mother cell P may divide unequally into two new daughter cells both of which differ from each other and also from the mother."}
{"_id": "WikiPedia_Hematology$$$corpus_5844", "text": "Any daughter cell will usually have new specialized abilities and if it is able to divide it will form a new sub-lineage. The difference of a daughter cell from the mother may be great, but it could also be much less, even subtle. What the P mother cell does  not  do is divide into two new P mother cells or a mother and a daughter; this is a matter of observation as such limited progenitor cells are known to not self-renew."}
{"_id": "WikiPedia_Hematology$$$corpus_5845", "text": "T and B lymphocytes are indistinguishable  under the microscope . The inactive B and T cells are so featureless with few cytoplasmic  organelles  and mostly inactive  chromatin  that until the 1960s textbooks could describe these cells, now the central focus of immunology, as having no known function! [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5846", "text": "However, T and B lymphocytes are very distinct cell lineages and they \u2018grow up\u2019 in different places in the body. They perform quite different (although co-operative) functions in the body. No evidence has ever been found that T and B cells can ever interconvert. T and B cells are  biochemically  distinct and this is reflected in the differing markers and receptors they possess on their cell surfaces. This seems to be true in all vertebrates, although there are many differences in the details between the species."}
{"_id": "WikiPedia_Hematology$$$corpus_5847", "text": "T cells are formed in  bone marrow  and then migrate to the cortex of the  thymus  to undergo maturation in an antigen-free environment for about one week where a mere 2\u20134% of the T cells succeed. The remaining 96\u201398% of T cells die by  apoptosis  and are  phagocytosed  by  macrophages  in the thymus. So many thymocytes (T cells) die during the maturation process because there is intensive screening to make sure each thymocyte can recognize  self-peptide:self-MHC complex [ 12 ]  and for  self-tolerance . Having experienced apoptosis, the thymocyte dies and is quickly recycled."}
{"_id": "WikiPedia_Hematology$$$corpus_5848", "text": "Upon maturity, there are several forms of thymocytes including  [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5849", "text": "When T\u00a0cells become  activated  they undergo a further series of developments. A small, resting T lymphocyte rapidly undergoes  blastogenic transformation  into a large lymphocyte (13\u201315\u00a0 \u03bcm ).  This large lymphocyte (known in this context as a  lymphoblast ) then divides several times to produce an expanded population of medium (9\u201312\u00a0\u03bcm) and small lymphocytes (5\u20138\u00a0\u03bcm) with the same   antigenic specificity . [ 14 ]  Final activated and differentiated T lymphocytes are once again  morphologically  indistinguishable from a small, resting lymphocyte. Thus the following developmental states may be noticed in sequence in blood tests:"}
{"_id": "WikiPedia_Hematology$$$corpus_5850", "text": "Basic Map of T Cell lymphopoiesis"}
{"_id": "WikiPedia_Hematology$$$corpus_5851", "text": "This basic map of T Cell formation in sequence, is simplified and is akin to textbook descriptions, and may not reflect latest research. (Medical Immunology, p.\u00a0119)"}
{"_id": "WikiPedia_Hematology$$$corpus_5852", "text": "In the thymus"}
{"_id": "WikiPedia_Hematology$$$corpus_5853", "text": "In the  Periphery"}
{"_id": "WikiPedia_Hematology$$$corpus_5854", "text": "Unlike other lymphoid lineages, T\u00a0cell development occurs almost exclusively in the thymus. T-lymphopoiesis does not occur automatically but requires signals generated from the thymus  stromal  cells. Several stages at which specific regulators and growth factors are required for T\u00a0cell development to proceed have been defined. Later in T\u00a0cell development and its maturation, these same regulatory factors again are used to influence T\u00a0cell specialization. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5855", "text": "T\u00a0cells are unique among the lymphocyte populations in their ability to further specialize as mature cells and become yet more mature. T\u00a0cells come in many flavors, for example: the conventional TcR\u03b1\u03b2 T cells; the so-called unconventional TcR\u03b3\u03b4 T\u00a0cells; NKT\u00a0cells; and T regulatory cells (T reg ).  Details regarding the developmental and life cycle of the unconventional T\u00a0cells are less well-described measured to the conventional T\u00a0cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5856", "text": "Stages of T cell maturation"}
{"_id": "WikiPedia_Hematology$$$corpus_5857", "text": "Stage One:  Thymus Migration"}
{"_id": "WikiPedia_Hematology$$$corpus_5858", "text": "Multi-potent lymphoid progenitors (MLP) enter the T\u00a0cell pathway as they immigrate to the thymus. The most primitive cells in the thymus are the early thymocyte progenitors (ETP), which retain all lymphoid and myeloid potential but exist only transiently, rapidly differentiating into T and NK lineages. (Medical Immunology, p.\u00a0118)"}
{"_id": "WikiPedia_Hematology$$$corpus_5859", "text": "Stage Two:  Proliferative Expansion and T Lineage Commitment"}
{"_id": "WikiPedia_Hematology$$$corpus_5860", "text": "Final commitment to the T\u00a0cell lineage occurs within the thymus microenvironment, the microscopic structures of the thymus where T\u00a0cells are nurtured. The most primitive T\u00a0cells retain multipotential ability and can differentiate into cells of the myeloid or lymphoid lineages (B\u00a0cells, DC, T\u00a0cells, or NK\u00a0cells)."}
{"_id": "WikiPedia_Hematology$$$corpus_5861", "text": "More differentiated double negative T\u00a0cells (DN2\u00a0cells) have more limited potentiality but are not yet fully restricted to the T\u00a0cell lineage (they can still develop into DC, T\u00a0cells, or NK\u00a0cells). Later on, they are fully committed to the T cell lineage- when thymocytes expressing Notch1 receptors engage thymus stromal cells expressing Notch1 ligands, the thymocytes become finally committed to the T-cell lineage. See Gallery Image \"Double Negatives\""}
{"_id": "WikiPedia_Hematology$$$corpus_5862", "text": "With the commitment to the T cell lineage, begins a very complex process known as  TCR  gene rearrangement. This creates an enormous diversity of T\u00a0cells bearing antigen receptors. Afterward some T cells leave the thymus to migrate to the skin and  mucosae ."}
{"_id": "WikiPedia_Hematology$$$corpus_5863", "text": "Stage Three:  \u03b2-Selection"}
{"_id": "WikiPedia_Hematology$$$corpus_5864", "text": "Stage Four:  T Cell Receptors Selection"}
{"_id": "WikiPedia_Hematology$$$corpus_5865", "text": "Only 2% to 3% of the differentiating thymocytes, those that express TcR capable of interaction with MHC molecules, but tolerant to self-peptides,  [ further explanation needed ]  survive the Stage Four selection process."}
{"_id": "WikiPedia_Hematology$$$corpus_5866", "text": "Stage Five:  Continuing Differentiation in the Periphery"}
{"_id": "WikiPedia_Hematology$$$corpus_5867", "text": "It was previously believed that the human thymus remained active as the site of T\u00a0cell differentiation only until early adulthood and that later in adult life the thymus  atrophies , perhaps even vanishing. Recent reports indicate that the human thymus is active throughout adult life. Thus, several factors may contribute to the supply of T\u00a0cells in adult life: generation in the thymus, extra-thymic differentiation, and the fact that memory T\u00a0cells are long-lived and survive for decades."}
{"_id": "WikiPedia_Hematology$$$corpus_5868", "text": "The thymus also gives rise to the so-called \u2018unconventional T\u00a0cells\u2019 such at \u03b3\u03b4 T\u00a0cells, natural killer T\u00a0cells (NKT) and regulatory T\u00a0cells (T reg ). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5869", "text": "\u03b3\u03b4T cells represent only 1% to 5% of the circulating T\u00a0cells but are abundant in the mucosal immune system and the skin, where they represent the dominant T\u00a0cell population. These \u2018non-MHC restricted T\u00a0cells\u2019 are involved in specific primary immune responses, tumor surveillance, immune regulation and wound healing. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5870", "text": "Several differences between \u03b1\u03b2 and \u03b3\u03b4 T cell development have been described. They emigrate from the thymus in \"waves\" of clonal populations, which home to discrete tissues. For example, one kind is found in the peripheral blood while another predominates in the intestinal tract."}
{"_id": "WikiPedia_Hematology$$$corpus_5871", "text": "Human NKT cells are a unique population and are thought to play an important role in tumor immunity [ 16 ]   and  immunoregulation ."}
{"_id": "WikiPedia_Hematology$$$corpus_5872", "text": "T reg  cells are considered as naturally occurring regulatory T cells. Tregs comprised about 5% of the circulating  CD4 +  T\u00a0cells. These cells are thought to possess an important autoimmunity property by regulating 'autoreactive' T\u00a0cells in the  periphery . (Medical Immunology, p.\u00a0117-122)"}
{"_id": "WikiPedia_Hematology$$$corpus_5873", "text": "B cells are formed and mature in bone marrow (and spleen)."}
{"_id": "WikiPedia_Hematology$$$corpus_5874", "text": "It is a good mnemonic aide that B cells are formed in the bone marrow, but it is a mere coincidence since B cells were first studied in the chicken's  bursa of Fabricius  and it is from this bursa that B cells get their name. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5875", "text": "These B cells then leave the bone marrow and migrate via bloodstream and the lymph to peripheral lymphoid tissues, such as a spleen, lymph nodes, tonsils and mucosal tissues. Once in a secondary lymphoid organ the B cell can be introduced to an antigen that it is able to recognize. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5876", "text": "Through this antigen recognition and other cell interactions the B cell becomes activated and then divides and differentiates to become a plasma cell. The plasma cell, a B cell end product, is a very active  antibody -secreting cell that helps protect the body by attacking and binding to antigen."}
{"_id": "WikiPedia_Hematology$$$corpus_5877", "text": "Even after many decades of research, some controversy remains as to where B cells mature and 'complete their education', with the possibility remaining that the site may also partially be  peri-intestinal lymphoid tissues . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5878", "text": "B lymphopoiesis occurs exclusively in the bone marrow and B lymphocytes are made continuously throughout life there in a 'microenvironment' composed of  stromal cells ,  extracellular matrix , cytokines and growth factors, which are critical for proliferation, differentiation, and survival of early lymphocyte and B-lineage precursors."}
{"_id": "WikiPedia_Hematology$$$corpus_5879", "text": "The relative proportion of precursor B cells in the bone marrow remains rather constant throughout the life span of an organism. There are stages such as Pre-B-I cells (5% to 10% of the total); Pre-B-II cells (60% to 70%) while the remaining 20% to 25% are immature B cells.  Most textbooks say that B Cells mature in the bone marrow but, generally, immature B cells migrate to the spleen for 'higher education' of some sort where they go through transitional stages before final maturation. (Medical Immunology, p.\u00a0136)"}
{"_id": "WikiPedia_Hematology$$$corpus_5880", "text": "B lymphocytes are identified by the presence of soluble  immunoglobulin G  (IgG). This is the most common protective immunoglobulin in the adult body. After antigenic stimulation, B cells differentiate into plasma cells that secrete large quantities of soluble IgG. This is the final stage of B lymphopoiesis, but it is the clincher because the plasma cells must either issue antibody close to a source of infection or disseminate it in the blood to fight an infection at a distance or in an inaccessible part of the body."}
{"_id": "WikiPedia_Hematology$$$corpus_5881", "text": "Basic map of B cell lymphopoiesis"}
{"_id": "WikiPedia_Hematology$$$corpus_5882", "text": "A generally regarded valid map of B cell lymphopoiesis is as follows in sequence, in two parts with the first being in the bone marrow and the second in the spleen:. [ 18 ]  The development process in the bone marrow occurs in  germinal centers"}
{"_id": "WikiPedia_Hematology$$$corpus_5883", "text": "In the bone marrow"}
{"_id": "WikiPedia_Hematology$$$corpus_5884", "text": "In the spleen"}
{"_id": "WikiPedia_Hematology$$$corpus_5885", "text": "NK cells, which lack antigen specific receptors, develop in the bone marrow. After maturation and release from the marrow they circulate in the blood through their lifetime seeking opportunity. The opportunity they seek is to encounter and recognize and then kill abnormal cells such as  cancer  or virally infected cells. It is well known that lymphocytes never have granules or at least not granules that are readily visible even upon  staining . However, NK cells are the exception. They do have numerous granules which provide their ability to  kill cells  and these granules are why NK cells have an alternate name- Large Granular Lymphocytes (LGLs). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5886", "text": "NK cells are the only lymphocytes considered part of the  innate immune system  (in contrast to the  adaptive immune system . Yet they are much more closely related to T cells (part of the  adaptive immune system ) than to other cells of the innate immune system. NK cells not only share many surface markers, functions and activities in common with T Cells, they also arise from a common T/NK progenitor.  The T/NK precursor is also believed to be the source of a subpopulation of lymphoid DC. (Medical Immunology, p.\u00a0121)"}
{"_id": "WikiPedia_Hematology$$$corpus_5887", "text": "NK cells have a definition 'barcode' as CD3, CD16+, CD56t lymphocytes. (See Barcode Section of this article). NK progenitors can be found mainly in the thymus (mouse), but the thymus is not absolutely required for NK development.  Probably NK cells can develop in a variety of organs, but the major site of NK cell development is not known. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5888", "text": "In humans, the majority (85\u201390%) of the NK cells have a high cytolytic capacity (the ability to  lyse  cells). A smaller subset (10\u201315%) called NK 'CD56 bright' is chiefly responsible for  cytokine  production and has  enhanced survival . Traveling to  lymph nodes  the 'CD56 bright' NK cells differentiate again into mature NK cells which express  killer cell immunoglobulin-like receptors  (KIR), natural cytotoxicity receptors (NCR), and critical  adhesion molecules . (Medical Immunology, p.\u00a0122)"}
{"_id": "WikiPedia_Hematology$$$corpus_5889", "text": "The process by which CLP cells may differentiate to generate  dendritic cells  of lymphoid lineage is not yet well defined. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5890", "text": "DCs are highly specialized and efficient  antigen-presenting cells . Cells identical in appearance come both from a myeloid lineage (referred to as myeloid dendritic cells) and also from a lymphoid lineage (referred to as  plasmacytoid dendritic cells ). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5891", "text": "The development and regulation of DC is not well-characterized. While the DC precursors have been identified in the human fetal liver, thymus, and bone marrow, during adult life DC are thought to be produced only from the bone marrow and released into the blood to wander and settle down. Overall, a large number of DC of varying types are dispatched throughout the body, especially at epithelia such as skin, to monitor invaders and nibble their antigens. (Medical Immunology, p.\u00a0122)"}
{"_id": "WikiPedia_Hematology$$$corpus_5892", "text": "Lymphocytes have a number of alarming properties such as the ability to wander around the body and take up lodging almost anywhere, and while on the way issue commands in the form of  cytokines  and  chemokines  and  lymphokines , commands that affect many cell types in the body and which may also recursively induce further lymphopoiesis. One strong behavior pattern that captivates researchers and the public alike is the ability of lymphocytes to act as police, judge and executioner to kill other cells or demand that they suicide, a command that is usually obeyed. There seems to be no other sentencing option available. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5893", "text": "Killers are distinguished from cells such as macrophages that eat other cells or munch debris by a method called  phagocytosis . Killers do not use phagocytosis; they just kill and leave the clean-up to other cells."}
{"_id": "WikiPedia_Hematology$$$corpus_5894", "text": "Killers are known to attack virus-infected cells and cells that have become cancerous. Because of these abilities much research has been done into transforming these qualities into medical therapy, but progress has been slow."}
{"_id": "WikiPedia_Hematology$$$corpus_5895", "text": "Here is the parade of killers and how they work:"}
{"_id": "WikiPedia_Hematology$$$corpus_5896", "text": "(also called  Tc  or antigen-specific cyto-lytic or -toxic T lymphocytes ( CTL) ). [ 20 ]  Tc kill by apoptosis and either splash their target with  perforin  or  granzymes  or else use  Fas-Fasl Interaction  to command target elimination. This kills cells that are infected and display antigen."}
{"_id": "WikiPedia_Hematology$$$corpus_5897", "text": "These kill with exactly the same methods as Tc but have no interaction with any antigen. They select their targets based on typical molecules displayed by cells that are under stress by viral infection. NK Cells mainly are in the circulation (5-15% of the circulating lymphocytes) yet are also distributed in tissues everywhere. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5898", "text": "Natural Killer T Cells. Human NK T cells are a unique population (which express NK cell markers such as CD56 and KIR). NKT cells are thought to play an important role in tumor immunity and immunoregulation (Medical Immunology, p.\u00a0135), yet little is known. Recent evidence suggests a role working together with  hepatic stellate cells  being a liver-resident antigen-presenting cell that presents lipid antigens to and stimulates proliferation of NKT cells."}
{"_id": "WikiPedia_Hematology$$$corpus_5899", "text": "A heterogeneous group with ill-defined properties."}
{"_id": "WikiPedia_Hematology$$$corpus_5900", "text": "However, in summary there is  no known cell or set of cells  that is capable of killing cancerous cells in general."}
{"_id": "WikiPedia_Hematology$$$corpus_5901", "text": "Because all WBCs are microscopic, colorless and often seemingly identical in appearance they are individually identified by their natural chemical markers, many of which have been analyzed and named. When two cells have the same markers, the reasonable assumption is made that the cells are identical at that time.  A set of markers is colloquially described as the  barcode  for that cell or that cell line."}
{"_id": "WikiPedia_Hematology$$$corpus_5902", "text": "HSCs are technically described as: lacking  FMS-like tyrosine kinase 3  (Flt3) and lacking the markers specific to discrete lymphoid lineages (Lin) but expressing high levels of Sca1 and c-kit; HSC also express CD44, low levels of Thy1.1 (CD90), but no IL-7Ra or CD27. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5903", "text": "This is called the (surface) phenotype of an HSC. It can be expressed as a set (Lin2, Sca1high, c-kit high, CD44+, Thy1.1low, CD27 2, and IL-7Ra2). This set is a \u2018barcode\u2019 for the HSC, akin to the barcode label attached to your chicken-wing plastic bag for checkout at a supermarket! Scientists use these barcodes to check, categorize and accumulate cells for many purposes often using laboratory methods such as  cell flow cytometry . These barcodes partially define the modern meaning of  phenotype  for  leukocytes ."}
{"_id": "WikiPedia_Hematology$$$corpus_5904", "text": "Progression of HSC differentiation and lineage commitment is indicated by changes in this  phenotype . That is, as the cell changes, the markers will also change, and the barcode will change."}
{"_id": "WikiPedia_Hematology$$$corpus_5905", "text": "New questions emerge in immunology continuously as though there were a  stem cell  for questions. For example, it was thought that the process of lymphopoiesis was a direct, orderly unidirectional sequence. But it is not clear  if end-stage lymphocytes come from progenitors that are homogeneous populations or overlapping populations. Nor is it clear whether lineages of lymphocytes develop via a continuum of differentiation with a progressive loss of lineage options or whether abrupt events result in the acquisition of certain properties. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5906", "text": "Changes in cytoplasm,  morphology  of the cell nucleus, granules, cell internal biochemistry, signaling molecules and cell surface markers are difficult to correlate with definite stages in lymphopoiesis. The morphological differences do not just correspond to steps in  mitosis  (somatic cell division), but result from continuous \"maturation processes\" of the cell nucleus, as well as of the cytoplasm and so one must not be too rigid about morphological distinctions between certain cell stages. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5907", "text": "Until recently the model of the CMP generating all myeloid cell and the CLP generating all lymphoid cells was considered necessary and sufficient to explain the known facts observed in the generation of WBCs, and it is still found in most basic textbooks. However, beginning around 2000 and gaining momentum after 2005 [ 25 ]  in both studies in humans and mice, new complexities were noted and published in papers. [ citation needed ]  These studies are important now mainly to immunology researchers but are likely to eventually lead to changes in medical treatments."}
{"_id": "WikiPedia_Hematology$$$corpus_5908", "text": "The changes were sparked by observations that lymphopoiesis did not always break into two lineages at the level of the CLP. Worse, some macrophages (long considered a myeloid lineage) could be generated by lymphoid lineage progenitors. In essence focus has been shifted away from the CLP to the MLP [ citation needed ]  (lymphoid-specified progenitors), which are clearly lymphoid progenitors yet retain some myeloid potential, particularly the ability in both humans and mice to make macrophages \u2013 one of the most versatile of immune cell defenders \u2013 and also many dendritic cells, the best 'watchdogs' of antigen invaders."}
{"_id": "WikiPedia_Hematology$$$corpus_5909", "text": "However, whatever the details may turn out to be, the process of lymphopoiesis always seems to relentlessly give rise to progeny with special attributes and abilities \u2013 \"superpowers\" so to speak \u2013 but with progressively more restricted lymphoid developmental potential."}
{"_id": "WikiPedia_Hematology$$$corpus_5910", "text": "This model of lymphopoiesis had the virtue of relative simplicity, agreement with nomenclature and terminology, and is still essentially valid for the laboratory mouse."}
{"_id": "WikiPedia_Hematology$$$corpus_5911", "text": "pHSC, MPP and ELP cells are not fully committed to the lymphoid lineage because if one is removed to a different location it may differentiate into non-lymphoid progeny. However CLP  are  committed to the lymphoid lineage. The CLP is the transit cell responsible for these (generally parallel) stages of development, below:"}
{"_id": "WikiPedia_Hematology$$$corpus_5912", "text": "By 2008 it was found that \"the majority of early thymic progenitor [ETP] cells do not commit to becoming T cells by the time they get to the thymus gland. ETP cells retained the ability to become either T cells or myeloid cells.\" [ 28 ] \n [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5913", "text": "See also\u00a0: [ 30 ] \n [ 31 ] \n [ 32 ] \n [ 33 ] \n [ 34 ] \n [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5914", "text": "Texts in bold  are the most heavily cited in this article."}
{"_id": "WikiPedia_Hematology$$$corpus_5915", "text": "Alternate views of lineages"}
{"_id": "WikiPedia_Hematology$$$corpus_5916", "text": "Hematopoietic stem cells  (HSCs) have high regenerative potentials and are capable of differentiating into all blood and immune system cells. Despite this impressive potential, HSCs have limited potential to produce more multipotent stem cells. [ 1 ]  This limited self-renewal potential is protected through maintenance of a quiescent state in HSCs. Stem cells maintained in this quiescent state are known as long term HSCs (LT-HSCs). During quiescence, HSCs maintain a low level of metabolic activity and do not divide. [ 2 ] [ 3 ] [ 4 ]  LT-HSCs can be signaled to proliferate, producing either  myeloid  or  lymphoid  progenitors. Production of these progenitors does not come without a cost: When grown under laboratory conditions that induce proliferation, HSCs lose their ability to divide and produce new progenitors. [ 5 ]  Therefore, understanding the pathways that maintain proliferative or quiescent states in HSCs could reveal novel pathways to improve existing therapeutics involving HSCs. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5917", "text": "All adult stem cells can undergo two types of division: symmetric and asymmetric. When a cell undergoes symmetric division, it can either produce two differentiated cells or two new stem cells. When a cell undergoes asymmetric division, it produces one stem and one differentiated cell. Production of new stem cells is necessary to maintain this population within the body. [ 7 ]  Like all cells, hematopoietic stem cells undergo metabolic shifts to meet their bioenergetic needs throughout development. [ 1 ]  These metabolic shifts play an important role in signaling, generating biomass, and protecting the cell from damage. Metabolic shifts also guide development in HSCs and are one key factor in determining if an HSC will remain quiescent, symmetrically divide, or asymmetrically divide. [ 1 ] [ 8 ] [ 9 ] [ 10 ]  As mentioned above, quiescent cells maintain a low level of oxidative phosphorylation and primarily rely on glycolysis to generate energy. Fatty acid  beta-oxidation  has been shown to influence fate decisions in HSCs. [ 11 ]  In contrast, proliferative HSCs primarily depend on oxidative phosphorylation. This switch is accompanied by an increase in intracellular  reactive oxygen species  (ROS) levels and increased anabolic activity in cells [ 3 ] [ 12 ] [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5918", "text": "It is well understood that quiescent HSCs have very low levels of metabolic activity. LT-HSCs primarily rely on  anaerobic glycolysis  to generate energy. Unlike other types of HSCs, little energy is produced from mitochondrial oxidative respiration. The reason from this is likely two-fold: LT-HSCs reside within the hypoxic niche of the bone marrow, and low levels of mitochondrial respiration protect quiescent cells from damage induced ROS. [ 15 ] [ 16 ]  When excessive levels of ROS are present, LT-HSCs undergo differentiation or  apoptosis , losing their ability to self-renew. [ 17 ]  This suggests that dependence on glycolysis is not only an environmental adaptation, but also a necessity for LT-HSCs to preserve their stemness."}
{"_id": "WikiPedia_Hematology$$$corpus_5919", "text": "LT-HSC preference for glycolysis is encoded by the transcription factor  MEIS1  and, to a lesser extent, the protein CBP/p300-interacting transactivator 2 ( CITED2 ). [ 18 ] [ 19 ] [ 20 ]  Both enzymes up regulate hypoxia-inducible factor 1\u03b1 ( HIF1\u03b1 ). Under hypoxic conditions, HIF1\u03b1 dimerizes with HIF1\u00df to increase expression of several glycolytic enzymes to lead to an enhanced rate of glycolysis. [ 19 ]  HIF1\u03b1 also activates  pyruvate dehydrogenase kinases  (PDK) 2 and 4. [ 15 ]  These enzymes inhibit  pyruvate dehydrogenase  (PDH). PDH converts  pyruvate  into  acetyl-CoA , a crucial first step for metabolite entry into the  TCA cycle  and  oxidative phosphorylation . Because this system inhibits mitochondrial metabolism and activates glycolysis, it is thought that the metabolic reprogramming by HIF1\u03b1 is a main driver of LT-HSC quiescence."}
{"_id": "WikiPedia_Hematology$$$corpus_5920", "text": "Metabolic reprogramming by HIF1\u03b1 does not always happen through action on PDKs. HIF1\u03b1 can also promote expression of the cytosolic protein  CRIPTO . CRIPTO then interacts with its cell surface receptor  GRP78  to activate glycolytic enzymes. [ 21 ] [ 22 ]  Extracellular cytokines and chemokines may also contribute to HIF1\u03b1 activity, but further work is required to elucidate the exact contribution of these signaling molecules."}
{"_id": "WikiPedia_Hematology$$$corpus_5921", "text": "In addition to HIF1\u03b1, MEIS1 induces transcription of  HIF2\u03b1 . Though this enzyme is structurally similar to HIF1\u03b1, HIF2\u03b1 has distinct functions. HIF2\u03b1 is thought to protect HSCs from mitochondrial ROS production. An accumulation of ROS in HSCs causes stress at the endoplasmic reticulum, eventually inducing the  unfolded protein response  and apoptosis. [ 23 ]  HIF2\u03b1 protects the cell from ROS accumulation by up regulating several genes involved in ROS quenching, including  catalase ,  glutathione peroxidase type I , and  superoxide dismutases . [ 8 ]  Activation of HIF2\u03b1 is therefore necessary to maintain cellular health during quiescence."}
{"_id": "WikiPedia_Hematology$$$corpus_5922", "text": "Despite low levels of mitochondrial respiration, emerging evidence shows that LT-HSCs with the highest regenerative potential also have a high number of mitochondria. [ 25 ]  Despite this, quiescent HSC mitochondria have a low membrane potential and low rates of oxidative phosphorylation. This again highlights the dependence of LT-HSCs on glycolysis to generate energy. Despite their inactivity, possessing many mitochondria may indicate that the quiescent HSCs are prepared for proliferation once an appropriate signal is received [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5923", "text": "Recently, it has been discovered that fatty acid oxidation (FAO) is a major determinant in whether a stem cell will symmetrically or asymmetrically divide. [ 26 ]  Transport of fatty acids into the mitochondria and their subsequent metabolism must be efficient in order for cells to maintain the ability to self-renew. In HSCs, transcriptional activation of nuclear genes involved in fatty acid transport and \u03b2-oxidation through a promyelocytic leukemia protein (PML)/peroxisome proliferation-activated receptor-gamma coactivator 1\u03b1 ( PGC-1\u03b1 )/peroxisome proliferator-activating receptor type \u03b4 ( PPAR\u03b4 ) mediates efficiency of these processes. This pathway is also essential for HSC self-renewal because it promotes maintenance of the stem cell population. [ 26 ]  FAO promotes asymmetric HSC division to produce one progenitor and one stem cell. Inhibition of FAO has been shown to expand the population of progenitor cells, thus decreasing the stem cell population. [ 27 ]  Despite correlations between FAO and asymmetrical HSC divisions, the exact mechanism by which FAO governs stem cell fate decisions is still unclear."}
{"_id": "WikiPedia_Hematology$$$corpus_5924", "text": "Though maintenance of quiescence is important to HSCs to preserve their self-renewal capacity, proliferation is necessary to regenerate blood cells and immune cells for the body. During divisions, HSCs leave the hypoxic niche and begin circulating. Under these normoxic conditions, HIF1\u03b1 is hydroxylated by prolyl hydroxylases PHD1, 2 and 3. [ 29 ] [ 30 ] [ 31 ]  This hydroxylation triggers the cell to degrade HIF1\u03b1 through the von Hippel-Lindau ( VHL ) ubiquitin ligases. Degradation of HIF1\u03b1 prevents dimerization with HIF1\u00df, impeding the transcription of glycolytic genes. Degrading HIF1\u03b1 also prevents activation of PDK2 and 4, thus resuming function of PDH in the mitochondria. Because the cell is now able to catalyze the production of acetyl-CoA, mitochondrial metabolism is able to resume. Restoration of this mitochondrial metabolism is coordinated by reentry into the cell cycle. Concurrent with reinitiation of mitochondrial metabolism is an upregulation in transcription of cell cycle genes and genes involved in anabolic activities. [ 32 ] [ 33 ]  As expected, HSCs with a high mitochondrial membrane potential have higher rates of expression for genes related to the cell cycle and metabolism. [ 33 ]  The accompanying increase in ROS levels in these proliferating HSCs may in part drive differentiation of HSCs, but more work is needed to fully elucidate the role of ROS in this process [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5925", "text": "Accompanying the processes driven by HIF1\u03b1 is an activation of mitochondrial oxidative phosphorylation through inactivation of the protein tyrosine phosphatase mitochondrial 1 ( PTPMT1 ) enzyme. [ 27 ]  PTPMT-1 is essential for differentiation of HSCs into progenitors, and loss of this enzyme results in failure to produce blood cells in mice. [ 34 ]  Targets of PTPMT-1 include phosphatidylinositol phosphates (PIPs). When PIPs are acted upon by PTPMT-1, the mitochondrial membrane potential decreases. This decrease inhibits glucose entry into the TCA cycle and subsequent ATP generation through the electron transport chain. [ 34 ]  Thus, PTPMT-1 activity is crucial for HSCs to differentiate."}
{"_id": "WikiPedia_Hematology$$$corpus_5926", "text": "Another important suppressor of mitochondrial metabolism during quiescence is mitochondrial carrier homolog 2 ( MTCH2 ). [ 16 ]  Loss of MTCH2 increases oxidative phosphorylation and triggers HSC differentiation. As expected, this increase in oxidative phosphorylation increases ROS levels, ATP levels, and mitochondrial size. These phenotypes highlight the importance of MTCH2 in directing HSC fate."}
{"_id": "WikiPedia_Hematology$$$corpus_5927", "text": "Upregulation of glycolysis in proliferative HSCs may drive the  pentose phosphate pathway  (PPP) to maintain redox balance upon mitochondrial activation. [ 35 ] [ 36 ]  The PPP generates nicotinamide adenine dinucleotide phosphate ( NADPH ), which is a powerful cellular reducing agent. Production of NADPH may protect cells against accumulation of ROS because it is a key component in the glutathione-reductase system. [ 36 ]  Additionally, NADPH is required for synthesis of nucleic acids and lipids. Thus, high intracellular NADPH may be essential to generate biomass for HSCs as they reenter the cell cycle. [ 35 ]  Work in ex- vivo  HSC expansion systems supports this idea, but further work is needed to characterize the role of the PPP  in vivo [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5928", "text": "Several signaling pathways also have roles in mediating the metabolic shift from quiescent to proliferative HSCs. For example, purine metabolism is upregulated and thus promotes entry into the cell cycle through signaling in the  p38 MAPK  pathway.  ERK  and  mTOR , other major signaling pathways, are also activated during cell cycle entry. Among other functions, these pathways promote protein, nucleotide, and lipid synthesis. Active ERK and mTOR pathways also lead to increased nutrient uptake in HSCs. In addition to this biosynthetic role, mTOR can also increase the rate of ATP production in cells. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5929", "text": "Thrombopoiesis  is the formation of  thrombocytes  (blood platelets) in the  bone marrow .  Thrombopoietin  is the main regulator of thrombopoiesis. Thrombopoietin affects most aspects of the production of platelets. This includes  self-renewal  and expansion of  hematopoietic stem cells , stimulating the increase of megakaryocyte progenitor cells, and supporting these cells so they mature to become platelet-producing cells. [ 2 ] \nThe process of thrombopoiesis is caused by the breakdown of proplatelets (mature megakaryocyte membrane  pseudopodial  projections). During the process almost all of the membranes, organelles, granules, and soluble macromolecules in the cytoplasm are being consumed. Apoptosis also plays a role in the final stages of thrombopoiesis by letting proplatelet processes to occur from the cytoskeleton of actin. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5930", "text": "Platelets are formed by megakaryocytes and are present in the bloodstream for 5\u20137 days. Platelets are regulators of hemostasis and thrombosis. Platelets become active in the blood following vascular injury. Vascular injury causes platelets to stick to the cellular matrix that is exposed under the endothelium, form a platelet plug, and then form a  thrombus . Platelets are essential in the formation of an occlusive thrombus and are the main target of preventing the formation of an arterial thrombus. Platelets are also important in innate immunity and regulating tumor growth and vessel leakage. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5931", "text": "The  megakaryoblast  is a platelet precursor that undergoes  endomitosis  to form megakaryocytes that have 8 to 64 nuclei. Megakaryocytes shed platelets into the bloodstream. \u03b21-tubulin microtubules, which are found in megakaryocytes, facilitate this process of shedding platelets into the bloodstream. [ 5 ]  Megakaryocytes are precursor cells that are highly specialized. Megakaryocytes give rise to 1,000 to 3,000 platelets. Megakaryocytes function in the process of Thrombopoiesis by producing platelets and releasing platelets into the bloodstream. [ 6 ]  Megakaryocyte development is regulated mainly by thrombopoietin. IL-3, IL-6, and IL-11 also play a role in the development of megakaryocytes by working closely with thrombopoietin. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5932", "text": "Thrombopoietin is the main regulator in the process of thrombopoiesis. In the liver and renal tubular epithelial cells, thrombopoietin is constantly being produced. Platelets and platelet precursors clear and destroy the thrombopoietin that is produced so the concentration of plasma thrombopoietin levels and platelet and platelet precursor mass are inversely proportional. If there is less platelet mass present, less thrombopoietin is cleared, which causes an increase in free plasma thrombopoietin that stimulates thrombopoiesis. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5933", "text": "Transfusion medicine  (or  transfusiology ) is the branch of medicine that encompasses all aspects of the  transfusion  of blood and  blood components  including aspects related to hemovigilance. It includes issues of  blood donation ,  immunohematology  and other laboratory testing for transfusion-transmitted diseases, management and monitoring of clinical transfusion practices,  patient blood management , therapeutic  apheresis ,  stem cell  collections,  cellular therapy , and  coagulation . Laboratory management and understanding of state and federal regulations related to blood products are also a large part of the field."}
{"_id": "WikiPedia_Hematology$$$corpus_5934", "text": "In most countries,  immunohematology  and transfusion medicine specialists provide expert opinion on  massive transfusions , difficult/incompatible transfusions and rational use of specialised blood product therapy like irradiated blood/ leukodepleted /washed blood products."}
{"_id": "WikiPedia_Hematology$$$corpus_5935", "text": "The blood donor center is the facility that collects blood components from screened blood donors, either whole blood or separate components such as plasma or platelets only via apheresis. These blood components are then transported to a central location for processing such as fractionation, testing and redistribution. The testing includes determining blood type and testing for infectious diseases. Whole blood is fractionated into red blood cells, platelets and plasma whilst plasma can be further refined into separate components such as albumin, clotting factor concentrates and immunoglobulin."}
{"_id": "WikiPedia_Hematology$$$corpus_5936", "text": "The  blood bank  is the section of the clinical laboratory where  laboratory scientists  store and distribute  blood components . Both areas are typically overseen by a specialist in transfusion medicine. Transfusion medicine was earlier a branch of  clinical pathology , however the field has now expanded into a clinical, hospital-based specialty. The practice of transfusion medicine involves both laboratory and clinical aspects of transfusion as communication between blood bank and patients, treating specialists and other medical staff is vital in situations such as massive transfusions or  transfusion reactions ."}
{"_id": "WikiPedia_Hematology$$$corpus_5937", "text": "To ensure the safety of blood components, regimented procedures and quality assurance systems must be in place covering all aspects of the transfusion chain, from donation to transfusion outcomes. Within hospitals, transfusion committees are established to ensure safe hospital transfusion practice such as compliance with standards and guidelines, reviewing transfusion reactions and management of blood supply. These multidisciplinary committees are composed of transfusion medicine specialists,  transfusion nurses , laboratory scientists, clinicians and staff from hospital management and the quality team."}
{"_id": "WikiPedia_Hematology$$$corpus_5938", "text": "In 1628,  English  physician  William Harvey  discovered that blood circulates around the body. Soon thereafter, the first blood transfusion was attempted. In 1665 another English doctor  Richard Lower  successfully used blood transfusion between dogs to keep them alive. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5939", "text": "Karl Landsteiner  is recognized as the father of transfusion medicine. Landsteiner is credited with the first classification of human blood into the four types (A, B, AB, O) of the  ABO blood group system ."}
{"_id": "WikiPedia_Hematology$$$corpus_5940", "text": "Australia"}
{"_id": "WikiPedia_Hematology$$$corpus_5941", "text": "In Australia, transfusion medicine is a sub-specialty of haematology. Training in transfusion medicine is covered by the Royal College of Pathologists of Australasia (RCPA)."}
{"_id": "WikiPedia_Hematology$$$corpus_5942", "text": "Australia has national blood services operated by the  Australian Red Cross Blood Service . There are a series of guidelines and standards relevant to the laboratory released by the National Association of Testing Authorities, Australia (NATA), [ 2 ]  Australian and New Zealand Society of Blood Transfusion (ANZSBT) [ 3 ]  and RCPA. [ 4 ]  Similarly, there are a series of clinical practice,  patient blood management guidelines  by the National Blood Authority."}
{"_id": "WikiPedia_Hematology$$$corpus_5943", "text": "In Australia, the Serious Transfusion Incident Reporting (STIR) system is in place to capture serious transfusion incidents and near-miss incidents. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5944", "text": "In Denmark, the subject is covered by the specialty, \"Clinical Immunology\"."}
{"_id": "WikiPedia_Hematology$$$corpus_5945", "text": "In Germany, transfusion medicine is an independent specialty. Physicians complete a three-year residency in transfusion medicine and two years in another relevant clinical settings like internal medicine or surgery."}
{"_id": "WikiPedia_Hematology$$$corpus_5946", "text": "In India, Immunohematology and Transfusion Medicine is a medical post graduate specialty (MD) recognized by Medical Council of India since 2009."}
{"_id": "WikiPedia_Hematology$$$corpus_5947", "text": "Physicians completing their internship may pursue a four-year Master of Medicine (Transfusion Medicine) programme to specialize in transfusion medicine in Malaysia. [ 6 ]  They are eligible for registration with National Specialist Registry as transfusion medicine specialists after completion of gazettement upon graduation. [ 7 ]  Transfusion medicine specialists in Malaysia may further their sub-specialty training in the field of immunohaematology, cord blood, patient blood management, cellular therapy, and regenerative medicine."}
{"_id": "WikiPedia_Hematology$$$corpus_5948", "text": "In Norway, the subject is covered by the specialty, \"Immunology and Transfusion medicine\""}
{"_id": "WikiPedia_Hematology$$$corpus_5949", "text": "In the United Kingdom, transfusion medicine is a sub-speciality of  hematology ."}
{"_id": "WikiPedia_Hematology$$$corpus_5950", "text": "Serious Hazards of Transfusion  (SHOT) collects and analyses reports of adverse events related to transfusion, aiming to improve patient safety. [ 8 ]  Its reports have led to wider training for medical staff in the UK and a central reporting scheme to allow errors to be reported. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5951", "text": "There is the Better Blood Continuing Education Programme, which is organised by the  EUB  which is part of the  SNBTS . The EUB consists of many specialist  healthcare professionals . The programme's aim is to improve transfusion medicine practise. The programme is reviewed each annually in January. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5952", "text": "In the UK, there are restrictions in place to decrease the risk of the transmission of  Creutzfeldt\u2013Jakob disease ."}
{"_id": "WikiPedia_Hematology$$$corpus_5953", "text": "Physicians from a wide range of backgrounds, including  pathology ,  internal medicine ,  anesthesiology  and  pediatrics , are eligible for board certification in Transfusion Medicine following a 1\u20132 year fellowship.  It is a board-certified sub-specialty recognized by the  American Board of Pathology . [ 11 ]   These specialists are often considered consultants for physicians who require expert advice on the subjects listed above. Transfusiology is not a recognized term in the US."}
{"_id": "WikiPedia_Hematology$$$corpus_5954", "text": "The  ABO blood group system  is used to denote the presence of one, both, or neither of the A and B  antigens  on  erythrocytes  (red blood cells). [ 1 ]  For human  blood transfusions , it is the most important of the 44 different  blood type  (or group) classification systems currently recognized by the  International Society of Blood Transfusions  (ISBT) as of \nDecember 2022. [ 2 ] [ 3 ]  A mismatch in this  serotype  (or in various others) can cause a potentially fatal  adverse reaction  after a transfusion, or an  unwanted immune response  to an organ transplant. [ 4 ]  Such mismatches are rare in modern medicine. The associated anti-A and anti-B  antibodies  are usually  IgM  antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses."}
{"_id": "WikiPedia_Hematology$$$corpus_5955", "text": "The ABO blood types were discovered by  Karl Landsteiner  in 1901; he received the  Nobel Prize in Physiology or Medicine  in 1930 for this discovery. [ 5 ]  ABO blood types are also present in other  primates  such as  apes , monkeys and  Old World monkeys . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5956", "text": "The ABO blood types were first discovered by an Austrian physician,  Karl Landsteiner , working at the Pathological-Anatomical Institute of the University of Vienna (now  Medical University of Vienna ). In 1900, he found that red blood cells would clump together ( agglutinate ) when mixed in test tubes with sera from different persons, and that some human blood also agglutinated with animal blood. [ 7 ]  He wrote a two-sentence footnote:"}
{"_id": "WikiPedia_Hematology$$$corpus_5957", "text": "The serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. It remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5958", "text": "This was the first evidence that blood variations exist in humans \u2014 it was believed that all humans have similar blood. The next year, in 1901, he made a definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human blood into three groups, namely group A, group B, and group C. He defined that group A blood agglutinates with group B, but never with its own type. Similarly, group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5959", "text": "This was the discovery of blood groups for which Landsteiner was awarded the  Nobel Prize in Physiology or Medicine  in 1930. In his paper, he referred to the specific blood group interactions as isoagglutination, and also introduced the concept of agglutinins (antibodies), which is the actual basis of  antigen-antibody reaction  in the ABO system. [ 10 ]  He asserted:"}
{"_id": "WikiPedia_Hematology$$$corpus_5960", "text": "[It] may be said that there exist at least two different types of agglutinins, one in A, another one in B, and both together in C. The red blood cells are inert to the agglutinins which are present in the same serum. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5961", "text": "Thus, he discovered two antigens ( agglutinogens  A and B) and two antibodies (agglutinins \u2014 anti-A and anti-B). His third group (C) indicated absence of both A and B antigens, but contains anti-A and anti-B. [ 10 ]  The following year, his students Adriano Sturli and Alfred von Decastello discovered the fourth type (but not naming it, and simply referred to it as \"no particular type\"). [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5962", "text": "In 1910,  Ludwik Hirszfeld  and  Emil Freiherr von Dungern  introduced the term 0 (null) for the group Landsteiner designated as C, and AB for the type discovered by Adriano sturli and Alfred von decastello ( https://www.rockefeller.edu/our-scientists/karl-landsteiner/2554-nobel-prize/ ). They were also the first to explain the genetic inheritance of the blood groups. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5963", "text": "Czech serologist  Jan Jansk\u00fd  independently introduced blood type classification in 1907 in a local journal. [ 15 ]  He used the Roman numerical I, II, III, and IV (corresponding to modern O, A, B, and AB). Unknown to Jansk\u00fd, an American physician  William L. Moss  devised a slightly different classification using the same numerical; [ 16 ]  his I, II, III, and IV corresponding to modern AB, A, B, and O. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5964", "text": "These two systems created confusion and potential danger in medical practice. Moss's system was adopted in Britain, France, and US, while Jansk\u00fd's was preferred in most European countries and some parts of US. To resolve the chaos, the  American Association of Immunologists , the  Society of American Bacteriologists , and the Association of Pathologists and Bacteriologists made a joint recommendation in 1921 that the Jansky classification be adopted based on priority. [ 17 ]  But it was not followed particularly where Moss's system had been used. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5965", "text": "In 1927, Landsteiner had moved to the  Rockefeller Institute for Medical Research  in New York. As a member of a committee of the  National Research Council  concerned with blood grouping, he suggested to substitute Jansk\u00fd's and Moss's systems with the letters O, A, B, and AB. (There was another confusion on the use of figure 0 for German  null  as introduced by Hirszfeld and von Dungern, because others used the letter O for  ohne , meaning without or zero; Landsteiner chose the latter. [ 18 ] ) This classification was adopted by the National Research Council and became variously known as the National Research Council classification, the International classification, and most popularly the \"new\" Landsteiner classification. The new system was gradually accepted and by the early 1950s, it was universally followed. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5966", "text": "The first practical use of blood typing in transfusion was by an American physician  Reuben Ottenberg  in 1907. Large-scale application began during the First World War (1914\u20131915) when  citric acid  began to be used for  blood clot prevention . [ 10 ]   Felix Bernstein  demonstrated the correct blood group inheritance pattern of multiple  alleles  at one locus in 1924. [ 20 ]  Watkins and Morgan, in England, discovered that the ABO  epitopes  were conferred by sugars, to be specific,  N -acetylgalactosamine  for the A-type and  galactose  for the B-type. [ 21 ] [ 22 ] [ 23 ]  After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Finne  et al . (1978) found that the human erythrocyte glycoproteins contain polylactosamine chains [ 24 ]  that contains ABH substances attached and represent the majority of the antigens. [ 25 ] [ 26 ] [ 27 ]  The main glycoproteins carrying the ABH antigens were identified to be the Band 3 and Band 4.5 proteins and glycophorin. [ 28 ]  Later, Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5967", "text": "Blood groups are inherited from both parents. The ABO blood type is controlled by a single  gene  (the  ABO gene ) with three types of  alleles  inferred from  classical genetics :  i ,  I A , and  I B . The  I  designation stands for  isoagglutinogen , another term for  antigen . [ 31 ]  The gene encodes a  glycosyltransferase \u2014that is, an  enzyme  that modifies the  carbohydrate  content of the  red blood cell  antigens. The gene is located on the long arm of the  ninth chromosome  (9q34). [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5968", "text": "The  I A  allele gives type A,  I B  gives type B, and  i  gives type O. As both  I A  and  I B  are dominant over  i , only  ii  people have type O blood. Individuals with  I A I A  or  I A i  have type A blood, and individuals with  I B I B  or  I B i  have type B.  I A I B  people have both  phenotypes , because A and B express a special dominance relationship:  codominance , which means that type A and B parents can have an AB child. A couple with type A and type B can also have a type O child if they are both heterozygous ( I B i  and  I A i ). The  cis-AB  phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A 1  or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5969", "text": "Individuals with the rare  Bombay phenotype  (hh) produce antibodies against the A, B, and O groups and can only receive transfusions from other hh individuals. The table above summarizes the various blood groups that children may inherit from their parents. [ 34 ] [ 35 ]  Genotypes are shown in the second column and in small print for the offspring: AO and AA both test as type A; BO and BB test as type B. The four possibilities represent the combinations obtained when one allele is taken from each parent; each has a 25% chance, but some occur more than once. The text above them summarizes the outcomes."}
{"_id": "WikiPedia_Hematology$$$corpus_5970", "text": "Historically, ABO blood tests were used in  paternity testing , but in 1957 only 50% of American men falsely accused were able to use them as evidence against paternity. [ 36 ]  Occasionally, the blood types of children are not consistent with expectations\u2014for example, a type O child can be born to an AB parent\u2014due to rare situations, such as  Bombay phenotype  and  cis AB . [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5971", "text": "The A blood type contains about 20 subgroups, of which A1 and A2 are the most common (over 99%). A1 makes up about 80% of all A-type blood, with A2 making up almost all of the rest. [ 38 ]  These two subgroups are not always interchangeable as far as transfusion is concerned, as some A2 individuals produce antibodies against the A1 antigen. Complications can sometimes arise in rare cases when typing the blood. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5972", "text": "With the development of  DNA sequencing , it has been possible to identify a much larger number of alleles at the ABO locus, each of which can be categorized as A, B, or O in terms of the reaction to transfusion, but which can be distinguished by variations in the  DNA  sequence. There are six common  alleles  in white individuals of the  ABO gene  that produce one's blood type: [ 39 ] [ 40 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5973", "text": "The same study also identified 18 rare alleles, which generally have a weaker glycosylation activity. People with weak alleles of A can sometimes express anti-A antibodies, though these are usually not clinically significant as they do not stably interact with the antigen at body temperature. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5974", "text": "Cis AB  is another rare variant, in which A and B genes are transmitted together from a single parent. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5975", "text": "The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5976", "text": "In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of  placenames  and to the successive invasions and migrations including  Celts ,  Norsemen ,  Danes ,  Anglo-Saxons , and  Normans  who contributed the  morphemes  to the placenames and the  genes  to the population. The native Celts tended to have more type O blood, while the other populations tended to have more type A. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5977", "text": "The two common O alleles, O01 and O02, share their first 261  nucleotides  with the group A allele A01. [ 44 ]  However, unlike the group A allele, a  guanosine  base is subsequently deleted. A premature  stop codon  results from this  frame-shift mutation . This variant is found worldwide, and likely predates human migration from  Africa . The O01 allele is considered to predate the O02 allele. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5978", "text": "Some evolutionary biologists theorize that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. [ 45 ]  From oldest to youngest, these lineages comprise the following alleles:  A101/A201/O09 ,  B101 ,  O02  and  O01 . The continued presence of the O alleles is hypothesized to be the result of  balancing selection . [ 45 ]  Both theories contradict the previously held theory that type O blood evolved first. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5979", "text": "It is possible that food and environmental antigens (bacterial, viral, or plant antigens) have  epitopes  similar enough to A and B glycoprotein antigens. The antibodies created against these environmental antigens in the first years of life can cross-react with ABO-incompatible red blood cells that it comes in contact with during blood transfusion later in life. Anti-A antibodies are hypothesized to originate from immune response towards  influenza virus , whose epitopes are similar enough to the \u03b1-D-N-galactosamine on the A glycoprotein to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to originate from antibodies produced against  Gram-negative bacteria , such as  E. coli , cross-reacting with the \u03b1-D-galactose on the B glycoprotein. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5980", "text": "However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5981", "text": "The carbohydrate molecules on the surfaces of red blood cells have roles in  cell membrane  integrity,  cell adhesion , membrane transportation of molecules, and acting as receptors for extracellular ligands, and enzymes. ABO antigens are found having similar roles on  epithelial cells  as well as red blood cells. [ 48 ] [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5982", "text": "The ABO antigen is also expressed on the  von Willebrand factor  (vWF)  glycoprotein , [ 50 ]  which participates in  hemostasis  (control of bleeding). In fact, having type O blood predisposes to bleeding, [ 51 ]  as 30% of the total genetic variation observed in plasma vWF is explained by the effect of the ABO blood group, [ 52 ]  and individuals with group O blood normally have significantly lower plasma levels of vWF (and  Factor VIII ) than do non-O individuals. [ 53 ] [ 54 ]  In addition, vWF is degraded more rapidly due to the higher prevalence of blood group O with the Cys1584 variant of vWF (an amino acid  polymorphism  in VWF): [ 55 ]  the gene for  ADAMTS13  (vWF-cleaving  protease ) maps to human  chromosome 9  band q34.2, the same  locus  as ABO blood type. Higher levels of vWF are more common amongst people who have had  ischemic stroke  (from blood clotting) for the first time. The results of this study found that the occurrence was not affected by ADAMTS13 polymorphism, and the only significant genetic factor was the person's blood group. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5983", "text": "ABO(H) blood group antigens are also carried by other hemostatically relevant glycoproteins, such as platelet glycoprotein Ib\u03b1, which is a ligand for vWF on platelets. [ 57 ]  The significance of ABO(H) antigen expression on these other hemostatic glycoproteins is not fully defined, but may also be relevant for bleeding and thrombosis."}
{"_id": "WikiPedia_Hematology$$$corpus_5984", "text": "ABO blood group incompatibilities between the mother and child do not usually cause  hemolytic disease of the newborn  (HDN) because antibodies to the ABO blood groups are usually of the  IgM  type, which do not cross the placenta. However, in an O-type mother,  IgG  ABO antibodies are produced and the baby can potentially develop  ABO hemolytic disease of the newborn . [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5985", "text": "In human cells, the ABO alleles and their encoded glycosyltransferases have been described in several oncologic conditions. [ 59 ]  Using anti-GTA/GTB monoclonal antibodies, it was demonstrated that a loss of these enzymes was correlated to malignant bladder and oral epithelia. [ 60 ] [ 61 ]  Furthermore, the expression of ABO blood group antigens in normal human tissues is dependent the type of differentiation of the epithelium. In most human carcinomas, including oral carcinoma, a significant event as part of the underlying mechanism is decreased expression of the A and B antigens. [ 62 ]  Several studies have observed that a relative down-regulation of GTA and GTB occurs in oral carcinomas in association with tumor development. [ 62 ] [ 63 ]  More recently, a genome wide association study (GWAS) has identified variants in the ABO locus associated with susceptibility to pancreatic cancer. [ 64 ] \nIn addition, another large GWAS study has associated ABO-histo blood groups as well as FUT2 secretor status with the presence in the intestinal microbiome of specific bacterial species. In this case the association was with  Bacteroides  and  Faecalibacterium spp .   Bacteroides  of the same OTU (operational taxonomic unit) have been shown to be associated with inflammatory bowel disease, [ 65 ] [ 66 ]  thus the study suggests an important role for the ABO histo-blood group antigens as candidates for direct modulation of the human microbiome in health and disease. [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5986", "text": "A multi-locus genetic risk score study based on a combination of 27 loci, including the ABO gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5987", "text": "In April 2007, an international team of researchers announced in the journal  Nature Biotechnology  an inexpensive and efficient way to convert types A, B, and AB blood into type O. [ 69 ]  This is done by using  glycosidase  enzymes from specific bacteria to strip the blood group antigens from  red blood cells . The removal of A and B antigens still does not address the problem of the  Rh blood group  antigen on the blood cells of Rh positive individuals, and so blood from Rh negative donors must be used. The modified blood is named \"enzyme converted to O\" (ECO blood) but despite the early success of converting B- to O-type RBCs and clinical trials without adverse effects transfusing into A- and O-type patients, [ 70 ]  the technology has not yet become clinical practice. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5988", "text": "Another approach to the blood antigen problem is the manufacture of  artificial blood , which could act as a substitute in emergencies. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5989", "text": "In Japan and other parts of East Asia, there is a popular belief in  Blood type personality theory , which claims that blood types predict or influence personality. This claim is not scientifically based, and there is  scientific consensus  that no such link exists; the scientific community considers it a  pseudoscience  and a  superstition . [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5990", "text": "The belief originated in the 1930s, when it was introduced as part of Japan's  eugenics  program. [ 74 ]  Its popularity faded following Japan's defeat in World War 2 and Japanese support for eugenics faltered, but it resurfaced in the 1970s by a journalist named  Masahiko Nomi . Despite its status as a pseudoscience, it remains widely popular throughout East Asia. [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5991", "text": "Other popular ideas are  blood type-specific dietary needs , that group A causes severe  hangovers , that group O is associated with better teeth, and that those with group A2 have the highest  IQ scores . As with blood type personality theory, these and other popular ideas lack scientific evidence, and many are discredited or pseudoscientific. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5992", "text": "An  acute hemolytic transfusion reaction  ( AHTR ), also called  immediate hemolytic transfusion reaction , is a life-threatening reaction to receiving a  blood transfusion . AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an  ABO blood group  incompatibility, and is most severe when type A donor blood is given to a type O recipient. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5993", "text": "Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by  rigors  (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by  shortness of breath ,  low blood pressure ,  hemoglobinuria , and may progress to  shock  and  disseminated intravascular coagulation . In anesthetized or unconscious patients,  hematuria  (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and  wheezing . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5994", "text": "The most common cause of acute hemolytic transfusion reaction is  ABO incompatibility , which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is  Kidd antigen  incompatibility. [ 4 ]   Rh ,  Kell , and  Duffy  antigen incompatibility have also been implicated in AHTR. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5995", "text": "Acute hemolytic transfusion reactions result when  antibodies  against A and/or B antigens (isohemagglutinins) present in the recipient's blood destroy the respective donor  red blood cells . [ 4 ] [ 5 ]  This is mediated through the antibodies  IgM  (and to a lesser extent  IgG ) which cause activation of the  complement cascade , with complement C5-C9 forming the  membrane attack complex  which leads to pore formation and red blood cell lysis. [ 6 ]  The lysed red blood cells release free hemoglobin into the bloodstream, overwhelming hemoglobin binding proteins such as  albumin ,  haptoglobin , and  hemopexin , with the excess free hemoglobin leading to renal vasoconstriction (via nitric oxide scavenging), which then leads to  acute tubular necrosis  and  acute kidney injury . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5996", "text": "The antibodies also activate the  coagulation cascade  (blood clotting system) via  factor XII , which can lead to disseminated intravascular coagulation and kidney damage. Isohemagglutinins also activate the complement cascade via  C3a  and  C5a , which then promote inflammatory  cytokine  release from  white blood cells . C3a and C5a also activate  mast cells  which release  serotonin  and  histamine , which along with fragments of red blood cells that were destroyed, further stimulate the release of inflammatory cytokines. [ 6 ]  These inflammatory cytokines include  IL-1 ,  IL-6 ,  IL-8 , and  TNF-alpha , which cause increased capillary permeability and vasodilation leading to symptoms of low blood pressure, fever, chest pain, nausea, vomiting, and wheezing. [ 4 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5997", "text": "The diagnosis of AHTR is made with microscopic examination of the recipient's blood and a  direct antiglobulin test  (direct Coombs test) which detects IgG antibodies or complement bound to red blood cells and is usually diagnostic of acute hemolytic transfusion reactions. [ 6 ]  The donor and recipient blood can be re-tested with a type, crossmatch, and antibody screen to determine the cause of the reaction. [ 4 ]  The donor blood should be examined for any labelling error or other possible errors from the blood bank, which may help prevent other mislabeled blood products from being distributed. [ 6 ]  Testing the donor blood using a  gram stain  and  blood culture  can also help to rule out an infectious cause of the symptoms (such as the donor receiving infected blood). [ 6 ]  Testing for urine or plasma free hemoglobin may also assist in the diagnosis. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5998", "text": "Initial treatment for any type of transfusion reaction, including AHTR, is discontinuation of the transfusion.  Fluid replacement  and close monitoring of vital signs are important. People with AHTR are managed with  supportive care , which may include  diuretics , blood pressure support, and treatment of disseminated intravascular coagulation (with  fresh frozen plasma ,  cryoprecipitate , and  platelet transfusion ). [ 6 ]  The use of steroids, intravenous immune-globulins ( IVIG ) or plasma exchange is not supported by evidence. [ 6 ]   Furosemide  is the diuretic of choice in treatment of AHTR with decreased urine output, because it increases the amount of blood that reaches the  renal cortex . [ 4 ]   Mannitol  may also be used. [ 5 ]   Dopamine  is used for blood pressure support because it causes  vasodilation  (dilation of blood vessels) in the kidneys as well as increasing the  cardiac output  (amount of blood pumped by the heart each minute). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_5999", "text": "The severity and prognosis of acute hemolytic transfusion depends on the rate of blood administration and the total volume of the transfusion. The levels of anti-A and anti-B antibodies in the recipients blood may also predict the prognosis, with higher levels of antibodies thought to portend a more severe course. [ 6 ]  Approximately 2% of cases are fatal. Reactions that begin sooner are typically more severe. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6000", "text": "Acute hemolytic transfusion reaction is estimated to occur in 1 in 38,000 to 1 in 70,000 transfusions. An estimated 41% of ABO-incompatible transfusions result in AHTR. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6001", "text": "An  allergic transfusion reaction  is when a  blood transfusion  results in  allergic reaction . It is among the most common  transfusion reactions  to occur.  Reported rates depend on the degree of active surveillance versus passing reporting to the blood bank. [ 1 ] [ 2 ]  Overall, they are estimated to complicate up to 3% of all transfusions. [ 3 ]   The incidence of allergic transfusion reactions is associated with the amount of plasma in the product. [ 3 ]  More than 90% of these reactions occur during transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_6002", "text": "Allergic reactions from blood transfusion may occur from the presence of allergy-causing antigens within the donor's blood, [ 4 ]  or transfusion of antibodies from a donor who has allergies, followed by antigen exposure. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6003", "text": "An allergic transfusion reaction is a type of transfusion reaction that is defined according to the Center for Disease Control (CDC)  [ 7 ]  as:"}
{"_id": "WikiPedia_Hematology$$$corpus_6004", "text": "An allergic transfusion reaction is diagnosed if two or more of the following occur within 4 hours of cessation of transfusion: [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6005", "text": "A probable diagnosis results if any one of the following occurring within 4 hours of cessation of transfusion: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6006", "text": "The UK hemovigilance reporting system ( SHOT ), has classified allergic reactions in to mild, moderate and severe. [ 9 ]  Reactions can occur that have features of both allergic and  febrile reactions . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6007", "text": "A rash,  urticaria , or flushing [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6008", "text": "Wheeze ( bronchospasm ) or  angioedema  but blood pressure normal and no respiratory compromise. There may or may not be an associated rash or  urticaria . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6009", "text": "This can be due to: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6010", "text": "To prevent allergic transfusion reaction it is possible to use patients own blood for transfusion, this is referred to as  autologous blood transfusion . Patients' own blood is collected and washed to produce concentrated red blood cells (this blood product is also called  packed red blood cells ). There are multiple ways to  wash red blood cells . The two main methods that are used to wash the cells are centrifugation, or filtration methods like the Hemoclear microfilter. The last option is reinfusion without washing. This is the least preferred method because of the chance of complications. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6011", "text": "There is no evidence that antihistamine premedication prevents allergic transfusion reactions, although these drugs can mitigate symptoms once they occur. [ 11 ] [ 12 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6012", "text": "Treatment of an allergic transfusion reaction is to immediately stop the transfusion. If the only symptoms are mild (i.e., hives and itching), the patient may be treated with an antihistamine and if the symptoms completely disappear and the patient feels well, the transfusion may be restarted. A mild transfusion reaction during infusion usually does not progress to a more severe anaphylactic reaction after infusion of additional product from the same unit. [ 3 ]  If the symptoms are more than mild, the transfusion should not be restarted. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6013", "text": "The  American Society for Apheresis  ( ASFA ) is an organization of  physicians , scientists,  nurses , and  allied health professionals  whose mission is to advance  apheresis  medicine for patients, donors and practitioners through education, evidence-based practice, research and advocacy.  ASFA represents a broad range of health care professionals involved in  apheresis  medicine including those practicing  pathology ,  transplantation ,  hematology ,  oncology ,  neurology ,  rheumatology ,  nephrology ,  hepatology ,  gastroenterology ,  cardiology , and  ophthalmology .  These health care providers are involved in the performance of therapeutic apheresis procedures including  plasma exchange ,  red cell exchange ,  leukocytapheresis ,  plateletapheresis ,  photopheresis ,  LDL apheresis , and hematopoietic progenitor cell collection. ASFA also represents those physicians and allied health professionals involved in the  collection of blood products from blood donors  using apheresis instruments. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6014", "text": "The major activities of ASFA are member driven and educational, including publication of the  Journal of Clinical Apheresis  Special Issue: Clinical Applications of Therapeutic Apheresis: An Evidence Based Approach, [ 2 ]  publication of Principles of Apheresis Technology Textbook, [ 3 ]  publication of Therapeutic Apheresis: A Physician's Handbook, [ 4 ]  monthly apheresis educational  webinar  program  [ 5 ]  and developing programming for the ASFA Annual Meeting. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6015", "text": "ASFA was formed in 1982. It grew from the merger of two organizations, the  Society of Hemapheresis Specialists  (SHS) and the original ASFA. The SHS was formed by nursing and allied health personnel, who were responsible for performing the donor and therapeutic procedures and operating the various  blood cell  separators.  It was formed provide educational and networking opportunities in the field of apheresis medicine that were not available and which were needed by the original members in order to advance the field. SHS became a national forum for the exchange of views and best practices and was the forerunner of the efforts directed toward apheresis practitioner  certification . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6016", "text": "The original ASFA developed from a physician-scientist symposia.  It was originally developed for the purpose to present scientific research on donor and therapeutic apheresis topics. The first apheresis symposium was held in  Chicago  in 1979, and was the first of annual symposia.  The subsequent symposia were named the ASFA Symposia. Most of the initial Officers and Board of Directors of ASFA presented at these symposia, from which the structure of the organization grew. In 1982,  John Verrier-Jones , became the first president of ASFA. He noted that the term \u201capheresis\u201d had been in use since 1914, and that the appropriate terms was \u201capheresis\u201d, not \u201cpheresis\u201d as was quite widely used at the time. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6017", "text": "In addition to providing education in apheresis medicine for healthcare professionals, ASFA also now seeks to provide education to patients undergoing apheresis treatment. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6018", "text": "Anemia  or  anaemia  ( British English ) is a  blood disorder  in which the  blood  has a reduced ability to carry  oxygen . This can be due to a lower than normal number of  red blood cells , a reduction in the amount of  hemoglobin  available for oxygen transport, or abnormalities in hemoglobin that impair its function. [ 3 ] [ 4 ]  The name is derived from  Ancient Greek     \u1f00\u03bd - (an-) \u00a0'not' and    \u03b1\u1f37\u03bc\u03b1  (haima) \u00a0'blood'. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6019", "text": "When anemia comes on slowly, the symptoms are often vague, such as  tiredness ,  weakness ,  shortness of breath ,  headaches , and a  reduced ability to exercise . [ 1 ]  When anemia is acute, symptoms may include  confusion ,  feeling like one is going to pass out ,  loss of consciousness , and  increased thirst . [ 1 ]  Anemia must be significant before a person becomes noticeably  pale . [ 1 ]  Additional symptoms may occur depending on the underlying cause. [ 1 ]  Anemia can be temporary or long term and can range from mild to severe. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6020", "text": "Anemia can be caused by  blood loss , decreased red blood cell production, and increased  red blood cell breakdown . [ 1 ]  Causes of blood loss include  bleeding due to inflammation of the stomach or intestines , bleeding from  surgery , serious  injury , or  blood donation . [ 1 ]  Causes of decreased production include  iron deficiency ,  folate deficiency ,  vitamin B 12  deficiency ,  thalassemia  and a number of  bone marrow tumors . [ 1 ]  Causes of increased breakdown include  genetic disorders  such as  sickle cell anemia , infections such as  malaria , and certain  autoimmune diseases  like  autoimmune hemolytic anemia . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6021", "text": "Anemia can also be classified based on the  size of the red blood cells  and  amount of hemoglobin in each cell . [ 1 ]  If the cells are small, it is called  microcytic anemia ; if they are large, it is called  macrocytic anemia ; and if they are normal sized, it is called  normocytic anemia . [ 1 ]  The diagnosis of anemia in men is based on a hemoglobin of less than 130 to 140\u00a0g/L (13 to 14\u00a0g/dL); in women, it is less than 120 to 130\u00a0g/L (12 to 13\u00a0g/dL). [ 1 ] [ 7 ]  Further testing is then required to determine the cause. [ 1 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6022", "text": "Treatment depends on the specific cause. Certain groups of individuals, such as pregnant women, can benefit from the use of  iron pills  for prevention. [ 1 ] [ 9 ]   Dietary supplementation , without determining the specific cause, is not recommended. [ 1 ]  The use of  blood transfusions  is typically based on a person's signs and symptoms. [ 1 ]  In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80\u00a0g/L (6 to 8\u00a0g/dL). [ 1 ] [ 10 ]  These recommendations may also apply to some people with acute bleeding. [ 1 ]   Erythropoiesis-stimulating agents  are only recommended in those with severe anemia. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6023", "text": "Anemia is the most common blood disorder, affecting about a fifth to a third of the global population. [ 1 ] [ 11 ] [ 12 ] [ 13 ]   Iron-deficiency anemia  is the most common cause of anemia worldwide, and affects nearly one billion people. [ 14 ]  In 2013, anemia due to iron deficiency resulted in about 183,000 deaths \u2013 down from 213,000 deaths in 1990. [ 15 ]  This condition is most prevalent in children [ 16 ] [ 17 ]  with also an above average prevalence in elderly [ 1 ]  and women of reproductive age (especially during pregnancy). [ 14 ]  Anemia is one of the six  WHO  global nutrition targets for 2025 and for diet-related global targets endorsed by  World Health Assembly  in 2012 and 2013. Efforts to reach global targets contribute to reaching  Sustainable Development Goals  (SDGs), [ 18 ]  with anemia as one of the targets in  SDG 2  for achieving zero world hunger. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6024", "text": "A person with anemia may not have any symptoms, depending on the underlying cause, and no symptoms may be noticed, as the anemia is initially mild, and then the symptoms become worse as the anemia worsens. A patient with anemia may report  feeling tired , weak, decreased ability to concentrate, and sometimes  shortness of breath  on  exertion . [ 21 ]  These symptoms are unspecific and none of the symptoms alone or in combination show a good predictive value for the presence of anemia in non-clinical patients. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6025", "text": "Symptoms of anemia can come on quickly or slowly. [ 23 ]  Early on there may be few or no symptoms. [ 23 ]  If the anemia continues slowly (chronic), the body may adapt and compensate for this change. In this case, no symptoms may appear until the anemia becomes more severe. [ 20 ] [ 24 ]  Symptoms can include feeling tired, weak,  dizziness , headaches,  intolerance to physical exertion , shortness of breath, difficulty concentrating,  irregular  or  rapid  heartbeat, cold hands and feet,  cold intolerance ,  pale  or  yellow  skin,  poor appetite , easy bruising and bleeding, and  muscle weakness . [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6026", "text": "Anemia that develops quickly, often, has more severe symptoms, including,  feeling faint ,  chest pain , sweating, increased thirst, and confusion. [ 23 ] [ 25 ] [ 26 ] [ 27 ]  There may be also additional symptoms depending on the underlying cause. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6027", "text": "In more severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing  cardiac output . The person may have symptoms related to this, such as  palpitations ,  angina  (if pre-existing  heart disease  is present), intermittent  claudication  of the legs, and symptoms of  heart failure . [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6028", "text": "On examination, the signs exhibited may include  pallor  (pale skin,  mucosa ,  conjunctiva  and  nail beds ), but this is not a reliable sign."}
{"_id": "WikiPedia_Hematology$$$corpus_6029", "text": "Iron-deficiency anemia may give symptoms that can include  spoon-shaped  nails, restless legs syndrome, and pica (the medical condition indicates the desire for things that are not food, such as ice, dirt, etc.). [ 29 ]  A blue coloration of the  sclera  may be noticed in some cases of iron-deficiency anemia. [ 30 ]  Vitamin B 12  deficiency anemia may result in decreased ability to think, memory loss, confusion, personality or mood changes, depression, difficulty walking, blurred vision, and irreversible nerve damage. [ 31 ] [ 32 ]  Other specific causes of anemia may have signs and/or complications such as,  jaundice  with the rapid break down of  red blood cells  as with  hemolytic anemia , bone abnormalities with  thalassemia major , or leg  ulcers  as seen in  sickle cell disease ."}
{"_id": "WikiPedia_Hematology$$$corpus_6030", "text": "In severe anemia, there may be signs of a  hyperdynamic circulation :  tachycardia  (a fast heart rate),  bounding pulse ,  flow murmurs , and  cardiac   ventricular hypertrophy  (enlargement). There may be signs of  heart failure .\n Pica , the consumption of non-food items such as ice, paper, wax, grass, hair or dirt, may be a symptom of iron deficiency; [ 29 ]  although it occurs often in those who have normal levels of  hemoglobin . Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age.  Restless legs syndrome  is more common in people with  iron-deficiency anemia  than in the general population. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6031", "text": "The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemia), blood loss and fluid overload ( hypervolemia ). Several of these may interplay to cause anemia. The most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn, most commonly by  iron deficiency . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6032", "text": "Anemias of increased  red blood cell destruction  are generally classified as  hemolytic anemias . These types generally feature  jaundice , and elevated levels of  lactate dehydrogenase . [ 38 ] [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6033", "text": "The roots of the words  anemia  and  ischemia  both refer to the basic idea of \"lack of blood\", but anemia and  ischemia  are not the same thing in modern medical terminology. The word  anemia  used alone implies  widespread   effects  from blood that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-supplying ability (due to whatever type of hemoglobin or erythrocyte problem). In contrast, the word  ischemia  refers solely to the lack of blood (poor  perfusion ). Thus ischemia in a body part can cause localized anemic effects within those tissues. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6034", "text": "Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia: [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6035", "text": "Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of  hepcidin  that leads to decreased access of iron to the circulation. [ 54 ] [ 55 ] [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6036", "text": "There are a number of definitions of anemia;  reviews  provide comparison and contrast of them. [ 62 ]  A strict but broad definition is an absolute decrease in red blood cell mass, [ 63 ]  however, a broader definition is a lowered ability of the blood to carry  oxygen . [ 64 ]  An  operational definition  is a decrease in whole-blood  hemoglobin  concentration of more than 2  standard deviations  below the  mean  of an age- and sex-matched  reference range . [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6037", "text": "It is difficult to directly measure RBC mass, [ 66 ]  so the  hematocrit  (amount of RBCs) or the hemoglobin (Hb) in the  blood  are often used instead to indirectly estimate the value. [ 67 ]  Hematocrit; however, is concentration dependent and is therefore not completely accurate. For example, during pregnancy a woman's RBC mass is normal but because of an increase in blood volume the hemoglobin and hematocrit are diluted and thus decreased. Another example would be bleeding where the RBC mass would decrease but the concentrations of hemoglobin and hematocrit initially remains normal until fluids shift from other areas of the body to the intravascular space. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6038", "text": "The anemia is also classified by severity into mild (110 g/L to normal), moderate (80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adults. [ 68 ]  Different values are used in pregnancy and children. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6039", "text": "Anemia is typically diagnosed on a  complete blood count . Apart from reporting the number of  red blood cells  and the hemoglobin level, the  automatic counters  also measure the size of the red blood cells by  flow cytometry , which is an important tool in distinguishing between the causes of anemia. Examination of a stained  blood smear  using a  microscope  can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6040", "text": "A blood test will provide counts of white blood cells, red blood cells and platelets. If anemia appears, further tests may determine what type it is, and whether it has a serious cause. although of that, it is possible to refer to the genetic history and physical diagnosis. [ 70 ]  These tests may also include  serum ferritin ,  iron studies ,  vitamin B 12 , genetic testing, and a  bone marrow sample , if needed. [ 71 ] [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6041", "text": "Reticulocyte counts, and the \"kinetic\" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A  reticulocyte  count is a quantitative measure of the  bone marrow 's production of new red blood cells. The  reticulocyte production index  is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a \"normal\" reticulocyte count actually may reflect an inadequate response."}
{"_id": "WikiPedia_Hematology$$$corpus_6042", "text": "If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of  erythropoiesis  can help assess whether the bone marrow will be able to compensate for the loss and at what rate."}
{"_id": "WikiPedia_Hematology$$$corpus_6043", "text": "When the cause is not obvious, clinicians use other tests, such as:  ESR , serum iron,  transferrin ,  RBC folate level ,  hemoglobin electrophoresis ,  renal function  tests (e.g.  serum creatinine ) although the tests will depend on the clinical hypothesis that is being investigated."}
{"_id": "WikiPedia_Hematology$$$corpus_6044", "text": "When the diagnosis remains difficult, a  bone marrow examination  allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6045", "text": "In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the  mean corpuscular volume  (MCV). If the cells are smaller than normal (under 80  fl ), the anemia is said to be  microcytic ; if they are normal size (80\u2013100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as  macrocytic . This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of  iron deficiency ."}
{"_id": "WikiPedia_Hematology$$$corpus_6046", "text": "In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the \"kinetic\" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.\nLimitations of MCV include cases where the underlying cause is due to a combination of factors \u2013 such as iron deficiency (a cause of microcytosis) and vitamin  B12 deficiency  (a cause of macrocytosis) where the net result can be normocytic cells. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6047", "text": "The \"kinetic\" approach to anemia yields arguably the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction or loss. Clinical signs of loss or destruction include abnormal  peripheral blood smear  with signs of hemolysis; elevated  LDH  suggesting cell destruction; or clinical signs of bleeding, such as guaiac-positive stool, radiographic findings, or frank bleeding. [ medical citation needed ] \nThe following is a simplified schematic of this approach: [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6048", "text": "*   For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B 12  and folate deficiency; and other instances of anemia with more than one cause. \n **   Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss. \nHere is a schematic representation of how to consider anemia with MCV as the starting point:"}
{"_id": "WikiPedia_Hematology$$$corpus_6049", "text": "Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal  white blood cells  may point to a cause in the  bone marrow ."}
{"_id": "WikiPedia_Hematology$$$corpus_6050", "text": "Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:"}
{"_id": "WikiPedia_Hematology$$$corpus_6051", "text": "Iron-deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope."}
{"_id": "WikiPedia_Hematology$$$corpus_6052", "text": "The  Mentzer index  (mean cell volume divided by the RBC count) predicts whether microcytic anemia may be due to iron deficiency or thalassemia, although it requires confirmation. [ 80 ] [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6053", "text": "Macrocytic anemia can be further divided into \"megaloblastic anemia\" or \"nonmegaloblastic macrocytic anemia\". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (six to 10 lobes). The nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired DNA globin synthesis,) which occur, for example, in alcoholism.\nIn addition to the nonspecific symptoms of anemia, specific features of vitamin B 12  deficiency include  peripheral neuropathy  and  subacute combined degeneration of the cord  with resulting balance difficulties from posterior column spinal cord pathology. [ 82 ]  Other features may include a smooth, red tongue and  glossitis .\nThe treatment for vitamin B 12 -deficient anemia was first devised by  William Murphy , who bled dogs to make them anemic, and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease.  George Minot  and  George Whipple  then set about to isolate the curative substance chemically and ultimately were able to isolate the  vitamin B 12  from the liver. All three shared the 1934  Nobel Prize in Medicine . [ 83 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6054", "text": "Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size ( mean corpuscular volume ) remains normal. Causes include:"}
{"_id": "WikiPedia_Hematology$$$corpus_6055", "text": "A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs."}
{"_id": "WikiPedia_Hematology$$$corpus_6056", "text": "A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6057", "text": "Heinz bodies  form in the cytoplasm of RBCs and appear as small dark dots under the microscope. In animals, Heinz body anemia has many causes. It may be drug-induced, for example in cats and dogs by  acetaminophen  (paracetamol), [ 84 ]  or may be caused by eating various plants or other substances:"}
{"_id": "WikiPedia_Hematology$$$corpus_6058", "text": "Hyperanemia is a severe form of anemia, in which the  hematocrit  is below 10%. [ 87 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6059", "text": "Refractory anemia, an anemia which does not respond to  treatment , [ 88 ]  is often seen secondary to myelodysplastic syndromes. [ 89 ]  Iron-deficiency anemia may also be refractory as a manifestation of gastrointestinal problems which disrupt  iron absorption  or cause  occult bleeding .\n [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6060", "text": "Transfusion dependent anemia is a form of anemia where ongoing blood transfusion are required. [ 91 ]  Most people with myelodysplastic syndrome develop this state at some point in time. [ 92 ]   Beta thalassemia  may also result in transfusion dependence. [ 93 ] [ 94 ]  Concerns from repeated blood transfusions include  iron overload . [ 92 ]  This iron overload may require  chelation therapy . [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6061", "text": "The global market for anemia treatments is estimated at more than USD 23 billion per year and is fast growing because of the rising prevalence and awareness of anemia. The types of anemia treated with drugs are iron-deficiency anemia,  thalassemia , aplastic anemia,  hemolytic anemia ,  sickle cell anemia , and pernicious anemia, the most important of them being deficiency and sickle cell anemia with together 60% of market share because of highest prevalence as well as higher treatment costs compared with other types. [ 13 ]  Treatment for anemia depends on cause and severity. Vitamin supplements given orally ( folic acid  or vitamin B 12 ) or intramuscularly ( vitamin B 12 ) will replace specific deficiencies. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6062", "text": "Apart from that, iron supplements, antibiotics, immunosuppressant, bone marrow stimulants, corticosteroids, gene therapy and iron chelating agents are forms of anemia treatment drugs, with immunosuppressants and corticosteroids accounting for 58% of the market share. A paradigm shift towards gene therapy and monoclonal antibody therapies is observed. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6063", "text": "Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and of women of childbearing age in most developing nations are estimated to have iron deficiency without anemia with one-third of them having an iron deficiency with anemia. [ 96 ]  Iron deficiency due to inadequate dietary iron intake is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of blood loss, such as gastrointestinal bleeding from ulcers or colon cancer. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6064", "text": "Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with  ferrous sulfate ,  ferrous fumarate , or  ferrous gluconate . Daily iron supplements have been shown to be effective in reducing anemia in women of childbearing age. [ 97 ]  When taking iron supplements, stomach upset or darkening of the feces are commonly experienced. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed.  Vitamin C  aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit. [ 98 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6065", "text": "In the anemia of chronic kidney disease,  recombinant   erythropoietin  or  epoetin alfa  is recommended to stimulate RBC production, and if iron deficiency and inflammation are also present, concurrent  parenteral iron  is also recommended. [ 99 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6066", "text": "In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively), or where absorption is impeded (for example in cases of inflammation),  parenteral iron  preparations can be used. Parenteral iron can improve iron stores rapidly and is also effective for treating people with postpartum haemorrhage, inflammatory bowel disease, and chronic heart failure. [ 100 ]  The body can absorb up to 6\u00a0mg iron daily from the gastrointestinal tract. In many cases, the patient has a deficit of over 1,000\u00a0mg of iron which would require several months to replace. This can be given concurrently with  erythropoietin  to ensure sufficient iron for increased rates of  erythropoiesis . [ 101 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6067", "text": "Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80\u00a0g/L (6 to 8\u00a0g/dL). [ 1 ]  In those with  coronary artery disease  who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL). [ 10 ]  Transfusing earlier does not improve survival. [ 102 ]  Transfusions otherwise should only be undertaken in cases of cardiovascular instability. [ 103 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6068", "text": "A 2012 review concluded that when considering blood transfusions for anaemia in people with advanced cancer who have fatigue and breathlessness (not related to cancer treatment or haemorrhage), consideration should be given to whether there are alternative strategies can be tried before a blood transfusion. [ 104 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6069", "text": "In many cases, vitamin B 12  is used by  intramuscular injection  in severe cases or cases of malabsorption of dietary-B 12 . Pernicious anemia caused by loss of intrinsic factor cannot be prevented. [ 105 ]  If there are other, reversible causes of low vitamin B 12  levels, the cause must be treated. [ 106 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6070", "text": "Vitamin B 12  deficiency anemia is usually easily treated by providing the necessary level of vitamin B 12  supplementation. [ 107 ]  The injections are quick-acting, and symptoms usually go away within one to two weeks. [ 107 ]  As the condition improves, doses are reduced to weeks and then can be given monthly. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe  neurologic  symptoms. [ 107 ]  Treatment should begin rapidly for severe neurological symptoms, as some changes can become permanent. [ 32 ]  In some individuals lifelong treatment may be needed. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6071", "text": "The objective for the administration of an  erythropoiesis-stimulating agent  (ESA) is to maintain hemoglobin at the lowest level that both minimizes transfusions and meets the individual person's needs. [ 108 ]  They should not be used for mild or moderate anemia. [ 102 ]  They are not recommended in people with  chronic kidney disease  unless hemoglobin levels are less than 10 g/dL or they have symptoms of anemia. Their use should be along with parenteral iron. [ 108 ] [ 109 ]  The 2020 Cochrane Anaesthesia Review Group review of erythropoietin (EPO) plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non-cardiac surgery  [ 110 ]  demonstrated that patients were much less likely to require red cell transfusion and in those transfused, the volumes were unchanged (mean difference -0.09, 95% CI -0.23 to 0.05). Pre-operative hemoglobin concentration was increased in those receiving 'high dose' EPO, but not 'low dose'. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6072", "text": "Treatment of exceptional blood loss (anemia) is recognized as an indication for  hyperbaric oxygen  (HBO) by the  Undersea and Hyperbaric Medical Society . [ 111 ] [ 112 ]  The use of HBO is indicated when  oxygen  delivery to tissue is not sufficient in patients who cannot be given  blood transfusions  for  medical  or  religious  reasons. HBO may be used for medical reasons when threat of  blood product  incompatibility or concern for  transmissible disease  are factors. [ 111 ]  The beliefs of some religions (ex:  Jehovah's Witnesses ) may require they use the HBO method. [ 111 ]  A 2005 review of the use of HBO in severe anemia found all publications reported positive results. [ 113 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6073", "text": "An estimated 30% of adults who require non-cardiac surgery have anemia. [ 114 ]  In order to determine an appropriate preoperative treatment, it is suggested that the cause of anemia be first determined. [ 115 ]  There is moderate level medical evidence that supports a combination of iron supplementation and erythropoietin treatment to help reduce the requirement for red blood cell transfusions after surgery in those who have preoperative anemia. [ 114 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6074", "text": "Anemia affects 27% of the world's population with iron-deficiency anemia accounting for more than 60% of it. [ 116 ]  A moderate degree of iron-deficiency anemia affected approximately 610\u00a0million people worldwide or 8.8% of the population. [ 14 ]  It is somewhat more common in females (9.9%) than males (7.8%). [ 14 ]  Mild iron-deficiency anemia affects another 375\u00a0million. [ 14 ]  Severe anaemia is prevalent globally, and especially in sub-Saharan Africa [ 117 ]  where it is associated with infections including malaria and invasive bacterial infections. [ 118 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6075", "text": "Signs of severe anemia in human bones from 4000 years ago have been uncovered in Thailand. [ 119 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6076", "text": "Anemia  is a condition in which  blood  has a lower-than-normal amount of  red blood cells  or  hemoglobin . [ 1 ]   Anemia in pregnancy  is a decrease in the total red blood cells (RBCs) or hemoglobin in the blood during  pregnancy . Anemia is an extremely common condition in pregnancy world-wide, conferring a number of health risks to mother and child. [ 2 ]  While anemia in pregnancy may be pathologic, in normal pregnancies, the increase in RBC mass is smaller than the increase in plasma volume, leading to a mild decrease in hemoglobin concentration referred to as physiologic (or dilutional) anemia. [ 3 ]  Maternal signs and symptoms are usually non-specific, but can include:  fatigue ,  pallor ,  dyspnea ,  palpitations , and  dizziness . [ 4 ]  There are numerous well-known maternal consequences of anemia including: maternal cardiovascular strain, reduced physical and mental performance, reduced peripartum blood reserves, increased risk for peripartum blood product transfusion, and increased risk for maternal mortality. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6077", "text": "Common symptoms are  headache , fatigue,  lethargy ,  tachycardia ,  tachypnea ,  paresthesia ,  pallor ,  glossitis  and  cheilitis . [ 6 ] [ 7 ]  Severe symptoms include  congestive heart failure ,  placenta previa ,  abruptio placenta , and operative delivery. [ 6 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6078", "text": "Dilutional anemia : There is an increase in overall blood volume during pregnancy, and even though there is an increase in overall red blood cell mass, the increase in the other parts of the blood like plasma decrease the overall percentage of red blood cells in circulation. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6079", "text": "Iron deficiency anemia : this can occur from the increased production of red blood cells, which requires a lot of iron and also from inadequate intake of iron, which increase in pregnancy. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6080", "text": "Hemoglobinopathies : Thalassemia and sickle cell disease. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6081", "text": "Dietary deficiencies :  Folate deficiency  and  vitamin B12 deficiency  are common causes of anemia in pregnancy. Folate deficiency occurs due to diets low in leafy green vegetables, and animal sources of protein. [ 10 ]  B12 deficiency tends to be more common in individuals with  Crohn's disease  or gastrectomies. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6082", "text": "Cell membrane disorders:   Hereditary spherocytosis [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6083", "text": "Autoimmune causes:  lead to the hemolysis of red blood cells (Ex:  autoimmune hemolytic anemia ). [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6084", "text": "Hypothyroidism  and chronic kidney disease [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6085", "text": "Parasitic infestations:  some examples are  hookworm  or  Plasmodium species [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6086", "text": "Bacterial or viral infections"}
{"_id": "WikiPedia_Hematology$$$corpus_6087", "text": "Iron deficiency is the most common cause of anemia in the pregnant woman. During pregnancy, the average total iron requirement is about 1200\u00a0mg per day for a 55\u00a0kg woman. This iron is used for the increase in red cell mass, placental needs and fetal growth. About 40% of women start their pregnancy with low to absent iron stores and up to 90% have iron stores insufficient to meet the increased iron requirements during pregnancy and the postpartum period. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6088", "text": "The majority of women presenting with postpartum anemia have pre-delivery iron deficiency anemia or iron deficiency anemia combined with acute blood loss during delivery. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6089", "text": "Studies have suggested that severe maternal morbidity (SMM) is increased approximately twofold in antepartum maternal anemia. SMM is defined by maternal death,  eclampsia , transfusion, hysterectomy, or intensive care unit admission at delivery. Additional complications may include  postpartum haemorrhage ,  preeclampsia ,  cesarean delivery , and infections. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6090", "text": "Iron deficiency during pregnancy is linked to a number of harmful effects on the fetus such as intrauterine growth restriction, death in utero, infection, preterm delivery and neurodevelopmental damage, which may be irreversible. [ 18 ] [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6091", "text": "The most useful test with which to render a diagnosis of anemia is a low RBC count, however hemoglobin and hematocrit values are most commonly used in making the initial diagnosis of anemia. Testing involved in diagnosing anemia in pregnant women must be tailored to each individual patient. Suggested tests include: hemoglobin and hematocrit (ratio of red blood cells to the total blood volume),  mean corpuscular volume  (MCV),  mean corpuscular hemoglobin  (MCH), erythrocyte count (number of red blood cells in the blood),  red cell distribution width  (RDW),  reticulocyte  count, and a  peripheral smear  to assess red blood cell morphology. If iron deficiency is suspected, additional tests such as: serum iron, total iron-binding capacity (TIBC),  transferrin  saturation, and plasma or serum  ferritin  may be warranted. It is important to note that references ranges for these values are often not the same for pregnant women. Additionally, laboratory values for pregnancy often change throughout the duration of a woman's gestation. For example, the reference values for what level of hemoglobin is considered anemic varies in each trimester of pregnancy. [ 21 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6092", "text": "-  First trimester hemoglobin < 11 g/dL"}
{"_id": "WikiPedia_Hematology$$$corpus_6093", "text": "-  Second trimester hemoglobin < 10.5 g/dL"}
{"_id": "WikiPedia_Hematology$$$corpus_6094", "text": "-  Third trimester hemoglobin < 11 g/dL"}
{"_id": "WikiPedia_Hematology$$$corpus_6095", "text": "-  Postpartum hemoglobin < 10 g/dL"}
{"_id": "WikiPedia_Hematology$$$corpus_6096", "text": "Listed below are normal ranges for important lab values in the diagnosis of anemia. Keep in mind that these ranges might change based on each patient's stage in pregnancy: [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6097", "text": "- Hemoglobin: Men (13.6-16.9), women (11.9-14.8)"}
{"_id": "WikiPedia_Hematology$$$corpus_6098", "text": "- Hematocrit: Men (40-50%), women (35-43%)"}
{"_id": "WikiPedia_Hematology$$$corpus_6099", "text": "- MCV: 82.5 - 98"}
{"_id": "WikiPedia_Hematology$$$corpus_6100", "text": "- Reticulocyte count: Men (16-130X10^3/microL or X10^9), Women (16-98/microL or     X10^9)"}
{"_id": "WikiPedia_Hematology$$$corpus_6101", "text": "Differential using MCV"}
{"_id": "WikiPedia_Hematology$$$corpus_6102", "text": "MCV can be a great measure for differentiating between different forms of anemia. MCV measures the average size of your red blood cells. There are three cut off measurements for MCV. If the MCV is < 80fL it is considered microcytic. If the MCV is from 80 to 100 fL then it is considered a normocytic anemia. If the MCV is > 100 fL it is considered a macrocytic anemia. Some causes of anemia can be characterized by different ranges of MCV depending upon the severity disease.  Here are common causes of anemia organized by MCV. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6103", "text": "MCV < 80 fL"}
{"_id": "WikiPedia_Hematology$$$corpus_6104", "text": "- Iron deficiency"}
{"_id": "WikiPedia_Hematology$$$corpus_6105", "text": "- Thalassemia"}
{"_id": "WikiPedia_Hematology$$$corpus_6106", "text": "- Anemia of chronic disease or anemia of inflammation"}
{"_id": "WikiPedia_Hematology$$$corpus_6107", "text": "MCV 80 - 100 fL"}
{"_id": "WikiPedia_Hematology$$$corpus_6108", "text": "-  Iron deficiency"}
{"_id": "WikiPedia_Hematology$$$corpus_6109", "text": "- Infection"}
{"_id": "WikiPedia_Hematology$$$corpus_6110", "text": "- Hypothyroidism"}
{"_id": "WikiPedia_Hematology$$$corpus_6111", "text": "- Liver disease or alcohol use"}
{"_id": "WikiPedia_Hematology$$$corpus_6112", "text": "- Drug-induced"}
{"_id": "WikiPedia_Hematology$$$corpus_6113", "text": "- Hemolysis"}
{"_id": "WikiPedia_Hematology$$$corpus_6114", "text": "- Vitamin B12 or folate deficiency"}
{"_id": "WikiPedia_Hematology$$$corpus_6115", "text": "MCV > 100 fL"}
{"_id": "WikiPedia_Hematology$$$corpus_6116", "text": "- Drug induced"}
{"_id": "WikiPedia_Hematology$$$corpus_6117", "text": "- Myelodysplastic Syndromes"}
{"_id": "WikiPedia_Hematology$$$corpus_6118", "text": "Pregnant women need almost twice as much iron as women who are not pregnant do. Not getting enough iron during pregnancy raises risk of  premature birth  or a  low-birth-weight  baby. [ 23 ]  Hormonal changes in the pregnant woman result in an increase in circulating blood volume to 100 mL/kg with a total blood volume of approximately 6000\u20137000 mL. While red cell mass increases by 15\u201320% during pregnancy, plasma volume increases by 40%. [ 24 ]  Hemoglobin levels less than 11 g/dL during the first trimester, less than 10.5 g/dL during the second and third trimesters and less than 10\u00a0mg/dL in the postpartum period are considered anemic. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6119", "text": "Anemia is a very common complication of pregnancy. A mild form of anemia can be a result of dilution of blood. There is a relatively larger increase in blood plasma compared to total red cell mass in all pregnancies, which results in dilution of the blood and causes physiologic anemia . These changes take place to ensure adequate amount of blood is supplied to the fetus and prepares body for expected blood loss at the time of delivery. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6120", "text": "Iron deficiency is the most common cause of non-physiologic anemia. Iron deficiency anemia can be prevented with supplemental oral iron 27\u201330\u00a0mg daily. [ 27 ]  This dose typically corresponds to the amount of iron found in iron-containing prenatal vitamins. Consult with your medical provider to determine whether additional supplements are needed. Complete routine labs during pregnancy for early detection of iron deficiency anemia. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6121", "text": "Iron deficiency anemia can also be prevented by eating iron-rich foods. This includes dark green leafy vegetables, eggs, meat, fish, dried beans, and fortified grains. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6122", "text": "This may be only applicable to select individuals."}
{"_id": "WikiPedia_Hematology$$$corpus_6123", "text": "Vitamin B12 : Women who consume strictly vegan diets are advised to take Vitamin B12 supplements; this helps prevent anemia due to low Vitamin B12 levels. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6124", "text": "Folic Acid:  Folic acid supplement recommended for women with history of documented folate deficiency. Folic acid supplementation also recommended for prevention of neural tube defects in the fetus. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6125", "text": "For treatment of iron deficiency anemia in pregnant women, iron supplementation at doses higher than prenatal supplements is recommended. The standard doses of oral iron ranges from 40\u00a0mg to 200\u00a0mg elemental iron daily. [ 30 ]  Consult with your medical provider to determine the exact dose needed for your condition, higher than needed doses of iron supplements may sometimes lead to more adverse effects. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6126", "text": "Iron supplements are easy to take, however adverse effects in some cases may include gastrointestinal side effects, nausea, diarrhea, and/or constipation. In cases when oral iron supplement is not tolerable, other options include longer intervals between each oral dose, liquid iron supplements, or intravenous iron. [ 21 ]  Intravenous iron may also be used in cases of severe iron deficiency anemia during second and third trimesters of pregnancy. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6127", "text": "Anemias due to other deficiencies such as folic acid or vitamin B12 can also be treated with supplementation as well; dose may vary based on level of deficiency. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6128", "text": "Other forms of anemias, such as inherited or acquired anemias prior to pregnancy, will require continuous management during pregnancy as well. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6129", "text": "Treatment should target the underlying disease or condition affecting the patient."}
{"_id": "WikiPedia_Hematology$$$corpus_6130", "text": "According to the WHO estimation, the global prevalence of anemia during pregnancy is over 40%, and the prevalence of anemia during pregnancy in North America is 6%. [ 36 ]  Prevalence of anemia in pregnancy is higher in developing countries compared to developed countries. 56% of pregnant women from low and middle income countries were reported to have anemia. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6131", "text": "An  antibody elution  is a  clinical laboratory  diagnostic procedure which removes sensitized  antibodies  from  red blood cells , in order to determine the  blood group system antigen  the antibody targets. [ 1 ]  An antibody elution is deemed necessary when antibodies of the  immunoglobulin class G  (IgG) are found sensitized (bound) to peripheral red cells collected from a blood product transfusion recipient. [ 2 ]  IgG antibodies are detected using an assay known as the  direct antiglobulin test . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6132", "text": "Antibody elutions are specialized tests used in clinical  blood banks . Examples of routine tests include  ABO/Rh , antibody screen, antibody identification, and  antiglobulin testing . Examples of other specialized tests used in blood banking include: treatment with thiol reagent,  monocyte monolayer assay , enzyme treatment, and adsorptions. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6133", "text": "This procedure aids in the investigation of antibodies that are difficult to identify, distinguishing  transfusion reactions ,  hemolytic disease of the fetus and newborn , and warm autoantibody workups. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6134", "text": "Red blood cell membranes consist of a  phospholipid  bilayer, littered with  proteins ,  lipids ,  carbohydrates , and combinations of these substances. [ 5 ]  These substances are called  antigens  because they stimulate an  immune response  when an individual is exposed to the substance, but the exposed individual does not carry nor express the genes which encode said antigens. [ 6 ]  Each individual has a unique genetic and phenotypic makeup of antigens, much like the dermatoglyphics of human  fingerprints ."}
{"_id": "WikiPedia_Hematology$$$corpus_6135", "text": "As of 2023, there are 44 blood group systems, each containing several red blood cell antigens totaling 354, determined by approximately 49 separate genes. [ 7 ]  Of these antigens, only a handful are considered clinically significant, meaning that they can stimulate the production of antibodies capable of causing red cell  hemolysis . This is particularly important for the transfusion of packed red blood cells and other cellular blood products. Examples of blood group systems that contain antigens capable of inducing clinically significant alloantibodies (antibodies against non-self antigens) include, but are not limited to the  ABO ,  Rh ,  Kell ,  Duffy ,  Kidd , and  MNS  blood group systems. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6136", "text": "Antibodies to blood group system antigens and their characteristics must be identified when such antibodies are detected in a potential recipient's  serum  or  plasma . [ 9 ]  The specificity of the antibody aids the  medical laboratory scientist  in determining if the antibody is clinically significant. Antibody identification is a very laborious process. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6137", "text": "Characteristics of clinically significant antibodies include: reactive at body temperature (37\u00b0C),  immunoglobulin (Ig) class G ,  IgM  that reacts at body temperature, ability to cross the  placenta , ability to cause red blood cell destruction, and/or antibodies directed against commonly known clinically significant red cell antigens. [ 10 ]  For example, if an individual is exposed to a red cell antigen (via blood transfusion, pregnancy, stem-cell transplant) that they do not inherently possess, they may form a clinically significant antibody directed against that antigen. If a patient receives a transfusion of packed red blood cells possessing the  Kell  antigen (big K or simply K), they may form an antibody called anti-K (anti big K). Subsequent transfusions with K-positive packed red blood cells would cause an immediate  hemolytic transfusion reaction . The K antibody reacts at 37\u00b0C, is IgG, capable of crossing the placenta, and known to cause immediate red blood cell destruction."}
{"_id": "WikiPedia_Hematology$$$corpus_6138", "text": "The presence of  autoantibodies  directed against self red blood cell antigens can complicate the antibody identification process. Red blood cell autoantibodies tend to be specific for red cell antigens of high frequency within the population. An antibody elution can aid in the identification of clinically significant  alloantibodies  when autoantibodies interfere with the antibody identification process. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6139", "text": "There are several methods of antibody elution used in clinical blood banking. Some of these methods include manipulating temperature, manipulating  pH , use of organic solvents, and  chloroquine . [ 2 ]  Each of these methods have advantages and disadvantages, and the method of elution will vary depending on clinical utility. One of the more commonly used methods is an acid elution, because it is quick, cheap, and relatively easy to perform. [ 3 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6140", "text": "The main steps involved in an acid elution include: [ 3 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6141", "text": "The main method of antibody and antigen detection used in a clinical laboratory is red blood cell  agglutination . [ 1 ]  Most IgM antibodies are easier to detect because they are larger and react at room temperature (20\u00b0C). [ 13 ] [ 14 ]  This concept is what makes ABO/Rh testing so quick and easy to perform. However, most clinically significant non-ABO antibodies react at body temperature (37\u00b0C) and will not result in agglutination without the addition of multiple steps: incubation, washing, and the addition of anti-human globulin (AHG) reagent. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6142", "text": "Anti-human globulin is an antibody directed against human IgG antibodies. [ 16 ]  When the smaller IgG antibody is attached to red blood cells, the larger AHG antibodies create a cross-link between IgG sensitized RBC forming visual agglutination. When this agglutination is observed, the antiglobulin test is considered positive for the detection of the antibody and/or antigen(s) present. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6143", "text": "There are two main types of antiglobulin testing: indirect and direct. [ 17 ] [ 18 ]  Indirect antiglobulin testing is used to detect antibodies in  plasma / serum , whereas direct antiglobulin testing is used to detect antibody bound to red blood cells. When the direct antiglobulin test is positive, we must perform an antibody elution to remove the antibody for identification and to determine the antibody's clinical significance. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6144", "text": "Antifibrinolytics  are a class of  medication  that are inhibitors of  fibrinolysis . [ 1 ]  Examples include  aminocaproic acid  (\u03b5-aminocaproic acid) and  tranexamic acid .  These  lysine -like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on the surface of fibrin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6145", "text": "Another example,  aprotinin , is a naturally-occurring broad-spectrum protease inhibitor; [ 2 ]  some countries refuse to approve this medication because it supposedly has a greater mortality rate than its alternatives (tranexamic acid and aminocaproic acid) and causes damage to the kidneys and heart. It is widely agreed that systemic aprotinin use should be minimized due to these concerns. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6146", "text": "An  antihemorrhagic  ( British English :  antihaemorrhagic ) agent is a substance that promotes  hemostasis  (stops  bleeding ). [ 1 ]  It may also be known as a  hemostatic  (also spelled  haemostatic ) agent. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6147", "text": "Antihemorrhagic agents used in medicine have various mechanisms of action:"}
{"_id": "WikiPedia_Hematology$$$corpus_6148", "text": "Hemostatic agents are used during surgical procedures to achieve hemostasis and are categorized as hemostats, sealants and adhesives. They vary based on their mechanism of action, composition, ease of application, adherence to tissue, immunogenicity and cost. These agents permit rapid hemostasis, better visualization of the surgical area, shorter operative times, decreased requirement for transfusions, decreased wound healing time and overall improvement in patient recovery time. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6149", "text": "There are several classes of antihemorrhagic drugs used in medicine.  These include  antifibrinolytics , blood  coagulation factors ,  fibrinogen , and  vitamin K . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6150", "text": "Topical hemostatic agents have been gaining popularity for use in  emergency bleeding control , especially in  military medicine .  They are available in three forms\u2014as a granular powder poured on wounds, as a styptic pencil [ 5 ]  or embedded in a  dressing . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6151", "text": "Microfibrillar  collagen  hemostat (MCH) is a topical agent composed of resorbable microfibrillar collagen. It attracts platelets and allows for the formation of a blood clot when it comes into contact with blood. Unlike the hemostatic clamp, no mechanical action is involved.  The surgeon presses the MCH against a bleeding site, and the collagen attracts and helps with the clotting process to eventually stop bleeding. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6152", "text": "The practical application for MCH is different from that of the hemostatic clamp. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6153", "text": "Chitosan  hemostats are topical agents composed of chitosan and its salts. Chitosan bonds with platelets and red blood cells to form a gel-like clot which seals a bleeding vessel. Unlike other hemostat technologies its action does not require the normal hemostatic pathway and therefore continues to function even when anticoagulants like heparin are present. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6154", "text": "Chitosan is used in some emergency hemostats which are designed to stop traumatic life-threatening bleeding.  Their use is well established in many military and trauma units. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6155", "text": "Kaolin  (and the  zeolite  in it) activate the coagulation cascade, and have been used as the active component of hemostatic dressings (for example, in  QuikClot ). [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6156", "text": "A  styptic  (also spelled  stiptic ) is a specific type of antihemorrhagic agent that works by contracting  tissue  to seal injured  blood vessels . Styptic pencils contain  astringents . [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6157", "text": "A common delivery system for this is a styptic or hemostatic pencil (not to be confused with a  caustic pencil ). This is a short stick of  medication .   Anhydrous   aluminium sulfate  is the main ingredient and acts as a vasoconstrictor in order to disable blood flow.  The stick is applied directly to the bleeding site. The high  ionic strength  promotes  flocculation  of the blood, and the astringent chemical causes local vasoconstriction.  Before  safety razors  were invented, a styptic pencil was a standard part of a shaving kit and was used to seal shaving cuts. [ 13 ]   Some people continue to use styptic pencils for minor skin wounds from safety or electric razors. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6158", "text": "Styptic powder is used in the  veterinary  trade to stop bleeding from nails that are clipped too closely.  This powder is generally used on animals, such as   cats ,  dogs , and  rabbits , whose vein is found in the center of the nail. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6159", "text": "360"}
{"_id": "WikiPedia_Hematology$$$corpus_6160", "text": "11828"}
{"_id": "WikiPedia_Hematology$$$corpus_6161", "text": "ENSG00000165272"}
{"_id": "WikiPedia_Hematology$$$corpus_6162", "text": "ENSMUSG00000028435"}
{"_id": "WikiPedia_Hematology$$$corpus_6163", "text": "Q92482"}
{"_id": "WikiPedia_Hematology$$$corpus_6164", "text": "Q8R2N1"}
{"_id": "WikiPedia_Hematology$$$corpus_6165", "text": "NM_004925 NM_001318144"}
{"_id": "WikiPedia_Hematology$$$corpus_6166", "text": "NM_016689"}
{"_id": "WikiPedia_Hematology$$$corpus_6167", "text": "NP_001305073 NP_004916"}
{"_id": "WikiPedia_Hematology$$$corpus_6168", "text": "NP_057898"}
{"_id": "WikiPedia_Hematology$$$corpus_6169", "text": "Aquaporin 3  ( AQP-3 ) is the protein product of the human  AQP3  gene. [ 5 ]  It is found in the basolateral cell membrane of principal  collecting duct  cells and provides a pathway for water to exit these cells. [ 6 ]  Aquaporin-3 is also permeable to   glycerol ,  ammonia ,  urea , and  hydrogen peroxide . It is expressed in various tissues including the skin, respiratory tract, and kidneys as well as various types of cancers. [ 7 ]  In the kidney, aquaproin-3 is unresponsive to the antidiuretic hormone  vasopressin , unlike  aquaporin-2 . [ 8 ]  This protein is also a determinant for the GIL blood group system. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6170", "text": "Suberoylanilide hydroxamic acid  (SAHA) (a  HDAC inhibitor ) increases expression of aquaporin-3 in normal skin cells ( keratinocytes ). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6171", "text": "Aquaporin 3 levels are often lower in  psoriasis  than in healthy skin. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6172", "text": "Aquaporin 3 is expressed more in  atopic eczema . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6173", "text": "Recent studies indicate that aquaporin 3 is overexpressed in many types of malignancies such as  melanoma [ 7 ]  and  primary effusion lymphomas [ 12 ]  as well as cancers of the lung, colon, stomach, esophagus, mouth, liver, and pancreatic duct. [ 5 ] [ 12 ]  Based on these as well as  cell culture  studies, it is suggested that this overexpression contributes to the growth and spread of at least some of these cancers and therefore may be a therapeutic target for the treatment of these cancers. [ 5 ] [ 7 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6174", "text": "Auberger's blood group  is a type of  human blood group [ 1 ]  in which the Aua  antigen  is expressed. It is found in 82% of  caucasians . It may be related to the  Lutheran antigen system . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6175", "text": "The blood group was named after patient Auberger, who was a 59-year-old  French  woman with  oesophageal varices . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6176", "text": "Auberger's blood group  at  Who Named It?"}
{"_id": "WikiPedia_Hematology$$$corpus_6177", "text": "The  Augustine blood group system  is a  human blood group system . It includes four  red blood cell  surface  glycoprotein   antigens  which are encoded by  alleles  of the gene  SLC29A1 . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6178", "text": "The protein which acts as the Augustine antigens is  equilibrative nucleoside transporter 1 , a transmembrane  glycoprotein  that mediates cellular uptake of  nucleosides . [ 2 ]  This protein is abundant in  erythroid progenitor cells  and in mature red blood cells. [ 3 ]  There are four known variants of the antigen: AUG1, AUG2, AUG3, and AUG4. [ 1 ]  One person may express multiple variants; AUG:1,2,4 (expressing AUG1, AUG2, and AUG4) is the common  phenotype . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6179", "text": "Antibodies  against Augustine system antigens can be stimulated by pregnancy or  blood transfusion  and have the potential to cause severe  hemolytic disease of the fetus and newborn  and  acute hemolytic transfusion reactions . [ 1 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6180", "text": "In red blood cells, the Augustine antigen protein seems to play a role in  adenosine  transport in  cell differentiation , when immature cells become red blood cells. [ 3 ]  Individuals with the null phenotype, lacking any form of the transporter protein, have  mineralization  around the joints,  ectopic calcification , and abnormal red blood cells. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6181", "text": "AUG2 was first identified as At a  in 1967 as a common human antigen. [ 3 ]  The SLC29A1 gene was identified in 1997 and found to encode AUG1 and AUG2 in 2015. [ 3 ]  In response to the 2015 discovery, the  International Society of Blood Transfusion  established the Augustine blood system as the 36th human blood group system. [ 3 ]  AUG3 and AUG4 were identified in 2018. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6182", "text": "The blood group system was named Augustine after the surname of the individual with the first identified anti-At a  antibody, a woman of African ancestry whose third child had a positive  direct antiglobulin test  at birth. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6183", "text": "Autoimmune hemolytic anemia  ( AIHA ) is an  autoimmune disorder  which occurs when  antibodies  directed against the person's own  red blood cells  (RBCs) cause them to burst ( lyse ), leading to an insufficient number of oxygen-carrying red blood cells in circulation ( anemia ). The lifetime of the RBCs is reduced from the normal 100\u2013120 days to just a few days in serious cases. [ 1 ] [ 2 ]  The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence  antigens , therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a  blood transfusion ). [ 3 ]  AIHA is a relatively rare condition, with an incidence of 5\u201310 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the  cold-antibody  type. [ 4 ]  Autoimmune hemolysis might be a precursor of later onset  systemic lupus erythematosus . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6184", "text": "The terminology used in this disease is somewhat ambiguous. Although  MeSH  uses the term \"autoimmune hemolytic anemia\", [ 6 ]  some sources prefer the term \" immunohemolytic anemia \" so drug reactions can be included in this category. [ 7 ] [ 8 ]  The  National Cancer Institute  considers \" immunohemolytic anemia \", \" autoimmune hemolytic anemia \", and \" immune complex hemolytic anemia \" to all be synonyms. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6185", "text": "Symptoms of AIHA may be due to the underlying anemia; including shortness of breath or  dyspnea , fatigue, headache, muscle weakness and  pallor . [ 10 ]  In  cold agglutinin disease  (cold antibody type), agglutination and impaired passage of red blood cells through capillaries in the extremities causes  acrocyanosis  and  Raynaud phenomenon  with a rare complication of  gangrene [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6186", "text": "Spherocytes  are found in immunologically mediated  hemolytic anemias . [ 11 ]  Signs of hemolysis that are present in AIHA include low  hemoglobin  (blood count), alterations in levels of cell markers of hemolysis; including elevated  lactate dehydrogenase (LDH) , decreased  haptoglobin  and elevated  unconjugated bilirubin . [ 4 ]  Reticulocytosis, or an increase in circulating immature red blood cells, may be seen. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6187", "text": "The causes of AIHA are poorly understood. The disease may be primary, or secondary to another underlying illness. The primary illness is  idiopathic  (the two terms used synonymously). Primary AIHA accounts for more than 60% of unselected  cases. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6188", "text": "Secondary AIHA can result from many other illnesses. Warm and cold type AIHA each have their own more common secondary causes. The most common causes of secondary warm-type AIHA include lymphoproliferative disorders (e.g.,  chronic lymphocytic leukemia ,  lymphoma ) and other autoimmune disorders (e.g.,  systemic lupus erythematosus ,  rheumatoid arthritis ,  scleroderma ,  Crohn's disease ,  ulcerative colitis ). Less common causes of warm-type AIHA include neoplasms other than lymphoid, and infection. Secondary warm type AIHA has been observed in cases of  Covid-19 . [ 4 ]  Secondary cold type AIHA is also caused primarily by lymphoproliferative disorders but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis, and other respiratory infections. Less commonly, it can be caused by concomitant autoimmune disorders. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6189", "text": "Drug-induced AIHA , though rare, can be caused by a number of drugs, including  \u03b1-methyldopa  and  penicillin . This is a  type II immune response  in which the drug binds to  macromolecules  on the surface of the RBCs and acts as an antigen. Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a, activate granular leukocytes (e.g., neutrophils), while other components of the system (C6, C7, C8, C9) either can form the membrane attack complex (MAC) or can bind the antibody, aiding phagocytosis by  macrophages  (C3b). This is one type of \"penicillin allergy\". [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6190", "text": "In about half of cases, the cause of autoimmune hemolytic anemia cannot be determined (idiopathic or primary). This condition can also be caused by or occur with another disorder (secondary) or rarely, occur following the use of certain drugs (such as  penicillin ) or after a person has a blood and marrow  stem cell transplant . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6191", "text": "Secondary causes of autoimmune hemolytic anemia include: [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6192", "text": "AIHA can be caused by a number of different classes of antibody, with  IgG  and  IgM  antibodies being the main causative classes. Depending on which is involved, the  pathology  will differ. IgG is not very effective at activating  complement  and effectively binds the  Fc receptor  (FcR) of  phagocytic cells , [ 15 ]  AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the  classical complement pathway , thus, AIHA involving IgM is characterized by complement-mediated opsonization and phagocytosis of RBCs as the amount of C3b deposited is sublytic. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). In general, IgG AIHA takes place in the  spleen , whereas IgM AIHA takes place in  Kupffer cells  \u2013 phagocytic cells of the  liver . Phagocytic AIHA is termed extravascular, whereas complement-mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable, it requires overwhelming complement activation, therefore most AIHA is extravascular \u2013 be it IgG- or IgM-mediated. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6193", "text": "AIHA cannot be attributed to any single autoantibody. To determine the autoantibody or autoantibodies present in a patient, the  Coombs test , also known as the antiglobulin test, is performed. There are two types of Coombs tests, direct and indirect; more commonly, the direct antiglobulin test (DAT) is used. Classification of the antibodies is based on their activity at different temperatures and their etiology. Antibodies with high activity at physiological temperature (approximately 37\u00a0\u00b0C) are termed warm autoantibodies. Cold autoantibodies act best at temperatures of 0\u20134\u00a0\u00b0C. Patients with cold-type AIHA, therefore, have higher disease activity when body temperature falls into a hypothermic state. Usually, the antibody becomes active when it reaches the limbs, at which point it opsonizes RBCs. When these RBCs return to central regions, they are damaged by complement. Patients may present with one or both types of autoantibodies; if both are present, the disease is termed \"mixed-type\" AIHA. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6194", "text": "When DAT is performed, the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with  antisera  to IgG antibodies with or without complement activation. Cases may also arise with complement alone or with  IgA , IgM or a combination of these three antibody classes and complement. Cold-type AIHA usually reacts with antisera to complement and occasionally to the above antibodies. This is the case in both cold agglutinin disease and cold paroxysmal hematuria. In general, mixed warm and cold AIHA shows a positive reaction to IgG and complement, sometimes IgG alone, and sometimes complement alone. Mixed-type can, like the others, present unusually with positive reactions to other antisera. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6195", "text": "Diagnosis is made by first ruling out other causes of hemolytic anemia, such as  G6PD ,  thalassemia ,  sickle-cell disease . Clinical history is also important to elucidate any underlying illness or medications that may have led to the disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6196", "text": "Laboratory investigations are carried out to determine the etiology of the disease. Following confirmation of hemolysis (seen with laboratory markers of low hemoglobin, elevated LDH, decreased haptoglobin, and elevated unconjugated bilirubin), a  direct antiglobulin test  (DAT)(also known as a Coomb's test) is done to show auto-immune pathogenesis with antibodies, complement or both on the erythrocyte surface. [ 4 ]  This is followed by a monospecific DAT that identifies the specific antibody and complement types on the erythrocyte surface. [ 4 ]  In cold agglutinin disease, the monospecific DAT is by definition positive for the complement molecule C3d but IgM may be negative as the molecule may detach at the time of testing. [ 4 ]  The diagnosis of cold agglutinin disease is confirmed with an elevated cold agglutinin titer. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6197", "text": "A  bone marrow biopsy  is used in AIHA to identify a possible underlying lymphoproliferative disorder. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6198", "text": "AIHA can be classified as  warm autoimmune hemolytic anemia   or  cold autoimmune hemolytic anemia , which includes  cold agglutinin disease  and  paroxysmal cold hemoglobinuria . These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6199", "text": "The following findings may be present: [ 20 ] [ 21 ] [ full citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6200", "text": "Steroids are the first line treatment in warm AIHA; with oral prednisone achieving an 80% initial response rate, with a 30-40% sustained remission rate at 1 year. [ 4 ]  Steroids may be decreased at 3 weeks and tapered at 3\u20136 months depending on the response. [ 4 ]   Rituximab  may be added to initial management to increase the response rate, or it may be used in cases of severe disease such as IgA mediated warm AIHA, mixed AIHA,  Evans syndrome  or in cases of high hemolysis levels). [ 4 ]  If a response cannot be achieved with steroids or rituximab,  splenectomy  can be done. [ 4 ]  Other third line options, that are less studied, include  azathioprine ,  cyclophosphamide ,  cyclosporine ,  mycophenolate mofetil  and  bortezomib . [ 4 ]  The treatments for secondary warm AIHA are generally the same as primary warm AIHA, but with the addition of treating the underlying disease if possible. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6201", "text": "Steroids are not indicated in the treatment of cold agglutinin disease due to low response rates. [ 4 ]  Cases of cold agglutinin disease with mild anemia with limited and compensated hemolysis can be monitored with adjunct supportive care (such as avoidance of cold exposure or thermal protection to prevent against hemolysis). [ 4 ]  Rituximab is used to treat pathogenic B-cell clones in cold agglutinin disease with response rates of 45-60%. [ 4 ]  Relapses are common upon discontinuation of rituximab, but the medication can be restarted to achieve subsequent remission. [ 4 ]  Rituximab can be combined with  bendamustine  to achieve a 71% overall and 40% complete response rate with an increased response seen with prolonged therapy (with a time to best response at a median of 30 months) due to the drugs' effect on  long lived plasma cells . [ 4 ]  Splenectomy is less efficacious in cold agglutinin disease. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6202", "text": "Special considerations are required when treating people with AIHA using  blood transfusion . In cold agglutinin disease; the patient and the extremity should be kept warm during transfusion to prevent agglutination and hemolysis of the donor and patient red blood cells. [ 4 ]  In warm AIHA; cross-matching of blood will show incompatibility so it is recommended to perform a bedside in vivo compatibility test prior to infusion. [ 4 ]   Erythropoietin  (EPO) has been shown to increase hemoglobin levels in cold and warm AIHA. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6203", "text": "\"Blood-induced icterus\" produced by the release of massive amounts of a coloring material from blood cells followed by the formation of bile was recognized and described by Vanlair and Voltaire Masius' in 1871. About 20 years later, Hayem distinguished between congenital hemolytic anemia and an acquired type of infectious icterus associated with chronic splenomegaly. In 1904, Donath and Landsteiner suggested a serum factor was responsible for hemolysis in paroxysmal cold hemoglobinuria. French investigators led by Chauffard stressed the importance of red-cell  autoagglutination  in patients with acquired hemolytic anemia. In 1930, Lederer and Brill described cases of acute  hemolysis  with rapid onset of anemia and rapid recovery after transfusion therapy. These hemolytic episodes were thought to be due to infectious agents. A clear distinction between congenital and acquired hemolytic anemia was not drawn, however, until Dameshek and Schwartz in 1938, and, in 1940, they demonstrated the presence of abnormal hemolysins in the sera of patients with acquired  hemolytic anemia  and postulated an  immune mechanism . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6204", "text": "During the past three decades, studies defining red-cell blood groups and serum antibodies have produced diagnostic methods that have laid the basis for immunologic concepts relevant to many of the acquired hemolytic states. Of these developments, the antiglobulin test described by Coombs, Mourant, and Race in 1945 has proved to be one of the more important, useful tools now available for the detection of immune hemolytic states. This technique demonstrated that a rabbit antibody against human globulin would induce agglutination of human red cells \"coated with an incomplete variety of rhesus antibodies\".   C. Moreschlit  had used the same method in 1908 in a goat antirabbit-red-cell system. The test was premature and was forgotten. In 1946, Boorman, Dodd, and Loutit applied the direct antiglobulin test to a variety of hemolytic anemias, and laid the foundation for the clear distinction of autoimmune from congenital hemolytic anemia. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6205", "text": "A hemolytic state exists whenever the red cell survival time is shortened from the normal average of 120 days. Hemolytic anemia is the hemolytic state in which anemia is present, and bone marrow function is inferentially unable to compensate for the shortened lifespan of the red cell. Immune hemolytic states are those, both anemic and nonanemic, which involve immune mechanisms consisting of antigen-antibody reactions. These reactions may result from unrelated antigen-antibody complexes that fix to an innocent-bystander erythrocyte, or from related antigen-antibody combinations in which the host red cell or some part of its structure is or has become antigenic. The latter type of antigen-antibody reaction may be termed \"autoimmune\", and hemolytic anemias so produced are autoimmune hemolytic anemias. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6206", "text": "In general, AIHA in children has a good prognosis and is self-limiting. However, if it presents within the first two years of life or in the teenage years, the disease often follows a more  chronic course , requiring long-term  immunosuppression , with serious developmental consequences. The aim of therapy may sometimes be to lower the use of steroids in the control of the disease. In this case,  splenectomy  may be considered, as well as other immunosuppressive drugs. Infection is a serious concern in patients on long-term immunosuppressant therapy, especially in very young children (less than two years). [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6207", "text": "Autologous blood therapy , also known as  autologous blood injection  or  autohemotherapy , comprises certain types of  hemotherapy  using a person's own  blood  ( auto-  +  hemo-  +  therapy ). There are several kinds, the original belonging only to  traditional medicine ,  alternative medicine , and some newer kind of medicine under investigation. The original, unscientific form is \"the immediate  intramuscular  or  subcutaneous  reinjection of freshly drawn  autologous  blood\". It was used in the early 20th century, when some  physicians  believed that it had  efficacy  and a logical  mechanism of action ; it was abandoned as advancing  science  made clear that it lacked those.  [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6208", "text": "The other forms involve some change to the blood before it is reinjected, typically  oxygenation ,  ozonation  (ozonated autohemotherapy), [ 2 ] [ 3 ]   ultraviolet light  exposure, or  centrifugation . Forms include  platelet-rich plasma  (PRP), and  autologous conditioned serum  (ACS). [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6209", "text": "It is possible that ozonated or UV autohemotherapy may have real  efficacy  and  effectiveness  in  autoimmune diseases , if they are  immunomodulatory  in some way (such as by interfering with the deranged  autoantibodies ), [ 2 ]  but this mechanism of action, if it exists, is not yet well understood; [ 2 ]  it is also logical that whatever molecular changes the ozone and UV bring about are unlikely to act  specifically  on just the desired target molecules, meaning that risks are involved."}
{"_id": "WikiPedia_Hematology$$$corpus_6210", "text": "Although  autologous blood donation  and  plasmapheresis  are conceptually analogous, they are differentiated from autologous blood therapy in the autohemotherapy sense of that term, having thoroughly scientific bases."}
{"_id": "WikiPedia_Hematology$$$corpus_6211", "text": "Autohemotherapy use in  dermatology  was popular in the early 1900s but was abandoned by conventional dermatologists due to a lack of supporting evidence of efficacy. A resurgence of interest in the 2000s [ 1 ]  has led to several investigations evaluating the use of autohemotherapy as a treatment for specific dermatological conditions such as  hives (urticaria)  and  eczema . [ 1 ]  A review of these studies concludes that, though safe, autohemotherapy is only somewhat more effective than injection of  saline solution . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6212", "text": "In 2022, autohemotherapy was studied for its effect on ME/CFS, in which 220 patients were treated with oxygen-ozone autohemotherapy for X weeks, at least two 30min long sessions per week. Significant improvements in ME/CFS were noted at statistically significant p-value < 0.0001. When treated with O2-O3-AHT fatigue symptoms within the first one-two weeks ameliorated from a score value of 7 (meaning the worst) to 1 (meaning the best, i.e., completely absent symptoms) in almost half of the oxygen-ozone treated patients (43.5%). However, researchers did not determine the mechanism of action resulting in patient improvement.  [1]  The study did not include a control group, [2]  making it impossible to know if the treatment had any effect greater than a placebo. No  randomized control trial , considered the standard for medical research, has shown ozone autohemotherapy to be effective."}
{"_id": "WikiPedia_Hematology$$$corpus_6213", "text": "One fringe  dermatologic  application of autohemotherapy, colloquially called a \"vampire facial\", came to public attention in 2013 when an Instagram posting by celebrity  Kim Kardashian West  portrayed her \"blood-soaked face\" during the administration of the procedure. [ 5 ]  Kardashian West later stated that she regretted undergoing the painful procedure. [ 6 ]  A vampire facial procedure involves a combination of  microneedling [ 6 ]  followed by topical application of  platelet-rich plasma  derived from the  centrifugation  of the subject's own blood into various autologous  blood products . [ 6 ]  Proponents claim that autologous  platelet-rich plasma  delivered subcutaneously to the skin of the face can improve its health by stimulating skin cell growth and  collagen [ 5 ]  though the treatment is considered to lie outside of mainstream medicine because claimed benefits are unsupported by scientific evidence from clinical studies. [ 6 ]  Side effects of the treatment may include redness, swelling, bruising, tenderness, tingling, numbness, lumpiness, and/or a feeling of pressure or fullness at the injection sites [ 6 ]  which, providers claim, people recover from within two days with outlying reports from patients whose recovery took a week or more with scabbing and other problems. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6214", "text": "More serious safety concerns have been cited for these treatments when performed in non-medical settings by people untrained in  infection control . [ 5 ] [ 7 ]  The New Mexico Department of Health issued a statement that at least one such business offering vampire facials \"could potentially spread blood-borne infections such as HIV, hepatitis B and hepatitis C to clients.\u201d [ 5 ]  This was subsequently confirmed by the CDC following a number of HIV infections first reported in 2024. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6215", "text": "In contrast, so-called \"vampire filler\" is autologous platelets used as dermal filler in the  platelet-rich fibrin matrix method  of cosmetic surgery; [ 9 ]  it is generally not described as autohemotherapy and the FDA-approved machines for it are approved for use by only licensed surgeons. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6216", "text": "Autotransfusion  is a process wherein a person receives their own  blood  for a  transfusion , instead of  banked  allogenic (separate- donor ) blood. There are two main kinds of autotransfusion: Blood can be  autologously  \"pre-donated\" (termed so despite \"donation\" not typically referring to giving to one's self) before a  surgery , or alternatively, it can be collected during and after the surgery using an  intraoperative blood salvage  device (such as a Cell Saver, HemoClear or CATS). The latter form of autotransfusion is utilized in surgeries where there is expected a large volume blood loss \u2013 e.g. aneurysm, total joint replacement, and spinal surgeries. The effectiveness, safety, and cost-savings of intraoperative cell salvage in people who are undergoing thoracic or abdominal surgery following trauma is not known. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6217", "text": "The first documented use of \"self-donated\" blood was in 1818, and interest in the practice continued until the  Second World War , at which point blood supply became less of an issue due to the increased number of blood donors.  Later, interest in the procedure returned with concerns about allogenic (separate-donor) transfusions.  Autotransfusion is used in a number of  orthopedic ,  trauma , and  cardiac  cases, amongst others. Where appropriate, it carries certain advantages, including the reduction of infection risk, and the provision of more functional cells not subjected to the significant storage durations common among banked allogenic (separate-donor) blood products. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6218", "text": "Autotransfusion also refers to the natural process, where (during fetal delivery) the uterus naturally contracts, shunting blood back into the maternal circulation. [ 2 ]  This is important in pregnancy, because the uterus (at the later stages of fetal development) can hold as much as 16% of the mother's blood supply. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6219", "text": "Autotransfusion is intended for use in situations characterized by the loss of one or more units of blood and may be particularly advantageous for use in cases involving rare  blood groups , risk of infectious disease transmission, restricted  homologous  blood supply or other medical situations for which the use of homologous blood is contraindicated. Autotransfusion is commonly used intraoperatively and postoperatively. Intraoperative autotransfusion refers to recovery of blood lost during surgery or the concentration of fluid in an extracorporeal circuit. Postoperative autotransfusion refers to the recovery of blood in the  extracorporeal  circuit at the end of surgery or from aspirated drainage. [ 3 ]  Further clinical research in the form of randomized controlled trials is required to determine the effectiveness and safety of this procedure due abdominal or thoracic trauma surgery. [ 1 ]  For elective surgeries, cell salvage techniques may not be linked to more negative outcomes or adverse effects and there is weak evidence indicating that this approach may reduce the chances that the person needs an allogenic transfusion. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6220", "text": "The disadvantage of autotransfusion is the depletion of  plasma  and  platelets . The washed autotransfusion system removes the plasma and platelets to eliminate activated  clotting factors  and activated platelets which would cause  coagulopathy  if they were reinfused to the patient, generating a  packed red blood cell  (PRBC) product. This disadvantage is only evident when very large blood losses occur. The  autotransfusionist  monitors blood loss and will recommend the transfusion of  fresh frozen plasma  (FFP) and platelets when the blood loss and return of autotransfusion blood increase. Typically the patient will require FFP and platelets as the estimated blood loss exceeds half of the patient's blood volume. When possible diagnostic tests should be performed to determine the need for any blood products (i.e. PRBC, FFP and platelets). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6221", "text": "The use of blood recovered from the operative field is contraindicated in the presence of  bacterial  contamination or  malignancy . The use of autotransfusion in the presence of such contamination may result in the dissemination of pathologic microorganisms or malignant cells. The following statements reflect current clinical concerns involving autotransfusion contraindications. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6222", "text": "Any abdominal procedure poses the risk of enteric contamination of shed blood. The surgical team must be diligent in observing for signs of  bowel  contamination of the blood. If there is a question of possible contamination the blood may be held until the surgeon determines whether or not bowel contents are in the  surgical field . If the blood is contaminated the entire contents should be discarded. If the patient's life depends upon this blood supply it may be reinfused with the surgeon's consent. While washing with large amounts of a  sodium chloride  solution will reduce the bacterial contamination of the blood, it will not be totally eliminated. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6223", "text": "There is a possibility of the reinfusion of  cancer  cells from the surgical site. [ 6 ]  There are possible exceptions to this contraindication:"}
{"_id": "WikiPedia_Hematology$$$corpus_6224", "text": "The use of leukocyte reduction filters is recommended. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6225", "text": "Autotransfusion is not normally used in  Caesarean sections , because the possibility of an  amniotic fluid   embolism  exists. Emerging literature suggests that amniotic fluid is being cleared during the wash cycle. It is possible that the utilization of autotransfusion in obstetrics may increase as more research is completed. However, if a patient is at risk for blood loss and is a Jehovah's witness, for example, the cell saver can be used with strict guidelines of irrigating profusely to remove amniotic fluid and then suctioning the blood that is being lost. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6226", "text": "In life saving situations with the consent of the surgeon, autotransfusion can be utilized in the presence of the previous stated contraindications i.e.  sepsis , bowel contamination and malignancy. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6227", "text": "Utilizing a special double lumen suction tubing, fluid is aspirated from the operative field and is mixed with an anticoagulant solution. Collected fluid is filtered in a sterile  cardiotomy  reservoir. The reservoir contains filter and has a capacity of between two and three liters of fluid. When a volume adequate to fill the wash bowl has been collected, processing may begin. The volume required to fill the bowl is dependent on the  hematocrit  (HCT) and size of the centrifuge wash bowl. If the patients HCT is normal, the amount needed to process a unit is roughly two times the bowl volume. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6228", "text": "When aspirating the blood it is important to utilize the following technique whenever possible: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6229", "text": "Following these techniques will help reduce  hemolysis  of the red cells and will help increase the amount of red cells that will be salvaged."}
{"_id": "WikiPedia_Hematology$$$corpus_6230", "text": "Antibiotics that are plasma bound can be removed during the autotransfusion wash cycle, however, topical antibiotics which are typically not plasma bound may not be washed out during autotransfusion, and may actually become concentrated to the point of being  nephrotoxic . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6231", "text": "When Avitene, Hemopad, Instat, or collagen type products are used, autotransfusion should be interrupted and a waste or wall suction source must be used. Autotransfusion can be resumed once these products are flushed from the surgical site. If Gelfoam, Surgicel, Thrombogen or Thrombostat are used, autotransfusion can continue, however, direct suctioning of these products should be avoided. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6232", "text": "Cement  is often used or encountered during primary or revision total  joint replacement surgery . Cement in the liquid or soft state should not be introduced into the autotransfusion system. When cement is being applied a waste or wall suction source must be used, however when the cement hardens autotransfusion may be resumed. The use of ultrasonic equipment during revision of total joints changes the cement to a liquid or soft state, which precludes the use of autotransfusion during the use of such equipment. Autotransfusion can only continue when the cement has hardened. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6233", "text": "In the prime phase, the  centrifuge  begins rotation and accelerates to the speed selected on the centrifuge speed control, typically 5,600 rpm. Simultaneously, the pump begins counterclockwise rotation, enabling the transfer of the reservoir contents to the wash bowl. The application of centrifugal force separates the components of the fluid according to their weight. The wash bowl filling continues until the  buffy coat  reaches the shoulder of the wash bowl. Some autotransfusion devices have automatic features including a buffy coat sensor, which is calibrated to detect a full bowl and advance the process to the wash phase automatically. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6234", "text": "The wash phase begins when the wash bowl is appropriately filled with red cells. The pump continues a counterclockwise rotation and clamps adjust, enabling the transfer of wash solution to the wash bowl. The washing phase removes cellular stromata, plasma free hemoglobin, anticoagulant solution, activated clotting factors, any plasma bound antibiotics, intracellular enzymes, plasma, platelets, and white cells. The unwanted fluid passes out of the wash bowl and into a waste reservoir bag. Washing continues until the reinfuse button is depressed (or the program ends, in the case of an automatic device) and the appropriate amount of wash solution has been delivered to the wash bowl. The wash phase is terminated when one to two liters of wash solution has been transferred, or the fluid transferred to the waste bag appears transparent (or both)."}
{"_id": "WikiPedia_Hematology$$$corpus_6235", "text": "When the empty phase is initiated, the centrifuge begins braking. The clamps change positions, enabling the transfer of the wash bowl contents to the reinfusion bag. The centrifuge bowl must come to a complete stop before the pump begins a clockwise rotation to empty the bowl. Once the bowl is emptied, the cycle is ended and a new cycle can be begun. The reinfusion bag attached to the autotransfusion wash set should not be used for high pressure infusion back to the patient. The reinfusion bag contains a significant amount of air, careful monitoring should take place during reinfusion to avoid the potential of air embolism. Therefore, it is recommended to use a separate blood bag attached to the reinfusion bag. This second bag can then be disconnected, air purged from it, and then tied off before giving to anesthesia for reinfusion. Thus reducing the chances of an air embolism. In accordance with Guidelines set by the  American Association of Blood Banks  the blood should be reinfused within 4 hours from washing. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6236", "text": "Postoperative autotransfusion is performed by connecting the double lumen autotransfusion suction line directly to the drain line placed at the conclusion of surgery. Postoperative autotransfusion begins in the operating room when the drain line is placed and the surgical site is closed. Typical postoperative cases are total  knee  and  hip  replacements. Autotransfusion is continued and is effective while the patient actively bleeds during the immediate postoperative phase of recovery. Autotransfusion is ended when bleeding is stopped or is significantly slow, and is discontinued by connecting an ordinary self draining device to the drain lines. Available for postoperative autotransfusion are universal bifurcated connectors which can accommodate two drain lines of any size, these connectors can be attached to the standard ten foot double lumen suction line for postoperative use. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6237", "text": "In some institutions to maximize the effectiveness of autotransfusion and provide the best conservation and return of red cells the soaking of sponges is employed. During the surgical procedure the blood soaked sponges are collected and placed in a sterile basin by the surgical team, sterile  heparinized   saline  is added to the basin to prevent clotting and facilitate the release of red cells. The sponges are periodically wrung out and removed from the basin, the remaining solution can be suctioned into the autotransfusion reservoir so that the red cells can be recovered. The usual ratio of heparinized saline is 5,000 units of heparin per 1,000 ml of 0.9% sodium chloride. The heparin is removed during the autotransfusion process. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6238", "text": "There is some evidence that in 1785 Philip Physic of Philadelphia transfused a  post-partum  patient. [ 10 ]  However the first documented use of autologous blood transfusion was in 1818 when an Englishman, Rey Paul Blundell, salvaged vaginal blood from patients with postpartum  hemorrhage . By swabbing the blood from the bleeding site and rinsing the swabs with saline, he found that he could re-infuse the result of the washings. This unsophisticated method resulted in a 75% mortality rate, but it marked the start of autologous blood transfusion. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6239", "text": "During the  American Civil War  Union Army physicians are said to have administered four transfusions. In 1886, J. Duncan used autotransfusion during the  amputation  of limbs by removing blood from the amputated limb and returning it to the patient by femoral injection. This method was apparently fairly successful. [ 12 ]  A German, M. J. Theis, reported the first successful use of intraoperative autotransfusion in 1914, with a ruptured  ectopic pregnancy . [ 13 ]  The earliest report in the American literature on the use of autotransfusion was by Lockwood in 1917 who used the technique during a  splenectomy  for Banti syndrome. [ 14 ]  Interest in the unrefined technique of autotransfusion continued through to the early 1940s, and was applied to various procedures including treatment of ectopic pregnancy, [ 15 ] [ 16 ]  hemothorax, [ 17 ]  ruptured spleen, [ 18 ] [ 19 ]  perforating abdominal injuries, [ 20 ]  and neurosurgical procedures. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6240", "text": "The interest in autotransfusion dwindled during  World War II , when there was a large pool of donors. After the war, blood testing, typing, and crossmatching techniques were improved making  blood banks  the answer to the increased demand for blood. In the 1960s, interest in autotransfusion revived. With the advances in all fields of surgery, new companies developed autotransfusion devices. Problems still arose, however, with air embolism,  coagulopathy , and hemolysis. [ 22 ]  The devices used during the Korean and Vietnam War collected and provided gross filtration of blood before it was reinfused. [ 23 ]  With the introduction of  cardiopulmonary bypass  in 1952, autotransfusion became an area of study. Klebanoff began a new era of autotransfusion by developing the first commercially available autotransfusion unit in 1968. [ 24 ]  His system, the Bentley Autotransfusion System aspirated, collected, filtered and reinfused autologous whole blood shed from the operative field. The problems with the Bentley system included the requirement of systemic anticoagulation of the patient, introduction of air embolism, and  renal  failure resulting from unfiltered particulate in the reinfused blood."}
{"_id": "WikiPedia_Hematology$$$corpus_6241", "text": "As the Bentley system lost favor  Wilson and associates proposed the use of a discontinuous flow centrifuge process for autotransfusion which would wash the red cells with normal saline solution. [ 25 ]  In 1976, this system was introduced by  Haemonetics Corp.  and is known commonly as \"Cell Saver\". [ 26 ]  More recently in 1995  Fresenius  introduced a continuous autotransfusion system. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6242", "text": "There are three types of systems: un-washed filtered blood; discontinuous flow centrifugal; and continuous flow centrifugal. The unwashed systems are popular because of their perceived inexpense and simplicity. However unwashed systems can cause increase potential for clinical complications. The washed system requires a properly trained and clinically skilled operator. It returns only red blood cells suspended in saline and is rarely associated with any clinical complications. Discontinuous autotransfusion can practically eliminate the need for exposure to homologous blood in elective surgical patients and can greatly reduce the risk of exposure to emergency surgical patients. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6243", "text": "Individuals of the  Jehovah's Witness  religion in particular refuse to accept homologous and autologous pre-donated blood. However some individual members may accept the use of autotransfusion by means of the Cell Saver. The process of autotransfusion using the Cell Saver is modified to maintain a continuous circuit of blood that maintains continuous contact with the body. This process when carefully explained to the patient may be acceptable when a patient otherwise refuses based on religious beliefs. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6244", "text": "Many of the newest autotransfusion machines are programmable to provide separation of blood into three groups; red cells, platelet poor plasma, and platelet rich plasma. Blood can be drawn from the patient just prior to surgery and then separated. The separated blood components which have been sequestered can be stored during the surgical procedure. The red cells and platelet poor plasma can be given back to the patient through  intravenous  transfusion during or after surgery. The platelet rich plasma can be mixed with  calcium  and  thrombin  to create a product known as  autologous platelet gel . This is an autologous product that can be used for a variety of techniques including use as a hemostatic aid, a dural sealant, and an aid to fusion of bone."}
{"_id": "WikiPedia_Hematology$$$corpus_6245", "text": "An  autotransfusionist , also known as a  perioperative blood management technologist ,  is a specialized allied  health professional  who operates the cell saver machine during surgeries that expect significant blood loss."}
{"_id": "WikiPedia_Hematology$$$corpus_6246", "text": "The autotransfusionist is responsible for collecting shed blood from the patient during the operation, scrubs or cleans the blood of impurities, then makes it available to be reinfused into the patient. The process is commonly known as \"cell-saver\" and is considered far superior to the use of blood from a donor, because it reduces the possibility of infection and provides more functional cells back to the patient. [ 1 ]  Because the blood is recirculated, there is no limit to the amount of blood that can be given back to the patient. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6247", "text": "Autotransfusion  can be achieved in the operating room,  intensive care unit , and  emergency department  and require varying degrees of expertise depending on the procedure. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6248", "text": "In order to become a  Certified Perioperative Blood Management Technologist  ( CPBMT ), one must: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6249", "text": "Autotransplantation  is the  transplantation  of  organs ,  tissues , or even particular  proteins  from one part of the body to another in the same person ( auto-  meaning \"self\" in  Greek [ 1 ] )."}
{"_id": "WikiPedia_Hematology$$$corpus_6250", "text": "The  autologous  tissue (also called  autogenous ,  autogeneic , or  autogenic  tissue) transplanted by such a procedure is called an  autograft  or  autotransplant . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6251", "text": "It is contrasted with  allotransplantation  (from other individual of the same species),  syngeneic  transplantation (grafts transplanted between two genetically identical individuals of the same species) and  xenotransplantation  (from other species)."}
{"_id": "WikiPedia_Hematology$$$corpus_6252", "text": "A common example is the removal of a piece of bone (usually from the hip) and its being ground into a paste for the reconstruction of another portion of bone."}
{"_id": "WikiPedia_Hematology$$$corpus_6253", "text": "Autotransplantation, although most common with blood, bone,  hematopoietic stem cells , or skin, can be used for a wide variety of organs. One of the rare examples is autotransplantation of a kidney from one side of the body to the other. Kidney autotransplantation is used as a treatment for  nutcracker syndrome . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6254", "text": "In  blood banking  terminology, autologous  blood donation  refers to a blood donation marked for use by the donor, typically for a scheduled surgery. (Generally, the notion of \"donation\" does not refer to giving to oneself, though in this context it has become somewhat acceptably idiomatic.) They are commonly called \"autos\" by blood bank personnel, and it is one major form of the more general concept of  autotransfusion  (the other being  intraoperative blood salvage )."}
{"_id": "WikiPedia_Hematology$$$corpus_6255", "text": "Some advantages of autologous blood donation are:"}
{"_id": "WikiPedia_Hematology$$$corpus_6256", "text": "The disadvantages are:"}
{"_id": "WikiPedia_Hematology$$$corpus_6257", "text": "Autologous blood is not routinely tested for infectious diseases markers such as  HIV  antibodies. In the United States, autologous blood is tested only if it is collected in one place and shipped to another."}
{"_id": "WikiPedia_Hematology$$$corpus_6258", "text": "There is also a risk that, in an emergency or if more blood is required than has been set aside in advance, the patient could still be exposed to donor blood instead of autologous blood. Autologous donation is also not suitable for patients who are medically unable to or advised not to give blood, such as  cardiac  patients or small  children  and infants. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6259", "text": "In  orthopaedic medicine , a  bone graft  can be sourced from a patient's own bone in order to fill space and produce an osteogenic response in a bone defect. However, due to the donor-site morbidity associated with autograft, other methods such as bone  allograft  and  bone morphogenetic proteins  and synthetic graft materials are often used as alternatives.  Autografts have long been considered the \"Gold Standard\" in oral surgery and implant dentistry because it offered the best regeneration results.  Lately, the introduction of morphogen-enhanced bone graft substitutes have shown similar success rates and quality of regeneration; however, their price is still very high. [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6260", "text": "Autotransplantation of selected organs is often preceded by  ex vivo  (also  bench ,  back-table , or  extracorporeal ) surgery. [ 6 ]  For example,  ex vivo  liver resection and autotransplantation is used in the treatment of selected cases of conventionally unresectable hepatic tumors. [ 7 ]  It can also be implemented in rare scenarios of a blunt abdominal trauma. [ 8 ]  Kidney autotransplantation is a method of a nephron-sparing renal tumor excision or complex renal artery aneurysm management. [ 9 ] [ 10 ]  The uses of  ex vivo  surgery followed by autotransplantation were reported also for heart, lungs and intestines, including  multivisceral  approaches. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6261", "text": "Induced pluripotent stem cells  (iPSCs), capable of differentiating into any cell type,  have potential for solving the problem of donor organ shortage. Reprogramming technology would be used to obtain a personalized, patient-specific, cell product without problems related to histocompatibility of the transplanted tissues and organs. However, the ability to generate such tissues and organs will depend on successful strategies to overcome immunogenicity of the manipulated product. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6262", "text": "Autologous stem-cell transplantation  involves harvesting peripheral blood mononuclear cells (PBMCs) by  apheresis  collection following mobilization of stem cells from the bone marrow into the peripheral blood.  This is typically used for treatment of  multiple myeloma  or aggressive  lymphoma .  Stem cells are  cryopreserved  after collection for infusion after the patient undergoes high-dose  chemotherapy .  Stem cell rescue permits the use of higher doses of chemotherapy than would be tolerated otherwise. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6263", "text": "1BH7 ,  1BNX ,  1BTQ ,  1BTR ,  1BTS ,  1BTT ,  1BZK ,  1HYN ,  3BTB ,  2BTA ,  2BTB ,  4KY9 ,  4YZF"}
{"_id": "WikiPedia_Hematology$$$corpus_6264", "text": "6521"}
{"_id": "WikiPedia_Hematology$$$corpus_6265", "text": "20533"}
{"_id": "WikiPedia_Hematology$$$corpus_6266", "text": "ENSG00000004939"}
{"_id": "WikiPedia_Hematology$$$corpus_6267", "text": "ENSMUSG00000006574"}
{"_id": "WikiPedia_Hematology$$$corpus_6268", "text": "P02730"}
{"_id": "WikiPedia_Hematology$$$corpus_6269", "text": "P04919"}
{"_id": "WikiPedia_Hematology$$$corpus_6270", "text": "NM_000342"}
{"_id": "WikiPedia_Hematology$$$corpus_6271", "text": "NM_011403"}
{"_id": "WikiPedia_Hematology$$$corpus_6272", "text": "NP_000333"}
{"_id": "WikiPedia_Hematology$$$corpus_6273", "text": "NP_035533"}
{"_id": "WikiPedia_Hematology$$$corpus_6274", "text": "Band 3 anion transport protein , also known as  anion exchanger 1  ( AE1 ) or  band 3   or  solute carrier family 4 member 1  (SLC4A1), is a  protein  that is encoded by the  SLC4A1   gene  in humans."}
{"_id": "WikiPedia_Hematology$$$corpus_6275", "text": "Band 3 anion transport protein is a  phylogenetically -preserved  transport protein  responsible for mediating the  exchange  of  chloride  (Cl \u2212 ) with  bicarbonate  (HCO 3 \u2212 ) across  plasma membranes . Functionally similar members of the AE clade are  AE2  and  AE3 . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6276", "text": "Band 3 is present in the basolateral face of the  \u03b1-intercalated cells  of the collecting ducts of the  nephron , which are the main acid-secreting cells of the kidney. They generate  hydrogen  ions and bicarbonate ions from carbon dioxide and water \u2013 a reaction catalysed by  carbonic anhydrase . The hydrogen ions are pumped into the collecting duct tubule by  vacuolar H +  ATPase , the apical  proton pump , which thus excretes acid into the  urine . kAE1, the kidney isoform of AE1, exchanges bicarbonate for chloride on the basolateral surface, essentially returning bicarbonate to the blood. Here it performs two functions: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6277", "text": "It is ubiquitous throughout the  vertebrates . In  mammals , it is present in two specific sites: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6278", "text": "The erythrocyte and kidney forms are different  isoforms  of the same  protein . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6279", "text": "The erythrocyte isoform of AE1, known as eAE1, is composed of 911 amino acids. eAE1 is an important structural component of the erythrocyte cell membrane, making up to 25% of the cell membrane surface. Each red cell contains approximately one million copies of eAE1. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6280", "text": "The kidney isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the  basolateral  membrane of alpha-intercalated cells in the  cortical collecting duct  of the kidney. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6281", "text": "Mutations of kidney AE1 cause distal (type 1)  renal tubular acidosis , which is an inability to acidify the urine, even if the blood is too  acidic . These mutations are disease causing as they cause mistargetting of the mutant band 3 proteins so that they are retained within the cell or occasionally addressed to the wrong (i.e. apical) surface. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6282", "text": "Mutations of erythroid AE1 affecting the extracellular domains of the molecule may cause alterations in the individual's blood group, as band 3 determines the  Diego antigen system  ( blood group ). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6283", "text": "More importantly erythroid AE1 mutations cause 15\u201325% of cases of  hereditary spherocytosis  (a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of  hereditary stomatocytosis [ 7 ]  and Southeast Asian  ovalocytosis . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6284", "text": "Band 3 has been shown to  interact  with  CA2 [ 9 ] [ 10 ] [ 11 ] [ 12 ]  and  CA4 . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6285", "text": "AE1 was discovered following  SDS-PAGE  (sodium dodecyl sulfate polyacrylamide gel electrophoresis) of erythrocyte  cell membrane . The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6286", "text": "Bleeding ,  hemorrhage ,  haemorrhage  or  blood loss  is  blood  escaping from the  circulatory system  from damaged  blood vessels . [ 1 ]  Bleeding can occur  internally , or externally either through a natural opening such as the  mouth ,  nose ,  ear ,  urethra ,  vagina  or  anus , or through a puncture in the  skin .\n Hypovolemia  is a massive decrease in blood volume, and death by excessive loss of blood is referred to as  exsanguination . [ 2 ]  Typically, a healthy person can endure a loss of 10\u201315% of the total blood volume without serious  medical difficulties  (by comparison,  blood donation  typically takes 8\u201310% of the donor's blood volume). [ 3 ]  The stopping or controlling of bleeding is called  hemostasis  and is an important part of both  first aid  and  surgery ."}
{"_id": "WikiPedia_Hematology$$$corpus_6287", "text": "Bleeding arises due to either traumatic injury, underlying medical condition, or a combination."}
{"_id": "WikiPedia_Hematology$$$corpus_6288", "text": "Traumatic bleeding is caused by some type of injury. There are different types of  wounds  which may cause traumatic bleeding. These include:"}
{"_id": "WikiPedia_Hematology$$$corpus_6289", "text": "The pattern of injury, evaluation and treatment will vary with the mechanism of the injury. Blunt trauma causes injury via a shock effect; delivering energy over an area. Wounds are often not straight and unbroken skin may hide significant injury. Penetrating trauma follows the course of the injurious device. As the energy is applied in a more focused fashion, it requires less energy to cause significant injury. Any body organ, including bone and brain, can be injured and bleed. Bleeding may not be readily apparent; internal organs such as the liver, kidney and spleen may bleed into the abdominal cavity. The only apparent signs may come with blood loss. Bleeding from a bodily orifice, such as the rectum, nose, or ears may signal internal bleeding, but cannot be relied upon. Bleeding from a  medical procedure  also falls into this category. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6290", "text": "\"Medical bleeding\" denotes hemorrhage as a result of an underlying medical condition (i.e. causes of bleeding that are not directly due to trauma). Blood can escape from  blood vessels  as a result of 3 basic patterns of injury: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6291", "text": "The underlying scientific basis for blood clotting and hemostasis is discussed in detail in the articles,  coagulation ,  hemostasis  and related articles. The discussion here is limited to the common practical aspects of blood clot formation which manifest as bleeding."}
{"_id": "WikiPedia_Hematology$$$corpus_6292", "text": "Some medical conditions can also make patients susceptible to bleeding. These are conditions that affect the normal hemostatic (bleeding-control) functions of the body. Such conditions either are, or cause,  bleeding diatheses .  Hemostasis  involves several components. The main components of the hemostatic system include  platelets  and the  coagulation  system."}
{"_id": "WikiPedia_Hematology$$$corpus_6293", "text": "Platelets  are small blood components that form a plug in the blood vessel wall that stops bleeding. Platelets also produce a variety of substances that stimulate the production of a blood clot. One of the most common causes of increased bleeding risk is exposure to  nonsteroidal anti-inflammatory drugs  (NSAIDs). The prototype for these drugs is aspirin, which inhibits the production of thromboxane. NSAIDs (for example Ibuprofen) inhibit the activation of  platelets , and thereby increase the risk of bleeding. The effect of aspirin is irreversible; therefore, the inhibitory effect of aspirin is present until the platelets have been replaced (about ten days). Other NSAIDs, such as \"ibuprofen\" (Motrin) and related drugs, are reversible and therefore, the effect on platelets is not as long-lived. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6294", "text": "There are several named coagulation factors that interact in a complex way to form blood clots, as discussed in the article on  coagulation . Deficiencies of coagulation factors are associated with clinical bleeding. For instance, deficiency of Factor VIII causes classic  hemophilia A  while deficiencies of Factor IX cause \"Christmas disease\"( hemophilia B ). Antibodies to Factor VIII can also inactivate the Factor VII and precipitate bleeding that is very difficult to control. This is a rare condition that is most likely to occur in older patients and in those with  autoimmune  diseases. Another common bleeding disorder is  Von Willebrand disease . It is caused by a deficiency or abnormal function of the \"Von Willebrand\" factor, which is involved in platelet activation. Deficiencies in other factors, such as factor XIII or factor VII are occasionally seen, but may not be associated with severe bleeding and are not as commonly diagnosed."}
{"_id": "WikiPedia_Hematology$$$corpus_6295", "text": "In addition to NSAID-related bleeding, another common cause of bleeding is that related to the medication,  warfarin  (\"Coumadin\" and others). This medication needs to be closely monitored as the bleeding risk can be markedly increased by interactions with other medications. Warfarin acts by inhibiting the production of  Vitamin K  in the gut. Vitamin K is required for the production of the clotting factors, II, VII, IX, and X in the liver. One of the most common causes of warfarin-related bleeding is taking antibiotics. The gut bacteria make vitamin K and are killed by antibiotics. This decreases vitamin K levels and therefore the production of these clotting factors."}
{"_id": "WikiPedia_Hematology$$$corpus_6296", "text": "Deficiencies of platelet function may require platelet transfusion while deficiencies of clotting factors may require transfusion of either  fresh frozen plasma  or specific clotting factors, such as  Factor VIII  for patients with hemophilia."}
{"_id": "WikiPedia_Hematology$$$corpus_6297", "text": "Infectious diseases such as  Ebola ,  Marburg virus disease  and  yellow fever  can cause bleeding. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6298", "text": "Dioxaborolane  chemistry enables radioactive  fluoride  ( 18 F ) labeling of  red blood cells , which allows for  positron emission tomography  (PET) imaging of intracerebral hemorrhages. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6299", "text": "Hemorrhaging is broken down into four classes by the American College of Surgeons'  advanced trauma life support  (ATLS). [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6300", "text": "This system is basically the same as used in the staging of  hypovolemic shock ."}
{"_id": "WikiPedia_Hematology$$$corpus_6301", "text": "Individuals in excellent physical and  cardiovascular  shape may have more effective compensatory mechanisms before experiencing cardiovascular collapse. These patients may look deceptively stable, with minimal derangements in vital signs, while having poor peripheral perfusion. Elderly patients or those with chronic medical conditions may have less tolerance to blood loss, less ability to compensate, and may take medications such as betablockers that can potentially blunt the cardiovascular response. Care must be taken in the assessment. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6302", "text": "Although there is no universally accepted definition of massive hemorrhage, the following can be used to identify the condition: \"(i) blood loss exceeding circulating blood volume within a 24-hour period, (ii) blood loss of 50% of circulating blood volume within a 3-hour period, (iii) blood loss exceeding 150 ml/min, or (iv) blood loss that necessitates plasma and platelet transfusion.\" [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6303", "text": "The  World Health Organization  made a standardized grading scale to measure the severity of bleeding. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6304", "text": "Acute bleeding from an injury to the skin is often treated by the application of direct pressure. [ 11 ]  For severely injured patients,  tourniquets  are helpful in preventing complications of  shock . [ 12 ]   Anticoagulant  medications may need to be discontinued and possibly reversed in patients with clinically significant bleeding. [ 13 ]  Patients that have lost excessive amounts of blood may require a  blood transfusion . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6305", "text": "The use of  cyanoacrylate glue  to prevent bleeding and seal battle wounds was designed and first used in the  Vietnam War . [ 15 ]   Skin glue, a medical version of \"super glue\", is sometimes used instead of using traditional stitches used for small wounds that need to be closed at the skin level. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6306", "text": "The word \"Haemorrhage\" (or  h\u00e6morrhage ; using the  \u00e6 ligature ) comes from Latin haemorrhagia, from Ancient Greek \u03b1\u1f31\u03bc\u03bf\u03c1\u03c1\u03b1\u03b3\u03af\u03b1 ( haimorrhag\u00eda , \"a violent bleeding\"), from \u03b1\u1f31\u03bc\u03bf\u03c1\u03c1\u03b1\u03b3\u03ae\u03c2 ( haimorrhag\u1e17s , \"bleeding violently\"), from \u03b1\u1f37\u03bc\u03b1 ( ha\u00eema , \"blood\") + -\u03c1\u03b1\u03b3\u03af\u03b1 ( -rag\u00eda ), from \u1fe5\u03b7\u03b3\u03bd\u03cd\u03bd\u03b1\u03b9 ( rh\u0113gn\u00fanai , \"to break, burst\"). [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6307", "text": "A  blood product  is any therapeutic substance prepared from human  blood . [ 1 ]  This includes  whole blood ; blood components; and plasma derivatives. Blood components include:  red blood cell concentrates  or suspensions;  platelets  produced from whole blood or via apheresis;  Granulocyte ,  plasma ; and  cryoprecipitate . Some products for topical use, such as serum eye drops, have also been recently classified as blood components. [ 2 ]  Plasma derivatives are plasma proteins prepared under pharmaceutical manufacturing conditions, including: albumin; coagulation factor concentrates; and  immunoglobulins ."}
{"_id": "WikiPedia_Hematology$$$corpus_6308", "text": "Blood products may also be called  blood-based products or blood-derived products.  to differentiate them from  blood substitutes , which generally refer to artificially produced products. Although many blood products have the effect of volume expansion, the group is usually distinguished from  volume expanders , which generally refers to artificially produced substances and are thereby within the scope of  blood substitutes ."}
{"_id": "WikiPedia_Hematology$$$corpus_6309", "text": "A  blood substitute  (also called  artificial blood  or  blood surrogate ) is a substance used to mimic and fulfill some functions of  biological   blood . It aims to provide an alternative to  blood transfusion , which is transferring blood or  blood-based products  from one person into another. Thus far, there are no well-accepted  oxygen-carrying  blood substitutes, which is the typical objective of a  red blood cell  transfusion; however, there are widely available non-blood  volume expanders  for cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of  Jehovah's Witnesses  and others who have religious objections to receiving transfused blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6310", "text": "The main categories of \"oxygen-carrying\" blood substitutes being pursued are hemoglobin-based oxygen carriers (HBOC) [ 1 ]  and  perfluorocarbon emulsions . [ 2 ]  Oxygen therapeutics are in clinical trials in the  U.S.  and  European Union , and  Hemopure  is available in  South Africa ."}
{"_id": "WikiPedia_Hematology$$$corpus_6311", "text": "After  William Harvey  discovered blood pathways in 1616, many people tried to use fluids such as beer, urine, milk, and non-human animal blood as blood substitute. [ 3 ]   Sir Christopher Wren  suggested wine and opium as blood substitute. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6312", "text": "At the beginning of the 20th century, the development of modern transfusion medicine initiated through the work of Landsteiner and co-authors opened the possibility to understanding the general principle of  blood group  serology. [ 5 ]   Simultaneously, significant progress was made in the fields of heart and circulation physiology as well as in the understanding of the mechanism of oxygen transport and tissue oxygenation. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6313", "text": "Restrictions in applied transfusion medicine, especially in disaster situations such as World War II, laid the grounds for accelerated research in the field of blood substitutes. [ 8 ]  Early attempts and optimism in developing blood substitutes were very quickly confronted with significant side effects, which could not be promptly eliminated due to the level of knowledge and technology available at that time. The  emergence of HIV  in the 1980s renewed impetus for development of infection-safe blood substitutes. [ 4 ]  Public concern about the safety of the blood supply was raised further by  mad cow disease . [ 4 ] [ 9 ]  The continuous decline of blood donation combined with the increased demand for blood transfusion (increased ageing of population, increased incidence of invasive diagnostic, chemotherapy and extensive surgical interventions, terror attacks, international military conflicts) and positive estimation of investors in biotechnology branch made for a positive environment for further development of blood substitutes. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6314", "text": "Efforts to develop blood substitutes have been driven by a desire to replace  blood transfusion  in emergency situations, in places where infectious disease is endemic and the risk of  contaminated blood products  is high, where refrigeration to preserve blood may be lacking, and where it might not be possible or convenient to find  blood type  matches. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6315", "text": "In 2023,  DARPA  announced funding twelve universities and labs for synthetic blood research. Human trials would be expected to happen between 2028-2030. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6316", "text": "Efforts have focused on molecules that can carry  oxygen , and most work has focused on recombinant  hemoglobin , which normally carries oxygen, and  perfluorocarbons  (PFC), chemical compounds which can carry and release oxygen. [ 10 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6317", "text": "The first approved oxygen-carrying blood substitute was a per fluorocarbon -based product called  Fluosol -DA-20, manufactured by  Green Cross  of Japan. It was approved by the  Food and Drug Administration  (FDA) in 1989. Because of limited success, complexity of use and side effects, it was withdrawn in 1994. However, Fluosol-DA remains the only oxygen therapeutic ever fully approved by the FDA.  As of 2017 no hemoglobin-based product had been approved. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6318", "text": "Perfluorochemicals are not  water soluble  and will not mix with blood, therefore  emulsions  must be made by dispersing small drops of PFC in  water . This liquid is then mixed with  antibiotics ,  vitamins ,  nutrients  and  salts , producing a mixture that contains about 80 different components, and performs many of the vital functions of natural blood. PFC particles are about  \u2060 1 / 40 \u2060  the size of the diameter of a  red blood cell  (RBC). This small size can enable PFC particles to traverse  capillaries  through which no RBCs are flowing. In theory this can benefit damaged, blood-starved  tissue , which conventional red cells cannot reach. PFC solutions can carry oxygen so well that  mammals , including  humans , can survive breathing liquid PFC solution, called  liquid breathing . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6319", "text": "Perfluorocarbon-based blood substitutes are completely man-made; this provides advantages over blood substitutes that rely on modified hemoglobin, such as unlimited manufacturing capabilities, ability to be heat-sterilized, and PFCs' efficient oxygen delivery and carbon dioxide removal. PFCs in solution act as an intravascular oxygen carrier to temporarily augment oxygen delivery to tissues. PFCs are removed from the bloodstream within 48 hours by the body's normal clearance procedure for particles in the blood \u2013 exhalation. PFC particles in solution can carry several times more oxygen per cubic centimeter (cc) than blood, while being 40 to 50 times smaller than hemoglobin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6320", "text": "Fluosol was made mostly of  perfluorodecalin  or  perfluorotributylamine  suspended in an  albumin  emulsion. It was developed in  Japan  and first tested in the  United States  in November 1979. [ 13 ]  In order to \"load\" sufficient amounts of oxygen into it, people who had been given it had to breathe pure oxygen by mask or in a  hyperbaric chamber . [ 14 ]  It was approved by the FDA in 1989, [ 15 ]  and was approved in eight other countries. [ citation needed ]  Its use was associated with a reduction in ischemic complications and with an increase in pulmonary edema and congestive heart failure. [ 16 ]   Due to difficulty with the emulsion storage of Fluosol use (frozen storage and rewarming), its popularity declined and its production ended in 1994. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6321", "text": "Oxygent was a second-generation,  lecithin -stabilized  emulsion  of a PFC that was under development by Alliance Pharmaceuticals. [ 21 ] [ 1 ] [ 22 ]    In 2002 a Phase III study was halted early due an increase in incidences of strokes in the study arm. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6322", "text": "Haemoglobin  is the main component of red blood cells, comprising about 33% of the cell mass. Haemoglobin-based products are called haemoglobin-based oxygen carriers (HBOCs). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6323", "text": "Unmodified cell-free haemoglobin is not useful as a blood substitute because its oxygen affinity is too high for effective tissue oxygenation, the half-life within the intravascular space that is too short to be clinically useful, it has a tendency to undergo dissociation in dimers with resultant kidney damage and toxicity, and because free haemoglobin tends to take up nitric oxide, causing vasoconstriction. [ 4 ] [ 24 ] [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6324", "text": "Efforts to overcome this toxicity have included making  genetically engineered  versions,  cross-linking ,  polymerization , and encapsulation. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6325", "text": "HemAssist, a diaspirin cross-linked haemoglobin (DCLHb) was developed by  Baxter Healthcare ; it was the most widely studied of the haemoglobin-based blood substitutes, used in more than a dozen animal and clinical studies. [ 8 ]    It reached Phase III clinical trials, in which it failed due to increased mortality in the trial arm, mostly due to severe vasoconstriction complications. [ 10 ] [ 8 ]    The results were published in 1999. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6326", "text": "Hemolink (Hemosol Inc., Mississauga, Canada) was a haemoglobin solution that contained cross-linked an o-rafinose polymerised human haemoglobin. [ 10 ]  Hemosol struggled after Phase II trials were halted in 2003 on safety concerns [ 28 ]  and declared bankruptcy in 2005. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6327", "text": "Hemopure was developed by Biopure Corp and was a chemically stabilized, cross-linked bovine (cow) haemoglobin in a salt solution intended for human use; the company developed the same product under the trade name Oxyglobin for veterinary use in dogs.  Oxyglobin was approved in the US and Europe and was introduced to veterinary clinics and hospitals in March 1998. Hemopure was approved in South Africa and Russia. Biopure filed for bankruptcy protection in 2009. [ 30 ]  Its assets were subsequently purchased by HbO2 Therapeutics in 2014. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6328", "text": "PolyHeme was developed over 20 years by  Northfield Laboratories  and began as a military project following the Vietnam War. It is human haemoglobin, extracted from red blood cells, then polymerized, then incorporated into an electrolyte solution. In April 2009, the FDA rejected Northfield's  Biologic License Application [ 31 ]  and in June 2009, Northfield filed for bankruptcy. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6329", "text": "Dextran-Haemoglobin was developed by Dextro-Sang Corp as a veterinary product, and was a conjugate of the polymer dextran with human haemoglobin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6330", "text": "Hemotech was developed by HemoBiotech and was a chemically modified haemoglobin."}
{"_id": "WikiPedia_Hematology$$$corpus_6331", "text": "Somatogen developed a genetically engineered and crosslinked tetramer it called Optro. It failed in a phase II trial and development was halted. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6332", "text": "A pyridoxylated Hb conjugated with  polyoxyethylene  was created by scientists at Ajinomoto and eventually developed by Apex Biosciences, a subsidiary of Curacyte AG; it was called \"PHP\" and failed in a Phase III trial published in 2014, due to increased mortality in the control arm, [ 10 ] [ 33 ]  which led to Curacyte shutting down. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6333", "text": "Similarly, Hemospan was developed by Sangart, and was a  pegylated  haemoglobin provided in a powdered form. While early trials were promising Sangart ran out of funding and closed down. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6334", "text": "Stem cells  offer a possible means of producing transfusable blood. A study performed by Giarratana et al. [ 35 ]  describes a large-scale ex-vivo production of mature human blood cells using  hematopoietic stem cells . The cultured cells possessed the same haemoglobin content and morphology as native red blood cells. The authors contend that the cells had a near-normal lifespan, when compared to natural red blood cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6335", "text": "Scientists from the experimental arm of the  United States Department of Defense  began creating artificial blood for use in remote areas and transfuse blood to wounded soldiers more quickly in 2010. [ 36 ]  The blood is made from the  hematopoietic  stem cells removed from the  umbilical cord  between human mother and newborn using a method called blood  pharming . Pharming has been used in the past on animals and plants to create medical substances in large quantities. Each cord can produce approximately 20 units of blood. The blood is being produced for the  Defense Advanced Research Projects Agency  by Arteriocyte. The  Food and Drug Administration  has examined and approved the safety of this blood from previously submitted O-negative blood. Using this particular artificial blood will reduce the costs per unit of blood from $5,000 to equal or less than $1,000. [ 36 ]  This blood will also serve as a blood donor to all common  blood types . [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6336", "text": "In 1994, the  Irish Blood Transfusion Service Board  (BTSB) informed the Minister for Health that a blood product they had distributed in 1977 for the treatment of pregnant mothers had been contaminated with the  hepatitis C  virus.\nFollowing a report by an expert group, it was discovered that the BTSB had produced and distributed a second infected batch in 1991.\nThe Government established a  Tribunal of Inquiry [ 1 ]  to establish the facts of the case and also agreed to establish a tribunal for the compensation of victims but seemed to frustrate and delay the applications of these, in some cases terminally, ill women."}
{"_id": "WikiPedia_Hematology$$$corpus_6337", "text": "This controversy also sparked an examination of the BTSB's lax procedures for screening blood products for the treatment of  haemophilia  and exposed the infection of many haemophiliacs with  HIV ,  hepatitis B  and hepatitis C."}
{"_id": "WikiPedia_Hematology$$$corpus_6338", "text": "The Blood Transfusion Service Board (BTSB) has responsibility for the production and supply of human blood products used for the treatment of various blood-related conditions. In 1970, it began production of  anti-D  human immunoglobulin for the treatment of  rhesus  negative (blood type) mothers who, having previously given birth to rhesus positive babies, could have anti-bodies that would cause  haemolytic disease  (HDFN) in the foetus of future pregnancies. [ citation needed ] \nIf, following a neo-natal blood test, the rhesus (Rh) factor of the infant is found to be incompatible with that of the mother, an anti-D injection can be given to the mother to protect her future pregnancies. If the mother were to develop her own rhesus anti-bodies, she would be required to undergo a course of  plasma exchange transfusion  throughout her pregnancy to reduce the level of rhesus antibodies in her blood. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6339", "text": "In 1970 the BTSB began manufacturing anti-D human immunoglobulin for intravenous application at its Dublin laboratory using a process developed in 1967 by Professor Hans-Hermann Hoppe of Hamburg's Central Institute for Transfusionmedicine, one of the founders of the German transfusion service,  StKB . The process involved the use of ion-exchange chromatography together with an ethanol precipitation, which was thought at the time to inactivate viruses that might be present in donated blood, thereby removing them from the plasma eventually fractionated in the process. In 1972 Professor Hoppe notified the BTSB that he had refined his process to include a plasma quarantine period and  ultrafiltration  (instead of ethanol precipitation) but the BTSB continued to use his 1967 process. [ 3 ]  By 1975 it was known that hepatitis was a blood-born disease and that multiple types of hepatitis virus were in circulation. Tests were available to identify the hepatitis A and hepatitis B viruses and although it was suspected that another strain of the virus was responsible for Jaundice in patients whose blood did not test positive for either type, there was no diagnostic test for hepatitis C until 1990. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6340", "text": "In 1976 a pregnant woman (referred to as \"Patient X\" in the report of the  Finlay Tribunal [ 1 ] ) was a patient of Dr. McGuinness, assistant master of the  Coombe Maternity Hospital .\nHaving had several pregnancies severely affected by haemolytic disease, Patient X was prescribed a therapeutic course of plasma exchange over a 25-week period, to reduce the antibodies that would damage her foetus. The obstetric consultant suggested to one of the BTSB staff that they could off-set the cost of Patient X's treatment by using the plasma extracted from her (which had high concentrations of anti-D) to manufacture anti-D immunoglobulin. Patient X was never asked to consent to her plasma being used in this way. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6341", "text": "Her treatment began in September 1976 and plasma from her first two treatments was mixed with that from other donors in 5 batches of anti-D produced by the BTSB and distributed between January and April 1977. On 4 November 1976, Patient X had a reaction to her plasma exchange and her treatment was suspended temporarily. On 17 November the Coombe Hospital notified the BTSB that Patient X had become jaundiced and was diagnosed as having hepatitis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6342", "text": "Dr. McGuinness requested that a sample of her blood be tested for hepatitis B and sent a second sample to the  Middlesex Hospital  in  London . These tests reported negative for hepatitis B (hepatitis C was not recognized not to mention testable at this time.)\nAs Patient X's plasma exchange treatments continued, regular blood samples were sent to the BTSB to monitor the level of rhesus anti-bodies in her blood, each sample labelled \"infective hepatitis\". Despite all senior medical staff at the BTSB being aware of this infection, they continued to take plasma donations from Patient X throughout January 1977 and include these in the pools used to make 16 batches of anti-D which were distributed to maternity hospitals for administration. The number of doses in each batch could vary from 250 to 400 injections. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6343", "text": "In July 1977, the BTSB received a report from the  Rotunda Hospital  that 3 mothers who had received injections from anti-D batch 238 had subsequently developed hepatitis. On 25 July, the chief biochemist of the BTSB laboratory was instructed to exclude Patient X's plasma from all pools used to manufacture anti-D. She did precisely this but did not, however, consider disposal or recall of existing batches in which Patient X's plasma had already been used and continued to distribute these to hospitals. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6344", "text": "Samples from the 16 batches of anti-D that included Patient X's plasma and samples from the 3 Rotunda patients were sent to the Middlesex Hospital for testing, which again were inconclusive as no test for hepatitis C existed. The Scientific Committee of the BTSB began to compile a list of the destinations to which doses from anti-D batch 238 had been sent. It is unclear however, if this was completed or used in any recall operation. Between August and December 1977, the BTSB received notifications of similar cases from the maternity hospitals at the  Coombe  and  Holles Street  in Dublin indicating contamination amongst two other batches of anti-D. Despite continued notifications of hepatitis cases in 1977 and 1978, the BTSB issued no national recall of its anti-D product. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6345", "text": "By 1990 scientists had developed multiple diagnostic test mechanisms for hepatitis C: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6346", "text": "HCV RNA can be detected by PCR typically one to two weeks after infection, while antibodies can take substantially longer to form and be detected. Screening a population usually relies on a combination of all three test types. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6347", "text": "With the development of a diagnostic test for hepatitis C in 1990, Dr Jeremy Garson of the Middlesex Hospital conducted retrospective testing on the many non-A, non-B hepatitis (NANBH) samples it had retained over many years. On 16 December 1991, the Middlesex Hospital FAXed a letter to the BTSB in Dublin to inform them that retained samples from Patient X and the 1977 batches of anti-D had tested positive for hepatitis C. Attached to his letter, Dr. Garson provided a list of questions that would need to be answered to determine the causes and extent of infection caused in 1977. The BTSB replied to this letter suggesting the questions be discussed at a meeting in London.  The meeting never happened and the BTSB seems to have taken no further action in respect of this letter. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6348", "text": "When check-back of the Patient X's case commenced in 1992, 8 of the 16 batches made from the BTSB's plasma pools in from January to July 1977 were shown to be contaminated with hepatitis C. These included batch 250 from which  Brigid McCole  received her anti-D injection on 5 November 1977."}
{"_id": "WikiPedia_Hematology$$$corpus_6349", "text": "In August 1989 a pregnant woman (referred to as \"Donor Y\" in the report of the Finlay Tribunal [ 1 ] ) began a course of plasma exchange transfusions at  St. James's Hospital  in Dublin. In the first month of her treatment 10 donations of plasma were taken from her, all of which were clear of hepatitis C when subsequently tested in 1992. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6350", "text": "On 13 September 1989 \"Donor Y\" received a unit of plasma from the BTSB which was almost certainly contaminated with hepatitis C. (Check back tests of her plasma donations after this date tested positive for hepatitis C, a sub-type different from the one that infected Patient X.) With the emergence of HIV in the 1980s and the BTSB's previous difficulties with hepatitis contamination, the BTSB now had a precautionary protocol surrounding plasma donations by mothers undergoing exchange transfusions: Plasma donations from such women could not be included in the production of blood products until they had given birth and had a blood test showing they were clear of HIV, hepatitis B and hepatitis C. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6351", "text": "All of the plasma donated by Donor Y, therefore was frozen and stored subject to clearance for anti-D production. In September and 12 October more donations of plasma were taken from Donor Y and placed in storage. Throughout 1990, the laboratory staff of the BTSB requested the blood test clearance of Donor Y from the BTSB medical staff responsible for her case. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6352", "text": "Despite receiving no test results, in January 1991 the BTSB lab began to include Donor Y's plasma in the plasma pools used to manufacture 46 batches of anti-D. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6353", "text": "In November 1991, Donor Y was tested for HIV, hepatitis B and hepatitis C (for which a new test was available) and was found negative for all three. (It is assumed that by this point she had \"sero converted\" for hepatitis C, having produced sufficient antibodies to eliminate it from her blood stream.) The 4 batches of anti-D suspected of infecting women at the various Dublin maternity hospitals (and which included plasma taken from Donor Y in 1989) tested positive for hepatitis C. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6354", "text": "It was not clearly established whether or not the BTSB laboratory chief was notified of these tests but she continued to manufacture and distribute 21 batches using Donor Y's plasma. Upon subsequent check-back of all 46 anti-D batches produced from the pools containing Donor Y's plasma, 20 batches were found to be positive for Hep-C, 3 were negative and in the remaining 23 \"infectivity could not be ruled out\"."}
{"_id": "WikiPedia_Hematology$$$corpus_6355", "text": "After the hepatitis C virus (HCV) was identified in 1988 and a diagnostic test developed in 1990, in 1991 the BTSB added this test to its screening of all blood donors (along with HIV and hepatitis B). The BTSB's regional director for Munster set up a survey of all donors in the region who tested positive for HCV, with a view to tracing the source of infection. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6356", "text": "She began to notice very soon that almost all positive cases were females and fell across a relatively narrow age range.\nAs a result of this survey, by 1994 she had identified a possible link between infected donors and the anti-D injections they had received many years previously. She made an interim report in this survey at a meeting of the BTSB Medical Consultants Group on 19 January 1994. It was decided to perform a similar study of HCV infection outside the Munster region. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6357", "text": "Samples from the Munster donors who had tested positive for HCV were sent to the Middlesex Hospital and compared with samples from Patient X. The results suggested \"a strong causative relationship\" between them and the 1977 hepatitis infections. It was decided to send samples of the BTSB's current stocks of anti-D to Middlesex for testing. These still contained some batches in which Donor Y's plasma had been used. The results indicated some contamination with HCV but of a different sub-type from that found in 1977 samples."}
{"_id": "WikiPedia_Hematology$$$corpus_6358", "text": "Throughout February 1994, the board of the BTSB held several crisis meetings and on 17 February 1994, the informed the Minister for Health,  Brendan Howlin  T.D. of the discovery. The BTSB and met with  Department of Health  officials to discuss a plan of action. Following meetings between the BTSB and officials at the Department of Health the following measures were agreed:"}
{"_id": "WikiPedia_Hematology$$$corpus_6359", "text": "On the advice of Department of Health officials the BTSB press release on 21 February made no mention of the second contamination of anti-D in 1991. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6360", "text": "On 22 February 1994, the Minister for Health made a Statement in  D\u00e1il \u00c9ireann  about the issue, which had already been reported in the press. He commended the BTSB for their thorough research, assured the public that only virally inactive anti-D would now be distributed and announced some aspects of the National Screening Programme. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6361", "text": "The BTSB's protocol for recall of its products consisted of the sending of a notification letter to each maternity hospital or GP that had been supplied with anti-D and a follow up phone call two weeks later. As the BTSB records were not up-to-date and letters were addressed to named individuals some of whom were no longer working, some of the hospitals did not receive notification and continued to dispense their stock of infected anti-D in 1994. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6362", "text": "In order to have an immediate replacement stock of anti-D following the recall of its own product, the BTSB quickly sourced  WinRho SDF  from the  Winnipeg Rh Institute   Manitoba ,  Canada  without first getting the product approved by the  National Drug Advisory Board  (NDAB)."}
{"_id": "WikiPedia_Hematology$$$corpus_6363", "text": "The BTSB launched its HCV National Screening Programme and set about trying to identify and contact all women who had received anti-D injections since it had begun issuing it in 1970. It did so by checking its own records and contacting Hospitals and GPs to whom infected doses has been sent and by publishing adverts in the national media appealing for women to come forward. By February 1997, 62,667 women had been tested for evidence of HCV infection. Almost 1,200 tested positive for HCV antibodies. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6364", "text": "Of the samples from women who had received anti-D manufactured in 1977, 704 showed signs of current or past infection. Another 53 showed a RIBA reaction but in which antibodies could not be confirmed and a further 74 showed no signs of infection or antibodies but had recovered from an episode of hepatitis in the past. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6365", "text": "Of the samples from women who had received anti-D manufactured in 1991, 72 showed signs of current or past infection. Another 26 showed a RIBA reaction but antibodies could not be confirmed. The BTSB noted that the number of women that came forward for testing from the cohort that received anti-D in 1991 was 30% lower than expected."}
{"_id": "WikiPedia_Hematology$$$corpus_6366", "text": "Because HCV is a blood-borne virus it is relatively difficult to transmit. However, the  risk of transmission  is greater where exposure to or exchange of blood is a factor. The risk to sexual partners is much lower.\nThe screening programme identified 11 individuals who had been infected with HCV through their contact with/treatment of anti-D recipients. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6367", "text": "The greatest risk of secondary infection to the population as a whole would be from infected people donating blood to the BTSB.\nBecause the rhesus negative factor is relatively rare, people with that factor are encouraged to donate blood. Of the infected anti-D recipients, 103 went on to donate blood to the BTSB following their infection. These donors made total of 504 donations which resulted in an estimated 606 potentially infectious labile blood components (Another donor was identified who had been indirectly infected by an anti-D recipient and whose donations went into 8 labile blood components.) As many blood products are administered to patients with critical health issues, the level of mortality amongst all blood product recipients is relatively high. Upon tracing the recipients of the blood products potentially infected by anti-D recipients, the BTSB found that many were deceased but of 61 living recipients, 30 tested positive for on-going infection with HCV. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6368", "text": "The development of ultra-sensitive HCV tests since the 1990s has made it possible to detect markers for the disease in people who seem to be fully recovered from hepatitis. It is accepted, however, that there may still be a level of  \"occult infection\"  in otherwise healthy populations."}
{"_id": "WikiPedia_Hematology$$$corpus_6369", "text": "The screening programme also examined the partners and children of anti-D recipients. As of 17 January 1995, the BTSB reported that 1,265 children and 363 partners have been screened for hepatitis C. Up to that date, ten children had tested positive for hepatitis C antibodies and two of these children have tested positive for the virus. Three partners have tested positive for hepatitis C antibodies. Further investigations were underway in these cases. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6370", "text": "Many of the women who tested positive for HCV experienced relief as the seemingly  inexplicable symptoms  they had suffered over many years could now be explained. However, they suddenly came to feel stigmatized and discriminated against by various members of society. There was a general confusion between HCV and HIV which were often mentioned together in communications about intravenous drug use. For a long time it was unclear whether women could infect their husbands with HCV through sexual intercourse or whether they might have infected their children in utero, which led to stress and tensions in families. Many of the women were refused treatment by dentists, had their employment terminated and were refused insurance. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6371", "text": "The state's largest health insurance company, the  Voluntary Health Insurance  (VHI) refused cover to several women on the grounds that they had acquired a \"sexually transmitted disease\". Some began to feel a deep sense of betrayal as they had contracted this virus and disease through no fault their own but through an agency of the state. Chronic hepatitis C infection when left untreated not only results in  cirrhosis  of the liver but can trigger other diseases not directly associated with the liver (cancers,  hypertension ,  Heart arrhythmia  ) and auto-immune conditions ( rheumatoid arthritis ), which may not be easily attributed to the HCV infection. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6372", "text": "The Department of Health established Hepatology Units in  Beaumont ,  the Mater ,  St. James's  and  St.Vincent's  Hospitals in Dublin,  Cork University Hospital ,  University Hospital Galway  and later in  St. Luke's Hospital Kilkenny  and  Crumlin Children's Hospital , where those infected were referred for medical supervision and treatment. A counseling service was also provided for the infected women although this soon proved unsatisfactory as it was under the auspices of the BTSB. This was augmented with the provision of counselling by  Well Woman centres  in Dublin and Cork and was subsequently extended to private psychologists in other regions. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6373", "text": "In July 2017 the  European Association for the Study of the Liver  (EASL) published the report [ 11 ]  of a study conducted jointly by the  Health Service Executive -Health Protection Surveillance Centre, Dublin, Ireland, the  European Programme for Intervention Epidemiology Training  ( EPIET ) and the  European Centre for Disease Prevention and Control  ( EDCD ), Stockholm, Sweden into the disease outcomes for the women infected by the anti-D contamination. Of the 682 women included in the study 72 (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36 years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6374", "text": "Having tested positive for HCV, the journalist Jane O'Brien made a request to the BTSB to put her in contact with other women in the same situation. They refused her request on grounds of patient confidentiality and privacy. [ 12 ]  She persisted through word of mouth and appeals in the media to make contact with other women affected and set up a meeting in May 1994 at the offices of the  Council for the Status for Women  with a view to forming a support group.\n25 women who had tested positive for HCV attended and elected a committee for the group. [ 13 ]  They decided to name the group \" Positive Action \" which simultaneously stated the purpose of the group and countered the stigma associated with their HCV positive status. The group set up its office at 56 Fitzwilliam Square, Dublin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6375", "text": "The group quickly gathered support from the Council for the Status of Women, Rosemary Daly of the  Irish Haemophilia Society ,  Theresa Ahern  TD, Chair of the Oireachtas Women's Rights Committee,  M\u00e1ire Geoghegan-Quinn  TD and President  Mary Robinson .\nDr. Geoff Dusheiko of the  Royal Free Hospital  London became their expert advisor on medical matters. When the group first published their list of grievances with their treatment and the responses of the BTSB, the Health Minister initially defended the BTSB's response [ 14 ] [ 15 ]  but following pressure in the D\u00e1il from opposition TDs, particularly Theresa Ahern, [ 16 ]  and  Bernard Durkan [ 17 ]  he agreed to meet first with one of the founders and then in June 1994 with the full support group. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6376", "text": "Minister Howlin acknowledged the women's grievances with the BTSB's queries into their sexual history and the fact that they were being counseled by the very organization that was responsible for their infection. The Minister announced that a limited ex-Gratia expenses scheme was being operated by the BTSB to ensure that all anti-D recipients could avail of the screening, counseling and treatment services but that no consideration could be given to a full compensation scheme until the Expert Group on the BTSB had completed and published its report. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6377", "text": "Positive Action's repeated requests for the BTSB to distribute their letter to all women affected by the anti-D contamination were ignored until Michael Noonan became Health Minister. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6378", "text": "The Fine Gael TD, Mr  Alan Shatter , called on the DPP to consider criminal prosecutions of those responsible for what he called the \"blood bank scandal\". [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6379", "text": "The HCV National Screening program revealed many people who had tested positive for hepatitis C but who had never received an anti-D injection. Many of these were men and women who had never had children but who had had at some point in their lives received blood transfusions supplied by the BTSB. These included people who had been in accidents, had surgical operations or were suffering from other illnesses such as haemophilia or kidney disease and need regular blood transfusions, which prior to 1994 had not been screened for hepatitis C (and several other viruses). [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6380", "text": "Inspired by the actions of the women of Positive Action, a group of men and women met in  Liberty Hall  on 22 April 1995 with a view to organizing and making representations based on their specific needs and circumstances. They called their group  Transfusion Positive [ 22 ]  and held their first official meeting on 13 May 1995, in Powers Hotel on  Kildare Street , Dublin. Unlike the mothers who had received anti-D injections from known infected batches, it was much more difficult to prove categorically the source of infection for those who had had transfusions or had secondary infections from transfusion patients who had been infected. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6381", "text": "On 5 March 1994, Minister for Health Brendan Howlin announced the establishment of an Expert Group under the leadership of   Miriam Hederman O'Brien , with the following terms of reference: [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6382", "text": "1. To examine and report to the Minister for Health on the following matters:"}
{"_id": "WikiPedia_Hematology$$$corpus_6383", "text": "2.  To make recommendations to the Minister for Health on the above matters and on any other matters relation to the Blood Transfusion Service Board which the Group considers necessary."}
{"_id": "WikiPedia_Hematology$$$corpus_6384", "text": "The other members of the Expert Group were:"}
{"_id": "WikiPedia_Hematology$$$corpus_6385", "text": "The Minister's decision to use an Expert Group rather than a Tribunal of Inquiry was influenced by the public outrage at the costs of the  Beef Tribunal  which with costs in excess of \u20ac27 million was at that time the most expensive inquiry in the history of the state.\nThe Expert Group format should establish the facts and make recommendations in a much quicker and cost-efficient manner.\nThe Expert Group met with and gathered evidence from senior management and technical staff of the BTSB, the NDAB, the department of health and from various medical experts and bodies both in Ireland and abroad.\nIts remit did not extend to interviewing the infected women or their representatives although it did make some observations on their treatment and counselling."}
{"_id": "WikiPedia_Hematology$$$corpus_6386", "text": "On 27 January 1995, the Expert Group delivered their report to the new Minister for Health,  Michael Noonan  T.D.\n [ 23 ]  who subsequently had it published."}
{"_id": "WikiPedia_Hematology$$$corpus_6387", "text": "The report [ 3 ]  clearly laid out the events that led to the 1977 contamination of anti-D and also those leading to the second contamination in 1991.\n(It also found that there had been infections with hepatitis during every year that anti-D was used \u2013 i.e., 1970\u20131994.) [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6388", "text": "The report highlighted operational and procedural shortcomings in the BTSB's response to each case and in its general operations:"}
{"_id": "WikiPedia_Hematology$$$corpus_6389", "text": "It also noted that while staff of the BTSB had at all times been courteous, they had not always been forthcoming with details:"}
{"_id": "WikiPedia_Hematology$$$corpus_6390", "text": "Some of our queries were answered in a manner which, although accurate, required considerable supplementary probing on our part before we felt reasonably confident that we had adequate information about the circumstances into which we were inquiring.\u00a0..."}
{"_id": "WikiPedia_Hematology$$$corpus_6391", "text": "The account which we have given and the inferences which we have drawn are on the basis of the information we have received. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6392", "text": "Indeed, some of the information they received would be amended during the course of the subsequent Tribunal of Inquiry.\nThe difficulties the Expert Group had obtaining information from BTSB staff had been reported in the press and were known to Minister Howlin. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6393", "text": "In D\u00e1il debates following the publication of the Expert Group's report, during which there were calls for dismissals and resignations at the BTSB, Michael Noonan TD, the new Minister for Health adopted a defensive position, going so far as to express full confidence in the board of the BTSB, 9 of whom had been appointed since 1993. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6394", "text": "Following publication of the Expert Group's report Positive Action entered into negotiations with the Department of Health for appropriate compensation (medical and financial). [ 10 ] \nNegotiations ceased in September 1995 [ 27 ]  and resumed on 1 November 1995 at the request of the Department of Health."}
{"_id": "WikiPedia_Hematology$$$corpus_6395", "text": "As a result, the following were introduced: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6396", "text": "Positive Action criticized the \"ad hoc\" nature of the proposed tribunal, which meant that any government could take a decision to simply wind it up without a vote in the D\u00e1il. [ 28 ] \nThey demanded that any compensation tribunal should be established on a statutory basis by an act of the Oireachtas.\nThey felt that the purpose of the tribunal was to enable the state to never admit its culpability in the case and to force women to accept smaller sums than would be awarded through a judicial process.\nPositive Action held a meeting in December 1995 at which 91% of members voted to reject and boycott the compensation tribunal. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6397", "text": "Transfusion Positive, the group representing people who had contracted hepatitis C through blood transfusions (rather than anti-D) from the BTSB also voiced concerns over the tribunal's requirement to prove infection \"on the balance of probabilities\". [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6398", "text": "In December 1995, despite the misgivings of the representative groups, the government announced the establishment of the tribunal to award compensation to those infected with hepatitis C through BTSB products (anti-D and transfusions) under the chairmanship of former  Supreme Court  judge  Mr. Justice Seamus Egan . [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6399", "text": "The tribunal chairman would adjudicate on cases together with two other members selected from a panel that included Ms. Alison Cross BL, Ms. Sheila Cooney Solicitor and Ms. Eileen Leyden BL. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6400", "text": "In February 1996, the tribunal made its first compensation awards to two women whose cases were accelerated due to their terminal illness, [ 31 ]  one of whom died within weeks of the award. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6401", "text": "At the end of February 1996 only 72 women had applied to the compensation tribunal [ 33 ]  and some 400 had issued writs against the BTSB in the courts."}
{"_id": "WikiPedia_Hematology$$$corpus_6402", "text": "The government announced that the closing date for applications to the compensation tribunal would be 17 June 1996."}
{"_id": "WikiPedia_Hematology$$$corpus_6403", "text": "Positive Action re-iterated their rejection of the tribunal claiming the government was using it to discourage women from taking legal action to expose the truth. [ 34 ] [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6404", "text": "Fearing they might miss out on all compensation members of Positive Action group took legal advice.\nSome members chose to apply to the tribunal while simultaneously initiating legal action against the BTSB."}
{"_id": "WikiPedia_Hematology$$$corpus_6405", "text": "Throughout the following weeks stories began to emerge of an aggressive legal strategy being pursued by lawyers acting for the Department of Health and opposition politicians accused the government of trying to bully the women into settling with the compensation tribunal. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6406", "text": "Over the following months the media reported on various awards made by the compensation tribunal. [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6407", "text": "By February 1997, the compensation tribunal had received 1,664 applications, of which 1,512 were primary claimants, 86 were dependents and 66 carers. [ 39 ] \nIn the 267 cases heard to that point, the tribunal had made 169 lump sum awards, 96 provisional awards and had disallowed two claims."}
{"_id": "WikiPedia_Hematology$$$corpus_6408", "text": "In subsequent years several of the awards made or denied by the tribunal were challenged in the High Court, most of which were reviewed by  Mr. Justice Bernard Barton ."}
{"_id": "WikiPedia_Hematology$$$corpus_6409", "text": "On 28 July 1995, lawyers acting for a HCV-positive Donegal woman with advanced liver disease who had received anti-D treatments during her 12 pregnancies made an application to the High Court to pursue for damages against the BTSB and the Irish State using an assumed name. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6410", "text": "It was proposed that to protect the woman and her family from the stigma associated with the hepatitis C, she would take the case using the name \"Bridget Roe\". [ 40 ] \nMs. Susan Stapleton, Solicitor said the woman wished to use an alias because she desired to protect her privacy, not merely as a means of preventing embarrassment to her but also to prevent real injustice to her. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6411", "text": "In January 1996, the Attorney General challenged the woman's right to take such a case using a false name. [ 42 ] \nOn 14 February 1996, Miss Justice Laffoy ruled that to do so would contravene Article 34 (1) of the Constitution. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6412", "text": "The woman decided to continue with her case for damages against the BTSB, the NDAB, the Minister for Health, the Attorney General and the Irish State using her real name Brigid Ellen McCole.\nGiven the advanced nature of her disease and poor prognosis, her legal team applied to the High Court to set a date for her action to be heard in June 1996.\nWhile adjudicating on the issue on 26 April, Mr Justice Costello, President of the High Court, asked if granting the request would mean 400 similar applications would follow and fixed 8 October as the date for the trial, which was expected to take six weeks\n. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6413", "text": "On 23 April the Oireachtas Select Committee on Social Affairs wrote to the BTSB requesting that it send a delegation to meet the Select Committee on Social Affairs on Thursday 2 May and discuss the hepatitis C issue.\nThe Chief Executive of the BTSB wrote a response saying it would not be appropriate for board could to enter into such discussions while Mrs. McCole's action was pending in the High Court. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6414", "text": "In June 1996 Mrs. McCole's legal team applied to the High Court for discovery of files held by the BTSB, which contained information relevant to Mrs. McCole's case.\nMs. Justice Laffoy ruled that the woman was entitled to seek information from the board's employees relating to the case dating back to 1976 and gave the BTSB until 19 July to answer certain questions about its documentation.\nOn 23 July Mr Donal O'Donnell SC, for the BTSB, said the BTSB was conducting an extensive search through a great volume of files and asked for an additional two to three weeks more to submit an affidavit concerning the discovery of documents.\nMiss Justice Laffoy said that it was an awkward situation for the BTSB and that she had no option but to grant its request\n. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6415", "text": "From files eventually disclosed by the BTSB, Mrs. McCole's legal team uncovered significant details that had not been shown to the Expert Group's investigation: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6416", "text": "Based on these revelations, Mrs. McCole's legal team formulated a long list of questions which it sent to the BTSB and as it became increasingly unlikely that they would ever come to trial, leaked them also to the press\n. [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6417", "text": "After attending a family wedding in Donegal in August 1996, Mrs. McCole was transferred to St. Vincent's Hospital in Dublin, where it quickly became clear that she was dying.\nThe legal teams acting for the plaintiffs contacted Mrs. McCole's team to negotiate a settlement.\nOn 20 September they wrote a letter of apology to Mrs. McCole and admitted liability in the case.\nIn a series of letters Counsel for the BTSB offered \u00a3175,000 in compensation from the BTSB compensation tribunal provided the McCole family would agree never to sue them following their mother's death\n. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6418", "text": "If Mrs. McCole died without accepting this offer, the maximum compensation her family might win in the courts would be \u00a37,500.\nCounsel for the BTSB also threatened her with legal costs if she did not accept the offer\n. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6419", "text": "When her doctors told her she would not live to the trial date, Mrs. McCole saw she had run out of time.\nNegotiations continued while she was on her deathbed where on 1 October 1996, she accepted the board's full admission and offer of \u00a3175,000\n. [ 49 ] \nShe died the next day."}
{"_id": "WikiPedia_Hematology$$$corpus_6420", "text": "The fact that the 1991 contamination of anti-D was not publicly announced until the report of the Export Group undermined confidence in the commitment of the BTSB and Department of Health to full transparency.\nThe legal case taken by Brigid McCole had led to the discovery of additional facts (such as the scope of the Therapeutic Substances Act, 1932 and the labelling of Patient X's blood tests as \"infective hepatitis\") which had been kept from the Expert Group and contributed further to the public disquiet.\nHowever, Minister Michael Noonan resisted all calls for a full Judicial Inquiry into the affair until. His position changed after Mrs. McCole died. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6421", "text": "In a statement to D\u00e1il \u00c9ireann on 3 October 1996, [ 50 ] \nMinister Noonan revealed that the BTSB had agreed to admit liability in the McCole case on 20 September but when  Maire Geoghegan-Quinn  demanded an full judicial Inquiry, he cited the huge legal costs and lack of clarity that resulted from the  Beef Tribunal ."}
{"_id": "WikiPedia_Hematology$$$corpus_6422", "text": "A few days later, the Minister had received a letter from the family of Brigid McCole in which they listed a series of questions they expected the Minister to answer."}
{"_id": "WikiPedia_Hematology$$$corpus_6423", "text": "On 8 October, the minister brought a motion before the D\u00e1il to institute a tribunal of Inquiry into the entire controversy.\nThe terms of reference for this tribunal were based in large part on the questions submitted in the McCole family's letter. [ 51 ] \nHe stated that he had previously felt such a tribunal unnecessary because he expected the McCole case in the High Court to clarify any issues outstanding from the Expert Group's investigation but given the death of Mrs. McCole, that case could no longer proceed. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6424", "text": "Under  Justice Thomas Finlay , this tribunal commenced on 5 November 1996 and sat for a total of 27 days, with the press reporting daily on hearings. Although the Expert Group's report had established most of the facts of the case, the reporting of first-hand testimonies and cross examinations of victims, [ 53 ] [ 54 ]  BTSB staff, [ 55 ] [ 56 ] [ 57 ] [ 58 ]  independent experts, [ 59 ] [ 60 ] [ 61 ]  civil servants [ 62 ]  and politicians [ 63 ] [ 64 ]  had a huge impact on public opinion."}
{"_id": "WikiPedia_Hematology$$$corpus_6425", "text": "One of the first witnesses to appear before the tribunal was 27-year old Br\u00edd McCole, [ 51 ] [ 65 ]  daughter of the late Brigid McCole who said it was her \"mother's dying wish that the truth of now she suffered and the circumstances surrounding it would be revealed\"."}
{"_id": "WikiPedia_Hematology$$$corpus_6426", "text": "At the final hearings on 4 February 1997, Justice Finlay expressed his deep admiration for those victims who had given evidence and for the manner in which they had contributed to the tribunal with rare courage and great moderation. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6427", "text": "At the final hearings of the tribunal, counsel for the tribunal, Mr James Nugent SC said that would not be appropriate for the tribunal to send its report to the DPP or to recommend prosecutions in the hepatitis C scandal.\nThis opinion was echoed by  Mr. Frank Clarke SC , counsel for the public interest, by Mr Patrick Hanratty, counsel for the NDAB and by Mr Paul Gallagher SC representing the BTSB. [ 67 ] [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6428", "text": "On behalf of the BTSB, Mr Paul Gallagher SC issued an apology to all those who had become infected with hepatitis C due to the BTSB's negligence, repeated wrong decisions and breach of protocols. [ 69 ] \nCounsel for the Department of Health used the final sitting to voice a comprehensive defense of the department's actions throughout the controversy. [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6429", "text": "Mr. Justice Thomas Finlay then took another four weeks to finalize his report and submit it to the Minister for Health who had it published on 11 March 1997. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6430", "text": "Amongst the findings in the report were:"}
{"_id": "WikiPedia_Hematology$$$corpus_6431", "text": "Responsibility for these failures lay to a major extent with 3 named employees of the BTSB:"}
{"_id": "WikiPedia_Hematology$$$corpus_6432", "text": "The report made many recommendations, which included re-structuring the BTSB and moving from its out-dated facilities at Pelican House."}
{"_id": "WikiPedia_Hematology$$$corpus_6433", "text": "Following the tribunal findings, Positive Action again lobbied for a statutory compensation tribunal with power to award exemplary and punitative damages.\nIn May 1997 the bill to establish this statutory compensation tribunal, [ 71 ]  was passed in the Oireachtas, and included provision for a reparation fund of 20% of the tribunal award for exemplary and punitive damages or the option of a hearing on such damages."}
{"_id": "WikiPedia_Hematology$$$corpus_6434", "text": "The speed and efficiency with which Thomas Finlay's BTSB Tribunal conducted its business, restored confidence in the tribunal as a mechanism of resolving great controversies in the public interest. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6435", "text": "Following the tribunal Cecily Cunningham was the only employee of the BTSB to be sacked and later took an action for unfair dismissal against them. [ 4 ]  Dr. Terry Walsh had retired but both he and Ms. Cunningham would be called before the  Lindsay Tribunal  examining the contamination of BTSB's products for the treatment of haemophilia with HIV and hepatitis C."}
{"_id": "WikiPedia_Hematology$$$corpus_6436", "text": "Walsh and Cunningham were arrested in 2003. [ 73 ]  Walsh died before facing court, and charges against Cunningham were dropped in 2009. [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6437", "text": "In a series of heated D\u00e1il debates that followed the death of Brigid McCole, [ 50 ] [ 75 ] [ 76 ] \nthe influence of the Government on the BTSB's legal strategy towards her case and those of other women seeking compensation came under scrutiny."}
{"_id": "WikiPedia_Hematology$$$corpus_6438", "text": "Minister Noonan's attempt to describe Mrs. McColes acceptance of an  ex gratia  payment from the ad-hoc compensation tribunal as a negotiated settlement were attacked by opposition TDs who pointed out her acceptance came only when she realized she had hours to live and might otherwise get no compensation for her family.\nThe minister faced many questions about his knowledge of and influence on the BTSB's legal strategy, its admission of liability, the scheduling of the McCole case in the High Court and the retirement of senior managers from the BTSB without ever facing sanction. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6439", "text": "In his statement to the D\u00e1il on 16 October 1996, [ 76 ] \nMr. Noonan suggested that Mrs. McCole's legal team had not properly represented her interests asking:\n\"Would not the solicitors for the plaintiff have served their client better if they had advised her to go to the compensation tribunal early this year?\nWas it in the interest of their client to attempt to run her case not only in the High Court, but also in the media and the D\u00e1il simultaneously?\""}
{"_id": "WikiPedia_Hematology$$$corpus_6440", "text": "This course of argument caused outrage amongst opposition TDs and in the public gallery of the D\u00e1il where representatives of Positive Action stood in protest and left.\nThe minister returned to the house later that evening to issue an unreserved apology, [ 77 ]  for any offense his statement may have caused but the episode would dog him for the remainder of his political career. [ 78 ] [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6441", "text": "While neither Brendan Howlin T.D. nor Michael Noonan T.D. were responsible for the Department of Health or any of its client organizations (BTSB/NDAB) when the contaminations occurred, their management of the crises and treatment of victims was subject to severe criticism by witnesses to the tribunal of inquiry chaired by Justice Finlay. [ 80 ] [ 81 ] [ 82 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6442", "text": "In June 1997 the new Fianna F\u00e1il Minister for Health, Mr.  Brian Cowen  TD released the McCole papers. [ 48 ] \nThese revealed that the BTSB had information since 3 April 1995 that they were negligent, had no defence in the McCole case, but continued to fight her application for anonymity and sent her a threatening letter on her death bed. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6443", "text": "The government sent the Finlay Report to the DPP who responded on 6 October 1997 with the decision that no criminal prosecutions would be forthcoming as a result of the report. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6444", "text": "The McCole family wrote first to the new Minister for Health [ 83 ]  and subsequently to the  Garda Commissioner , Patrick Byrne [ 84 ]  to demand an investigation. A Garda investigation began in late November 1997 which in 2003 resulted in charges being brought against two former employees of the BTSB - Dr. Terry Walsh and Ms Cecily Cunningham (Dr. Jack O'Riordan had since died) - on seven counts of Grievous Bodily Harm."}
{"_id": "WikiPedia_Hematology$$$corpus_6445", "text": "Both Dr. Walsh [ 85 ]  and Ms. Cunningham [ 86 ]  sought court injunctions to prevent their prosecutions but failed."}
{"_id": "WikiPedia_Hematology$$$corpus_6446", "text": "While their court cases were pending, the untimely death of Dr. Terry Walsh [ 87 ]  was announced and the case against Ms. Cecily Cunningham was dropped by the DPP due to the deaths of crucial witnesses."}
{"_id": "WikiPedia_Hematology$$$corpus_6447", "text": "In January 2002,  RT\u00c9  broadcast a four-part TV drama series called  No Tears [ 88 ]  based on the story of the anti-D contamination and the scandals that ensued."}
{"_id": "WikiPedia_Hematology$$$corpus_6448", "text": "Written by Brian Phelan the drama was based on real events but did not use the real names of any of the parties involved and through artistic license amalgamated aspects and experiences of different people into composite characters.\nIt starred the  Oscar -winning actress,  Brenda Fricker  as Gr\u00e1inne McFadden (based very closely on Brigid McCole),  Tina Kellegher  as Monica O'Callaghan (based on Jane O'Brien) and  Mark Lambert  as \"The Minister for Health\".\nMost other characters were composites of real women and families that were impacted by the contamination and employees of the BTSB and State Agencies who are focused on damage limitation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6449", "text": "Whereas, most viewers' knowledge of the story came from factual and often dry court reports and newspaper articles, the TV drama could show the emotional impact of many years of inexplicable illness on these women all over Ireland, as it first explored their back stories before the events that brought the controversy to light.\nThe series proved hugely popular, [ 89 ]  breaking viewing figures for an Irish-produced TV drama serial but attracted a certain amount of controversy also."}
{"_id": "WikiPedia_Hematology$$$corpus_6450", "text": "Some members of Positive Action challenged the sequence of and participants in certain events but it was whether the depiction of the Minister for Health was unfair or unduly unsympathetic that stimulated most discussion.\n [ 90 ] [ 91 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6451", "text": "The family of Brigid McCole denied ever giving their \"blessing\" to the production. [ 92 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6452", "text": "Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1 , also known as  C1GALT1 , is an  enzyme  which in humans is encoded by the  C1GALT1   gene . [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6453", "text": "The common core 1  O-glycan  structure Gal-beta-1-3GalNAc-R is a precursor for many extended  mucin -type O-glycan structures in animal cell surface and secreted  glycoproteins . Core 1 is synthesized by the transfer of  Gal  from  UDP -Gal to GalNAc-alpha-1-R by core 1 beta-3-galactosyltransferase (C1GALT1). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6454", "text": "C1GALT1 is associated with the  T-Tn antigen  system. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6455", "text": "There is some evidence that mutations in the  C1GALT1  gene may be associated with  kidney disease . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6456", "text": "This article on a  gene  on human  chromosome 7  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_6457", "text": "1HZF ,  4FXG ,  4FXK ,  4XAM"}
{"_id": "WikiPedia_Hematology$$$corpus_6458", "text": "720"}
{"_id": "WikiPedia_Hematology$$$corpus_6459", "text": "12268"}
{"_id": "WikiPedia_Hematology$$$corpus_6460", "text": "ENSG00000244207 ENSG00000206340 ENSG00000244731 ENSG00000227746"}
{"_id": "WikiPedia_Hematology$$$corpus_6461", "text": "ENSMUSG00000073418"}
{"_id": "WikiPedia_Hematology$$$corpus_6462", "text": "P0C0L4"}
{"_id": "WikiPedia_Hematology$$$corpus_6463", "text": "P01029"}
{"_id": "WikiPedia_Hematology$$$corpus_6464", "text": "NM_001252204 NM_007293"}
{"_id": "WikiPedia_Hematology$$$corpus_6465", "text": "NM_009780"}
{"_id": "WikiPedia_Hematology$$$corpus_6466", "text": "NP_001239133 NP_009224"}
{"_id": "WikiPedia_Hematology$$$corpus_6467", "text": "NP_033910"}
{"_id": "WikiPedia_Hematology$$$corpus_6468", "text": "Complement C4-A  is a kind of the  Complement component 4   protein  that in humans is encoded by the  C4A   gene . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6469", "text": "This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic  lupus  erythematosus and  type I diabetes mellitus . [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]  Excess production due to a copy number that is higher than normal has shown a high probability of a causal relationship with  schizophrenia  and  bipolar disorder  with psychosis, which could explain the hereditary nature of these illnesses. [ 12 ]  This gene localizes to the  RCCX locus  within the major  histocompatibility complex (MHC) class III  region on chromosome 6. [ 13 ] [ 14 ]  Varying  haplotypes  of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. [ 5 ]  Each copy of the gene, due to five adjacent nucleotide substitutions cause four amino acid changes and immunological subfunctionalization, [ 15 ]  can be of one of two types:  C4A  and  C4B . [ 16 ]  Each gene contains 41 exons and has a dichotomous size variation between approximately 22 kb and 16 kb, with the longer variant being the result of the integration of the endogenous retrovirus HERV-K(C4) into intron 9. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6470", "text": "This article on a  gene  on human  chromosome 6  is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_6471", "text": "Cadaveric blood transfusion  is the  transfusion  of blood from a dead body to a living person."}
{"_id": "WikiPedia_Hematology$$$corpus_6472", "text": "In 1929, surgeon Vladimir Shamov of  Kharkiv ,  USSR , reported the experimental use of cadaveric  blood  and demonstrated the absence of toxicity. Russian surgeon  Sergei Yudin  pioneered the transfusion of cadaveric blood and performed this successfully for the first time on March 23, 1930. Yudin also reported his first seven  clinical   transfusions  with cadaveric blood at the Fourth Congress of  Ukrainian  Surgeons at Kharkiv in September 1930. The discovery that cadaveric blood could be stored safely provided time for both  serological  tests and  bacteriological  examinations. Cadaveric blood was never used widely, even in Russia. From these studies, however, developed a variety of means and methods for the collection, preservation, and storage of blood for transfusion, all of which may be grouped under the umbrella term \" blood bank \". Although cadaver blood transfusion did not catch on in the  United States , physician  Bernard Fantus  modified the Soviet idea by preserving blood from healthy living persons. Drawing on earlier work involving preservatives and anticoagulants, Fantus added the element of refrigeration and in 1937 established the first blood bank in the United States at  Chicago's   Cook County Hospital .  [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6473", "text": "1POZ ,  1UUH ,  2I83 ,  4PZ3 ,  4PZ4"}
{"_id": "WikiPedia_Hematology$$$corpus_6474", "text": "960"}
{"_id": "WikiPedia_Hematology$$$corpus_6475", "text": "12505"}
{"_id": "WikiPedia_Hematology$$$corpus_6476", "text": "ENSG00000026508"}
{"_id": "WikiPedia_Hematology$$$corpus_6477", "text": "ENSMUSG00000005087"}
{"_id": "WikiPedia_Hematology$$$corpus_6478", "text": "P16070"}
{"_id": "WikiPedia_Hematology$$$corpus_6479", "text": "P15379"}
{"_id": "WikiPedia_Hematology$$$corpus_6480", "text": "NM_001202555 NM_001202556 NM_001202557"}
{"_id": "WikiPedia_Hematology$$$corpus_6481", "text": "NM_009851"}
{"_id": "WikiPedia_Hematology$$$corpus_6482", "text": "NP_001189484 NP_001189485 NP_001189486"}
{"_id": "WikiPedia_Hematology$$$corpus_6483", "text": "NP_033981"}
{"_id": "WikiPedia_Hematology$$$corpus_6484", "text": "The  CD44 antigen  is a  cell -surface  glycoprotein  involved in cell\u2013cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the  CD44   gene  on chromosome 11. [ 5 ]  CD44 has been referred to as HCAM (homing  cell adhesion molecule ), Pgp-1 (phagocytic  glycoprotein -1), Hermes antigen, lymphocyte homing receptor, ECM-III, and HUTCH-1."}
{"_id": "WikiPedia_Hematology$$$corpus_6485", "text": "CD44 is expressed in a large number of mammalian cell types.  The standard  isoform , designated CD44s, comprising  exons  1\u20135 and 16\u201320 is expressed in most cell types. CD44 splice variants containing variable exons are designated CD44v.  Some  epithelial cells  also express a larger isoform (CD44E), which includes exons v8\u201310. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6486", "text": "CD44 participates in a wide variety of cellular functions including  lymphocyte  activation,  recirculation and homing,  hematopoiesis , and  tumor   metastasis ."}
{"_id": "WikiPedia_Hematology$$$corpus_6487", "text": "CD44 is a receptor for  hyaluronic acid [ 7 ]  and internalizes metals bound to hyaluronic acid [ 8 ] [ 9 ]  and can also interact with other  ligands , such as  osteopontin ,  collagens , and  matrix metalloproteinases  (MMPs).  CD44 function is controlled by its posttranslational modifications. One critical modification involves discrete sialofucosylations rendering the selectin-binding glycoform of CD44 called HCELL (for Hematopoietic Cell E-selectin/L-selectin Ligand). [ 10 ]  (see below)"}
{"_id": "WikiPedia_Hematology$$$corpus_6488", "text": "Transcripts for this  gene  undergo complex  alternative splicing  that results in many functionally distinct  isoforms ; however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis.  Splice variants of CD44 on colon cancer cells display sialofucosylated HCELL glycoforms that serve as P-, L-, and E-selectin ligands and fibrin, but not fibrinogen, receptors under hemodynamic flow conditions pertinent to the process of cancer metastasis. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6489", "text": "CD44 gene  transcription  is at least in part activated by  beta-catenin  and  Wnt signalling  (also linked to tumour development)."}
{"_id": "WikiPedia_Hematology$$$corpus_6490", "text": "The HCELL glycoform was originally discovered on human hematopoietic stem cells and leukemic blasts, [ 10 ] [ 13 ] [ 14 ] [ 15 ]  and was subsequently identified on cancer cells. [ 12 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ]  HCELL functions as a \"bone  homing  receptor\", directing migration of human hematopoietic stem cells and  mesenchymal stem cells  to bone marrow. [ 14 ]    Ex vivo glycan engineering of the surface of live cells has been used to enforce HCELL expression on any cell that expresses CD44. [ 20 ]  CD44 glycosylation also directly controls its binding capacity to fibrin and immobilized fibrinogen. [ 11 ] [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6491", "text": "The protein is a determinant for the  Indian blood group system ."}
{"_id": "WikiPedia_Hematology$$$corpus_6492", "text": "In addition, variations in CD44 are reported as cell surface markers for some breast and prostate  cancer stem cells . In breast cancer research CD44+/CD24- expression is commonly used as a marker for breast CSCs and is used to sort breast cancer cells into a population enriched in cells with stem-like characteristics [ 22 ]  and has been seen as an indicator of increased survival time in  epithelial   ovarian cancer  patients. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6493", "text": "Endometrial cells in women with  endometriosis  demonstrate increased expression of splice variants of CD44, and increased adherence to peritoneal cells. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6494", "text": "CD44 variant  isoforms  are also relevant to the progression of  head and neck squamous cell carcinoma . [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6495", "text": "Monoclonal antibodies  against CD44 variants include  bivatuzumab  for v6."}
{"_id": "WikiPedia_Hematology$$$corpus_6496", "text": "CD44 is a multistructural and multifunctional  cell surface molecule  involved in  cell proliferation ,  cell differentiation ,  cell migration ,  angiogenesis , presentation of  cytokines ,  chemokines , and growth factors to the corresponding  receptors , and docking of  proteases  at the  cell membrane , as well as in signaling for  cell survival . All these biological properties are essential to the physiological activities of normal cells, but they are also associated with the pathologic activities of  cancer cells . Experiments in animals have shown that targeting of CD44 by  antibodies ,  antisense  oligonucleotides, and CD44-soluble proteins markedly reduces the malignant activities of various  neoplasms , stressing the therapeutic potential of anti-CD44 agents."}
{"_id": "WikiPedia_Hematology$$$corpus_6497", "text": "High levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia. [ 27 ]  Furthermore, because  alternative splicing  and  posttranslational modifications  generate many different CD44 sequences, including, perhaps, tumor-specific sequences, the production of anti-CD44 tumor-specific agents may be a realistic therapeutic approach. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6498", "text": "In many cancers ( renal cancer  and  non-Hodgkin's lymphomas  are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome. [ 29 ]  On the contrary, in some neoplasms CD44  upregulation  is associated with a favorable outcome. This is true of  prostate cancer , where the  transcript variant  CD44v5 (includes the fifth 'v5' exon) is associated with better prognosis (increased time to recurrence following surgery). [ 30 ] [ 29 ]  In prostate cancer, the exclusion of the v5 exon through alternative splicing was associated with the presence of RNA binding protein  KHDRBS1  and became included in the presence of increased  YTHDC1  or  metadherin  expression. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6499", "text": "In other cases different research groups analyzing the same neoplastic disease reached contradictory conclusions regarding the correlation between CD44 expression and disease prognosis, possibly due to differences in methodology. These problems must be resolved before applying anti-CD44 therapy to human cancers. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6500", "text": "CD44 has been shown to  interact  with:"}
{"_id": "WikiPedia_Hematology$$$corpus_6501", "text": "1CDQ ,  1CDR ,  1CDS ,  1ERG ,  1ERH ,  2J8B ,  2OFS ,  2UWR ,  2UX2 ,  4BIK"}
{"_id": "WikiPedia_Hematology$$$corpus_6502", "text": "966"}
{"_id": "WikiPedia_Hematology$$$corpus_6503", "text": "333883"}
{"_id": "WikiPedia_Hematology$$$corpus_6504", "text": "ENSG00000085063"}
{"_id": "WikiPedia_Hematology$$$corpus_6505", "text": "ENSMUSG00000068686"}
{"_id": "WikiPedia_Hematology$$$corpus_6506", "text": "P13987 Q6FHM9"}
{"_id": "WikiPedia_Hematology$$$corpus_6507", "text": "P58019"}
{"_id": "WikiPedia_Hematology$$$corpus_6508", "text": "NM_001127227 NM_203329 NM_203330"}
{"_id": "WikiPedia_Hematology$$$corpus_6509", "text": "NM_181858 NM_001368215"}
{"_id": "WikiPedia_Hematology$$$corpus_6510", "text": "NP_976074 NP_976075 NP_976076 NP_000602.1 NP_001120695.1 NP_001120697.1 NP_001120698.1 NP_001120699.1 NP_976074.1 NP_976075.1 NP_976076.1"}
{"_id": "WikiPedia_Hematology$$$corpus_6511", "text": "NP_862906 NP_001355144"}
{"_id": "WikiPedia_Hematology$$$corpus_6512", "text": "CD59 glycoprotein , also known as  MAC-inhibitory protein  (MAC-IP),  membrane inhibitor of reactive lysis  (MIRL), or  protectin ,  is a  protein  that in humans is encoded by the  CD59   gene . [ 5 ]  It is an  LU domain  and belongs to the  LY6 / uPAR / alpha-neurotoxin   protein family . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6513", "text": "CD59 attaches to host cells via a  glycophosphatidylinositol  (GPI) anchor.  Cholesterol-containing microdomains aid in CD59 activity by stimulating a \"pinch point\" in the lipid membrane during MAC assembly to prevent pore-formation and inhibit lysing. [ 7 ]  When  complement  activation leads to deposition of C5b678 on host cells, CD59 can prevent  C9  from polymerizing and forming the  complement membrane attack complex . [ 8 ]  It may also  signal  the cell to perform active measures such as  endocytosis  of the CD59-C9 complex. [ 6 ]  Endocytosis of this complex leads to the destruction of the ion channel formation that this complex provides to the MAC. These ion channels are used for transfer of different ions to maintain the correct concentration of minerals inside and outside of the membrane, and without this correct maintenance, severe symptoms and diseases can occur such as neuron degeneration and  Alzheimer's disease . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6514", "text": "Mutations affecting GPI that reduce expression of CD59 and  decay-accelerating factor  on  red blood cells  result in  paroxysmal nocturnal hemoglobinuria . [ 10 ]  GPI mutation and consequent reduction in CD59 expression results from a cysteine to tyrosine missense mutation, which prevents disulfide bridge formation, ultimately disrupting tertiary protein structure and preventing proper GPI-CD59 complex binding. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6515", "text": "Viruses  such as  HIV , human  cytomegalovirus  and  vaccinia  incorporate host cell CD59 into their own  viral envelope  to prevent lysis by complement. [ 12 ]  Additionally, CD59 has been investigated as a target for immunotherapy when treating certain cancers such as breast cancer. Researchers have found that once CD59 had been targeted, there is an upregulation in fas and caspase-3, creating an increase in apoptosis and tumor growth suppression in MCF-7 cells. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6516", "text": "977"}
{"_id": "WikiPedia_Hematology$$$corpus_6517", "text": "12476"}
{"_id": "WikiPedia_Hematology$$$corpus_6518", "text": "ENSG00000177697"}
{"_id": "WikiPedia_Hematology$$$corpus_6519", "text": "ENSMUSG00000025510"}
{"_id": "WikiPedia_Hematology$$$corpus_6520", "text": "P48509 Q6ZNZ0"}
{"_id": "WikiPedia_Hematology$$$corpus_6521", "text": "O35566"}
{"_id": "WikiPedia_Hematology$$$corpus_6522", "text": "NM_139030 NM_001039490 NM_004357 NM_139029"}
{"_id": "WikiPedia_Hematology$$$corpus_6523", "text": "NM_001111049 NM_001111050 NM_009842"}
{"_id": "WikiPedia_Hematology$$$corpus_6524", "text": "NP_004348.2 NP_620598.1 NP_620599.1"}
{"_id": "WikiPedia_Hematology$$$corpus_6525", "text": "NP_001104519 NP_001104520 NP_033972"}
{"_id": "WikiPedia_Hematology$$$corpus_6526", "text": "CD151 molecule  ( Raph blood group ), also known as  CD151   ( C luster of  D ifferentiation  151 ), is a human  gene . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6527", "text": "The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [ 5 ]  Abnormalities in CD151 have been implicated in a form of epidermolysis bullosa. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6528", "text": "CD151 has been shown to  interact  with  CD46 . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6529", "text": "This  membrane protein \u2013related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_6530", "text": "Cis AB  is a type of rare  mutation  in the  ABO gene . It happens when the  transferase   allele  contains a mix of  amino acids  from either A or B alleles, producing a bifunctional  enzyme  that can produce both types of  antigens , usually with one weaker than the other. This results in a serum test result much like the standard, separate (trans) AB phenotype, although the weaker antigen can occasionally fail to be detected. It complicates the basic inheritance pattern (as the allele comes from one parent only) and blood-transfusion compatibility matching for  ABO blood typing ."}
{"_id": "WikiPedia_Hematology$$$corpus_6531", "text": "Different DNA mutations of either type A or Type B alleles change amino acids in enzyme transferase A or B, homologous enzymes differing in only four of 354 amino acids (R176G, G235S, L266M, and G268A). A single change in ABO gene DNA could switch type B to type A and then, a new hybrid enzyme can produce both weak B and A2 (in serum test, A2B, and A2B3). The most common mutation is an A105  allele  variation in  exon  7  nucleotide  position G803C changing  glycine  (type A) to  alanine  (type B). Another 8 alleles are reported in  BGMUT , most recently in China and Taiwan. Some Cis-AB carriers need components like washed red blood cells or autotransfusion of serum and blood."}
{"_id": "WikiPedia_Hematology$$$corpus_6532", "text": "Cis-AB type was studied first in humans in Japan (Shikoku Island) and South Korea (Gwangju area) where this rare type is more common (Chinese coast provinces and Taiwan also), although it is seen in a few European families (from France, Spain, Belgium, Germany, and Poland). In the year 2004, the  American Red Cross  described a family in Nebraska with a father of type cis-AB negative, a mother type O and their baby of type cis-AB. Since then, several cases in the United States have been reported. [ 1 ]  Antigen expression is weaker than A1 or B."}
{"_id": "WikiPedia_Hematology$$$corpus_6533", "text": "When one parent carries a Cis AB allele, the other allele can be any of O, A or B. The phenotype of this parent is always AB, but the children will inherit either the AB or the other allele from this parent."}
{"_id": "WikiPedia_Hematology$$$corpus_6534", "text": "ABO inheritance is generally derived assuming the children are not the rare  Bombay phenotype , which would require both parents to be carriers of it."}
{"_id": "WikiPedia_Hematology$$$corpus_6535", "text": "When testing paternity or maternity by ABO blood group alone, it is possible to have a paradoxical result in the rare instance that a cis-AB  genotype  is involved. [ citation needed ]  For example, (scenario 1.1 above) a child of a cis AB individual (who will test as a regular AB phenotype) and an O individual will be either AB or O instead of the usual A or B (see diagram above). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6536", "text": "If the child of an AB and an O individual is O (the green-colored offspring in the scenario 1 image above), then a rare alternative possibility is that the parents were carriers (heterozygous) for the  Bombay phenotype  (Hh) and the child is a Bombay (hh) homozygous by genotype thus expressing  Bombay phenotype  also called O h  where, despite the presence of the ABO alleles, the substrate from which those antigens are made is not made and thus A, B and even O antigen are not expressed at all and are completely absent from the red cells."}
{"_id": "WikiPedia_Hematology$$$corpus_6537", "text": "The  Cohn process , developed by  Edwin J. Cohn , is a series of purification steps with the purpose of extracting  albumin  from  blood plasma . The process is based on the differential  solubility  of albumin and other plasma proteins based on  pH ,  ethanol  concentration, temperature, ionic strength, and protein concentration. [ 1 ] [ 2 ]  Albumin has the highest solubility and lowest  isoelectric point  of all the major plasma proteins. This makes it the final product to be precipitated, or separated from its solution in a solid form. Albumin was an excellent substitute for human plasma in World War Two. When administered to wounded soldiers or other patients with blood loss, it helped expand the volume of blood and led to speedier recovery. Cohn's method was gentle enough that isolated albumin protein retained its  biological activity . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6538", "text": "During the operations, the  ethanol concentration change from zero initially to 40%. The pH decreases from neutral at 7 to more acidic at 4.8 over the course of the fractionation. The temperature starts at room temperature and decreases to \u22125 degrees Celsius. Initially, the blood is frozen. There are five major fractions. Each fraction ends with a specific precipitate. These precipitates are the separate fractions. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6539", "text": "Fractions I, II, and III are precipitated out at earlier stages. The conditions of the earlier stages are 8% ethanol, pH 7.2, \u22123\u00a0\u00b0C, and 5.1% protein for Fraction I; 25% ethanol, pH of 6.9, \u22125\u00a0\u00b0C, and 3% protein. The albumin remains in the supernatant fraction during the solid/liquid separation under these conditions. Fraction IV has several unwanted proteins that need to be removed. In order to do this, the conditions are varied in order to precipitate the proteins out. The conditions to precipitate these proteins are raising the ethanol concentration from 18 to 40% and raising the pH from 5.2 to 5.8. Finally, albumin is located in fraction V. The precipitation of albumin is done by reducing the pH to 4.8, which is near the pI of the protein, and maintaining the ethanol concentration to be 40%, with a protein concentration of 1%. Thus, only 1% of the original plasma remains in the fifth fraction. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6540", "text": "However, albumin is lost at each process stage, with roughly 20% of the albumin   lost through  precipitation  stages before fraction V. In order to purify the albumin, there is an extraction with water, and adjustment to 10% ethanol, pH of 4.5 at \u22123\u00a0\u00b0C. Any precipitate formed here is done so by filtration and is an impurity. These precipitates are discarded. Reprecipitation, or repetition of the precipitation step in order to improve purity, is done so by raising ethanol concentration back to 40% from the extraction stage. The pH is 5.2 and it is conducted at \u22125\u00a0\u00b0C. Several variations of Cohn fraction were created to account for lower cost and higher yield. Generally, if the yield is high, the purity is lowered, to roughly 85\u201390%. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6541", "text": "Cohn was able to start the Plasma Fractionation Laboratory after he was given massive funding from the government agencies and the private pharmaceutical companies. This led to the fractionation of human plasma. Human plasma proved to have several useful components other than albumin. Human  blood plasma fractionation  yielded  human serum albumin , serum gamma  globulin ,  fibrinogen ,  thrombin , and blood group globulins. [ 5 ]   The fibrinogen and thrombin fractions were further combined during the War  into additional products, including liquid  fibrin sealant , [ 6 ]  solid  fibrin  foam and a fibrin film. [ 7 ] \nGamma globulins are found in Fractions II and III and proved to be essential in treating measles for soldiers. Gamma globulin also was useful in treatment for polio, but did not have much effect in treating mumps or scarlet fever. Most importantly, the gamma globulins were useful in modifying and preventing infectious hepatitis during the Second World War. It eventually became a treatment for children exposed to this type of hepatitis. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6542", "text": "Liquid fibrin sealant was used in treating burn victims, including some from the attack at Pearl Harbor, to attach skin grafts with an increased success rate. [ 6 ]  It was also found  helpful at re-connecting or anastomosing severed nerves. [ 6 ]   Fibrin foam and thrombin were used to control blood vessel oozing especially in liver injuries and near tumors. It also minimized bleeding from large veins as well as dealing with blood vessel malformations within the brain. Fibrin film was used to stop bleeding in various surgical applications, including neurosurgery. [ 6 ]  However, it was not useful in controlling arterial bleeding. [ 5 ]   The first fibrinogen/fibrin based product capable of stopping arterial hemorrhage  was the \"Fibrin Sealant Bandage\" or \"Hemostatic Dressing (HD)\" invented by  Martin MacPhee  at the American Red Cross in the early 1990s, and tested in collaboration with the U.S. Army. [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6543", "text": "The Gerlough method, developed in 1955 improved process economics by reducing the consumption of ethanol. Instead of 40% in certain steps, Gerlough used 20% ethanol for precipitation. This is especially used for Fractions II and III. In addition, Gerlough combined the two fractions with IV into one step to reduce the number of fractionations required. While this method proved less expensive, it was not adopted by industry because of this combination of fractions II, III, and IV, for fear of mixing and high impurities. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6544", "text": "The Hink method developed in 1957. This method gave higher yields through recovery of some of the plasma proteins discarded in the Fractions of IV. The improved yields, however, balanced by the  lower purities obtained,  within the 85% range. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6545", "text": "The Mulford method, akin to the Hink, used the fractions II and III supernatant as the last step before finishing and heat treatment. The method combined fractions IV and V, but in this case, the albumin would not be as pure, although the yields may be higher. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6546", "text": "Another variation was developed by Kistler and Nitschmann, to provide a purer form of albumin, even though   offset by lower yields. Similar to Gerlough, the Precipitate A, which is equivalent to Cohn\u2019s Fraction II and III, was done at a lower ethanol concentration of 19%, but the pH, in this case, was also lower to 5.85. Also similar to Gerlough and Mulford, the fraction IV was combined and precipitated at conditions of 40% ethanol, pH of 5.85, and temperature of \u22128 degrees C. The albumin, which is recovered in fraction V, is recovered in Precipitate C at a pH adjustment to 4.8. Similar to the Cohn Process, the albumin is purified by extraction into water followed by precipitation of the impurities at 10% ethanol, pH 4.6, and \u22123 degrees C. Akin to the Cohn Process, the precipitate formed here is filtered out and discarded. Then Precipitate C (fraction V) is reprecipitated at pH 5.2 and stored as a paste at \u221240 degrees C. [ 10 ]  This process has been more widely accepted because it separates the fractions and makes each stage independent of each other."}
{"_id": "WikiPedia_Hematology$$$corpus_6547", "text": "Another variation involved a heat ethanol fractionation. It was originally developed to inactivate the hepatitis virus. In this process, recovery of high yield, high purity albumin is the most important goal, while the other plasma proteins are neglected. In order to make sure the albumin does not denature in the heat, there are stabilizers such as sodium octanoate, which allow the albumin to tolerate higher temperatures for long periods. In heat ethanol, the plasma is heat treated at 68 degrees C with sodium octanoate with 9% ethanol at pH of 6.5. This results in improved albumin recovery with yields of 90%, and purities of 100%. It is not nearly as expensive as cold ethanol procedures such as the Cohn Process. One drawback is the presences of new antigens due to possible heat denaturation of the albumin. In addition, the other plasma proteins have practical uses and to neglect them would not be worth it. Finally, the expensive heat treatment vessels offset the lower cost compared to the cold ethanol format that do not need it. For these reasons, several companies haven not adopted this method even though it has the most impressive results. However, one prominent organization that uses it is the German Red Cross. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6548", "text": "The latest variation was developed by Hao in 1979. This method is significantly simplified compared to the Cohn Process. Its goal is to create high albumin yields as long as albumin is the sole product. Through a two-stage process, impurities are precipitated directly from fractions II and III supernatant at 42% ethanol, pH 5.8, temperature \u22125 degrees C, 1.2% protein, and 0.09 ionic strength. Fraction V is precipitated at pH 4.8. Fractions I, II, III, and IV are  coprecipitated  at 40% ethanol, with pH of 5.4 to 7.0, and temperature \u22123 to \u22127 degrees C. Fraction V is then precipitated at pH 4.8 and \u221210 degrees C. The high yields are due to a combination of a simplified process, with lower losses due to coprecipitation, and use of filtration. Higher purities were also achieved at 98% because of the higher ethanol levels, but the yields were lowered with the high purity. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6549", "text": "More recent methods involve the use of  chromatography . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6550", "text": "The Cohn process was a major development in the field of blood fractionation. It has several practical uses in treating diseases such as hepatitis and polio. It was most useful during the Second World War where soldiers recovered at a faster rate because of the transfusions with albumin. The Cohn Process has been modified over the years as seen above. In addition, it has influenced other processes with the blood fractionation industry. This has led to new forms of fractionation such as chromatographic plasma fractionation in ion exchange and albumin finishing processes. In general, the Cohn Process and its variations have given a huge boost to and serve as a foundation for the fractionation industry to this day. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6551", "text": "However, the process has not been studied well because it is archaic. Most importantly, it has never been modernized by manufacturing companies. The cold ethanol format may be too gentle to kill off certain viruses that require heat inactivation. Since this process remains unchanged for so long, several built-in inefficiencies and inconsistencies affect the economics of the process for pharmaceutical and manufacturing companies. [ 12 ]   One exception to this was the application in Scotland of continuous-flow processing instead of batch processing. This process was devised at the Protein Fractionation Centre (PFC), the plasma fractionation facility of the Scottish National Blood Transfusion Service (SNBTS). This process involved in-line monitoring and control of pH and temperature, with flow control of plasma and ethanol streams using precision gear pumps, all under computerised feedback control . As a result, Cohn Fractions I+II+III, IV and V were produced in a few hours, rather than over many days. The continuous-flow preparation of cryoprecipitate was subsequently integrated into the process upstream of Cohn Fractionation. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6552", "text": "Nevertheless, this process still serves as a major foundation for the blood industry in general and its influence can be seen as it is referred to in the development of newer methods. Although it has its drawbacks depending on the variation, the Cohn Process\u2019 main advantage is its practical uses and its utility within pharmacological and medical industries. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6553", "text": "Cold autoimmune hemolytic anemia  caused by  cold-reacting antibodies . Autoantibodies that bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) characterize  autoimmune hemolytic anemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_6554", "text": "A common complaint among patients with  cold agglutinin disease  is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months."}
{"_id": "WikiPedia_Hematology$$$corpus_6555", "text": "Cold agglutinin-mediated acrocyanosis differs from Raynaud phenomenon. In  Raynaud phenomena , caused by  vasospasm , a triphasic color change occurs, from white to blue to red, based on vasculature response. No evidence of such a response exists in cold agglutinin disease."}
{"_id": "WikiPedia_Hematology$$$corpus_6556", "text": "Other symptoms"}
{"_id": "WikiPedia_Hematology$$$corpus_6557", "text": "Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare."}
{"_id": "WikiPedia_Hematology$$$corpus_6558", "text": "Classic chronic cold agglutinin disease is idiopathic, associated with symptoms and signs in relation to cold exposure."}
{"_id": "WikiPedia_Hematology$$$corpus_6559", "text": "Causes of the monoclonal secondary disease include the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_6560", "text": "Causes of polyclonal secondary cold agglutinin disease include the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_6561", "text": "Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4\u00a0\u00b0C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31\u00a0\u00b0C and sometimes at 37\u00a0\u00b0C."}
{"_id": "WikiPedia_Hematology$$$corpus_6562", "text": "Cold agglutinin disease usually results from the production of a specific  IgM  antibody directed against the I/i antigens (precursors of the ABH and Lewis blood group substances) on red blood cells (RBCs). Cold agglutinins commonly have variable heavy-chain regions encoded by VH, with a distinct idiotype identified by the 9G4 rat murine monoclonal antibody."}
{"_id": "WikiPedia_Hematology$$$corpus_6563", "text": "AIHA can be classified as  warm autoimmune hemolytic anemia   or cold autoimmune hemolytic anemia, which includes  cold agglutinin disease  and  paroxysmal cold hemoglobinuria . These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6564", "text": "[ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6565", "text": "Cold agglutinin disease may be managed successfully using protective measures (clothing) alone in most cases. Special protective clothing is sometimes necessary in extreme cases. Therapy is directed at serious symptoms and the underlying disorder, if any is found."}
{"_id": "WikiPedia_Hematology$$$corpus_6566", "text": "Keep in mind that the idiopathic variety of cold agglutinin disease is generally a benign disorder with prolonged survival and spontaneous exacerbations and remissions in the course of the disease. Acute post infectious syndromes usually resolve spontaneously.\nAnemia is generally mild. Only patients who have serious symptoms related to anemia or have a Raynaud type syndrome that constitutes a threat to life or quality of life require active therapy. The presence of an associated malignancy requires specific therapy."}
{"_id": "WikiPedia_Hematology$$$corpus_6567", "text": "Cold agglutinin disease is so uncommon in children that no specific recommendations for therapy are available. Intravenous immunoglobulin (IVIG) was used successfully in an infant with IgA-associated autoimmune hemolytic anemia."}
{"_id": "WikiPedia_Hematology$$$corpus_6568", "text": "Splenectomy is usually ineffective for the treatment of cold agglutinin disease because the liver is the predominant site of sequestration. However, if the patient has splenomegaly, then the disease may respond to splenectomy. More importantly, a lymphoma localized to the spleen may only be found after splenectomy."}
{"_id": "WikiPedia_Hematology$$$corpus_6569", "text": "Patients with cold agglutinin disease should include good sources of folic acid, such as fresh fruits and vegetables, in their diet. Activities for these individuals should be less strenuous than those for healthy people, particularly for patients with anemia. Jogging in the cold could be very hazardous because of the added windchill factor."}
{"_id": "WikiPedia_Hematology$$$corpus_6570", "text": "A hematologist-oncologist working in collaboration with a blood banker is helpful in complicated cases of cold agglutinin disease.\nCareful planning and coordination with multiple personnel are needed if patients are to undergo a procedure during which their body temperature could fall."}
{"_id": "WikiPedia_Hematology$$$corpus_6571", "text": "The  Colton antigen system  ( Co ) is present on the membranes of  red blood cells  and in the tubules of the  kidney [ 1 ]  and helps determine a person's  blood type . The Co  antigen  is found on a  protein  called  aquaporin-1  which is responsible for water  homeostasis  and urine concentration. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6572", "text": "The Co antigen is important in  transfusion medicine . 99.8% of people possess the Co(a)  allele . Individuals with Co(b) allele or who are missing the Colton antigen are at risk for a  transfusion reaction  such as  hemolytic anemia  or  alloimmunization . Antibodies against the Colton antigen may also cause  hemolytic disease of the newborn , in which a pregnant woman's body creates antibodies against the blood of her fetus, leading to destruction of the fetal blood cells. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6573", "text": "ImpactLife ,  formerly  Community Blood Services of Illinois,  is a  blood center  located in  Urbana, Illinois ."}
{"_id": "WikiPedia_Hematology$$$corpus_6574", "text": "ImpactLife provides lifesaving blood products to more than 123 hospitals in a four-state region. Headquartered in Davenport, Iowa, with distribution hubs and donor centers in Iowa, Illinois, Missouri, and Wisconsin."}
{"_id": "WikiPedia_Hematology$$$corpus_6575", "text": "In addition to its headquarters, ImpactLife has regional distribution hubs in central Illinois (Peoria, Illinois and Springfield, Illinois), eastern Illinois (Urbana, Illinois); southeastern Iowa (Ottumwa, Iowa), the St. Louis region (Earth City, Missouri) and southern Wisconsin (Madison, Wisconsin)."}
{"_id": "WikiPedia_Hematology$$$corpus_6576", "text": "[ 1 ]  ImpactLife collects blood at 19 fixed site donor centers and at more than 5,000 mobile blood drives held each year."}
{"_id": "WikiPedia_Hematology$$$corpus_6577", "text": "ImpactLife is licensed and regulated by the  U.S. Food and Drug Administration  and holds membership in  America's Blood Centers , the  American Association of Blood Banks  and participate in the  National Marrow Donor Program ."}
{"_id": "WikiPedia_Hematology$$$corpus_6578", "text": "1GKG ,  1GKN ,  1PPQ ,  2Q7Z ,  2MCY ,  2MCZ ,  5FO9"}
{"_id": "WikiPedia_Hematology$$$corpus_6579", "text": "1378"}
{"_id": "WikiPedia_Hematology$$$corpus_6580", "text": "ENSG00000203710"}
{"_id": "WikiPedia_Hematology$$$corpus_6581", "text": "P17927"}
{"_id": "WikiPedia_Hematology$$$corpus_6582", "text": "NM_000573 NM_000651 NM_001381851"}
{"_id": "WikiPedia_Hematology$$$corpus_6583", "text": "NP_000564 NP_000642 NP_001368780"}
{"_id": "WikiPedia_Hematology$$$corpus_6584", "text": "Complement receptor type 1  ( CR1 ) also known as  C3b/C4b receptor  or  CD35  (cluster of differentiation 35) is a  protein  that in humans is encoded by the  CR1   gene . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6585", "text": "This gene is a member of the  regulators of complement activation  (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The gene encodes a monomeric single-pass type I membrane  glycoprotein  found on  erythrocytes ,  leukocytes , glomerular  podocytes ,  hyalocytes , and splenic follicular  dendritic cells . The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in its gene have been associated with gallbladder carcinomas,  mesangiocapillary glomerulonephritis ,  systemic lupus erythematosus  and  sarcoidosis . Mutations in this gene have also been associated with a reduction in  Plasmodium falciparum  rosetting, conferring protection against severe malaria. Alternate allele-specific splice variants, encoding different isoforms, have been characterized. Additional allele specific isoforms, including a secreted form, have been described but have not been fully characterized. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6586", "text": "In primates,  CR1 serves as the main system for processing and clearance of complement  opsonized   immune complexes . It has been shown that CR1 can act as a negative regulator of the  complement  cascade, mediate  immune adherence  and  phagocytosis  and inhibit both the classic and alternative pathways. The number of CR1 molecules decreases with aging of  erythrocytes  in normal individuals and is also decreased in pathological conditions such as  systemic lupus erythematosus  (SLE),  HIV  infection, some  haemolytic anaemias  and other conditions featuring  immune complexes . [ 5 ]   In mice, CR1 is an alternatively spliced variant of the complement receptor 2 (CR2) gene."}
{"_id": "WikiPedia_Hematology$$$corpus_6587", "text": "Certain  alleles  of this gene have been statistically associated with an increased risk of developing late-onset  Alzheimer's disease . [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6588", "text": "In humans, the  CR1  gene is located on the long arm of chromosome 1 at band 32 (1q32) and lies within a complex of immunoregulatory genes. In 5'-3' order the genes in this region are: membrane cofactor protein \u2013 CR1 \u2013 complement receptor type 2 \u2013 decay-accelerating factor \u2013 C4-binding protein."}
{"_id": "WikiPedia_Hematology$$$corpus_6589", "text": "Factor H , another immunoregulatory protein, also maps to this location. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6590", "text": "The canonical Cr2/CD21 gene of subprimate mammals produces two types of complement receptor (CR1, ca. 200 kDa; CR2, ca. 145 kDa) via alternative mRNA splicing. The murine Cr2 gene contains 25 exons; a common first exon is spliced to exon 2 and to exon 9 in transcripts encoding CR1 and CR2, respectively. A transcript with an  open reading frame  of 4,224 nucleotides encodes the long isoform, CR1; this is predicted to be a protein of 1,408 amino acids that includes 21 short consensus repeats (SCR) of ca. 60 amino acids each, plus transmembrane and cytoplasmic regions. Isoform CR2 (1,032 amino acids) is encoded by a shorter transcript (3,096 coding nucleotides) that lacks exons 2\u20138 encoding SCR1-6. CR1 and CR2 on murine B cells form complexes with a co-accessory activation complex containing CD19, CD81, and the fragilis/Ifitm (murine equivalents of LEU13) proteins. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6591", "text": "The  complement receptor 2  (CR2) gene of primates produces only the smaller isoform, CR2; primate CR1, which recapitulates many of the structural domains and presumed functions of Cr2-derived CR1 in subprimates, is encoded by a distinct CR1 gene (apparently derived from the gene Crry of subprimates)."}
{"_id": "WikiPedia_Hematology$$$corpus_6592", "text": "Isoforms CR1 and CR2 derived from the Cr2 gene possess the same C-terminal sequence, such that association with and activation through CD19 should be equivalent. CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein produced primarily by  follicular dendritic cells , appears to be critical for generation of appropriately activated B cells of the germinal centre and for mature antibody responses to bacterial infection. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6593", "text": "The most common allelic variant of the human CR1 gene (CR1*1) is composed of 38  exons  spanning 133kb encoding a  protein  of 2,039  amino acids  with a predicted molecular weight of 220 kDa. Large  insertions  and  deletions  have given rise to four structurally variant  genes  and some alleles may extend up to 160 kb and 9 additional exons. The  transcription  start site has been mapped to 111 bp upstream of the  translation  initiation codon ATG and there is another possible start site 29 bp further upstream. The  promoter  region lacks a distinct  TATA box  sequence. The gene is expressed principally on  erythrocytes ,  monocytes ,  neutrophils  and  B cells  but is also present on some  T lymphocytes ,  mast cells  and  glomerular podocytes ."}
{"_id": "WikiPedia_Hematology$$$corpus_6594", "text": "The encoded protein has a 47 amino acid  signal peptide , an extracellular domain of 1930 residues, a 25 residue transmembrane domain and a 43 amino acid C terminal cytoplasmic region. The  leader sequence and 5'-untranslated region  are contained in one exon. The large extracellular domain of CR1, which has 25 potential  N-glycosylation  sites, can be divided into 30 short consensus repeats (SCRs) (also known as  complement control protein  repeats (CCPs) or sushi domains), each having 60 to 70 amino acids. The sequence homology between SCRs ranges between 60 and 99 percent. The transmembrane region is encoded by 2 exons and the cytoplasmic domain and the 3'-untranslated regions are coded for by two separate exons."}
{"_id": "WikiPedia_Hematology$$$corpus_6595", "text": "The 30 or so SCRs are further grouped into four longer regions termed long homologous repeats (LHRs) each encoding approximately 45 kDa of protein and designated LHR-A, -B, -C, and -D. The first three have seven SCRs while LHR-D has 9 or more. Each LHR is composed of 8 exons and within an LHR, SCR 1, 5, and 7 are each encoded by a single exon, SCR 2 and 6 are each encoded by 2 exons, and a single exon codes for SCR 3 and 4. The LHR seem to have arisen as a result of unequal crossing over and the event that gave rise to LHR-B seems to have occurred within the fourth exon of either LHR-A or \u2013C.  To date the atomic structure have been solved for SCRs 15\u201316, 16 & 16\u201317."}
{"_id": "WikiPedia_Hematology$$$corpus_6596", "text": "Four known human alleles encode proteins with predicted molecular weights of 190 kDa, 220 kDa, 250 kDa and 280 kDa. [ 5 ]  Multiple size variants (55\u2013220 kDa) are also found among non-human  primates  and a partial amino-terminal duplication (CR1-like gene) that encodes the short (55\u201370 kDa) forms expressed on non human erythrocytes. These short CR1 forms, some of which are  glycosylphosphatidylinositol  (GPI) anchored, are expressed on erythrocytes and the 220-kDa CR1 form is expressed on monocytes. The gene including the repeats is highly conserved in primates possibly because of the ability of the repeats to bind complement. LHR-A binds preferentially to the complement component C4b: LHR-B and LHR-C bind to C3b and also, albeit with a lower affinity, to C4b. Curiously the human CR1 gene appears to have an unusual protein conformation but the significance of this finding is not clear."}
{"_id": "WikiPedia_Hematology$$$corpus_6597", "text": "The mean number of complement receptor 1 (CR1) molecules on erythrocytes in normal individuals lies within the range of 100\u20131000 molecules per cell. Two  codominant   alleles  exist \u2013 one controlling high and the other low expression.  Homozygotes  differ by a factor of 10\u201320:  heterozygotes  typically have 500\u2013600 copies per erythrocyte. These two alleles appear to have originated before the divergence of the European and African populations."}
{"_id": "WikiPedia_Hematology$$$corpus_6598", "text": "Plasmodium falciparum  erythrocyte membrane protein 1  (PfEMP1) interacts with uninfected erythrocytes. This 'stickiness', known as  rosetting , is believed to be a strategy used by the  parasite  to remain sequestered in the  microvasculature  to avoid destruction in the  spleen  and  liver . Erythrocyte rosetting causes obstruction of the  blood  flow in  microcapillaries . There is a direct interaction between PfEMP1 and a functional site of complement receptor type 1 on uninfected erythrocytes. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6599", "text": "The  Knops antigen  was the 25th blood group system recognized and consists of the single  antigen   York  (Yk) a with the following allelic pairs:"}
{"_id": "WikiPedia_Hematology$$$corpus_6600", "text": "The antigen is known to lie within the CR1 protein repeats and was first described in 1970 in a 37-year-old  Caucasian  woman. Racial differences exist in the frequency of these antigens: 98.5% and 96.7% of  American  Caucasians and  Africans  respectively are positive for McC(a). 36% of a Mali population were Kn(a) and 14% of exhibited the null (or Helgeson) phenotype compared with only 1% in the American population. The frequencies of McC (b) and Sl (2) are higher in Africans compared with  Europeans  and while the frequency of McC (b) was similar between Africans from the United States or  Mali , the Sl (b) phenotype is significantly more common in Mali \u2013 39% and 65% respectively. In Gambia the Sl (2)/McC(b) phenotype appears to have been positively selected \u2013 presumably due to malaria. 80% of  Papua New Guineans  have the  Helgeson   phenotype  and  case\u2013control studies  suggest this phenotype has a protective effect against severe  malaria ."}
{"_id": "WikiPedia_Hematology$$$corpus_6601", "text": "Convalescent plasma  is the blood plasma collected from a survivor of an infectious disease.  This plasma contains  antibodies  specific to a pathogen and can be used therapeutically by providing passive immunity when transfusing it to a newly infected patient with the same condition. Convalescent plasma can be transfused as it has been collected or become the source material for hyperimmune serum or anti-pathogen monoclonal antibodies; the latter consists exclusively of  IgG , while convalescent plasma also includes  IgA   and  IgM . Collection is typically achieved by  apheresis , but in low-to-middle income countries, the treatment can be administered as convalescent whole blood."}
{"_id": "WikiPedia_Hematology$$$corpus_6602", "text": "Specific  antibodies  to a pathogen are thought to be the primary driver of clinical benefit from convalescent plasma. [ 1 ]  In the case of viral pathogens, the subset of antibodies that retain most of the activity is the one that drives viral neutralization, i.e. neutralizing antibodies, which can be quantified in a  viral neutralization assay . This belief is based on dose-response clinical studies demonstrating that clinical benefit is directly related to the content of neutralizing antibodies, [ 2 ] [ 3 ] [ 4 ] [ 5 ]  and mechanistic studies that have established the antiviral activity of antibodies in convalescent plasma. [ 6 ] [ 7 ]   In addition to higher antibody concentrations being more effective, the timing of therapy is essential.  Preparations are typically most effective when given prophylactically or early in the disease course (i.e. until pathogen replication persists or until the infected host's endogenous immune response develops). [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6603", "text": "In addition to antibodies, convalescent plasma includes a mix of many different proteins and nonprotein factors that can occur in healthy individuals as well as develop in parallel with convalescence. These compounds may affect infection, coagulation, and inflammation independently of the effect of anti-pathogen antibodies. [ 1 ]  Because convalescent plasma therapy is generally safe, [ 9 ]  and the effects of neutralizing antibodies dominate the therapeutic response, the current understanding of these potential additional effects is limited and constitutes an area of ongoing research. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6604", "text": "In 1890,  Emil von Behring  and  Shibasaburo Kitasato  used convalescent serum obtained from large mammals to treat infectious diseases and found that it was particularly effective at preventing and treating  diphtheria . [ 10 ]  Convalescent serum and plasma differ in that the former has all the coagulation components intact, but both are comparable regarding their antibody content.  Hence, the older literature is focused on serum while today most preparations use plasma.  Following the discovery by von Behring and Kitasato, antibody therapy garnered support worldwide as a treatment for infections. Von Behring was awarded the first Nobel Prize in Physiology or Medicine in 1901 for his discoveries. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6605", "text": "Before the development of  antimicrobial treatment  in the 1930s, antibody therapy in the form of serum therapy were the primary means of treating many bacterial and viral infections. [ 11 ]  This treatment appears to have reduced the mortality of  meningococcal meningitis , [ 12 ]   pneumonia , [ 13 ]  and  erysipelas . [ 14 ]   Additionally, antibody therapy seems to have been used successfully to prevent infection after exposure to  measles , [ 15 ] [ 16 ] [ 17 ]   mumps , [ 18 ]  and  chickenpox . [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6606", "text": "The 1918  Spanish influenza  pandemic was caused by an H1N1 influenza virus of avian origin, and around 500 million people, or one-third of the world's population, became infected with this virus. [ 20 ]   The Spanish influenza pandemic was the first pandemic in which convalescent plasma was used as a therapy. A 2006 meta-analysis of eight studies from the Spanish influenza pandemic, including 1,703 patients, found that infected patients who received convalescent plasma had a 21% lower absolute mortality risk than patients not treated with convalescent plasma (16% vs. 37%). [ 21 ]  Consistent with the general treatment principles of antiviral therapy, the most significant clinical and mortality benefits were noted among patients receiving convalescent serum in the early stages of the disease course. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6607", "text": "After the introduction of  antibiotics , the use of convalescent serum or plasma as a therapy for infectious diseases has been restricted mainly to replacement therapy for patients with immunoglobulin deficiencies [ 11 ]  or in the context of viral epidemics or pandemics for which no widely available antiviral could be repurposed. Modern use has also included several randomized controlled trials providing conclusive evidence of efficacy. Selected viral epidemics or pandemics in which convalescent plasma has been used are reviewed below."}
{"_id": "WikiPedia_Hematology$$$corpus_6608", "text": "First identified in 1958,  Argentine hemorrhagic fever  is a rodent-borne illness caused by the arenavirus Junin that is endemic to the humid pampas of Argentina. [ 22 ]  Convalescent plasma has been used during Argentine hemorrhagic fever epidemics; a double-blind, randomized clinical trial conducted from 1974 to 1978 demonstrated that patients treated with convalescent plasma within eight days of disease onset had a 15.4% lower absolute mortality rate than patients who received control plasma without neutralizing antibodies to Argentine hemorrhagic fever virus (1.1% vs. 16.5%). [ 23 ]  Comparable results were described in subsequent outbreaks of Argentine hemorrhagic fever. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6609", "text": "In 2003, a novel coronavirus  SARS-CoV-1  led to an epidemic of the  severe acute respiratory syndrome . [ 25 ]  Convalescent plasma was used to treat SARS; [ 26 ]  in a retrospective analysis from Hong Kong that included 80 patients, early convalescent plasma treatment (14 days between the onset of symptoms and the transfusion date) was associated with an improved prognosis vs late transfusion (after 14 days since symptom onset) in terms of a higher hospital discharge rate by day 22 (58% vs 16%). [ 27 ]  A review and meta-analysis that included eight observational studies (214 total patients) with SARS found a mortality benefit associated with convalescent plasma treatment. [ 28 ]  Further studies were not conducted because the pandemic was extinguished."}
{"_id": "WikiPedia_Hematology$$$corpus_6610", "text": "In 2009, a particular influenza strain  A(H1N1)pdm09  that evaded seasonal flu vaccines caused an influenza pandemic, which was referred to as the  swine flu pandemic . Convalescent plasma was used to treat individuals with severe  H1N1  infections requiring intensive care. [ 29 ]  Despite usage very late in the disease course, patients treated with convalescent plasma had reduced respiratory viral burden, reduced serum cytokine responses, and reduced mortality. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6611", "text": "Middle East respiratory syndrome  (MERS) is a viral respiratory infection caused by the Middle East respiratory syndrome-related coronavirus (MERS-CoV), which is believed to have originated from bats. [ 30 ]  The first identified case occurred in June 2012 in Jeddah, Saudi Arabia, and most cases have occurred in the Arabian Peninsula. [ 30 ]  Convalescent plasma therapy has been used to treat MERS with mixed results; initial case reports and case series in the MERS epidemic failed to show a clinical benefit for patients transfused with convalescent plasma containing uncharacterized neutralizing antibody titers. [ 31 ]  Consistent with the principle that higher antibody content in convalescent plasma results in improved efficacy, a subsequent study demonstrated that transfusion of convalescent plasma containing a high MERS-CoV neutralizing antibody titer resulted in detectable concentrations of antibodies in the blood of the recipient ( seroconversion ). However, seroconversion was not achieved in patients who received convalescent plasma with a low neutralizing antibody titer. [ 32 ]  These findings highlight a challenge of convalescent plasma therapy, namely, that recovered survivors of viral diseases may not produce high-titer neutralizing antibodies, and thus not all convalescent plasma is equally potent. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6612", "text": "Ebola virus disease  was discovered in 1976 when two consecutive outbreaks of fatal hemorrhagic fever occurred in different parts of Central Africa. [ 34 ]  Convalescent plasma treatment was used during the 2013\u20132016 Ebola outbreak; a small nonrandomized study in Sierra Leone revealed significantly longer survival for patients treated with convalescent whole blood compared to patients receiving standard treatment. [ 35 ]  Furthermore, two patients with Ebola who were transferred to the U.S. were treated with convalescent plasma, and an experimental  small interfering RNA  drug, and both survived their infections. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6613", "text": "In 2019, a novel coronavirus,  severe acute respiratory syndrome coronavirus 2  (SARS-CoV-2), causing  coronavirus disease 2019  (COVID-19) spread rapidly around the globe after first being identified in Wuhan, China. [ 37 ]  In early 2020, convalescent plasma started to be used in isolated cases and small series in China [ 38 ]  and Italy. [ 39 ]  Convalescent plasma therapy was deployed at scale in the United States through a Mayo Clinic-led  Expanded Access Program for convalescent plasma [ 40 ]  and a subsequent Emergency Use Authorization issued by the United States Food & Drug Administration. [ 41 ]  Data from the Expanded Access Program demonstrated that among patients who were not mechanically ventilated, patients transfused with high-titer convalescent plasma had lower mortality than patients who received low-titer convalescent plasma (14.2% vs. 22.2%). [ 5 ]  Relatively early during the pandemic, several randomized controlled trials concluded that convalescent plasma therapy was not effective for COVID-19, [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ 46 ]  but most of them focused on patients already seropositive or late in the disease course [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ 46 ]  and/or used plasma units with insufficient antibody levels. [ 44 ] [ 47 ]  Furthermore, there were methodological problems with some of the major trials raising concerns about the validity of negative results\u00a0with regards to convalescent plasma efficacy. [ 48 ]  Randomized controlled trials that instead focused on administering high-titer convalescent plasma early after diagnosis found that convalescent plasma treatment reduced hospital admission by ~50-80%, [ 4 ] [ 49 ]  which is in line with results achieved with monoclonal antibodies and small chemical antivirals. [ 50 ]  Similarly, a randomized controlled trial that administered high-titer convalescent plasma in patients requiring mechanical ventilation found an absolute reduction in mortality of 14% in patients who received convalescent plasma within 48 hours of the initiation of mechanical ventilation. [ 51 ]  Meta-analyses found that convalescent plasma treatment is associated with a mortality benefit, [ 52 ]  particularly if it contains high antibody levels, is administered early, and in immunocompromised patients. [ 53 ]  An epidemiologic analysis of convalescent plasma use and mortality in the United States showed a strong inverse correlation, providing strong evidence of efficacy at a population level. [ 54 ]  From this data, it was estimated that the deployment of convalescent plasma had resulted in approximately 100,000 fewer deaths than had no plasma been used in the USA. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6614", "text": "In the post-vaccine COVID-19 pandemic, a resurgence in the usage of convalescent plasma occurred starting in the spring of 2022, when the SARS-CoV-2 variant Omicron sublineages proved non-responsive to all anti-spike monoclonal antibody treatments authorized, [ 55 ] [ 56 ]  and concerns emerged about contraindications and chronic exposure to small-chemical antivirals which had never been studied in immunocompromised patients at that point. Considering the urgent need to treat immunocompromised patients who were not protected after vaccination, the United States Food & Drug Administration re-authorized convalescent plasma for these patients; [ 57 ]  accordingly, convalescent plasma was recommended in guidelines issued by the Infectious Disease Society of America [ 58 ]  and the European Conference on Infections in Leukemia. [ 59 ]  In the context of the wide deployment of COVID-19 vaccines, a unique product that can be collected from convalescent vaccinees, dubbed \u201chybrid plasma\u201d or \u201cVax-plasma\u201d has been of interest; [ 60 ]  such double status creates heterologous immunity able to cross-react against any SARS-CoV-2 variant so far. [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6615", "text": "An online petition was launched on April 27, 2022, [ 62 ]  asking the World Health Organization to revise its guidelines issued in December 2021, [ 63 ]  which discouraged convalescent plasma usage based on the evidence available until July 2021. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6616", "text": "In the European Directorate for the Quality of Medicines and HealthCare guidelines for blood component manufacturing, no monography exists for convalescent plasma yet as of 2022. Outside clinical trials, the only way thus far to prescribe convalescent plasma is so-called compassionate usage, a procedure which requires authorization by a local ethical committee. In the United States, the use of convalescent plasma for the treatment of COVID-19 remains under Food & Drug Administration Emergency Use Authorization."}
{"_id": "WikiPedia_Hematology$$$corpus_6617", "text": "Cryoprecipitate , also called  cryo  for short, or Cryoprecipitate Antihemophilic factor (AHF), is a frozen  blood product  prepared from  blood plasma . [ 1 ]  To create cryoprecipitate,  Plasma  is slowly thawed to 1\u20136\u00a0\u00b0C. A cold-insoluble precipitate is formed, which is collected by centrifugation, resuspended in a small amount of residual plasma (generally 10\u201315 mL) and then re-frozen for storage. Cryoprecipitate contains fibrinogen, Factor VIII, Factor XIII and vWF. In many clinical contexts, use of cryoprecipitate has been replaced with use of  clotting factor  concentrates (where available), but the whole form is still routinely stocked by many hospital  Blood bank . Cryo can be stored at \u221218\u00a0\u00b0C or colder for 12 months from the original collection date [ 1 ]  or up to 36 months in Europe if stored below -25\u00a0\u00b0C. [ 2 ]  After thawing, single units of cryo (or units pooled using a sterile method) can be stored at 20\u201324\u00a0\u00b0C for up to 6 hours. If units of cryo are pooled in an open system, they can only be held at 20\u201324\u00a0\u00b0C for up to 4 hours. [ 3 ]  Presently cryo cannot be re-frozen for storage after it is thawed for use if it is not transfused."}
{"_id": "WikiPedia_Hematology$$$corpus_6618", "text": "Compatibility testing ( Cross-matching ) before transfusion of cryoprecipitate are not necessary. However, cryoprecipitate should preferably be ABO compatible with the recipient's red cells. ABO-incompatible cryoprecipitate can be used with caution, particularly with large volumes. If a large volume of ABO-incompatible cryoprecipitate can be used with caution, particularly with large volumes. If a large volume of ABO-incompatible cryoprecipitate is used, the recipient may develop a positive direct antiglobulin test and, very rarely, mild haemolysis. Matching for RhD type is not necessary."}
{"_id": "WikiPedia_Hematology$$$corpus_6619", "text": "Medical uses for giving cryoprecipitate include: [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6620", "text": "Cryoprecipitate should not be used to treat haemophilia, von Willebrand\u2019s disease or deficiencies of Factor XIII or fibronectin except in cases where alternative therapies are unavailable."}
{"_id": "WikiPedia_Hematology$$$corpus_6621", "text": "A typical adult dose is 10 units of whole blood-derived cryoprecipitate, equivalent to a fibrinogen dose of approximately 3\u22124 g."}
{"_id": "WikiPedia_Hematology$$$corpus_6622", "text": "Adverse effects reported with the usage of cryoprecipitate include hemolytic  transfusion reactions , febrile non-hemolytic reactions, allergic reactions (ranging from  urticaria  to  anaphylaxis ), septic reactions,  transfusion related acute lung injury , circulatory overload, transfusion-associated  graft-versus-host disease , and  post-transfusion purpura . [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6623", "text": "Each unit (around 10 to 15 mL) typically provides: [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6624", "text": "Cryoprecipitate also contains  fibronectin ; however there are no clear indications for fibronectin replacement."}
{"_id": "WikiPedia_Hematology$$$corpus_6625", "text": "US standards require manufacturers to test at least four units each month, and the products must have a minimum of 150\u00a0mg or more of fibrinogen and 80 IU of factor VIII per unit. [ 7 ] [ 8 ]  European standards require 140\u00a0mg or more of fibrinogen, 70 IU of factor VIII and 100 IU of vWF per unit."}
{"_id": "WikiPedia_Hematology$$$corpus_6626", "text": "While the current method for producing cryoprecipitate was developed by Judith Graham Pool from  Stanford University  in 1964, it was initially approved in 1971 by the  U.S. Food and Drug Administration  under the name  Cryoprecipitated AHF  for the Hoxworth Blood Center  University of Cincinnati Medical Center ."}
{"_id": "WikiPedia_Hematology$$$corpus_6627", "text": "The term  cryosupernatant  (also called  cryo-poor plasma ,  cryoprecipitate depleted ,  cryoprecipitate reduced plasma ) refers to  plasma  from which the  cryoprecipitate  has been removed. It is used to treat  thrombocytopenic purpura . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6628", "text": "The resulting plasma has reduced levels of  factor VIII  (FVIII),  von Willebrand factor  (VWF),  factor XIII  (FXIII),  fibronectin  and  fibrinogen .  While the levels of FVIII are greatly reduced, levels of fibrinogen can be as much as 70% of original levels. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6629", "text": "Cryosupernatant plasma can be used when replacement of FVIII is not required, [ 2 ]  and is indicated for plasma exchange for patients with  thrombotic thrombocytopenic purpura  (TTP) [ 1 ]  as well as for treatment of  hemolytic-uremic syndrome  (HUS) by plasma exchange, when plasma exchange is indicated. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6630", "text": "Damage control surgery  is surgical intervention to keep the patient alive rather than correct the  anatomy . [ 1 ] [ 2 ] \nIt addresses the  \"lethal triad\"  for critically ill patients with severe  hemorrhage  affecting  homeostasis  leading to  metabolic acidosis ,  hypothermia , and increased  coagulopathy . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6631", "text": "This lifesaving method has significantly decreased the morbidity and mortality of critically ill patients, though complications can result.\nIt stabilizes patients for clinicians to subsequently reverse the physiologic insult prior to completing a definitive repair. While the temptation to perform a definitive operation exists, surgeons should avoid this practice because the deleterious effects on patients can result in them succumbing to the physiologic effects of the injury, despite the anatomical correction.\nThe leading cause of death among trauma patients remains uncontrolled hemorrhage and accounts for approximately 30\u201340% of trauma-related deaths. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6632", "text": "While typically  trauma surgeons  are heavily involved in treating such patients, the concept has evolved to other sub-specialty services.\nA multi-disciplinary group of individuals is required: nurses, respiratory therapist, surgical-medicine intensivists, blood bank personnel and others."}
{"_id": "WikiPedia_Hematology$$$corpus_6633", "text": "Damage control surgery can be divided into the following three phases: Initial laparotomy, Intensive Care Unit (ICU) resuscitation, and definitive reconstruction. Each of these phases has defined timing and objectives to ensure best outcomes. The following goes through the different phases to illustrate, step by step, how one might approach this. There are clearly different approaches throughout the country, and no one way is necessarily correct. However, the ability to evaluate objectively the differences and then choose the one that fits your team is important. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6634", "text": "This is the first part of the damage control process whereby there are some clear-cut goals surgeons should achieve. The first is controlling hemorrhage followed by contamination control, abdominal packing, and placement of a temporary closure device. [ 5 ]  Minimizing the length of time spent in this phase is essential."}
{"_id": "WikiPedia_Hematology$$$corpus_6635", "text": "For groups (i.e., trauma centers) to be effective in damage control surgery, a multi-disciplinary team is critical. The approach to caring for such critically ill patients is dependent on nurses, surgeons, critical care physicians, operating room staff, blood bank personnel, and administrative support. In addition to having the right team in place is having a prepared team. The more facile the team is enhances the ability for centers to effectively implement damage control surgery. This is referred to by some as damage control ground zero (DC0). [ 6 ]  The ability to mobilize personnel, equipment, and other resources is bolstered by preparation; however, standardized protocols ensure that team members from various entities within the health care system are all speaking the same language. This has been seen during implementation of complex processes such as the  massive transfusion protocol  (MTP)."}
{"_id": "WikiPedia_Hematology$$$corpus_6636", "text": "Controlling of hemorrhage as discussed above is the most important step in this phase. Eviscerating the intra-abdominal small bowel and packing all four  abdominal quadrants  usually helps surgeons establish initial hemorrhagic control. Depending up on the source of hemorrhage a number of different maneuvers might need to be performed allowing for control of aortic inflow. Solid organ injury (i.e., spleen, kidney) should be dealt with by resection. When dealing with hepatic hemorrhage a number of different options exist such as performing a  Pringle maneuver  that would allow for control of hepatic inflow. [ 7 ]  Surgeons can also apply manual pressure, perform  hepatic packing , or even plugging penetrating wounds. Certain situations might require leaving the liver packed and taking the patient for angio-embolization or if operating in a hybrid operating room having perform an on table  angio-embolization . Vessels that are able to be ligated should, and one should consider shunting other vessels that do not fall into this category. This has been described by Reilly and colleagues when they shunted the superior mesenteric artery to decrease the length of time in the operating room. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6637", "text": "Once hemorrhage control is achieved one should quickly proceed to controlling intra-abdominal contamination from hollow-viscus organs. The perception might be that one could quickly perform an  anastomosis . This should not be attempted in the damage control setting. The key is to simply prevent continued intra-abdominal contamination, and to leave patients in discontinuity. A number of different techniques can be employed such as using staplers to come across the bowel, or primary suture closure in small perforations. Once this is complete the abdomen should be packed. Many of these patients become coagulopathic and can develop diffuse oozing. It is important to not only pack areas of injury but also pack areas of surgical dissection. There are various methods that can be used to pack the abdomen. Packing with radiopaque laparotomy pads allow for the benefit of being able to detect them via x-ray prior to definitive closure. As a rule abdomens should not be definitively closed until there has been radiologic confirmation that no retained objects are present in the abdomen."}
{"_id": "WikiPedia_Hematology$$$corpus_6638", "text": "The final step of this phase is applying a temporary closure device. Numerous methods of temporary closure exist, with the most common technique being a negative-vacuum type device. Regardless of which method one decides to use it is important that the abdominal fascia is not reapproximated. The ability to develop  abdominal compartment syndrome  is a real concern and described by Schwab. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6639", "text": "On completion of the initial phase of damage control, the key is to reverse the physiologic insult that took place. This specifically relates to factors such as acidosis, coagulopathy, and hypothermia ( lethal triad ) that many of these critically ill patients develop. When developing a strategy to best care for these patients, the same principles of having a multi-disciplinary team that work together in parallel for the same result apply. The intensivist is critical in working with the staff to ensure that the physiologic abnormalities are treated. This typically requires close monitoring in the intensive care unit, ventilator support, laboratory monitoring of resuscitation parameters (i.e., lactate)."}
{"_id": "WikiPedia_Hematology$$$corpus_6640", "text": "In using a number of different resuscitation parameters, the critical care team can have a better idea as to which direction is progressing. The first 24 hours often require a significant amount of resources (i.e., blood products) and investment of time from personnel within the critical care team. In many circumstances, especially trauma patients, require that other specialties address a variety of injuries. Moving the patient early on, unless absolutely necessary,  can be detrimental. Certain circumstances might require this, and the patients should continue to receive care from the critical care team during the entire transport period. As the literature begins to grow within the field of damage control surgery, the medical community is continuously learning how to improve the process. Certain pitfalls have also become evident, one of which is the potential to develop abdominal compartment syndrome."}
{"_id": "WikiPedia_Hematology$$$corpus_6641", "text": "In some cases, temporary abdominal closure itself or underlying conditions may contribute to abdominal compartment syndrome, causing increased intraabdominal pressure and compromising organ perfusion. [ 10 ]  Temporary abdominal dressings with high negative pressures can be a cause of recurrent abdominal compartment syndrome and one should not hesitate to turn off the dressing's suction when evaluating a patient with signs of recurrent abdominal compartment syndrome. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6642", "text": "While it might sound counterintuitive since the fascia is left open during the placement of these temporary closure devices, they can create a similar type process that leads to abdominal compartment syndrome. If this occurs the temporary closure device should be taken down immediately. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6643", "text": "The third step in damage control surgery is addressing closure of the abdomen. Definitive reconstruction occurs only when the patient is improving. At this point in process the critical care team has been able to correct the physiologic derangements. The optimization typically takes 24 to 48 hours, depending on how severe the initial insult is. Prior to being taken back to the operating room it is paramount that the resolution of acidosis, hypothermia, and coagulopathy has occurred. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6644", "text": "The first step after removing the temporary closure device is to ensure that all abdominal packs are removed. Typically the number of packs has been documented in the initial laparotomy; however, an abdominal radiograph should be taken prior to definitive closure of the fascia to ensure that no retained sponges are left in the abdomen. Once the abdominal packs are removed the next step is to re-explore the abdomen allowing for the identification of potentially missed injuries during the initial laparotomy and re-evaluating the prior injuries. Attention is then turned to performing the necessary bowel anastomosis or other definitive repairs (i.e., vascular injuries). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6645", "text": "An attempt should be made to close the abdominal fascia at the first take back, to prevent complications that can result from having an open abdomen. The concern for early closure of the abdomen with development of compartment syndrome is a real one. A method to pre-emptively evaluate whether fascial closure is appropriate would be to determine the difference in peak airway pressure (PAP) prior to closure and the right after closure. An increase of over 10 would suggest that the abdomen be left open. [ 9 ]  As mentioned above, it is important to obtain an abdominal radiograph to ensure that no retained sponges are left intra-operatively."}
{"_id": "WikiPedia_Hematology$$$corpus_6646", "text": "Considering that not all patients can undergo definitive reconstruction at first return, there are other options that surgeons can consider. Data would suggest that the longer the abdomen is left open from initial laparotomy the higher the rate of complications. [ 12 ]  After about one week, if surgeons can't close the abdomen, they should consider placing a Vicryl mesh to cover the abdominal contents. This lets granulation occur over a few weeks, with the subsequent ability to place a split-thickness skin graft (STSG) on top for coverage. These patients clearly have a hernia that must be fixed 9 to 12 months later."}
{"_id": "WikiPedia_Hematology$$$corpus_6647", "text": "Damage control resuscitation has had a dramatic impact on how care for critically ill patients is administered. [ citation needed ] . The core principles of resuscitation involve permissive hypotension, transfusion ratios, and massive transfusion protocol. The resuscitation period lets any physiologic derangements be reversed to give the best outcome for patient care."}
{"_id": "WikiPedia_Hematology$$$corpus_6648", "text": "Typical resuscitation strategies have used an approach where aggressive crystalloid and/or blood product resuscitation is performed to restore blood volume. The term permissive hypotension refers to maintaining a low blood pressure to mitigate hemorrhage; however, continue providing adequate end-organ perfusion [Duchesene, 2010]. The key is to prevent exacerbation of hemorrhaging until definitive vascular control can be achieved, the theory being that if clots have formed within a vessel then increasing the patient's blood pressure might dislodge those established clots resulting in more significant bleeding. Permissive hypotension is not a new concept, and had been described in penetrating thoracic trauma patients during World War I by Bickell and colleagues demonstrating an improvement in both survival and complications. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6649", "text": "Subsequent animal studies have shown equivalent outcomes with no real benefit in mortality  [ 4 ]  Recently there has been further data in trauma patients that has demonstrated increased survival rates [Morrison, 2011]. Cotton and colleagues found that the use of a permissive hypotension resuscitation strategy resulted in better outcomes (increased 30-day survival) in those undergoing damage control laparotomy. This would not be used in situations where patients might have injuries such as a traumatic brain injury considering that such patients are excluded from the studies."}
{"_id": "WikiPedia_Hematology$$$corpus_6650", "text": "For over a century the casualties of war have provided valuable lessons that can be applied within the civilian sector. Specifically the past decade has seen a paradigm shift in early resuscitation of critically injured patients. Instead of replacing blood volume with high volumes of crystalloid and packed red blood cells with the sporadic use of fresh frozen plasma and platelets, we have now learned that maintaining a transfusion ratio of 1:1:1 of plasma to red blood cells to platelets in patients requiring massive transfusion results in improved outcomes [Borgman 2007] [ 4 ]  While this was initially demonstrated in the military setting, Holcomb and colleagues extrapolated this to the civilian trauma center showing improved results as well  [ 14 ] [ 15 ]  Broad implementation across both the military and civilian sector has demonstrated a decreased mortality in critically injured patients. [ 4 ]  Debate has gone back and forth as to the correct ratio that should be used; however, recently Holcomb and colleagues published the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study. [ 15 ] [ 16 ]  They compared administration a higher ratio of plasma and platelets (1:1:1) compared to a lower ratio (1:1:2). The patients that received a higher ratio had an associated three to four-fold decrease in mortality. To help mitigate confounding variables a randomized control trial called the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) has been performed to evaluate the transfusion requirement. There was no difference in 24 hour or 30 day mortality between the 1:1:1 group and the 1:1:2 group -  https://jamanetwork.com/journals/jama/fullarticle/2107789 . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6651", "text": "Initial resuscitation of trauma patients continues to evolve. Massive transfusion (defined as receiving greater than or equal to 10 units of packed red blood cells with a 24-hour period) is required in up to 5% of civilian trauma patients that arrive severely injured. [ 17 ]  Patients who are arriving severely injured to trauma centers can be coagulopathic. Data suggests that around 25% of patients arrive with coagulopathy. [ 18 ]  New ways of measuring coagulopathy such at thromboelastography and rotational thromboelastometry have allowed for a more robust assessment of the coagulation cascade compared to traditional methods of measuring international normalized ratio allowing clinicians to better target areas of deficiency. [ 4 ]  For trauma teams to systematically and efficiently deliver blood products institutions have created protocols that allow for this. The protocols allow for clear communication between the trauma center, blood bank, nurses, and other ancillary staff. They also allow for the quick delivery of certain set of blood products depending upon the institution. One example might be that a \u201ccooler\u201d would contain 10 units of packed red blood cells, 10 units of plasma, and 2 packs of platelets. The idea is that the coolers would continue to be delivered to the location where the patient is being treated until the trauma team leader (typically the trauma surgeon) would discontinue the order. [ 17 ]  Systolic blood pressure <90\u00a0mmHg, hemoglobin <11\u00a0g/dL, temperature <35.5 o C, international normalized ratio >\u00a01.5, base deficit \u22656\u00a0mEq/L, heart rate \u2265120\u00a0bpm, presence of penetrating trauma, and Focused Abdominal Sonography Trauma exam have been evaluated to determine their predictive ability in patients arriving at trauma centers. All were be predictive of the need of massive transfusion protocol except for temperature. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6652", "text": "Surgeons have used the concept of damage control surgery for years, and controlling hemorrhage with packing is over a century old. Pringle described this technique in patients with substantial hepatic trauma in the early twentieth century. [ 7 ]  The U.S. military did not encourage this technique during World War II and the Vietnam War. Lucas and Ledgerwood described the principle in a series of patients. [ 19 ]  Subsequent studies were repeated by Feliciano and colleagues, [ 20 ]  and they found that hepatic packing increased survival by 90%. This technique was then specifically linked to patients who were hemorrhaging, hypothermic, and coagulopathic. [ 21 ]  This extrapolation allowed for the first article in 1993 by Rotondo and Schwab specifically adapting the term \u201cdamage control\u201d. [ 22 ]  This term was taken from the United States Navy who initially used the term as \u201cthe capacity of a ship to absorb damage and maintain mission integrity\u201d (DOD 1996). This was the first article that brought together the concept of limiting operative time in these critically ill patients to allow for reversal of physiologic insults to improve survival. In addition, the description illustrated how the three phases of damage control surgery can be implemented. Since this description the development of this concept has grown both within the trauma community and beyond."}
{"_id": "WikiPedia_Hematology$$$corpus_6653", "text": "The data that have been published regarding definitive laparotomy versus damage control surgery demonstrate a decrease in mortality when performed in the critically ill patient. [ 21 ] [ 6 ]  Subsequent studies by Rotondo and colleagues in a group of 961 patients that had undergone damage control surgery demonstrate an overall mortality of 50% and a 40% morbidity rate. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6654", "text": "There are four main complications. The first is development of an intra-abdominal abscess. This has been reported as high as 83%. [ 20 ] [ 21 ]  Next is the development of an entero-atmospheric fistula, which ranges from 2 to 25%. [ 5 ] [ 24 ]  The third is abdominal compartment syndrome that has been reported anywhere from 10 to 40% of the time. [ 25 ] [ 26 ]  Finally fascial dehiscence has been shown to result in 9\u201325% of patients that have undergone damage control surgery. [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6655", "text": "This page is currently under construction."}
{"_id": "WikiPedia_Hematology$$$corpus_6656", "text": "Transfusion-related acute lung injury"}
{"_id": "WikiPedia_Hematology$$$corpus_6657", "text": "Febrile non-hemolytic transfusion reaction"}
{"_id": "WikiPedia_Hematology$$$corpus_6658", "text": "Transfusion-associated graft versus host disease"}
{"_id": "WikiPedia_Hematology$$$corpus_6659", "text": "A  delayed hemolytic transfusion reaction (DHTR)  is a type of  adverse reaction  to a  blood transfusion . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  DHTR is the later-onset manifestation of hemolytic transfusion reaction, which may also present as  acute hemolytic transfusion reaction  (AHTR) in a shorter timeframe from transfusion administration. The prevalence of AHTR has been estimated at 1 in 70,000 blood transfusions, whereas the prevalence of DHTR is thought to be underreported, although various studies estimate the prevalence of DHTR as between 1 in 800, to 1 in 11,000 transfusions. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6660", "text": "Hemolytic transfusion reactions are a possible complication from red blood cell  transfusions . Hemolysis refers to the  lysis  (rupture) of  red blood cells , and the resulting leakage of their contents. Hemolytic reactions may be immune or non-immune mediated. Immune-mediated hemolytic reactions, such as DHTR, represent a type of  alloimmunity . Non-immune hemolysis may result from  thermal ,  osmotic , or  mechanical  damage to red blood cells in transfusion products."}
{"_id": "WikiPedia_Hematology$$$corpus_6661", "text": "In immune-mediated DHTR, the transfusion recipient has  antibodies  that react with  antigens  on incompatible donor red blood cells, [ 5 ]  prompting lysis of the red blood cells by the recipient's  immune cells , such as  macrophages . The severity of immune-mediated hemolytic reactions may vary based on the type and quantity of both the transfused red blood cell antigens and the recipient's antibodies against them, as well as the ability of the antibodies to activate  complement  or  opsonization . Some recipients do not have significant pre-existing antibodies against transfused red blood cells, but then develop higher levels of such antibodies following immune stimulation by the transfused red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_6662", "text": "While AHTR usually presents within the first 24 hours after transfusion, DHTR has the possibility to present up to 30 days later. Even though DHTR may have a lower chance of severe outcomes than AHTR, it can still be fatal or result in serious complications, and must be treated as an  urgent medical issue ."}
{"_id": "WikiPedia_Hematology$$$corpus_6663", "text": "If a person without a Kidd blood antigen (for example a Jka-Jkb+ patient) receives a  Kidd antigen (Jka-antigen for example)  in a red blood cell transfusion and forms an alloantibody (anti-Jka); upon subsequent transfusion with Jka-antigen positive red blood cells, the patient may have a delayed hemolytic transfusion reaction as their anti-Jka antibody hemolyzes the transfused Jka-antigen positive red blood cells. Other common blood groups with this reaction are  Duffy ,  Rhesus  and  Kell . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6664", "text": "Immune-mediated hemolytic reactions may be classified as either intravascular or extravascular hemolysis. Intravascular hemolysis takes place while the red blood cells are still when the recipient's antibodies bind to the donor's red blood cells and cause complement activation. Extravascular hemolysis is produced when the recipient's antibodies opsonize the donor's red blood cells, leading to their sequestration and  phagocytosis  by phagocyte immune cells such as macrophages. Macrophage activation, in response to antibody-mediated targeting of red blood cells, can also increase production of  cytokines  that induce a systemic response that results in clinical symptoms, such as  fever ,  chills ,  abdominal pain , and  back pain ."}
{"_id": "WikiPedia_Hematology$$$corpus_6665", "text": "Some hemolytic reactions are the product of incompatibility between different blood types of the  ABO blood group system . Hemolytic reactions may also be caused by incompatibilities with  Rh factors ,  Duffy antigens ,  Kell antigens ,  Kidd antigens , [ 6 ]  and  Lewis antigens ."}
{"_id": "WikiPedia_Hematology$$$corpus_6666", "text": "Many people have antibodies to red blood cell antigens not found on the surface of their own red blood cells. Therefore, to use the ABO types as an example, those with type O blood are likely to have antibodies to type A and type B blood. Those with type A blood are likely to have antibodies to type B blood, and vice versa."}
{"_id": "WikiPedia_Hematology$$$corpus_6667", "text": "Antibodies against Kidd antigens may be difficult to detect because of significant variability in their molecular features, and weak  in vitro  expression. They have been reported to cause severe immediate or delayed hemolytic transfusion reactions, [ 6 ]  with anti-Jk antibodies responsible for 13 of 44 cases of DHTR reported in the UK during 2021. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6668", "text": "Symptoms may include a drop in hemoglobin level, fever, jaundice, or hemoglobinuria. [ 6 ]  It is also \"associated with a fall in Hb or failure to increment, rise in bilirubin and LDH and an incompatible crossmatch not detectable pre transfusion.\" [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6669", "text": "DHTR may be diagnosed by the presence of antibodies that react to red blood cells. An  antiglobulin test , also known as a Coombs test, is a type of blood test used in  immunohematology . An antiglobulin test may either be direct (e.g., \"direct antiglobulin test\" or \"direct Coombs test\"), or indirect. The direct test is designed to detect antibodies already bound to the surface of red blood cells in a clinical blood sample. By contrast, the indirect test is designed to detect antibodies that are freely floating in the blood, and that display  in vitro  reactivity against red blood cells. Both direct and indirect Coombs tests may be useful for investigating suspected blood transfusion reactions. The indirect test may also be used to determine a patient's reactivity to foreign red blood cell antigens prior to transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_6670", "text": "Hyperhemolysis  differs from DHTR in that it involves the lysis of the recipient's own red blood cells in addition to those introduced from the donor. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6671", "text": "Delayed blood transfusion reactions occur at an incidence of about 1/500 to 1/10,000 transfusions in the United States. The subacute presentation, milder symptoms and paucity of reporting data make determination of the true incidence difficult. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6672", "text": "The  Diego antigen (or blood group) system  is composed of 21 blood factors or  antigens  carried on the  Band 3   glycoprotein , also known as Anion Exchanger 1 (AE1). The antigens are inherited through various  alleles  of the gene  SLC4A1  ( Solute carrier family  4), located on  human chromosome 17 . The AE1 glycoprotein is expressed only in  red blood cells  and, in a shortened form, in some cells in the  kidney . The Diego a  antigen is fairly common in  Indigenous peoples of the Americas  (in both North and South America) and  East Asians , but very rare or absent in most other populations, supporting the theory that the two groups share common ancestry."}
{"_id": "WikiPedia_Hematology$$$corpus_6673", "text": "The Diego system is named after a pair of types, Diego a  (Di a ) and Diego b  (Di b ), which differ by one  amino acid  in the AE1 glycoprotein, corresponding to one difference in the  nucleotide  sequence of the SLC4A1 gene. Di b  is common or ubiquitous in all populations which have been screened for it, while Di a  has been found only in Indigenous peoples of the Americas (in both North and South America) and East Asians, and in people with some ancestors from those groups. People  heterozygous  for the two alleles produce both antigens. No individual has been tested who does not produce one, or both, of the two antigens. [ 1 ]  Anti-Di a  (the  antibody  to Di a ) can cause severe  hemolytic disease of the newborn  and severe  transfusion reaction . Anti-Di b  usually causes milder reactions. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6674", "text": "The Wright blood system is another pair of types, Wright a  (Wr a ) and Wright b  (Wr b ), also differing by one amino acid on the AE1 glycoprotein and one nucleotide on the SLC4A1 gene. Wr a  always expresses antigens, but the antibody reaction of Wr b  depends on a variation in the structure of  glycophorin A , which binds with Wr b . [ 3 ]  Anti-Wr a  can also cause severe  hemolytic disease of the newborn  and severe  transfusion reaction . Anti-Wr b  is very rare, and little data is available on its severity. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6675", "text": "Seventeen other rare blood types (as of 2002) are included in the Diego antigen system, as they are produced by mutations on the SLC4A1 gene. These include the Waldner (Wd a ), Redelberger (Rb a ), Warrior (WARR), ELO, Wulfsberg (Wu), Bishop (Bp a ), Moen (Mo a ), Hughes (Hu a ), van Vugt (Vg a ), Swann (Sw a ), Bowyer (BOW), NFLD, Nunhart (Jn a ), KREP, Traversu (Tr a ), Froese (Fra) and SW1 types. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6676", "text": "The first Diego antigen, Di a , was discovered in 1953, when a child in  Venezuela  died of hemolytic disease three days after birth.  Rh  and  ABO  blood type mismatches were soon ruled out, and investigators began searching for a rare blood factor. Red blood cells from the father reacted strongly to  blood serum  from the mother. Rare blood types known at the time were eliminated, and the new type was classified as a \"private\" or \"family\" blood type. The investigators, with the agreement of the father, named the new type after his surname, \"Diego\". In 1955 investigators found that the Diego family included ancestry from Indigenous peoples of the Americas, and that the Diego factor (Di a ) was not restricted to the Diego family, but occurred in several populations in Venezuela and elsewhere in South America. Investigators suspected that the Diego factor might be a  Mongoloid  trait, and tested groups of  Native Americans in the United States  and people of  Chinese  and  Japanese  ancestry, and found Di a  in those groups. Anti-Di b  was found in 1967, establishing the Diego group as a two-antigen system. In 1993 the Diego pair of antigens was found to result from a single point mutation (nucleotide 2561) on what is now called the SLC4A1 gene on chromosome 17. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6677", "text": "The Wright a  antigen (Wr a ), a very low frequency blood type, was also discovered in 1953. The Wright b  antigen (Wr b ), a very high frequency blood type, was discovered about a decade later, but the two types were not recognized as a pair for another 20 years. The Wright group was eventually identified as a single point mutation on the SLC4A1 gene. The Wright group was subsumed into the Diego group in 1995, since its location on the SLC4A1 gene had been determined after the Diego group had been located there. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6678", "text": "Starting in 1995, various rare antigen types, some of which had been known for 30 years, were found to also be caused by mutations on the SLC4A1 gene, and were therefore added to the Diego system. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6679", "text": "The Di b  antigen has been found in all populations tested. The Di a  antigen, however, has been found only in populations of  indigenous peoples of the Americas  and East Asians, and people with some ancestry in those populations. Some groups in South America have a relatively high frequency of Di a +. A sample of the  Kaingang people  of Brazil was 49% Di a +. Samples of other groups in  Brazil  and Venezuela were 14% to 36% Di a +. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6680", "text": "While the Di a  antigen is found at moderate to high frequencies in most populations of indigenous peoples in South America, it is absent in the  Waica people , and occurs at very low frequencies in the  Warao  and  Yaruro  people of interior northern South America. Layrisse and Wilbert, who characterize these people as \"Marginal Indians\", proposed that they are remnants of a first migration into South America of people who had not acquired the allele for the Di a  antigen, with other indigenous peoples of South America resulting from a later migration. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6681", "text": "Samples of groups in  Guatemala  and  Mexico  have 20% to 22% Di a +. Samples from Native American groups in the United States and  First Nations  groups in  Canada  have 4% to 11% Di a +. [ 1 ] [ 7 ]  Although the incidence of Diego a + is relatively high in  Siberian Eskimos  and  Aleut people  (the incidence of Diego a + in Aleuts is comparable to South American levels), it occurs at a much lower frequency (less than 0.5%) among  Alaskan   Eskimos  and has not been found in the  Inuit  of Canada. [ 8 ] [ 9 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6682", "text": "The Di a  antigen is widespread in East Asian populations. Samples of East Asian populations show 4% Di a + for the  Ainu  of  Hokkaido , [ 11 ]  2% to 10% Di a + for Japanese, 6% to 15% Di a + for  Koreans , 7% to 13% Di a + for  Mongolians , 10% Di a + for northern Chinese and 3% to 5% Di a + for southern Chinese. [ 1 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6683", "text": "The Di a  antigen is also found in northern  India  and in  Malaysia , where there are populations of East Asian ancestry. North Indians (of unspecified ethnicity) are reported to be 4% Di a +. On the other hand, a sample of Indian students attending the University of Michigan, the majority of which were  Gujarati , found none to be Di a +. [ 7 ]  A survey of residents of the  Klang Valley  in Malaysia found the incidence of Di a + in ethnic Chinese to be 4%, in  ethnic Malays  to be a little over 1%, and in ethnic Indians (descended from southern Indians) to be a little under 1%. (A smaller sample of Malays in  Penang , Malaysia, were 4% Di a +.) [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6684", "text": "The Di a  antigen is very rare in  African  and European populations. [ 12 ]  One  West African  subject had an ambiguous possible reaction to Di a . [ 7 ]  About 0.5% of Europeans of  Polish  ancestry have been found to be Di a +. This incidence has been attributed to gene mixture from  Tatars  who invaded Poland five to seven centuries ago. [ 2 ]  Diego Antigen has been found in 0.89% of Germans from Berlin. [ 13 ]  The Di a  antigen is very rare or absent in  Aboriginal Australians ,  Papuans , natives of  New Britain , and  Polynesians . [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6685", "text": "The distribution of the Di a  antigen has been cited as proof that the Americas were populated by migrations from Siberia. Differences in the frequency of the antigen in populations of indigenous people in the Americas correlate with major language families, modified by environmental conditions. [ 14 ]  Another study suggests that the distribution of the Di a  antigen in central and eastern Asia has been shaped by the expansion of Mongolian and related populations that resulted in the creation of the  Mongol Empire  in the 13th- and 14th-centuries. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6686", "text": "4NUU ,  4NUV"}
{"_id": "WikiPedia_Hematology$$$corpus_6687", "text": "2532"}
{"_id": "WikiPedia_Hematology$$$corpus_6688", "text": "13349"}
{"_id": "WikiPedia_Hematology$$$corpus_6689", "text": "ENSG00000213088"}
{"_id": "WikiPedia_Hematology$$$corpus_6690", "text": "ENSMUSG00000037872"}
{"_id": "WikiPedia_Hematology$$$corpus_6691", "text": "Q16570"}
{"_id": "WikiPedia_Hematology$$$corpus_6692", "text": "Q9QUI6"}
{"_id": "WikiPedia_Hematology$$$corpus_6693", "text": "NM_002036 NM_001122951"}
{"_id": "WikiPedia_Hematology$$$corpus_6694", "text": "NM_010045"}
{"_id": "WikiPedia_Hematology$$$corpus_6695", "text": "NP_001116423 NP_002027"}
{"_id": "WikiPedia_Hematology$$$corpus_6696", "text": "NP_034175"}
{"_id": "WikiPedia_Hematology$$$corpus_6697", "text": "Duffy antigen/chemokine receptor  ( DARC ), also known as  Fy glycoprotein  ( FY ) or   CD234  ( Cluster of Differentiation 234 ), is a  protein  that in humans is encoded by the  ACKR1   gene . [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6698", "text": "The Duffy antigen is located on the surface of  red blood cells , and is named after the patient in whom it was discovered. The protein encoded by this gene is a  glycosylated   membrane protein  and a non-specific  receptor  for several  chemokines . The protein is also the receptor for the human malarial parasites  Plasmodium vivax ,  Plasmodium knowlesi  and simian malarial parasite  Plasmodium cynomolgi . [ 8 ]   Polymorphisms  in this gene are the basis of the Duffy blood group system. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6699", "text": "It was noted in the 1920s that black Africans had some intrinsic resistance to malaria, but the basis for this remained unknown. The Duffy antigen gene was the fourth gene associated with the resistance after the genes responsible for  sickle cell anaemia ,  thalassemia  and  glucose-6-phosphate dehydrogenase . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6700", "text": "In 1950, the Duffy  antigen  was discovered in a multiply-transfused  hemophiliac  named Richard Duffy, whose serum contained the first example of anti-Fya  antibody . [ 10 ] \nIn 1951, the antibody to a second antigen, Fyb, was discovered in  serum . Using these two antibodies, three common  phenotypes  were defined: Fy(a+b+), Fy(a+b-), and Fy(a-b+). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6701", "text": "Several other types were later discovered bringing the current total up to 6: Fya, Fyb, Fy3, Fy4, Fy5 and Fy6. Only Fya, Fyb and Fy3 are considered clinically important. Reactions to Fy5 have also rarely been reported.  The Fy4 antigen, originally described on Fy (a\u2013b\u2013) RBCs, is now thought to be a distinct, unrelated antigen and is no longer included in the FY system. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6702", "text": "The Duffy antigen/chemokine  receptor  gene (gp-Fy; CD234) is located on the long arm of  chromosome 1  (1.q22-1.q23) and was cloned in 1993. [ 6 ]  The gene was first localised to chromosome 1 in 1968, and was the first blood system antigen to be localised. It is a single copy gene spanning over 1500 bases and is in two  exons . The gene encodes a 336 amino acid acidic  glycoprotein . It carries the antigenic determinants of the Duffy blood group system which consist of four codominant  alleles \u2014FY*A and FY*B\u2014coding for the Fy-a and Fy-b antigens respectively, FY*X and FY*Fy, five  phenotypes  (Fy-a, Fy-b, Fy-o, Fy-x and Fy-y) and five antigens. Fy-x is a form of Fy-b where the Fy-b gene is poorly expressed. Fy-x is also known as Fy-b weak  or Fy-b Wk ."}
{"_id": "WikiPedia_Hematology$$$corpus_6703", "text": "This gene has been redesignated  ACKR1 ."}
{"_id": "WikiPedia_Hematology$$$corpus_6704", "text": "Fy-a and Fy-b differ by in a single  amino acid  at position 42:  glycine  in Fy-a and  aspartic acid  in Fy-b ( guanine  in Fy-a and  adenosine  in Fy-b at position 125). A second mutation causing a Duffy negative phenotype is known: the responsible mutation is G -> A at position 298. The genetic basis for the Fy(a-b-) phenotype is a  point mutation  in the erythroid specific  promoter  (a T -> C mutation at position -33 in the  GATA box ). [ 11 ]  This mutation occurs in the Fy-b allele and has been designated Fy-b Es  (erythroid silent). Two isotypes have been identified. The Fy-x allele is characterized by a weak anti-Fy-b reaction and appears to be the result of two separate  transitions :  Cytosine 265 Threonine  ( Arginine 89 Cysteine ) and  Guanine 298 Adenosine  ( Alanine 100 Threonine ). A third mutation (a  transversion ) in this gene has also been described - G145T ( Alanine 49 Serine ) - that has been associated with the Fy-x phenotype."}
{"_id": "WikiPedia_Hematology$$$corpus_6705", "text": "Most Duffy negative  black people  carry a silent Fy-b  allele  with a single T to C substitution at  nucleotide  -33, impairing the  promoter  activity in erythroid cells by disrupting a binding site for the  GATA1  erythroid  transcription factor . The gene is still transcribed in non erythroid cells in the presence of this  mutation ."}
{"_id": "WikiPedia_Hematology$$$corpus_6706", "text": "The Duffy negative phenotype occurs at low frequency among whites (~3.5%) and is due to a third mutation that results in an unstable protein (Arg89Cys:  cytosine  ->  thymidine  at position 265). [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6707", "text": "The silent allele has evolved at least twice in the black population of Africa and evidence for selection for this allele has been found. [ 13 ]  The selection pressure involved here appears to be more complex than many text books might suggest. [ 14 ]  An independent evolution of this phenotype occurred in  Papua New Guinea  has also been documented. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6708", "text": "A comparative study of this gene in seven mammalian species revealed significant differences between species. [ 16 ]  The species examined included  Pan troglodytes  (chimpanzee),  Macaca mulatta  (rhesus monkey),  Pongo pygmaeus  (orangutan),  Rattus norvegicus  (brown rat),  Mus musculus  (mouse),  Monodelphis domestica  (opossum),  Bos taurus  (cow) and  Canis familiaris  (dog)."}
{"_id": "WikiPedia_Hematology$$$corpus_6709", "text": "Three exons are present in humans and chimpanzees, whereas only two exons occur in the other species. This additional exon is located at the 5' end and is entirely non coding. Both intron and exon size vary considerably between the species examined. Between the chimpanzee and the human, 24 differences in the nucleotide sequence were noted. Of these 18 occurred in non coding regions. Of the remaining 6, 3 were synonymous and 3 non synonymous mutations. The significance of these mutations if any is not known."}
{"_id": "WikiPedia_Hematology$$$corpus_6710", "text": "The mouse ortholog has been cloned and exhibits 63% homology to the human gene at the amino acid level. The mouse gene is located on chromosome 1 between the genetic markers Xmv41 and D1Mit166. The mouse gene has two exons (100 and 1064 nucleotides in length), separated by a 461 base pair intron. In the mouse DARC is expressed during embryonic development between days 9.5 and 12. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6711", "text": "In yellow baboons ( Papio cynocephalus ) mutations in this gene have been associated with protection from infection with species of the genus  Hepatocystis . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6712", "text": "The ancestral form of extant DARC alleles in humans appears to be the FY*B allele. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6713", "text": "The gene appears to be under strong purifying selection. [ 19 ]  The cause of this selective pressure has not yet been identified."}
{"_id": "WikiPedia_Hematology$$$corpus_6714", "text": "Biochemical analysis of the Duffy antigen has shown that it has a high content of \u03b1-helical secondary structure - typical of chemokine receptors. [ 20 ]  Its N-glycans are mostly of the triantennary complex type terminated with \u03b12-3- and \u03b12-6-linked sialic acid residues with bisecting GlcNAc and \u03b11-6-linked fucose at the core."}
{"_id": "WikiPedia_Hematology$$$corpus_6715", "text": "The Duffy antigen is expressed in greater quantities on  reticulocytes  than on mature erythrocytes. [ 21 ]   While the Duffy antigen is expressed on bone marrow  erythroblasts  and circulating  erythrocytes  it is also found on  Purkinje cells  of the  cerebellum , [ 22 ]  endothelial cells of  thyroid   capillaries , the post-capillary  venules  of some organs including the spleen, liver and kidney [ 23 ]  and the large pulmonary venules. Duffy antigen has then a very unique cell expression profile in cerebellar neurons, venular endothelial cells and erythroid cells. [ 24 ] \nIn some people who lack the Duffy antigen on their erythrocytes it is still expressed in the other cell types. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6716", "text": "It has two potential N-linked glycosylation sites at  asparagine  (Asn) 16 and Asn27."}
{"_id": "WikiPedia_Hematology$$$corpus_6717", "text": "The Duffy antigen has been found to act as a multispecific receptor for chemokines of both the C-C and C-X-C families, including:"}
{"_id": "WikiPedia_Hematology$$$corpus_6718", "text": "and the angiogenic CXC chemokines:"}
{"_id": "WikiPedia_Hematology$$$corpus_6719", "text": "Consequently, the Fy protein is also known as DARC (Duffy Antigen Receptor for Chemokines). The chemokine binding site on the receptor appears to be localised to the  amino terminus . [ 30 ]  The antigen is predicted to have 7 transmembrane domains, an exocellular N-terminal domain and an endocellular C-terminal domain. Alignment with other seven transmembrane  G-protein-coupled receptors  shows that DARC lacks the highly conserved DRY motif in the second intracellular loop of the  protein  that is known to be associated with G-protein signaling. Consistent with this finding ligand binding by DARC does not induce G-protein coupled signal transduction nor a Ca2+ flux unlike other chemokine receptors. Based on these alignments the Duffy antigen is considered to be most similar to the  interleukin-8B receptors ."}
{"_id": "WikiPedia_Hematology$$$corpus_6720", "text": "Scatchard analysis  of competition binding studies has shown high affinity binding to the Duffy antigen with dissociation constants (KD) binding values of 24 \u00b1 4.9, 20 \u00b1 4.7, 41.9 \u00b1 12.8, and 33.9 \u00b1 7 nanoMoles for MGSA, interleukin-8, RANTES and monocyte chemotactic peptide-1 respectively. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6721", "text": "In DARC-transfected cells, DARC is internalized following ligand binding and this led to the hypothesis that expression of DARC on the surface of erythrocytes,  endothelial , neuronal cells and  epithelial  cells may act as a sponge and provide a mechanism by which inflammatory chemokines may be removed from circulation as well as their concentration modified in the local environment. [ 32 ]   This hypothesis has also been questioned after  knock out  mice were created. These animals appeared healthy and had normal responses to infection. While the function of the Duffy antigen remains presently (2006) unknown, evidence is accumulating that suggests a role in  neutrophil  migration from the blood into the tissues [ 33 ]  and in modulating the inflammatory response. [ 34 ] [ 35 ] [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ] [ 41 ] [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6722", "text": "The protein is also known to interact with the protein KAI1 ( CD82 ) a surface glycoprotein of  leukocytes  and may have a role in the control of cancer."}
{"_id": "WikiPedia_Hematology$$$corpus_6723", "text": "The Duffy antigen has been shown to exist as a constitutive homo-oligomer and that it hetero-oligomerizes with the CC chemokine receptor CCR5 ( CD195 ). The formation of this heterodimer impairs  chemotaxis  and calcium flux through CCR5, whereas internalization of CCR5 in response to ligand binding remains unchanged. [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6724", "text": "DARC has been shown to internalise chemokines but does not scavenge them. [ 45 ]  It mediates chemokine transcytosis, which leads to apical retention of intact chemokines and more leukocyte migration."}
{"_id": "WikiPedia_Hematology$$$corpus_6725", "text": "Binding melanoma growth-stimulating activity inhibits the binding of  P. knowlesi  to DARC."}
{"_id": "WikiPedia_Hematology$$$corpus_6726", "text": "Differences in the racial distribution of the Duffy antigens were discovered in 1954, when it was found that the overwhelming majority of people of African descent had the  erythrocyte  phenotype Fy(a-b-): 68% in  African Americans  and 88-100% in African people (including more than 90% of  West African  people). [ 46 ]  This phenotype is exceedingly rare in Whites. Because the Duffy antigen is uncommon in those of  Black African  descent, the presence of this antigen has been used to detect  genetic admixture . In a sample of unrelated African Americans (n = 235), Afro-Caribbeans (n = 90) and Colombians (n = 93), the frequency of the -46T (Duffy positive) allele was 21.7%, 12.2% and 74.7% respectively. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6727", "text": "Overall the frequencies of Fya and Fyb antigens in Whites are 66% and 83% respectively, in Asians 99% and 18.5% respectively and in blacks 10% and 23% respectively. The frequency of Fy3 is 100% Whites, 99.9% Asians and 32% Blacks. Phenotype frequencies are:"}
{"_id": "WikiPedia_Hematology$$$corpus_6728", "text": "While a possible role in the protection of humans from malaria had been previously suggested, this was only confirmed clinically in 1976. [ 48 ]  Since then many surveys have been carried out to elucidate the prevalence of Duffy antigen alleles in different populations including:"}
{"_id": "WikiPedia_Hematology$$$corpus_6729", "text": "There appears to have been a selective sweep in Africa which reduced the incidence of this antigen there. This sweep appears to have occurred between 6,500 and 97,200 years ago (95% confidence interval) [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6730", "text": "The distribution within India has been studied in some detail. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6731", "text": "Historically the role of this antigen other than its importance as a receptor for  Plasmodium  protozoa has not been appreciated. Recent work has identified a number of additional roles for this protein."}
{"_id": "WikiPedia_Hematology$$$corpus_6732", "text": "On erythrocytes, the Duffy antigen acts as a  receptor  for invasion by the human  malarial  parasites  P. vivax  and  P. knowlesi . This was first shown in 1980. Duffy negative individuals whose erythrocytes do not express the receptor are believed to be resistant to merozoite invasion [ 65 ]  although  P. vivax  infection has been reported in Duffy negative children in Kenya, suggesting a role in resistance to disease, not infection. [ 65 ]  This antigen may also play a role in  erythrocyte  invasion in the rodent malarial parasite  P. yoelii . The  epitope  Fy6 is required for  P. vivax  invasion. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6733", "text": "The protection to  P. vivax  malaria conferred by the absence of the Duffy antigen appears to be very limited at best in  Madagascar . Although 72% of the population are Duffy antigen negative, 8.8% of the Duffy antigen negative individuals were  asymptomatic carriers  of  P. vivax . [ 66 ]  Malaria has also been found in  Angola  and  Equatorial Guinea  in Duffy negative individuals. [ 67 ]   P. vivax  malaria in a Duffy antigen negative individual in  Mauritania  has also been reported. [ 68 ]  Similar infections have been reported in Brazil [ 69 ] [ 70 ]  and  Kenya . [ 65 ]  Additional cases of infection in Duffy antigen negative individuals have been reported from the Congo [ 71 ]  and Uganda. [ 72 ]  A study in  Brazil  of the protection against  P. vivax  offered by the lack of the Duffy antigen found no differential resistance to malaria vivax between Duffy antigen positive and negative individuals. [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6734", "text": "Nancy Ma's night monkey ( A. nancymaae ) is used as an animal model of  P. vivax  infection. This species' erythrocytes possess the Duffy antigen and this antigen is used as the receptor for  P. vivax  on the erythrocytes in this species. [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6735", "text": "Examination of this gene in 497 patients in the  Amazonas State , Brazil, made by the doctor S\u00e9rgio Albuquerque, suggests that the genotypes FY*A/FY*B-33 and FY*B/FY*B-33 (where -33 refers to the null mutation at position -33 in the GATA box) may have an advantage over the genotypes FY*A/FY*B and FY*A/FY*A, FY*A/FY*B, FY*A/FY*X and FY*B/FY*X. [ 75 ]  FY*A/FY*B and FY*A/FY*A genotypes showed to be associated with increased rates of  P. vivax  infection and FY*B/FY*X and FY*A/FY*X were shown to be associated with the low levels of parasitism."}
{"_id": "WikiPedia_Hematology$$$corpus_6736", "text": "A difference between the susceptibility to  Plasmodium vivax  malaria has been reported. [ 76 ]  Erythrocytes expressing Fya had 41-50% lower binding of  P. vivax  compared with Fyb cells. Individuals with the Fy(a+b-) phenotype have a 30-80% reduced risk of clinical vivax but not falciparum malaria."}
{"_id": "WikiPedia_Hematology$$$corpus_6737", "text": "The binding of platelet factor 4 ( CXCL4 ) appears to be critical for the platelet induced killing of  P. falciparum . [ 77 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6738", "text": "The Duffy antigen binding protein in  P. vivax   is composed of three subdomains and is thought to function as a dimer. [ 78 ]  The critical DARC binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains."}
{"_id": "WikiPedia_Hematology$$$corpus_6739", "text": "A study in Brazil confirmed the protective effect of FY*A/FY*O against malaria. [ 79 ]  In contrast the genotype FY*B/FY*O was associated with a greater risk."}
{"_id": "WikiPedia_Hematology$$$corpus_6740", "text": "Asthma  is more common and tends to be more severe in those of African descent. There appears to be a correlation with both total  IgE  levels and asthma and mutations in the Duffy antigen. [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6741", "text": "Duffy antigen plays a fundamental role on  hematopoiesis . [ 81 ]  Indeed,  nucleated red blood cells  present in the bone marrow have high expression of DARC, which facilitates their direct contact with  hematopoietic stem cells . The absence of erythroid DARC alters hematopoiesis including stem and progenitor cells, which ultimately gives rise to phenotypically distinct neutrophils. As a result, mature neutrophils of Duffy-negative individuals carry more molecular \"weapons\" against infectious pathogens. [ 82 ]  Therefore, alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of DARC in the erythroid lineage. [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6742", "text": "Individuals with the Duffy-null genotype have a persistently lower  neutrophil  count than the typical laboratory normal range, [ 83 ]  but the lower amount of circulating neutrophils associated with this genotype does not seem to confer an increased risk of infection. [ 84 ] [ 85 ]   Clinical use of the term \"benign ethnic neutropenic\" to describe this phenomenon remains widespread, but the term is problematic as the Duffy-null genotype is common in individuals with African and certain Middle Eastern ancestries, and the term implies that individuals with European ancestry have the normal reference neutrophil count. [ 81 ] [ 82 ]   The term \"Duffy-null associated neutrophil count\" (DANC) has been proposed as a replacement. [ 86 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6743", "text": "The distinctive neutrophils that are formed in the absence of DARC on erythroid lineage (see above - role of DARC on hematopoiesis) readily leave the blood stream, which explains the apparent lower numbers of neutrophils in the blood of Duffy-null individuals. [ 81 ] [ 82 ]  Failure to recognize that individuals with African ancestry often have healthy Duffy-null antigen-associated neutrophil counts instead of neutropenia has historically contributed to inequity in access to medications that require blood monitoring due to risk of neutropenia, including chemotherapy and the antipsychotic medication clozapine. [ 87 ]  The lower number of circulating neutrophils can cause individuals with the Duffy-null genotype to fall below what typically would be considered safe to continue these treatments, despite new data showing that neutrophil functioning is preserved in these individuals. [ 88 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6744", "text": "Interactions between the metastasis suppressor  KAI1  on tumor cells and the cytokine receptor DARC on adjacent vascular cells suppresses tumor  metastasis . [ 89 ]  In human breast cancer samples low expression of the DARC protein is significantly associated with estrogen receptor status, both lymph node and distant metastasis and poor survival. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6745", "text": "The procoagulant response to lipopolysaccharide (bacterial endotoxin) is reduced in Duffy antigen negative Africans compared with Duffy positive Whites. [ 91 ]  This difference is likely to involve additional genes."}
{"_id": "WikiPedia_Hematology$$$corpus_6746", "text": "A connection has been found between  HIV  susceptibility and the expression of the Duffy antigen. The absence of the DARC receptor appears to increase the susceptibility to infection by HIV. However once established, the absence of the DARC receptor appears to slow down the progression of the disease. [ 92 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6747", "text": "HIV-1 appears to be able to attach to erythrocytes via DARC. [ 92 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6748", "text": "The association between the Duffy antigen and HIV infection appears to be complex.  Leukopenia  (a low total white cell count) is associated with relatively poor survival in HIV infection and this association is more marked in  whites  than in  people of Black African descent , despite the (on average) lower white cell counts found in black Africans. This difference appears to correlate with a particular genotype (-46C/C) associated with the absence of the Duffy antigen. [ 93 ]  This genotype has only been found in black Africans and their descendants. The strength of this association increases inversely with the total white cell count. The basis for this association is probably related to the role of the Duffy antigen in  cytokine  binding but this has yet to be verified."}
{"_id": "WikiPedia_Hematology$$$corpus_6749", "text": "A study of 142 black South African high-risk female sex workers over 2 years revealed a seroconversion rate of 19.0%. [ 94 ]  Risk of seroconversion appeared to be correlated with Duffy-null-associated low neutrophil counts."}
{"_id": "WikiPedia_Hematology$$$corpus_6750", "text": "An association with the levels  monocyte chemoattractant protein-1  has been reported. [ 95 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6751", "text": "In the  Sardinian population , an association of several variants in the DARC gene (coding and non-coding) correlates with increased serum levels of monocyte chemoattractant protein (MCP -1). A new variant in this population, consisting of the amino acid substitution of arginine for a cysteine at position 89 of the protein diminishes the ability to bind chemokines. [ 96 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6752", "text": "DARC has also been linked to rheumatoid arthritis (RA), possibly displaying chemokines such as CXCL5 on the surface of endothelial cells within the synovium, increasing the recruitment of neutrophils in the disease state. [ 97 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6753", "text": "The Duffy antigen has been implicated in lung transplantation rejection. [ 98 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6754", "text": "An increased incidence of Duffy antigen has been reported in patients with multiple myeloma compared with healthy controls. [ 99 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6755", "text": "The Duffy antigen is present in the normal pulmonary vascular bed. Its expression is increased in the vascular beds and alveolar septa of the lung parenchyma during suppurative pneumonia. [ 100 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6756", "text": "Duffy antigen has been implicated in haemolytic disease of the newborn."}
{"_id": "WikiPedia_Hematology$$$corpus_6757", "text": "Experimental work has suggested that DARC expression inhibits prostate tumor growth. Men of black African descent are at greater risk of prostate cancer than are men of either European or Asian descendant (60% greater incidence and double the mortality compared to Whites). However, the contribution of DARC to this increased risk has been tested in  Jamaican  males of black African descent. [ 101 ]  It was found that none of the increased risk could be attributed to the DARC gene. The reason for this increased risk is as yet unknown."}
{"_id": "WikiPedia_Hematology$$$corpus_6758", "text": "Antibodies and a cellular response to the Duffy antigen have been associated with renal transplant rejection. [ 102 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6759", "text": "Duffy antigen-negative individuals with  sickle cell anaemia  tend to sustain more severe organ damage than do those with the Duffy antigen. [ 103 ]  Duffy-positive patients exhibit higher counts of white blood cells, polynuclear neutrophils, higher plasma levels of IL-8 and RANTES than Duffy-negative patients. [ 104 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6760", "text": "There is a ~10% increase in Fy expression in  Southeast Asian ovalocytosis  erythrocytes. [ 105 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6761", "text": "A Duffy negative blood recipient may have a transfusion reaction if the donor is Duffy positive. [ 47 ]  Since most Duffy-negative people are of African descent, blood donations from people of black African origin are important to transfusion banks."}
{"_id": "WikiPedia_Hematology$$$corpus_6762", "text": "International Society for Blood Transfusion (ISBT) symbol: FY"}
{"_id": "WikiPedia_Hematology$$$corpus_6763", "text": "ISBT number: 008"}
{"_id": "WikiPedia_Hematology$$$corpus_6764", "text": "Gene symbol: FY"}
{"_id": "WikiPedia_Hematology$$$corpus_6765", "text": "Gene name: Duffy blood group"}
{"_id": "WikiPedia_Hematology$$$corpus_6766", "text": "Number of Duffy antigens: 6"}
{"_id": "WikiPedia_Hematology$$$corpus_6767", "text": "Almost entirely IgG. IgG1 usually predominates.  IgM does occur but is rare."}
{"_id": "WikiPedia_Hematology$$$corpus_6768", "text": "Anti-Fy a  is a common antibody while anti-Fy b  is approximately 20 times less common., [ 106 ] [ 107 ]  They are reactive at body temperature and are therefore clinically significant, although they do not typically bind complement.  Antibodies are acquired through exposure (pregnancy or history of blood transfusion) and subsequent alloimmunization. They display dosage (react more strongly to homozygous cells versus heterozygous cells). [ 106 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6769", "text": "Typically mild but may be serious, even fatal. Although these usually occur immediately they may occur after a delay (up to 24 hours). These reactions are usually caused by anti-Fy a  or anti-Fy b . anti-Fy3 may cause acute or delayed  hemolytic transfusion reactions , but only rarely. Anti-Fy5 may also cause delayed hemolytic transfusion reactions. [ 106 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6770", "text": "Hemolytic disease of the fetus and newborn  is typically mild but rarely may be serious. Almost always due to anti-Fy a  and rarely anti-Fyb or Fy3."}
{"_id": "WikiPedia_Hematology$$$corpus_6771", "text": "Emergency bleeding control  describes actions that control  bleeding  from a  patient  who has suffered a  traumatic injury  or who has a medical condition that has caused bleeding. Many bleeding control techniques are taught as part of  first aid  throughout the world. [ 1 ]  Other advanced techniques, such as  tourniquets , are taught in advanced first aid courses and are used by  health professionals  to prevent blood loss by arterial bleeding. [ 2 ]  To manage bleeding effectively, it is important to be able to readily identify types of wounds and types of bleeding."}
{"_id": "WikiPedia_Hematology$$$corpus_6772", "text": "Wounds are normally described in a variety of ways.  Descriptions may include wound size (length) and thickness; plainly visible wound characteristics such as shape and open or closed; and origin, acute or chronic. [ 3 ]   The most common descriptors of wounds are these:"}
{"_id": "WikiPedia_Hematology$$$corpus_6773", "text": "External bleeding is generally described in terms of the origin of the blood flow by vessel type.  The basic categories of external  bleeding  are:"}
{"_id": "WikiPedia_Hematology$$$corpus_6774", "text": "The treatment of wounds depends on whether they are external or internal."}
{"_id": "WikiPedia_Hematology$$$corpus_6775", "text": "The  type of wound  ( incision ,  laceration ,  puncture , etc.) has a major effect on the way a wound is managed, as does the area of the body affected and presence of any foreign objects in the wound. A serious wound or any complication may require a call to  emergency medical services . Any wound requires being disinfected after it stops bleeding. The eyes and other delicate tissue require special products for disinfection."}
{"_id": "WikiPedia_Hematology$$$corpus_6776", "text": "Main methods of wound management are: [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6777", "text": "Direct pressure is the common method. The pressure on the wound constricts the blood vessels manually, helping to stem blood flow.  When applying pressure, the type and direction of the wound may have an effect, for instance, a cut lengthways on the hand would be opened up by closing the hand into a fist, whilst a cut across the hand would be sealed by making a fist. A patient can apply pressure directly to their own wound, if their level of  consciousness  allows."}
{"_id": "WikiPedia_Hematology$$$corpus_6778", "text": "Ideally, a barrier, such as sterile, low-adherent gauze should be used between the pressure supplier and the wound, to help reduce chances of  infection  and help the wound to seal. Third parties assisting a patient are always advised to use protective  latex  or  nitrile   medical gloves  to reduce risk of infection or contamination passing either way."}
{"_id": "WikiPedia_Hematology$$$corpus_6779", "text": "Direct pressure can be used with some foreign objects protruding from a wound. Then, padding is applied from each side of the object to push in and seal the wound. The foreign objects are not removed until arriving to a medical center."}
{"_id": "WikiPedia_Hematology$$$corpus_6780", "text": "Elevation was commonly recommended for the control of haemorrhage. Some protocols continue to include it, but recent studies have failed to find any evidence of its effectiveness and it was removed from the  PHTLS  guidance in 2006. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6781", "text": "The cold can add some utility, at least to compress the blood vessels."}
{"_id": "WikiPedia_Hematology$$$corpus_6782", "text": "In situations where direct pressure and elevation are either not possible or proving ineffective, and there is a risk of  exsanguination , some training protocols advocate the use of pressure points to constrict the major artery that feeds the point of the bleed.  This is usually performed at a place where a  pulse  can be found, such as in the  femoral artery . [ 15 ]   There are significant risks involved in performing pressure point constriction, including  necrosis  of the area below the constriction, and most protocols give a maximum time for constriction (often around 10 minutes).  There is particularly high danger if constricting the  carotid artery  in the neck, as the brain is sensitive to  hypoxia  and brain damage can result within minutes of application of pressure. Pressure on the carotid artery can also cause vagal tone induced bradycardia, which can eventually stop the heart. Other dangers in use of a constricting method include  rhabdomyolysis , which is a buildup of toxins below the pressure point, which if released back into the main bloodstream may cause  kidney failure . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6783", "text": "Another method of achieving constriction of the supplying artery is a  tourniquet  - a band tied tightly around a limb to restrict blood flow.  Tourniquets are routinely used to bring  veins  to the surface for  cannulation , though their use in emergency medicine is more limited.  Many armies carry a tourniquet as part of their personal first aid kit."}
{"_id": "WikiPedia_Hematology$$$corpus_6784", "text": "Improvised tourniquets, in addition to creating potential problems for the ongoing medical management of the patient, usually fail to achieve force enough to adequately compress the arteries of the limb.  As a result, they not only fail to stop arterial bleeding, but may actually increase bleeding by impairing venous bloodflow. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6785", "text": "Some protocols call for the use of clotting accelerating agents, which can be either externally applied as a powder or gel, or pre-dosed in a dressing or as an  intravenous  injection. These may be particularly useful in situations where the wound is not clotting, which can be due to external factors, such as size of wound, or medical factors such as  haemophilia . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6786", "text": "For stopping or preventing bleeding in people who do not have haemophilia, there is weak to little evidence to support the use of clotting factors to prevent death. [ 18 ]  Prophylactic fibrinogen may reduce the risk of bleeding after heart or orthoscopic surgery and prophylactic factor XII may be effective after heart surgery, however, both medications require high-quality randomized clinical trials to understand more about the potential benefits and risks. [ 18 ]   Recombinant factor VIIa ( rFVIIa ) is not, as of 2012, supported by the evidence for most cases of major bleeding. [ 19 ]  Its use brings a significant risk of arterial thrombosis, and therefore it should only be used in clinical trials or with patients with  factor VII deficiency . [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6787", "text": "A new product of this type (Cresilon Hemostatic Gel or  CHG ,  Vetigel  in its veterenary version) [ 21 ] [ 22 ]  allows to close great wounds in a few moments."}
{"_id": "WikiPedia_Hematology$$$corpus_6788", "text": "Internal wounds (usually to the  torso ) are harder to deal with than external wounds, although they often have an external cause. The key dangers of internal bleeding include  hypovolaemic shock  (leading to  exsanguination ), a  tamponade  on the heart or a  haemothorax  on the lung. The  aortic aneurysm  is a special case where the  aorta , the body's main blood vessel, becomes ruptured through an inherent weakness, although exertion, raised blood pressure or sudden movements could cause a sudden catastrophic failure. [ 23 ]  This is one of the most serious  medical emergencies  a patient can face, as the only treatment is rapid surgery."}
{"_id": "WikiPedia_Hematology$$$corpus_6789", "text": "An internal bleeding require to  call to emergency medical services ."}
{"_id": "WikiPedia_Hematology$$$corpus_6790", "text": "In the event of bleeding caused by an external source (trauma, penetrating wound), the patient is usually inclined to the injured side, so that the 'good' side can continue to function properly, without interference from the blood inside the body cavity. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6791", "text": "Use of cold around the damaged area (for example: with ice) can help to compress the blood vessels."}
{"_id": "WikiPedia_Hematology$$$corpus_6792", "text": "Treatment of internal bleeding is beyond the scope of simple first aid, and a person giving first aid should consider it potentially life-threatening.  The definitive treatment for internal bleeding is always surgical treatment, and medical advice must be sought urgently for any victim of internal bleeding. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6793", "text": "The  Er blood group system  consists of five human  red blood cell  surface  antigens , Er a , Er b , Er3, Er4 and Er5. [ 1 ]  The incidences of Er a  and Er3 are each greater than 99% of the human population, while the incidence of Er b  is less than 0.01%. [ 2 ] [ 3 ]  Er4 and Er5 are found at a high frequency in the general population. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6794", "text": "Individuals with  antibodies  against Er3 may develop  acute hemolytic transfusion reaction  upon transfusion with an incompatible unit, while Er a  and Er b  are unlikely to be clinically significant. [ 4 ]  The clinical significance of antibodies against Er4 and Er5 is poorly understood due to a lack of data, but two cases of severe  hemolytic disease of the fetus and newborn  have been reported in women with these antibodies. [ 1 ]  Expression of the Er blood group antigens is controlled by the gene  PIEZO1 . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6795", "text": "Er a  was first identified in 1982 and Er b  was identified in 1988. [ 2 ]  Er was recognized as a blood group collection by the  International Society of Blood Transfusion  in 1990 [ 2 ]  and promoted to a blood group in 2022. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6796", "text": "An  exchange transfusion  is a  blood transfusion  in which the  patient 's  blood  or components of it are exchanged with (replaced by) other blood or  blood products . [ 1 ]  The patient's blood is removed and replaced by donated blood or blood components. This exchange transfusion can be performed manually or using a machine ( apheresis ). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6797", "text": "Most blood transfusions involve adding blood or blood products without removing any blood, these are also known as  simple transfusions  or  top-up transfusions . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6798", "text": "Exchange transfusion is used in the treatment of a number of  diseases , including  sickle-cell disease  and  hemolytic disease of the newborn . Partial exchange might be required for  polycythemia ."}
{"_id": "WikiPedia_Hematology$$$corpus_6799", "text": "Nearly all exchange transfusions are  allogeneic  (that is, the new blood or blood products come from another person or persons, via donated blood);  autologous  exchange transfusion is possible (using autologous blood banking), but there are not many situations in which a need for it arises, as most autologous transfusions involve no exchange."}
{"_id": "WikiPedia_Hematology$$$corpus_6800", "text": "An exchange transfusion requires that the patient's blood can be removed and replaced. In most cases, this involves placing one or more thin tubes, called catheters, into a blood vessel. The exchange transfusion is done in cycles: each one usually lasts a few minutes. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6801", "text": "The patient\u2019s blood is slowly withdrawn (usually about 5 to 20 mL at a time, depending on the patient\u2019s size and the severity of illness), and a slightly larger amount of fresh, prewarmed blood or plasma flows into the patient's body. This cycle is repeated until the correct volume of blood has been replaced. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6802", "text": "After the exchange transfusion, catheters may be left in place in case the procedure needs to be repeated."}
{"_id": "WikiPedia_Hematology$$$corpus_6803", "text": "In diseases such as  sickle cell anemia , blood is removed and replaced with donor blood. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6804", "text": "In conditions such as neonatal polycythemia, a specific amount of the child\u2019s blood is removed and replaced with normal saline, plasma (the clear liquid portion of blood), or an albumin solution. This decreases the total number of red blood cells in the body and makes it easier for blood to flow through the body. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6805", "text": "Transfusion therapy  is used as an emergency procedure to treat life-threatening complications of  sickle-cell disease  as well as an elective procedure to stop these complications occurring. [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6806", "text": "The commonest emergency reason is to treat an acute chest syndrome. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6807", "text": "The most common routine reason is to prevent a stroke occurring or re-occurring. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6808", "text": "Exchange transfusion to treat  hemolytic disease of the newborn  is now uncommon since the introduction of  Anti-D prophylaxis  in pregnancy. However, it can occur due to the development of other antibodies such as  anti-c ,  anti-E , and  ABO . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6809", "text": "Polycythemia , a condition in which the number of red cells in the blood is too high, is usually diagnosed when the  hematocrit  is above 65%. [ 8 ] [ 9 ]  Polycythemia can occur in neonates for multiple different reasons including: babies born after 42 weeks gestation (post-term), babies born to diabetic mothers,  twin to twin transfusion ,  intrauterine growth restriction , and babies with genetic abnormalities. [ 8 ]  Polycythemia can make the blood thicker than normal and therefore lead to complications. Partial exchange transfusion has been used as a treatment to prevent complications, and has been shown to improve cerebral blood flow, [ 10 ]  but there is no evidence that it prevents long-term complications. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6810", "text": "Exchange transfusion has been used for the treatment of severe  malaria  in the past. [ 11 ] [ 12 ]  However, in 2013 the CDC examined the limited evidence available and found no evidence that exchange transfusion has any beneficial effects (decreased mortality) in people with very high parasite loads (> 10%). [ 12 ]  Also, although uncommon, exchange transfusion can cause complications (low blood pressure ( hypotension ), abnormal heart rhythms ( ventricular fibrillation ) and breathing problems ( acute respiratory distress syndrome )). [ 12 ]  Based on this evidence, the CDC no longer recommend the use of exchange transfusion in the treatment of malaria. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6811", "text": "General risks are the same as with any transfusion. Other possible complications include: [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6812", "text": "The person may need to be monitored for several days in the hospital after the transfusion, but the length of stay generally depends on the condition for which the exchange transfusion was performed. Sickle Cell Disease patients may be exchanged in an outpatient setting and can be sent home the very same day. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6813", "text": "The technique was originally developed by  Alexander S. Wiener , soon after he co-discovered the  Rh factor [ broken anchor ] . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6814", "text": "Febrile non-hemolytic transfusion reaction (FNHTR)  is the most common type of  transfusion reaction . It is a benign occurrence with symptoms that include  fever  but not directly related with  hemolysis . [ 1 ]  It is caused by  cytokine  release from leukocytes within the donor product as a consequence of white blood cell breakdown. [ 2 ] [ 3 ] [ 4 ]  These inflammatory mediators accumulate during the storage of the donated blood, [ 5 ]  and so the frequency of this reaction increases with the storage length of donated blood. [ 6 ]  This is in contrast to  transfusion-associated acute lung injury , in which the donor plasma has antibodies directed against the recipient HLA antigens, mediating the characteristic lung damage. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6815", "text": "Symptoms must manifest within 4 hours of cessation of the transfusion, and should not be due to another cause such as an underlying infection, bacterial contamination of the blood component, or another type of transfusion reaction, e.g.  acute hemolytic transfusion reaction . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6816", "text": "Fever must be at least 38\u00a0\u00b0C/100.4\u00a0\u00b0F oral and a change of at least 1\u00a0\u00b0C/1.8\u00a0\u00b0F from pre-transfusion value OR chills and/or rigors must be present. [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6817", "text": "The UK hemovigilance system ( SHOT ) categorizes the severity of the reaction. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6818", "text": "Fever of at least 38\u00a0\u00b0C/100.4\u00a0\u00b0F oral and a change of between 1 and 2\u00a0\u00b0C from pre-transfusion values but no other symptoms or signs. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6819", "text": "Fever of at least 39\u00a0\u00b0C, OR a rise in temperature of at least 2\u00a0\u00b0C from pre-transfusion values AND/OR other symptoms or signs, including chills ( rigors ), painful muscles ( myalgia ), or  nausea  that are severe enough that the transfusion is stopped. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6820", "text": "Fever of at least 39\u00a0\u00b0C, OR a rise in temperature of at least 2\u00a0\u00b0C from pre-transfusion values AND/OR other symptoms or signs, including chills ( rigors ), painful muscles ( myalgia ), or  nausea  that are severe enough that the transfusion is stopped AND requires immediate medical treatment, admission to hospital, or lengthens the duration of hospital admission. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6821", "text": "Paracetamol  has been used in treatment, and  leukoreduction  of future transfusions is sometimes performed. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6822", "text": "Fresh frozen plasma  ( FFP ) is a  blood product  made from the liquid portion of  whole blood . [ 3 ]  It is used to treat conditions in which there are low  blood clotting factors  (INR > 1.5) or low levels of other  blood proteins . [ 3 ] [ 1 ]  It may also be used as the replacement fluid in  plasma exchange . [ 2 ] [ 4 ]  Using  ABO compatible  plasma, while not required, may be recommended. [ 5 ] [ 6 ]  Use as a  volume expander  is not recommended. [ 3 ]  It is administered by  slow injection into a vein . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6823", "text": "Side effects include nausea and itchiness. [ 3 ]  Rarely there may be  allergic reactions ,  blood clots , or  infections . [ 1 ] [ 3 ]  It is unclear if use during  pregnancy  or  breastfeeding  is safe for the baby. [ 2 ]  Greater care should be taken in people with  protein S deficiency ,  IgA deficiency , or  heart failure . [ 2 ]  Fresh frozen plasma is made up of a complex mixture of water,  proteins ,  carbohydrates , fats, and  vitamins . [ 1 ]  When frozen it lasts about a year. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6824", "text": "Plasma first came into medical use during the  Second World War . [ 1 ]  It is on the  World Health Organization's List of Essential Medicines . [ 7 ]  In the United Kingdom it costs about \u00a330 per unit. [ 8 ]  A number of other versions also exist including  plasma frozen within 24 hours after phlebotomy ,  cryoprecipitate reduced plasma , thawed plasma, and  solvent detergent plasma . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6825", "text": "In the United States it refers to the fluid portion of one unit of  whole blood  that has been centrifuged, separated, and frozen solid at \u221218\u00a0\u00b0C (0\u00a0\u00b0F) or colder within eight hours of collection from whole blood donation or was otherwise collected via apheresis device. [ 9 ]  The phrase \"FFP\" is often used to mean any transfused plasma product. The other commonly transfused plasma, plasma frozen within 24 hours after phlebotomy ( PF24 ), has similar indications as those for FFP. PF24 has slightly lower levels of Factors V and VIII than FFP. PF24 is more commonly used than FFP in the United States."}
{"_id": "WikiPedia_Hematology$$$corpus_6826", "text": "There are few specific indications for FFP. These generally are limited to the treatment of deficiencies of coagulation proteins for which specific factor concentrates are unavailable or undesirable. A usual dose of plasma is 10\u201320 mL/kg recipient weight. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6827", "text": "Indications for the use of FFP include the following:"}
{"_id": "WikiPedia_Hematology$$$corpus_6828", "text": "FFP is not recommended unless there is ongoing bleeding or there is a significant blood clotting problem. That is, FFP is not used in people to reverse warfarin if there is no bleeding, even for an INR >\u00a09 unless they need urgent surgery. It is also not used in elective surgery, or non-emergency surgery. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6829", "text": "Thawed plasma is made from FFP or PF24 and kept refrigerated (at 1\u20136\u00a0\u00b0C) after thawing can be stored for 5 days post thaw. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6830", "text": "Prophylactic plasma  transfusions  might have an effect for people with a blood clotting disorder and receive an invasive procedure."}
{"_id": "WikiPedia_Hematology$$$corpus_6831", "text": "For people with a blood clotting disorder and receive a planned invasive non-cardiac procedure it is not certain if prophylactic plasma transfusions improve all-cause mortality up to 30 days, major bleeding within 24 hours, number of transfusions per participants within one week, number of individuals requiring a transfusion within one week and serious adverse events measured by plasma-related complications within 24 hours. [ 14 ]   Different triggers for fresh frozen plasma may have little to no effect on major bleeding within 24 hours and serious adverse events measured by plasma transfusion-related complications within 24 hours. Furthermore, different triggers for fresh frozen plasma may reduce the number of individuals requiring a transfusion within 7 days. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6832", "text": "The risks of FFP include disease transmission, anaphylactoid reactions, and excessive intravascular volume (transfusion associated circulatory overload (TACO)), as well as  transfusion related acute lung injury  (TRALI). Risks of transfusion transmitted infections are similar to that of whole blood and red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_6833", "text": "FFP is made by  centrifugation  of whole blood or apheresis device followed by freezing and preservation."}
{"_id": "WikiPedia_Hematology$$$corpus_6834", "text": "The use of plasma and its products has evolved over a period of four decades. The use of FFP has increased tenfold in the United States between the years 2000 and 2010 and has reached almost 2 million units annually. [ citation needed ]  This trend may be attributable to multiple factors, possibly including decreased availability of whole blood due to widespread acceptance of the concept of component therapy."}
{"_id": "WikiPedia_Hematology$$$corpus_6835", "text": "Evidence indicates that other plasma components (e.g., single-donor plasma) that do not meet the criteria of FFP may have adequate levels of coagulation factors and are suitable for patients in whom FFP is indicated. Single-donor plasma is efficacious in the treatment of mild deficiencies of stable clotting factors. It also is of value in treatment of multiple deficiencies as in reversal of warfarin effects or in liver disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6836", "text": "Safe and effective alternative treatment often exists so that FFP is no longer the therapy of choice in many conditions.  Cryoprecipitate  or fibrinogen concentrates should be used when fibrinogen is needed. For treatment of  hemophilia A , recombinant factor VIII concentrates are available. For treatment of severe  hemophilia B , recombinant factor IX concentrates are available."}
{"_id": "WikiPedia_Hematology$$$corpus_6837", "text": "Crystalloid or colloid solutions such as  human serum albumin  or plasma protein fraction, are preferable to FFP for volume replacement."}
{"_id": "WikiPedia_Hematology$$$corpus_6838", "text": "For nutritional support,  amino acid  solutions and  dextrose  are available. [ citation needed ]  The most important alternative to the use of FFP is a comprehensive program of blood conservation. This includes measures such as  intraoperative cell salvage [ 10 ]  and the realization that in many patients  normovolemic anemia  is not an indication for transfusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6839", "text": "Gastrointestinal bleeding  ( GI bleed ), also called  gastrointestinal hemorrhage  ( GIB ), is all forms of  bleeding  in the  gastrointestinal tract , from the  mouth  to the  rectum . [ 9 ]  When there is significant  blood  loss over a short time, symptoms may include  vomiting red blood ,  vomiting black blood ,  bloody stool , or  black stool . [ 1 ]  Small amounts of bleeding over a long time may cause  iron-deficiency anemia  resulting in  feeling tired  or  heart-related chest pain . [ 1 ]  Other symptoms may include  abdominal pain ,  shortness of breath ,  pale skin , or  passing out . [ 1 ] [ 9 ]  Sometimes in those with small amounts of bleeding no symptoms may be present. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6840", "text": "Bleeding is typically divided into two main types:  upper gastrointestinal bleeding  and  lower gastrointestinal bleeding . [ 2 ]  Causes of upper GI bleeds include:  peptic ulcer  disease,  esophageal varices  due to liver  cirrhosis  and  cancer , among others. [ 3 ]   Causes of lower GI bleeds include:  hemorrhoids , cancer, and  inflammatory bowel disease  among others. [ 2 ] [ 1 ]  Small amounts of bleeding may be detected by  fecal occult blood  test. [ 1 ]   Endoscopy  of the lower and upper gastrointestinal tract may locate the area of bleeding. [ 1 ]   Medical imaging  may be useful in cases that are not clear. [ 1 ]  Bleeding may also be diagnosed and treated during  minimally invasive   angiography  procedures such as  hemorrhoidal artery embolization . [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6841", "text": "Initial treatment focuses on  resuscitation  which may include  intravenous fluids  and  blood transfusions . [ 4 ]  Often blood transfusions are not recommended unless the  hemoglobin  is less than 70 or 80\u00a0g/L. [ 7 ] [ 12 ]  Treatment with  proton pump inhibitors ,  octreotide , and  antibiotics  may be considered in certain cases. [ 5 ] [ 6 ] [ 13 ]  If other measures are not effective, an  esophageal balloon  may be attempted in those with presumed esophageal varices. [ 2 ]   Endoscopy of the esophagus, stomach, and duodenum  or  endoscopy of the large bowel  are generally recommended within 24\u00a0hours and may allow treatment as well as diagnosis. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6842", "text": "An upper GI bleed is more common than lower GI bleed. [ 2 ]  An upper GI bleed occurs in 50 to 150 per 100,000 adults per year. [ 8 ]  A lower GI bleed is estimated to occur in 20 to 30 per 100,000 per year. [ 2 ]  It results in about 300,000 hospital admissions a year in the  United States . [ 1 ]  Risk of death from a GI bleed is between 5% and 30%. [ 1 ] [ 7 ]  Risk of bleeding is more common in males and increases with age. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6843", "text": "Gastrointestinal bleeding can be roughly divided into two clinical syndromes:  upper gastrointestinal bleeding  and  lower gastrointestinal bleeding . [ 2 ]  About 2/3 of all GI bleeds are from upper sources and 1/3 from lower sources. [ 14 ]  Common causes of gastrointestinal bleeding include  infections ,  cancers , vascular disorders, adverse effects of medications, and  blood clotting disorders . [ 2 ]  Obscure gastrointestinal bleeding (OGIB) is when a source is unclear following investigation. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6844", "text": "Upper gastrointestinal bleeding is from a source between the  pharynx  and the  ligament of Treitz . An upper source is characterised by  hematemesis  (vomiting up blood) and  melena  (tarry stool containing altered blood). About half of cases are due to  peptic ulcer disease  ( gastric  or  duodenal ulcers ). [ 3 ]   Esophageal inflammation  and erosive disease are the next most common causes. [ 3 ]  In those with  liver cirrhosis , 50\u201360% of bleeding is due to  esophageal varices . [ 3 ]  Approximately half of those with peptic ulcers have an  H. pylori  infection. [ 3 ]  Other causes include  Mallory-Weiss tears , cancer, and  angiodysplasia . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6845", "text": "A number of medications are found to cause upper GI bleeds. [ 16 ]   NSAIDs  or  COX-2 inhibitors  increase the risk about fourfold. [ 16 ]   SSRIs ,  corticosteroids , and  anticoagulants  may also increase the risk. [ 16 ]  The risk with  dabigatran  is 30% greater than that with  warfarin . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6846", "text": "Lower gastrointestinal bleeding is typically from the colon, rectum or anus. [ 2 ]  Common causes of lower gastrointestinal bleeding include  hemorrhoids , cancer, angiodysplasia,  ulcerative colitis ,  Crohn's disease , and  aortoenteric fistula . [ 2 ]  It may be indicated by the passage of  fresh red blood rectally , especially in the absence of  bloody vomiting . Lower gastrointestinal bleeding could also lead to melena if the bleeding occurs in the small intestine or proximal colon. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6847", "text": "Gastrointestinal bleeding can range from small non-visible amounts, which are only detected by laboratory testing, to massive bleeding where bright red blood is passed and  shock  develops. Rapid bleeding may cause  syncope . [ 18 ]  The presence of bright red blood in stool, known as  hematochezia , typically indicates lower gastrointestinal bleeding. Digested blood from the upper gastrointestinal tract may appear black rather than red, resulting in \"coffee ground\" vomit or melena. [ 2 ]  Other signs and symptoms include  feeling tired ,  dizziness , and pale skin color. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6848", "text": "A number of foods and medications can turn the stool either red or black in the absence of bleeding. [ 2 ]   Bismuth  found in many antacids may turn stools black as may  activated charcoal . [ 2 ]  Blood from the vagina or urinary tract may also be confused with blood in the stool. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6849", "text": "Diagnosis is often based on direct observation of blood in the stool or vomit.  Although  fecal occult blood  testing has been used in an emergency setting, this use is not recommended as the test has only been validated for colon cancer screening. [ 19 ]  Differentiating between upper and lower bleeding in some cases can be difficult. The severity of an upper GI bleed can be judged based on the  Blatchford score [ 4 ]  or  Rockall score . [ 16 ]  The Rockall score is the more accurate of the two. [ 16 ]  As of 2008 there is no scoring system useful for lower GI bleeds. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6850", "text": "Gastric aspiration and or lavage , where a tube is inserted into the stomach via the nose in an attempt to determine if there is blood in the stomach, if negative does not rule out an upper GI bleed [ 20 ]  but if positive is useful for ruling one in. [ 14 ]  Clots in the stool indicate a lower GI source while melana stools an upper one. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6851", "text": "Recommended laboratory blood testing includes: cross-matching blood, hemoglobin, hematocrit, platelets, coagulation time, and electrolytes. [ 4 ]  If the ratio of  blood urea nitrogen  to  creatinine  is greater than 30 the source is more likely from the upper GI tract. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6852", "text": "A  CT angiography  is useful for determining the exact location of the bleeding within the gastrointestinal tract. [ 21 ]  Nuclear scintigraphy is a sensitive test for detecting occult gastrointestinal bleeding when direct imaging with upper and lower endoscopies are negative. Direct angiography allows for embolization of a bleeding source, but requires a bleeding rate faster than 1mL/minute. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6853", "text": "In patients with significant varices or cirrhosis  nonselective \u03b2-blockers  reduce the risk of future bleeding. [ 13 ]  With a target heart rate of 55\u00a0beats per minute B-blockers reduce the absolute risk of bleeding by 10%. [ 13 ]   Endoscopic band ligation  (EBL) is also effective at improving outcomes. [ 13 ]  Either B-blockers or EBL is recommended as initial preventative measures. [ 13 ]  In patients who have had a previous variceal bleed both treatments are recommended. [ 13 ]  Some evidence supports the addition of  isosorbide mononitrate . [ 23 ]  Testing for and treating those who are positive for  H. pylori  is recommended. [ 16 ]   Transjugular intrahepatic portosystemic shunting  (TIPS) may be used to prevent bleeding in people who re-bleed despite other measures. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6854", "text": "Among patients admitted to the ICU with high risk of bleeding, a PPI or H2RA appears useful. [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6855", "text": "The initial focus is on  resuscitation  beginning with airway management and fluid resuscitation using either intravenous fluids and or blood. [ 4 ]  A number of medications may improve outcomes depending on the source of the bleeding. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6856", "text": "Based on evidence from people with other health problems  crystalloid  and  colloids  are believed to be equivalent for peptic ulcer bleeding. [ 4 ]   Proton pump inhibitor  (PPI) treatment before endoscopy may decrease the need for endoscopic hemostatic treatment, however it is not clear if this treatment reduces mortality, the risk of re-bleeding, or the  [ clarification needed ]  and the need for surgery. [ 26 ]  Oral and intravenous formulations may be equivalent; however, the evidence to support this is suboptimal. [ 27 ]  In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance. [ 26 ]  There is tentative evidence of benefit for  tranexamic acid  which inhibits clot breakdown. [ 28 ]   Somatostatin  and  octreotide , while recommended for varicial bleeding, have not been found to be of general use for non variceal bleeds. [ 4 ]  After treatment of a high risk bleeding ulcer endoscopically giving a PPI once or a day rather than as an infusion appears to work just as well and is less expensive (the method may be either by mouth or intravenously). [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6857", "text": "For initial fluid replacement, colloids or  albumin  is preferred in people with cirrhosis. [ 4 ]  Medications typically include  octreotide  or, if not available,  vasopressin  and  nitroglycerin  to reduce portal venous pressures. [ 13 ]   Terlipressin  appears to be more effective than octreotide, but it is not available in many areas of the world. [ 16 ] [ 30 ]  It is the only medication that has been shown to reduce mortality in acute variceal bleeding. [ 30 ]  This is in addition to  endoscopic banding  or  sclerotherapy  for the varices. [ 13 ]  If this is sufficient then  beta blockers  and  nitrates  may be used for the prevention of re-bleeding. [ 13 ]  If bleeding continues, balloon tamponade with a  Sengstaken-Blakemore tube  or  Minnesota tube  may be used in an attempt to mechanically compress the varices. [ 13 ]  This may then be followed by a  transjugular intrahepatic portosystemic shunt . [ 13 ]  In those with cirrhosis,  antibiotics  decrease the chance of bleeding again, shorten the length of time spent in hospital, and decrease mortality. [ 5 ]  Octreotide reduces the need for blood transfusions [ 31 ]  and may decrease mortality. [ 32 ]  No trials of  vitamin K  have been conducted. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6858", "text": "The evidence for benefit of blood transfusions in GI bleed is poor with some evidence finding harm. [ 8 ]  In those in  shock   O-negative packed red blood cells  are recommended. [ 2 ]  If large amounts of pack red blood cells are used additional  platelets  and  fresh frozen plasma  (FFP) should be administered to prevent  coagulopathies . [ 4 ]  In  alcoholics  FFP is suggested before confirmation of a coagulopathy due to presumed blood clotting problems. [ 2 ]  Evidence supports holding off on blood transfusions in those who have a  hemoglobin  greater than 7 to 8 g/dL and moderate bleeding, including in those with preexisting  coronary artery disease . [ 7 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6859", "text": "If the INR is greater than 1.5 to 1.8 correction with fresh frozen plasma or  prothrombin complex  may decrease mortality. [ 4 ]  Evidence of a harm or benefit of  recombinant activated factor VII  in those with liver diseases and gastrointestinal bleeding is not determined. [ 34 ]  A  massive transfusion protocol  may be used, but there is a lack of evidence for this indication. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6860", "text": "The benefits versus risks of placing a  nasogastric tube  in those with upper GI bleeding are not determined. [ 4 ]  Endoscopic evaluation within 24\u00a0hours is recommended, [ 4 ]  in addition to medical management. [ 35 ]  A number of endoscopic treatments may be used, including:  epinephrine  injection, band ligation, sclerotherapy, and fibrin glue depending on what is found. [ 2 ]  Prokinetic agents such as  erythromycin  before endoscopy can decrease the amount of blood in the stomach and thus improve the operators view. [ 4 ]  They also decrease the amount of blood transfusions required. [ 36 ]  Early endoscopy decreases hospital and the amount of blood transfusions needed. [ 4 ]  A second endoscopy within a day is routinely recommended by some [ 16 ]  but by others only in specific situations. [ 22 ]  Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found. [ 4 ]  High and low dose PPIs appear equivalent at this point. [ 37 ]  It is also recommended that people with high risk signs are kept in hospital for at least 72\u00a0hours. [ 4 ]  Those at low risk of re-bleeding may begin eating typically 24 hours following endoscopy. [ 4 ]  If other measures fail or are not available,  esophageal balloon tamponade  may be attempted. [ 2 ]  While there is a success rate up to 90%, there are some potentially significant complications including  aspiration  and  esophageal perforation . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6861", "text": "Colonoscopy  is useful for the diagnosis and treatment of lower GI bleeding. [ 2 ]  A number of techniques may be employed including clipping, cauterizing, and sclerotherapy. [ 2 ]  Preparation for colonoscopy takes a minimum of six hours which in those bleeding briskly may limit its applicability. [ 38 ]  Surgery, while rarely used to treat upper GI bleeds, is still commonly used to manage lower GI bleeds by cutting out the part of the intestines that is causing the problem. [ 2 ]   Angiographic embolization  may be used for both upper and lower GI bleeds. [ 2 ]   Transjugular intrahepatic portosystemic shunting  (TIPS) may also be considered. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6862", "text": "Death in those with a GI bleed is more commonly due to other illnesses (some of which may have contributed to the bleed, such as cancer or cirrhosis) than the bleeding itself. [ 2 ]  Of those admitted to a hospital because of a GI bleed, death occurs in about 7%. [ 16 ]  Despite treatment, re-bleeding occurs in about 7\u201316% of those with upper GI bleeding. [ 3 ]  In those with esophageal varices, bleeding occurs in about 5\u201315% a year and if they have bled once, there is a higher risk of further bleeding within six weeks. [ 13 ]  Testing and treating  H. pylori  if found can prevent re-bleeding in those with peptic ulcers. [ 4 ]  The benefits versus risks of restarting blood thinners such as  aspirin  or  warfarin  and  anti-inflammatories  such as  NSAIDs  need to be carefully considered. [ 4 ]  If aspirin is needed for cardiovascular disease prevention, it is reasonable to restart it within seven days in combination with a PPI for those with nonvariceal upper GI bleeding. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6863", "text": "Gastrointestinal bleeding from the upper tract occurs in 50 to 150 per 100,000 adults per year. [ 8 ]  It is more common than lower gastrointestinal bleeding which is estimated to occur at the rate of 20 to 30 per 100,000 per year. [ 2 ]  Risk of bleeding is more common in males and increases with age. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6864", "text": "Globosides  (also known as  globo-series glycosphingolipids ) are a sub-class of the lipid class  glycosphingolipid [ 1 ]  with three to nine  sugar  molecules as the side chain (or  R group ) of  ceramide . The sugars are usually a combination of  N -acetylgalactosamine ,  D -glucose  or  D -galactose . One characteristic of globosides is that the \"core\" sugars consists of Glucose-Galactose-Galactose (Ceramide-\u03b2Glc4-1\u03b2Gal4-1\u03b1Gal), like in the case of the most basic globoside,  globotriaosylceramide  (Gb3), [ 2 ]  also known as pk-antigen. Another important characteristic of globosides is that they are neutral at pH 7, because they usually do not contain  neuraminic acid , a sugar with an acidic carboxy-group. However, some globosides with the core structure Cer-Glc-Gal-Gal do contain neuraminic acid, e.g. the globo-series glycosphingolipid \"SSEA-4-antigen\"."}
{"_id": "WikiPedia_Hematology$$$corpus_6865", "text": "The side chain can be cleaved by  galactosidases  and  glucosidases . The deficiency of  \u03b1-galactosidase A  causes  Fabry's disease , an inherited metabolic disease characterized by the accumulation of the globoside  globotriaosylceramide . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6866", "text": "Globoside 4 (Gb4) has been known as the receptor for  parvovirus B19 , due to observations that B19V binds to the thin-layered  chromatogram  of the  structure .  However, the binding on its surface does not match well with the  virus , which raised debates on whether or not GB4 is the cause for productive infection. [ 4 ]  Additional research using the technique Knockout Cell Line has shown that although GB4 does not have the direct entry  receptor  for B19V, it plays a post-entry role in productive infection. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6867", "text": "Globoside 4 (Gb4) are a type of  SSEA , stage-specific embryonic antigen, that is present in cellular development and tumorous tissues without the mechanism of Gb4 being completely known. However a study has shown Gb4 directly activates the epidermal growth factor receptor through a ERK signaling. When the globo-series glycosphingolipid (GSL) was reduced in the experiment the ERK signaling from the receptor tyrosine kinase was also inhibited. The ERK was reactivated with the addition of the Gb4 and henceforth heightened proliferation of tumorous cells and opened up the possibility of testing Gb4 for further studies on potential drugs that can target cancerous cells. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6868", "text": "Globoside-5 is also known as  stage-specific embryonic antigen 3 ."}
{"_id": "WikiPedia_Hematology$$$corpus_6869", "text": "Glycophorin C  ( GYPC ;  CD236 / CD236R ;  glycoprotein beta ;  glycoconnectin ;  PAS-2 ' ) plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through its interaction with protein 4.1. Moreover, it has previously been shown that membranes deficient in protein 4.1 exhibit decreased content of glycophorin C. It is also an  integral membrane protein  of the  erythrocyte  and acts as the  receptor  for the  Plasmodium falciparum  protein PfEBP-2 (erythrocyte binding protein 2; baebl; EBA-140)."}
{"_id": "WikiPedia_Hematology$$$corpus_6870", "text": "The antigen was discovered in 1960 when three women who lacked the antigen made anti-Gea in response to pregnancy. The antigen is named after one of the patients \u2013 a Mrs Gerbich. [ 1 ]  The following year a new but related antigen was discovered in a Mrs Yus for whom an antigen in this system is also named. In 1972 a numerical system for the antigens in this blood group was introduced."}
{"_id": "WikiPedia_Hematology$$$corpus_6871", "text": "Despite the similar names glycophorin C and D are unrelated to the other three glycophorins which encoded on  chromosome 4  at location 4q28-q31. These latter proteins are closely related.  Glycophorin A  and  glycophorin B  carry the  blood group   MN  and  Ss   antigens  respectively. There are ~225,000 molecules of GPC and GPD per erythrocyte. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6872", "text": "Originally it was thought that glycophorin C and D were the result of a gene duplication event but it was only later realised that they were encoded by the same gene. Glycophorin D (GPD) is generated from the glycophorin C  messenger RNA  by  leaky translation  at an in frame AUG at  codon  30: glycophorin D =  glycophorin  C residues 30 to 128. This leaky translation appears to be a uniquely human trait. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6873", "text": "Glycophorin C (GPC) is a single  polypeptide  chain of 128  amino acids  and is encoded by a  gene  on the long arm of  chromosome 2  (2q14-q21). The gene was first cloned in 1989 by High  et al. [ 4 ]  The GPC gene is organized in four  exons  distributed over 13.5 kilobase pairs of  DNA . Exon 1 encodes residues 1-16, exon 2 residues 17-35, exon 3 residues 36-63 and exon 4 residues 64-128. Exons 2 and 3 are highly homologous, with less than 5% nucleotide divergence. These exons also differ by a 9 amino acid insert at the 3' end of exon 3. The direct repeated segments containing these exons is 3.4 kilobase pairs long and may be derived from a recent duplication of a single ancestral domain. Exons 1, 2 and most of exon 3 encode the N-terminal extracellular domain while the remainder of exon 3 and exon 4 encode transmembrane and cytoplasmic domains."}
{"_id": "WikiPedia_Hematology$$$corpus_6874", "text": "Two  isoforms  are known and the gene is expressed in a wide variety of  tissues  including  kidney ,  thymus ,  stomach ,  breast , adult  liver  and erythrocyte. In the non erythroid cell lines, expression is lower than in the erythrocyte and the protein is differentially  glycosylated . In the erythrocyte glycophorin C makes up ~4% of the membrane  sialoglycoproteins . The average number of O linked chains is 12 per molecule."}
{"_id": "WikiPedia_Hematology$$$corpus_6875", "text": "The  gene  is expressed early in the development of the erythrocyte, specifically in the erythroid  burst-forming unit  and erythroid  colony-forming unit . The mRNA from human erythroblasts is ~1.4 kilobases long and the transcription start site in erythroid cells has been mapped to 1050 base pairs 5' of the start codon. It is expressed early in development and before the  Kell antigens ,  Rhesus-associated glycoprotein , glycophorin A,  band 3 , the  Rhesus antigen  and glycophorin B. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6876", "text": "In melanocytic cells Glycophorin C gene expression may be regulated by  MITF . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6877", "text": "GPC appears to be synthesized in excess in the erythrocyte and that the membrane content is regulated by band 4.1 (protein 4.1). Additional data on the regulation of glycophorin C is  here ."}
{"_id": "WikiPedia_Hematology$$$corpus_6878", "text": "In a study of this gene among the  Hominoidea  two finding unique to humans emerged: (1) an excess of non-synonymous divergence among species that appears to be caused solely by accelerated evolution and (2) the ability of the single GYPC gene to encode both the GPC and GPD proteins. [ 3 ]  The cause for this is not known but it was suggested that these findings might be the result of infection by  Plasmodium falciparum ."}
{"_id": "WikiPedia_Hematology$$$corpus_6879", "text": "After separation of red cell membranes by  SDS-polyacrylamide gel electrophoresis  and staining with  periodic acid-Schiff staining  (PAS) four glycophorins have been identified. These have been named glycophorin A, B, C and D in order of the quantity present in the membrane \u2013 glycophorin A being the most and glycophorin D the least common. A fifth ( glycophorin E ) has been identified within the human genome but cannot easily be detected on routine gel staining. In total the glycophorins constitute ~2% of the total erythrocyte membrane protein mass. Confusingly these proteins are also known under different nomenclatures but they are probably best known as the glycophorins."}
{"_id": "WikiPedia_Hematology$$$corpus_6880", "text": "Glycophorin C was first isolated in 1978. [ 7 ]  Glycophorin C and D are minor sialoglycoproteins contributing to 4% and 1% to the PAS-positive material and are present at about 2.0 and 0.5 x 10 5  copies/cell respectively. In polyacrylimide gels glycophorin C's apparent weight is 32 kilodaltons (32 kDa). Its structure is similar to that of other glycophorins: a highly glycoslated extracellular domain (residues 1-58), a transmembrane domain (residues 59-81) and an intracellular domain (residues 82-128). About 90% of the glycophorin C present in the erythrocyte is bound to the cytoskeleton and the remaining 10% moves freely within the membrane."}
{"_id": "WikiPedia_Hematology$$$corpus_6881", "text": "Glycophorin D's apparent molecular weight is 23kDa. On average this protein has 6 O linked oligosaccharides per molecule."}
{"_id": "WikiPedia_Hematology$$$corpus_6882", "text": "Within the erythrocyte it interacts with  band 4.1  (an 80-kDa protein) and p55 (a  palmitoylated  peripheral membrane phosphoprotein and a member of the membrane-associated guanylate kinase family) to form a  ternary complex  that is critical for the shape and stability of erythrocytes. The major attachment sites between the erythrocyte  spectrin - actin   cytoskeleton  and the lipid bilayer are glycophorin C and  band 3 . The interaction with band 4.1 and p55 is mediated by the N terminal 30 kD domain of band 4.1 binding to a 16 amino acid segment (residues 82-98: residues 61-77 of glycophorin D) within the cytoplasmic domain of glycophorin C and to a positively charged 39 amino acid motif in p55. [ 8 ]  The majority of  protein 4.1  is bound to glycophorin C. The magnitude of the strength of the interaction between glycophorin C and band 4.1 has been estimated to be 6.9 microNewtons per meter, a figure typical of protein\u2013protein interactions."}
{"_id": "WikiPedia_Hematology$$$corpus_6883", "text": "Glycophorin C normally shows oscillatory movement in the erythrocyte membrane. This is reduced in  Southeast Asian ovalocytosis  a disease of erythrocytes due to a mutation in band 3. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6884", "text": "These glycophorins are associated with eleven antigens of interest to transfusion medicine: the Gerbich (Ge2, Ge3, Ge4), the Yussef (Yus), the Webb (Wb or Ge5), the Duch (Dh(a) or Ge8), the Leach, the Lewis II (Ls(a) or Ge6), the Ahonen (An(a) or Ge7) and GEPL (Ge10*), GEAT (Ge11*) and GETI (Ge12*). Six are of high prevalence (Ge2, Ge3, Ge4, Ge10*, Ge11*, Ge12*) and five of low prevalence (Wb, Ls(a), An(a), Dh(a) and Ge9). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6885", "text": "Glycophorin C and D encode the Gerbich (Ge)  antigens . There are four  alleles , Ge-1 to Ge-4. Three types of Ge antigen negativity are known: Ge-1,-2,-3 (Leach phenotype), Ge-2,-3 and Ge-2,+3. A 3.4 kilobase pair deletion within the gene, which probably arose because of unequal crossing over between the two repeated domains, is responsible for the formation of the Ge-2,-3  genotype . The breakpoints of the deletion are located within  introns  2 and 3 and results in the deletion of  exon  3. This mutant gene is transcribed as a  messenger RNA  with a continuous  open reading frame  extending over 300  nucleotides  and is translated into the  sialoglycoprotein  found on Ge-2,-3 red cells. A second 3.4 kilobase pair deletion within the glycophorin C gene eliminates only exon 2 by a similar mechanism and generates the mutant  gene  encoding for the abnormal glycoprotein found on Ge-2,+3 erythrocytes."}
{"_id": "WikiPedia_Hematology$$$corpus_6886", "text": "The Ge2 epitope is antigenic only on glycophorin D and is a  cryptic antigen  in glycophorin C. It is located within exon 2 and is sensitive to  trypsin  and  papain  but resistant to  chymotrypsin  and  pronase . The Ge3 epitope is encoded by exon 3. It is sensitive to  trypsin  but resistant to  chymotrypsin ,  papain  and  pronase . It is thought to lie in the between amino acids 42-50 in glycophorin C (residues 21-49 in glycophorin D). Ge4 is located within the first 21 amino acids of glycophorin C. It is sensitive to trypsin, papain, pronase and  neuraminidase ."}
{"_id": "WikiPedia_Hematology$$$corpus_6887", "text": "The relatively rare Leach phenotype is due either to a deletion in exons 3 and 4 or to a  frameshift mutation  causing a premature stop codon in the glycophorin C gene, and persons with this phenotype are less susceptible (~60% of the control rate) to invasion by  Plasmodium falciparum . Such individuals have a subtype of a condition called  hereditary elliptocytosis . \nThe abnormally shaped cells are known as elliptocytes or cameloid cells. The basis for this phenotype was first reported by Telen  et al. [ 11 ]  The phenotype is Ge:-2,-3,-4."}
{"_id": "WikiPedia_Hematology$$$corpus_6888", "text": "The Yussef (Yus)  phenotype  is due to a 57 base pair deletion corresponding to exon 2. The antigen is known as GPC Yus."}
{"_id": "WikiPedia_Hematology$$$corpus_6889", "text": "Glycophorin C mutations are rare in most of the Western world, but are more common in some places where malaria is endemic. In  Melanesia  a greater percentage of the population is Gerbich negative (46.5%) than in any other part of the world. The incidence of Gerbich-negative phenotype caused by an exon 3 deletion in the Wosera ( East Sepik Province ) and Liksul ( Madang Province ) populations of  Papua New Guinea  is 0.463 and 0.176 respectively. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6890", "text": "The rare Webb (Wb) antigen (~1/1000 donors), originally described in 1963 in  Australia , is the result of an alteration in  glycosylation  of glycophorin C: an A to G transition at nucleotide 23 results in an  asparagine  residue instead of the normal  serine  residue with the resultant loss of glycosylation. [ 13 ]  The antigen is known as GPC Wb."}
{"_id": "WikiPedia_Hematology$$$corpus_6891", "text": "The rare Duch (Dh) antigen was discovered in  Aarhus ,  Denmark  (1968) and is also found on glycophorin C. It is due to a C to T  transition  at  nucleotide  40 resulting in the replacement of  leucine  by  phenylalanine . [ 14 ]  This antigen is sensitive to trypsin but resistant to chymotrypsin and Endo F. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6892", "text": "The Lewis II (Ls(a); Ge-6) antigen has insert of 84 nucleotides into the ancestral GPC gene: the insert corresponds to the entire sequence of exon 3. [ 16 ]  Two subtypes of this antigen are known: beta Ls(a) which carries the Ge3 epitope and gamma Ls(a) which carries both the Ge2 and Ge3 epitopes. This antigen is also known as the Rs(a) antigen. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6893", "text": "The Ahonen (Ana) antigen was first reported in 1972. [ 18 ] \nThe antigen is found on glycophorin D. This antigen was discovered in a Finnish man on May 5, 1968, during post operative blood cross matching for an aortic aneurism repair. In Finland the incidence of this antigen was found to be 6/10,000 donors. In Sweden the incidence was 2/3266 donors. The molecular basis for the origin of this antigen lies within exon 2 where a G->T substitution in codon 67 (base position 199) converts an  alanine  to a  serine  residue. While this epitope exists within glycophorin C there it is a cryptantigen. It is only antigenic in glycophorin D because of the truncated N terminus."}
{"_id": "WikiPedia_Hematology$$$corpus_6894", "text": "A duplicated exon 2 has erythrocytes also been reported in Japanese blood donors (~2/10,000). This mutation has not been associated with a new antigen. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6895", "text": "Antibodies to the Gerbich antigens have been associated with transfusion reactions and mild  hemolytic disease  of the newborn. \nIn other studies naturally occurring anti-Ge antibodies have been found and appear to be of no clinical significance. Immunological tolerance towards Ge antigen has been suggested."}
{"_id": "WikiPedia_Hematology$$$corpus_6896", "text": "High expression of glycophorin C has been associated with a poor prognosis for acute lymphoblastic leukaemia in Chinese populations. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6897", "text": "Glycophorin C is the receptor for the protein erythrocyte binding antigen 140 (EBA140) of  Plasmodium falciparum . [ 21 ]  This interaction mediates a principal invasion pathway into the erythrocytes. The partial resistance of erythrocytes lacking this protein to invasion by  P. falciparum  was first noted in 1982. [ 22 ]  The lack of Gerbich antigens in the population of Papua New Guinea was noted in 1989. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6898", "text": "Influenza A and B bind to glycophorin C. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6899", "text": "A  granulocyte transfusion  is a medical procedure in which  granulocytes  are infused into a person's blood. Granulocytes are a category of  white blood cell  that includes  neutrophils ,  eosinophils , and  basophils . [ 1 ] :\u200a99\u200a  Granulocyte transfusions were historically used to prevent and treat infections in people with  neutropenia  (an abnormally low level of  neutrophils ), but the practice declined in popularity in the 1980s. Interest in the procedure increased in the 1990s due to the development of more effective methods for harvesting granulocytes and a growing population of people with severe neutropenia from  chemotherapy . However, the treatment's efficacy remains poorly understood and its use is controversial. [ 2 ] [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6900", "text": "Granulocytes are most often collected through  leukapheresis , a process that separates the donor's white blood cells from their  red blood cells  and  plasma . Donors may be given  corticosteroids  or  granulocyte colony-stimulating factor  to increase their granulocyte count prior to the blood collection. Granulocytes have a short shelf life and it is recommended that they are transfused within hours of collection. Adverse effects from granulocyte transfusions include  fever ,  chills ,  respiratory  symptoms,  transfusion-transmitted infections , and the development of  antibodies  against  human leukocyte antigens , which can interfere with subsequent transfusions. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6901", "text": "Neutrophils are the most common type of granulocyte in normal blood, [ 5 ] :\u200a82\u200a  and they play a major role in defending against infections, especially those caused by  fungi  and  bacteria . [ 6 ]  People with severe  neutropenia , a low neutrophil count, have an increased risk of developing serious infections. One of the approaches to preventing and treating infections in people with neutropenia is to increase the neutrophil count, which is commonly done using drugs like  G-CSF  to stimulate the production of neutrophils in the  bone marrow . [ 6 ]  However, another approach is to directly transfuse granulocytes from a donor into the person's blood. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6902", "text": "As of 2015, there is some evidence that granulocyte transfusions may help to prevent  bacteremia  and  fungemia  in adults who have neutropenia caused by  chemotherapy  or  hematopoietic stem cell transplantation . However, it is unclear whether this has any impact on  mortality  or major adverse events, [ 7 ]  and the use of granulocyte transfusions to prevent infections is considered controversial because of the potential for serious  side effects . [ 2 ]  Although the studies performed to date have been low-quality, a 2016 review suggested that granulocyte transfusion may not be effective for treating infections in adults with neutropenia. [ 8 ]  In both cases, the treatment is considered  investigational . [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6903", "text": "Granulocyte transfusion is still used in some cases, such as in cases of severe neutropenia and where the patient has a life-threatening infection that does not respond to  antimicrobial treatment . [ 2 ]  The treatment has also been studied in people with  aplastic anemia  (a condition in which a person's bone marrow does not produce enough blood cells) and  chronic granulomatous disease  (a disorder in which a person has a normal number of neutrophils, but they do not function correctly). Newborn babies who have neutropenia and  sepsis  are sometimes given granulocyte transfusions, [ 2 ]  although a 2011 study found that there was insufficient evidence to determine whether or not this practice is effective. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6904", "text": "Prior to donating granulocytes, potential donors must undergo screening and testing procedures. They are required to meet the general criteria for  blood donation . [ 2 ]  Because the granulocyte concentrate also contains  red blood cells , the donor's  ABO blood type  is usually matched to the recipient's. [ note 1 ]  If the recipient has  antibodies  against  human leukocyte antigens  (HLA), proteins found on the surface of  white blood cells , the donor's cells need to be tested for compatibility, because antibodies against donor granulocytes can reduce the effectiveness of the transfusion and cause  transfusion reactions . [ 10 ] :\u200a630"}
{"_id": "WikiPedia_Hematology$$$corpus_6905", "text": "In order to collect enough granulocytes for the transfusion to be effective, donors are frequently given drugs to increase their neutrophil count prior to the blood collection. The treatment typically includes  corticosteroids  or G-CSF, often in combination. [ 3 ] [ 10 ] :\u200a627\u200a  Donors may experience minor side effects from steroid and G-CSF treatment, including headaches, bone and joint pain,  insomnia  and  fatigue . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6906", "text": "The donor blood undergoes  leukapheresis , a process by which white blood cells are separated from  red blood cells  and  plasma . During the blood collection, the donor's blood is mixed with  hydroxyethyl starch , which helps separate the granulocytes from other blood components during sample processing. [ 2 ] [ 11 ] :\u200a297\u200a  The other components of the blood are returned to the donor's circulation. [ 11 ] :\u200a297\u200a  The process of collecting the granulocytes takes about four to five hours. [ 2 ]  Because a large amount of blood (seven to ten litres) is processed during apheresis, donors may experience adverse effects from changes in  fluid balance . [ 4 ]  An alternative approach, more commonly used in the United Kingdom, is to combine the  buffy coats  (the fraction of blood containing white blood cells) from multiple routine blood donations to create a blood product containing a high amount of granulocytes. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6907", "text": "Once collected, granulocytes have a 24-hour shelf life. [ 12 ]  It is recommended that they are transfused within a few hours of collection. [ 2 ]  They cannot be frozen, as this severely inhibits the cells' functions. [ 10 ] :\u200a628\u200a  The white blood cell concentrate obtained through leukapheresis contains a high number of active  T lymphocytes , which can cause  graft-versus-host disease  in the recipient, so it is often exposed to radiation to inactivate these cells. [ 10 ] :\u200a628"}
{"_id": "WikiPedia_Hematology$$$corpus_6908", "text": "Adverse effects  are more common with granulocyte transfusions than with  red blood cell transfusions . 25 to 50 percent of people who receive granulocyte transfusions experience mild to moderate side effects, while 1 percent experience severe complications. [ 2 ]   Fever  and chills are common side effects. [ 2 ] [ 3 ]  Granulocyte transfusions may affect the  lungs , causing cough,  difficulty breathing ,  low oxygen levels , and abnormal  chest X-rays . [ 2 ]  These lung complications may potentially be fatal. [ 3 ]  A review paper found that the frequency of lung-related side effects ranged from 0 to 53 percent. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6909", "text": "On rare occasions, recipients can develop  transfusion-transmitted diseases  if  pathogens  are present in the donor blood. This is a particular problem with granulocyte transfusions because of their short shelf life, which means they must be transfused before infectious disease testing is complete. [ 2 ]  Infection with  cytomegalovirus  (CMV) is a concern, as this virus is found in white blood cells, so if the recipient is at risk of developing severe disease from CMV, it is recommended that granulocytes be collected from a CMV-negative donor. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6910", "text": "If the donor white blood cells are not irradiated, the recipient may be at risk of developing  graft-versus-host  disease. Finally, people who receive granulocyte transfusions may develop  antibodies  against the  human leukocyte antigens  found on the surface of white blood cells, which can predispose them to transfusion reactions, decrease the lifespan of donor white blood cells in their circulation, and reduce the efficacy of  platelet transfusions  and  allogeneic stem cell transplants . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6911", "text": "In a 1934 experiment, Strumia gave neutropenic patients  intramuscular injections  of neutrophils, but this proved ineffective in improving their neutrophil function. [ 14 ] [ 15 ]  In 1953, Brecher et al. demonstrated the principle behind granulocyte transfusion by infusing neutrophils into dogs and showing that they travelled to sites of inflammation. [ 16 ]  The first human granulocyte transfusions were carried out in the 1960s, using white blood cells harvested from people with chronic myeloid leukemia and concentrated using  centrifugation . Steroid treatment and leukapheresis were later introduced, allowing granulocytes to be collected from healthy donors. However, these techniques were not very effective as they did not produce a high granulocyte count. Owing to poor efficacy, an undesirable side effect profile, and the impracticality of storing granulocytes for an extended period of time, the use of granulocyte transfusions declined. [ 4 ]  Improvements in antimicrobial therapy and supportive care also played a role in the treatment's decreasing popularity. [ 2 ]  However, the introduction of donor treatment with G-CSF in the 1990s allowed high numbers of granulocytes to be collected from healthy donors. This, combined with an increasing number of people with severe neutropenia as a result of chemotherapy and the growing prevalence of  multidrug resistant infections , led to a renewal of interest in granulocyte transfusions. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6912", "text": "Gulf Coast Regional Blood Center  is an  nonprofit , independent  blood donor  center that gathers blood through donations and provides  whole blood  and  blood products . The center meets the blood and blood component needs of patients being treated in more than 170 health care institutions in a 25-county  Texas   Gulf Coast , Brazos Valley and east Texas regions. [ 1 ]  Located in the  Texas Medical Center  in  Houston , the center began operations on January 1, 1975. The Blood Center encourages individuals to Commit for Life, which is a partnership between the community and Gulf Coast Regional Blood Center that is focused on saving lives and permanently increasing the blood supply. The center is headquartered in  Houston . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6913", "text": "The center stated that, for it to serve its area effectively, it would have to collect 333,000 units in 2010, with more \nthan 1,000 donations per day. [ 3 ]   Gulf Coast Regional Blood Center is a non-profit  501 (c) (3)  organization and is accredited, licensed and inspected by  American Association of Blood Banks , the  Food and Drug Administration ,  Medicare  as well as local and state authorities. In 2007, the center collected a total of 291,319 units of blood and blood components, exceeding 2006's record by more than 18,000 units. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6914", "text": "The center is an accredited donor center for the  National Marrow Donor Program  and has recruited more than 90,000 potential donors who can donate  bone marrow  or  hematopoietic  cells. [ 5 ]  The center is one of the leading bone-marrow donor centers in the country and is the leading center for minority recruitment according to the National Marrow Donor Program. The center's marrow donor registry has a donor base of more than 100,000 donors, and through 2007, facilitated 329 matches. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6915", "text": "\"Commit for Life\" refers to the blood center's blood donation programs. Blood donations may be done on an individual basis, on a group basis, or on a volunteer basis. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6916", "text": "This  Houston -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_6917", "text": "Hemolytic disease of the newborn , also known as  hemolytic disease of the fetus and newborn ,  HDN ,  HDFN , or  erythroblastosis fetalis , [ 1 ] [ 2 ]  is an  alloimmune  condition that develops in a  fetus  at or around birth, when the  IgG  molecules (one of the five main types of  antibodies ) produced by the mother pass through the  placenta . Among these antibodies are some which attack  antigens  on the  red blood cells  in the  fetal circulation ,  breaking down and destroying the cells . The fetus can develop  reticulocytosis  and  anemia . The intensity of this fetal disease ranges from mild to very severe, and fetal death from heart failure ( hydrops fetalis ) can occur. When the disease is moderate or severe, many  erythroblasts  (immature red blood cells) are present in the fetal blood, earning these forms of the disease the name  erythroblastosis fetalis  ( British English :  erythroblastosis foetalis )."}
{"_id": "WikiPedia_Hematology$$$corpus_6918", "text": "HDFN represents a breach of  immune privilege  for the fetus or some other form of impairment of the  immune tolerance in pregnancy . Various types of HDFN are classified by which alloantigen provokes the response. The types include  ABO ,  anti-RhD ,  anti-RhE ,  anti-Rhc , anti-Rhe, anti-RhC, multiantigen combinations, and  anti-Kell . Although global prevalence studies of the differential contribution of those types are lacking, regional  population studies  have shown the anti-RhD type to be the most common cause of HDFN, followed by anti-RhE, anti-RhC, and anti-Rhc. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6919", "text": "Signs of hemolytic disease of the newborn include a positive  direct Coombs test  (also called direct agglutination test), elevated cord bilirubin levels, and  hemolytic anemia . It is possible for a newborn with this disease to have  neutropenia  and  neonatal alloimmune thrombocytopenia  as well. [ citation needed ]   Hemolysis  leads to elevated  bilirubin  levels. After delivery, bilirubin is no longer cleared (via the placenta) from the neonate's blood and the  symptoms  of  jaundice  (yellowish skin and yellow discoloration of the whites of the eyes, or  icterus ) increase within 24 hours after birth. Like other forms of severe  neonatal jaundice , there is the possibility of the neonate developing acute or chronic  kernicterus , however the risk of kernicterus in HDN is higher because of the rapid and massive destruction of blood cells. Isoimmunization is a risk factor for  neurotoxicity  and lowers the level at which kernicterus can occur. Untreated profound anemia can cause high-output  heart failure , with  pallor ,  enlarged liver  and/or  spleen , generalized  swelling , and  respiratory distress . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6920", "text": "HDN can be the cause of  hydrops fetalis , an often-severe form of prenatal  heart failure  that causes fetal  edema . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6921", "text": "Complications of HDN could include  kernicterus ,  hepatosplenomegaly , inspissated (thickened or dried) bile syndrome and/or greenish staining of the  teeth ,  hemolytic anemia  and damage to the liver due to excess bilirubin. Conditions that may cause similar symptoms in the newborn period include:  acquired hemolytic anemia , congenital  toxoplasma , congenital  syphilis  infection, congenital obstruction of the  bile duct , and  cytomegalovirus  (CMV) infection. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6922", "text": "Antibodies are produced when the body is exposed to an  antigen  foreign to the make-up of the body. If a mother is exposed to a foreign antigen and produces IgG (as opposed to  IgM  which does not cross the placenta), the IgG will target the antigen, if present in the fetus, and may affect it  in utero  and persist after delivery. However, the antibodies of the mother do not go away after the first incompatible pregnancy due to immunological memory. The maternal blood is likely to secrete more antibodies and attack the fetal erythrocytes during subsequent pregnancies because of re-exposure to the antigen.  [ 15 ]  The three most common models in which a woman becomes sensitized toward (i.e., produces IgG  antibodies  against) a particular antigen are hemorrhage, blood transfusion, and ABO incompatibility. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6923", "text": "Fetal-maternal hemorrhage , which is the movement of fetal blood cells across the placenta, can occur during  abortion ,  ectopic pregnancy ,  childbirth , ruptures in the  placenta  during  pregnancy  (often caused by trauma), or medical procedures carried out during pregnancy that breach the uterine wall. In subsequent pregnancies, if there is a similar incompatibility in the fetus, these antibodies are then able to cross the placenta into the fetal bloodstream to attach to the  red blood cells  and cause their destruction ( hemolysis ). This is a major cause of HDN, because 75% of pregnancies result in some contact between fetal and maternal blood, and 15\u201350% of pregnancies have hemorrhages with the potential for immune sensitization. The amount of fetal blood needed to cause maternal sensitization depends on the individual's immune system and ranges from 0.1\u00a0mL to 30\u00a0mL. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6924", "text": "The woman may have received a therapeutic  blood transfusion .  ABO blood group system  and the D antigen of the  Rhesus (Rh) blood group system  typing are routine prior to transfusion. Suggestions have been made that women of child-bearing age or young girls should not be given a transfusion with Rhc-positive blood or  Kell 1 -positive blood to avoid possible sensitization, but this would strain the resources of blood transfusion services, and it is currently considered uneconomical to screen for these blood groups. HDFN can also be caused by antibodies to a variety of other  blood group system  antigens, but Kell and Rh are the most frequently encountered. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6925", "text": "The third sensitization model can occur in women of blood type O. The  immune response  to A and B antigens, which are widespread in the environment, usually leads to the production of IgM or IgG anti-A and anti-B antibodies early in life. Women of blood type O are more prone than women of types A and B to making IgG anti-A and anti-B antibodies, and these IgG antibodies are able to cross the placenta. For unknown reasons, the incidence of maternal antibodies against type A and B antigens of the IgG type that could potentially cause hemolytic disease of the newborn is greater than the observed incidence of \"ABO disease.\" About 15% of pregnancies involve a type O mother and a type A or type B child; only 3% of these pregnancies result in hemolytic disease due to A/B/O incompatibility. In contrast to antibodies to A and B antigens, production of Rhesus antibodies upon exposure to environmental antigens seems to vary significantly across individuals. [ 16 ]  In cases where there is ABO incompatibility and Rh incompatibility, the risk of alloimmunization is decreased because fetal red blood cells are removed from maternal circulation due to anti-ABO antibodies before they can trigger an anti-Rh response. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6926", "text": "HDN is classified by the type of antigens involved. The main types are ABO HDN, Rhesus HDN, Kell HDN, and other antibodies. Combinations of antibodies (for example, anti-Rhc and anti-RhE occurring together) can be especially severe. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6927", "text": "ABO hemolytic disease of the newborn  can range from mild to severe, but generally, it is a mild disease. It can be caused by anti-A and anti-B antibodies. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6928", "text": "Rhesus D hemolytic disease of the newborn  (often called Rh disease) is the most common and only preventable form of severe HDN. Since the introduction of Rho-D immunoglobulin, ( Rhogam , at 1968, which prevents the production of maternal Rho-D antibodies, the incidence of anti-D HDN has decreased dramatically. [ 5 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6929", "text": "Rhesus c HDFN  can range from a mild to severe disease and is the third most common form of severe HDN. [ 19 ]  Rhesus e and rhesus C hemolytic disease of the newborn are rare. Anti-C and anti-c can both show a negative DAT but still have a severely affected infant. [ 20 ] [ 21 ]  An indirect Coombs must also be run."}
{"_id": "WikiPedia_Hematology$$$corpus_6930", "text": "Anti-Kell hemolytic disease of the newborn  is most commonly caused by anti-K 1  antibodies, the second most common form of severe HDN. Over half of the cases of anti-K 1  related HDN are caused by multiple blood transfusions. Antibodies to the other Kell antigens are rare. [ 19 ]  Anti-Kell can cause severe anemia regardless of titer. [ 22 ]  It suppresses the bone marrow by inhibiting the erythroid progenitor cells. [ 23 ] [ 24 ] [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6931", "text": "Anti-M also recommends antigen testing to rule out the presence of HDN as the direct coombs can come back negative in a severely affected infant. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6932", "text": "Kidd antigens are also present on the endothelial cells of the kidneys. [ 27 ] [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6933", "text": "One study states that it would be unwise to routinely dismiss anti-E as being of little clinical consequence. It also found that the most severe case of anti-E HDFN occurred with titers 1:2, concluding that titers are not reliable for the diagnosis of the anti-E type. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6934", "text": "The  diagnosis  of HDFN is based on history and laboratory findings. If a newly pregnant woman has red cell antibodies in her serum, the antibody titer should be followed with subsequent blood draws. The titer will rise if the fetus expresses the red cell antigen to which she is alloimmunized. In that case, fetal  middle cerebral artery   doppler ultrasonography  is used to determine the degree of fetal anemia and the need for  intrauterine transfusion . [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6935", "text": "Blood tests done on the newborn baby"}
{"_id": "WikiPedia_Hematology$$$corpus_6936", "text": "Blood tests done on the mother"}
{"_id": "WikiPedia_Hematology$$$corpus_6937", "text": "Blood tests done on the father  (rarely needed)"}
{"_id": "WikiPedia_Hematology$$$corpus_6938", "text": "In cases of Rho(D) incompatibility,  Rho(D) immunoglobulin  is given to prevent sensitization. However, there is no comparable immunotherapy available for other blood group incompatibilities. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6939", "text": "Early pregnancy"}
{"_id": "WikiPedia_Hematology$$$corpus_6940", "text": "Mid- to late- pregnancy"}
{"_id": "WikiPedia_Hematology$$$corpus_6941", "text": "Rhesus-negative mothers who are pregnant with a rhesus-positive infant are offered Rho(D) immune  globulin  (RhIG, or RhoGam) at 28 weeks during pregnancy, at 34 weeks, and within 48 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red blood cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG. [ 5 ]  A drawback to pre-partum administration of RhIG is that it causes a positive antibody screen when the mother is tested, which can be difficult to distinguish from natural immunological responses that result in antibody production. [ citation needed ]  Without Rho(D) immunoglobulin, the risk of isoimmunization is approximately 17%; with proper administration, the risk is reduced to less than 0.1\u20130.2%. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6942", "text": "In some cases, the direct Coombs will be negative but severe, even fatal HDN can occur. [ 20 ]  An indirect Coombs needs to be run in cases of anti-C, [ 21 ]  anti-c, [ 21 ]  and anti-M. Infants with Anti-M are also recommended to receive antigen testing to rule out the presence of HDN. [ 26 ]  The below tests are often useful in cases of hemolytic disease of the newborn but are not required for treatment of all newborns."}
{"_id": "WikiPedia_Hematology$$$corpus_6943", "text": "After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring,  phototherapy , transfusion with compatible packed red blood,  exchange transfusion ,  sodium bicarbonate  for correction of  acidosis  and/or assisted ventilation. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6944", "text": "Once a woman has antibodies, she is at high risk for a future transfusion reaction if she is in need of a blood transfusion. [ 48 ]  For this reason, she is advised to carry a medical alert card at all times and inform all doctors and emergency personnel of her antibody status. [ citation needed ]  The absence of antibodies however does not preclude a woman from having a transfusion reaction:"}
{"_id": "WikiPedia_Hematology$$$corpus_6945", "text": "\"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A, B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures.\" [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6946", "text": "For a summary of transfusion reactions in the US, see reference. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6947", "text": "In 2003, the incidence of Rh(D) sensitization in the United States was 6.8 per 1000 live births; 0.27% of women with an Rh incompatible fetus experience alloimmunization. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6948", "text": "In  ABO hemolytic disease of the newborn  (also known as ABO HDN) maternal  IgG   antibodies  with specificity for the  ABO blood group system  pass through the  placenta  to the  fetal  circulation where they can cause  hemolysis  of fetal  red blood cells  which can lead to fetal  anemia  and  HDN . In contrast to  Rh disease , about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6949", "text": "The ABO blood group system is the best known surface antigen system, expressed on a wide variety of human cells. For  Caucasian  populations about one fifth of all pregnancies have ABO incompatibility between the fetus and the mother, but only a very small minority develop symptomatic ABO HDN. [ 1 ]  The latter typically only occurs in mothers of blood group O, because they can produce enough IgG antibodies to cause hemolysis. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6950", "text": "Although very uncommon, cases of ABO HDN have been reported in infants born to mothers with blood groups A [ 2 ] [ 3 ]  and B. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6951", "text": "In about a third of all ABO incompatible pregnancies maternal IgG anti-A or IgG anti-B antibodies pass through the placenta to the fetal circulation leading to a weakly positive  direct Coombs test  for the neonate's blood. [ citation needed ]   However, ABO HDN is generally mild and short-lived and only occasionally severe because:"}
{"_id": "WikiPedia_Hematology$$$corpus_6952", "text": "Routine  antenatal  antibody screening blood tests ( indirect Coombs test ) do not screen for ABO HDN. [ citation needed ]   If IgG anti-A or IgG anti-B antibodies are found in the pregnant woman's blood, they are not reported with the test results, because they do not correlate well with ABO HDN. [ citation needed ]   Diagnosis is usually made by investigation of a newborn baby who has developed  jaundice  during the first week of life."}
{"_id": "WikiPedia_Hematology$$$corpus_6953", "text": "Testing"}
{"_id": "WikiPedia_Hematology$$$corpus_6954", "text": "The antibodies in ABO HDN cause  anemia  due to destruction of fetal red blood cells and  jaundice  due to the rise in blood levels of  bilirubin  a by-product of  hemoglobin  break down. If the anemia is severe, it can be treated with a blood transfusion, however this is rarely needed. On the other hand, neonates have underdeveloped livers that are unable to process large amounts of bilirubin and a poorly developed  blood\u2013brain barrier  that is unable to block bilirubin from entering the brain. This can result in  kernicterus  if left unchecked. If the bilirubin level is sufficiently high as to cause worry, it can be lowered via  phototherapy  in the first instance or an  exchange transfusion  if severely elevated. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6955", "text": "Hemolytic disease of the newborn (anti-Kell 1 )  is the second most common cause of severe  hemolytic disease of the newborn  (HDN) after  Rh disease . [ 1 ]   Anti-Kell 1  is becoming relatively more important as prevention of Rh disease is also becoming more effective."}
{"_id": "WikiPedia_Hematology$$$corpus_6956", "text": "Hemolytic  disease of the  newborn  (anti-Kell 1 ) is caused by a mismatch between the  Kell antigens  of the  mother  and  fetus .  About 91% of the population are Kell 1  negative and about 9% are Kell 1  positive.  A fraction of a percentage are  homozygous  for Kell 1 . Therefore, about 4.5% of babies born to a Kell 1  negative mother are Kell 1  positive. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6957", "text": "The disease results when maternal  antibodies  to Kell 1  are transferred to the fetus across the  placental barrier , breaching  immune privilege . These antibodies can cause severe  anemia  by interfering with the early proliferation of  red blood cells  as well as causing  alloimmune  hemolysis.  Very severe disease can occur as early as 20 weeks gestation.   Hydrops fetalis  can also occur early.  The finding of anti-Kell antibodies in an antenatal screening blood test ( indirect Coombs test ) is an indication for early referral to a specialist service for assessment, management and treatment. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6958", "text": "Mothers who are negative for the Kell 1  antigen develop antibodies after being exposed to red blood cells that are positive for Kell 1 .  Over half of the cases of hemolytic disease of the newborn owing the anti-Kell antibodies are caused by multiple blood transfusions, with the remainder due to a previous pregnancy with a Kell 1  positive baby. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6959", "text": "Hemolytic disease of the fetus and newborn (HDN) is a condition where the passage of maternal antibodies results in the hemolysis of fetal/neonatal red cells. The antibodies can be naturally occurring such as anti-A, and anti-B, or immune antibodies developed following a sensitizing event. [ 11 ]  Isoimmunization occurs when the maternal immune system is sensitized to red blood cell surface antigens. The most common causes of isoimmunization are blood transfusion, and fetal-maternal hemorrhage. [ 12 ]  The hemolytic process can result in anemia, hyperbilirubinemia, neonatal thrombocytopenia, and neonatal neutropenia. [ 6 ]  With the use of RhD Immunoprophylaxis, (commonly called Rhogam), the incidence of anti-D has decreased dramatically and other alloantibodies are now a major cause of HDN. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6960", "text": "Anti-Kell can cause severe anemia regardless of titer. [ 13 ]  Anti-Kell suppresses the bone marrow, [ 14 ]  by inhibiting the erythroid progenitor cells. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6961", "text": "Hemolytic disease of the newborn can also be caused by anti-Kell 2 , anti-Kell 3  and anti-Kell 4  IgG antibodies.  These are rarer and generally the disease is milder. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6962", "text": "Testing for HDN involves blood work from both mother and father, and may also include assessment with amniocentesis and Middle Cerebral Artery scans. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6963", "text": "Blood testing for the mother is called an Indirect Coombs Test (ICT) or an Indirect Agglutination Test (IAT). This test tells whether there are antibodies in the maternal plasma. If positive, the antibody is identified and given a titer. Titers of 1:4 or higher is considered critical for Kell (compared to 1:16 for most other antibodies) and is considered to confer a high risk of fetal anemia. [ 17 ]  Such high titers may be managed by weekly follow-up by  obstetric ultrasound , assessing the peak systolic velocity of the fetal middle cerebral arterial (MCA), amniotic fluid volume, as well as fetal signs of anemia or hydrops. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6964", "text": "Blood is generally drawn from the father to help determine fetal antigen status. [ 18 ]  If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDN. If he is heterozygous, there is a 50% chance of offspring to be positive for the antigen. [ 19 ]  This test can help with knowledge for the current baby, as well as aid in the decision about future pregnancies. With RhD, the test is called the RhD genotype. With RhCE, and Kell antigen it is called an antigen phenotype. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6965", "text": "There are 3 possible ways to test the fetal antigen status. Cell-free DNA, Amniocentesis, and Chorionic Villus Sampling (CVS). Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6966", "text": "Middle cerebral artery - peak systolic velocity is changing the way sensitized pregnancies are managed. [ 22 ]  This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with  intrauterine transfusion  (IUT). [ 23 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6967", "text": "There are several intervention options available in early, mid and late pregnancies."}
{"_id": "WikiPedia_Hematology$$$corpus_6968", "text": "In some cases, the direct coombs will be negative but severe, even fatal HDN can occur. [ 35 ]  An indirect coombs needs to be run in cases of anti-C, [ 36 ]  anti-c, [ 36 ]  and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6969", "text": "Suggestions have been made that women of child-bearing age or young girls should not be given a  transfusion  with Kell 1  positive blood. Donated blood is not currently screened (in the U.S.A.) for the Kell blood group antigens as it is not considered cost effective at this time. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6970", "text": "It has been hypothesized [ by whom? ]  that IgG anti-Kell 1  antibody injections would prevent sensitization to RBC surface Kell 1  antigens in a similar way that IgG anti-D antibodies ( Rho(D) Immune Globulin ) are used to prevent  Rh disease , but the methods for IgG anti-Kell  1  antibodies have not been developed at the present time. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6971", "text": "Once a woman has antibodies, she is at high risk for a transfusion reaction. [ 42 ]  For this reason, she must carry a medical alert card at all times and inform all doctors of her antibody status. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6972", "text": "\"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A,B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures\" [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6973", "text": "Summary of transfusion reactions in the US [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6974", "text": "Hemolytic disease of the newborn  ( anti-Rhc ) can range from a mild to a severe disease. It is the third most common cause of severe HDN.  Rh disease  is the most common and  hemolytic disease of the newborn (anti-Kell)  is the second most common cause of severe HDN. It occurs more commonly in women who are Rh D negative. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6975", "text": "Once a woman has antibodies, she is at high risk for a transfusion reaction. [ 10 ]  For this reason, she must carry a medical alert card at all times and inform all doctors of her antibody status. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6976", "text": "\"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A,B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures.\" [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6977", "text": "A Rhc negative mother can become sensitised by  red blood cell  (RBC) Rhc antigens by her first pregnancy with a Rhc positive fetus.  The mother can make  IgG  anti-Rhc  antibodies , which are able to pass through the  placenta  and enter the fetal circulation.  If the fetus is Rhc positive  alloimmune   hemolysis  can occur leading to HDN.  This is similar as for  Rh disease , which is usually caused when a RhD negative mother is sensitised by her first pregnancy with a RhD positive fetus. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6978", "text": "Sensitization to Rhc antigens can also be caused by blood transfusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6979", "text": "Anti-C and anti-c can both show a negative DAT but still have a severely affected infant. [ 12 ] [ 13 ]  An indirect coombs must also be run."}
{"_id": "WikiPedia_Hematology$$$corpus_6980", "text": "In the case of anti-c, the woman should be checked around 28 weeks to see if she has developed anti-E as well. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6981", "text": "Blood testing for the mother is called an Indirect Coombs Test (ICT) or an Indirect Agglutination Test (IAT). This test tells whether there are antibodies in the maternal plasma. If positive, the antibody is identified and given a titer. Critical titers are associated with significant risk of fetal anemia and hydrops. [ 14 ]  Titers of 1:8 or higher is considered critical for Kell. Titers of 1:16 or higher are considered critical for all other antibodies. After critical titer is reached, care is based on MCA scans. If antibodies are low and have a sudden jump later in pregnancy, an MCA scan is warranted. If the titer undergoes a 4 fold increase, it should be considered significant regardless of if the critical value has been reached. Maternal titers are not useful in predicting fetal anemia after the first affected gestation and should not be used for the basis of care. [ 15 ]  Titers are tested monthly until 24 weeks, after which they are done every 2 weeks. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6982", "text": "\"In only 2 situations are patients not monitored identically to patients who are Rh sensitized. The first is that of alloimmunization to the c, E, or, C antigens. Some concern exists that hemolysis may occur in these patients with a lower than 1:16 titer. Thus, if the initial titer is 1:4 and stable but increases at 26 weeks' gestation to 1:8, assessment with MCA Doppler velocity at that point is reasonable. However, if the patient presents in the first trimester with a 1:8 titer that remains stable at 1:8 throughout the second trimester, continued serial antibody titers are appropriate.\nThe second situation in which patients should not be treated identically to patients who are Rh D sensitized is that of Kell isoimmunization because several cases of severe fetal hemolysis with anti-Kell antibodies have occurred in the setting of low titers.\" [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6983", "text": "In the case of a positive ICT, the woman must carry a medical alert card or bracelet for life because of the risk of a transfusion reaction. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6984", "text": "There are 3 possible ways to test the fetal antigen status. Free Cell DNA, Amniocentesis, and Chorionic Villus Sampling (CVS). Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6985", "text": "MCA scans: Middle cerebral artery - peak systolic velocity is changing the way sensitized pregnancies are managed. [ 22 ]  This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with IUT. [ 23 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6986", "text": "It has been suggested that women of child-bearing age or young girls should not be given a  transfusion  with Rhc positive blood (or Kell  1  positive blood for similar reasons).  This would require a lot of extra work in blood transfusion departments and it is considered not economical to do the blood group screening at the present time. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6987", "text": "It is theoretically likely that IgG anti-Rhc antibody injections would prevent sensitization to RBC surface Rhc antigens in a similar way that IgG anti-D antibodies ( Rho(D) immune globulin ) are used to prevent  Rh disease , but the methods for IgG anti-Rhc antibodies have not been developed at the present time. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6988", "text": "In some cases, the direct coombs will be negative but severe, even fatal HDN can occur. [ 12 ]  An indirect coombs needs to be run in cases of anti-C, [ 13 ]  anti-c, [ 13 ]  and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6989", "text": "Hemolytic disease of the fetus and newborn (HDN) is a condition where the passage of maternal antibodies results in the hemolysis of fetal/neonatal red cells. The antibodies can be naturally occurring such as anti-A, and anti-B, or immune antibodies developed following a sensitizing event. [ 38 ]  Isoimmunization occurs when the maternal immune system is sensitized to red blood cell surface antigens. The most common causes of isoimmunization are blood transfusion, and fetal-maternal hemorrhage. [ 16 ]  The hemolytic process can result in anemia, hyperbilirubinemia, neonatal thrombocytopenia, and neonatal neutropenia. [ 5 ]  With the use of RhD Immunoprophylaxis, (commonly called Rhogam), the incidence of anti-D has decreased dramatically and other alloantibodies are now a major cause of HDN. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6990", "text": "Hemolytic disease of the newborn  ( anti-RhE ) is caused by the anti-RhE antibody of the  Rh blood group system . The anti-RhE  antibody  can be naturally occurring, or arise following  immune  sensitization after a  blood transfusion  or pregnancy."}
{"_id": "WikiPedia_Hematology$$$corpus_6991", "text": "The anti-RhE antibody is quite common especially in the Rh genotype CDe/CDe; it usually only causes a mild hemolytic disease, but can cause a severe condition in the newborn.  It can occur with other antibodies, usually the anti-Rhc antibody, which can also cause a severe hemolytic disease. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6992", "text": "One study done by Moran et al., found that titers are not reliable for anti-E. Their most severe case of  hemolytic disease of the newborn  occurred with titers 1:2. Moran states that it would be unwise routinely to dismiss anti-E as being of little clinical consequence. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6993", "text": "Hemolytic disease of the fetus and newborn (HDN) is a condition where the passage of maternal antibodies results in the hemolysis of fetal/neonatal red cells. The antibodies can be naturally occurring such as anti-A, and anti-B, or immune antibodies developed following a sensitizing event. [ 12 ]  Isoimmunization occurs when the maternal immune system is sensitized to red blood cell surface antigens. The most common causes of isoimmunization are blood transfusion, and fetal-maternal hemorrhage. [ 13 ]  The hemolytic process can result in anemia, hyperbilirubinemia, neonatal thrombocytopenia, and neonatal neutropenia. [ 7 ]  With the use of RhD Immunoprophylaxis, (commonly called Rhogam), the incidence of anti-D has decreased dramatically and other alloantibodies are now a major cause of HDN. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6994", "text": "In the case of anti-E, the woman should be checked around 28 weeks to see if she has developed anti-c as well. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6995", "text": "Blood testing for the mother is called an indirect  Coombs test  (ICT) or an indirect agglutination test (IAT). This test tells whether there are antibodies in the maternal plasma. If positive, the antibody is identified and given a titer. Critical titers are associated with significant risk of fetal anemia and hydrops. [ 1 ]  Titers of 1:8 or higher is considered critical for Kell. Titers of 1:16 or higher are considered critical for all other antibodies. After critical titer is reached, care is based on MCA scans. If antibodies are low and have a sudden jump later in pregnancy, an MCA scan is warranted. If the titer undergoes a 4 fold increase, it should be considered significant regardless of if the critical value has been reached. Maternal titers are not useful in predicting fetal anemia after the first affected gestation and should not be used for the basis of care. [ 14 ]  Titers are tested monthly until 24 weeks, after which they are done every 2 weeks. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6996", "text": "\"In only 2 situations are patients not monitored identically to patients who are Rh sensitized. The first is that of alloimmunization to the c, E, or, C antigens. Some concern exists that hemolysis may occur in these patients with a lower than 1:16 titer. Thus, if the initial titer is 1:4 and stable but increases at 26 weeks' gestation to 1:8, assessment with MCA Doppler velocity at that point is reasonable. However, if the patient presents in the first trimester with a 1:8 titer that remains stable at 1:8 throughout the second trimester, continued serial antibody titers are appropriate.\nThe second situation in which patients should not be treated identically to patients who are Rh D sensitized is that of Kell isoimmunization because several cases of severe fetal hemolysis with anti-Kell antibodies have occurred in the setting of low titers.\" [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6997", "text": "In the case of a positive ICT, the woman must carry a medical alert card or bracelet for life because of the risk of a transfusion reaction. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6998", "text": "Blood is generally drawn from the father to help determine fetal antigen status. [ 15 ]  If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDN. If he is heterozygous, there is a 50% chance of offspring to be positive for the antigen. [ 16 ]  This test can help with knowledge for the current baby, as well as aid in the decision about future pregnancies. With RhD, the test is called the RhD genotype. With RhCE, and Kell antigen it is called an antigen phenotype. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_6999", "text": "There are three possible ways to test the fetal antigen status. Free cell DNA,  amniocentesis , and  chorionic villus sampling  (CVS). Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7000", "text": "Middle cerebral artery \u2013 peak systolic velocity is changing the way sensitized pregnancies are managed. [ 18 ]  This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with IUT. [ 19 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7001", "text": "There are several intervention options available in early, mid and late pregnancies. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7002", "text": "In some cases, the direct Coombs will be negative but severe, even fatal HDN can occur. [ 29 ]  An indirect Coombs needs to be run in cases of anti-C, [ 30 ]  anti-c, [ 30 ]  and anti-M. Anti-M also recommends antigen testing to rule out the presence of HDN. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7003", "text": "Once a woman has antibodies, she is at high risk for a transfusion reaction. [ 36 ]  For this reason, she must carry a medical alert card at all times and inform all doctors of her antibody status. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7004", "text": "\"Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated. Immune-mediated hemolytic transfusion reactions caused by immunoglobulin M (IgM) anti-A, anti-B, or anti-A,B typically result in severe, potentially fatal complement-mediated intravascular hemolysis. Immune-mediated hemolytic reactions caused by IgG, Rh, Kell, Duffy, or other non-ABO antibodies typically result in extravascular sequestration, shortened survival of transfused red cells, and relatively mild clinical reactions. Acute hemolytic transfusion reactions due to immune hemolysis may occur in patients who have no antibodies detectable by routine laboratory procedures.\" [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7005", "text": "Summary of transfusion reactions in the US: [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7006", "text": "Hemoperfusion  or  h\u00e6moperfusion  (see  spelling differences ) is a method of filtering the  blood  extracorporeally (that is, outside the body) to remove a  toxin . As with other extracorporeal methods, such as  hemodialysis  (HD),  hemofiltration  (HF), and  hemodiafiltration  (HDF), the blood travels from the patient into a machine, gets filtered, and then travels back into the patient, typically by venovenous access (out of a  vein  and back into a vein)."}
{"_id": "WikiPedia_Hematology$$$corpus_7007", "text": "In hemoperfusion, the blood perfuses a filter composed of  artificial cells  filled with  activated carbon  or another  microporous material . Small  molecules  in  solution  within the  serum  (such as the toxin) cross the membranes into the microporous material (and get trapped therein), but formed elements (the  blood cells ) brush past the artificial cells just as they brush past each other. In this way, the microporous material's filtering ability can be used  without destroying the blood cells ."}
{"_id": "WikiPedia_Hematology$$$corpus_7008", "text": "First introduced in the 1940s, hemoperfusion was refined during the 1950s through 1970s, and then introduced clinically for the treatment of  poisoning  in the 1970s and 1980s. It is sometimes used to treat  drug overdose , sometimes in conjunction with the other extracorporeal techniques previously mentioned. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7009", "text": "The US  Food and Drug Administration  (FDA) defines sorbent hemoperfusion as follows:"}
{"_id": "WikiPedia_Hematology$$$corpus_7010", "text": "\u2033(a) Identification. A sorbent hemoperfusion system is a prescription device that consists of an extracorporeal blood system similar to that identified in the hemodialysis system and accessories (876.5820) and a container filled with adsorbent material that removes a wide range of substances, both toxic and normal, from blood flowing through it. The adsorbent materials are usually activated-carbon or resins which may be coated or immobilized to prevent fine particles entering the patient's blood. The generic type of device may include lines and filters specifically designed to connect the device to the extracorporeal blood system. The device is used in the treatment of poisoning, drug overdose, hepatic coma, or metabolic disturbances.\u2033\n [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7011", "text": "Hemoperfusion is also used in the treatment of specific intoxications, such as  valproic acid ,  theophylline , and  meprobamate . [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7012", "text": "Despite its availability, this technique is only infrequently utilized as a medical process used to remove toxic substances from a patient's blood. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7013", "text": "Two types of hemoperfusion are commonly used: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7014", "text": "Complications of hemoperfusion may include  thrombocytopenia ,  leucopenia ,  hypoglycemia , and some reduction in clotting factors, with recovery typically occurring in 1\u20132 days. Risk of bleeding is also higher because of the high heparin dose and reduction in platelets and clotting factors. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7015", "text": "During hemoperfusion, the blood passes through a column with absorptive properties aiming at removing specific toxic substances from the patient's blood. It especially targets small- to medium-sized  molecules  that tend to be more difficult to remove by conventional  hemodialysis . The adsorbent substance most commonly used in hemoperfusion are resins and  activated carbon . [ 7 ]  Hemoperfusion is an  extracorporeal  form of treatment because the blood is pumped through a device outside the patient's body. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7016", "text": "Its major uses include removing  drugs  or  poisons  from the blood in emergency situations, removing waste products from the blood in patients with  kidney failure , and as a supportive treatment for patients before and after  liver transplantation . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7017", "text": "Hemotherapy  ( / h i\u02d0 m \u0259 \u02c8 \u03b8 \u025br \u0259 p i /   HEE -m\u0259- THERR -\u0259-pee ) or  hemotherapeutics  ( / h i\u02d0 m \u0259 \u03b8 \u025br \u0259 \u02c8 p ju\u02d0 t \u026a k s /   HEE -m\u0259- THERR -\u0259- PEW -tiks ) is the treatment of  disease  by the use of  blood  or  blood products  from  blood donation  ( by others  or  for oneself ). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7018", "text": "It includes various types, such as: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7019", "text": "hh , [ 1 ]  or the  Bombay blood  group, is a rare  blood type . This blood  phenotype  was first discovered in  Bombay  by Dr. Y. M. Bhende in 1952. It is mostly found in the  Indian subcontinent  ( India ,  Bangladesh ,  Pakistan ) and  Iran ."}
{"_id": "WikiPedia_Hematology$$$corpus_7020", "text": "The first person found to have the Bombay phenotype had a blood type that reacted to other blood types in a way never seen before. The serum contained  antibodies  that attacked all  red blood cells  of normal  ABO phenotypes . The red blood cells appeared to lack all of the ABO blood group antigens and to have an additional antigen that was previously unknown. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7021", "text": "Individuals with the rare Bombay phenotype (hh) do not express  H antigen  (also called substance H), the antigen which is present in blood group O. As a result, they cannot make  A antigen  (also called substance A) or  B antigen  (substance B) on their red blood cells, whatever alleles they may have of the A and B blood-group genes, because A antigen and B antigen are made from H antigen.  For this reason people who have Bombay phenotype can donate red blood cells to any member of the ABO blood group system (unless some other blood factor gene, such as  Rh , is incompatible), but they cannot receive blood from any member of the ABO blood group system (which always contains one or more of A, B or H antigens), but only from other people who have Bombay phenotype. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7022", "text": "Receiving blood that contains an antigen which has never been in the patient's own blood causes an immune reaction due to the immune system of a hypothetical receiver producing immunoglobulins against that antigen\u2014in the case of a Bombay patient, not only against antigens A and B, but also against H antigen."}
{"_id": "WikiPedia_Hematology$$$corpus_7023", "text": "In order to avoid complications during a  blood transfusion , it is very important to detect Bombay phenotype individuals, but the usual tests for ABO blood group system would show them as group O. Since anti-H  immunoglobulins  can activate the  complement cascade , it will lead to the lysis of red blood cells while they are still in the circulation, provoking an  acute hemolytic transfusion reaction . This cannot be prevented unless those typing the blood and providing care are aware of the existence of the Bombay blood group and have the means to test for it. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7024", "text": "This very rare phenotype is generally present in about 0.0004% (about 4 per million) of the human population, though in some places such as  Mumbai  (formerly Bombay) locals can have occurrences in as much as 0.01% (1 in 10,000) of inhabitants. Given that this condition is very rare, any person with this blood group who needs an urgent blood transfusion will probably be unable to get it, as no  blood bank  would have any in stock. Those anticipating the need for blood transfusion may bank blood for their own use, but this option is not available in cases of accidental injury. For example, by 2017 only one  Colombian  person was known to have this phenotype, and blood had to be imported from  Brazil  for a transfusion. [ 2 ]  In 2023, it was reported that only three registered Brazilians nationwide possessed this phenotype. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7025", "text": "Biosynthesis  of the H, A and B antigens involves a series of  enzymes  (glycosyl transferases) that transfer  monosaccharides . The resulting antigens are  oligosaccharide  chains, which are attached to  lipids  and  proteins  that are anchored in the red blood cell membrane. The function of the H antigen, apart from being an intermediate substrate in the synthesis of ABO blood group antigens, is not known, although it may be involved in  cell adhesion . People who lack the H antigen do not suffer from deleterious effects, and being H-deficient is only an issue if they need a blood transfusion, because they would need blood without the H antigen present on red blood cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7026", "text": "The specificity of the H antigen is determined by the sequence of  oligosaccharides . More specifically, the minimum requirement for H antigenicity is the terminal disaccharide  fucose - galactose , where the fucose has an alpha(1-2)linkage. This antigen is produced by a specific fucosyl transferase ( Galactoside 2-alpha-L-fucosyltransferase 2 ) that catalyzes the final step in the synthesis of the molecule. Depending upon a person's ABO blood type, the H antigen is converted into either the A antigen, B antigen, or both. If a person has group O blood, the H antigen remains unmodified. Therefore, the H antigen is present more in blood type O and less in blood type AB."}
{"_id": "WikiPedia_Hematology$$$corpus_7027", "text": "Two regions of the genome encode two enzymes with very similar substrate specificities: the H locus ( FUT1 ) which encodes the fucosyl transferase and the Se locus ( FUT2 ) that instead indirectly encodes a soluble form of the transferase, which is found in bodily secretions. Both genes are on  chromosome 19  at q.13.3. \u2014 FUT1 and FUT2 are tightly linked, being only 35 kb apart. Because they are highly  homologous , they are likely to have been the result of a gene duplication of a common gene ancestor."}
{"_id": "WikiPedia_Hematology$$$corpus_7028", "text": "The H locus contains four  exons  that span more than 8 kb of genomic DNA. Both the Bombay and para-Bombay phenotypes are the result of point mutations in the FUT1 gene. At least one functioning copy of FUT1 needs to be present (H/H or H/h) for the H antigen to be produced on red blood cells. If both copies of FUT1 are inactive (h/h), the Bombay phenotype results. The classical Bombay phenotype is caused by a Tyr316Ter mutation in the coding region of FUT1. The mutation introduces a stop codon, leading to a truncated enzyme that lacks 50 amino acids at the C-terminal end, rendering the enzyme inactive. In Caucasians, the Bombay phenotype may be caused by a number of mutations. Likewise, a number of mutations have been reported to underlie the para-Bombay phenotype. The Se locus contains the FUT2 gene, which is expressed in secretory glands. Individuals who are \"secretors\" (Se/Se or Se/se) contain at least one copy of a functioning enzyme. They produce a soluble form of H antigen that is found in saliva and other bodily fluids. \"Non-secretors\" (se/se) do not produce soluble H antigen. The enzyme encoded by FUT2 is also involved in the synthesis of antigens of the Lewis blood group."}
{"_id": "WikiPedia_Hematology$$$corpus_7029", "text": "Bombay phenotype occurs in individuals who have inherited two recessive alleles of the H gene (i.e. their genotype is hh). These individuals do not produce the H carbohydrate that is the precursor to the A and B antigens, meaning that individuals may possess alleles for either or both of the A and B alleles without being able to express them. Because both parents must carry this recessive allele to transmit this blood type to their children, the condition mainly occurs in small closed-off communities where there is a good chance of both parents of a child either being of Bombay type, or being heterozygous for the h allele and so carrying the Bombay characteristic as recessive. Other examples may include noble families, which are inbred due to custom rather than local genetic variety."}
{"_id": "WikiPedia_Hematology$$$corpus_7030", "text": "In theory, the maternal production of anti-H during pregnancy might cause hemolytic disease (HDN) in a fetus who did not inherit the mother's Bombay phenotype. In practice, cases of HDN caused in this way have not been described. This may be due to the rarity of the Bombay phenotype."}
{"_id": "WikiPedia_Hematology$$$corpus_7031", "text": "The term  human blood group systems  is defined by the  International Society of Blood Transfusion  (ISBT) as systems in the human species where cell-surface  antigens \u2014in particular, those on blood cells\u2014are \"controlled at a single gene  locus  or by two or more very closely linked  homologous  genes with little or no observable  recombination  between them\", [ 1 ]  and include the common  ABO  and  Rh (Rhesus)  antigen systems, as well as many others; 44 human systems are identified as of 31\u00a0December\u00a02022 [update] . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7032", "text": "Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems: [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7033", "text": "Blood compatibility testing is performed before  blood transfusion , including matching of the  ABO blood group system  and the  Rh blood group system , as well as screening for recipient antibodies against other human blood group systems. Blood compatibility testing is also routinely performed on pregnant women and on the  cord blood  from newborn babies, because incompatibility puts the baby at risk for developing  hemolytic disease of the newborn . [ 13 ] [ 14 ]  It is also used before  hematopoietic stem cell transplantation , as it may be responsible for some cases of acute  graft-versus-host disease . [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7034", "text": "Other human blood group systems than ABO and Rh have a relatively small risk of complications when blood is mixed. [ 16 ]  Therefore, in emergencies such as major  hemorrhage , the urgency of transfusion can exceed the need for compatibility testing against other blood group systems (and potentially Rh as well). [ 16 ]  Also, blood compatibility testing beyond ABO and Rh is generally limited to antibody detection (not necessarily including forward typing). Still, in Europe, females who require blood transfusions are often typed for the  K  and extended Rh antigens to prevent sensitization to these antigens, which could put them at risk for developing  hemolytic disease of the newborn  during pregnancy. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7035", "text": "When needing to give red blood cell transfusion to a patient, the presence of clinically significant antibodies produced by the patient can be detected by mixing patient serum with 2 to 4 \"screening\" or \"control\" red blood cells that together display essentially all relevant antigens. If any of these mixes display a reaction (evidence of patient antibodies binding to the screening red blood cells), a more extensive antibody panel is warranted (as imaged at right). [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7036", "text": "The  human leukocyte antigen  ( HLA ) system is a complex of  genes  on  chromosome 6  in humans that encode  cell-surface proteins  responsible for regulation of the  immune system . [ 1 ]  The HLA system is also known as the human version of the  major histocompatibility complex  (MHC) found in many animals. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7037", "text": "Mutations in HLA genes may be linked to  autoimmune diseases  such as  type I diabetes , and  celiac disease . The HLA gene complex resides on a 3  Mbp  stretch within  chromosome 6, p-arm  at 21.3. HLA genes are highly  polymorphic , which means that they have many different  alleles , allowing them to fine-tune the  adaptive immune system . The proteins encoded by certain genes are also known as  antigens , as a result of their  historic discovery  as factors in  organ transplants . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7038", "text": "HLAs corresponding to  MHC class I  ( A ,  B , and  C ), all of which are the HLA Class1 group, present peptides from inside the cell. For example, if the cell is infected by a virus, the HLA system brings fragments of the virus to the surface of the cell so that the cell can be destroyed by the immune system. These peptides are produced from digested proteins that are broken down in the  proteasomes . In general, these particular peptides are small  polymers , of about 8-10  amino acids  in length. [ 4 ]  Foreign antigens presented by MHC class I attract T-lymphocytes called  killer T-cells  (also referred to as  CD8 -positive or cytotoxic T-cells) that destroy cells. Some new work has proposed that antigens longer than 10 amino acids, 11-14 amino acids, can be presented on MHC I, eliciting a cytotoxic T-cell response. [ 5 ]  MHC class I proteins associate with  \u03b22-microglobulin , which, unlike the HLA proteins, is encoded by a gene on  chromosome 15 ."}
{"_id": "WikiPedia_Hematology$$$corpus_7039", "text": "HLAs corresponding to  MHC class II  ( DP ,  DM ,  DO ,  DQ , and  DR ) present antigens from outside of the cell to T-lymphocytes. These particular antigens stimulate multiplication of  T-helper cells  (also called  CD4 -positive T cells), which in turn stimulate  antibody -producing  B-cells  to produce antibodies to that specific antigen. Self-antigens are suppressed by  regulatory T cells . Predicting which (fragments of) antigens will be presented to the immune system by a certain HLA type is difficult, but the technology involved is improving. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7040", "text": "HLAs corresponding to  MHC class III  encode components of the  complement system ."}
{"_id": "WikiPedia_Hematology$$$corpus_7041", "text": "HLAs have other roles. They are important in disease defense. They are the major cause of  organ transplant rejection . They may protect against cancers or fail to protect (if down-regulated by an infection). [ 7 ]  HLA may also be related to people's perception of the odor of other people, and may be involved in mate selection, as at least one study found a lower-than-expected rate of HLA similarity between spouses in an isolated community. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7042", "text": "Aside from the genes encoding the six major antigen-presenting proteins, many other genes, many involved in immune function, are located on the HLA complex. Diversity of HLAs in the human population is one aspect of disease defense, and, as a result, the chance of two unrelated individuals with identical HLA molecules on all  loci  is extremely low. HLA genes have historically been identified as a result of the ability to successfully transplant organs between HLA-similar individuals. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7043", "text": "The  proteins  encoded by HLAs are those on the outer part of body cells that are (in effect) unique to that person. The  immune system  uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person's HLA type belongs to that person and is therefore not an invader."}
{"_id": "WikiPedia_Hematology$$$corpus_7044", "text": "When a foreign  pathogen  enters the body, specific  cells  called  antigen-presenting cells  (APCs) engulf the pathogen through a process called  phagocytosis .  Proteins  from the pathogen are digested into small pieces ( peptides ) and loaded on to HLA antigens (to be specific,  MHC class II ). They are then displayed by the  antigen-presenting cells  to  CD4+ helper T cells , [ 10 ]  which then produce a variety of effects and cell-to-cell interactions to eliminate the pathogen."}
{"_id": "WikiPedia_Hematology$$$corpus_7045", "text": "Through a similar process, proteins (both native and foreign, such as the proteins of viruses) produced inside most cells are displayed on HLAs (to be specific,  MHC class I ) on the cell surface. Infected cells can be recognized and destroyed by  CD8+ T cells . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7046", "text": "The image off to the side shows a piece of a poisonous bacterial protein (SEI peptide) bound within the binding cleft portion of the HLA-DR1 molecule. In the illustration far below, a different view, one can see an entire DQ with a bound peptide in a similar cleft, as viewed from the side. Disease-related peptides fit into these \"slots\" much like a hand fits into a glove."}
{"_id": "WikiPedia_Hematology$$$corpus_7047", "text": "When bound, peptides are presented to T-cells. T-cells require presentation via MHC molecules to recognize foreign antigens\u2014a requirement known as  MHC restriction . T-cells have receptors that are similar to B-cell receptors, and each T-cell recognizes only a few MHC class II-peptide combinations. Once a T-cell recognizes a peptide within an MHC class II molecule, it can stimulate B-cells that also recognize the same molecule in their B-cell receptors. Thus, T-cells help B-cells make antibodies to the same foreign antigens. Each HLA can bind many peptides, and each person has 3 HLA types and can have 4 isoforms of DP, 4 isoforms of DQ and 4 Isoforms of DR (2 of DRB1, and 2 of DRB3, DRB4, or DRB5) for a total of 12 isoforms. In such heterozygotes, it is difficult for disease-related proteins to escape detection."}
{"_id": "WikiPedia_Hematology$$$corpus_7048", "text": "Any cell displaying some other HLA type is \"non-self\" and is seen as an invader by the body's immune system, resulting in the rejection of the tissue bearing those cells. This is particularly important in the case of transplanted tissue, because it could lead to  transplant rejection . Because of the importance of HLA in transplantation, the HLA loci are some of the most frequently typed by serology and PCR. It has been shown that high resolution HLA typing (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1) may be relevant in transplantation to identify a full match, even when the donor is related. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7049", "text": "HLA types are inherited, and some of them are connected with  autoimmune disorders  and other diseases. People with certain HLA antigens are more likely to develop certain autoimmune diseases, such as  type I diabetes ,  ankylosing spondylitis ,  rheumatoid arthritis , [ 15 ]   celiac disease ,  SLE  (systemic lupus erythematosus),  myasthenia gravis ,  inclusion body myositis ,  Sj\u00f6gren syndrome , and  narcolepsy . [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7050", "text": "HLA typing has led to some improvement and acceleration in the diagnosis of celiac disease and type 1 diabetes; however, for DQ2 typing to be useful, it requires either high-resolution B1*typing (resolving *02:01 from *02:02), DQA1*typing, or DR  serotyping . Current serotyping can resolve, in one step, DQ8. HLA typing in autoimmunity is being increasingly used as a tool in diagnosis. In  celiac disease , it is the only effective means of discriminating between first-degree relatives that are at risk from those that are not at risk, prior to the appearance of sometimes-irreversible symptoms such as allergies and secondary autoimmune disease."}
{"_id": "WikiPedia_Hematology$$$corpus_7051", "text": "Some HLA-mediated diseases are directly involved in the promotion of cancer. Gluten-sensitive enteropathy is associated with increased prevalence of enteropathy-associated T-cell lymphoma, and DR3-DQ2 homozygotes are within the highest risk group, with close to 80% of gluten-sensitive enteropathy-associated T-cell lymphoma cases. More often, however, HLA molecules play a protective role, recognizing increases in antigens that are not tolerated because of low levels in the normal state. Abnormal cells might be targeted for  apoptosis , which is thought to mediate many cancers before diagnosis."}
{"_id": "WikiPedia_Hematology$$$corpus_7052", "text": "There is evidence for non-random  mate choice  with respect to certain genetic characteristics. [ 17 ] [ 18 ]  This has led to a field known as  genetic matchmaking ."}
{"_id": "WikiPedia_Hematology$$$corpus_7053", "text": "MHC class I proteins form a functional receptor on most nucleated cells of the body. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7054", "text": "There are three major and three minor MHC class I genes in HLA."}
{"_id": "WikiPedia_Hematology$$$corpus_7055", "text": "Major MHC class I"}
{"_id": "WikiPedia_Hematology$$$corpus_7056", "text": "Minor genes are  HLA-E ,  HLA-F  and  HLA-G .  \u03b2 2 -microglobulin  binds with major and minor gene subunits to produce a heterodimer."}
{"_id": "WikiPedia_Hematology$$$corpus_7057", "text": "There are three major and two minor MHC class II proteins encoded by the HLA.\nThe genes of the class II combine to form heterodimeric (\u03b1\u03b2) protein\nreceptors that are typically expressed on the surface of  antigen-presenting cells ."}
{"_id": "WikiPedia_Hematology$$$corpus_7058", "text": "Major MHC class II proteins only occur on  antigen-presenting cells ,  B cells , and  T cells . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7059", "text": "The other MHC class II proteins, DM and DO, are used in the internal processing of antigens, loading the antigenic peptides generated from pathogens onto the HLA molecules of  antigen-presenting cell ."}
{"_id": "WikiPedia_Hematology$$$corpus_7060", "text": "Modern HLA alleles are typically noted with a variety of levels of detail. Most designations begin with HLA- and the locus name, then * and some (even) number of digits specifying the allele. The first two digits specify a group of alleles, also known as supertypes. Older typing methodologies often could not completely distinguish alleles and so stopped at this level. The third through fourth digits specify a nonsynonymous allele. Digits five through six denote any synonymous mutations within the coding frame of the gene. The seventh and eighth digits distinguish mutations outside the coding region. Letters such as L, N, Q, or S may follow an allele's designation to specify an expression level or other non-genomic data known about it. Thus, a completely described allele may be up to 9 digits long, not including the HLA-prefix and locus notation. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7061", "text": "MHC loci are some of the most genetically variable coding loci in mammals, and the human HLA loci are no exceptions. Despite the fact that the human population went through a constriction several times during its history that was capable of fixing many loci, the HLA loci appear to have survived such a constriction with a great deal of variation. [ 20 ]  Of the 9 loci mentioned above, most retained a dozen or more allele-groups for each locus, far more preserved variation than the vast majority of human loci. This is consistent with a heterozygous or  balancing selection  coefficient for these loci. In addition, some HLA loci are among the fastest-evolving coding regions in the human genome. One mechanism of diversification has been noted in the study of Amazonian tribes of South America that appear to have undergone intense  gene conversion  between variable alleles and loci within each HLA gene class. [ 21 ]  Less frequently, longer-range productive recombinations through HLA genes have been noted producing chimeric genes."}
{"_id": "WikiPedia_Hematology$$$corpus_7062", "text": "Six loci have over 100 alleles that have been detected in the human population. Of these, the most variable are HLA B and HLA DRB1. As of 2012, the number of alleles that have been determined are listed in the table below. To interpret this table, it is necessary to consider that an allele is a variant of the nucleotide (DNA) sequence at a locus, such that each allele differs from all other alleles in at least one (single nucleotide polymorphism, SNP) position. Most of these changes result in a change in the amino acid sequences that result in slight to major functional differences in the protein."}
{"_id": "WikiPedia_Hematology$$$corpus_7063", "text": "There are issues that limit this variation. Certain alleles like DQA1*05:01 and DQA1*05:05 encode proteins with identically processed products. Other alleles like DQB1*0201 and DQB1*0202 produce proteins that are functionally similar. For class II (DR, DP and DQ), amino acid variants within the receptor's peptide-binding cleft tend to produce molecules with different binding capability."}
{"_id": "WikiPedia_Hematology$$$corpus_7064", "text": "However, the gene frequencies of the most common alleles (>5%) of HLA-A, -B, -C and HLA-DPA1, -DPB1, -DQA1, -DQB1,  and -DRB1 from South America have been reported from the typing and sequencing carried out in genetic diversity studies and cases and controls. [ 22 ]  In addition, information on the allele frequencies of HLA-I and HLA-II genes for the European population has been compiled. [ 23 ] [ 24 ]  In both cases the distribution of allele frequencies reveals a regional variation related with the history of the populations."}
{"_id": "WikiPedia_Hematology$$$corpus_7065", "text": "Number of variant alleles at class I loci according to the IMGT-HLA database, last updated October 2018:"}
{"_id": "WikiPedia_Hematology$$$corpus_7066", "text": "Number of variant alleles at class II loci (DM, DO, DP, DQ, and DR):"}
{"_id": "WikiPedia_Hematology$$$corpus_7067", "text": "The large extent of variability in HLA genes poses significant challenges in investigating the role of HLA genetic variations in diseases. Disease association studies typically treat each HLA allele as a single complete unit, which does not illuminate the parts of the molecule associated with disease. Karp D. R. et al. describes a novel  sequence feature variant type  (SFVT) approach for HLA genetic analysis that categorizes HLA proteins into biologically relevant smaller sequence features (SFs), and their variant types (VTs). [ 27 ]  Sequence features are combinations of amino acid sites defined based on structural information (e.g., beta-sheet 1), functional information (e.g., peptide antigen-binding), and polymorphism. These sequence features can be overlapping and continuous or discontinuous in the linear sequence. Variant types for each sequence feature are defined based upon all known polymorphisms in the HLA locus being described. SFVT categorization of HLA is applied in genetic association analysis so that the effects and roles of the epitopes shared by several HLA alleles can be identified. Sequence features and their variant types have been described for all classical HLA proteins; the international repository of HLA SFVTs will be maintained at IMGT/HLA database. [ 28 ]   A tool to convert HLA alleles into their component SFVTs can be found on the Immunology Database and Analysis Portal (ImmPort) website. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7068", "text": "Although the number of individual HLA alleles that have been identified is large, approximately 40% of these alleles appear to be unique, having only been identified in single individuals. [ 30 ] [ 31 ]  Roughly a third of alleles have been reported more than three times in unrelated individuals. [ 31 ] [ 32 ]  Because of this variation in the rate at which of individual HLA alleles are detected, attempts have been made to categorize alleles at each expressed HLA locus in terms of their prevalence. The result is a catalog of common and well-documented (CWD) HLA alleles, [ 32 ] [ 33 ]  and a catalogue of rare and very rare HLA alleles. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7069", "text": "Common HLA alleles are defined as having been observed with a frequency of at least 0.001 in reference populations of at least 1500 individuals. [ 32 ] [ 33 ]  Well-documented HLA alleles were originally defined as having been reported at least three times in unrelated individuals, [ 32 ]  and are now defined as having been detected at least five times in unrelated individuals via the application of a sequence-based typing (SBT) method, or at least three times via a SBT method and in a specific haplotype in unrelated individuals. [ 33 ]  Rare alleles are defined as those that have been reported one to four times, and very rare alleles as those reported only once. [ 30 ] [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7070", "text": "While the current CWD and rare or very rare designations were developed using different datasets and different versions of the  IMGT/HLA Database , [ 31 ] [ 33 ]  the approximate fraction of alleles at each HLA locus in each category is shown below."}
{"_id": "WikiPedia_Hematology$$$corpus_7071", "text": "There are two parallel systems of nomenclature that are applied to HLA. The first, and oldest, system is based on serological (antibody based) recognition. In this system, antigens were eventually assigned letters and numbers (e.g.,  HLA-B27  or, shortened, B27). A parallel system that allowed more refined definition of alleles was developed. In this system, an \"HLA\" is used in conjunction with a letter, *, and a four-or-more-digit number (e.g., HLA-B*08:01, A*68:01, A*24:02:01N N=Null) to designate a specific  allele  at a given HLA  locus . HLA loci can be further classified into  MHC class I  and  MHC class II  (or rarely, D locus). Every two years, a nomenclature is put forth to aid researchers in interpreting serotypes to alleles. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7072", "text": "In order to create a typing reagent, blood from animals or humans would be taken, the blood cells allowed to separate from the serum, and the serum diluted to its optimal sensitivity and used to type cells from other individuals or animals. Thus, serotyping became a way of crudely identifying HLA receptors and receptor isoforms. Over the years, serotyping antibodies became more refined as techniques for increasing sensitivity improved and new serotyping antibodies continue to appear. One of the goals of serotype analysis is to fill gaps in the analysis. It is possible to predict based on 'square root','maximum-likelihood' method, or analysis of familial haplotypes to account for adequately typed alleles. These studies using serotyping techniques frequently revealed, in particular for non-European or north East Asian populations many null or blank serotypes. This was particularly problematic for the Cw locus until recently, and almost half of the Cw serotypes went untyped in the 1991 survey of the human population."}
{"_id": "WikiPedia_Hematology$$$corpus_7073", "text": "There are several types of serotypes. A broad antigen serotype is a crude measure of identity of cells. For example, HLA A9 serotype recognizes cells of A23- and A24-bearing individuals. It may also recognize cells that A23 and A24 miss because of small variations. A23 and A24 are split antigens, but antibodies specific to either are typically used more often than antibodies to broad antigens."}
{"_id": "WikiPedia_Hematology$$$corpus_7074", "text": "A representative cellular assay is the mixed lymphocyte culture (MLC) and used to determine the HLA class II types. [ 34 ]  The cellular assay is more sensitive in detecting HLA differences than serotyping. This is because minor differences unrecognized by alloantisera can stimulate T cells. This typing is designated as Dw types. Serotyped DR1 has cellularly defined as either of Dw1 or of Dw20 and so on for other serotyped DRs. Table [ 35 ]  shows associated cellular specificities for DR alleles. However, cellular typing has inconsistency in the reaction between cellular-type individuals, sometimes resulting differently from predicted. Together with difficulty of cellular assay in generating and maintaining cellular typing reagents, cellular assay is being replaced by DNA-based typing method. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7075", "text": "Minor reactions to subregions that show similarity to other types can be observed to the gene products of alleles of a serotype group. The sequence of the antigens determines the antibody reactivities, and so having a good sequencing capability (or sequence-based typing) obviates the need for serological reactions. Therefore, different serotype reactions may indicate the need to sequence a person's HLA to determine a new gene sequence."}
{"_id": "WikiPedia_Hematology$$$corpus_7076", "text": "Broad antigen types are still useful, such as typing very diverse populations with many unidentified HLA alleles (Africa, Arabia, [ 36 ]  Southeastern Iran [ 37 ]  and Pakistan, India [ 38 ] ). Africa, Southern Iran, and Arabia show the difficulty in typing areas that were settled earlier. Allelic diversity makes it necessary to use broad antigen typing followed by gene sequencing because there is an increased risk of misidentifying by serotyping techniques."}
{"_id": "WikiPedia_Hematology$$$corpus_7077", "text": "In the end, a workshop, based on sequence, decides which new allele goes into which serogroup either by sequence or by reactivity. Once the sequence is verified, it is assigned a number. For example, a new allele of B44 may get a serotype (i.e. B44) and allele ID i.e. B*44:65, as it is the 65th B44 allele discovered. Marsh et al. (2005) [ 25 ]  can be considered a code book for HLA serotypes and genotypes, and a new book biannually with monthly updates in  Tissue Antigens ."}
{"_id": "WikiPedia_Hematology$$$corpus_7078", "text": "Gene typing is different from gene sequencing and serotyping.\nWith this strategy, PCR primers specific to a variant region of DNA are used (called sequence-specific primers). If a product of the right size is found, the assumption is that the HLA allele has been identified. New gene sequences often result in an increasing appearance of ambiguity. Because gene typing is based on SSP-PCR, it is possible that new variants, in particular in the class I and DRB1 loci, may be missed."}
{"_id": "WikiPedia_Hematology$$$corpus_7079", "text": "For example, SSP-PCR within the clinical situation is often used for identifying HLA phenotypes. An example of an extended phenotype for a person might be:"}
{"_id": "WikiPedia_Hematology$$$corpus_7080", "text": "A *01:01 / *03:01 , C *07:01 / *07:02 , B *07:02 / *08:01 , DRB1 *03:01 / *15:01 , DQA1 *05:01 / *01:02 , DQB1 *02:01 / *06:02"}
{"_id": "WikiPedia_Hematology$$$corpus_7081", "text": "In general, this is identical to the extended serotype:\nA1,A3,B7,B8,DR3,DR15(2), DQ2,DQ6(1)"}
{"_id": "WikiPedia_Hematology$$$corpus_7082", "text": "For many populations, such as the Japanese or European populations, so many patients have been typed that new alleles are relatively rare, and thus SSP-PCR is more than adequate for allele resolution. Haplotypes can be obtained by typing family members in areas of the world where SSP-PCR is unable to recognize alleles and typing requires the sequencing of new alleles. Areas of the world where SSP-PCR or serotyping may be inadequate include Central Africa, Eastern Africa, parts of southern Africa, Arabia, S. Iran, Pakistan, and India."}
{"_id": "WikiPedia_Hematology$$$corpus_7083", "text": "An HLA haplotype is a series of HLA \"genes\" (loci-alleles) by chromosome, one passed from the mother and one from the father."}
{"_id": "WikiPedia_Hematology$$$corpus_7084", "text": "The phenotype exampled above is one of the more common in Ireland and is the result of two common genetic  haplotypes :"}
{"_id": "WikiPedia_Hematology$$$corpus_7085", "text": "A *01:01 \u00a0; C *07:01 \u00a0; B *08:01 \u00a0; DRB1 *03:01 \u00a0; DQA1 *05:01 \u00a0; DQB1 *02:01 \n(By serotyping  A1-Cw7-B8-DR3-DQ2 )"}
{"_id": "WikiPedia_Hematology$$$corpus_7086", "text": "which is called ' 'super B8' ' or ' 'ancestral haplotype' ' and"}
{"_id": "WikiPedia_Hematology$$$corpus_7087", "text": "A *03:01 \u00a0; C *07:02 \u00a0; B *07:02 \u00a0; DRB1 *15:01 \u00a0; DQA1 *01:02 \u00a0; DQB1 *06:02 \n(By serotyping A3-Cw7-B7-DR15-DQ6 or the older version  \"A3-B7-DR2-DQ1\")"}
{"_id": "WikiPedia_Hematology$$$corpus_7088", "text": "These haplotypes can be used to trace migrations in the human population because they are often much like a fingerprint of an event that has occurred in evolution. The Super-B8 haplotype is enriched in the Western Irish, declines along gradients away from that region, and is found only in areas of the world where Western Europeans have migrated. The \"A3-B7-DR2-DQ1\" is more widely spread, from Eastern Asia to Iberia. The Super-B8 haplotype is associated with a number of diet-associated autoimmune diseases. There are 100,000s of extended haplotypes, but only a few show a visible and nodal character in the human population."}
{"_id": "WikiPedia_Hematology$$$corpus_7089", "text": "Studies of humans and animals imply a heterozygous selection mechanism operating on these loci as an explanation for this variability. [ 39 ]  One proposed mechanism is sexual selection in which females are able to detect males with different HLA relative to their own type. [ 40 ]   While the DQ and DP encoding loci have fewer alleles, combinations of A1:B1 can produce a theoretical potential of 7,755 DQ and 5,270 DP \u03b1\u03b2 heterodimers, respectively. While nowhere near this number of isoforms exist in the human population, each individual can carry 4 variable DQ and DP isoforms, increasing the potential number of antigens that these receptors can present to the immune system."}
{"_id": "WikiPedia_Hematology$$$corpus_7090", "text": "Studies of the variable positions of DP, DR, and DQ reveal that peptide antigen contact residues on class II molecules are most frequently the site of variation in the protein primary structure. Therefore, through a combination of intense allelic variation and/or subunit pairing, the class II peptide receptors are capable of binding an almost endless variation of peptides of 9 amino acids or longer in length, protecting interbreeding subpopulations from nascent or epidemic diseases. Individuals in a population frequently have different haplotypes, and this results in many combinations, even in small groups. This diversity enhances the survival of such groups, and thwarts evolution of epitopes in pathogens, which would otherwise be able to be shielded from the immune system."}
{"_id": "WikiPedia_Hematology$$$corpus_7091", "text": "HLA antibodies are typically not naturally occurring, and with few exceptions are formed as a result of an immunologic challenge to a foreign material containing non-self HLAs via blood transfusion, pregnancy (paternally inherited antigens), or organ or tissue transplant."}
{"_id": "WikiPedia_Hematology$$$corpus_7092", "text": "Antibodies against disease-associated HLA haplotypes have been proposed as a treatment for severe autoimmune diseases. [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7093", "text": "Donor-specific HLA antibodies have been found to be associated with graft failure in renal, heart, lung, and liver transplantation. These donor-specific HLA antibodies can exist pretransplant as consequence of sensitization to prior transplants or through pregnancies, but also occur de novo post-transplantation. There is a clear link between the risk of HLA antibody sensitisation and the donor-recipient HLA (molecular) mismatch. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7094", "text": "In some diseases requiring  hematopoietic stem cell transplantation ,  preimplantation genetic diagnosis  may be used to give rise to a sibling with matching HLA, although there are ethical considerations. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7095", "text": "Human platelet antigens (HPA)  are  polymorphisms  in  platelet   antigens . These can stimulate production of  alloantibodies  (that is,  antibodies  against other people's antigens) in recipients of  transfused  platelets from  donors  with different HPAs. These antibodies cause  neonatal alloimmune thrombocytopenia ,  post-transfusion purpura , and some cases of  platelet transfusion refractoriness  to infusion of donor platelets. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7096", "text": "A  nomenclature  was devised by International Society of Blood Transfusion (ISBT), platelet working party to overcome problems generated by many different nomenclatures in use. Since inception of this list, a greater number of antigens have been described and the molecular basis of many has been resolved. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7097", "text": "To date, 24 platelet-specific alloantigens have been defined by  immune sera , of which 12 are grouped in six biallelic systems (HPA-1, -2, -3, -4, -5, -15). For the remaining 12,  alloantibodies  against the  thetical  but not the  antithetical  antigen have been observed. The molecular basis of 22 of the 24 serologically defined antigens has been resolved. In all but one of the 22, the difference between self and non-self is defined by a single amino acid substitution generally caused by a  single-nucleotide polymorphism  (SNP). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7098", "text": "Iatrogenic anemia , also known as  nosocomial anemia  or  hospital-acquired anemia , is a condition in which a person develops  anemia  due to medical interventions, most frequently repeated  blood draws . [ 1 ] [ 2 ] [ 4 ]  Other factors that contribute to iatrogenic anemia include bleeding from medical procedures and dilution of the blood by  intravenous fluids . [ 2 ]  People may receive  blood transfusions  to treat iatrogenic anemia, which carries risks for complications like  transfusion reactions  and  circulatory overload . [ 3 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7099", "text": "A 2013 study of over 400,000 people admitted to US hospitals found that 74% developed anemia at some point during their hospital stay. [ 5 ]  Iatrogenic anemia is of particular concern in  intensive care medicine , [ 6 ] :\u200a629\u200a  because people who are critically ill require frequent blood tests and have a higher risk of developing anemia due to lower  hemoglobin  levels and impaired production of red blood cells ( erythropoesis ) at baseline. The average  intensive care unit  (ICU) patient loses up to 660 mL of blood per week to laboratory testing. [ 3 ]  For each day in the ICU, it is estimated that a person's hemoglobin level falls by 5 g/L (0.5 g/dL), 80% of which is due to phlebotomy. [ 7 ] :\u200a20\u200a  On the second day of admission to the ICU, more than 70% of adults exhibit anemia, over half of whom will go on to require a  blood transfusion . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7100", "text": "In the  neonatal intensive care unit  (NICU), the issue is exacerbated by the patients' low body weight: it is estimated that during their first six weeks of life, infants in NICUs may lose 15\u221230% of their blood volume to blood draws. [ 3 ] [ 8 ]  Premature babies often suffer from  anemia of prematurity , which is caused by low production of  erythropoietin  (a hormone that stimulates red blood cell production) and the short lifespan of neonates' red blood cells, and is worsened by blood loss through phlebotomy. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7101", "text": "People who are receiving  dialysis  lose blood not only through sampling for laboratory tests, but from the dialysis process itself and from bleeding caused by accessing veins to attach the dialysis equipment. This iatrogenic anemia often occurs alongside the anemia caused by  kidney disease . [ 6 ] :\u200a629"}
{"_id": "WikiPedia_Hematology$$$corpus_7102", "text": "Another factor that contributes to anemia in hospitalized people is the use of  intravenous fluids . Infusion with large volumes of intravenous fluids dilutes the blood, causing a decreased hemoglobin and hematocrit level. This is not a true anemia, as no red blood cells are lost and the body eventually compensates for the effects of the infusion. However, the decreased hemoglobin and hematocrit may lead to unnecessary transfusion. Blood loss through surgery and through medical procedures such as  central line  placement also play a role, as does the use of certain drugs which can suppress the  bone marrow 's ability to produce red blood cells. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7103", "text": "People who develop iatrogenic anemia spend a longer amount of time in the hospital and have an increased risk of mortality. They are also more likely to receive  blood transfusions , [ 1 ]  which carries risks for various conditions, including  transfusion reactions ,  lung injury ,  circulatory overload  and  alloimmunization . [ 2 ] [ 3 ]  After the initial development of anemia, further testing may be ordered to monitor and investigate the condition, which worsens the anemia and the attendant risks for complications. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7104", "text": "The volume of blood needed for most laboratory tests is  lower than the amount that is commonly drawn; a 2008 study found that only 9% of the blood in standard sized blood tubes was used for testing. Using smaller tubes for blood tests can decrease the risk of anemia, but it may increase the risk of laboratory errors. [ 3 ]   Point-of-care testing , meaning testing performed at a patient's bedside rather than in a  medical laboratory , typically uses much smaller blood volumes than conventional testing;  [ 7 ] :\u200a20\u200a  however, as of 2019, there is insufficient evidence regarding the effects of point-of-care testing on iatrogenic anemia. The use of closed blood sampling devices, which return excess blood from blood draws or  line flushes  to the person's circulation, can decrease the amount of blood loss in hospitalized patients. [ 3 ]  Strategies to decrease the amount of blood tests ordered, such as clinician education and  auditing , or restricting test orders through the  electronic health record , have also been investigated. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7105", "text": "The  LW blood system  was first described by  Landsteiner  and  Wiener  in 1940. [ 1 ]  It was often confused with the  Rh  system, not becoming a separate antigen system until 1982. The LW and RhD antigens are genetically independent though they are phenotypically related and the LW antigen is expressed more strongly on RhD positive cells than on RhD negative cells. In most populations, the antithetical LW antigens, LW a  and LW b  are present as very high and very low frequency, respectively. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7106", "text": "The LW locus is located on the short arm of  chromosome 19  (19p13.3). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7107", "text": "LW antigens reside on a 40- to 42-kilo dalton  red cell membrane  glycoprotein  named  CD242 . [ 2 ]  The LW glycoprotein has recently been renamed ICAM-4 due to its similarity to  intercellular adhesion molecule , although exactly which  integrins  bind to ICAM-4 is subject to controversy."}
{"_id": "WikiPedia_Hematology$$$corpus_7108", "text": "The function of ICAM-4 is not fully understood but appears to be restricted to  erythroid  cells. During in vitro  erythropoesis , LW appears at either the erythroid colony forming stage or later at the proerythroblast stage. A vital part of erythropoesis is the clustering of erythroblasts around  bone marrow   macrophages  to form erythroblastic islands. The erythroblast is then able to remove its  nucleus , which is in turn ingested and broken down by the macrophages, to become a mature  erythrocyte . During this process ICAM-4 binds to VLA-4, an erythroblast binding site, on adjacent erythroblasts and to  \u03b1v integrins  on macrophages to help stabilise the erythroblastic islands. The binding of red cells to macrophages in the spleen by ICAM-4 could also play a part in the removal of senescent red cells. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7109", "text": "Despite the functional aspects of ICAM-4, its apparent absence in LW(a-b-) and Rh null  phenotypes does not appear to lead to any obvious pathological effects. ICAM-4 expression is elevated on sickle red cells and its binding to \u03b1v integrins on the endothelial cells may cause the pain associated with  sickle cell  crises. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7110", "text": "Auto anti-LW is not uncommon as an  autoantibody  but usually presents with transient suppression of the LW antigen in genetically LW+ individuals, and so appears to be an  alloantibody . True alloanti-LW is a very rare occurrence, with only two known examples of alloanti-LW ab , produced by patients with an LW(a-b-) phenotype. Anti-LW can be present as a clinically insignificant autoantibody and not be associated with increased red cell destruction. Anti-LW has also been associated with cases of warm type  autoimmune haemolytic anaemia ;  Philip Levine  suggested that it was the most common antibody in cases of AIHA with a positive  Coombs test . [ 1 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7111", "text": "Haemolytic disease of the newborn  (HDFN) due to alloanti-LW is described as mild and very rare, even the very potent anti-LW ab  of one known patient caused minimal evidence of HDFN in her three pregnancies. [ 6 ]  To date auto anti-LW has only been implicated as the cause of one case of HDFN. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7112", "text": "The  Ii antigen system  is a  human blood group system  based upon  a gene  on  chromosome 6  and consisting of the  I antigen  and the  i antigen . [ 1 ]  The I antigen is normally present on the cell membrane of  red blood cells  in all adults, while the i antigen is present in  fetuses  and newborns. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7113", "text": "Adult red blood cells express I antigen abundantly. [ 3 ]  Developing fetuses and newborns express i antigen until around 13-20 months after birth, when I antigen starts to be expressed instead. [ 3 ]  Like  ABH antigens , which make up the ABO blood group, I and i antigens are not restricted to the red blood cell membrane, but are found on most human cells and in body fluids such as  saliva . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7114", "text": "The I and i antigens are  carbohydrate  structures composed of repeating units of  N -acetyllactosamine  (LacNAc), and are located on the interior of structures carrying ABH and  Lewis  antigens. [ 1 ] [ 3 ]  LacNAc repeats are made by the enzymes  B3GNT1  and  B4GALT1 . [ 4 ]  The i antigen is made of linear repeats, while the structure of the I antigen is branched. [ 3 ]  Unlike most other blood groups, the two antigens are not encoded by different  alleles ; rather,  I-branching enzyme  converts i antigen to I antigen by adding branches. [ 5 ] [ 6 ]  The gene encoding I-branching enzyme is located on chromosome 6. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7115", "text": "The function of I and i antigens are unknown but may be related to  hematopoiesis , the production of blood. [ 6 ]  The rapid conversion from i to I antigens after birth suggests that I antigen plays an important role in adult red blood cells. [ 3 ]  The presence of the linear i antigen in fetuses, rather than the branched I antigen, may have developed as an  evolutionary  mechanism to prevent  ABO hemolytic disease of the fetus and newborn . [ 1 ]  Enhanced expression of i antigen is associated with conditions involving  stress hematopoiesis  such as  leukemia  and  sickle cell disease . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7116", "text": "Transient  autoantibodies  against I antigen are common, especially after infection by  Mycoplasma pneumoniae , and are rarely significant except in  cold agglutinin disease . [ 1 ]  Transient antibodies against i antigen are common after  infectious mononucleosis  and are also not clinically significant. [ 1 ]  Antibodies which recognize both I and i antigens are termed anti-j antibodies. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7117", "text": "The autoantibodies involved in cold agglutinin disease are usually against I antigen. [ 8 ]  The antibodies are usually  IgM  ( kappa  subtype), unlike transient autoantibodies which are generally  IgG . [ 1 ]  Cold-reactive IgM antibodies ( cold agglutinins ) bind to I antigen on red blood cells, and unlike IgG, are able to cause  agglutination  of red blood cells and activate  complement  to cause  hemolysis , leading to  anemia . [ 1 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7118", "text": "Rarely, individuals have the i antigen on their red blood cells into adulthood, known as the adult i phenotype. [ 1 ]  This is due to the presence of a  mutation  in the  GCNT2 gene  which encodes the I-branching enzyme. [ 1 ] [ 3 ]  These individuals have  alloantibodies  against the I antigen, though these are typically cold agglutinins and are unlikely to cause  transfusion reactions . [ 2 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7119", "text": "The adult i phenotype is associated with  congenital cataracts , most markedly in Japanese and Taiwanese people and least markedly in Caucasian people. [ 1 ] [ 6 ]  Cataracts occur when i antigen rather than I antigen is present on the  epithelium  of the  lens , due to a mutation in the form of the I-branching enzyme which is expressed in lens epithelium, IGNTB. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7120", "text": "The adult i phenotype is inherited in a  recessive  manner. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7121", "text": "The I antigen was first described in 1956 and the i antigen was discovered in 1960. [ 1 ]  I and i were the first discovered antigens which change significantly during  human development . [ 4 ]  The letter I was chosen to reflect the \"individuality\" of a person studied who lacked the I antigen. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7122", "text": "A similar blood group system with a developmental change resembling the Ii system (with human neonatal cells expressing i antigen and adult cells expressing I antigen) has been observed in most  primates , including  chimpanzees  and  monkeys . [ 1 ]  This is not seen in non-primates:  cats ,  dogs , or  guinea pigs . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7123", "text": "Immunoglobulin therapy  is the use of a mixture of  antibodies  (normal human immunoglobulin) to treat several health conditions. [ 13 ] [ 14 ]  These conditions include  primary immunodeficiency ,  immune thrombocytopenic purpura ,  chronic inflammatory demyelinating polyneuropathy ,  Kawasaki disease , certain cases of  HIV/AIDS  and  measles ,  Guillain\u2013Barr\u00e9 syndrome , and certain other infections when a more specific immunoglobulin is not available. [ 13 ]  Depending on the formulation it can be given by  injection into muscle , a  vein , or  under the skin . [ 13 ]  The effects last a few weeks. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7124", "text": "Common side effects include pain at the site of injection, muscle pain, and  allergic reactions . [ 13 ]  Other severe side effects include  kidney problems ,  anaphylaxis ,  blood clots , and  red blood cell breakdown . [ 13 ]  Use is not recommended in people with some types of  IgA deficiency . [ 13 ]  Use appears to be relatively safe during  pregnancy . [ 13 ]  Human immunoglobulin is made from human  blood plasma . [ 13 ]  It contains antibodies against many  viruses . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7125", "text": "Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981. [ 15 ]  It is on the  World Health Organization's List of Essential Medicines . [ 16 ] [ 17 ]  Each formulation of the product is somewhat different. [ 14 ]  A number of  specific immunoglobulin  formulations are also available including for  hepatitis B ,  rabies ,  tetanus ,  varicella infection , and  Rh positive blood exposure . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7126", "text": "Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to  IgG subclass deficiencies  (usually involving IgG2 or IgG3), to other disorders in which antibodies are within a normal quantitative range, but lacking in quality \u2013 unable to respond to antigens as they normally should \u2013 resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of  IgG  they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as  dermatomyositis  in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for  secondary immunodeficiencies   such as  human immunodeficiency virus  (HIV), some autoimmune disorders (such as  immune thrombocytopenia  and  Kawasaki disease ), some neurological diseases ( multifocal motor neuropathy ,  stiff person syndrome ,  multiple sclerosis  and  myasthenia gravis ) some acute infections and some complications of organ transplantation. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7127", "text": "Immunoglobulin therapy is especially useful in some acute infection cases such as  pediatric   HIV  infection and is also considered the standard of treatment for some autoimmune disorders such as  Guillain\u2013Barr\u00e9 syndrome . [ 19 ] [ 20 ]  The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7128", "text": "The Australian Red Cross Blood Service developed their own guidelines for the appropriate use of immunoglobulin therapy in 1997. [ 22 ]  Immunoglobulin is funded under the National Blood Supply and indications are classified as either an established or emerging therapeutic role or conditions for which immunoglobulin use is in exceptional circumstances only. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7129", "text": "Subcutaneous immunoglobulin access programs have been developed to facilitate hospital based programs. [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7130", "text": "Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7131", "text": "The National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7132", "text": "Brands include HyQvia (human normal immunoglobulin), Privigen (human normal immunoglobulin (IVIg)), Hizentra (human normal immunoglobulin (SCIg)), Kiovig (human normal immunoglobulin), and Flebogamma DIF (human normal immunoglobulin). [ 12 ] [ 27 ] [ 28 ] [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7133", "text": "In the EU human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins. [ 27 ]  It is used to treat the following conditions:"}
{"_id": "WikiPedia_Hematology$$$corpus_7134", "text": "It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as:"}
{"_id": "WikiPedia_Hematology$$$corpus_7135", "text": "Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0\u201318 years) in:"}
{"_id": "WikiPedia_Hematology$$$corpus_7136", "text": "and for the immunomodulation in adults, children and adolescents (0\u201318 years) in:"}
{"_id": "WikiPedia_Hematology$$$corpus_7137", "text": "The United Kingdom's  National Health Service  recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in  sepsis  (unless a specific toxin has been identified), multiple sclerosis, neonatal sepsis, and pediatric  HIV/AIDS . [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7138", "text": "The  American Academy of Allergy, Asthma, and Immunology  supports the use of  immunoglobulin  for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions, [ 32 ]  including neonatal sepsis (citing a sixfold decrease in mortality), considered in cases of HIV (including pediatric HIV), considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as  chronic fatigue syndrome ,  PANDAS  (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) until further evidence to support its use is found (though noting that it may be useful in PANDAS patients with an autoimmune component), cystic fibrosis, and a number of other conditions. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7139", "text": "Brands include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7140", "text": "Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration). Patients who are receiving immunoglobulin and experience adverse events are sometimes recommended to take  acetaminophen  and  diphenhydramine  before their infusions to reduce the rate of adverse effects. Additional premedication may be required in some instances (especially when first getting accustomed to a new dosage),  prednisone  or another oral steroid. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7141", "text": "Local side effects of immunoglobulin infusions most frequently include an  injection site reaction  (reddening of the skin around the injection site), itching, rash, and hives. [ 48 ]  Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain. [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7142", "text": "Serious side effects of immunoglobulin infusions in infants, children, [ 49 ]  and adults include chest discomfort or pain,  myocardial infarction ,  tachycardia ,  hyponatremia ,  hemolysis ,  hemolytic anemia ,  thrombosis ,  hepatitis ,  anaphylaxis , backache,  aseptic meningitis ,  acute kidney injury , hypokalemic  nephropathy ,  pulmonary embolism , and  transfusion related acute lung injury . [ 48 ]   hemoThere is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient. [ 48 ]  Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7143", "text": "IVIG has long been known to induce a decrease in peripheral blood neutrophil count, or  neutropenia  in neonates, [ 51 ]  and in patients with  Idiopathic Thrombocytopenic Purpura , resolving spontaneously and without complications within 48 h. [ 52 ]  Possible pathomechanisms include  apoptosis /cell death due to antineutrophil antibodies with or without neutrophil migration into a storage pool outside the blood circulation. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7144", "text": "Immunoglobulin therapy interferes with the ability of the body to produce a normal immune response to an attenuated  live-virus vaccine  (like MMR) for up to a year, [ 48 ]  can result in falsely elevated blood glucose levels, [ 48 ]  and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7145", "text": "After immunoglobulin therapy's discovery in 1952, weekly  intramuscular injections  of immunoglobulin (IMIg) were the norm until  intravenous  formulations (IVIg) began to be introduced in the 1980s. [ 55 ]  During the mid and late 1950s, [ vague ]  one-time IMIg injections were a common public health response to outbreaks of  polio  before the widespread availability of vaccines. Intramuscular injections were extremely poorly tolerated due to their extreme pain and poor efficacy \u2013 rarely could intramuscular injections alone raise plasma immunoglobulin levels enough to make a clinically meaningful difference. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7146", "text": "Intravenous formulations began to be approved in the 1980s, which represented a significant improvement over intramuscular injections, as they allowed for a sufficient amount of immunoglobulin to be injected to reach clinical efficacy, although they still had a fairly high rate of adverse effects (though the addition of stabilizing agents reduced this further). [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7147", "text": "The first description of a  subcutaneous  route of administration for immunoglobulin therapy dates back to 1980, [ 56 ]  but for many years subcutaneous administration was considered to be a secondary choice, only to be considered when peripheral venous access was no longer possible or tolerable. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7148", "text": "During the late 1980s and early 1990s, [ vague ]  it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an  ad hoc  clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the  ad hoc  trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7149", "text": "In the later 1990s, [ vague ]  large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency ( Vivaglobin , which was voluntarily discontinued in 2011). [ 55 ] [ 57 ]  A number of other brand names of subcutaneous immunoglobulin have since been approved, although some small-scale studies have indicated that a particular cohort of patients with  common variable immunodeficiency  (CVID) may develop intolerable side effects with subcutaneous immunoglobulin (SCIg) that they do not with intravenous immunoglobulin (IVIg). [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7150", "text": "Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US  Food and Drug Administration  (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use. [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7151", "text": "The precise mechanism by which immunoglobulin therapy suppresses harmful  inflammation  is likely multifactorial. [ 58 ]  For example, it has been reported that immunoglobulin therapy can block  Fas -mediated cell death. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7152", "text": "Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgG's  Fc glycosylation . By binding to receptors on  antigen presenting cells , IVIG can increase the expression of the inhibitory  Fc receptor , FcgRIIB, and shorten the half-life of auto-reactive antibodies. [ 60 ] [ 61 ] [ 62 ]  The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG. [ 60 ]  Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7153", "text": "Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings. [ 63 ] [ 64 ] [ 65 ] [ 66 ]  On the other hand, several other mechanisms of action and the actual primary targets of immunoglobulin therapy have been reported. In particular, F(ab')2-dependent action of immunoglobulin to inhibit activation of human dendritic cells, [ 67 ]  induction of autophagy, [ 68 ]  induction of COX-2-dependent PGE-2 in human dendritic cells leading to expansion of regulatory T cells, [ 69 ]  inhibition of pathogenic Th17 responses, [ 70 ]  and induction of human basophil activation and IL-4 induction via anti-IgE autoantibodies. [ 71 ] [ 72 ]  Some believe that immunoglobulin therapy may work via a multi-step model where the injected immunoglobulin first forms a type of  immune complex  in the patient. [ 73 ]  Once these immune complexes are formed, they can interact with Fc receptors on  dendritic cells , [ 74 ]  which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state."}
{"_id": "WikiPedia_Hematology$$$corpus_7154", "text": "Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the host's  complement system , leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells ( macrophages ), leading to decreased damage by these cells, or regulation of macrophage  phagocytosis . Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on  T cells ,  B cells , and  monocytes  that are pertinent to autoreactivity and induction of tolerance to self. [ 60 ] [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7155", "text": "A report stated that immunoglobulin application to activated T cells leads to their decreased ability to engage  microglia . As a result of immunoglobulin treatment of T cells, the findings showed reduced levels of  tumor necrosis factor-alpha  and  interleukin-10  in T cell-microglia co-culture. The results add to the understanding of how immunoglobulin may affect inflammation of the central nervous system in autoimmune inflammatory diseases. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7156", "text": "Hyperimmune globulins are a class of  immunoglobulins  prepared in a similar way as for  normal human immunoglobulin , except that the donor has high titers of  antibody  against a specific organism or  antigen  in their  plasma . Some agents against which hyperimmune globulins are available include  hepatitis B ,  rabies ,  tetanus  toxin,  varicella-zoster , etc. Administration of hyperimmune globulin provides  \"passive\" immunity  to the patient against an agent. This is in contrast to  vaccines  that provide  \"active\" immunity . However, vaccines take much longer to achieve that purpose while hyperimmune globulin provides instant \"passive\" short-lived immunity. Hyperimmune globulin may have serious  side effects , thus usage is taken very seriously. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7157", "text": "Hyperimmune  serum  and  plasma  contain high amounts of an antibody, as a consequence of disease convalescence [ 77 ]  or of repeated immunization. [ 78 ]  Hyperimmune plasma is used in veterinary medicine, [ 79 ]  and hyperimmune plasma derivatives are used to treat snakebite. [ 80 ]  It has been hypothesized that hyperimmune serum may be an effective therapy for persons infected with the  Ebola virus . [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7158", "text": "In the United Kingdom a dose cost the  NHS  between  \u00a3 11.20 and  \u00a3 1,200.00 depending on the type and amount. [ 14 ]  In the United States, antivenoms may cost thousands of dollars per dose because of markups that occur after manufacturing. [ 82 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7159", "text": "As  biologicals , various brand names of immunoglobulin products are not necessarily interchangeable, and care must be exercised when changing between them. [ 83 ]  Brand names of intravenous immunoglobulin formulations include Flebogamma, Gamunex, Privigen, Octagam, and Gammagard, while brand names of subcutaneous formulations include Cutaquig, Cuvitru, HyQvia, Hizentra, [ 27 ] [ 84 ] [ 85 ]  Gamunex-C, and Gammaked. [ 86 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7160", "text": "The United States is one of a handful of countries that allow plasma donors to be paid, meaning that the US supplies much of the plasma-derived medicinal products (including immunoglobulin) used across the world, including more than 50% of the European Union's supply. [ 87 ]  The Council of Europe has officially endorsed the idea of not paying for plasma donations for both ethical reasons and reasons of safety, but studies have found that relying on entirely voluntary plasma donation leads to shortages of immunoglobulin and forces member countries to import immunoglobulin from countries that do compensate donors. [ 87 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7161", "text": "In Australia, blood donation is voluntary and therefore to cope with increasing demand and to reduce the shortages of locally produced immunoglobulin, several programs have been undertaken including adopting plasma for first time blood donors, better processes for donation, plasma donor centres and encouraging current blood donors to consider plasma only donation. [ 88 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7162", "text": "Experimental results from a small  clinical trial  in humans suggested protection against the progression of  Alzheimer's disease , but no such benefit was found in a subsequent phase III clinical trial. [ 89 ] [ 90 ] [ 91 ]  In May 2020, the US approved a phase three clinical trial on the efficacy and safety of high-concentration intravenous immune globulin therapy in severe  COVID-19 . [ 92 ]  Efficacy of heterologous immunoglobulin derivatives has been demonstrated in clinical trials of antivenoms for scorpion sting [ 93 ]  and for snakebite. [ 94 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7163", "text": "The  Indian blood group system  ( In ) is a classification of  blood  based on the presence or absence of  inherited   antigens  that reside within the  CD44  molecule that is expressed on the surface of  blood cells . [ 1 ]  It is named so because 4% of the population in India possess it. [ 2 ]  Most individuals express the In b  antigen that results from an  arginine  residue at position 46 of CD44 .  The In a  blood type results from a substitution  proline  for arginine at this same position."}
{"_id": "WikiPedia_Hematology$$$corpus_7164", "text": "The  International Society of Blood Transfusion  ( ISBT ) is a  scientific  society founded in 1935 which promotes the study of  blood transfusion  and provides information about the ways in which blood transfusion medicine and science can best serve patients' interests. The society's central office is in  Amsterdam , and there are around 1900 members in 103 countries. [ 1 ]  As of June 2024, the president of the ISBT is Pierre Tiberghien. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7165", "text": "ISBT is governed by a voluntary board of 16 directors, representing all  WHO  regions. [ 1 ] [ 2 ]  ISBT has 16 scientific working parties, which are groups of ISBT members promoting science, research and best practice in their specific areas of expertise. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7166", "text": "ISBT advocates for  standardisation  and  harmonisation  in the field of blood transfusion. [ 4 ]  The other major impact on the transfusion community is the classification of various  human blood group systems  under a common nomenclature. [ 5 ] [ 6 ]  ISBT's coordination also extends to obtaining donors with rare  antigens , a process that often involves international searches in which common terminology is critical."}
{"_id": "WikiPedia_Hematology$$$corpus_7167", "text": "The ISBT Code of Ethics was developed in response to the  World Health Assembly  resolution WHA 28.72. [ 7 ] [ 8 ]  \u00a0This resolution called for the establishment of: appropriately governed national blood services; voluntary non-remunerated blood donations (VNRBD); and the promotion of the health of both blood donors and recipients of blood. ISBT works as a  non-state actor  in official relations with WHO. ISBT collaborated with WHO to produce \"Educational modules on clinical use of blood\". [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7168", "text": "In a 2015 review of the history of the ISBT, Hans Erik Heier distinguished four phases in the formation of the society: [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7169", "text": "The formation of the International Society of Blood Transfusion, or Societ\u00e9 International de Transfusion Sanguine, as it was called at the time, was initiated in  Rome  at a meeting between representatives from 20 nations, the  International Red Cross  and the Bogdanov institute in  Moscow . Blood transfusion was a rather new therapeutic option, and therefore, it was decided that transfusion-specific congresses should be organised to highlight the potential importance of transfusion. To organize these congresses, a society was needed."}
{"_id": "WikiPedia_Hematology$$$corpus_7170", "text": "After it was decided that a society dedicated to organizing transfusion-related congresses should be created, it did not take long until ISBT was founded. In 1937, the ISBT central office (CO) was established in  Paris , led by newly appointed Secretary General  Arnault Tzanck . Two years later, in 1939, the activities of the ISBT CO had to be suspended because of the  Second World War  (WWII)."}
{"_id": "WikiPedia_Hematology$$$corpus_7171", "text": "In the period surrounding WWII,  immunohaematology  and transfusion technology developed rapidly.  Blood banks  were created, voluntary  blood donations  came in great numbers in the allied nations, plasma-transfusion became a standard anti-shock treatment, Rh and  Kell  systems were discovered, and industrial  blood plasma fractionation  was developed to produce  albumin , which can be used as a substitute for  plasma . In 1947, the first post-war congress of the ISBT was organised in  Turin, Italy . Here, some specific future goals were laid out to complement the main activity of the Society, the organization of congresses:"}
{"_id": "WikiPedia_Hematology$$$corpus_7172", "text": "After the congress in Turin, the society was able to organise congresses and develop without great difficulties for the next forty years, until 1985."}
{"_id": "WikiPedia_Hematology$$$corpus_7173", "text": "In 1985, the  HIV/AIDS  epidemic struck transfusion medicine. During that time, the ISBT CO was still located in Paris as a part of the Centre National de Transfusion Sanguine (CNTS) (English: National Centre for Blood Transfusion) as their head, Michel Garretta, was also ISBT Secretary General at the time. In June 1991, he stepped down as head of CNTS, as the HIV/AIDS crisis had become a catastrophe for the transfusion system in France and eventually led to a reorganisation of CNTS in 1991. Subsequently, at the ISBT Congress in Hong Kong it was decided that ISBT could no longer be linked to CNTS, ruling out Garretta's succession of a French colleague. Harold Gunson, who was President of ISBT in 1991, agreed to take on a second role as acting Secretary General. Together with CNTS, and ISBT Secretary Claudine Hossenlopp, he supervised the move of the CO from Paris to Manchester, UK. In 1994, he resigned from his post as blood centre director in Manchester and moved the CO to Lancaster, into his own home. He upheld the CO together with his wife until 1999. The end of Gunson's term meant having to find a new location for the CO, and a new Secretary General."}
{"_id": "WikiPedia_Hematology$$$corpus_7174", "text": "In 1999, the new location for the ISBT CO was Amsterdam, where it became a part of professional congress organiser (PCO) Eurocongress. Paul Strengers, a doctor at Sanquin Blood Supply, took up the role of Secretary General. A new vision for the 2002\u20132006 period of ISBT was created by the executive committee, focusing on developing ISBT into an umbrella organization, improving communication with the membership, educational and scientific activities, and professionalizing the CO. In the coming ten years, the society worked to achieve these goals, with Strengers to remain Secretary General for that period. Eurocongress organised ISBT congresses together with the ISBT CO and local organizing committees. The help of Eurocongress took away economic risks attached to congresses, as they were able to provide professional assistance and detailed advice. As the CO had moved to a different country, the ISBT statutes and by-laws were also updated and adapted to Dutch law."}
{"_id": "WikiPedia_Hematology$$$corpus_7175", "text": "The reformations made in the previous years had led to an increase in workload for the ISBT CO. In order to continue the fulfilment of the strategic plans of the ISBT, a full-time, paid chief executive officer (CEO) was hired in 2010. In 2012, the CO moved to a separate location in Amsterdam as the shared space with Eurocongress did not meet the needs of the expanded office staff. Currently, five paid persons are employed full-time at the CO, managed by CEO Judith Chapman (2010 \u2013 today). Congresses are organised by MCI, of which Eurocongress became a part in 2010. In that same year, Martin Olsson was appointed as Scientific Secretary (non-remunerated) to overlook the scientific programming of ISBT congresses and guarantee the high scientific quality. The second Scientific Secretary, Ellen van der Schoot, was in office until 2018. John Semple succeeded Ellen van der Schoot in 2019 through 2021. As of 2024, Jason Ackers is the current ISBT Scientific Secretary until 2025."}
{"_id": "WikiPedia_Hematology$$$corpus_7176", "text": "Intraoperative blood salvage  ( IOS ), also known as  cell salvage,  is a specific type of autologous blood transfusion. Specifically IOS is a  medical  procedure involving recovering blood lost during  surgery  and re-infusing it into the patient. It is a major form of  autotransfusion ."}
{"_id": "WikiPedia_Hematology$$$corpus_7177", "text": "It has been used for many years and gained greater attention over time as risks associated with allogenic (separate-donor)  blood transfusion  have seen greater  publicity  and become more fully appreciated.  [ citation needed ]  Several  medical devices  have been developed to assist in salvaging the patient's own blood in the perioperative setting. The procedure is frequently used in cardiothoracic and vascular  surgery , during which blood usage has traditionally been high. A greater effort to avoid adverse events due to  transfusion  has also increased the emphasis on blood conservation (see  bloodless surgery )."}
{"_id": "WikiPedia_Hematology$$$corpus_7178", "text": "Providing safe blood for transfusion remains a challenge despite advances in preventing transmission of  hepatitis B  virus (HBV),  hepatitis C  virus (HCV),  AIDS/HIV , HTLV-I/II,  West Nile virus  (WNV),  syphilis ,  Chagas disease ,  Zika virus , and transfusion-transmitted  bacterial infection . Human errors such as misidentifying  patients  and drawing blood samples from the wrong person (i.e., wrong blood in tube or WBIT) is more of a risk than transmissible diseases in many developed nations. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7179", "text": "Much more common risks of allogeneic transfusion include  allergic transfusion reactions  as well as  febrile non-hemolytic transfusion reactions . Additional risks include  transfusion related acute lung injury  (TRALI),   transfusion associated circulatory overload  (TACO) and transfusion-associated immunomodulation. TRALI is a potentially life-threatening condition with symptoms such as  dyspnea ,  fever , and  hypotension  occurring within hours of transfusion. TACO is a much more common (even with cases being underreported) potentially life-threatening condition involving respiratory compromise within hours of a transfusion. TACO must be suspected when there is respiratory distress with other signs, including pulmonary edema, unanticipated cardiovascular system changes, and evidence of fluid overload (including improvement after diuresis), during or up to 24 hours after transfusion. [ 1 ]  Transfusion-associated immunomodulation, which may suppress the  immune response  and cause adverse effects such as a small increase in the risk of postoperative infection. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7180", "text": "Other risks such as classic or variant  Creutzfeldt\u2013Jakob disease  (vCJD), an invariably fatal disease, remain worrisome as there are currently no approved tests for which to screen blood donors for this disease. Blood centers worldwide have instituted criteria to reject donors who may have been exposed to classic CJD and vCJD. Screening for transmissible diseases and deferral policies for classic CJD and vCJD designed to improve safety have unfortunately contributed to shrinking the donor pool. Blood shortages exist in the  United States  and worldwide. In many industrialized countries 5% or less of the eligible population are blood donors. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7181", "text": "As a result, some in the global medical community have moved from allogeneic blood (blood collected from another person) towards  autologous  transfusion, in which patients receive their own blood. Another impetus for autologous transfusion is the position of  Jehovah's Witnesses on blood transfusions . For religious reasons, Jehovah's Witnesses may choose not to accept any allogeneic transfusions from a volunteer's  blood donation  but may accept the use of autologous blood salvaged during surgery to restore their blood volume and homeostasis during the course of an operation, although not autologous blood donated beforehand. Each Jehovah's Witness patient must be individually counselled as to all the possible blood products that are available as they may choose to accept some and not others (i.e., while not accepting whole blood nor any of the four main components of blood, [plasma; platelets; red cells; white cells] some may accept fractions derived from those components, or medications containing such minor fractions); it is an individual choice for each patient.\nThere are other religious/ non-religious individuals besides Jehovah's Witnesses that would refuse allogeneic blood products but may choose to accept intraoperative blood salvage. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7182", "text": "Ways to avoid the adverse events associated with  allogenic  transfusion are often grouped under the umbrella phrase  bloodless surgery . There are several so-called bloodless options. These include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7183", "text": "Regardless of manufacturer, there are many types of cell processors. Cell processors are red cell washing devices that collect anticoagulated shed or recovered blood, wash and separate the  red blood cells  (RBC) by centrifugation or filtration such as the HemoClear filter. After, the washed RBCs can be returned to the same patient by reinfusion. RBC washing devices can help remove byproducts in salvaged blood such as activated  cytokines ,  anaphylatoxins , and other waste substances that may have been collected in the reservoir suctioned from the surgical field. However, they also remove viable  platelets ,  clotting factors , and other  plasma proteins  essential to whole blood and  homeostasis . The various RBC-savers also yield RBC concentrates with different characteristics and quality. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7184", "text": "Direct transfusion is a blood salvaging method associated with  cardiopulmonary bypass  (CPB) circuits or other extracorporeal circuits (ECC) that are used in surgery such as coronary artery bypass grafts ( CABG ), valve replacement, or surgical repair of the great vessels. Following bypass surgery, the ECC circuit contains a significant volume of diluted whole blood that can be harvested in transfer bags and re-infused into patients. Residual CPB blood is fairly dilute ([Hb] = 6\u20139 g/dL; 60\u201390 g/L) compared to normal values (12\u201318 g/dL; 120\u2013180 g/L) and can also contain potentially harmful contaminants such as activated cytokines, anaphylatoxins, and other waste substances that have been linked to organ  edema  and organ dysfunction and need a  diuretic  to reverse."}
{"_id": "WikiPedia_Hematology$$$corpus_7185", "text": "Acute normovolemic hemodilution (ANH) is a form of autologous transfusion where whole blood is collected from a patient at the start of surgery into a standard blood collection bag with anticoagulant with the simultaneous replacement of intracellular volume using acellular fluids (such as normal saline). The patient's own blood is re-infused at the end of the surgical case (presumably when any bleeding has stopped). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7186", "text": "Hemofiltration or ultrafiltration devices constitute the third major type of blood salvage in operating rooms.  In general, ultrafiltration devices filter the patient's anticoagulated whole blood. The filter process removes unwanted excess non-cellular plasma water, low molecular weight solutes, platelet inhibitors and some particulate matter through hemoconcentration, including activated cytokines, anaphylatoxins, and other waste substances making concentrated whole blood available for reinfusion.\nHemofilter devices return the patient's whole blood with all the blood elements and fractions including platelets, clotting factors, and plasma proteins with a substantial Hb level. Presently, the only whole blood ultrafiltration device in clinical use is the Hemobag. [ 3 ] [ 4 ]  These devices do not totally remove potentially harmful contaminants that can be washed away by most RBC-savers. However, the contaminants that are potentially reduced by using RBC-savers, as shown by data from  in vitro  laboratory tests, are transient and reversible  in vivo  with hemostatic profiles returning to baselines within hours. The key is that  coagulation  and homeostasis are immediately improved with the return of concentrated autologous whole blood."}
{"_id": "WikiPedia_Hematology$$$corpus_7187", "text": "Over the years numerous studies have been done to compare these methods of blood salvage in terms of safety, patient outcomes, and cost effectiveness, often with equivocal or contradictory results. [ 5 ] [ 6 ] [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7188", "text": "An  Intrauterine transfusion (IUT)  is a procedure that provides blood to a fetus, most commonly through the umbilical cord. [ 1 ] [ 2 ]  It is used in cases of severe fetal anemia, such as when fetal red blood cells are being destroyed by maternal antibodies, or  parvovirus B19  infection, homozygous  alpha-thalassemia , or  twin-to-twin transfusion syndrome . [ 3 ]  IUTs are performed by  perinatologists  at hospitals or specialized centers. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7189", "text": "Intrauterine transfusion (IUT) was introduced in 1963 by A.W. Liley. Early IUTs involved transfusion into the fetal peritoneum (abdomen). Almost 20 years later, the procedure was improved to a transfusion into the umbilical vein, which allowed for better absorption of red blood cells. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7190", "text": "Hemolytic disease of the fetus and newborn  (HDFN) is a rare condition that affects 3 out of 100,000 to 80 out of 100,000 patients per year. It occurs when maternal  antibodies  cross the  placenta  during pregnancy and destroy fetal  red blood cells  (RBCs). This process can lead to fetal  anemia , and in severe cases can progress to  hydrops  (edema), ascites, heart failure, and death. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7191", "text": "For HDFN to occur, the fetus must be  antigen  positive (paternally inherited) and the mother must have antibodies to the given antigen. Such antibodies typically form when the mother undergoes  alloimmunization  to the antigen during a previous pregnancy or transfusion. Historically,  RhD  alloimmunization accounted for the majority of cases. However, the rates of these cases have been significantly reduced by RhIg ( RhoGam ) administration. Measures are not available for preventing alloimmunization to non-RhD antigens ( Kell ,  Duffy ,  Rhc ,  RhE , etc.), which can also cause HDFN. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7192", "text": "Fetal anemia is monitored throughout pregnancy using  Doppler  measurement of the middle cerebral artery (MCA) peak systolic velocity (PSV). This non-invasive technique is used as a surrogate measurement for assessing fetal anemia. Doppler multiples of median (MoM) measurements exceeding 1.5 are correlated with moderate to severe anemia. At this point, invasive testing via  percutaneous umbilical cord blood sampling  (PUBS, also called cordocentesis), potentially followed by fetal transfusion is indicated. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7193", "text": "Prior to the procedure, compatible blood is obtained. This is usually type O, RhD-negative, and antigen-negative for maternal RBC antibodies. The selected blood then undergoes irradiation and leukocyte reduction. [ 6 ]  Antenatal corticosteroids are typically given to mothers before IUT to anticipate the need for an emergency cesarean section [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7194", "text": "The procedure is usually performed in a hospital under sterile conditions, within or near an operating room in case an emergency cesarean section is necessary due to complications caused by the procedure. The mother's abdomen is cleaned with an antiseptic solution, and she may or may not be given a local anesthetic injection to numb the abdominal area where the transfusion needle will be inserted. During the procedure, medicine may be given to the fetus to temporarily stop fetal movement. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7195", "text": "An ultrasound is performed to view the position of the fetus and to help guide the needle. The first step is to locate a relatively stable segment of the umbilical cord. The procedure may be achieved with more ease if the placenta is in the anterior position. However, if the placenta is in the posterior position, the fetus might block direct access to the umbilical cord. Once a suitable location is established, the needle is inserted through the mother's abdomen into an umbilical vessel using ultrasound guidance. If insertion into an umbilical vessel is not possible, blood may be transfused into the fetal abdomen. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7196", "text": "Prior to the transfusion, percutaneous umbilical cord blood sampling (PUBS) is conducted. The fetal blood sample is drawn and immediately analyzed for  hematocrit  using an automated analyzer in the operating room or hospital hematology laboratory. The result confirms the level of fetal anemia and indicates the correct amount of blood to be transfused."}
{"_id": "WikiPedia_Hematology$$$corpus_7197", "text": "With the needle still in place, the blood is delivered into the fetus's umbilical cord blood vessel. Following the transfusion, an additional blood sample is drawn and analyzed to determine the ending hematocrit level. The target hematocrit is usually at least 40. In a study of 135 IUTs performed on 56 fetuses, the mean hematocrit was 25.2 before IUT and 40.3 after IUT. This study also noted that repeated IUTs were generally needed in anemic fetuses. In this study, there was a median of two IUTs per fetus, with a range of one to seven. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7198", "text": "An IUT is typically only performed when the fetus is known or suspected to have life-threatening anemia. Risks of intrauterine transfusions may include uterine infection, fetal infection, preterm labor, excessive bleeding and mixing of fetal and maternal blood,  amniotic fluid  leakage from the uterus, or (rarely) fetal death. Fetal survival rates after intrauterine transfusion through the umbilical cord are more than 90% for fetuses that do not have hydrops and about 75% for fetuses that have hydrops. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7199", "text": "In a study of 135 IUTs performed on 56 fetuses over 14 years, 121 (90%) of the procedures were uneventful. In 14 cases, (10%), mild adverse events occurred. The most common mild events were prolonged hemorrhage from the puncture site and uterine contractions. In two cases, these led to a severe adverse event: one emergency  cesarean section  within 24 hours after IUT and one  preterm birth  within 7 days after IUT. There were no fetal or neonatal deaths in the study population. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7200", "text": "Risks associated with an IUT may be avoided by delivering the fetus (via  induction  or cesarean section) if an acceptable gestational age has been reached. Following delivery, the majority of neonates will require treatment such as phototherapy and top-up transfusion and/or exchange transfusion. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7201", "text": "The  Irish Blood Transfusion Service  ( IBTS ), or  Seirbh\u00eds Fuilaistri\u00fach\u00e1in na h\u00c9ireann  in  Irish , was established in  Ireland  as the  Blood Transfusion Service Board  ( BTSB ) by the  Blood Transfusion Service Board (Establishment) Order, 1965 . [ 1 ]  It took its current name in April 2000 by  Statutory Instrument  issued by the  Minister for Health and Children  to whom it is responsible. The Service provides blood and blood products for humans."}
{"_id": "WikiPedia_Hematology$$$corpus_7202", "text": "The service is the successor to the  National Blood Transfusion Association  which was established in 1948 and was, itself, born from the work carried out by the  St. John Ambulance Brigade of Ireland  in setting up an 'on call' blood donor panel [ 2 ]  to serve hospitals in the  Dublin  area. In 1975 the  Cork  Blood Transfusion Service  was amalgamated with the board, and in 1991 the  Limerick  Blood Transfusion Service  was amalgamated with the board."}
{"_id": "WikiPedia_Hematology$$$corpus_7203", "text": "The symbol of the service is a stylised  pelican , recalling the legend of the  Pelican in her piety . For most of its existence, the headquarters of the service was located at Pelican House (first in  Lower Leeson Street  and then Mespil Road) in Dublin. In 2000 the service moved to the National Blood Centre on the grounds of  St. James's Hospital  near  Dublin Heuston railway station , on which it remains. The service maintains regional facilities at  Ardee ,  Carlow ,  Cork ,  Limerick  and  Tuam ."}
{"_id": "WikiPedia_Hematology$$$corpus_7204", "text": "In 1994, the BTSB informed the Minister for Health that a batch of \"Anti-D\" blood product they had distributed in 1977 for the treatment of pregnant mothers had been contaminated with the Hepatitis C virus. Following a report by an expert group, it was discovered that the BTSB had produced and distributed a second infected batch in 1991. The Government established a  Tribunal of Enquiry [ 3 ]  to establish the facts of the case and also agreed to establish a tribunal for the compensation of victims. \nThe  Hepatitis C and HIV Compensation Tribunal  was established by the  Hepatitis C Compensation Tribunal Act, 1997 , and amended by the  Hepatitis C Compensation Tribunal (Amendment) Act, 2002 , to compensate people who contracted Hepatitis C or  HIV  as a result of receiving blood or blood products from the Service."}
{"_id": "WikiPedia_Hematology$$$corpus_7205", "text": "The  BTSB anti-D scandal  triggered a general examination of the BTSB's procedures for screening blood products for the treatment of Hemophilia and exposed the unwitting infection of many Hemophiliacs with HIV, Hepatitis B and Hepatitis C.  This resulted in the closure of the BTSB's main laboratory, curtailment in the production of some blood products, widespread changes to the management and structure of the organization and its eventual renaming in 2000."}
{"_id": "WikiPedia_Hematology$$$corpus_7206", "text": "The frequency of  blood groups  in Ireland is as follows: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7207", "text": "It is important that the IBTS collects enough O Rh D positive blood as almost half the population are that blood type. Donors with O Rh D negative are known as universal donors. Their blood can be transfused to patients of any other blood group in an emergency or if the patient's own blood group is unavailable. Because any patient can receive O Rh D negative blood, the IBTS need to have extra O Rh D negative blood available at all times."}
{"_id": "WikiPedia_Hematology$$$corpus_7208", "text": "The service depends entirely on voluntary donations from the public. New donors must be aged between 18 and 64, weigh over 50 kilograms (7 stone 12\u00a0lbs), and be in good health. At every donation  haemoglobin  levels are checked and donors complete a detailed health and lifestyle questionnaire. Donors can donate blood every 90 days."}
{"_id": "WikiPedia_Hematology$$$corpus_7209", "text": "The IBTS imposes a number of restrictions on those who can give blood. A four-month restriction is placed on donors who have had piercings or tattoos or had acupuncture, and a similar restriction on anyone who has visited a tropical country (three months). There is a year-long deferral for those who have visited a  malarial  area.\nAdditionally, there are groups of people who are permanently barred from donating blood based on their membership of high-risk groups. People who have ever been injected with any kind of non-prescription drug, and anyone who have ever been paid for sex with money or drugs are also permanently barred from donating blood."}
{"_id": "WikiPedia_Hematology$$$corpus_7210", "text": "Up to 28 November 2022,  men who have sex with men  (MSM) could not donate blood if they had engaged in oral or anal sex with another man at least 4 months prior to a donation. This policy came into effect from 28 March 2022 and came under heavy criticism from politicians, such as the Labour Party's Senator  Annie Hoey  and Sinn F\u00e9in Senator  Lynn Boylan , [ 5 ]  as well as the public [ 6 ]  due to a perceived lack of scientific basis for the policy and the lack of information on the reason for the rule. [ 7 ]  The IBTS has also been criticised for rolling back on the recommendation formally adopted by its Board in September 2021 to remove oral sex between men as a grounds for deferral from March 2022. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7211", "text": "From January 2017 to March 2022, MSM were required to abstain from all oral and anal sex for a 12-month period prior to donation. This position had replaced the previous lifetime deferral for any man who had ever engaged in oral or anal sex with another man."}
{"_id": "WikiPedia_Hematology$$$corpus_7212", "text": "From the end of November 2022, all prospective blood donors, regardless of sexual orientation or gender, may donate blood if they have not engaged in anal sex with a new partner, or multiple partners, in the 4 months prior to the donation. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7213", "text": "Donors are recognised for their commitment by being awarded as follows: A silver award is given for 10 donations; a gold award for 20 donations; a gold drop-shaped lapel pin (representing blood) for 50 donations; and presentation at an awards dinner ceremony, and a porcelain pelican, for 100 donations."}
{"_id": "WikiPedia_Hematology$$$corpus_7214", "text": "The Irish Blood Transfusion Service is also responsible for the collection of blood  platelets  and for managing the Unrelated Bone Marrow registry in Ireland. Donors can give platelets at the National Blood Centre in St James Hospital in Dublin or at  St Finbarr's Hospital  in Cork. Donors can join the unrelated bone marrow registry through their local blood clinic by offering an extra blood sample and satisfying suitability criteria."}
{"_id": "WikiPedia_Hematology$$$corpus_7215", "text": "ISBT 128  is a global standard for the identification, labeling, and information transfer of medical products of human origin (MPHO) across international borders and disparate health care systems. MPHO includes  blood ,  cells ,  tissues ,  human milk , and  organ  products among others. The Standard is managed by the  International Council for Commonality in Blood Banking Automation (ICCBBA) ."}
{"_id": "WikiPedia_Hematology$$$corpus_7216", "text": "The  International Society of Blood Transfusion  (ISBT) working group on automation and data processing began in the early 1990s and was later joined by the  AABB , the  American Red Cross  (ARC), the US  Department of Defense , [ 1 ]  and the Health Industry Manufacturers Association in the development of the symbology which would come to be known as the ISBT 128 international standard."}
{"_id": "WikiPedia_Hematology$$$corpus_7217", "text": "The acronym ISBT was originally derived from the important role played by the  International Society of Blood Transfusion  (ISBT) in the development of the standard. [ citation needed ]   Today it expands as International Standard for Blood and Transplant. The number 128 reflects the 128 characters of the  ASCII  7 bit character set that the standard uses. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7218", "text": "ICCBBA  was established in 1995 and given the responsibility for implementation and management of the new standard. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7219", "text": "Version 1.0 of the ISBT 128 Standard Technical Specification was first published in 1997, and was intended to replace the ABC  Codabar  and other similar CODABAR-based standards in use in  transfusion medicine  at that time with a more secure bar code symbology which contains more information. The current version of the ISBT 128 Standard Technical Specification can be found at the ISBT 128 website  [1] ."}
{"_id": "WikiPedia_Hematology$$$corpus_7220", "text": "Information transfer involves text on labels, but it also involves information transfer among computer systems. Increasingly, facilities"}
{"_id": "WikiPedia_Hematology$$$corpus_7221", "text": "involved in MPHO operate sophisticated computer systems to enhance safety and efficiency. Transfer of information between such facilities by electronic means ensures accuracy, but can only be effectively achieved in a global context by use of internationally agreed standards to define the information environment."}
{"_id": "WikiPedia_Hematology$$$corpus_7222", "text": "The ISBT 128 standard provides the specification for many of the elements of the information environment required in transfusion and transplantation. It contains definitions, reference tables, and data structures. Minimum requirements are also defined for delivery mechanisms and labeling. By complying with ISBT 128, collection and processing facilities can provide electronically readable information that can be read by any other compliant system. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7223", "text": "ISBT 128 specifies:"}
{"_id": "WikiPedia_Hematology$$$corpus_7224", "text": "The delivery mechanism is the means of delivering the electronic information. Probably the most well-known delivery mechanism is the linear bar code that has been used in blood transfusion practice for many years. There are in fact several types of linear bar codes, including Code 128, a bar code standard widely used in coding standards such as  GS1  and ISBT 128."}
{"_id": "WikiPedia_Hematology$$$corpus_7225", "text": "Higher capacity delivery systems are available using  2-dimensional  or reduced space symbology bar codes. These codes can carry much more information in each symbol.  Data Matrix  has been chosen as the 2-D symbology used with ISBT 128 in labeling applications."}
{"_id": "WikiPedia_Hematology$$$corpus_7226", "text": "More recently the use of  Radio frequency identification  (RFID) chips that can carry encoded information is being developed for medical products of human origin."}
{"_id": "WikiPedia_Hematology$$$corpus_7227", "text": "It is important to recognize that a range of delivery systems can sit at this level of the hierarchy. The standardized terminology, reference tables, and data structures of the information standard can be delivered as easily in a linear bar code as they can in an RFID tag. The standards themselves need to be adaptable in order to make best use of new delivery mechanisms as they are developed."}
{"_id": "WikiPedia_Hematology$$$corpus_7228", "text": "The final element in the information environment is the associated  labeling . Although there will be other labeling requirements that fall outside the information environment described in this document, an effective system needs to consider the physical association between the information and the product. Whether incorporated into a  bar code  or an electronic tag, there needs to be a mechanism that will ensure correct physical assignment of information to the product, and confidence in the association between electronically stored information and eye-readable printed information. This latter requirement must not be overlooked in the enthusiasm to embrace remotely re-writable tags."}
{"_id": "WikiPedia_Hematology$$$corpus_7229", "text": "Following meetings between  FACT ,  JACIE , and  ICCBBA , an agreement was reached to support the use of ISBT 128 for coding and labeling cellular therapy products, and this decision has been  endorsed  by the Boards of major cellular therapy professional organizations."}
{"_id": "WikiPedia_Hematology$$$corpus_7230", "text": "Jehovah's Witnesses  believe that the  Bible  prohibits Christians from accepting  blood transfusions . Their literature states that, \"'abstaining from ... blood' means not accepting blood transfusions and not donating or storing their own blood for transfusion.\" [ 1 ] [ 2 ]  The belief is based on an interpretation of scripture that differs from other Christian denominations. [ 3 ]  It is one of the doctrines for which Jehovah's Witnesses are best known. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7231", "text": "Jehovah's Witnesses' literature teaches that their refusal of transfusions of whole blood or its four primary components\u2014red cells, white cells, platelets, and plasma\u2014is a non-negotiable religious stand and that those who respect life as a gift from  God  do not try to sustain life by taking in blood, [ 5 ] [ 6 ]  even in an emergency. [ 7 ]  Witnesses are taught that the use of fractions such as  albumin ,  immunoglobulins , and  hemophiliac  preparations are not absolutely prohibited and are instead a matter of personal choice. [ 6 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7232", "text": "The doctrine was introduced in 1945 and has undergone some changes since then. Members of the group who voluntarily accept a transfusion and are not deemed repentant are regarded as having disassociated themselves from the group by abandoning its doctrines [ 9 ] [ 10 ] [ 11 ]  and are subsequently  shunned  by members of the organization. [ 12 ]  Although the majority of Jehovah's Witnesses accept the doctrine, a minority do not. [ 13 ] [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7233", "text": "The Watch Tower Society has established Hospital Information Services to provide education and facilitate  bloodless surgery . This service also maintains Hospital Liaison Committees. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7234", "text": "On the basis of various biblical texts, including  Genesis 9:4 ,  Leviticus 17:10 , and  Acts 15:28\u201315:29 , Jehovah's Witnesses believe:"}
{"_id": "WikiPedia_Hematology$$$corpus_7235", "text": "Certain medical procedures involving blood are specifically prohibited by Jehovah's Witnesses' blood doctrine. This includes the use of  red blood cells ,  white blood cells ,  platelets , and  blood plasma . Other fractions derived from blood are not prohibited.  Watch Tower  publications state that some products derived from one of the four primary components may be so similar to the function of the whole component and carry on such a life-sustaining role in the body that \"most Christians would find them objectionable\". [ 6 ]  For procedures where there is no specific doctrinal prohibition, individuals are to obtain details from medical personnel and then make a personal decision. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7236", "text": "The following medical procedures are prohibited:"}
{"_id": "WikiPedia_Hematology$$$corpus_7237", "text": "The following procedures and products are not prohibited and are left to the decision of individual members: [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7238", "text": "Many physicians have expressed a willingness to respect patients' preferences and provide bloodless treatment [ 27 ] [ need quotation to verify ]  and about 200 hospitals offer bloodless medicine and surgery programs for patients who wish to avoid or limit blood transfusions. [ 27 ]  Bloodless surgery has been successfully performed in significant procedures including  open-heart surgery  and total  hip replacements . [ 28 ]  A 2012 study in  JAMA Internal Medicine  concluded that \"Witnesses do not appear to be at increased risk for surgical complications or long-term mortality when comparisons are properly made by transfusion status. Thus, current extreme blood management strategies do not appear to place patients at heightened risk for reduced long-term survival.\" The study also stated that \"Survival estimates of Witnesses were 86%, 69%, 51%, and 34% at 5, 10, 15, and 20 years after surgery, respectively, vs 74%, 53%, 35%, and 23% among non-Witnesses who received transfusions.\" [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7239", "text": "Bloodless medical and surgical techniques have limitations, and surgeons say the use of various allogeneic blood products and pre-operative autologous blood transfusion are appropriate standards of care for certain patient presentations. [ 30 ] [ 31 ]  The Watch Tower Society states that in  medical emergencies  where blood transfusions seem to be the only available way to save a life, Jehovah's Witnesses request that doctors provide the best alternative care possible under the circumstances with respect for their personal conviction. [ 32 ]  The Watch Tower Society has acknowledged that some members have died after refusing blood. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7240", "text": "In some countries, including Canada and the United Kingdom, a parent or guardian's decision can be legally overruled by medical staff. In this case, medical staff may act without consent, by obtaining a  court order  in a non-emergency situation, or without such in an emergency. [ 34 ] [ 35 ]  In Japan, children under 15 can be administered blood transfusions against their and their parents' wishes, and children between the ages of 15 and 18 can be similarly treated provided they, or at least one of their legal guardians, consent to the procedure. [ 36 ]  In the  United States , the  American Academy of Pediatrics  recommends that in cases of \"an imminent threat to a child's life\", physicians in some cases may \"intervene over parental objections\". [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7241", "text": "In 1988, the Watch Tower Society formed  Hospital Information Services , a department to help locate doctors or surgical teams who are willing to perform medical procedures on Witnesses without blood transfusions. [ 38 ]  The department was given oversight of each branch office's  Hospital Information Desk , [ 39 ] [ 40 ] [ 41 ]  and of one hundred  Hospital Liaison Committees  established throughout the United States. [ 32 ] [ 42 ]  As of 2003, about 200 hospitals worldwide provide bloodless medical programs. [ 27 ]  As of 2006, there are 1,535 Hospital Liaison Committees worldwide coordinating communication between 110,000 physicians. [ 42 ] [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7242", "text": "Hospital Information Services researches medical journals to locate information on the availability and effectiveness of bloodless surgery methods. [ 32 ]  It disseminates information about treatment options to local Hospital Liaison Committees, and to doctors and hospitals. [ 43 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7243", "text": "Annually since 2004, Jehovah's Witnesses in the United States have been informed that \"with your consent, the law allows for the  elders  to learn of your admission [to hospital] and provide spiritual encouragement\", [ 44 ]  but that \"elders serving on a Patient Visitation Group [could] have access to your name\" only if patients made their wishes known according to the  Health Insurance Portability and Accountability Act  (HIPAA). [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7244", "text": "Jehovah's Witnesses' branch offices communicate directly with congregations regarding \"ways to benefit from the activities of the Hospital Liaison Committee (HLC) and the Patient Visitation Group (PVG).\" [ 46 ]  A Jehovah's Witnesses publication in 2000 reported that Argentina had fewer than a hundred HLC committeemen \"giving vital information to the medical community\", adding that \"their work is complemented by hundreds of other self-sacrificing elders who make up Patient Visitation Groups that call on Witness patients to help and encourage them\". [ 47 ]  Each branch office appoints PVG committeemen, who serve as volunteers. [ 48 ] [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7245", "text": "Since the elaboration of the blood doctrine to the point of prohibiting transfusion, the majority of Jehovah's Witnesses have adopted the organization's position. [ 50 ] [ 51 ]  Those Jehovah's Witnesses who accept the blood doctrine typically hold strongly to their convictions. [ 52 ]  In the August 1998 issue of  Academic Emergency Medicine , Donald Ridley, a Jehovah's Witness and organization staff attorney, argued that carrying an up-to-date Medical Directive card issued by the organization indicates that an individual personally agrees with the established religious position of Jehovah's Witness. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7246", "text": "In 1958,  The Watchtower  reported on a particular member of Jehovah's Witnesses who voluntarily accepted blood transfusion, contrary to Watch Tower Society doctrine. [ 54 ]  The organization confirms that members have accepted blood transfusions, despite the imposition in 1961 of a communal shunning policy for willful acceptance. [ 55 ] [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7247", "text": "In 1982, a peer-reviewed case study of a congregation of 59 Jehovah's Witnesses was undertaken by Drs. Larry J. Findley and Paul M. Redstone to evaluate individual belief in respect to blood among Jehovah's Witnesses. The researchers stated, \"The members of this congregation are adamant in their refusal to accept all blood products... Not one of the members stated they would receive a blood transfusion even if their refusal meant death, Almost one-third of the respondents had personally refused blood transfusions\". However, the study also showed that seven respondents were willing to accept plasma transplants and one member an autotransfusion, both therapies forbidden by Jehovah's Witnesses' doctrine. The researchers commented, \"There is either some lack of understanding or refusal to follow doctrine among some members\". The researchers noted that the contact details of the respondents were provided by congregation elders, which may have influenced the responses given. [ 57 ]  Another peer-reviewed study examining medical records indicated a similar percentage of Jehovah's Witnesses willing to accept blood transfusions for their children. Young adults also showed a willingness to accept blood transfusions. [ 50 ]  In another study, Jehovah's Witness patients presented for labor and delivery showed a willingness to accept some form of blood or blood products. Of these patients, 10 percent accepted whole blood transfusion. [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7248", "text": "Watch Tower publications have noted that within religions, the personal beliefs of members often differ from official doctrine. [ 58 ]  Regarding Jehovah's Witnesses' acceptance of the organization's official position on blood, Drs Cynthia Gyamfi and Richard Berkowitz state, \"It is na\u00efve to assume that all people in any religious group share the exact same beliefs, regardless of doctrine. It is well known that Muslims, Jews, and Christians have significant individual variations in their beliefs. Why should that not also be true of Jehovah's Witnesses?\" [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7249", "text": "Ambivalence and rejection of the blood doctrine dates back to at least the 1940s. After the Watch Tower Society established the doctrine, teaching that blood should not be eaten ( c. \u20091927 \u20131931), Margaret Buber, who was never a member of the denomination, offered a firsthand eyewitness account of Jehovah's Witnesses in the  Nazi   Ravensbr\u00fcck concentration camp . She relates that an overwhelming majority were willing to eat  blood sausage  despite having alternate food to choose from, specifically after considering biblical statements regarding blood. [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7250", "text": "From 1931, [ 61 ]  when the name \"Jehovah's witnesses\" was adopted, Watch Tower Society publications maintained the view of Society founder  Charles Taze Russell  that the reference to abstaining from the eating of blood in the  Apostolic Decree  of Acts 15:19\u201329 was a \"suggestion\" to be given to  Gentile  converts. [ 62 ] [ 63 ]  Watch Tower publications during the presidency of  Joseph Franklin Rutherford  commended the commercial and emergency uses of blood. [ 64 ] [ 65 ]  A 1925 issue of  The Golden Age  commended a man for donating blood 45 times without payment. [ 66 ]  In 1927,  The Watchtower  noted, without elaboration, that in Genesis 9, God decreed that  Noah  and his offspring \"must not eat the blood, because the life is in the blood\". [ 67 ]  In 1940,  Consolation  magazine reported on a woman who accidentally shot herself with a revolver in her heart and survived a major surgical procedure during which an attending physician donated a quart of his own blood for transfusion. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7251", "text": "In 1944, with the Watch Tower Society under the administration of president  Nathan Homer Knorr ,  The Watchtower  asserted that the decrees contained in Genesis 9:4 and Leviticus 17:10\u201314 forbade the eating or drinking of blood in biblical times \"whether by transfusion or by the mouth\" and that this applied \"in a spiritual way to the consecrated persons of good-will today, otherwise known as ' Jonadabs ' of the Lord's 'other sheep'.\" [ 69 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7252", "text": "In September 1945, representatives of the Watch Tower Society in the  Netherlands  commented on blood transfusion in the  Dutch  edition of  Consolation . A translation of their comments into English reads:"}
{"_id": "WikiPedia_Hematology$$$corpus_7253", "text": "When we lose our life because we refuse inoculations, that does not bear witness as a justification of Jehovah's name. God never issued regulations which prohibit the use of drugs, inoculations or blood transfusions. It is an invention of people, who, like the Pharisees, leave Jehovah's mercy and love aside. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7254", "text": "According to sociologist Richard Singelenbreg, the statement appearing in the Dutch edition of  Consolation  may have been published without knowledge of the doctrinal position published in the English July 1945 issue of  Consolation  by the Watch Tower Society's headquarters in the United States. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7255", "text": "In 1945, the application of the doctrine on blood was expanded to prohibit blood transfusions of whole blood, whether allogeneic or autologous. [ 72 ]  The prohibition did not specify any punitive measures for accepting a transfusion, but by January 1961\u2014in what was later described as an application of \"increased strictness\" [ 73 ] \u2014it was ruled that it was a disfellowshipping offense to conscientiously accept a blood transfusion. [ 55 ]  The Watch Tower Society warned that accepting a blood transfusion \"may result in the immediate and very temporary prolongation of life, but that at the cost of eternal life for a dedicated Christian.\" [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7256", "text": "In September 1956,  Awake!  stated, \"certain blood fractions ... also come under the Scriptural ban\". [ 75 ]  A position against \"the various blood fractions\" was reiterated in September 1961. [ 76 ]  In November of the same year, the doctrine was modified to allow individual members to decide whether they could conscientiously accept fractions used from blood for purposes such as vaccination. [ 77 ]  This position has been expanded on since; the pre-formatted Durable Power of Attorney form provided by the Watch Tower Society includes an option for Jehovah's Witnesses to \"accept all fractions derived from any primary component of blood.\" [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7257", "text": "In 1964, Jehovah's Witnesses were prohibited from obtaining transfusions for  pets , from using fertilizer containing blood, and were even advised (if their conscience troubled them) to write to dog food manufacturers to verify that their products were blood-free. [ 79 ]  Later that year, it was stated that doctors or nurses who are Jehovah's Witnesses would not administer blood transfusions to fellow dedicated members. As to administering transfusions to non-members,  The Watchtower  stated that such a decision is \"left to the Christian doctor's own conscience.\" [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7258", "text": "In 1982, an article in  The Watchtower  stated that it would be wrong for Witnesses to allow leeches to feed on their own blood as part of a medical procedure, due to the sacredness of blood. [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7259", "text": "In 1989,  The Watchtower  stated, \"Each individual must decide\" whether to accept hemodilution and autologous blood salvage (cell saver) procedures. [ 21 ]  In 1990, a brochure entitled  How Can Blood Save Your Life?  was released, outlining Jehovah's Witnesses' general doctrine on blood."}
{"_id": "WikiPedia_Hematology$$$corpus_7260", "text": "In 2000, the Watch Tower Society's stand on blood fractions was clearly stated. [ 22 ]  Members were instructed to personally decide if accepting a fraction would violate the doctrine on blood. In a later article, members were reminded that Jehovah's Witnesses do not donate blood or store their own blood prior to surgery. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7261", "text": "In May 2001, the Watch Tower Society revised its medical directives and identity cards addressing its doctrinal position on blood; the revised materials were distributed from May 3, 2001. [ 82 ]  These revised documents specified that \"allogeneic blood transfusions\" were unacceptable whereas the former document (dated 1999) stated that \"blood transfusions\" were unacceptable. The revised 2001 documents were active until December 20, 2001. The Watch Tower Society then rescinded the revised document, stating, \"After further review, it has been determined that the cards dated \"md-E 6/01\" and \"ic-E 6/01\" should not be used. Please destroy these items and make sure that they are not distributed to the publishers.\" Elders were instructed to revert to the older 1999 edition of the medical directives and identity cards. [ 83 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7262", "text": "Watch Tower Society publications frequently claim negative consequences of blood transfusions:"}
{"_id": "WikiPedia_Hematology$$$corpus_7263", "text": "Opposition to the Watch Tower doctrines on blood transfusions has come from both members and non-members. A group of dissident Witnesses known as  Associated Jehovah's Witnesses for Reform on Blood  (AJWRB) states that there is no biblical basis for the prohibition of blood transfusions and seeks to have some policies changed. [ 13 ]  In a series of articles in the  Journal of Medical Ethics , US neurologist Osamu Muramoto, who is a medical adviser to the AJWRB, has raised issues including what he claims is coercion to refuse transfusions, doctrinal inconsistency, selective use of information by the Watch Tower Society to exaggerate the dangers of transfusions and the use of outdated medical beliefs. [ 89 ] [ 90 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7264", "text": "Dissident Witnesses say the Society's use of Leviticus 17:12 to support its opposition to blood transfusions [ 91 ] [ 92 ]  conflicts with its own teachings that Christians are not under the Mosaic law. [ 93 ] [ 89 ]  Theologian  Anthony Hoekema  claims the blood prohibited in Levitical laws was not human, but animal. He cites other authors who support his view that the direction in Acts 15 to abstain from blood was intended not as an everlasting covenant but a means of maintaining a peaceful relationship between Jewish and Gentile Christians. [ 94 ] [ 95 ]  He has described as \"absurd literalism\" the Witnesses' use of a scriptural prohibition on eating blood to prohibit the medical transfusion of human blood. [ 96 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7265", "text": "Osamu Muramoto has argued that the refusal by Jehovah's Witnesses of \"life-saving\" blood treatment [ 9 ]  creates serious bio-medical ethical issues. He has criticized the \"controlling intervention\" of the Watch Tower Society by means of what he claims is information control and its policy of penalising members who accept blood transfusions or advocate freedom to choose blood-based treatment. [ 89 ] [ 9 ]  He says the threat of being classified as a disassociated Witness and subsequently shunned by friends and relatives who are members coerces Jehovah's Witnesses to accept and obey the prohibition on blood transfusions. [ 10 ] [ 89 ] [ 90 ]  In one particular case involving a Russian district court decision, however, the  European Court of Human Rights  (ECHR) found nothing in the judgments to suggest that any form of improper pressure or undue influence was applied. It noted: \"On the contrary, it appears that many Jehovah's Witnesses have made a deliberate choice to refuse blood transfusions in advance, free from time constraints of an emergency situation.\" The court said: \"The freedom to accept or refuse specific medical treatment, or to select an alternative form of treatment, is vital to the principles of self-determination and personal autonomy. A competent adult patient is free to decide ... not to have a blood transfusion. However, for this freedom to be meaningful, patients must have the right to make choices that accord with their own views and values, regardless of how irrational, unwise or imprudent such choices may appear to others.\" [ 97 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7266", "text": "Muramoto has claimed the intervention of Hospital Liaison Committees can add to \"organisational pressure\" applied by family members, friends, and congregation members on Witness patients to refuse blood-based treatment. He notes that while HLC members, who are church elders, \"may give the patient 'moral support', the influence of their presence on the patient is known to be tremendous. Case reports reveal JW patients have changed their earlier decision to accept blood treatment after a visit from the elders.\" He claims such organizational pressure compromises the autonomy of Witness patients and interferes with their privacy and confidentiality. He has advocated a policy in which the Watch Tower organization and congregation elders would not question patients on the details of their medical care and patients would not disclose such information. He says the Society adopted such a policy in 1983 regarding details of sexual activity between married couples. [ 9 ] [ 98 ] [ 99 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7267", "text": "Watch Tower spokesman Donald T. Ridley says neither elders nor HLC members are instructed or encouraged to probe into the health care decisions of Witness patients and do not involve themselves in patient hospitalisations unless patients request their assistance. Yet Watch Tower Society HLC representative David Malyon says he would respond to the \"sin\" of Witnesses he is privy to by effectively saying \"Are you going to tell them or shall I!\" [ 100 ]  Nevertheless Ridley says Muramoto's suggestion that Witnesses should be free to disregard Watch Tower scriptural teachings and standards is preposterous. He says loving God means obeying commandments, not disobeying them, and hiding one's disobedience from others. [ 99 ] [ 101 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7268", "text": "Muramoto recommends doctors have a private meeting with patients to discuss their wishes, and that church elders and family members not be present, enabling patients to feel free of church pressure. He suggests doctors question patients on (a) whether they have considered that the Watch Tower Society might soon approve some medical practices they currently find objectionable, in the same manner that it has previously abandoned its opposition to vaccination and organ transplants; (b) whether Witness patients know which blood components are allowed and which are prohibited, and whether they acknowledge that those rulings are organizational policy rather than biblical teachings; and (c) whether they realize that although some Bible scriptures proscribe the eating of blood, eating and transfusing blood have entirely different effects on the body. [ 90 ]  HLC representative David Malyon has responded that Muramoto's suggested questions are an affront to coerce Jehovah's Witnesses with a \"complicated philosophical inquisition\" and, if used by doctors, would be \"an abusive transformation of the medical role of succour and care into that of devil's advocate and trickster\". [ 100 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7269", "text": "Muramoto has claimed many Watch Tower Society publications employ exaggeration and emotionalism to emphasize the dangers of transfusions and the advantages of alternative treatments but present a distorted picture by failing to report any benefits of blood-based treatment. Nor do its publications acknowledge that in some situations, including rapid and massive  haemorrhage , there are no alternatives to blood transfusions. [ 89 ] [ 90 ]  He states that Watch Tower Society publications often discuss the risk of death as a result of refusing blood transfusions, but give little consideration to the prolonged suffering and disability, producing an added burden on family and society, that can result from refusal. [ 90 ]  Attorney and former Witness Kerry Louderback-Wood [ 102 ]  also claims that Witness publications exaggerate the medical risks of taking blood and the efficiency of non-blood medical therapies in critical situations. [ 103 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7270", "text": "Douglas E. Cowan , an academic in the sociology of religion, has claimed that members of the  Christian countercult movement  who criticize the Watch Tower Society make selective use of information themselves. For example,  Christian apologist  Richard Abanes wrote that their ban on blood transfusions \"has led to countless Witness deaths over the years, including many children.\" [ 104 ]  Cowan wrote: \"When the careful reader checks [Abanes' footnote], however, looking perhaps for some statistical substantiation, he or she finds only a statistical conjecture based on 1980 Red Cross blood use figures.\" Cowan also says Abanes omits \"critical issues\" in an attempt to \"present the most negative face possible.\" Cowan wrote that \"the reader is left with the impression that the Watchtower Society knowingly presides over a substantial number of preventable deaths each year.\" [ 105 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7271", "text": "Osamu Muramoto says the Watch Tower Society relies on discarded, centuries-old medical beliefs to support its assertion that blood transfusions are the same as eating blood. [ 106 ]  The Watch Tower Society's 1990 brochure  How Can Blood Save Your Life?  quoted 17th-century anatomist  Thomas Bartholin  to support its view. [ 107 ]  Muramoto says the view that blood is nourishment\u2014still espoused in Watch Tower publications [ 108 ] \u2014was abandoned by modern medicine many decades ago. [ 89 ]  He has criticized an analogy commonly used by the Society [ 109 ]  in which it states: \"Consider a man who is told by the doctor that he must abstain from alcohol. Would he be obedient if he quit drinking alcohol but had it put directly into his veins?\" [ 106 ]  Muramoto says the analogy is false, explaining: \"Orally ingested alcohol is absorbed as alcohol and circulated as such in the blood, whereas orally eaten blood is digested and does not enter the circulation as blood. Blood introduced directly into the veins circulates and functions as blood, not as nutrition. Hence, blood transfusion is a form of cellular organ transplantation. And ... organ transplants are now permitted by the WTS.\" [ 89 ]  He says the objection to blood transfusions on the basis of biblical proscriptions against eating blood is similar to the refusal of a heart transplant on the basis that a doctor warned a patient to abstain from eating meat because of his high cholesterol level. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7272", "text": "David Malyon, chairman of the English Hospital Liaison Committee in  Luton ,  England , has claimed that Muramoto's discussion of the differences between consuming blood and alcohol is pedantic and says blood laws in the Bible are based upon the reverence for life and its association with blood, and that laws should be kept in the spirit as much as in the letter. [ 100 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7273", "text": "Muramoto has described as peculiar and inconsistent the Watch Tower policy of acceptance of all the individual components of blood plasma as long as they are not taken at the same time. [ 89 ]  He says the Society offers no biblical explanation for differentiating between prohibited treatments and those considered a \"matter of conscience\", explaining the distinction is based entirely on arbitrary decisions of the  Governing Body , to which Witnesses must adhere strictly on the premise of them being Bible-based truth. [ 89 ]  He has questioned why white blood cells (1 per cent of blood volume) and platelets (0.17 per cent) are forbidden, yet albumin (2.2 per cent of blood volume) is permitted. [ 89 ]  He has questioned why donating blood and storing blood for autologous transfusion is deemed wrong, but the Watch Tower Society permits the use of blood components that must be donated and stored before Witnesses use them. [ 90 ]  He has questioned why Witnesses, although viewing blood as sacred and symbolizing life, are prepared to let a person die by placing more importance on the symbol than the reality it symbolizes. [ 90 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7274", "text": "Kerry Louderback-Wood says that by labeling the currently acceptable blood fractions as \"minute\" in relation to whole blood, the Watch Tower Society causes followers to misunderstand the scope and extent of allowed fractions. [ 103 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7275", "text": "The Watch Tower Society's response is that the real issue is not of the fluid  per se , but of respect and obedience to God. [ 77 ] [ 110 ]  They say their principle of abstaining from blood as a display of respect is demonstrated by the fact that members are allowed to eat  meat  that still contains some blood. As soon as blood is drained from an animal, the  respect  has been shown to God, and then a person can eat the meat even though it may contain a small amount of blood. [ 77 ]  Jehovah's Witnesses' view of meat and blood is different from that of kosher Jewish adherents, who go to great lengths to remove minor traces of blood. [ 111 ] [ 112 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7276", "text": "The  Junior blood group system  (or  JR ) is a human  blood group  defined by the presence or absence of the  Jr(a) antigen , a high-frequency antigen that is found on the red blood cells of most individuals. [ 1 ]  People with the rare Jr(a) negative blood type can develop  anti-Jr(a)  antibodies, which may cause  transfusion reactions  and  hemolytic disease of the newborn  on subsequent exposures. Jr(a) negative blood is most common in people of Japanese heritage. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7277", "text": "The gene  ABCG2 , located on chromosome 4q22.1, encodes an  ATP-binding cassette transporter  protein that carries the Jr(a) antigen. The Jr(a) negative blood type is inherited in an  autosomal recessive  manner: individuals who are  homozygous  for a  null mutation  of  ABCG2  express this phenotype. [ 1 ]  Homozygosity for certain  missense mutations , or heterozygosity for a missense mutation and a null mutation, can result in a weak phenotype with decreased expression of Jr(a) antigen. [ 2 ] [ 3 ]  As of 2018, over 25 null and weak alleles of  ABCG2  have been described. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7278", "text": "The highest rates of the Jr(a) negative blood type have been reported in Japan, [ 5 ]  where its prevalence ranges from 1 in 60 in the  Niigata  region to 1 in 3800 in the  Tokyo  region. [ 1 ]  Additionally, a number of cases have been documented in European  Romani  populations. [ 6 ]  The Jr(a) negative blood type is very rare in America: a study of 9,545 Americans failed to identify any Jr(a) negative individuals. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7279", "text": "Anti-Jr(a) antibodies are generally composed of  Immunoglobulin G  and develop when individuals are exposed to Jr(a) positive blood through pregnancy or  blood transfusion . Some cases of anti-Jr(a) have been reported in patients who have not been previously transfused or pregnant. [ 2 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7280", "text": "Jr(a) is more strongly expressed on  cord blood  cells than on adult red blood cells, [ 4 ]  and anti-Jr(a) has been reported to cause  hemolytic disease of the newborn  (HDN), [ 2 ]  including fatal cases of HDN. [ 5 ] [ 7 ]   The antibody has also been implicated in  delayed hemolytic transfusion reactions . [ 2 ]  However, the clinical significance of the antibody is variable: in some cases, individuals with anti-Jr(a) have been transfused with Jr(a) positive blood or given birth to Jr(a) positive babies without incident. It is recommended to transfuse individuals with anti-Jr(a) with Jr(a) negative blood if the  antibody titer  is high. In other cases, \"least incompatible\" blood (the blood unit that gives the weakest reactions during  crossmatching ) may be suitable. [ 5 ] [ 4 ]  It is difficult to secure Jr(a) negative donor blood due to the rarity of this blood type. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7281", "text": "ABCG2 is a  uric acid  transporter, and the Jr(a) negative phenotype is associated with  gout  in Japanese populations. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7282", "text": "An individual's Junior blood type can be determined by  serologic testing , which uses a  monoclonal antibody  reagent directed against the Jr(a) antigen. [ 6 ]   DNA testing  may be impractical due to the high number of mutations affecting Jr(a) expression. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7283", "text": "Anti-Jr(a) antibodies are most easily detected by the  indirect antiglobulin test , and their reactivity is enhanced by enzyme treatment with  ficin  or  papain . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7284", "text": "The Junior blood group system was discovered in 1970 by researchers Stroup and MacIllroy, who reported on five patients whose blood was incompatible with all samples tested except each other's. They named the causative antigen \"JR\" after Rose Jacobs, one of the five patients \u2014 the common name \"Junior\" is in fact a misnomer. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7285", "text": "In 2012, two research groups [ 6 ] [ 10 ]  independently identified ABCG2 as the basis of the Junior blood group system. The Junior system was officially designated a blood group by the  International Society of Blood Transfusion  that year. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7286", "text": "The  Kell antigen system  (also known as the  Kell\u2013Cellano system ) is a  human blood group system , that is, a group of  antigens  on the human red blood cell surface which are important determinants of  blood type  and are targets for  autoimmune  or  alloimmune  diseases which destroy red blood cells. The Kell antigens are  K ,  k ,  Kp a ,  Kp b ,  Js a  and  Js b . [ 1 ]  The Kell antigens are  peptides  found within the  Kell protein , a 93- kilodalton   transmembrane   zinc -dependent  endopeptidase  which is responsible for cleaving  endothelin-3 . [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7287", "text": "The  KEL  gene encodes a type II transmembrane  glycoprotein [ 4 ]  that is the highly  polymorphic  Kell blood group antigen. The Kell glycoprotein links via a single  disulfide bond  to the  XK membrane protein [ 5 ]  that carries the  Kx antigen . The encoded protein contains sequence and structural similarity to members of the  neprilysin  (M13) family of  zinc   endopeptidases . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7288", "text": "There are several  alleles  of the  gene  which creates Kell protein. Two such alleles,  K 1  (Kell) and  K 2  (Cellano), are the most common. The kell protein is tightly bound to a second protein,  XK , by a  disulfide bond . Absence of the XK protein (such as through  genetic deletion  or through a single point mutation within the coding region of the XK gene [ 7 ] ), leads to marked reduction of the Kell antigens on the red blood cell surface. Absence of the Kell protein (K 0 ), however, does not affect the XK protein. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7289", "text": "The Kell protein has also recently been designated  CD238  ( cluster of differentiation  238)."}
{"_id": "WikiPedia_Hematology$$$corpus_7290", "text": "Kell antigens are important in  transfusion medicine ,  autoimmune hemolytic anemia  and  hemolytic disease of the newborn (anti-Kell) . Anti-K is the next most common immune red cell antibody after those in the ABO and Rh system. Anti-K typically presents as IgG class alloantibody. Individuals lacking a specific Kell antigen may develop  antibodies  against Kell antigens when transfused with blood containing that antigen. This is particularly true for the \"K\" antigen which shows a relatively high antigenicity and moderately low frequency (~9%) in Caucasian populations. Anti-K can also occur following transplacental hemorrhage associated with childbirth making Kell an important concern for  hemolytic disease of the newborn . Following the formation of anti-K, subsequent blood transfusions may be marked by destruction of the new cells by these antibodies, a process known as  hemolysis . Anti-K does not bind complement, therefore hemolysis is extravascular. Individuals without K antigens(K 0 ) who have formed an antibody to a K antigen, must be transfused with blood from donors who are also K 0  to prevent hemolysis. [ citation needed ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7291", "text": "Autoimmune hemolytic anemia  (AIHA) occurs when the body produces an antibody against a blood group antigen on its own red blood cells. The antibodies lead to destruction of the red blood cells with resulting  anemia . Similarly, a pregnant woman may develop antibodies against fetal red blood cells, resulting in destruction, anemia, and  hydrops fetalis  in a process known as  hemolytic disease of the newborn  (HDN). Both AIHA and HDN may be severe when caused by anti-Kell antibodies, [ 10 ]  as they are the most immunogenic antigens after those of the  ABO  and  Rhesus blood group systems . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7292", "text": "McLeod phenotype (or McLeod syndrome) is an  X-linked  anomaly of the Kell blood group system in which Kell antigens are poorly detected by laboratory tests. The McLeod gene encodes the XK protein, a protein with structural characteristics of a membrane transport protein but of unknown function. The XK appears to be required for proper synthesis or presentation of the Kell antigens on the red blood cell surface. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7293", "text": "The Kell group was named after the first patient described with antibodies to K 1 , a pregnant woman named Mrs. Kellacher in 1945. [ 11 ]  Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K 2 . The K 0   phenotype  was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a  Harvard  dental student, in 1961. [ 12 ] [ 13 ] \nKing  Henry VIII of England  may have had Kell-positive blood type, explaining the deaths of seven of his ten children at, or soon after, birth, and suggesting that his mental deterioration around age 40 could be explained by McLeod Syndrome; [ 14 ]  this was supported by the revelation that Henry may have inherited Kell from his maternal great-grandmother,  Jacquetta of Luxembourg . [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7294", "text": "Evidence supports a genetic link between the Kell blood group (on  chromosome 7  q33) and the ability to taste  phenylthiocarbamide , or PTC, a bitter-tasting  thiourea  compound. [ 16 ] [ 17 ]  Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome  locus  7 q35-6. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7295", "text": "The  Kidd antigen system  (also known as  Jk antigen ) are proteins found in the Kidd's blood group, which act as antigens, i.e., they have the ability to produce antibodies under certain circumstances. The Jk  antigen  is found on a  protein  responsible for  urea  transport in the red blood cells and the kidney. [ 1 ]  They are important in  transfusion medicine . People with two Jk(a) antigens, for instance, may form  antibodies  against donated blood containing two Jk(b) antigens (and thus no Jk(a) antigens). This can lead to  hemolytic anemia , in which the body destroys the transfused blood, leading to low red blood cell counts. Another disease associated with the Jk antigen is  hemolytic disease of the newborn , in which a pregnant woman's body creates antibodies against the blood of her fetus, leading to destruction of the fetal blood cells. Hemolytic disease of the newborn associated with Jk antibodies is typically mild, though fatal cases have been reported. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7296", "text": "The  gene  encoding this protein is found on  chromosome 18 . [ 3 ]  Three Jk  alleles  are Jk (a), Jk (b)and Jk3. Jk (a) was discovered by Allen et al. in 1951 and is named after a patient (Mrs Kidd delivered a baby with a haemolytic disease of the newborn associated with an antibody directed against a new antigen Jk (a). Whereas Jk (b) was discovered by Plant et al. in 1953, individuals who lack the Jk antigen (Jk null) are unable to maximally concentrate their urine. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7297", "text": "Kidd comprises three antigens on a  glycoprotein  with 10  transmembrane  spanning  domains ,  cytoplasmic   N-  and  C-termini  and one extracellular  N-glycosylation  site. [ 5 ] \nThe Kidd gene has 11  exons  with exons 4-11 encoding the mature protein. The Kidd gene ( SLC14A1 ) is on chromosome 18q12.3. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7298", "text": "Jka and Jkb are the products of alleles with Asp280 and Asn280 in the fourth external loop of the Kidd glycoprotein. Jka and Jkb have similar prevalences in White and Asian populations but Jka is more common in Black populations than Jkb. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7299", "text": "Kidd antigens are enhanced by enzymes [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7300", "text": "Jk(a-b-) represents the null phenotype and usually results from homozygosity for a silent gene at the JK locus. [ 5 ]  The null phenotype is rare in most populations but does have increased prevalence in Polynesians (one in 400) and Niueans (1.4%). [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7301", "text": "In Polynesians the null allele contains a splice site mutation in intron 5 causing a loss of exon 6 from the mRNA product. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7302", "text": "In Finns (null phenotype less rare than in other European populations), the null phenotype results from a mutation encoding a Ser291Pro substitution. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7303", "text": "A rare null phenotype in Japanese individuals results from heterozygosity for an inhibitor gene. In(Jk) in analogy with the In(Lu) dominant inhibitor of Lutheran and other antigens. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7304", "text": "Immunized individuals with the Jk(a-b-) phenotype may produce anti-Jk3. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7305", "text": "Very weak expression of Jka and/or Jkb can be detected on In(Jk) red blood cells in adsorption/elution tests. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7306", "text": "Anti-Jka and -Jkb are not common. They are usually warm-reacting IgG1 and IgG3 but may also include IgG2, IgG4 or IgM. Approximately 50% of anti-Jka and -Jkb antibodies are capable of binding complement. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7307", "text": "Kidd antibodies display dosage: red cells from  homozygous  individuals (JkaJka or Jk(a+b-)) express more antigen than  heterozygous  individuals (JkaJkb or Jk(a+b+)). [ 7 ]  Anti-Kidd antibodies appear to react more strongly against cells that are homozygous. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7308", "text": "Kidd antibodies can be difficult to detect by direct agglutination testing and generally require addition of antihuman globulin after a warm incubation period. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7309", "text": "Kidd antibodies are dangerous as they are capable of causing severe acute  hemolytic transfusion reactions . They are unique in that they are capable of dropping to low or even undetectable levels after several months following an exposure. [ 5 ]  Thus, on pre-transfusion testing, an anti-Jka or -Jkb may go undetected. Following transfusion, a subsequent robust antibody response in the patient can occur ( anamnestic response ), resulting in hemolysis of the transfused red blood cells. Kidd antibodies are often capable of binding complement and causing intravascular hemolysis.  More often, however, Kidd antibodies cause acute extravascular hemolysis. [ 7 ]  They are a notorious cause of delayed hemolytic transfusion reactions, and may occur up to a week after transfusion in some instances. Kidd antibodies only rarely cause  hemolytic disease of the fetus and newborn . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7310", "text": "Kidd antigens are located on a red blood cell urea transporter (human urea transporter 11- HUT11 or UT-B1). [ 8 ]  As red blood cells approach the renal medulla (where there is a high concentration of urea), the urea transporter allows for rapid uptake of urea and prevents cell shrinkage in the hypertonic environment of the medulla. [ 5 ]  As the red cell leaves the medulla, the urea is transported back out of the cell, preventing cellular swelling and preventing the urea from being carried away from the kidney. [ 5 ]   HUT11 was detected on endothelial cells of the vasa recta (vascular supply of the renal medulla) but it is not present in renal tubules. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7311", "text": "Due to absence of the urea transporter, Jk(a-b-) cells are not hemolyzed by 2M urea. This can be used as a screening test for Jk(a-b-) donors. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7312", "text": "The Jk(a-b-) phenotype has no clinical defect, although two individuals with this phenotype have been reported to have mild urine-concentrating defects. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7313", "text": "Kidd antibodies are capable of behaving as histocompatibility antigens in renal transplants and may be responsible for allograft rejection in some cases. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7314", "text": "The  Lan blood group system  (short for  Langereis ) is a human  blood group  defined by the presence or absence of the  Lan antigen  on a person's red blood cells. More than 99.9% of people are positive for the Lan antigen. Individuals with the rare Lan-negative blood type, which is a  recessive trait , can produce an  anti-Lan   antibody  when exposed to Lan-positive blood. Anti-Lan antibodies may cause  transfusion reactions  on subsequent exposures to Lan-positive blood, and have also been implicated in mild cases of  hemolytic disease of the newborn . However, the clinical significance of the antibody is variable. The antigen was first described in 1961, and Lan was officially designated a blood group in 2012. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7315", "text": "The Lan antigen is carried on the protein  ABCB6 , an  ATP-binding cassette transporter  encoded by the  ABCB6  gene on chromosome 2q36. The Lan-negative blood type is inherited in an  autosomal recessive  manner, being expressed by individuals who are  homozygous  for nonfunctional  alleles  of  ABCB6 . [ 1 ] [ 2 ]  Some variant alleles cause a weak positive phenotype, which may be mistaken for a Lan-negative phenotype in serologic testing. [ 2 ]  As of 2018, more than 40 null or weak alleles of  ABCB6  have been described. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7316", "text": "ABCB6 is involved in  heme  synthesis and  porphyrin  transport and is widely expressed throughout the body, particularly in the heart,  skeletal muscle , eye, fetal liver,  mitochondrial membrane , and  Golgi bodies . [ 4 ] :\u200a220\u200a  The Lan antigen is more strongly expressed on  cord blood  cells than on adult red blood cells. [ 5 ] :\u200a490\u200a  Despite the protein's wide distribution, Lan-negative individuals do not appear to experience any adverse effects from the absence of ABCB6. [ 1 ] [ 2 ]  It is thought that other porphyrin transporters, such as  ABCG2  (which carries the  Junior blood group antigen ), may compensate. [ 4 ] :\u200a220\u200a [ 6 ]  A 2018 study found that Lan-negative blood cells exhibited resistance to  Plasmodium falciparum   in vitro . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7317", "text": "The prevalence of the Lan antigen exceeds 99.9% in most populations. The frequency of the Lan-negative blood type is estimated at 1 in 50,000 in Japanese populations, 1 in 20,000 in Caucasians, and 1 in 1,500 in black people from South Africa. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7318", "text": "When Lan-negative individuals are exposed to Lan-positive blood through  transfusion  or pregnancy, they may develop an anti-Lan antibody. Anti-Lan is considered a clinically significant antibody, [ 4 ] :\u200a220\u200a  but its effects are variable. It has been associated with severe  transfusion reactions  and mild cases of  hemolytic disease of the newborn , but in some cases individuals with the antibody have not experienced any adverse effects from exposure to Lan-positive blood. It is recommended that individuals with anti-Lan are transfused with Lan-negative blood, especially if the  antibody titer  is high. [ 2 ]  One case of  autoimmune hemolytic anemia  involving auto-anti-Lan has been described. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7319", "text": "Serologic reagents and molecular assays for Lan  antigen typing  were not commercially available as of 2013. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7320", "text": "Anti-Lan antibodies are typically composed of  immunoglobulin G  and may bind  complement . As an IgG antibody, anti-Lan can be detected using the  indirect antiglobulin test . The antibody is resistant to treatment with  ficin ,  papain ,  trypsin ,  DTT , and EDTA/glycine-acid. [ 2 ] [ 4 ] :\u200a220"}
{"_id": "WikiPedia_Hematology$$$corpus_7321", "text": "The Lan antigen was first described in 1961 by Van der Hart et al., [ 8 ]  when a Dutch patient suffered a severe hemolytic transfusion reaction. [ 4 ] :\u200a220\u200a [ 5 ] :\u200a489\u200a  The patient was found to produce an antibody that reacted with all but 1 out of 4,000 blood donors tested. The causative antigen was identified and designated \"Langereis\" after the patient's last name. [ 2 ]  Lan was officially designated a blood group by the  International Society of Blood Transfusion  in 2012, following the discovery of the molecular basis of the Lan-negative phenotype. [ 4 ] :\u200a220\u200a [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7322", "text": "Samuel Armstrong Lane  FRCS (1802 \u2013 2 August 1892) was an English  surgeon , consulting surgeon to  St Mary's Hospital ."}
{"_id": "WikiPedia_Hematology$$$corpus_7323", "text": "In 1840 while practicing in London England, Samuel Armstrong Lane, aided by consultant Dr. Blundell, performed the first successful whole Blood transfusion in an attempt to treat  hemophilia ."}
{"_id": "WikiPedia_Hematology$$$corpus_7324", "text": "In 1843 he was elected one of the original 300  Fellow of the Royal College of Surgeons"}
{"_id": "WikiPedia_Hematology$$$corpus_7325", "text": "Media related to  Samuel Armstrong Lane  at Wikimedia Commons"}
{"_id": "WikiPedia_Hematology$$$corpus_7326", "text": "Leukoreduction  is the removal of  white blood cells  (or  leukocytes ) from the  blood  or blood components supplied for  blood transfusion .  After the removal of the leukocytes, the blood product is said to be  leukoreduced ."}
{"_id": "WikiPedia_Hematology$$$corpus_7327", "text": "It is theorized that  transfusions  that contain white blood cells may cause adverse effects through multiple mechanisms.  White blood cells may themselves harbor infectious disease and some  pathogens  will be more concentrated in white blood cells than the rest of the blood product. [ 1 ]   It is also theorized that the donor white blood cells may  suppress  the recipient's  immune system  by interacting with it. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7328", "text": "An April 2007  meta-analysis  by Dr. Neil Blumberg and others and covering 3093 patients who received leukoreduced blood was published in the scientific journal  Transfusion .  According to the meta-analysis, use of leukoreduced blood reduced the frequency of post-transfusion infection by 50%. [ 2 ]    In a previous study, Blumberg and others reported that a change to universal use of leukoreduced blood at  Strong Memorial Hospital  at  University of Rochester  reduced post-transfusion infection by 33-45%. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7329", "text": "However, other scientific studies question the effectiveness of leukoreduction.  A March 2007 study by researchers at  University of South Alabama  Medical Center found no reduction of mortality or length of hospital stay in 439 trauma patients who received leukoreduced transfusions compared to 240 patients who did not. [ 4 ]   University of Washington  researchers reported in October 2006 that a study of 286 transfused injury patients showed no reduction in mortality or length of stay, although a 16% reduction in rate of infection was shown with marginal statistical significance. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7330", "text": "Leukoreduction has the inadvertent effect of removing approximately 10% of  red blood cells  from a processed unit of Red Blood Cells. [ 6 ]   Because blood from persons who possess the  sickle cell  mutation is difficult to filter, leukoreduction is often not performed on donors who may have the sickle cell gene, which is most common in people of  African  descent. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7331", "text": "Dr. Blumberg, the lead author of the meta-analysis covering 3093 patients, stated in the press that the cost savings due to universal leukoreduction exceeds the cost of performing the leukoreduction. [ 7 ] [ medical citation needed ]   The cost of leukoreduction is an increase of approximately US$30 per unit of blood product. [ 4 ] [ medical citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7332", "text": "Universal leukoreduction is currently not practiced in all countries. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7333", "text": "As of 2008, most developed nations have adopted universal leukoreduction of transfusions (defined as the routine application of this blood-processing step to all units of whole blood, red blood cells, and platelets prior to storage) with the notable exception of the  United States . [ 8 ]   Canada ,  Britain  and  France  adopted universal leukoreduction in the late 1990s.  Germany  adopted it in 2001. [ 9 ]  Leukoreduced products are commonly available in the United States and some hospitals use only leukoreduced blood while others only use leukoreduced products in certain patient populations.  For example,  Strong Memorial Hospital  began universal use of leukoreduced blood in July 2000; [ 7 ]  University of South Alabama Medical Center began use in January 2002. [ 4 ] \nWoodlands Medical Centre is beginning a randomised controlled trial to look into the benefits of transfusing leukoreduced whole blood for the ICCU patients."}
{"_id": "WikiPedia_Hematology$$$corpus_7334", "text": "The  Lewis antigen system  is a  human blood group system . It is based upon two genes on  chromosome 19 :  FUT3 , or Lewis gene; and  FUT2 , or Secretor gene. Both genes are expressed in glandular epithelia. FUT2 has a dominant allele which codes for an enzyme (designated Se) and a recessive allele which does not produce a functional enzyme (designated se). Similarly, FUT3 has a functional dominant allele (Le) and a non-functional recessive allele (le)."}
{"_id": "WikiPedia_Hematology$$$corpus_7335", "text": "The proteins produced by the FUT2 and FUT3 genes modify type I oligosaccharide chains to create Lewis antigens. These oligosaccharide chains are similar to the type II chains of the  ABO blood system , with a single bond in a different position. The link between the Lewis blood group and secretion of the ABO blood group  antigens  was possibly the first example of multiple effects of a human  gene : [ 1 ]  the same enzyme (fucosyltransferase2) which converts the Le-a antigen to Le-b is also responsible for the presence of soluble A, B and H antigens in bodily fluids."}
{"_id": "WikiPedia_Hematology$$$corpus_7336", "text": "There are two main types of Lewis antigens, Lewis a (Le-a) and Lewis b (Le-b). There are three common phenotypes: Le(a+b-), Le(a-b+), and Le(a-b-). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7337", "text": "The enzyme fucosyltransferase 3 (FUT3), encoded by Le gene, adds a fucose to the precursor  oligosaccharide  substrate, converting it to the Le-a antigen. People who have the Le allele and who are non-secretors (homozygous for the nonfunctional se allele) will express the Le-a antigen in their bodily fluids and on their erythrocytes."}
{"_id": "WikiPedia_Hematology$$$corpus_7338", "text": "If a person has both the Le and Se alleles, their exocrine cells will also have the enzyme fucosyltransferase 2 (FUT2). This adds fucose to the oligosaccharide precursor in a different position from the FUT3 enzyme. This produces the Le-b antigen. In most people having both Le and Se, it is difficult to detect the antigen Le-a. This is because the activity of the FUT2 enzyme is more efficient than the FUT3 enzyme, so the type I oligosaccharide chain is mostly converted into Le-b instead of Le-a. Therefore, people with readily detectable Lewis-a antigen are non-secretors; they do not have FUT2 activity. Lewis-b antigen is found only in secretors: people who possess the Se allele and thus have FUT2 activity. Lewis negative people (Le a-, Le b-) are homozygous for the recessive le allele and can be either secretors or non-secretors."}
{"_id": "WikiPedia_Hematology$$$corpus_7339", "text": "Lewis antigens are expressed on the surface of  red blood cells ,  endothelium , kidney, genitourinary and  gastrointestinal epithelium . [ 3 ] [ 4 ] [ 5 ]  Lewis antigens are  red blood cell  antigens which are not produced by the cell itself. Instead, Lewis antigens are components of  exocrine   epithelial  secretions, and are subsequently adsorbed onto the surface of the red cell. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7340", "text": "The three above-stated common Lewis phenotypes represent the presence or absence of Lewis and Secretor enzymes. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7341", "text": "Le(a+b-) individuals have at least one functional Lewis gene (Le) but are homozygous for nonfunctional Secretor alleles (sese).  Thus, these individuals synthesize and secrete Le(a) antigen but lack Le(b) and type 1 chain ABH. [ 7 ] \nLe(a-b+) individuals inherit both Le and Se alleles, leading to the synthesis of Le(a), Le(b), and type 1 chain ABH.  Most type 1 chain precursor is converted to Le(b), therefore these individuals appear as if they are Le(a-). [ 7 ] \nLe(a+b+) phenotype is transiently observed in infants (Secretor activity increases with age). [ 7 ]   This phenotype is also encountered in 16% of Japanese individuals (who inherit a weak Secretor gene- Se(w))."}
{"_id": "WikiPedia_Hematology$$$corpus_7342", "text": "In absence of a functional Lewis gene (lele), neither Le(a) nor Le(b) are synthesized, leading to the Le(a-b-) phenotype. This phenotype is more common in persons of African descent. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7343", "text": "Two precursor oligosaccharides exist, type 1 and type 2.  Type 1 is found in secretions and in the serum.  Type 2 is found exclusively on the surface of red blood cells.  No type 1 oligosaccharide is found on RBCs.  Unbranched type 1 and 2 oligosaccharides represent  i antigen .  Branched type 1 and 2 oligosaccharides are  I antigens . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7344", "text": "In neonates,  i antigen  oligosaccharides predominate (high in cord blood samples).  Oligosaccharide branching increases with age, thus adults have mostly  I antigen . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7345", "text": "The H gene of the  ABO system  encodes a  fucosyltransferase  that adds fucose to type 2 precursor substances on the surface of RBCs to make H antigen.  The h allele is an amorphic form of the gene.  If no further modifications are made to the H antigen, the person is type O.  When the A gene product acts on the H antigen and adds an N-acetylgalactosamine, the A antigen results and the person is type A.  When the B gene product acts on the H antigen to add a galactose, the B antigen results and the person is type B. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7346", "text": "The Le gene encodes a fucosyltransferase that adds fucose to type 1 precursor substance (both free in serum and in secretions) to make the Le(a) antigen.  The le gene is an amorph.  The Lewis antigen produced on free type 1 precursor substance passively adsorbs onto the surfaces or red blood cells. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7347", "text": "The Se gene encodes a fucosyltransferase that adds fucose to type 1 precursor generating H antigen. After this step, the Le gene product (FUT3) can add another fucose producing Le(b) antigen.  Thus, individuals with the Le gene but no Se gene will have red blood cells bearing only the passively-adsorbed Le(a) but no Le(b).  Individuals with both the Le gene and the Se gene will have red blood cells bearing only the passively adsorbed Le(b) and no Le(a).  Individuals with no Le gene have neither Le(a) nor Le(b). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7348", "text": "In addition, the Se gene product is responsible for the presence of A, B and H substances in secretions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7349", "text": "Lewis antibodies are naturally occurring antibodies, almost always IgM type, found almost exclusively in Le(a-b-) individuals. [ 7 ]  Lewis antibodies may include a mixture of anti-Le(a), anti-Le(b) and anti-Le(a+). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7350", "text": "Lewis antibodies are almost always clinically insignificant because:"}
{"_id": "WikiPedia_Hematology$$$corpus_7351", "text": "Therefore, it is not necessary to transfuse antigen-negative blood components for most patients."}
{"_id": "WikiPedia_Hematology$$$corpus_7352", "text": "Lewis antibodies are generally reactive at room temperature and only occasionally at 37 C and AHG phase (antihuman globulin)."}
{"_id": "WikiPedia_Hematology$$$corpus_7353", "text": "Lewis antibodies are not a cause of  hemolytic disease of the fetus and newborn  (HDFN), as stated below."}
{"_id": "WikiPedia_Hematology$$$corpus_7354", "text": "Lewis antigens cannot be reliably detected until the 2nd birthday.  Lewis antibodies in a pregnant woman are essentially totally insignificant because they are IgM subtype (don't cross the placenta) and Lewis antigen is weakly expressed during pregnancy (Lewis Le(a-b-) phenotype is commonly seen during gestation). [ 2 ]   Most newborns will type as Le(a-b-). [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7355", "text": "Lewis antigen is often decreased on RBCs during pregnancy with some women transiently typing as Le(a-b-). [ 7 ]  This is thought to be due in part to increased circulating plasma volume in pregnancy and increased lipoprotein. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7356", "text": "The Le(b) and H antigens are receptors for the bacteria  Helicobacter pylori , a  gram-negative  bacterium that can cause  gastritis  and has been implicated in  peptic ulcer disease ,  gastric adenocarcinoma , mucosa-associated lymphoma (or  mucosal associated lymphatic tissue lymphoma  \u2013 MALToma) and  idiopathic thrombocytopenic purpura  (ITP). [ 7 ] [ 8 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7357", "text": "Le(b) and type 1 H antigens are also receptors for Norwalk virus (common cause of acute gastroenteritis). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7358", "text": "The Le(a-b-) phenotype is associated with an increased susceptibility to infections by Candida and  uropathogenic  Escherichia coli . [ 7 ] [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7359", "text": "In patients with pancreatic adenocarcinoma and not harbouring a functional Lewis enzyme (Lea-b- genotype: 7%\u201310% of the population), levels of  CA 19-9  are typically undetectable or below 1.0 U/ml. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7360", "text": "The  LU domain  ( Ly-6 antigen / uPAR ) is an evolutionarily conserved protein domain of the  three-finger protein  superfamily. This domain is found in the  extracellular domains  of  cell-surface receptors  and in either  GPI-anchored  or  secreted   globular proteins , for example the Ly-6 family,  CD59 , and Sgp-2. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7361", "text": "A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved LU domain of about 100 amino-acid residues. [ 4 ] [ 5 ]  Among these proteins, most contain only a single LU domain, though small numbers of exceptions are known; well-studied family member  uPAR  has three tandem LU domains. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7362", "text": "This domain folds into five antiparallel  beta sheets , a structure common to the  three-finger protein   family . The domain typically contains ten well- conserved   cysteine  residues involved in five  disulfide bonds , though some examples such as two of the three  uPAR  domains have fewer. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7363", "text": "Besides uPAR, other receptors with LU domains include members of the  transforming growth factor beta receptor  (TGF-beta) superfamily, such as the  activin type 2 receptor ; [ 6 ]  and  bone morphogenetic protein receptor, type IA . [ 7 ]  Other LU domain proteins are small globular proteins such as  CD59 antigen ,  LYNX1 ,  SLURP1 , and  SLURP2 . [ 2 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7364", "text": "ARS;        CD177 ;      CD59 ;       LY6D ;       LY6E ;       LY6H ;       LYNX1 ;   \n LYPD2 ;      LYPD3 ;      LYPD4 ;      LYPD5 ;      LYPD6 ;   PLAUR ;      PSCA ;    \n SLURP2 ;    SLURP1 ;     SPACA4 ;     TEX101 ;"}
{"_id": "WikiPedia_Hematology$$$corpus_7365", "text": "Many LU domain containing proteins are involved in  cholinergic  signaling and bind  acetylcholine  receptors, notably linking their function to a common  mechanism  of 3FTx toxicity. [ 2 ] [ 3 ] [ 9 ]  Members of the Ly6/uPAR family are believed to be the evolutionary ancestors of the  three-finger toxin  (3FTx). [ 10 ]  Other LU proteins, such as the  CD59 antigen , have well-studied functions in regulation of the  immune system . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7366", "text": "The  Lutheran antigen systems  is a  classification of human blood  based on the presence of substances called Lutheran  antigens  on the surfaces of red blood cells. There are 19 known Lutheran antigens. [ 1 ] \nThe name Lutheran stems from a blood donor's misspelled last name, reportedly named Lutteran or Lutheran. [ 2 ] [ 3 ] [ 4 ] [ 5 ] \nAll of these antigens arise from variations in a gene called  BCAM (basal cell adhesion molecule) . The system is based on the expression of two codominant alleles, designated Lua and Lub. The antigens Aua and Aub, known as the  Auberger  antigens, were once thought to make up a separate blood group but were later shown to be Lutheran antigens arising from variations in the BCAM gene."}
{"_id": "WikiPedia_Hematology$$$corpus_7367", "text": "The  phenotypes  Lu(a+b\u2212) and Lu(a+b+) are found at various frequencies within populations. The Lu(a\u2212b+) phenotype is the most common in all populations, whereas the Lu(a\u2212b\u2212) phenotype is uncommon. Though present in the  fetus , it is seldom the cause of  erythroblastosis fetalis  or of transfusion reactions."}
{"_id": "WikiPedia_Hematology$$$corpus_7368", "text": "In  transfusion medicine ,  mixed-field agglutination  refers to mixed reactions during cell typing where two distinct cell populations are present: agglutinated cells admixed with many unagglutinated cells. The presence of two or more cell populations is known as  chimerism . Mixed-field agglutination is an important cause of ABO typing and genotype discrepancies. The cause of mixed field agglutinations should be sought prior to setting up blood for transfusion. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7369", "text": "By far the most common cause of mixed-field agglutination is false chimerism. There are several causes of false chimerism;"}
{"_id": "WikiPedia_Hematology$$$corpus_7370", "text": "1) Transfusion of donor red cells. For example, a blood group B individual who has received a transfusion of group O donor red cells may show mixed field agglutination with anti-B sera. His own group B red cells are agglutinated by the anti-B sera while the group O donor red cells in his circulation are unagglutinated [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7371", "text": "2) After an ABO mismatched  stem cell transplant  for example a blood group O stem cell donor and a blood group A stem cell recipient. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7372", "text": "3) Weak expression of the A or  B blood group  antigen [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7373", "text": "4) In some diseases, for example leukaemia [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7374", "text": "A true chimerism is a rare sporadic phenomenon whereby an individual has a dual cell population derived from more than one zygote. This may result from intrauterine exchange of erythrocyte precursors between twins (twin chimerism) or two fertilized eggs fuse into one individual. Twin chimerism results from mixing of blood between two twin fetuses through placental blood vessel anastomoses, leading to engraftment of hematopoietic stem cells from one twin within the marrow of the other. Each twin ends up with two distinct cell populations of varying proportions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7375", "text": "The  MNS antigen system  is a  human blood group system  based upon two genes ( glycophorin A  and  glycophorin B ) on  chromosome 4 .  There are currently 50  antigens  in the system, [ 1 ] [ 2 ] [ 3 ] [ 4 ]  but the five most important are called M, N, S, s, and U."}
{"_id": "WikiPedia_Hematology$$$corpus_7376", "text": "The system can be thought of as two separate groups: the M and N  antigens  are at one location on the  ECM  and S, s, and U are on a closely related location.  The two groups are very closely located together on  chromosome 4  and are inherited as a  haplotype ."}
{"_id": "WikiPedia_Hematology$$$corpus_7377", "text": "The  MN blood group  in humans is under the control of a pair of  co-dominant   alleles , L M  and L N . Most people in the  Inuit  population are M/M, while this genotype is rare among  Aborigines . In fact, they tend to possess the opposite genotype (N/N). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7378", "text": "The MN blood group system is under the control of an  autosomal  locus found on chromosome 4, with two alleles designated L M  and L N . The blood type is due to a  glycoprotein  present on the surface of a red blood cell (RBC), which behaves as a native  antigen .  Phenotypic  expression at this locus is  codominant  because an individual may exhibit either one or both antigenic substances. Frequencies of the two  alleles  vary widely among human populations. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7379", "text": "M+ and N+ RBCs are common (75% of population) and M+N+ cells are the most common genotype (50% of population).  These antigens were an early discovery and are some of the oldest blood antigens known after the  ABO system .  They were first described by  Karl Landsteiner  and  Philip Levine  in 1927.  Anti-M and anti-N antibodies are usually  IgM  and are rarely associated with  transfusion reactions . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7380", "text": "Anti-N is sometimes seen in  dialysis  patients due to cross-reactions with the residual  formaldehyde  from sterilizing the equipment.  This is usually irrelevant for transfusion since this variant of the antibody does not react at body temperature. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7381", "text": "The S antigen is relatively common (~55% of the population) and the s antigen is very common (~89% of the population).  Anti-S and anti-s can cause  hemolytic transfusion reactions  and  hemolytic disease of the newborn .The U antigen is a high incidence antigen, occurring in more than 99.9% of the population. The U was originally short for \"Universal\", though this is not the case. U negative RBCs can be found in people of  African  descent.  This mutation in red cell surface structure also makes the RBCs S- and s-.  Anti-U has been associated with both hemolytic transfusion reactions and hemolytic disease of the newborn. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7382", "text": "The other 41 identified antigens in the MNS group are low incidence, such as He (0.8% of the population) or  high incidence, such as EN a  (>99.9% of the population)."}
{"_id": "WikiPedia_Hematology$$$corpus_7383", "text": "Antigens of the MNS system are located on one of two glycoproteins: glycophorin A (GPA, CD235A) and glycophorin B (GPB, CD235B). [ 6 ]   Each glycoprotein crosses the membrane once and has an external N-terminal domain (varying in length from 44 amino acids for GPB to 72 amino acids in length for GPA) [ 6 ]  as well as a C-terminal cytosolic domain (GPB, 8 amino acids in length; GPA, 36 amino acids in length). [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7384", "text": "Neonatal alloimmune thrombocytopenia  ( NAITP ,  NAIT ,  NATP  or  NAT ) is a  disease  that affects babies in which the  platelet count is decreased  because the mother's immune system attacks her  fetus ' or newborn's  platelets . A low platelet count increases the risk of bleeding in the fetus and newborn.\u00a0 If the bleeding occurs in the brain, there may be long-term effects."}
{"_id": "WikiPedia_Hematology$$$corpus_7385", "text": "Platelet  antigens  are inherited from both mother and father.   NAIT  is caused by antibodies specific for platelet antigens inherited from the father but which are absent in the mother. [ 1 ]   Fetomaternal transfusions (or fetomaternal hemorrhage) results in the recognition of these antigens by the mother's immune system as non-self, with the subsequent generation of allo-reactive antibodies which cross the placenta.  NAIT , hence, is caused by transplacental passage of maternal platelet-specific  alloantibody  and rarely  human leukocyte antigen  ( HLA ) allo-antibodies [ 2 ]  (which are expressed by platelets) to fetuses whose platelets express the corresponding antigens."}
{"_id": "WikiPedia_Hematology$$$corpus_7386", "text": "NAIT  occurs in somewhere between 1/800 [ 3 ]  and 1/5000 [ 4 ]  live births. More recent studies of  NAIT  seem to indicate that it occurs in around 1/600 live births in the Caucasian population. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7387", "text": "The diagnosis of NAIT is usually made after an incidental finding of a low platelet count on a blood test or because of bleeding complications ranging from bruising or  petechiae  to  intracranial hemorrhage  in the fetus or newborn. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7388", "text": "Frequently, the reduction in platelet count is mild and the affected neonates remain largely asymptomatic. [ 6 ]   NAIT is the commonest cause of a very low platelet count, and the commonest cause of intracranial haemorrhage in the term neonate. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7389", "text": "In case of severe thrombocytopenia, the neonates may exhibit bleeding complications at or a few hours after delivery. The most serious complication is intracranial hemorrhage, leading to death in approximately 10% of symptomatic babies [ 6 ]  or neurologic sequelae in 20% of cases. 80% of intracranial hemorrhages occur before birth. [ 6 ]  After birth the greatest risk of bleeding is in the first four days of life. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7390", "text": "Immune thrombocytopenic purpura  ( ITP ), sometimes called  idiopathic thrombocytopenic purpura  is a condition in which autoantibodies are directed against a patient's own platelets, causing platelet destruction and thrombocytopenia.  Anti-platelet autoantibodies in a pregnant woman with  immune thrombocytopenic purpura  will attack the patient's own platelets and will also cross the placenta and react against fetal platelets.  Therefore,  ITP  is a significant cause of fetal and neonatal immune thrombocytopenia.  Approximately 10% of newborns affected by  ITP  will have platelet counts <50,000 \u03bcL \u22121  and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with  NAIT . [ 1 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7391", "text": "Mothers with thrombocytopenia or a previous diagnosis of  ITP  should be tested for serum anti-platelet antibodies.  A woman with symptomatic thrombocytopenia and an identifiable anti-platelet antibody should be started on therapy for their  ITP  which may include steroids or  IVIG .  Fetal blood analysis to determine the platelet count is not generally performed as  ITP -induced thrombocytopenia in the fetus is generally less severe than  NAIT . Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7392", "text": "Other conditions that can cause a low platelet count in the neonate include bacterial and viral infection,  disseminated intravascular coagulation  and other rare congenital conditions associated with a low platelet count. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7393", "text": "Platelets have many proteins on their surface. Each person has a different set of proteins, which are inherited from their parents. These different platelet proteins make different platelet groups, just like different proteins on  red blood cells  make different  blood groups . These differences do not affect how the platelets work. However, if a baby inherits a protein that is found on the father's platelets but is absent from the mother's platelets, the mother may respond to this foreign protein by developing an antibody that fights against it. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7394", "text": "This antibody may pass from the mother's blood into the baby's blood and attach to the baby's platelets. This antibody destroys the baby's platelets and suppresses production of fetal platelets, they are also thought to weaken the blood vessel walls (vascular integrity) and affect production of new blood vessels ( angiogenesis ). [ 9 ]  This results in an increased risk of bleeding for the baby, and this can lead to the baby's death. [ 9 ]  The mother's antibodies can remain in the baby's bloodstream for weeks, and bleeding can occur in the baby before birth (fetal), during birth or after birth (neonatal). [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7395", "text": "A number of different proteins can cause NAIT, about 80% of cases are caused by antibodies against platelet antigen  HPA -1a , 15% by anti- HPA -5b , and 5% by other antibodies (e.g.  HPA -1b ,  HPA -15,  HPA -3 and  HPA -9b). [ 10 ] [ 11 ]   HPA -1a is present in 98% of the population of the United States, suggesting that approximately 2% of women who are  HPA -1a negative may be at risk for  NAIT  during pregnancy. [ 1 ] [ 12 ]  Of course, the antigen expression of the father must also be taken into account - in most cases the father is  HPA -1a/1a or 1a/1b and the mother is  HPA -1b/1b with anti- HPA -1a antibodies.  In women of Asian descent,  HPA -4 antigens are the most frequently implicated. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7396", "text": "Studies have shown a relationship between maternal  HLA  type DRw52a (DRB3* 0101) and the development of anti- HPA -1a. [ 14 ] [ 15 ] [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7397", "text": "The offending antibodies are IgG subtype and therefore capable of crossing the placenta and entering the fetal circulation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7398", "text": "Unlike  hemolytic disease of the fetus and newborn ,  NAIT  occurs during the first pregnancy in up to 50% of cases, [ 1 ]  and the affected fetuses may develop severe thrombocytopenia (<50,000 \u03bcL \u22121 ) very early during pregnancy (as early as 20 weeks gestation, consistent with the development of platelet antigens, [ 1 ]  and the majority of the time  in utero [ 18 ] ). Usually, the thrombocytopenia increases as gestation progresses. During the first pregnancy,  NAIT  is often not detected until birth when the newborn presents with classic symptoms of thrombocytopenia including  petechiae , bruising or intracranial hemorrhage. [ 1 ]  In utero intracranial hemorrhage occurs in about 10% to 30% of affected cases (and  NAIT  is thought to be the underlying cause in the majority of cases of intracranial hemorrhage due to thrombocytopenia- greater than all other causes of thrombocytopenia combined). The risk of hemorrhage is inversely related to the platelet count with the greatest risk when the platelet count is below 100,000 \u03bcL \u22121 . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7399", "text": "The recurrence of  NAIT  has been estimated to be more than 80% in subsequent pregnancies in which the fetus also carries the target platelet antigen. [ 6 ]   Subsequent cases of  NAIT  may be equivalent or more severe. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7400", "text": "The fetal response to  NAIT  is variable and may include compensatory extramedullary hematopoiesis.  Rarely, fetal hydrops may develop.  Fetal anemia (in presence of red cell incompatibility) may also occur. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7401", "text": "Doctors may consider a diagnosis of NAIT if they notice bleeding or bruising in a baby, or low platelet counts on a blood test after birth, or neurologic symptoms. Some babies may have a specific pinpoint rash called \u201c petechiae \u201d. If a diagnosis of NAIT is suspected, then the baby should be treated as if it had NAIT until the diagnosis is confirmed. [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7402", "text": "The diagnosis is confirmed by taking blood samples from the baby's parents, and sometimes the baby. Maternal and paternal platelet antigen phenotyping and screening of the maternal serum for anti-platelet antibodies can be performed. [ 12 ]  Additionally, platelet antigen  genotyping  can be performed on the maternal and paternal blood to determine the exact nature of the incompatibility. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7403", "text": "Neonatal platelet counts on laboratory testing are typically under 20,000 \u03bcL \u22121 .  Higher counts may suggest a different diagnosis, such as maternal  immune thrombocytopenic purpura . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7404", "text": "Even in mildly affected babies, it is important to fully investigate and diagnose the baby because the results can be critical for the effective management of any future pregnancies. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7405", "text": "Antenatal management only occurs if a mother has had a previously affected baby or a family member has had an affected baby. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7406", "text": "Interventions can be classified as invasive or non-invasive. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7407", "text": "A review of the evidence has shown that invasive management resulted in a relatively high complication rate (mainly preterm emergency  cesarean section ) of 11% per treated pregnancy. [ 9 ]  Noninvasive management was also shown to be effective, but without the relatively high rate of adverse outcomes seen with invasive management. [ 9 ]  They concluded that first-line antenatal management in NAIT should be non-invasive with weekly  intravenous immunoglobulin  administration, with or without the addition of  corticosteroids . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7408", "text": "Recent international guidelines have now recommended non-invasive management of NAIT. [ 19 ] [ 20 ]  Previously there had been no international consensus on the optimal antenatal management of NAIT, [ 9 ]  and numerous strategies had been used in different centers that specialized in antenatal treatment. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7409", "text": "Fetal blood sampling from the umbilical cord and intrauterine platelet transfusion was the first antenatal treatment for NAIT to prevent intracerebral hemorrhage. [ 9 ]  However, this is no longer recommended routinely because of the serious risk of harms. [ 9 ] [ 19 ]   Cordocentesis  in the presence of a low platelet count may lead to serious complications, these included slowing of the baby's heart (fetal bradycardia),  tamponade  of the cord, and bleeding complications in the baby, including  exsanguination .  Fetal blood sampling is estimated to cause death of the baby in 1.3% of procedures, however the incidence varies significantly from center to center. [ 22 ]  With an overall risk of death of the fetus due to the repeated procedures of about 3% (17 deaths out of 485 pregnancies). [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7410", "text": "In addition, given the short life span of transfused platelets, transfusions are needed regularly, increasing the overall risk of death of the baby. If intrauterine platelet transfusions are performed, they are generally repeated weekly (platelet lifespan after transfusion is approximately 8 to 10 days).   Platelets administered to the fetus must be negative for the culprit antigen (often  HPA -1a, as stated above).  Many blood suppliers (such as  American Red Cross ;  NHS Blood and Transplant ;  United Blood Services ) have identified  HPA -1a and 5b negative donors.  An alternative donor is a mother who is, of course, negative for the culprit antigen.  However, she must meet general criteria for donation and platelets received from the mother must be washed to remove the offending alloantibody and irradiated to reduce the risk of  graft-versus-host disease .  If platelet transfusions are needed urgently, incompatible platelets may be used, with the understanding that they may be less effective and that the administration of any blood product carries risk. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7411", "text": "Any administered cellular blood products must be irradiated to reduce the risk of  graft-versus-host disease  in the fetus. Additionally, all administered blood products should be  CMV  reduced-risk ( CMV  seronegative and leukoreduced are considered essentially equivalent for the purposes of  CMV  risk reduction). [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7412", "text": "The use of  Intravenous immunoglobulin  ( IVIG ) during pregnancy and immediately after birth has been shown to help reduce or alleviate the effects of  NAIT  in infants and reduce the severity of thrombocytopenia.  The most common treatment is weekly  IVIG  infusions at a dosage of 1 g/kg beginning at 12 to 16 weeks of pregnancy in women who have had a previously affected child with an intracranial hemorrhage. [ 19 ]  For all other pregnancies, use of IVIG should be discussed, and, if indicated, should be started before 24 weeks of pregnancy and continued until the birth of the child. [ 19 ] [ 23 ] [ 24 ] [ 9 ] [ 25 ]  In some cases this dosage is increased to 2 g/kg and/or combined with a course of  prednisolone   depending on the exact circumstances of the case. [ 9 ] [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7413", "text": "In a review they found that giving IVIG alone during pregnancy prevented intracranial hemorrhage in 98.7% of treated pregnancies (4 cases occurred in 315 pregnancies). [ 9 ]  This is a similar estimate to a previous review that only assessed the evidence within randomised controlled trials. [ 25 ]  They also found no consistent benefit of adding steroids to IVIG. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7414", "text": "The goal of both  IVIG  and platelet transfusion is to avoid hemorrhage.  Ultrasound monitoring to detect hemorrhage in the fetus is not recommended as detection of intracranial hemorrhage generally indicates permanent brain damage (there is no intervention that can be performed to reverse the damage once it has occurred). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7415", "text": "Before delivery, the fetal platelet count may not be known, due to the high risks associated with cordocentesis (see above). [ 19 ]   If the platelet count is not known then assisted forms of delivery, for example  forceps  or  ventouse , should be avoided to reduce the risk of harm. [ 19 ]  If the delivery has been planned then antigen negative platelets should be available in case the infant's platelet count is low on a cord blood sample. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7416", "text": "The most rapidly effective treatment in infants with severe hemorrhage and/or a very low platelet count (<30,000  \u03bcL \u22121 ) is the transfusion of compatible platelets (i.e. platelets from a donor who, like the mother, lacks the causative antigen). [ 20 ]  If  antigen negative platelets are unavailable, then standard neonatal platelet transfusions should be given until antigen negative platelets become available. [ 20 ] [ 19 ]  If a platelet transfusion is not available immediately then the infant can be given IVIG (1g/kg) however, this will have no effect on the platelet count before 24 to 72 hours. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7417", "text": "A platelet transfusion is required immediately if there is severe or life-threatening bleeding. [ 19 ] [ 20 ]  If life-threatening bleeding occurs, for example an  intracranial hemorrhage , then the platelet count needs to be increased to decrease the risk of further bleeding (> 100,000  \u03bcL \u22121 ). [ 19 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7418", "text": "Any infant with suspected NAIT should have an ultrasound of the head within the first 24 hours after birth to make sure that there is no evidence of an  intracranial hemorrhage . [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7419", "text": "If the infant has a platelet count >30,000  \u03bcL \u22121  and no evidence of bleeding, then the baby can be monitored with blood counts until the blood counts return to normal, without the need for any additional treatment. [ 19 ]  In the past, infusions of  IVIG  (1 g/kg/day for two days) have been given to the infant and have been shown to rapidly increase the  platelet count . [ 6 ]  However, IVIG and platelet transfusions are also associated with harm and therefore should be avoided if they are not necessary. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7420", "text": "After a first affected pregnancy, if a mother has plans for a subsequent pregnancy, then the mother and father should be typed for platelet antigens and the mother screened for alloantibodies.  Testing is available through reference laboratories (such as  ARUP ).   DNA  testing of the father can be used to determine zygosity of the involved antigen and therefore risk to future pregnancies (if homozygous for the antigen, all subsequent pregnancies will be affected, if heterozygous, there is an approximate 50% risk to each subsequent pregnancy).  During subsequent pregnancies, the genotype of the fetus can also be determined using amniotic fluid analysis or maternal blood as early as 18 weeks gestation to definitively determine the risk to the fetus. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7421", "text": "NHS Blood and Transplant   is an executive  special health authority  of the United Kingdom's  Department of Health and Social Care .\nIt was established on 1 October 2005 to take over the responsibilities of two separate NHS agencies: UK Transplant (now renamed Organ Donation and Transplantation), founded by  Dr. Geoffrey Tovey  in 1972, [ 3 ]  and the National Blood Service [ 4 ]  (now renamed Blood Donation). Its remit is to provide a reliable, efficient supply of blood, organs and associated services to the NHS. Since NHSBT was established, the organisation has maintained or improved the quality of the services delivered to patients, stabilised the rising cost of blood, and centralised a number of corporate services."}
{"_id": "WikiPedia_Hematology$$$corpus_7422", "text": "It has the responsibility for optimising the supply of blood, organs and tissues and raising the quality, effectiveness and efficiency of blood and  transplant  services. Its roles are stated to include: [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7423", "text": "In 2009/10 its strategic objectives were focused on the efficient provision of a safe and sustainable supply of blood and its components, the identification and referral of more organ donors and the establishment of NHSBT as an effective and responsive organisation, focused on the needs of donors and patients. The year saw a record high in organ donation and transplantation together with an increase in the number of people signing up to donate blood. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7424", "text": "The Core System Modernisation Programme which was meant to modernise the organisation\u2019s information technogy systems was abandoned in 2018 with costs of \u00a326 million written off. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7425", "text": "The National Blood Service, now renamed NHS  Blood Donation , is the organisation for England which collects blood and other tissues, tests, processes, and supplies all the hospitals in England. Other official blood services in the United Kingdom include the  Northern Ireland Blood Transfusion Service ,  Scottish National Blood Transfusion Service  and the  Welsh Blood Service . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7426", "text": "The National Blood Service was formed in 1946 as the National Blood Transfusion Service of England and Wales (NBTS). The National Blood Authority was established as a Special Health Authority in 1993 and assumed control of the 12 English Regional Transfusion Centres in 1994. The National Blood Service became a nationally coordinated body in 1996. The service operates out of fifteen centres, and collects around 2.1 million donations per year and supplies 8,000 units of blood every day. Service directors proposed a reconfiguration and centralisation strategy in 2006, based on the closure of most local processing and testing labs, and subsequent operation out of just three large 'supercentres' to serve the same geographical area. [ 8 ]  Staff opposed this strategy. [ 9 ]  In July 2015 it was decided to shut the blood supply chain manufacturing facilities in Sheffield and Newcastle in 2017 and transfer their work to Manchester. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7427", "text": "Blood donation vehicles are allowed the use of  blue lights and sirens  (known commonly \" blues and twos \") for the use of emergency blood transports. In some cases this will also require the use of a police escort for the transporting vehicle in order to safely and quickly navigate major road junctions. Escort is normally provided by several motorbike units."}
{"_id": "WikiPedia_Hematology$$$corpus_7428", "text": "The service depends entirely on voluntary donations from the public. Originally, blood was collected from various donor clinics located over the country. In 1994, the first mobile session was held in Elstree, hosted by  The Joely Bear Appeal . In the South West from 1946 and since the formation of the NHS the service was primarily a mobile collection service visiting all parts of the mainly rural community. Originally Local Organisers called up the Donors from their own lists; this only changed in the 1990s. This link with the Local Organisers was inherited from the Wartime Red Cross (mainly) and St. Johns blood collection teams.  These mobile teams continue to collect, but two centres \u2013 Bristol and Plymouth (Derriford) \u2013 have static bases in local venues. Currently, blood donation sessions are set up throughout the country and take place in many diverse venues, from village halls, workplaces and mobile collection units (known as  Bloodmobiles ). Donors are generally required to be fit and healthy, weigh 50 kilograms (110\u00a0lb; 7\u00a0st 12\u00a0lb) and aged between 17 and 60. However, regular (healthy) donors are permitted to donate past the age of 60 as long as they remain healthy. Donors are encouraged to give blood up to three times a year (once every 16 weeks). Since February 2012, male donors have been allowed to donate up to four times a year. [ 11 ]   In 2013\u201314 1,986 people complained they had been turned away from walk-in sessions. 1,949 said they did not have their blood taken even when they had made an appointment. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7429", "text": "Besides the main blood donations, known as \"whole blood\",  platelets  are also collected. As platelets can only be stored for a few days, regular and frequent donors are in great demand and that is why platelet donors are asked to attend at least 8\u201310 times per year."}
{"_id": "WikiPedia_Hematology$$$corpus_7430", "text": "Organ Donation and Transplantation ensures that organs donated for transplant are matched and allocated to patients in a fair and unbiased way. Matching, particularly in the case of kidneys, is so important that donation and allocation needs to be organised nationally. The larger the pool of organs, the better the likelihood there is of a good match. Unlike some other NHS organisations, it does not have a direct relationship with patients and do not provide \"hands on\" care. However, in providing support to transplantation services across England, everything it does affects the quality of service delivered to individual patients. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7431", "text": "In 1968, the National Tissue Typing and Reference Laboratory was established at  Southmead Hospital  in Bristol. [ 4 ] [ 13 ] [ 14 ]  The National Organ Matching and Distribution Service  was founded in 1972 and the two organisations merged in 1979 to form the UK Transplant Service. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7432", "text": "In 1991 the UK Transplant Service became an NHS special health authority and was renamed the United Kingdom Transplant Support Service Authority. It moved to purpose-built accommodation at  Stoke Gifford , in the northern suburbs of Bristol, in 1993. In July 2000, UK Transplant was formed with a new, extended remit to increase organ donation rates. In October 2005 UK Transplant merged with the National Blood Service and the  Bio Products Laboratory  to form NHS Blood and Transplant. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7433", "text": "In 2010, the Bio Products Laboratory became a  limited company  owned directly by the Department of Health. The Department of Health partly privatised it in 2013, selling a significant majority stake to Bain Capital. The business benefited from investment and growth, enabling full privatisation, achieved when a group controlled by Creat Group Corporation acquired it in 2016."}
{"_id": "WikiPedia_Hematology$$$corpus_7434", "text": "The NHS Organ Donor Register is a national, confidential list of people who are willing to become donors after their death. It can be quickly accessed to see whether an individual has registered a willingness to be an organ donor. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7435", "text": "NHSBT operates the largest blood processing facility in Europe, capable of processing 1 million units a year. [ 15 ] [ 16 ]  The site also houses the International Blood Group Reference Laboratory, one of the world\u2019s leading laboratories in rare blood identification. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7436", "text": "Northfield Laboratories Inc.  (former NASDAQ:  NFLD ) was the maker of  PolyHeme , a  hemoglobin-based oxygen carrier  (HBOC).  The company was based in  Evanston, Illinois , with Dr. Steven A. Gould as its  chief executive officer .  As of May 31, 2005, the company had 68 employees."}
{"_id": "WikiPedia_Hematology$$$corpus_7437", "text": "It was founded in 1985 and has since been a mainly  research and development  company.  Northfield's only product was PolyHeme, an oxygen-carrying  blood substitute , which failed to receive  Food and Drug Administration  (FDA) regulatory approval.  On May 9, 2009, after being informed by the FDA the product's risks outweighed the benefits, the company shut down operations. During their operations, they incurred losses of about 220 million dollars. [ 1 ]  The corporation was also criticized for some design elements of its clinical trials related to the need to perform critical care and resuscitation while patients were in grave clinical conditions due to the mechanisms of injury incurred and the consequent inability of patients to provide informed consent for treatment. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7438", "text": "This  chemical corporation -related article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_7439", "text": "This United States corporation or company article is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_7440", "text": "In  Osborn v. Irwin Memorial Blood Bank , 5 Cal.App.4th 234 (1992), the  Court of Appeals of California  considered certain questions pertaining to whether a  blood bank  could be held liable for  negligence  or  negligent misrepresentation  after a patient contracted  HIV/AIDS  as a result of a  blood transfusion ."}
{"_id": "WikiPedia_Hematology$$$corpus_7441", "text": "In 1983, Michael Osborn, an infant, underwent surgery to repair a  congenital heart defect .  During that surgery, Osborn received a blood transfusion.  At the time of the transfusion, donated blood was not routinely tested for  human immunodeficiency virus , because the cause of  AIDS  had not definitively been identified yet."}
{"_id": "WikiPedia_Hematology$$$corpus_7442", "text": "Fearing that AIDS could be transmitted by blood, the Osborns had requested to make  directed blood donations  specifically earmarked for use by Michael.  They first contacted the surgeon, who informed them that they needed to contact the blood bank.  The receptionist at the blood bank, however, said that directed donations were not allowed, and so the surgery proceeded using blood from the public supply.  He subsequently was diagnosed with  acquired immune deficiency syndrome  (AIDS)."}
{"_id": "WikiPedia_Hematology$$$corpus_7443", "text": "The patient and his family sued the University of California (where the surgery occurred) and the  Irwin Memorial Blood Bank  (which supplied the blood) for multiple  causes of action .  A jury trial took place.  The blood bank introduced evidence that its safety procedures were at least as good as those generally prevailing at the time.  The blood bank also sought to introduce evidence that, because the patient was  type A negative , he could not receive any donations from members of his family, as a result of which only a small amount of blood (or no blood at all) would have been able to be provided by means of  directed donation , but the judge did not allow defendants to present this evidence to the jury."}
{"_id": "WikiPedia_Hematology$$$corpus_7444", "text": "At the conclusion of the evidence the trial judge granted the defendants' motions for  nonsuit  on several of the causes of action, and  directed a verdict  in favor of the university on the remaining causes of action.  Thus, only the blood bank remained as a defendant, and the following questions were submitted to the jury:"}
{"_id": "WikiPedia_Hematology$$$corpus_7445", "text": "The jury returned a general verdict in favor of the plaintiffs and awarded them a total of $750,000.  The blood bank moved for  judgment notwithstanding the verdict  and also moved for an amended judgment on the grounds that the damages awarded were in excess of those allowed under the  Medical Injury Compensation Reform Act  (MICRA).  The trial court acknowledged that it had erred when it had held that MICRA did not apply, and the blood bank moved for a new trial."}
{"_id": "WikiPedia_Hematology$$$corpus_7446", "text": "The court granted the blood bank's motion for  judgment notwithstanding the verdict  as to the counts of negligence and intentional  misrepresentation  and, conditioned on the plaintiffs' acceptance, reduced the award to $416,307.  Both sides appealed."}
{"_id": "WikiPedia_Hematology$$$corpus_7447", "text": "There were three issues on appeal:"}
{"_id": "WikiPedia_Hematology$$$corpus_7448", "text": "The California Court of Appeals ruled in favor of defendants on the count of negligence, held that the defendants were entitled to a new trial on the issue of negligent misrepresentation, and ruled in favor of the university."}
{"_id": "WikiPedia_Hematology$$$corpus_7449", "text": "P1PK  (formerly: P) is a  human blood group system  ( International Society of Blood Transfusion  system 003) based upon the  A4GALT  gene on  chromosome 22 . The P antigen (later renamed P1) was first described by  Karl Landsteiner  and  Philip Levine  in 1927. [ 1 ]  The P1PK blood group system consists of three  glycosphingolipid  antigens: P k , P1 and NOR. [ 2 ] [ 3 ]  In addition to glycosphingolipids, terminal Gal\u03b11\u21924Gal\u03b2 structures are present on complex-type N-glycans. [ 4 ]  The GLOB antigen (formerly P) is now the member of the separate GLOB (globoside) blood group system."}
{"_id": "WikiPedia_Hematology$$$corpus_7450", "text": "The P1PK antigens are carbohydrate antigens that include P k  (Gb3), P1 and NOR1, NOR int  and NOR2. All are synthesized by Gb3/CD77 synthase (\u03b11,4-galactosyltransferase, P1/P k  synthase). [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7451", "text": "The presence or absence of P1 antigen depends on the  A4GALT  transcript level. It was found that differential binding of transcription factors  early growth response 1  (EGR1) and  runt-related transcription factor 1  (RUNX1) to the SNP rs5751348 [ 9 ]  genomic region with the different genotypes in the  A4GALT  gene leads to differential activation of  A4GALT  expression, leading to two genotypes: P 1  and P 2 . [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7452", "text": "P1PK phenotypes are defined by reactivity to antibodies to anti-P 1 , anti-P, anti-P k  anti-PP 1 P k . and anti-NOR antibodies."}
{"_id": "WikiPedia_Hematology$$$corpus_7453", "text": "Anti-P1P k  antibodies are not usually detected with routine laboratory methods.  It is possible to detect them using the Donath-Landsteiner test.  This test is performed on 2 vials of blood at two different temperatures: 4\u00a0\u00b0C and 37\u00a0\u00b0C (body temperature).  A test is interpreted as positive only after a patient's red blood cells have been incubated at both temperatures and subsequently hemolyzed. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7454", "text": "Pathogen reduction using riboflavin and UV light  is a method by which infectious  pathogens  in  blood for transfusion  are inactivated by adding  riboflavin  and irradiating with  UV light . [ 1 ] [ 2 ] [ 3 ]  This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as \u201cpathogen inactivation\u201d in the industry."}
{"_id": "WikiPedia_Hematology$$$corpus_7455", "text": "Despite measures that are in place in the developed world to ensure the safety of blood products for transfusion, a risk of disease transmission still exists.  Consequently, the development of pathogen inactivation/reduction technologies for blood products has been an ongoing effort in the field of transfusion medicine. A new procedure for the treatment of individual units of single-donor (apheresis) or whole blood\u2013derived, pooled, platelets has recently been introduced. This technology uses riboflavin and light for the treatment of platelets and plasma."}
{"_id": "WikiPedia_Hematology$$$corpus_7456", "text": "This pathogen reduction process involves adding riboflavin (vitamin B2) to the blood component, which is then placed into an illuminator where it is exposed to UV light for about five to ten minutes. Exposure to UV light activates riboflavin and when it is associated with  nucleic acids  ( DNA  and  RNA ), riboflavin causes a chemical alteration to functional groups of the nucleic acids thereby making pathogens unable to replicate. [ 1 ] [ 4 ] [ 5 ]  In this way the process prevents viruses, bacteria, parasites and white blood cells, from replicating and causing disease. [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7457", "text": "This method using riboflavin and UV light renders pathogens harmless by using a non-mutagenic, non-toxic method. Riboflavin and its photoproducts are already present in the human body and do not need to be removed from blood products prior to transfusion. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7458", "text": "The riboflavin and UV light method for pathogen reduction of platelets and plasma is in routine use in multiple countries throughout Europe. [ 10 ] [ 11 ] [ 12 ] [ 13 ]  This same process is currently in development for the treatment of whole blood, resulting in pathogen reduction of the three components (RBCs, platelets and plasma)."}
{"_id": "WikiPedia_Hematology$$$corpus_7459", "text": "Plasma frozen within 24 hours after phlebotomy , commonly called  FP24 , [ 1 ]   PF\u201124 , or similar names, is a frozen human  blood plasma  product used in  transfusion medicine . It differs from  fresh-frozen plasma  (FFP) in that it is frozen within 24 hours of blood collection, whereas FFP is frozen within 8 hours. The phrase \"FFP\" is sometimes used to refer to any frozen blood plasma product intended for transfusion."}
{"_id": "WikiPedia_Hematology$$$corpus_7460", "text": "PF24 is stored, thawed, and infused with the same procedures used for FFP. Although it is technically a different product, most healthcare providers continue to refer to FFP when the actual component is PF24."}
{"_id": "WikiPedia_Hematology$$$corpus_7461", "text": "The production of PF24 began in response to an increase in reported cases of  transfusion-related acute lung injury , or TRALI. The proposed mechanism of TRALI involves antibodies from donor blood components (predominantly plasma) that are directed against  human leukocyte antigens  (HLA). [ 2 ]  These antibodies are most numerous in women who have been pregnant more than once. Thus, removing these women from the donor pool for frozen plasma was proposed as a solution to the TRALI problem (the women's plasma could still be used for production of other components, including cryoprecipitate). However, removing roughly half of the donor pool was not a viable alternative, given the increasing need for plasma transfusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7462", "text": "The PF24 approach was pioneered in the United Kingdom beginning in 2004 [ 3 ]  and in the United States beginning in 2007. [ 4 ]  The use of PF24 has been accompanied by a decrease in the incidence of TRALI\u2014a roughly 50% reduction in reported cases. [ 3 ]   Long-term studies on the effectiveness of PF24 in massive transfusion have not been conducted."}
{"_id": "WikiPedia_Hematology$$$corpus_7463", "text": "This does not address the question of risk from plasma in other components, particularly  apheresis   platelets . Removing multiparous women from this limited donor pool would likely cause too great a shortage of platelets, resulting in more deaths (due to hemorrhage) than are seen due to TRALI after platelet infusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7464", "text": "PF24 has roughly 70% of the blood coagulation-factor activity of FFP. Given the fact that there is typically an overabundance of coagulation factors in normal plasma, the decrease noted in PF24 is not thought to be clinically significant. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7465", "text": "Much of the donor blood supply is obtained at \"remote\" blood donation events, such as blood drives at colleges, community events, etc., rather than at dedicated donation centers. The time required for transportation and processing often precludes production of FFP in such cases; that is the plasma cannot be separated and frozen within 8 hours of collection. However, the (male) donor blood can be separated into packed red blood cells and plasma within 24 hours (and usually less). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7466", "text": "Plasmapheresis  (from the  Greek  \u03c0\u03bb\u03ac\u03c3\u03bc\u03b1,  plasma , something molded, and \u1f00\u03c6\u03b1\u03af\u03c1\u03b5\u03c3\u03b9\u03c2  aphairesis , taking away) is the removal, treatment, and return or exchange of  blood plasma  or components thereof from and to the  blood circulation . It is thus an  extracorporeal therapy , a medical procedure performed outside the body. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7467", "text": "Three general types of plasmapheresis can be distinguished:"}
{"_id": "WikiPedia_Hematology$$$corpus_7468", "text": "Plasmapheresis of the autologous and exchange types is used to treat a variety of disorders, including those of the  immune system , such as  Goodpasture's syndrome , [ 3 ]   Guillain\u2013Barr\u00e9 syndrome ,  lupus ,  myasthenia gravis , [ 4 ] [ 5 ]  and  thrombotic thrombocytopenic purpura ."}
{"_id": "WikiPedia_Hematology$$$corpus_7469", "text": "During plasmapheresis,  blood , which consists of  blood cells  and a clear liquid called  blood plasma , is initially taken out of the body through a needle or previously implanted  catheter . Plasma is then removed from the blood by a cell separator. Three procedures are commonly used to  separate  the plasma from the blood cells, with each method having its own advantages and disadvantages: [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7470", "text": "After plasma separation, the blood cells are returned to the person undergoing treatment, while the plasma, which contains the  antibodies , is first treated and then returned to the patient in traditional plasmapheresis. Rarely, other replacement fluids, such as  hydroxyethyl starch , may be used in individuals who object to blood transfusion but these are rarely used due to severe side-effects. Medication to keep the blood from clotting (an  anticoagulant ) is given to the patient during the procedure. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7471", "text": "Plasmapheresis is used as a therapy in particular  diseases . It is an uncommon treatment in the United States, but it is more common in Europe and particularly Japan. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7472", "text": "An important use of plasmapheresis is in the therapy of  autoimmune disorders , where the rapid removal of disease-causing  autoantibodies  from the circulation is required in addition to other medical therapy. It is important to note that plasma exchange therapy in and of itself is useful to temper the disease process, while simultaneous medical and  immunosuppressive therapy  is required for long-term management. Plasma exchange offers the quickest short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be suppressed, usually by the use of medications such as  cyclophosphamide ,  cyclosporine ,  mycophenolate mofetil ,  prednisone ,  rituximab , or a mixture of these. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7473", "text": "Other uses are the removal of blood  proteins  where these are overly abundant and cause  hyperviscosity syndrome . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7474", "text": "There is weak evidence that therapeutic plasma exchange (TPE) might be of benefit in severe cases of  COVID-19 . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7475", "text": "Though plasmapheresis is helpful in certain medical conditions, like any other therapy, there are potential risks and complications. Insertion of a rather large  intravenous  catheter can lead to bleeding, lung puncture (depending on the site of catheter insertion), and, if the catheter is left in too long, it can get infected. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7476", "text": "Aside from placing the catheter, the procedure itself has complications. When patient blood is outside of the body passing through the plasmapheresis machine, the blood has a tendency to clot. To reduce this tendency, in one common protocol, [ which? ]   sodium citrate  is infused while the blood is running through the circuit. Citrate binds to  calcium  in the blood, calcium being essential for blood to clot. Citrate is very effective in preventing blood from clotting; however, its use can lead to life-threateningly low calcium levels. This can be detected using the  Chvostek's sign  or  Trousseau's sign . To prevent this complication, calcium is infused intravenously while the patient is undergoing the plasmapheresis; in addition, calcium supplementation by mouth may also be given. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7477", "text": "Other complications include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7478", "text": "Donating plasma is similar in many ways to  whole blood donation , though the end product is used for different purposes.  Most plasmapheresis is for  fractionation  into other products; other blood donations are transfused with relatively minor modifications.  Plasma that is collected solely for further manufacturing is called Source Plasma. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7479", "text": "Plasma donors undergo a screening process to ensure both the donor's safety and the safety of the collected product.  Factors monitored include  blood pressure ,  pulse , temperature, total protein,  protein electrophoresis , health history screening similar to that for whole blood, as well as an annual physical exam with a licensed physician or an approved physician substitute under the supervision of the physician. Donors are screened at each donation for viral diseases that can be transmitted by blood, sometimes by multiple methods.  For example, donations are tested for  HIV  by  ELISA , which shows if they have been exposed to the disease, as well as by nucleic acid methods ( PCR  or similar) to rule out recent infections that the ELISA test might miss and are also screened for  hepatitis B  and  hepatitis C . Industry standards require at least two sets of negative test results before the collected plasma is used for injectable products.  The plasma is also treated in processing multiple times to inactivate any virus that was undetected during the screening process. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7480", "text": "In a few countries, plasma (like blood) is donated by unpaid volunteers. In others, including the United States, Austria, Germany and some Canadian facilities plasma donors are paid for their donations. [ 20 ]  Standards for donating plasma are set by national regulatory agencies such as the  U.S. Food and Drug Administration  (FDA), [ 21 ]  the  European Union , and by a professional organization, the Plasma Protein Therapeutics Association (or PPTA), [ 22 ]  which audits and accredits collection facilities. A  National Donor Deferral Registry  (NDDR) is also maintained by the PPTA for use in keeping donors with prior positive  viral   antibody  test results from donating at any facility."}
{"_id": "WikiPedia_Hematology$$$corpus_7481", "text": "Almost all plasmapheresis in the US is performed by automated methods. [ 23 ]  In some cases, automated plasmapheresis is used to collect plasma products like  fresh frozen plasma  for direct transfusion purposes, often at the same time as  plateletpheresis . These procedures are performed at facilities such as  community blood centers . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7482", "text": "Since returning  red cells  causes the body to replace plasma more rapidly, a donor can provide up to a liter of plasma at a time and can donate with only a few days between donations, unlike the 56-day deferral for blood donation. The amount allowed in a donation varies vastly from country to country, but generally does not exceed two donations, each as much as a liter (one-third of the total plasma volume), per seven-day period. If a significant amount of red blood cells cannot be returned, the donor may not donate for 56 days, just as if they had donated a unit of blood.  Depending on the collection system and the operation, the removed plasma may be replaced by  saline .  The body typically replaces the collected volume within 24 hours, and donors typically donate up to twice a week, though this varies by country. [ 25 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7483", "text": "The collected plasma is promptly frozen at lower than -20\u00a0\u00b0C (-4\u00a0\u00b0F) and is typically shipped to a processing facility for fractionation. This process separates the collected plasma into specific components, such as  albumin  and  immunoglobulins , most of which are made into medications for human use. Sometimes the plasma is thawed and transfused as Fresh Frozen Plasma (FFP), much like the plasma from a normal blood donation. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7484", "text": "Plasmapheresis was originally described by doctors Vadim A. Yurevick and Nicolay Rosenberg of the  Imperial Medical and Surgical Academy of Saint Petersburg  in 1913. [ 30 ]  and John Abel and  Leonard Rowntree  of  Johns Hopkins Hospital  in 1914. [ 31 ]  Both studies carried out on animals, are considered precedent to subsequent studies held in humans and offered the first description of the technique. The first studies of the effects of plasmapheresis on humans were undertaken during the WWII period, and the results were reported in a study over six plasma donors presented by doctors Co Tui, F.C. Bartter and A.M. Wright in 1944. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7485", "text": "Aware of the rising demand for plasma for transfusion, Dr.  Josep Antoni Gr\u00edfols-Lucas  conducted the first systematic study of the application of plasmapheresis in a series of plasma donors. Performed in 1951, this was the most exhaustive study to date of the medium-term effects on the human body, and involved more than 320 plasmapheresis procedures. Grifols-Lucas concluded that it was possible for donors to undergo plasmapheresis on a weekly basis without the quality of their plasma suffering, while the method also made it possible to obtain a larger quantity of plasma when compared to the conventional method of whole blood donation. The results of the study were presented at the 4th International Congress of Blood Transfusion in Lisbon (1951), and were published in 1952 in the  British Medical Journal [ 33 ]  and Medicina Cl\u00ednica in Spain. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7486", "text": "At the Lisbon congress, Grifols-Lucas met  Edwin Cohn . While Grifols-Lucas was presenting a safe technique for obtaining large quantities of plasma from healthy donors, Cohn presented a plasma fractionator, a device that separated out the proteins contained in plasma. These two major contributions marked the birth of a new industry: plasma fractionation to obtain plasma products. [ 35 ]  In 1955, further data were presented at the 5th Congress of the European Hematology Society, in Freiburg, Germany, based on the ongoing performance of plasmapheresis over a five-year period. In 1956 Grifols-Lucas presented the results at the 6th Congress of the International Hematology Society in Boston, US. [ 35 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7487", "text": "Michael Rubinstein was the first to use plasmapheresis to treat an immune-related disorder when he saved the life of an adolescent boy with  thrombotic thrombocytopenic purpura  (TTP) at the  Cedars of Lebanon Hospital  in Los Angeles in 1959. [ 36 ]  The modern plasmapheresis process itself originated in the U.S.  National Cancer Institute  between 1963 and 1968, where investigators drew upon an old dairy creamer separation technology first used in 1878 and refined by  Edwin Cohn 's centrifuge marketed in 1953. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7488", "text": "In 1965, Dr. V\u00edctor Grifols-Lucas, brother of Josep Antoni Grifols-Lucas, patented the device, along with the procedure for performing plasmapheresis  in situ , [ 37 ]  that is, with the donor present. This replaced a fragmented, manual process with a continuous automatic method which enabled blood components to be extracted, separated and returned to the donor in a single procedure. The new device made plasmapheresis faster and simpler, and also made it safer for donors. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7489", "text": "Platelets  or  thrombocytes  (from  Ancient Greek     \u03b8\u03c1\u03cc\u03bc\u03b2\u03bf\u03c2  ( thr\u00f3mbos ) \u00a0'clot' and    \u03ba\u03cd\u03c4\u03bf\u03c2  ( k\u00fatos ) \u00a0'cell') are a  blood  component whose function (along with the  coagulation factors ) is to react to  bleeding  from  blood vessel  injury by clumping, thereby initiating a  blood clot . [ 1 ]  Platelets have no  cell nucleus ; they are fragments of  cytoplasm  derived from the  megakaryocytes [ 2 ]  of the  bone marrow  or lung, [ 3 ]  which then enter the circulation. Platelets are found only in mammals, whereas in other  vertebrates  (e.g.  birds ,  amphibians ), thrombocytes circulate as intact  mononuclear cells . [ 4 ] :\u200a3"}
{"_id": "WikiPedia_Hematology$$$corpus_7490", "text": "One major function of platelets is to contribute to  hemostasis : the process of stopping bleeding at the site of interrupted  endothelium . They gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium:  adhesion . Second, they change shape, turn on receptors and secrete  chemical messengers :  activation . Third, they connect to each other through receptor bridges:  aggregation . [ 5 ]  Formation of this  platelet plug  (primary hemostasis) is associated with activation of the  coagulation cascade , with resultant  fibrin  deposition and linking (secondary hemostasis). These processes may overlap: the spectrum is from a predominantly platelet plug, or \"white clot\" to a predominantly fibrin, or \"red clot\" or the more typical mixture. Berridge adds  retraction  and  platelet inhibition  as fourth and fifth steps, [ 6 ]  while others would add a sixth step,  wound repair . [ citation needed ]  Platelets participate in both innate [ 7 ]  and adaptive [ 8 ]  intravascular immune responses."}
{"_id": "WikiPedia_Hematology$$$corpus_7491", "text": "In addition to facilitating the clotting process, platelets contain  cytokines  and  growth factors  which can promote wound healing and regeneration of damaged tissues. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7492", "text": "The term  thrombocyte  (clot cell) came into use in the early 1900s and is sometimes used as a synonym for platelet; but not generally in the scientific literature, except as a root word for other terms related to platelets (e.g.  thrombocytopenia  meaning low platelets). [ 4 ] :\u200av3\u200a  The term thrombocytes are proper for mononuclear cells found in the blood of non-mammalian vertebrates: they are the functional equivalent of platelets, but circulate as intact cells rather than cytoplasmic fragments of bone marrow megakaryocytes. [ 4 ] :\u200a3"}
{"_id": "WikiPedia_Hematology$$$corpus_7493", "text": "In some contexts, the word  thrombus  is used interchangeably with the word  clot , regardless of its composition (white, red, or mixed). In other contexts it is used to contrast a normal from an abnormal clot:  thrombus  arises from physiologic hemostasis,  thrombosis  arises from a pathologic and excessive quantity of clot. [ 11 ]  In a third context it is used to contrast the result from the process:  thrombus  is the result,  thrombosis  is the process."}
{"_id": "WikiPedia_Hematology$$$corpus_7494", "text": "Structurally the platelet can be divided into four zones, from peripheral to innermost: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7495", "text": "Circulating inactivated platelets are biconvex discoid (lens-shaped) structures, [ 12 ] [ 4 ] :\u200a117\u2013118\u200a  2\u20133\u00a0\u03bcm in greatest diameter. [ 13 ]  Activated platelets have cell membrane projections covering their surface."}
{"_id": "WikiPedia_Hematology$$$corpus_7496", "text": "In a first approximation, the shape can be considered similar to  oblate spheroids , with a semiaxis ratio of 2 to 8. [ 14 ]  This approximation can be used to model the hydrodynamic and optical properties of a population, as well as to restore the geometric parameters of individual measured platelets by  flow cytometry . [ 15 ]  More accurate biophysical models of platelet surface morphology that model its shape from first principles, make it possible to obtain a more realistic platelet geometry in a calm and activated state. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7497", "text": "The fundamental function of platelets is to clump together to stop acute bleeding. This process is complex, as more than 193 proteins and 301 interactions are involved in platelet dynamics. [ 5 ]   Despite much overlap, platelet function can be modeled in three steps:"}
{"_id": "WikiPedia_Hematology$$$corpus_7498", "text": "Thrombus  formation on an intact  endothelium  is prevented by  nitric oxide , [ 19 ]   prostacyclin , [ 20 ]  and  CD39 . [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7499", "text": "Endothelial cells  attach to the subendothelial  collagen  by  von Willebrand factor  (VWF), which these cells produce. VWF is also stored in the  Weibel-Palade bodies  of the endothelial cells and secreted constitutively into the blood. Platelets store vWF in their alpha granules."}
{"_id": "WikiPedia_Hematology$$$corpus_7500", "text": "When the endothelial layer is disrupted, collagen and VWF anchor platelets to the subendothelium. Platelet  GP1b-IX-V  receptor binds with VWF; and GPVI receptor and integrin \u03b12\u03b21 bind with collagen. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7501", "text": "The intact endothelial lining  inhibits  platelet activation by producing  nitric oxide , endothelial- ADPase , and  PGI 2  (prostacyclin). Endothelial-ADPase degrades the platelet activator  ADP . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7502", "text": "Resting platelets maintain active calcium  efflux  via a  cyclic AMP -activated calcium pump. Intracellular calcium concentration determines platelet activation status, as it is the  second messenger  that drives platelet conformational change and degranulation. Endothelial  prostacyclin  binds to  prostanoid  receptors on the surface of resting platelets. This event stimulates the coupled  Gs  protein to increase  adenylate cyclase  activity and increases the production of cAMP, further promoting the efflux of calcium and reducing intracellular calcium availability for platelet activation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7503", "text": "ADP on the other hand binds to  purinergic receptors  on the platelet surface. Since the thrombocytic purinergic receptor  P2Y12  is coupled to  Gi  proteins, ADP reduces platelet adenylate cyclase activity and cAMP production, leading to accumulation of calcium inside the platelet by inactivating the cAMP calcium efflux pump. The other ADP-receptor  P2Y1  couples to Gq that activates phospholipase C-beta 2 ( PLCB2 ), resulting in  inositol 1,4,5-trisphosphate  (IP3) generation and intracellular release of more calcium. This together induces platelet activation. Endothelial ADPase degrades ADP and prevents this from happening.  Clopidogrel  and related antiplatelet medications also work as purinergic receptor  P2Y12   antagonists . [ citation needed ]  Data suggest that ADP activates the  PI3K/Akt  pathway during a first wave of aggregation, leading to thrombin generation and  PAR\u20101  activation, which evokes a second wave of aggregation. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7504", "text": "Platelet activation begins seconds after adhesion occurs. It is triggered when  collagen  from the subendothelium binds with its receptors ( GPVI  receptor and integrin \u03b12\u03b21) on the platelet. GPVI is associated with the Fc receptor gamma chain and leads via the activation of a tyrosine kinase cascade finally to the activation of PLC-gamma2 ( PLCG2 ) and more calcium release. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7505", "text": "Tissue factor  also binds to  factor VII  in the blood, which initiates the extrinsic  coagulation  cascade to increase  thrombin  production. Thrombin is a potent platelet activator, acting through Gq and G12. These are  G protein-coupled receptors  and they turn on calcium-mediated  signaling pathways  within the platelet, overcoming the baseline calcium efflux. Families of three G proteins (Gq, Gi, G12) operate together for full activation. Thrombin also promotes secondary fibrin-reinforcement of the platelet plug. Platelet activation in turn degranulates and releases  factor V  and  fibrinogen , potentiating the coagulation cascade. Platelet plugging and coagulation occur simultaneously, with each inducing the other to form the final fibrin-crosslinked thrombus. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7506", "text": "Collagen-mediated GPVI signalling increases the platelet production of  thromboxane A2  (TXA2) and decreases the production of  prostacyclin . This occurs by altering the metabolic flux of platelet's  eicosanoid  synthesis pathway, which involves enzymes  phospholipase A2 ,  cyclo-oxygenase 1 , and  thromboxane-A synthase . Platelets secrete thromboxane A2, which acts on the platelet's own  thromboxane receptors  on the platelet surface (hence the so-called \"out-in\" mechanism), and those of other platelets. These receptors trigger intraplatelet signaling, which converts  GPIIb/IIIa  receptors to their active form to initiate  aggregation . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7507", "text": "Platelets contain  dense granules , lambda granules, and  alpha granules . Activated platelets secrete the contents of these granules through their canalicular systems to the exterior. Bound and activated platelets degranulate to release platelet  chemotactic  agents to attract more platelets to the site of endothelial injury. Granule characteristics:"}
{"_id": "WikiPedia_Hematology$$$corpus_7508", "text": "As shown by flow cytometry and  electron microscopy , the most sensitive sign of activation, when exposed to platelets using ADP, are morphological changes. [ 24 ]  Mitochondrial hyperpolarization is a key event in initiating morphology changes. [ 25 ]  Intraplatelet calcium concentration increases, stimulating the interplay between the microtubule/actin filament complex. The continuous changes in shape from the unactivated to the fully activated platelet are best seen via  scanning electron microscopy . The three steps along this path are named  early dendritic ,  early spread,  and  spread . The surface of the unactivated platelet looks similar to the surface of the brain\u2013a wrinkled appearance from numerous shallow folds that increase the surface area;  early dendritic , an octopus with multiple arms and legs;  early spread , an uncooked frying egg in a pan, the \"yolk\" is the central body; and the  spread , a cooked fried egg with a denser central body."}
{"_id": "WikiPedia_Hematology$$$corpus_7509", "text": "These changes are all brought about by the interaction of the microtubule/actin complex with the platelet cell membrane and open canalicular system (OCS), which is an extension and invagination of that membrane. This complex runs just beneath these membranes and is the chemical motor that pulls the invaginated OCS out of the interior of the platelet, like turning pants pockets inside out, creating the dendrites. This process is similar to the mechanism of contraction in a  muscle cell . [ 26 ]  The entire OCS thus becomes indistinguishable from the initial platelet membrane as it forms the \"fried egg\". This dramatic increase in surface area comes about with neither stretching nor adding phospholipids to the platelet membrane. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7510", "text": "Platelet activation causes its membrane surface to become negatively charged. One of the signaling pathways turns on  scramblase , which moves negatively charged  phospholipids  from the inner to the outer platelet membrane surface. These phospholipids then bind the  tenase  and  prothrombinase  complexes, two of the sites of interplay between platelets and the coagulation cascade. Calcium ions are essential for the binding of these coagulation factors."}
{"_id": "WikiPedia_Hematology$$$corpus_7511", "text": "In addition to interacting with vWF and fibrin, platelets interact with thrombin, Factors X, Va, VIIa, XI, IX, and prothrombin to complete formation via the coagulation cascade. [ 28 ] [ 29 ]  Human platelets do not express  tissue factor . [ 28 ]  Rat platelets do express tissue factor protein and carry both tissue factor pre-mRNA and mature mRNA. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7512", "text": "Platelet aggregation begins minutes after activation, and occurs as a result of turning on the  GPIIb/IIIa  receptor, allowing these receptors to bind with  vWF  or  fibrinogen . [ 5 ]  Each platelet has around 60,000 of these receptors. [ 31 ]  When any one or more of at least nine different platelet surface receptors are turned on during activation, intraplatelet signaling pathways cause existing GpIIb/IIIa receptors to change shape \u2014 curled to straight \u2014 and thus become capable of binding. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7513", "text": "Since fibrinogen is a rod-like protein with nodules on either end capable of binding GPIIb/IIIa, activated platelets with exposed GPIIb/IIIa can bind fibrinogen to aggregate. GPIIb/IIIa may also further anchor the platelets to subendothelial vWF for additional structural stabilisation."}
{"_id": "WikiPedia_Hematology$$$corpus_7514", "text": "Classically it was thought that this was the only mechanism involved in aggregation, but three other mechanisms have been identified which can initiate aggregation, depending on the velocity of blood flow (i.e. shear range). [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7515", "text": "Platelets have a central role in  innate immunity , initiating and participating in multiple inflammatory processes, directly binding and even destroying pathogens. Clinical data show that many patients with serious bacterial or viral infections have  thrombocytopenia , thus reducing their contribution to inflammation. Platelet-leukocyte aggregates (PLAs) found in circulation are typical in  sepsis  or  inflammatory bowel disease , showing the connection between thrombocytes and immune cells. [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7516", "text": "The platelet cell membrane has receptors for collagen. Following rupture of the blood vessel wall, platelets are exposed and adhere to the collagen in the surrounding tissue."}
{"_id": "WikiPedia_Hematology$$$corpus_7517", "text": "As hemostasis is a basic function of thrombocytes in mammals, it also has its uses in possible infection confinement. [ 7 ]  In case of injury, platelets, together with the coagulation cascade, provide the first line of defense by forming a blood clot. Hemostasis and host defense were thus intertwined in evolution. For example, in the  Atlantic horseshoe crab  (estimated to be over 400\u00a0million years old), the only blood cell type, the  amebocyte , facilitates both the hemostatic function and the encapsulation and phagocytosis of  pathogens  by means of  exocytosis  of intracellular granules containing  bactericidal  defense molecules. Blood clotting supports immune function by trapping the bacteria. [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7518", "text": "Although thrombosis, blood coagulation in intact blood vessels, is usually viewed as a pathological immune response, leading to obturation of lumen of blood vessel and subsequent hypoxic tissue damage, in some cases, directed thrombosis, called immunothrombosis, can locally control the spread of an infection. The thrombosis is directed in concordance of platelets,  neutrophils  and  monocytes . The process is initiated either by immune cells by activating their pattern recognition receptors (PRRs), or by platelet-bacterial binding. Platelets can bind to bacteria either directly through thrombocytic PRRs [ 33 ]  and bacterial surface proteins, or via plasma proteins that bind both to platelets and bacteria. [ 35 ]  Monocytes respond to bacterial  pathogen-associated molecular patterns  (PAMPs), or  damage-associated molecular patterns  (DAMPs) by activating the extrinsic pathway of coagulation. Neutrophils facilitate the blood coagulation by  NETosis , while platelets facilitate neutrophils' NETosis. NETs bind tissue factor, binding the coagulation centers to the location of infection. They also activate the intrinsic coagulation pathway by providing its negatively charged surface to the factor XII. Other neutrophil secretions, such as proteolytic enzymes which cleave coagulation inhibitors, also bolster the process. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7519", "text": "In case of imbalance throughout the regulation of immunothrombosis, this process can become aberrant. Regulatory defects in immunothrombosis are suspected to be a major factor in pathological thrombosis in forms such as  disseminated intravascular coagulation  (DIC) or  deep vein thrombosis . DIC in sepsis is a prime example of both the dysregulated coagulation process as well as an undue systemic inflammatory response, resulting in a multitude of microthrombi of similar composition to that in physiological immunothrombosis \u2014 fibrin, platelets, neutrophils and NETs. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7520", "text": "Platelets rapidly deploy to sites of injury or infection, and potentially modulate inflammatory processes by interacting with  leukocytes  and secreting  cytokines ,  chemokines , and other inflammatory mediators. [ 36 ] [ 37 ] [ 38 ] [ 39 ] [ 40 ]  Platelets also secrete  platelet-derived growth factor  (PDGF)."}
{"_id": "WikiPedia_Hematology$$$corpus_7521", "text": "Platelets modulate neutrophils by forming platelet-leukocyte aggregates (PLAs). These formations induce upregulated production of \u03b1m\u03b22 ( Mac-1 ) integrin in neutrophils. Interaction with PLAs also induces degranulation and increased phagocytosis in neutrophils."}
{"_id": "WikiPedia_Hematology$$$corpus_7522", "text": "Platelets are the largest source of soluble  CD40L  which induces production of  reactive oxygen species  (ROS) and upregulate expression of adhesion molecules, such as  E-selectin ,  ICAM-1 , and  VCAM-1 , in neutrophils, activates macrophages and activates cytotoxic response in  T  and  B lymphocytes . [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7523", "text": "Mammalian platelets lacking nucleus are able to conduct autonomous locomotion. [ 41 ]  Platelets are active scavengers, scaling walls of blood vessels and reorganising the thrombus. They are able to recognize and adhere to many surfaces, including bacteria, and can envelop them in their open canalicular system (OCP), leading to a proposal to name the process as  covercytosis  (OCS) rather than phagocytosis, as OCS is merely an invagination of outer plasma membrane. These platelet-bacteria bundles provide an interaction platform for neutrophils that destroy bacteria using the NETosis and phagocytosis."}
{"_id": "WikiPedia_Hematology$$$corpus_7524", "text": "Platelets also participate in chronic inflammatory disease, such as  synovitis  or  rheumatoid arthritis . [ 42 ]  Platelets are activated by collagen receptor  glycoprotein IV  (GPVI). Proinflammatory platelet microvesicles trigger constant cytokine secretion from neighboring  fibroblast-like synoviocytes , most prominently  Il-6  and  Il-8 . Inflammatory damage to the surrounding extracellular matrix continuously reveals more collagen, maintaining microvesicle production."}
{"_id": "WikiPedia_Hematology$$$corpus_7525", "text": "Activated platelets are able to participate in  adaptive immunity , interacting with  antibodies . They are able to specifically bind  IgG  through  Fc\u03b3RIIA , a receptor for IgG's constant fragment (Fc). When activated and bound to IgG  opsonised  bacteria, platelets release reactive oxygen species (ROS), antimicrobial peptides,  defensins , kinocidins and  proteases , killing the bacteria directly. [ 43 ]  Platelets also secrete proinflammatory and procoagulant mediators such as inorganic  polyphosphates  or  platelet factor 4  (PF4), connecting innate and adaptive immune responses. [ 43 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7526", "text": "Spontaneous and excessive bleeding can occur because of platelet disorders. This bleeding can be caused by deficient numbers of platelets, dysfunctional platelets, or platelet densities over 1\u00a0million/microliter. (The excessive numbers create a relative von Willebrand factor deficiency due to sequestration.) [ 45 ] [ 46 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7527", "text": "Bleeding due to a platelet disorder or a coagulation factor disorder can be distinguished by the characteristics and location of the bleeding. [ 4 ] :\u200a815,\u200aTable 39-4\u200a  Platelet bleeding involves bleeding from a cut that is prompt and excessive, but can be controlled by pressure; spontaneous bleeding into the skin which causes a purplish stain named by its size:  petechiae ,  purpura ,  ecchymoses ; bleeding into mucous membranes causing bleeding gums, nose bleed, and gastrointestinal bleeding; menorrhagia; and intraretinal and intracranial bleeding."}
{"_id": "WikiPedia_Hematology$$$corpus_7528", "text": "Excessive numbers of platelets, and/or normal platelets responding to abnormal vessel walls, can result in  venous thrombosis  and  arterial thrombosis . The symptoms depend on the thrombosis site."}
{"_id": "WikiPedia_Hematology$$$corpus_7529", "text": "Platelet concentration in the blood (i.e. platelet count), can be measured manually using a  hemocytometer , or by placing blood in an automated platelet analyzer using particle counting, such as a  Coulter counter  or optical methods. [ 47 ]  Most common  blood testing methods  include platelet count in their measurements, usually reported as  PLT . [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7530", "text": "Platelet concentrations vary between individuals and over time, with the population average between 250,000 and 260,000 cells per mm 3  (equivalent to per microliter), but the typical laboratory accepted normal range is between 150,000 and 400,000 cells per mm 3  or 150\u2013400 \u00d7 10 9  per liter. [ 48 ] [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7531", "text": "On a stained  blood smear , platelets appear as dark purple spots, about 20% of the diameter of red blood cells. The smear reveals size, shape, qualitative number, and  clumping . A healthy adult typically has 10 to 20 times more red blood cells than platelets."}
{"_id": "WikiPedia_Hematology$$$corpus_7532", "text": "Bleeding time  was developed as a test of platelet function by Duke in 1910. [ 49 ]  Duke's test measured the time taken for bleeding to stop from a standardized wound in the ear lobe that was blotted every 30 seconds, considering less than 3 minutes as normal. [ 50 ]  Bleeding time has low sensitivity and specificity for mild to moderate platelet disorders and is no longer recommended for screening. [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7533", "text": "In  multiple electrode aggregometry , anticoagulated whole blood is mixed with saline and a platelet agonist in a single-use cuvette with two pairs of electrodes. The increase in impedance between the electrodes as platelets aggregate onto them, is measured and visualized as a curve. [ 52 ] [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7534", "text": "In light transmission aggregometry (LTA),  platelet-rich plasma  is placed between a light source and a  photocell . Unaggregated plasma allows relatively little light to pass through. After adding an agonist, the platelets aggregate, increasing light transmission, which is detected by a photocell. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7535", "text": "Whole blood impedance aggregometry (WBA) measures the change in electrical impedance between two electrodes when platelet aggregation is induced by an agonist. Whole blood lumiaggregometry may increase the test sensitivity to impairment of platelet granule secretion. [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7536", "text": "The  PFA-100  (Platelet Function Assay \u2014 100) is a system for analysing platelet function in which citrated whole blood is aspirated through a disposable cartridge containing an aperture within a membrane coated with either collagen and epinephrine or collagen and ADP. These agonists induce platelet adhesion, activation and aggregation, leading to rapid occlusion of the aperture and cessation of blood flow termed the closure time (CT). An elevated CT with EPI and collagen can indicate intrinsic defects such as  von Willebrand disease ,  uremia , or circulating platelet inhibitors. A follow-up test involving collagen and ADP is used to indicate if the abnormal CT with collagen and EPI was caused by the effects of acetyl sulfosalicylic acid (aspirin) or medications containing inhibitors. [ 58 ]  The PFA-100 is highly sensitive to von Willebrand disease, but is only moderately sensitive to defects in platelet function. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7537", "text": "Low platelet concentration is called  thrombocytopenia , and is due to either decreased production or increased destruction. Elevated platelet concentration is called  thrombocytosis , and is either  congenital , reactive (to  cytokines ), or due to unregulated production: one of the  myeloproliferative neoplasms  or certain other myeloid  neoplasms . A disorder of platelet function is called a  thrombocytopathy  or a platelet function disorder. [ 4 ] :\u200avii"}
{"_id": "WikiPedia_Hematology$$$corpus_7538", "text": "Normal platelets can respond to an abnormality on the vessel wall rather than to hemorrhage, resulting in inappropriate platelet adhesion/activation and  thrombosis : the formation of a clot within an intact vessel. This type of thrombosis arises by mechanisms different from those of a normal clot: extending the fibrin of  venous thrombosis ; extending an unstable or ruptured arterial plaque, causing  arterial thrombosis ; and microcirculatory thrombosis. An arterial  thrombus  may partially obstruct blood flow, causing downstream  ischemia , or may completely obstruct it, causing downstream  tissue death .: [ 4 ] :\u200avii"}
{"_id": "WikiPedia_Hematology$$$corpus_7539", "text": "The three broad categories of platelet disorders are \"not enough\", \"dysfunctional\", and \"too many\". [ 4 ] :\u200avii"}
{"_id": "WikiPedia_Hematology$$$corpus_7540", "text": "Some drugs used to treat inflammation have the unwanted side effect of suppressing normal platelet function. These are the  non-steroidal anti-inflammatory drugs  (NSAIDS).  Aspirin  irreversibly disrupts platelet function by inhibiting  cyclooxygenase -1 (COX1), and hence normal hemostasis. The resulting platelets are unable to produce new cyclooxygenase because they have no DNA. Normal platelet function does not return until the use of aspirin has ceased and enough of the affected platelets have been replaced by new ones, which can take over a week.  Ibuprofen , another  NSAID , does not have such a long duration effect, with platelet function usually returning within 24 hours, [ 66 ]  and taking ibuprofen before aspirin prevents the irreversible effects of aspirin. [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7541", "text": "These drugs are used to prevent thrombus formation."}
{"_id": "WikiPedia_Hematology$$$corpus_7542", "text": "Platelet transfusion  is most frequently used to correct unusually low platelet counts, either to prevent spontaneous bleeding (typically at counts below 10\u00d710 9 /L) or in anticipation of medical procedures that necessarily involve some bleeding. For example, in patients undergoing  surgery , a level below 50\u00d710 9 /L is associated with abnormal surgical bleeding, and  regional anaesthetic  procedures such as  epidurals  are avoided for levels below 80\u00d710 9 /L. [ 68 ]  Platelets may also be transfused when the platelet count is normal but the platelets are dysfunctional, such as when an individual is taking aspirin or  clopidogrel . [ 69 ]  Finally, platelets may be transfused as part of a  massive transfusion protocol , in which the three major blood components (red blood cells, plasma, and platelets) are transfused to address severe  hemorrhage . Platelet transfusion is contraindicated in  thrombotic thrombocytopenic purpura  (TTP), as it fuels the  coagulopathy .  Platelet transfusion is generally ineffective, and thus contraindicated, for prophylaxis in  immune thrombocytopenia  (ITP), because the transfused platelets are immediately cleared; however, it is indicated to treat bleeding. [ 70 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7543", "text": "Platelets are either isolated from collected units of whole blood and pooled to make a therapeutic dose, or collected by  platelet apheresis : blood is taken from the donor, passed through a device which removes the platelets, and the remainder is returned to the donor in a closed loop. The industry standard is for platelets to be tested for bacteria before transfusion to avoid septic reactions, which can be fatal. Recently the AABB Industry Standards for  Blood Banks  and Transfusion Services (5.1.5.1) has allowed use of pathogen reduction technology as an alternative to bacterial screenings in platelets. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7544", "text": "Pooled whole-blood platelets, sometimes called \"random\" platelets, are separated by one of two methods. [ 72 ]  In the US, a unit of whole blood is placed into a large  centrifuge  in what is referred to as a \"soft spin\". At these settings, the platelets remain suspended in the plasma. The  platelet-rich plasma  (PRP) is removed from the red cells, then centrifuged at a faster setting to harvest the platelets from the plasma. In other regions of the world, the unit of whole blood is centrifuged using settings that cause the platelets to become suspended in the \" buffy coat \" layer, which includes the platelets and the white blood cells. The \"buffy coat\" is isolated in a sterile bag, suspended in a small amount of red blood cells and plasma, then centrifuged again to separate the platelets and plasma from the red and white blood cells. Regardless of the initial method of preparation, multiple donations may be combined into one container using a sterile connection device to manufacture a single product with the desired therapeutic dose."}
{"_id": "WikiPedia_Hematology$$$corpus_7545", "text": "Apheresis platelets are collected using a mechanical device that draws blood from the donor and centrifuges the collected blood to separate out the platelets and other components to be collected. The remaining blood is returned to the donor. The advantage to this method is that a single donation provides at least one therapeutic dose, as opposed to the multiple donations for whole-blood platelets. This means that a recipient is exposed to fewer donors and has less risk of transfusion-transmitted disease and other complications. Sometimes a person such as a  cancer  patient who requires routine transfusions of platelets receives repeated donations from a specific donor to minimize risk. Pathogen reduction of platelets using for example,  riboflavin and UV light treatments  can reduce the infectious load of pathogens contained in donated blood products. [ 73 ] [ 74 ]  Another photochemical treatment process utilizing amotosalen and UVA light has been developed for the inactivation of viruses, bacteria, parasites, and leukocytes. [ 75 ]  In addition, apheresis platelets tend to contain fewer contaminating red blood cells because the collection method is more efficient than \"soft spin\" centrifugation."}
{"_id": "WikiPedia_Hematology$$$corpus_7546", "text": "Platelets collected by either method have a typical shelf life of five days. This results in supply shortages, as testing donations often requires up to a full day. No effective preservative solutions have been devised for platelets."}
{"_id": "WikiPedia_Hematology$$$corpus_7547", "text": "Platelets are stored under constant agitation at 20\u201324\u00a0\u00b0C (68\u201375\u00a0\u00b0F). Units cannot be refrigerated as this causes platelets to change shape and lose function. Storage at room temperature provides an environment where any introduced bacteria may proliferate and subsequently cause  bacteremia . The United States requires products to be tested for the presence of bacterial contamination before transfusion. [ 76 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7548", "text": "Platelets do not need to belong to the same A-B-O blood group as the recipient or be cross-matched to ensure immune compatibility between donor and recipient unless they contain a significant amount of red blood cells (RBCs). The presence of RBCs imparts a reddish-orange color to the product and is usually associated with whole-blood platelets. Some sites may type platelets, but this is not critical."}
{"_id": "WikiPedia_Hematology$$$corpus_7549", "text": "Prior to issuing platelets to the recipient, they may be irradiated to prevent  transfusion-associated graft versus host disease  or they may be washed to remove the plasma."}
{"_id": "WikiPedia_Hematology$$$corpus_7550", "text": "The change in the recipient's platelet count after transfusion is termed the \"increment\" and is calculated by subtracting the pre-transfusion platelet count from the post-transfusion count. Many factors affect the increment including body size, the number of platelets transfused, and clinical features that may cause premature destruction of the transfused platelets. When recipients fail to demonstrate an adequate post-transfusion increment, this is termed  platelet transfusion refractoriness ."}
{"_id": "WikiPedia_Hematology$$$corpus_7551", "text": "Platelets, either apheresis-derived or random-donor, can be processed through a volume reduction process. In this process, the platelets are spun in a centrifuge and plasma is removed, leaving 10 to 100 mL of platelet concentrate. Such volume-reduced platelets are normally transfused only to neonatal and pediatric patients when a large volume of plasma could overload the child's small circulatory system. The lower volume of plasma also reduces the chances of an adverse transfusion reaction to plasma proteins. [ 77 ]  Volume reduced platelets have a shelf life of four hours. [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7552", "text": "The blood clot is only a temporary solution to stop bleeding; tissue repair is needed. Small interruptions in the endothelium are handled by physiological mechanisms; large interruptions by a trauma surgeon. [ 79 ]  The fibrin is slowly dissolved by the fibrinolytic enzyme,  plasmin , and the platelets are cleared by  phagocytosis . [ 80 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7553", "text": "Platelets release  platelet-derived growth factor  (PDGF), a potent  chemotactic  agent; and  TGF beta , which stimulates the deposition of  extracellular matrix ;  fibroblast growth factor ,  insulin-like growth factor 1 , platelet-derived  epidermal growth factor , and  vascular endothelial growth factor . Local application of these factors in increased concentrations through  platelet-rich plasma  (PRP) is used as an adjunct in wound healing. [ 81 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7554", "text": "Instead of platelets, non-mammalian vertebrates have nucleated thrombocytes, which resemble  B lymphocytes  in morphology. They aggregate in response to thrombin, but not to ADP, serotonin, nor adrenaline, as platelets do. [ 82 ] [ 83 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7555", "text": "Platelet concentrates  are products containing platelet enriched blood, which are used for  platelet transfusions"}
{"_id": "WikiPedia_Hematology$$$corpus_7556", "text": "Platelets can be isolated from whole blood using three methods, the platelet rich plasma method, the buffy coat method and with apheresis. Platelets are normally stored at room temperature (20 to 24\u00a0\u00b0C) in order to preserve their ability to circulate after transfusion. [ 1 ]  However, platelets can be stored at other temperatures, including refrigeration and cryopreservation for use in specific instances."}
{"_id": "WikiPedia_Hematology$$$corpus_7557", "text": "When stored at room temperature, the platelet concentrates are gently agitated at a speed of 60 strokes per minutes, so that the platelets to remain in suspension. Platelets can be stored for up to seven days with maintenance of their function in patients. [ 2 ]  Due to their storage at room temperature, platelet concentrates are at risk of bacterial outgrowth if a unit is contaminated. Therefore, measures have been taken to prevent this. Bacterial screening within 24 to 36 hours after blood collection can be performed, pathogen inactivation can be performed, or the storage time can be shortened to 3 to 5 days."}
{"_id": "WikiPedia_Hematology$$$corpus_7558", "text": "During storage, platelet mainly metabolize glucose. Oxidative metabolism leads to the formation of carbon dioxide, and anaerobic metabolism leads to the formation of lactic acid. Both types of metabolism occur simultaneously. Both carbon dioxide and lactic acid acidify the storage medium, and the lowering of the pH of the storage medium affects the quality of the platelets. Below pH 6.2, the damage to the platelets is irreversible, and platelets do not circulate when transfused. [ 3 ]  Platelets are therefore stored in gas-permeable containers with a large volume-to-surface ratio, in order to expel carbon dioxide, which elevates the pH. Also, these containers allow for the entry of oxygen, favoring oxidative metabolism."}
{"_id": "WikiPedia_Hematology$$$corpus_7559", "text": "Originally, platelets were stored in the donor\u2019s own plasma. Nowadays, many blood banks have switched to using platelet additive solution to store platelets. Typically, when platelets are isolated from whole blood, not all plasma is removed, as platelets need to be in a certain volume of plasma in order to have a clear separation from other cells. Platelet additive solution is added to bring the platelets to a concentration that sustains five to seven day storage. Consequently, platelets are typically stored in approximately one-third plasma and two-thirds platelet additive solution."}
{"_id": "WikiPedia_Hematology$$$corpus_7560", "text": "Platelet additive solutions contain nutrients to support platelet metabolism during their storage. Acetate is often used as nutrient. When acetate is metabolized, an hydroxy-ion is consumed, which elevates the pH. [ 4 ]  Platelet additive solutions may additionally contain a buffer to keep the pH above 6.2. Potassium and magnesium may be added to prevent untimely platelet activation. [ 5 ]  Due to the dilution of plasma, allergic reactions to plasma antigens are less frequent. [ 6 ]  Also, ABO antibody titers are fourfold lower, making ABO-incompatible transfusions easier."}
{"_id": "WikiPedia_Hematology$$$corpus_7561", "text": "Platelet transfusion , is the process of infusing platelet concentrate into the body via vein, to prevent or treat the  bleeding  in people with either a  low platelet count  or  poor platelet function . [ 1 ]  Often this occurs in people receiving  cancer chemotherapy . [ 1 ]  Preventive transfusion is often done in those with platelet levels of less than 10 x 10 9 /L. [ 2 ]  In those who are bleeding transfusion is usually carried out at less than 50 x 10 9 /L. [ 2 ]  Blood group matching ( ABO ,  RhD ) is typically recommended before platelets are given. [ 2 ]  Unmatched platelets, however, are often used due to the unavailability of matched platelets. [ 3 ]  They are given by  injection into a vein . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7562", "text": "Side effects can include  allergic reactions  such as  anaphylaxis ,  infection , and  lung injury . [ 2 ]   Bacterial infections  are relatively more common with platelets as they are stored at warmer temperatures. [ 2 ]  Platelets can be produced either from  whole blood  or by  apheresis . [ 1 ]  They keep for up to five to seven days. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7563", "text": "Platelet transfusions came into medical use in the 1950s and 1960s. [ 1 ] [ 5 ]  It is on the  World Health Organization's List of Essential Medicines . [ 6 ] [ 7 ]  Some versions of platelets have had the  white blood cells  partially removed or been  gamma irradiated  which have specific benefits for certain populations. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7564", "text": "International guidelines recommend that platelets transfusions are given to people with reversible bone marrow failure to reduce the risk of spontaneous bleeding when the platelet count is less than 10 x 10 9 /L. [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ]  If the person is well using a higher platelet count threshold does not reduce the risk of bleeding further. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7565", "text": "A review in people with  blood cancers  receiving intensive  chemotherapy  or a  stem cell transplant  found that overall giving platelet transfusions when the platelet count is less than 10 x 10 9 /L reduced the number of bleeding events and days with significant bleeding. [ 15 ]  However, this benefit was only seen in certain patient groups, and people undergoing an autologous  stem cell transplant  derived no obvious benefit. [ 15 ]  Despite prophylactic platelet transfusions, people with blood cancers often bleed, and other risk factors for bleeding such as inflammation and duration of thrombocytopenia should be considered. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7566", "text": "There is little evidence for the use of preventive platelet transfusions in people with chronic bone marrow failure, such as  myelodysplasia  or  aplastic anemia . [ 16 ]  Multiple guidelines recommend prophylactic platelet transfusions are not used routinely in people with chronic bone marrow failure, and instead an individualised approach should be taken. [ 11 ] [ 10 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7567", "text": "Several studies have now assessed the benefit of using preventive platelet transfusions in adults with dengue who have profound thrombocytopenia (platelet count < 20 x 10 9 /L. [ 17 ]  There is no evidence that this reduce the risk of bleeding, but there is evidence that they increase the risk of harm due to the platelet transfusion (increased risk of a transfusion reaction including  anaphylaxis ). [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7568", "text": "Two reviews in people with  blood cancers  receiving intensive  chemotherapy  or a  stem cell transplant  found that overall giving platelet transfusions when the platelet count is less than 10 x 10 9 /L compared to giving platelet transfusions when the platelet count is less than 20 or 30 x 10 9 /L had no effect on the risk of bleeding. [ 14 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7569", "text": "Higher platelet transfusion thresholds have been used in premature neonates, but this has been based on limited evidence. [ 19 ]  There is now evidence that using a high platelet count threshold (50 x 10 9 /L) increases the risk of death or bleeding compared to a lower platelet count threshold (25 x 10 9 /L) in premature neonates. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7570", "text": "A review in people with  blood cancers  compared different platelet transfusion doses. [ 21 ]  This review found no difference in the number of people who had clinically significant bleeding between platelet transfusions that contained a small number of platelets (low dose \u2013 1.1 x 10 11 /m 2 ) and those that contained an intermediate number of platelets (intermediate dose \u2013 2.2 x 10 11 /m 2 ).  This review also found no difference in the number of people who had clinically significant bleeding between platelet transfusions that contained a small number of platelets and those that contained a large number of platelets (high dose \u2013 4.4 x 10 11 /m 2 ). [ 21 ]  One of the review's included studies reported on transfusion reactions. This study's authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7571", "text": "In people with a low platelet count, prophylactic platelet transfusions do not need to be given prior to procedures that have a low risk of causing bleeding. [ 10 ] [ 13 ] [ 9 ]  Low-risk procedures include surgical sites that do not contain many blood vessels e.g. cataract surgery, [ 13 ]  or minor procedures. [ 10 ] [ 13 ]  The evidence is very uncertain about the effect of platelet transfusions prior to surgery for people with a low platelet count on the all-cause mortality, the number of participants with bleeding events after surgery, serious surgery-related or transfusion-related adverse events. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7572", "text": "Guidelines recommend that it is safe to perform  central venous catheter  insertion when the platelet count is 20 x 10 9 /L or above. [ 9 ] [ 13 ]  The evidence for this is based on observational studies in which bleeding occurred due to procedure error rather than due to the platelet count. [ 13 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7573", "text": "Platelet transfusion thresholds for more major procedures are based on expert opinion alone. [ 25 ]  Guidelines recommend a threshold of 50 x 10 9 /L for major surgery and a threshold of 100 x 10 9 /L for surgery on the brain or the back of the eye. [ 10 ] [ 13 ] [ 11 ]  Platelet transfusion may be indicated for patients with spontaneous intracerebral hemorrhage to reverse aspirin effect if they require emergency\nneurosurgery, but not if they are managed without surgery. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7574", "text": "There is little evidence for the effectiveness of platelet transfusions or the optimal dose when a person with a low platelet count is actively bleeding.\u00a0Current recommendations are based on consensus guidelines from around the world. [ 10 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7575", "text": "Side effects can include  allergic reactions  such as  anaphylaxis ,  infection , and  lung injury . [ 2 ]   Bacterial infections  are relatively more common with platelets as they are stored at warmer temperatures. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7576", "text": "People with hematological disorders or  cancer  receive the largest proportion of platelet transfusions. [ 27 ] [ 28 ] [ 29 ]  Most are given to prevent bleeding during treatment with  chemotherapy  or  stem cell transplant . [ 29 ] [ 28 ] [ 30 ]  Much of the remainder are used in general medicine,  cardiac surgery  and in  intensive care . [ 29 ] [ 28 ] [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7577", "text": "Unlike other blood products demand for platelet transfusions appears to be increasing in several countries around the world. [ 27 ]  An ageing population, an increase in the number of people with  blood cancer , and changes to the management of these cancers are likely the major reasons for the rise in demand for platelets. [ 27 ]  Since 1990, the number of stem cell transplants performed in Europe has risen from 4,200 to over 40,000 annually. [ 31 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7578", "text": "Platelet transfusions came into medical use in the 1950s and 1960s. [ 1 ]  It is on the  World Health Organization's List of Essential Medicines . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7579", "text": "In the United Kingdom it costs the NHS about 200 pounds per unit. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7580", "text": "Platelets can be produced either from  whole blood  donations or by  apheresis . [ 1 ]  They keep for up to five to seven days. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7581", "text": "Platelet components can have had the  white blood cells  partially removed (leucodepleted) which decreases the risk of having a transfusion reaction. [ 33 ]  They can be treated with ultraviolet light which decreases the risk of transmission of certain infections. [ 34 ]  They can be  gamma irradiated  which have specific benefits for certain populations (those at risk of  transfusion-associated graft versus host disease ). [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7582", "text": "Platelet transfusion refractoriness  is the repeated failure to achieve the desired level of  blood platelets  in a patient following a platelet  transfusion . The cause of refractoriness may be either  immune  or non-immune. Among immune-related refractoriness, antibodies against  HLA antigens  are the primary cause.  Non-immune causes include  splenomegaly  (enlargement of the spleen),  fever , and sepsis. [ 1 ] [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7583", "text": "Platelet refractoriness can be due to immune causes or non-immune causes. [ 3 ]  Non-immune causes account for over 80% of cases of platelet refractoriness, and sepsis is one of the most common non-immune causes. [ 2 ] [ 3 ] [ 4 ] [ 5 ]   HLA   alloimmunization  is the commonest immune cause of platelet refractoriness. [ 2 ] [ 3 ] [ 4 ] [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7584", "text": "Platelet transfusion refractoriness can be defined in several different ways. All measures of platelet refractoriness are defined by the timing of the post-transfusion platelet count, usually 1 hour post transfusion or 24 hours post transfusion or both. [ 2 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7585", "text": "This is the simplest method, and only requires data on the platelet count before and after the transfusion. [ 9 ]  The platelet increment is also known as the  absolute count increment  and  count increment . [ 5 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7586", "text": "PI = post-transfusion platelet count - pre-transfusion platelet count"}
{"_id": "WikiPedia_Hematology$$$corpus_7587", "text": "However, it is affected by the number of platelets given in the transfusion (platelet dose) and the patient's blood volume. Larger patients and smaller platelet doses decrease the platelet increment. [ 2 ] [ 9 ]  These factors are adjusted for in the other methods of defining platelet refractoriness. [ 2 ] [ 3 ] [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7588", "text": "A 1-hour post-transfusion PI of less than 5 to 10 x 10 9 /l is considered evidence of platelet refractoriness. [ 5 ] [ 10 ]  Due to lack of data on platelet dose this is often the only measure of platelet refractoriness that can be performed in routine clinical practice. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7589", "text": "Requires data on the platelet increment (PI), the patient's total blood volume (TBV) - estimated using the patient's weight multiplied by 0.075, and the number of platelets transfused (platelet dose) [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7590", "text": "PPR = ((PI x TBV)/PD) x 100"}
{"_id": "WikiPedia_Hematology$$$corpus_7591", "text": "At 1 hour post-transfusion, a PPR < 20% is considered evidence of platelet refractoriness. [ 5 ] [ 10 ]  At 16 hours post-transfusion a PPR < 10% is considered evidence of platelet refractoriness. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7592", "text": "PPI is very similar to the percentage platelet recovery (PPR) but there has been an additional adjustment for splenic pooling of platelets (PPR multiplied by 2/3) [ 5 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7593", "text": "PPI = PPR/0.67 = ((PI / 0.67) x TBV)/PD x 100"}
{"_id": "WikiPedia_Hematology$$$corpus_7594", "text": "This requires data on the platelet increment (PI, in platelets/\u03bcL), the patient's  Body surface area  (BSA, in m 2 ), and the number of platelets transfused (PD, in 10 11 ). [ 5 ] [ 10 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7595", "text": "C \n C \n I \n \n = \n P \n I \n \u2217 \n \n \n \n B \n S \n A \n \n \n P \n D \n \n \n \n \n \n {\\displaystyle {CCI}=PI*{\\frac {BSA}{PD}}}"}
{"_id": "WikiPedia_Hematology$$$corpus_7596", "text": "For example, a PI of 25,000 platelets/\u03bcL, a BSA of 1.8m 2  and a PD of 4x10 11  gives a CCI of 11,250 platelets*m 2 /10 11 \u03bcL"}
{"_id": "WikiPedia_Hematology$$$corpus_7597", "text": "At 1 hour post-transfusion a CCI greater than 7500 indicates a sufficient post-transfusion increment, whereas a CCI less than 7500 is considered diagnostic of platelet refractoriness. [ 10 ]  At 24 hours post transfusion a CCI less than 5000 suggests platelet refractoriness. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7598", "text": "Some blood banks maintain records of the estimated number of platelets in each unit. [ 5 ]  Current requirements in the US stipulate that a unit of apheresis platelets must contain at least 3.0 x10 11  platelets. [ 12 ]  In England only 1% of adult platelet components are tested to check the number of platelets meet the minimum required standard of 2.4 x 10 11  platelets. [ 13 ] [ 14 ]  Only components that contain fewer than 1.6 x 10 11  platelets are discarded. [ 13 ] [ 14 ]  This means that there can be a lot of variability in the number of platelets contained within each transfusion. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7599", "text": "Treatment depends on the underlying cause. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7600", "text": "Non-immune causes are usually treated by treating the underlying cause e.g.  sepsis . [ 3 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7601", "text": "If there is no obvious non-immune cause, a first step can be to use platelet components that are likely to produce the greatest platelet increment (less than 3 days old and ABO-matched), while further investigations are performed (testing for HLA antibodies). [ 3 ] [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7602", "text": "If an immune cause is suspected and  HLA antibodies are detected, then HLA-selected platelet components can be used. [ 3 ] [ 4 ]  Although HLA-selected platelets lead to improved platelet increments at 1 hour post-transfusion, [ 17 ]  there is currently insufficient evidence to demonstrate their clinical effectiveness at preventing bleeding. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7603", "text": "If HLA antibodies are not detected, and HPA antibodies are detected, then HPA-selected or crossmatched platelet components can be used. [ 3 ] [ 7 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7604", "text": "HLA and HPA-selected components should not be used if no HLA or HPA antibodies are detected. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7605", "text": "Other strategies for managing patients with platelet refractoriness who require procedures include  thrombopoietin receptor agonists , [ 18 ]  complement inhibitors such as  eculizumab , [ 19 ]  and slow infusion. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7606", "text": "Platelet-Poor Plasma  ( PPP ) is  blood plasma  with very  low number of platelets  (< 10 X 10 3 /\u03bcL).  Traditionally, PPP was recommended for use in  platelet  aggregation studies to both adjust the  platelet-rich plasma  concentration, and to serve as a control. [ 1 ]   PPP may have elevated levels of  fibrinogen , which has the ability to form a fibrin-rich clot once activated.  Wound healing requires cell migration and attachment, which is facilitated by this fibrin clot. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7607", "text": "Fibrin sealants have found use in many clinical situations such as blood management, [ 3 ]  orthopaedic surgery, [ 4 ]  and cosmetic surgery. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7608", "text": "As a byproduct of PRP preparation, PPP may also find use in tissue engineering applications as an  autologous  degradable scaffold.  This plasma portion is frequently discarded when used with PRP treatments. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7609", "text": "Platelet-rich fibrin  ( PRF ) or  leukocyte- and platelet-rich fibrin  ( L-PRF ) is a derivative of  PRP  where  autologous   platelets  and leukocytes are present in a complex fibrin matrix [ 1 ] [ 2 ]  to accelerate the healing of soft and hard tissue [ 3 ]  and is used as a tissue-engineering scaffold in oral and maxillofacial surgeries. PRF falls under FDA Product Code KST, labeling it as a blood draw/Hematology product classifying it as 510(k) exempt."}
{"_id": "WikiPedia_Hematology$$$corpus_7610", "text": "To obtain PRF, the required quantity of blood is drawn into test tubes without an anticoagulant and centrifuged immediately. Blood can be centrifuged using a tabletop centrifuge from 3-8 minutes for 1300 revolutions per minute. The resultant product consists of the following three layers: the topmost layer consisting of platelet poor plasma, the PRF clot in the middle, and the red blood cells (RBC) at the bottom. The PRF clot can be removed from the test tube using a pickup instrument (such as Gerald tissue forceps). The RBC layer attached to the PRF clot can be carefully removed using scissors or a blunt instrument. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7611", "text": "Platelet activation in response to tissue damage occurs during the process of making PRF release several biologically active proteins including; platelet alpha granules, platelet\u2011derived growth factor (PDGF), transforming growth factors\u2011\u03b2 (TGF\u2011\u03b2), vascular endothelial growth factor (VEGF), and epidermal growth factor. [ 5 ]  Actually, the platelets and leukocyte cytokines play important parts in role of this biomaterial, but the fibrin matrix supporting them is the most helpful in constituting the determining elements responsible for real therapeutic potential of PRF. Cytokines are immediately used and destroyed in a healing wound. The harmony between cytokines and their supporting fibrin matrix has much more importance than any other platelet derivatives. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7612", "text": "Ridge preservation (Colloquially  Socket preservation ), a procedure to reduce bone loss after  tooth extraction  to preserve the  dental alveolus  (containing the tooth socket) in the  alveolar bone . A platelet-rich fibrin (PRF) membrane containing bone growth enhancing elements can be stitched over the wound or a graft material or scaffold is placed in the socket of an extracted tooth at the time of extraction. The socket is then directly closed with stitches or covered with a non-resorbable or resorbable membrane and  sutured . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7613", "text": "A platelet-rich fibrin can be used if a  sinus lift  is required for a  dental implant . [ 7 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7614", "text": "Reproduction or reconstitution of a lost or injured part to restore the architecture and function of the periodontium becomes the integral part of comprehensive periodontal therapy. Conventional  open flap debridement  falls short of regenerating tissues destroyed by the disease.  Platelet derived growth factor  along with bone morphogenetic proteins are among the most researched growth factors in periodontal regeneration. [ 9 ] [ 10 ]  Platelet rich fibrin showed significant improvement in clinical periodontal parameter as well as in radiograph when compared with open flap debridement alone in a  meta analysis . [ 11 ]  Several bone graft materials have been used in the treatment of infrabony defects.  Demineralized freeze dried bone allograft  (DFDBA) has been histologically proven to be the material of choice for regeneration. Platelet-rich fibrin has shown significant results comparable to DFDBA for periodontal regeneration. [ 12 ]  One of the most common aesthetic problem encountered in the field of periodontology is gingival recession, which is perceived by the patients as increase in length of teeth. Though connective tissue graft is a gold standard procedure, PRF can be used as an alternative procedure by keeping patient's comfort in mind. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7615", "text": "PRF is used in  guided bone and tissue regeneration . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7616", "text": "PRF enhances  alveolar bone augmentation [ 15 ]  and  necrotic  dental pulp  and open  tooth apex  can be revitalized in  regenerative endodontics  with platelet-rich fibrin. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7617", "text": "Platelet-rich plasma  ( PRP ), also known as  autologous conditioned plasma , is a concentrate of  plasma protein  derived from whole  blood ,  centrifuged  to remove  red blood cells  but retaining  platelets . Though promoted for treating various medical conditions, evidence of its benefits was mixed as of  2020 , showing effectiveness in certain conditions and ineffectiveness in others. [ 1 ] [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7618", "text": "As a concentrated source of  blood plasma  and autologous conditioned plasma, PRP contains multiple  growth factors  and other  cytokines  that can stimulate the healing of  soft tissues  and  joints . Indications for its use include  sports medicine  and  orthopaedics  (such as acute muscle strains, tendinopathy,tendinosis, muscle-fascial injuries, and osteoarthritis, [ 4 ] )  dermatology  (for  androgenic alopecia ,  wound healing , and  skin rejuvenation ), and even  proctology  (for  fistula en ano [ 5 ] ). [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7619", "text": "Various preparation protocols exist, with the underlying principle of concentrating platelets to 3\u20135 times physiological levels, then injecting this concentrate into the  tissue  where  healing  is desired. [ 7 ]  Beyond clinical practice, PRP has been utilized in various  tissue engineering  applications involving  bone ,  cartilage ,  skin , and soft tissue repair. It serves as a source for the delivery of growth factors and/or cells within tissue-engineered constructs, often in combination with  biomaterials .\n [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7620", "text": "Evidence for benefit of PRP is mixed, with some evidence for use in certain conditions and against use in other conditions. [ 9 ] [ 10 ] [ 3 ]  It has been investigated for chronic  tendinitis , [ 11 ]   osteoarthritis , [ 12 ]  in  oral surgery , [ 13 ]  and in  plastic surgery . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7621", "text": "A 2022 study from the Journal of Clinical Medicine compared PRP injections to physical therapy. They found that PRP significantly lowered pain scores and increased elbow function. [ 15 ]  A 2022 study considered PRP for elbow tendinopathy. They found that PRP was effective and that the concentration of the platelets and healing factors such as epidermal growth factor (EGF) were correlated with success of treatment. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7622", "text": "A 2022 meta-analysis reviewed 26 studies on PRP for elbow tendinopathy. They found that PRP-treated patients rated their results significantly better using validated patient rated outcomes measures. [ 17 ]  A 2021 systematic review by the  Cochrane Library  examined PRP and autologous whole blood injections and concluded that it was \"uncertain\" if PRP or autologous whole blood injections improved elbow tendon healing. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7623", "text": "A 2018 systematic review and meta-analysis of high quality studies found that PRP was beneficial for treatment of  lateral epicondylitis . [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7624", "text": "Numerous reviews and meta-analyses have found that for elbow tendinopathy, PRP is superior to  cortisone  injections. [ 20 ] [ 21 ] [ 22 ] [ 23 ] [ 24 ]  It has been shown to have similar [ 25 ]  or equal [ 26 ] [ 27 ]  effects compared to surgery."}
{"_id": "WikiPedia_Hematology$$$corpus_7625", "text": "A 2022 review and meta-analysis showed improved patient-rated outcomes in patients with partial  rotator cuff  tears. At 8 weeks post injection, they found PRP to be effective. [ 28 ]  A 2021 prospective study examined the effectiveness of PRP for partial thickness rotator cuff tears. Patients were given 2 separate PRP injections and followed for 2 years. The study noted: \u201cNo adverse events were seen in any patient. Based on global rating scores positive results were seen in 77.9\u00a0% of patients at 6 months, 71.6\u00a0% at 1 year, and 68.8\u00a0% of patients at 2 years\u201d. They found PRP most effective in more damaged tendons. [ 29 ]  A 2021 meta-analysis found that PRP was effective for partial rotator cuff tears but the effects were no longer evident at 1 year. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7626", "text": "PRP has been shown to be superior to cortisone injections in several studies. [ 31 ]  This is especially evident in the longer term. [ 32 ] [ 33 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7627", "text": "A 2019 review found it not to be useful in  rotator cuff disease . [ 3 ]  A 2018 review found that it may be useful. [ 19 ]  A 2009 review found few randomized controlled trials that adequately evaluated the safety and efficacy of PRP treatments and concluded that PRP was \"a promising, but not proven, treatment option for joint, tendon, ligament, and muscle injuries\". [ 34 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7628", "text": "Tentative evidence supports the use of PRP in  osteoarthritis  of the knee. [ 35 ] [ 36 ]  A 2019 meta-analysis found that PRP might be more effective in reducing pain and improving function than  hyaluronic acid  in knee arthritis. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7629", "text": "A 2022 review found that in people with  meniscus tears , PRP treatment reduced the failure rate of meniscus repair surgery and reduced postoperative pain. However, the review did not find consistent evidence that PRP improved knee function. [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7630", "text": "Platelet-rich plasma  (PRP) is an emerging technique in tissue regeneration, increasingly used to enhance healing in dental and  oral surgery , particularly for aging patients. PRP is derived from the patient's blood through  centrifugation , concentrating growth factors that are crucial for wound healing and tissue repair."}
{"_id": "WikiPedia_Hematology$$$corpus_7631", "text": "Tooth Extractions and Periodontal Surgery:  PRP application in the alveolar socket after  tooth extractions  improves soft tissue healing and positively affects bone regeneration, although the effect on bone tends to diminish after a few days.\nIn periodontal therapy, PRP yields better results when combined with other materials compared to its use alone."}
{"_id": "WikiPedia_Hematology$$$corpus_7632", "text": "Implant Surgery: \nPRP has shown promising outcomes when used as a coating material in implant procedures, enhancing the  healing process."}
{"_id": "WikiPedia_Hematology$$$corpus_7633", "text": "Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) :\nCombining necrotic bone curettage with PRP application has been effective for treating refractory BRONJ, offering successful outcomes with minimal  invasiveness .\n [ 39 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7634", "text": "A 2014 Cochrane review of musculoskeletal injuries found very weak evidence for a decrease in pain in the short term, and no difference in function in the short, medium or long term. It has not been shown to be useful for bone healing. [ 40 ]  A 2016 review of bone graft augmentation found only one study reporting a difference in bone augmentation, while four studies found no difference. [ 41 ]  As compared to other conservative treatments for non-surgical orthopedic illnesses (e.g. steroid injection for  plantar fasciitis ), evidence does not support the use of PRP as a conservative treatment. [ 42 ]  A 2018 review found that evidence was lacking for  Achilles tendinopathy . [ 43 ]  A 2019 meta-analysis found that, for most outcomes in Achilles tendinopathy, PRP treatment did not differ from placebo treatment. [ 44 ]  A 2019 study conducted an umbrella review that \"considered studies that included populations with differing levels of physical activity, including studies on the sporting population (professional and/or recreational athletes) and studies didn't explicitly mention involving a sporting population.\" This inquiry reported only poor quality evidence that PRP offers any clinical benefits for treatment in acute muscle, tendon, and ligament injuries in any population. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7635", "text": "Studies have reported that PRP is beneficial for  alopecia areata [ 46 ]  and  androgenetic alopecia  and can be used as an alternative to  minoxidil  or  finasteride . [ 47 ]  A review reported it to improve hair density and thickness in both genders. [ 48 ]  A minimum of 3 treatments, once a month for 3 months are recommended, and afterwards a 3-6 month period of continual appointments for maintenance. [ 49 ]  Factors that determine efficacy include number of sessions, double versus single centrifugation, age and gender, and where  insertion site. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7636", "text": "PRP can be inoculated into the  uterine cavity , to improve endometrial receptivity in cases of refractory  endometrium . Studies have reported that intrauterine inoculation of PRP before embryo transfer can thicken the endometrium and improve reproductive prognosis. [ 51 ]  PRP has been studied for the management of  Asherman's Syndrome . [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7637", "text": "PRP can be inoculated experimentally into the  ovary  to promote ovarian tissue regeneration. The main applications would be in cases of diminished  ovarian reserve  or  premature ovarian failure . [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7638", "text": "A 2023 retrospective observational study reported PRP's effectiveness in rejuvenating ovarian fertility and viability in terms of \"the influence of intraovarian injection of autologous PRP on the levels of  E2 \". [ 53 ]  and pregnancy outcome in women treated with PRP who had a history of infertility, hormonal abnormalities, an absence of menstrual cycle, and premature ovarian failure in a single centre.\" [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7639", "text": "A 2024 review showed that PRP is beneficial when used as intraovarian injections for women with decreased fertility. PRP used for fertility trouble increases AFC, [ 54 ]  number of  cleavage embryos , and improves cancellation rate in women with  poor ovarian reserve . However, \"Although there was an improvement of baseline hormones ( anti-M\u00fcllerian hormone ,  follicle-stimulating hormone , and estradiol) after intraovarian injection of PRP, this improvement failed to reach statistical significance (except the improvement of serum AMH analyzed in quasi-experimental studies).\" [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7640", "text": "Venous ulcers  are persistent ankle or lower leg wounds that become open. [ 56 ]  A 2024 meta-analysis reported a positive effect on the size of ulcers as well as complete healing time for venous ulcers compared to standard treatments. A study combining a PRP therapy with conventional venous ulcer treatments reported improved quality of life and healing time. \"In terms of safety, the recurrence rate in the PRP group was significantly lower than that in the control group, while the rates of infection and irritative dermatitis showed no significant difference from the control group.\" [ 57 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7641", "text": "A 2024 meta-analysis reported that the growth factors present in PRP are vital in the healing of  diabetic foot ulcers ; specifically in their closure. The \ntreatments were reported to significantly increase the healing rate in comparison to conventional treatments. [ 58 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7642", "text": "Platelet-rich plasma therapy is a  minimally invasive procedure  that may be used in  aesthetic medicine  to treat skin conditions such as the removal of  wrinkles , the reduction of lines, and improvement of blemishes, and  hair loss . Concentrated PRP solution is injected into the treatment area to target damaged cells and tissues. The growth factors and proteins in PRP aid in rejuvenating the skin, and improving the condition of the scalp stimulating hair growth. [ 59 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7643", "text": "Adverse effects have been reported to be low in most trials. A review reported weak evidence of harm, occurring at comparable, low rates in treated and untreated people. [ 60 ] [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7644", "text": "The three general categories of preparation of PRP based on  leukocyte  and  fibrin  content are leukocyte-rich PRP, leukocyte reduced PRP, and leukocyte platelet-rich fibrin. [ 7 ] [ 61 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7645", "text": "The efficacy of certain growth factors in healing various injuries and the concentrations of these growth factors found within PRP are the theoretical basis for the use of PRP in tissue repair. [ 62 ]  Though not required for the process, platelets can be activated by the addition of  thrombin  or  calcium chloride , which induce the release of the factors from  alpha granules . The addition of thrombin or calcium chloride is not required as natural thrombin activates the cells upon injection. The growth factors and other cytokines present in PRP include: [ 62 ] [ 63 ] [ 64 ] [ 65 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7646", "text": "PRP is prepared by taking blood from the person, and then putting it through  centrifugation  designed to separate PRP from  platelet-poor plasma  and  red blood cells . This is usually done in the clinic, using commercially available kits and equipment. [ 66 ]  The resulting substance varies from person to person and from facility to facility. [ 66 ] [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7647", "text": "Use in an office setting is not approved by the  FDA . [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7648", "text": "PRP has received attention in media [ 69 ] [ 70 ] [ 71 ]  as a result of its use by athletes. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7649", "text": "In the 2010s, cosmetic procedures marketed under the name of \"vampire facials\" grew in popularity, fueled by celebrity endorsement. These facials generally center on PRP treatment, and usually involve  microneedling . [ 73 ] [ 74 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7650", "text": "In April 2024, the  CDC  announced that three women who had been patients at the Albuquerque, New Mexico, VIP Spa had been diagnosed with HIV after getting such facials. Another almost 200 former clients and their sexual partners tested negative. [ 75 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7651", "text": "PRP has been injected into the  vagina , in a procedure called \"O-shot [ 76 ] \" or \"orgasm shot\", with claims to improve  orgasms . [ 77 ]  No evidence supports such claims. [ 77 ] [ 78 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7652", "text": "PRP treatments may violate anti- doping  rules. [ 62 ]  As of 2010, it was not clear whether PRP could have a systemic impact on circulating  cytokine  levels, affecting doping tests and whether PRP treatments had systemic anabolic effects or affect performance. [ 62 ]  In January 2011, the  World Anti-Doping Agency  removed intramuscular injections of PRP from its prohibitions after determining that there is a \"lack of any current evidence concerning the use of these methods for purposes of performance enhancement\". [ 79 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7653", "text": "In the early 1940s clinicians used extracts of growth factors and cytokines for healing. The term 'platet-rich plasma' was first used in 1954 by Kingsley and in the 1960s the first PRP blood banks were established, becoming popular by the 1970s. [ 80 ]  In the 1970s PRP was used in hematology, originally for transfusions to treat  thrombocytopenia . Ten years later it was used for maxillofacial surgeries. [ 6 ]  PRP was first used in Italy in 1987 in an open heart surgery procedure. [ 81 ]  In 2006 PRP was starting to be considered of potential use for both  androgenic alopecia  and  alopecia areata . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7654", "text": "Post-transfusion purpura  ( PTP ) is a delayed adverse reaction to a  blood transfusion  or  platelet transfusion  that occurs when the body has produced  alloantibodies  to the allogeneic transfused  platelets'   antigens . These alloantibodies destroy the patient's platelets leading to  thrombocytopenia , a rapid decline in platelet count. [ 1 ]  PTP usually presents 5\u201312 days after transfusion, and is a potentially fatal condition in rare cases. Approximately 85% of cases occur in women. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7655", "text": "PTP is rare, but usually occurs in women who have had multiple pregnancies or in people who have undergone previous transfusions.  The precise mechanism leading to PTP is unknown, but it most commonly occurs in individuals whose platelets lack the  HPA-1a  antigen (old name: PL A1 ).  The patient develops antibodies to the HPA-1a antigen leading to platelet destruction. In some cases, HPA-5b has also been implicated. It is unclear why alloantibodies attack the patient's own, as well as any transfused allogeneic random donor platelets. Probable explanation for this is that the recipient's platelets acquire the phenotype of donor's platelet by binding of the soluble antigens from the donor onto the recipient's platelet. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7656", "text": "Symptoms are usually sudden in onset and self-limiting, most often resolving within 2 weeks. [ 2 ]   IVIG  therapy is the primary treatment. [ 4 ]  Additionally, PTP is an  American Society for Apheresis  Category III indication for plasmapheresis. [ 5 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7657", "text": "Postpartum bleeding  or  postpartum hemorrhage  ( PPH ) is often defined as the loss of more than 500\u00a0ml or 1,000\u00a0ml of blood  following  childbirth . [ 2 ]  Some have added the requirement that there also be signs or symptoms of  low blood volume  for the condition to exist. [ 6 ]  Signs and symptoms may initially include: an  increased heart rate ,  feeling faint upon standing , and an increased breathing rate. [ 1 ]  As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become restless or unconscious. [ 1 ]  In severe cases circulatory collapse,  disseminated intravascular coagulation  and death can occur. The condition can occur up to twelve weeks following delivery in the secondary form. [ 7 ]  \nThe most common cause is  poor contraction of the uterus  following childbirth. [ 2 ]   Not all of the placenta being delivered , a tear of the  uterus , or poor  blood clotting  are other possible causes. [ 2 ]  It occurs more commonly in those who already have a  low amount of red blood , are  Asian , have a larger  fetus  or more than one fetus, are  obese  or are older than 40 years of age. [ 2 ]  It also occurs more commonly following  caesarean sections , those in whom medications are used to start labor, those requiring the use of a vacuum or  forceps , and those who have an  episiotomy . [ 2 ] [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7658", "text": "Prevention involves decreasing known risk factors including procedures associated with the condition, if possible, and giving the medication  oxytocin  to stimulate the uterus to contract shortly after the baby is born. [ 2 ]   Misoprostol  may be used instead of oxytocin in resource-poor settings. [ 2 ]  Treatments may include: intravenous fluids,  blood transfusions , and the medication  ergotamine  to cause further uterine contraction. [ 2 ]  Efforts to compress the uterus using the hands may be effective if other treatments do not work. [ 2 ]  The  aorta  may also be compressed by pressing on the abdomen. [ 2 ]  The World Health Organization has recommended the  non-pneumatic anti-shock garment  to help until other measures such as surgery can be carried out. [ 2 ]   Tranexamic acid  has also been shown to reduce the risk of death, [ 3 ]  and has been recommended within three hours of delivery. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7659", "text": "In the  developing world  about 1.2% of deliveries are associated with PPH and when PPH occurred about 3% of women died. [ 2 ]  It is responsible for 8% of maternal deaths during childbirth in developed regions and 20% of maternal deaths during childbirth in developing regions. [ 7 ]  Globally it occurs about 8.7 million times and results in 44,000 to 86,000 deaths per year making it the leading cause of death during pregnancy. [ 4 ] [ 2 ] [ 10 ]  About 0.4 women per 100,000 deliveries die from PPH in the United Kingdom while about 150 women per 100,000 deliveries die in  sub-Saharan Africa . [ 2 ]  Rates of death have decreased substantially since at least the late 1800s in the United Kingdom. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7660", "text": "Depending on the source, primary postpartum bleeding is defined as blood loss in excess of 500 ml following  vaginal delivery  or 1000 mL following  caesarean section  in the first 24 hours following birth. Others have defined the condition as blood loss of greater than 1000 mL after either delivery method, or any amount of blood loss with signs and symptoms of hypovolemia. [ 7 ]  Secondary postpartum bleeding is that which occurs after the 24 hours up to 12 weeks after childbirth. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7661", "text": "Symptoms generally include heavy bleeding from the vagina that doesn't slow or stop over time. [ 11 ]  Initially there may be an  increased heart rate ,  feeling faint upon standing , and an increased respiratory rate. [ 1 ]  As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become unconscious. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7662", "text": "Signs and symptoms of  circulatory shock  may also include blurry vision, cold and clammy skin, confusion, and feeling sleepy or weak. [ 1 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7663", "text": "Causes of postpartum hemorrhage are  uterine atony ,  trauma , retained  placenta  or  placental abnormalities , and  coagulopathy , commonly referred to as the \"four Ts\": [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7664", "text": "Other risk factors include  endometriosis , [ 14 ]   obesity , fever during pregnancy, bleeding before delivery, and heart disease. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7665", "text": "Oxytocin  is typically used right after the delivery of the baby to prevent PPH. [ 2 ]   Misoprostol  may be used in areas where oxytocin is not available. [ 2 ]  Early clamping of the  umbilical cord  does not decrease risks and may cause  anemia  in the baby, and thus is usually not recommended. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7666", "text": "Active management of the third stage is a method of shortening the stage between when the baby is born and when the placenta is delivered. [ 15 ]  This stage is when the mother is at risk of having a PPH. Active management involves giving a drug which helps the uterus contract before delivering the placenta by a gentle but sustained pull on the umbilical cord whilst exerting upward pressure on the lower abdomen to support the uterus (controlled cord traction). [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7667", "text": "Active management of the third stage of labor with uterotonics (oxytocin or Misoprostol) and gentle umbilical cord traction have been shown to reduce the incidence of PPH by 66%. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7668", "text": "Another method of active management which is no longer recommended is fundal pressure during the delivery of the placenta. A review into this method found no benefit to its use and advises only controlled cord traction because fundal pressure can cause the mother unnecessary pain. [ 15 ]  Allowing the cord to drain appears to shorten the third stage and reduce blood loss but evidence around this subject is not strong enough to draw solid conclusions. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7669", "text": "Nipple stimulation and breastfeeding triggers the release of natural oxytocin in the body, therefore it is thought that encouraging the baby to suckle soon after birth may reduce the risk of PPH for the mother. [ 17 ]  A review looking into this did not find enough good research to say whether or not nipple stimulation did reduce PPH. More research is needed to answer this question. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7670", "text": "Uterine massage is a simple first line treatment as it helps the uterus to contract to reduce bleeding. [ 18 ]  Although the evidence around the effectiveness of uterine massage is inconclusive, it is common practice after the delivery of the placenta. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7671", "text": "Intravenous or intramuscular  oxytocin  is the drug of choice for postpartum hemorrhage. [ 19 ] [ 20 ]   Ergotamine  may also be used. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7672", "text": "Oxytocin helps the uterus to contract quickly and the contractions to last longer. [ 21 ]  It is the first line treatment for PPH when its cause is the uterus not contracting well. [ 22 ]  A combination of syntocinon and  ergometrine  is commonly used as part of active management of the third stage of labour. [ 23 ]  This is called syntometrine. Syntocinon alone lowers the risk of PPH. [ 24 ]  Based on limited research available it is unclear whether syntocinon or syntometrine is most effective in preventing PPH but adverse effects are worse with syntometrine making syntocinon a more attractive option. [ 24 ]  Ergometrine also has to be kept cool and in a dark place so that it is safe to use. [ 25 ]  It may reduce the risk of PPH by improving the tone of the uterus when compared with no treatment, however it must be used with caution due to its effects of raising blood pressure and worsening pain. [ 25 ]  More research would be useful in determining the best doses of ergometrine [ 25 ]  and syntocinon. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7673", "text": "Oxytocin requires refrigeration, which may not always be available, particularly in low-resourced settings. [ 26 ]  When oxytocin is not available, misoprostol can be used. [ 22 ]  Misoprostol does not need to be kept at a certain temperature and research into its effectiveness in reducing blood loss appears promising when compared with a placebo in a setting where it is not appropriate to use oxytocin. [ 26 ]  Misoprostol can cause unpleasant side effects such as very high body temperatures and shivering. [ 27 ]  Lower doses of misoprostol appear to be safer and cause less side effects. [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7674", "text": "Giving oxytocin in a solution of saline into the umbilical vein is a method of administering the drug directly to the placental bed and uterus. [ 28 ]  However quality of evidence around this technique is poor and it is not recommended for routine use in the management of the third stage. [ 28 ]  More research is needed to ascertain whether this is an effective way of administering uterotonic drugs. [ 28 ]  As a way of treating a retained placenta, this method is not harmful and has shown low certainty evidence of effectiveness. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7675", "text": "Carbetocin  compared with oxytocin produced a reduction in women who needed uterine massage and further uterotonic drugs for women having caesarean sections. [ 30 ]  There was no difference in rates of PPH in women having caesarean sections or women having vaginal deliveries when given carbetocin. [ 30 ]  Carbetocin appears to cause less adverse effects. More research is needed to find the cost effectiveness of using carbetocin. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7676", "text": "Tranexamic acid , a clot stabilizing medication, may also be used to reduce bleeding and blood transfusions in low-risk patients, [ 31 ]  however evidence as of 2015 was not strong. [ 2 ]  A 2017 trial found that it decreased the risk of death from bleeding from 1.9% to 1.5% in women with postpartum bleeding. [ 3 ]  The benefit was greater when the medication was given within three hours. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7677", "text": "In some countries, such as Japan,  methylergometrine  and other herbal remedies are given following the delivery of the placenta to prevent severe bleeding more than a day after the birth. However, there is not enough evidence to suggest that these methods are effective. [ 32 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7678", "text": "Surgery may be used if medical management fails or in case of cervical lacerations, tears in the uterine wall or a uterine rupture. Methods used may include uterine artery ligation, ovarian artery ligation, internal iliac artery ligation, selective arterial embolization, B-lynch suture, and  hysterectomy . [ 33 ] [ 34 ] [ 35 ] [ 36 ]  Bleeding caused by traumatic causes should be managed by surgical repair. When there is bleeding due to uterine rupture a repair can be performed but most of the time a hysterectomy is needed. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7679", "text": "There is currently no reliable evidence from randomised clinical trials about the effectiveness or risks of mechanical and surgical methods of treating postpartum bleeding. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7680", "text": "In those with  placenta accreta  (in which the placenta invades into the muscular layer of the uterus) planned caesarian delivery is recommended due to the very high risk of PPH although the optimal time for planned delivery is not well established with the  American College of Obstetricians and Gynecologists  recommending planned caesarian at delivery between 34 weeks and 35 weeks and 6 days gestation and the  Royal College of Obstetricians and Gynaecologists  recommending it between 35 and 36 weeks and 6 days. [ 7 ]  A hysterectomy is sometimes required, or planned, after the planned delivery. [ 7 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7681", "text": "The  World Health Organization  recommends the use of a device called the  non-pneumatic anti-shock garment  (NASG) for use in delivery activities outside of a hospital setting, the aim being to improve shock in a mother with  obstetrical bleeding  long enough to reach a hospital. [ 39 ]  External aortic compression devices (EACD) may also be used. [ 40 ] [ 41 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7682", "text": "Uterine balloon tamponade  (UBT) can improve postpartum bleeding. [ 42 ]  Inflating a  Sengstaken\u2013Blakemore tube  in the uterus successfully treats atonic postpartum hemorrhage refractory to medical management in approximately 80% of cases. [ 43 ]  Such procedure is relatively simple, inexpensive and has low surgical morbidity. [ 43 ]  A  Bakri balloon  is a balloon tamponade specifically constructed for uterine postpartum hemorrhage. [ 44 ]  While effective, commercially available devices may be expensive for settings in which postpartum hemorrhage is most common. Low-cost devices, such as the ESM-UBT, have been shown to be effective without the need for operative intervention. [ 45 ] [ 46 ] [ 47 ]  Uterine balloon tamponade devices may be left in place for up to 24 hours in the treatment of PPH. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7683", "text": "Uterine and vaginal packing are not recommended in the treatment of PPH and are associated with a high risk of infection. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7684", "text": "Protocols to manage postpartum bleeding are recommended to ensure the rapid giving of blood products when needed. [ 48 ]  A detailed stepwise management protocol has been introduced by the California Maternity Quality Care Collaborative. [ 49 ]  It describes four stages of obstetrical hemorrhage after childbirth and its application reduces maternal mortality. [ 50 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7685", "text": "A  Cochrane review  suggests that active management (use of uterotonic drugs, cord clamping and controlled cord traction) during the third stage of labour may reduce severe bleeding and  anemia . [ 51 ]  However, the review also found that active management increased the patient's blood pressure, nausea, vomiting, and pain. In the active management group more patients returned to hospital with bleeding after discharge, and there was also a reduction in birthweight due to infants having a lower blood volume. The effects on the baby of early cord clamping was discussed in another review which found that delayed cord clamping improved iron stores longer term in the infants. [ 52 ]  Although they were more likely to need phototherapy (light therapy) to treat jaundice, the improved iron stores are expected to be worth increasing the practice of delayed cord clamping in healthy term babies. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7686", "text": "For preterm babies (babies born before 37 weeks) a review of the research found that delaying cord clamping may lead to fewer babies with bleeding in the brain, compared to early cord clamping. [ 53 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7687", "text": "Another Cochrane review looking at the timing of the giving  oxytocin  as part of the active management found similar benefits with giving it before or after the expulsion of the placenta. [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7688", "text": "There is no good quality evidence on how best to treat a secondary PPH (PPH occurring 24 hrs or more after the birth). [ 55 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7689", "text": "Methods of measuring blood loss associated with childbirth vary, complicating comparison of prevalence rates. [ 56 ]  A systematic review reported the highest rates of PPH in Africa (27.5%), and the lowest in Oceania (7.2%), with an overall rate globally of 10.8%. [ 56 ]  The rate in both Europe and North America was around 13%. [ 56 ]  The rate is higher for multiple pregnancies (32.4% compared with 10.6% for singletons), and for first-time mothers (12.9% compared with 10.0% for women in subsequent pregnancies). [ 56 ]  The overall rate of severe PPH (>1000 ml) was much lower at an overall rate of 2.8%, again with the highest rate in Africa (5.1%). [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7690", "text": "Prothrombin complex concentrate  ( PCC ), also known as  factor IX complex , sold under the brand name  Kcentra  among others, is a  combination medication  made up of  blood clotting factors   II ,  IX , and  X [ 9 ] (3-factor PCC) or, when also containing  factor VII  as does Kcentra, 4-factor PCC. [ 10 ]  It is used to treat and prevent bleeding in  hemophilia B  if pure factor IX is not available. [ 9 ] [ 11 ]  It may also be used for reversal of  warfarin  therapy. [ 11 ]  It is given by  slow injection into a vein . [ 9 ]  Another product, activated prothrombin complex concentrate or FEIBA (Factor Eight Inhibitor Bypassing Agent), may be used for acquired hemophilia. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7691", "text": "Common side effects include  allergic reactions , headache, vomiting, and sleepiness. [ 9 ] [ 13 ]  Other serious side effects include  blood clots  which may result in a  heart attack ,  stroke ,  pulmonary embolism , or  deep vein thrombosis . [ 13 ]   Antibodies  may form after long term use such that future doses are less effective. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7692", "text": "Prothrombin complex concentrate came into medical use in the 1960s. [ 14 ]  It is on the  World Health Organization's List of Essential Medicines . [ 15 ] [ 16 ]  It is made from  human plasma . [ 13 ]   Recombinant  factor IX is also available in a stand-alone preparation. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7693", "text": "Prothrombin complex concentrate reverses the effects of  warfarin  and other  vitamin K antagonist  anti-coagulants and is used in cases of significant bleeding in people with a  coagulopathy . It is also used when such a person must undergo an emergency operation. [ 18 ]  Other uses include a deficiency of one of the included clotting factors, either congenital or due to  liver disease , and  hemophilia . [ 18 ]  Several guidelines, including those from the  American College of Chest Physicians , recommend prothrombin complex concentrate for warfarin reversal in people with serious bleeding. [ 19 ] [ 20 ] [ 21 ] [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7694", "text": "For rapid anticoagulation reversal for surgery, four-factor prothrombin complex concentrate reduces  international normalized ratio  (INR) and decreases bleeding during surgery when compared with administration of fresh frozen plasma. No differences in thromboembolic event was found. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7695", "text": "The package insert states that prothrombin complex concentrate is contraindicated in patients with  disseminated intravascular coagulation , a pathological activation of coagulation, [ 24 ]  because giving clotting factors would only further fuel this process. However, if the PCC is given because factor levels are low, it can restore normal coagulation. As PCC products contain  heparin , they are contraindicated in patients with  heparin-induced thrombocytopenia . [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7696", "text": "Prothrombin complex concentrate contains a number of blood clotting factors. Typically this includes  factor II ,  IX , and  X . [ 9 ]  Some versions also contain  factor VII ,  protein C , and  protein S . [ 10 ] [ 24 ]   Heparin  may be added to stop early activation of the factors. [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7697", "text": "The US  Food and Drug Administration  (FDA) announced its approval in 2013. [ 25 ]  The FDA approved Kcentra's orphan drug status in December 2012. [ 25 ] [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7698", "text": "In the United States a dose of prothrombin complex concentrate costs about US $3200 [ 27 ]  though one study described the cost as $11 650. [ 28 ]  The Australian National Blood Authority sets Prothrombinex (500 IU) at around AUD$327.  [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7699", "text": "A number of different formulations are available globally. [ 30 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7700", "text": "The  Rh blood group system  is a  human blood group system . It contains proteins on the surface of red blood cells. After the  ABO blood group system , it is the most likely to be involved in transfusion reactions. The Rh blood group system consisted of 49 defined blood group  antigens [ 1 ]  in 2005. As of 2023, [update]  there are over 50 antigens among which the five antigens D, C, c, E, and e are among the most prominent. There is no d antigen. Rh(D) status of an individual is normally described with a  positive  (+) or  negative  (\u2212) suffix after the  ABO  type (e.g., someone who is A+ has the A antigen and Rh(D) antigen, whereas someone who is A\u2212 has the A antigen but lacks the Rh(D) antigen). The terms  Rh factor ,  Rh positive , and  Rh negative  refer to the Rh(D) antigen only. Antibodies to Rh antigens can be involved in  hemolytic transfusion reactions  and antibodies to the Rh(D) and Rh antigens confer significant risk of  hemolytic disease of the newborn ."}
{"_id": "WikiPedia_Hematology$$$corpus_7701", "text": "The Rh blood group system has two sets of nomenclatures: one developed by  Ronald Fisher  and  R. R. Race , the other by  Wiener . Both systems reflected alternative theories of inheritance. The Fisher\u2013Race system, which is more commonly in use today, uses the CDE nomenclature. This system was based on the theory that a separate  gene  controls the product of each corresponding antigen (e.g., a \"D gene\" produces D antigen, and so on). However, the d gene was hypothetical, not actual."}
{"_id": "WikiPedia_Hematology$$$corpus_7702", "text": "The Wiener system used the Rh\u2013Hr nomenclature. This system was based on the theory that there was one gene at a single locus on each of the two copies of chromosome 1, each contributing to production of multiple antigens. In this theory, a gene R 1  is supposed to give rise to the \"blood factors\" Rh 0 , rh\u2032, and rh\u2033 (corresponding to modern nomenclature of the D, C, and E antigens) and the gene r to produce hr\u2032 and hr\u2033 (corresponding to modern nomenclature of the c and e antigens). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7703", "text": "Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D) meaning RhD positive). Wiener's notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher\u2013Race theory has become more widely used. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7704", "text": "DNA testing has shown that both are partially correct: There are in fact two linked genes, the  RHD  gene which produces a single immune specificity (anti-D) and the  RHCE  gene with multiple specificities (anti-C, anti-c, anti-E, anti-e). Thus, Wiener's postulate that a gene could have multiple specificities (something many did not give credence to originally) has been proved to be correct. On the other hand, Wiener's theory that there is only one gene has proved to be incorrect, as has the Fisher\u2013Race theory that there are three genes, rather than the two. The CDE notation used in the Fisher\u2013Race nomenclature is sometimes rearranged to DCE to more accurately represent the co-location of the C and E encoding on the RhCE gene, and to make interpretation easier. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7705", "text": "The proteins which carry the Rh antigens are  transmembrane proteins , whose structure suggests that they are  ion channels . [ 4 ]  The main antigens are D, C, E, c and e, which are encoded by two adjacent gene loci, the  RHD  gene which encodes the RhD protein with the D antigen (and variants) [ 5 ]  and the  RHCE  gene which encodes the RhCE protein with the C, E, c and e antigens (and variants). [ 6 ]  There is no d antigen. Lowercase \"d\" indicates the absence of the D antigen (the gene is usually deleted or otherwise nonfunctional). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7706", "text": "Rh  phenotypes  are readily identified through the presence or absence of the Rh surface antigens. As can be seen in the table below, most of the Rh phenotypes can be produced by several different Rh  genotypes . The exact genotype of any individual can only be identified by DNA analysis. Regarding patient treatment, only the phenotype is usually of any clinical significance to ensure a patient is not exposed to an antigen they are likely to develop antibodies against. A probable genotype may be speculated on, based upon the statistical distributions of genotypes in the patient's place of origin. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7707", "text": "R 0  (cDe or Dce) is today most common in Africa. The allele was thus often assumed in early blood group analyses to have been typical of populations on the continent, particularly in areas below the Sahara. Ottensooser et al. (1963) suggested that high R 0  frequencies were likely characteristic of the ancient  Judean  Jews, who had emigrated from  Egypt  prior to their dispersal throughout the  Mediterranean Basin  and Europe [ 7 ]  on the basis of high R 0  percentages among  Sephardi  and  Ashkenazi   Jews  compared to native  European  populations and the relative genetic isolation of Ashkenazim. However, more recent studies have found R 0  frequencies as low as 24.3% among some  Afroasiatic -speaking groups in the Horn of Africa, [ 8 ]  as well as higher R 0  frequencies among certain other Afroasiatic speakers in  North Africa  (37.3%) [ 9 ]  and among some  Palestinians  in the  Levant  (30.4%). [ 10 ]  On the contrary, at a frequency of 47.2% of the population of Basque country having the lack of the D antigen, these people display the highest frequency of the Rh negative phenotype. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7708", "text": "\u2022 Figures taken from a study performed in 1948 on a sample of 2000 people in the United Kingdom. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7709", "text": "Rh antibodies are  Immunoglobulin G  (IgG) antibodies which are acquired through exposure to Rh-positive blood (generally either through pregnancy or transfusion of blood products). The D antigen is the most immunogenic of all the non-ABO antigens.  Approximately 80% of individuals who are D-negative and exposed to a single D-positive unit will produce an anti-D antibody. The percentage of alloimmunization is significantly reduced in patients who are actively  exsanguinating . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7710", "text": "All Rh antibodies  except  D display dosage (antibody reacts more strongly with red cells homozygous for an antigen than cells heterozygous for the antigen (EE stronger reaction vs Ee))."}
{"_id": "WikiPedia_Hematology$$$corpus_7711", "text": "If anti-E is detected, the presence of anti-c should be strongly suspected (due to combined genetic inheritance). It is therefore common to select c-negative and E-negative blood for transfusion patients who have an anti-E and lack the c antigen (in general, a patient will not produce antibodies against their own antigens). Anti-c is a common cause of delayed hemolytic transfusion reactions. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7712", "text": "The hemolytic condition occurs when there is an incompatibility between the blood types of the mother and fetus. There is also potential incompatibility if the mother is Rh negative, and the father is positive. When the mother conceives for the first time, with a positive child, she will become extremely sensitive. When any incompatibility is detected when she conceives the second time in less than two years then, the mother often receives an injection at 28 weeks' gestation and at birth to avoid the development of antibodies towards the fetus. If not given, then the baby will be dead and must be aborted. These terms do not indicate which specific antigen-antibody incompatibility is implicated. The disorder in the fetus due to Rh D incompatibility is known as  erythroblastosis fetalis ."}
{"_id": "WikiPedia_Hematology$$$corpus_7713", "text": "When the condition is caused by the Rh D antigen-antibody incompatibility, it is called Rh D Hemolytic disease of the newborn or Rh disease. Here, sensitization to Rh D antigens (usually by feto-maternal transfusion during pregnancy) may lead to the production of maternal  IgG  anti-D antibodies which can pass through the  placenta . This is of particular importance to D negative females at or below childbearing age, because any subsequent pregnancy may be affected by the  Rh D hemolytic disease of the newborn  if the baby is D positive. The vast majority of  Rh disease  is preventable in modern  antenatal  care by injections of IgG anti-D antibodies ( Rho(D) Immune Globulin ). The incidence of Rh disease is mathematically related to the frequency of D negative individuals in a population, so Rh disease is rare in old-stock populations of Africa and the eastern half of Asia, and the Indigenous peoples of Oceania and the Americas, but more common in other genetic groups, most especially Western Europeans, but also other West Eurasians, and to a lesser degree, native Siberians, as well as those of mixed-race with a significant or dominant descent from those (e.g. the vast majority of Latin Americans and Central Asians)."}
{"_id": "WikiPedia_Hematology$$$corpus_7714", "text": "Rh disease only occurs in human fetuses, however a similar disease called Neonatal isoerythrolysis (NI) can be observed in animal species of newborn horses, mules, pigs, cats, cattle, and dogs.\u00a0 What differs between Rh disease and NI is the pathogenesis of hemolysis between human fetuses and the animal species.\u00a0 With human mothers, the maternal antibodies are formed from the sensitization of foreign antigens of her unborn fetus\u2019s red blood cells passing through the placenta causing hemolysis before birth. With other animals, however, these maternal antibodies are not passed through the placenta, but through  colostrum .\u00a0 The newborn animal is without NI but soon develops hemolytic anemia after initial ingestion of its mother\u2019s colostrum that contain antibodies that can be absorbed through the newborn\u2019s intestines and are incompatible to its red blood cell antigen. After 48 hours of birth, the newborn may be allowed to nurse from its mother as her antibodies can no longer be absorbed through the neonate\u2019s intestines.\u00a0 Because the most active newborn animals consume the most colostrum, they may be the ones who are most affected by the blood incompatibility of antigen and antibody. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7715", "text": "According to a comprehensive study, the worldwide frequency of Rh-positive and Rh-negative blood types is approximately 94% and 6%, respectively. The same study concluded that the share of the population with Rh-negative blood type is set to fall further in the future primarily due to low population growth in  Europe . [ 17 ]  The frequency of Rh factor blood types and the RhD neg  allele  gene differs in various populations. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7716", "text": "The D antigen is inherited as one gene ( RHD ) (on the short arm of the  first chromosome , p36.13\u2013p34.3) with various alleles. Typically, Rhesus positive people have an intact RHD gene while negative people lack the gene (or have mutations in it). However, there are exceptions: for instance, Japanese and black Africans may have an intact gene that is not expressed or only at very low levels. [ 27 ]  The gene codes for the RhD  protein  on the red blood cell membrane. D\u2212 individuals who lack a functional  RHD  gene do not produce the D antigen and may be immunized by D+ blood. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7717", "text": "The D antigen is a dominant trait. If both of a child's parents are  Rh negative,  the child will definitely be  Rh negative . Otherwise, the child may be  Rh positive  or  Rh negative,  depending on the parents' specific genotypes. [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7718", "text": "The  epitopes  for the next 4 most common Rh antigens, C, c, E and e are expressed on the highly similar RhCE protein that is genetically encoded in the  RHCE  gene, also found on chromosome 1. It has been shown that the  RHD  gene arose by duplication of the  RHCE  gene during primate evolution. Mice have just one RH gene. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7719", "text": "The RHAG gene, which is responsible for encoding Rh-associated glycoprotein (RhAG), is found on chromosome 6a."}
{"_id": "WikiPedia_Hematology$$$corpus_7720", "text": "The polypeptides produced from the RHD and RHCE genes form a complex on the red blood cell membrane with the Rh-associated glycoprotein. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7721", "text": "On the basis of structural homology it has been proposed that the product of RHD gene, the RhD protein, is a  membrane transport protein  of uncertain specificity (CO 2  or NH 3 ) and unknown physiological role. [ 30 ] [ 31 ]  The three-dimensional structure of the related  RHCG  protein and biochemical analysis of the RhD protein complex indicates that the RhD protein is one of three subunits of an  ammonia transporter . [ 32 ] [ 33 ]  Three recent studies [ 34 ] [ 35 ] [ 36 ]  have reported a protective effect of the RhD-positive phenotype, especially RhD  heterozygosity , against the negative effect of latent  toxoplasmosis  on psychomotor performance in infected subjects. RhD-negative compared to RhD-positive subjects without  anamnestic  titres of anti- Toxoplasma  antibodies have shorter reaction times in tests of simple reaction times. And conversely, RhD-negative subjects with anamnestic titres (i.e. with latent toxoplasmosis) exhibited much longer reaction times than their RhD-positive counterparts. The published data suggested that only the protection of RhD-positive heterozygotes was long term in nature; the protection of RhD-positive  homozygotes  decreased with duration of the infection while the performance of RhD-negative homozygotes decreased immediately after the infection. The overall change in reaction times was always larger in the RhD-negative group than in the RhD-positive. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7722", "text": "Rh-like proteins can be found even in species other than vertebrates (which have  red blood cells ) \u2013 worms, bacteria, and algae. All these Rh proteins have the same biochemical function of transporting CO 2 , differing slightly in their amino acid sequences. The Rh family as a whole is related to  ammonia transporters  (Amt). In  C. elegans  worms, disruption of the Rh1 gene causes growth defects under high CO 2  levels.  Chlamydomonas reinhardtii  algae fail to grow rapidly if its Rh gene is knocked down. Although  in vitro  evidence shows the Rh complex is capable of moving ammonia, its disruption does not cause growth defects under modified ammonia levels. [ 37 ] [ 38 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7723", "text": "For a long time, the origin of RHD polymorphism was an evolutionary enigma. [ 39 ] [ 40 ] [ 41 ]  Before the advent of modern medicine, the carriers of the rarer allele (e.g. RhD-negative women in a population of RhD positives or RhD-positive men in a population of RhD negatives) were at a disadvantage as some of their children (RhD-positive children born to preimmunised RhD-negative mothers) were at a higher risk of fetal or newborn death or health impairment from hemolytic disease. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7724", "text": "Natural selection aside, the RHD-RHCE region is structurally predisposed to many mutations seen in humans, since the pair arose by gene duplication and remain similar enough for  unequal crossing over  to occur. [ 29 ]  In addition to the case where D is deleted, crossover can also produce a single gene mixing  exons  from both  RHD  and  RHCE , forming the majority of partial D types. [ 43 ] :\u200a323"}
{"_id": "WikiPedia_Hematology$$$corpus_7725", "text": "In serologic testing, D positive blood is easily identified. Units that are D negative are often retested to rule out a weaker reaction. This was previously referred to as D u , which has been replaced. [ 43 ] :\u200a322\u200a  By definition, weak D phenotype is characterized by negative reaction with anti-D reagent at immediate spin (IS), negative reaction after 37\u00a0\u00b0C incubation, and positive reaction at anti-human globulin (AHG) phase. Weak D phenotype can occur in several ways. In some cases, this phenotype occurs because of an altered surface protein that is more common in people of European descent. An inheritable form also occurs, as a result of a weakened form of the R0 gene. Weak D may also occur as \"C in trans\", whereby a C gene is present on the opposite chromosome to a D gene (as in the combination R0r', or \"Dce/dCe\"). The testing is difficult, since using different anti-D reagents, especially the older polyclonal reagents, may give different results."}
{"_id": "WikiPedia_Hematology$$$corpus_7726", "text": "The practical implication of this is that people with this sub-phenotype will have a product labeled as \"D positive\" when donating blood. When receiving blood, they are sometimes typed as a \"D negative\", though this is the subject of some debate. Most \"Weak D\" patients can receive \"D positive\" blood without complications. [ 43 ] :\u200a323\u200a  However, it is important to correctly identify the ones that have to be considered D+ or D\u2212. This is important, since most blood banks have a limited supply of \"D negative\" blood and the correct transfusion is clinically relevant. In this respect,  genotyping of blood groups  has much simplified this detection of the various variants in the Rh blood group system."}
{"_id": "WikiPedia_Hematology$$$corpus_7727", "text": "It is important to differentiate weak D (due to a  quantitative  difference in the D antigen) from partial D (due to a  qualitative  difference in the D antigen). Simply put, the weak D phenotype is due to a reduced number of D antigens on a red blood cell. In contrast, the partial D phenotype is due to an alteration in D-epitopes. Thus, in partial D, the number of D antigens is not reduced but the protein structure is altered. These individuals, if alloimmunized to D, can produce an anti-D antibody. Therefore, partial D patients who are donating blood should be labeled as D-positive but, if receiving blood, they should be labeled as D-negative and receive D-negative units. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7728", "text": "In the past, partial D was called 'D mosaic' or 'D variant.' Different partial D phenotypes are defined by different D epitopes on the outer surface of the red blood cell membrane. More than 30 different partial D phenotypes have been described. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7729", "text": "Rh null  individuals have no Rh antigens (no Rh or RhAG) on their red blood cells. [ 44 ]  This rare condition [ 44 ]  has been called \"Golden Blood\". [ 45 ]  As a consequence of Rh antigen absence, Rh null  red blood cells also lack LW and Fy5 and show weak expression of S, s, and U antigens."}
{"_id": "WikiPedia_Hematology$$$corpus_7730", "text": "Red blood cells lacking Rh/RhAG proteins have structural abnormalities (such as  stomatocytosis ) and cell membrane defects that can result in  hemolytic anemia . [ 15 ] [ 44 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7731", "text": "The first Rh null  blood was discovered in an  Aboriginal Australian  woman, in 1961. [ 46 ]  Only 43 individuals have been reported to have it worldwide. Only nine active donors have been reported. [ 45 ]  Its properties make it attractive in numerous medical applications, but scarcity makes it expensive to transport and acquire. [ 47 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7732", "text": "As of 2023, over 50 antigens have been described in the Rh group system; among those described here, the D, C, c, E and e antigens are the most important. The others are much less frequently encountered or are rarely clinically significant. Each is given a number, though the highest assigned number (CEVF or RH61 according to the  ISBT  terminology) is not an accurate reflection of the antigens encountered since many (e.g. Rh38) have been combined, reassigned to other groups, or otherwise removed. [ 43 ] :\u200a324"}
{"_id": "WikiPedia_Hematology$$$corpus_7733", "text": "Some of the other Rh \"antigens\" are f (\"ce\", RH6), Ce (RH7), C w  (RH8), C x  (RH9), V (RH10), E w  (RH11), G (RH12), Tar (RH40), VS (RH20), D w  (RH23), and CE (RH22). Some of these groups, including f, Ce and CE, describe grouping of some existing groups. Others, like V, describe an  epitope  created by some other mutation on the  RHD  and  RHCE  genes. V in particular is caused by a mutation on  RHCE . [ 48 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7734", "text": "The term \"Rh\" was originally an abbreviation of \"Rhesus factor\". It was discovered in 1939 by  Karl Landsteiner  and  Alexander S. Wiener , who, at the time, believed it to be a similar antigen found in  rhesus macaque  red blood cells. It was subsequently discovered that the human factor is not identical to the rhesus monkey factor, but by then, \"Rhesus Group\" and like terms were already in widespread, worldwide use. Thus, notwithstanding it is a misnomer, the term survives (e.g.,  rhesus blood group system  and the obsolete terms  rhesus factor ,   rhesus positive , and  rhesus negative  \u2013 all three of which actually refer specifically and  only  to the Rh D factor and are thus misleading when unmodified). Contemporary practice is to use \"Rh\" as a term of art instead of \"Rhesus\" (e.g., \"Rh Group\", \"Rh factors\", \"Rh D\", etc.)."}
{"_id": "WikiPedia_Hematology$$$corpus_7735", "text": "The significance of their discovery was not immediately apparent and was only realized in 1940, after subsequent findings by  Philip Levine  and Rufus Stetson. [ 42 ]   The serum that led to the discovery was produced by immunizing rabbits with red blood cells from a  rhesus macaque . The antigen that induced this immunization was designated by them as  Rh factor  to indicate that  rhesus  blood had been used for the production of the serum. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7736", "text": "In 1939, Phillip Levine and Rufus Stetson published in a first case report the clinical consequences of non-recognized  Rh factor , hemolytic  transfusion reaction , and  hemolytic disease of the newborn  in its most severe form. [ 50 ]  It was recognized that the serum of the reported woman  agglutinated  with  red blood cells  of about 80% of the people although the then known blood groups, in particular  ABO  were matched. No name was given to this  agglutinin  when described. In 1940, Landsteiner and Wiener made the connection to their earlier discovery, reporting a serum that also reacted with about 85% of different human red blood cells. [ 51 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7737", "text": "In 1941, Group O: a patient in  Irvington, New Jersey , US, delivered a normal [ clarification needed ]  infant in 1931; this pregnancy was followed by a long period of sterility. The second pregnancy (April, 1941) resulted in an infant with  icterus gravis . [ 52 ]  In May 1941, the third anti-Rh serum (M.S.) of Group O became available. [ 52 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7738", "text": "Based on the serologic similarities, 'Rh factor' was later also used for antigens, and  anti-Rh  for antibodies, found in humans such as those previously described by Levine and Stetson. Although differences between these two sera were shown already in 1942 and clearly demonstrated in 1963, the already widely used term \"Rh\" was kept for the clinically described human antibodies which are different from the ones related to the rhesus monkey. This real factor found in  rhesus macaque  was classified in the  Landsteiner-Weiner antigen system  (antigen LW, antibody anti-LW) in honor of the discoverers. [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7739", "text": "It was recognized that the  Rh factor  was just one in a system of various antigens. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use."}
{"_id": "WikiPedia_Hematology$$$corpus_7740", "text": "The clinical significance of this highly immunizing D antigen (i.e., Rh factor) was soon realized. Some keystones were to recognize its importance for blood transfusion (including reliable diagnostic tests), hemolytic disease of the newborn (including  exchange transfusion ), and very importantly the prevention of it by screening and  prophylaxis ."}
{"_id": "WikiPedia_Hematology$$$corpus_7741", "text": "The discovery of  cell-free fetal DNA  in maternal circulation by Holzgrieve et al. led to the noninvasive genotyping of fetal Rh genes in many countries."}
{"_id": "WikiPedia_Hematology$$$corpus_7742", "text": "Rh deficiency syndrome  is a type of  hemolytic anemia  that involves  erythrocytes  whom membranes are deficient in  Rh antigens . It is considered a rare condition. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7743", "text": "Clinically, people with Rh deficiency show mild to moderate chronic  hemolytic anemia  with variable degrees of spherostomatocytosis. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7744", "text": "The condition is caused by silent alleles at the RH locus (amorph type) or suppressor genes unrelated to the locus (regulator type) that individuals inherit in an autosomal recessive manner. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7745", "text": "Vos originally described\u00a0Rh-deficiency syndrome\u00a0in 1961, when a sample of blood failed to respond with several Rh antisera. However, R. Ceppellini used the term \"Rhnull\" for the first time. So far, at least 43 people from 14 families have been reported in the literature as having the Rhnull phenotype. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7746", "text": "6005"}
{"_id": "WikiPedia_Hematology$$$corpus_7747", "text": "19743"}
{"_id": "WikiPedia_Hematology$$$corpus_7748", "text": "ENSG00000112077"}
{"_id": "WikiPedia_Hematology$$$corpus_7749", "text": "ENSMUSG00000023926"}
{"_id": "WikiPedia_Hematology$$$corpus_7750", "text": "Q02094"}
{"_id": "WikiPedia_Hematology$$$corpus_7751", "text": "Q9QUT0"}
{"_id": "WikiPedia_Hematology$$$corpus_7752", "text": "NM_000324"}
{"_id": "WikiPedia_Hematology$$$corpus_7753", "text": "NM_011269"}
{"_id": "WikiPedia_Hematology$$$corpus_7754", "text": "NP_000315"}
{"_id": "WikiPedia_Hematology$$$corpus_7755", "text": "NP_035399"}
{"_id": "WikiPedia_Hematology$$$corpus_7756", "text": "Rh-associated glycoprotein  ( RHAG ) is an  ammonia transporter   protein  that in humans is encoded by the  RHAG   gene . [ 5 ] [ 6 ]  RHAG has also recently been designated  CD241  ( cluster of differentiation  241). Mutations in the RHAG gene can cause  stomatocytosis . [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7757", "text": "The  Rh blood group  antigens (MIM 111700) are associated with human erythrocyte membrane proteins of approximately 30 kD, the so-called Rh30 polypeptides. Heterogeneously glycosylated membrane proteins of 50 and 45 kD, the Rh50 glycoproteins, are coprecipitated with the Rh30 polypeptides on immunoprecipitation with anti-Rh-specific mono- and polyclonal antibodies. The Rh antigens appear to exist as a multisubunit complex of CD47 (MIM 601028), LW (MIM 111250), glycophorin B (MIM 111740), and play a critical role in the Rh50 glycoprotein [supplied by OMIM]. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7758", "text": "RHAG has been shown to  interact  with  ANK1 . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7759", "text": "Secretor status  refers to the presence or absence of water-soluble  ABO blood group antigens  in a person's  bodily fluids , such as  saliva ,  tears ,  breast milk ,  urine , and  semen . People who secrete these antigens in their bodily fluids are referred to as  secretors , while people who do not are termed  non-secretors . Secretor status is controlled by the  FUT2  gene (also called the  Se  gene), and the secretor  phenotype  is inherited in an  autosomal   dominant  manner, being expressed by individuals who have at least one functioning copy of the gene. The non-secretor phenotype ( se ) is a  recessive trait . [ 1 ] :\u200a125\u20137\u200a  Approximately 80% of White people are secretors, while 20% are non-secretors. Non-secretors have reduced susceptibility to the most common strains of  norovirus . [ 2 ]  Expression of the antigens in the  Lewis blood group  is also affected by secretor status: non-secretors cannot produce the Le(b) antigen. [ 3 ] :\u200a190"}
{"_id": "WikiPedia_Hematology$$$corpus_7760", "text": "The expression of  ABO blood group antigens  is determined by the interaction of three genes: the  ABO gene , which controls expression of the A and B antigens; the  FUT1  or  H  gene, which controls expression of the  H antigen , the precursor of ABO antigens; and the secretor gene,  FUT2  or  Se . All of these genes encode  glycosyltransferases , which are  enzymes  that add  sugars  to precursor substances to create new substances. [ 1 ] :\u200a123"}
{"_id": "WikiPedia_Hematology$$$corpus_7761", "text": "The H antigen is required for ABO blood group antigens to be formed. [ note 1 ]  The  Se  gene, which encodes the enzyme \u03b1-2-L-fucosyltransferase, controls the formation of H antigen in bodily secretions. In people with the secretor genotype, the enzyme converts a precursor substance found in body fluids to the H antigen, which is then modified by the glycosyltransferases encoded by the ABO gene to produce the antigens corresponding to the person's ABO blood type. Because non-secretors cannot form H antigen in body fluids, they cannot express soluble ABO antigens. [ 1 ] :\u200a124\u20136"}
{"_id": "WikiPedia_Hematology$$$corpus_7762", "text": "Lewis blood group  phenotypes are controlled by the  FUT3  or  Le  gene and the  Se  gene. There are two major antigens in the Lewis system: Le(a) and Le(b). Individuals who are negative for  Le  express neither antigen and their blood type is designated as Le(a-b-). In individuals who are positive for  Le , the blood type is determined by the person's secretor status. The  Le  gene encodes a glycosyltransferase that produces the Le(a) antigen from a precursor substance. In secretors, \u03b1-2-L-fucosyltransferase modifies this precursor substance, which causes it to form Le(b) when acted on by the enzyme encoded by the  Le  gene. Thus, secretors who are positive for  Le  express the Le(a-b+) type, while non-secretors who are positive for  Le  express the Le(a+b-) blood type. [ note 2 ] [ 1 ] :\u200a178\u201381\u200a [ 3 ] :\u200a196"}
{"_id": "WikiPedia_Hematology$$$corpus_7763", "text": "Noroviruses  bind to secreted blood group antigens on the  mucosa  of the  digestive tract . [ 4 ] :\u200a537\u200a  Because non-secretors do not express these antigens, they exhibit decreased susceptibility to most strains of the disease. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7764", "text": "Secretor status can be determined through genotyping or through  serologic  methods. In the serologic method, the person's saliva is boiled, then added to  reagents  containing  antibodies  against the A, B, and H antigens.  Red blood cells  expressing these antigens are then added to the saliva-reagent mixtures. If the person is a secretor, the antibodies will bind to the antigens in their saliva rather than the red blood cells, and will not cause red blood cells to  agglutinate . [ 5 ] :\u200a25"}
{"_id": "WikiPedia_Hematology$$$corpus_7765", "text": "Secretor status testing was historically used in  forensic science , but this has been made obsolete by advances in  DNA testing . [ 6 ] :\u200a226"}
{"_id": "WikiPedia_Hematology$$$corpus_7766", "text": "Approximately 80% of Caucasian people possess the  Se  gene and are secretors; the other 20% are non-secretors. [ 2 ]  The  frequency  of the  Se  gene is approximately 50% in most ethnic groups, but  Aboriginal Australians ,  Inuit , and some  Native American  and  Melanesian  groups exhibit a frequency of nearly 100%, while the frequency is only 22% in South India. [ 5 ] :\u200a25"}
{"_id": "WikiPedia_Hematology$$$corpus_7767", "text": "Selective immunoglobulin A (IgA) deficiency  ( SIgAD [ 1 ] ) is a kind of  immunodeficiency , a type of  hypogammaglobulinemia . People with this deficiency lack  immunoglobulin A  (IgA), a type of  antibody  that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable serum IgA level in the presence of normal serum levels of  IgG  and  IgM , in persons older than 4 years. It is the most common of the primary antibody deficiencies. Most such persons remain healthy throughout their lives and are never diagnosed."}
{"_id": "WikiPedia_Hematology$$$corpus_7768", "text": "85\u201390% of IgA-deficient individuals are asymptomatic, although the reason for lack of symptoms is relatively unknown and continues to be a topic of interest and controversy. [ 2 ]  Some patients with IgA deficiency have a tendency to develop recurrent sinopulmonary infections, gastrointestinal infections and disorders, allergies, autoimmune conditions, and malignancies. [ 2 ]  These infections are generally mild and would not usually lead to an in-depth workup except when unusually frequent. They rarely present with severe reactions, including  anaphylaxis , to  blood transfusions  or  intravenous immunoglobulin  due to the presence of IgA in these blood products.  Patients have an increased susceptibility to  pneumonia  and recurrent episodes of other  respiratory infections  and a higher risk of developing  autoimmune diseases  in middle age. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7769", "text": "IgA deficiency and  common variable immunodeficiency  (CVID) feature similar  B cell   differentiation  arrests, [ 4 ]  but it does not present the same  lymphocyte  subpopulation abnormalities. [ 5 ]  IgA-deficient patients may progress to  panhypogammaglobulinemia  characteristic of  CVID . [ 4 ]  Selective IgA and  CVID  are found in the same family. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7770", "text": "Selective IgA deficiency is inherited in less than half of cases, [ 6 ]  but has been associated with differences in  chromosomes   18 ,  14  and  6 . Selective IgA deficiency is often inherited, but fewer than half of all cases  but has been associated with some  congenital intrauterine infections . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7771", "text": "Pathogenesis of IgA Deficiency"}
{"_id": "WikiPedia_Hematology$$$corpus_7772", "text": "\u2018In IgA-deficient patients, the common finding is a maturation defect in B cells to produce IgA\u2019. \u2018In IgA deficiency, B cells express IgA; however, they are of immature  phenotype  with the coexpression of IgM and IgD, and they cannot fully develop into IgA-secreting plasma cells\u2019.  [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7773", "text": "There is an inherited inability to produce  immunoglobulin A (IgA) , a part of the body's defenses against infection at the body's surfaces (mainly the surfaces of the respiratory and digestive systems).  As a result, bacteria at these locations are somewhat more able to cause disease. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7774", "text": "Types include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7775", "text": "When suspected, the diagnosis can be confirmed by laboratory measurement of IgA level in the blood.  SIgAD is an IgA level < 7\u00a0mg/dL with normal IgG and IgM levels (reference range 70\u2013400\u00a0mg/dL for adults; children somewhat less). [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7776", "text": "The treatment consists of identification of co-morbid conditions, preventive measures to reduce the risk of infection, and prompt and effective treatment of infections. Infections in an IgA-deficient person are treated as usual (i.e., with antibiotics). There is no treatment for the underlying disorder. [ 11 ]  All SIgAD patients, even if asymptomatic, should receive pneumococcal and influenza vaccines, but should avoid live attenuated vaccines. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7777", "text": "There is a historical popularity in using  intravenous immunoglobulin  (IVIG) to treat SIgAD, but the consensus is that there is no evidence that IVIG treats this condition. [ 13 ] [ 14 ] [ 15 ]   In cases where a patient presents SIgAD and another condition which is treatable with IVIG, then a physician may treat the other condition with IVIG. [ 14 ]  The use of IVIG to treat SIgAD without first demonstrating an impairment of specific antibody formation is not recommended. [ 14 ] [ 16 ] [ 17 ] [ 15 ] [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7778", "text": "Prognosis is excellent, although there is an association with  autoimmune disease .  Of note, selective IgA deficiency can complicate the diagnosis of one such condition,  celiac disease , as the deficiency masks the  high levels of certain IgA antibodies  usually seen in celiac disease. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7779", "text": "As opposed to the related condition  CVID , selective IgA deficiency is not associated with an increased risk of  cancer . [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7780", "text": "Patients with Selective IgA deficiency rarely have severe reactions to blood transfusions. [ 20 ]  Although Selective IgA deficiency is common, [ 21 ] [ 22 ] [ 23 ]  severe reactions to blood transfusions are very rare. [ 20 ] [ 22 ] [ 24 ]   People with selective IgA deficiency do not require special blood products unless they have a history of a severe allergic reaction to a blood transfusion. [ 25 ] [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7781", "text": "Prevalence varies by population, but is on the order of 1 in 100 to 1 in 1000 people, [ 21 ]  making it relatively common. SIgAD occurs in 1 in 39 to 1 in 57 people with celiac disease. This is much higher than the prevalence of selective IgA deficiency in the general population. [ 28 ]  It is also significantly more common in those with type 1  diabetes . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7782", "text": "It is more common in males than in females. [ 29 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7783", "text": "EDAR  ( EDAR hypohidrotic ectodermal dysplasia )"}
{"_id": "WikiPedia_Hematology$$$corpus_7784", "text": "3NVQ"}
{"_id": "WikiPedia_Hematology$$$corpus_7785", "text": "8482"}
{"_id": "WikiPedia_Hematology$$$corpus_7786", "text": "20361"}
{"_id": "WikiPedia_Hematology$$$corpus_7787", "text": "ENSG00000138623 ENSG00000288455"}
{"_id": "WikiPedia_Hematology$$$corpus_7788", "text": "ENSMUSG00000038264"}
{"_id": "WikiPedia_Hematology$$$corpus_7789", "text": "O75326"}
{"_id": "WikiPedia_Hematology$$$corpus_7790", "text": "Q9QUR8"}
{"_id": "WikiPedia_Hematology$$$corpus_7791", "text": "NM_003612 NM_001146029 NM_001146030"}
{"_id": "WikiPedia_Hematology$$$corpus_7792", "text": "NM_011352"}
{"_id": "WikiPedia_Hematology$$$corpus_7793", "text": "NP_001139501 NP_001139502 NP_003603"}
{"_id": "WikiPedia_Hematology$$$corpus_7794", "text": "NP_035482"}
{"_id": "WikiPedia_Hematology$$$corpus_7795", "text": "Semaphorin 7A, GPI membrane anchor  ( John Milton Hagen blood group ) ( SEMA7A ) also known as  CD108  ( C luster of  D ifferentiation 108), is a human  gene . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7796", "text": "SEMA7A is a membrane-bound  semaphorin  that associates with cell surfaces via a glycosylphosphatidylinositol (GPI) linkage. SEMA7A is also known as the John-Milton-Hagen (JMH) blood group antigen, an 80-kD glycoprotein expressed on activated  lymphocytes  and  erythrocytes .[supplied by OMIM] [ 5 ]  SEMA7A is expressed in various adult tissues such as adipose, colon, esophagus, heart, brain, spleen, testis, lung, ovary, and uterus. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7797", "text": "SEMA7A promotes axonal growth and is involved in  mesoderm  derived somite formation. Murine embryonic Sema7A expression is highest on day 7, which is indicative of its role on the differentiation of germ layer structure. [ 7 ]  Embryonic Sema7A expression is noticeable at all developmental stages as well as in the newborn and adult thymus, indicative of a development T-cell role. [ 7 ]  In wild type neurons, addition of Sema7A under  in vitro  conditions promotes elongation and branching in a dose dependent manner. [ 8 ]  Unlike the majority of semaphorins, SEMA7A enhances axonal growth and is imperative for proper embryonic axonal tract formation. [ 9 ]  Limited expression of SEMA7A is found in the hindbrain as opposed to an abundance of SEMA7A expression found in both the cranial and trunk neural crest cells, which indicates an involvement in migration and differentiation. [ 10 ]  Sema7A -/- mice show defects in olfactory tract development. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7798", "text": "In normal breast tissue, mRNA expression of SEMA7A is low or not expressed, but activation to re-express SEMA7A occurs in these adult tissues to cause pleiotropic effects which increase tumorigenesis. [ 12 ] [ 13 ]  Tumor cell growth, EMT, lung metastasis and angiogenesis have been linked to increased Sema7a expression in murine models. [ 14 ] [ 15 ] [ 16 ]  Increased SEMA7A expression correlates with poor prognosis in breast cancer patients. [ 13 ]  Tumors increase SEMA7A expression in an involuting environment, but knockout of SEMA7a in mouse models undergoing involution decreases lymphangiogenesis. [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7799", "text": "This protein is known to have eight variants in the extracellular region: seven lie within the Sema domain and one within the PSI domain. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7800", "text": "This protein forms dimers. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7801", "text": "This protein acts as a receptor for the malaria parasite  Plasmodium falciparum ."}
{"_id": "WikiPedia_Hematology$$$corpus_7802", "text": "Serious Hazards of Transfusion (SHOT)  is the  United Kingdom 's haemovigilance scheme."}
{"_id": "WikiPedia_Hematology$$$corpus_7803", "text": "It collects and analyses anonymized information on  adverse events  and  blood transfusion  reactions. When SHOT has identified risks related to transfusion, it produces recommendations within its annual reports to improve  patient safety . These reports are freely available on its website."}
{"_id": "WikiPedia_Hematology$$$corpus_7804", "text": "SHOT, together with the  Medicines and Healthcare products Regulatory Agency (MHRA) , works to support haemovigilance reporting in the UK."}
{"_id": "WikiPedia_Hematology$$$corpus_7805", "text": "SHOT's statistical data has been used to decrease  bacterial infections  through better skin cleansing procedures and the incidence of life-threatening  transfusion-related acute lung injury  (TRALI) in the UK, by discouraging the use of  fresh frozen plasma  from female donors. [ 1 ]  The cause of TRALI is not fully understood, and may have more than one mechanism, [ 2 ]  but most cases are associated with transfusion of plasma or other blood products that contain some  antibodies  that the donor developed during  pregnancy . [ 3 ] [ 4 ]   Not using plasma donation from female donors for transfusions eliminates the risk of exposing the recipient to pregnancy-related antibodies, and therefore reduces the risk of TRALI. [ 4 ]   The collected information has also provided evidence to support the pre-existing practice of leukodepletion (depleting the number of  leukocytes , or white blood cells, from the product) to reduce the risk of transfusion-associated  graft-versus-host disease  and  post-transfusion purpura  in immunocompromised patients. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7806", "text": "SHOT's data has also focused attention on  human errors , with the result that staff training and procedures have been improved.  For example, SHOT's data demonstrated that increasing the use of wristbands for patient identification and portable, bedside  barcode readers  reduced the risk of an error caused by  human factors . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7807", "text": "SHOT was established in 1996. [ 5 ]   During the first ten years, it collected more than 2,000 confidential reports about  transfusion safety  problems or  near misses . [ 5 ]   During the first two years of voluntary reports, about half of these errors involved giving the wrong  type of blood  or blood component to a patient. [ 6 ]   This happens, for example, if hospital staff accidentally take the wrong item out of the blood bank refrigerator. [ 6 ]   Less than 1% of errors resulted in an infection. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7808", "text": "By 2012, almost all NHS hospitals, trusts, and health boards had registered with SHOT and were submitting reports. [ 1 ]   Participation is now mandatory. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7809", "text": "The \"Better Blood Transfusion\" strategy by the UK's Department of Health was based on evidence collected by SHOT. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7810", "text": "Solvent detergent plasma  is a form of  blood plasma  made from plasma collected from many people which is then processed with  solvents  as a form of  virus processing , to try to get rid of  viruses . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7811", "text": "Stem cell   fat grafting  is the  autotransplantation  of adipose-derived stem cells (ADSCs) extracted from fat-abundant donor sites (e.g. thigh or stomach) to other areas such as the face, breast, and hip to reconstruct the operative areas into desirable shapes. [ 1 ]  ADSCs are  multipotent   stem cells  found in adipose tissues, displaying similar  differentiation  potentials to bone marrow-derived  mesenchymal stem cells  (BM-MSCs). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7812", "text": "The discovery of ADSCs brought advances to the field of regenerative medicine and aesthetic procedures. While the use of embryonic stem cells was reconsidered for ethical reasons, ADSCs were noticed by plastic surgeons for their characteristics such as  pluripotent   differentiation  potential,  paracrine  activities,  immunomodulatory  functions, and homing effect. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7813", "text": "Regardless of the numerous benefits, there are few side effects and  oncology  safety issues. The rising investment in stem cell cosmetic therapy reflects high expectation and demands, especially in South Korea.  Further research on the effectiveness of ADSCs grafting proposed that the aftermath of the therapy can be affected by the quality of stem cells and diet by fostering adequate conditions for stem cell growth and sufficient consumption of nutrients. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7814", "text": "James Thomson  at the University of Wisconsin first isolated human  embryonic stem cells  in 1998. However, due to the ethical controversies regarding embryonic stem cells,  induced pluripotent stem cells  (iPSCs) were proposed as a substitute. The remaining oncological concern of iPSCs was eased by suggesting  adult stem cells  as the most primary resource of  regenerative medicine . [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7815", "text": "The first isolation of mesenchymal stem cells from the bone marrow was done by Friednstein  et al.  in 1986 and considered as a primary clinical stem cell source. However, the painful acquisition and low cell yield limited further research. Zuk  et al.  later isolated ADSCs and found them to have the same potential as BM-MSCs. Although later other stem cells were identified from different parts of the human body, ADSCs were considered to be the safest as it was the easiest stem cell to isolate and did not require cell expansion, and so they are still used as a primary source of fat transfer therapies. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7816", "text": "The concept of autologous fat grafting was first suggested in 1893. The first report described that the adipose tissue without changing its structure was implanted to the adherent scars from  osteomyelitis . The result was successful and soon widely used in different fields of aesthetic procedures such as breast augmentation and  rhinoplasties . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7817", "text": "In 1978, a  liposuction  procedure was invented to remove the excessive fat depositions. Later, Illouz found that this procedure is the ideal supplier of fat tissue and used impurified lipoaspirate as a transplant in 1983 and Fournier proposed a reinjection technique of aspirated fat. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7818", "text": "The third period started in 1994 when S.R. Coleman introduced the Coleman technique, which uses adipose tissue for lipid cell transfer. The lipoaspirate was centrifuged to separate the  stromal vascular fraction  (SVF), including ADSCs, from blood, tissue, fluid, and lipids, [ 3 ]  though the fat cell retention rate varied from 30% to 95%. The first theory that explains graft survival is the Cell Survival Theory, which suggests that the transfer of viable adipocytes for adequate circulation enhances the survival rate and this can be done by developing the processing and injection techniques to minimize trauma. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7819", "text": "Host replacement theory suggests that the retention rate after fat grafting is determined by the ADSCs replacing adipocytes, as the successful ADSC activation and replacement of adipocytes is related to the early death of transferred adipocytes in ischemic conditions. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7820", "text": "Fang  et al.  proposed that ADSCs are the most widely used due to their  pluripotent   differentiation  potentials,  paracrine activity  and  immunomodulatory  function. ADSCs are one type of  mesenchymal stem cells  (MSCs), and they exhibit high similarities with BM-MSCs, [ 7 ]  and they are capable of multilineage differentiation into fats,  cartilages ,  cardiac muscles ,  nerves , skins, and  Skeletal muscles . They also tend to survive for a longer period with a higher proliferative capacity than other stem cells. ADSCs secret pro- angiogenic  factors and anti- apoptotic  factors like  cytokines ,  chemokines ,  growth factors ,  mRNAs , and  microRNAs . Then, they act on different systems where they were transplanted and regenerate cells in these transplanted systems. Moreover, as ADSCs resemble BM-MSCs, they have  immunosuppressive  characteristics that inhibit both innate and adaptive immune systems. However, their capacity is even stronger than BM-MSCs by secretion of immunosuppressive factors such as  IL-6  and  TGF-B . Additionally, they perform as immune tolerators to suppress lymphocyte proliferation; such a property suggests the possibility of ADSCs being used for  xenotransplantation . [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7821", "text": "The homing effect refers to the engraftment of ADSCs to bone marrow  endothelium  due to the arrest of ADSCs within the  vasculature  of a tissue. ADSCs are engrafted to the bone marrow endothelium;  adhesion  interactions are activated to the bone marrow endothelium. Thus, such engraftment increases the probability of long-term survival of transferred fats. The homing effect follows three main processes: rolling, adhesion, and transmigration. During the rolling, ADSCs migrate and interacts with vascular endothelial cells in bone marrow in shear-resistant and low-affinity manners. As ADSCs adhere to bone marrow endothelium, MSCs express several different molecules that increase the adhesion such as  CD44 isoforms  and  integrins . As ADSCs transmigrate through vessels in bone marrow, interaction and signaling between stromal-derived chemokine factor -1 ( SDF-1 ) and receptor  CXCR4  is the most crucial process. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7822", "text": "Mechanical and enzymatic (ME) methods are the most common isolation methods, although there is no standard method. [ 11 ]  Accordingly, Glass and Ferretti proposed one of the ME methods which is to apply tumescent-assisted liposuction using a mechanical or ultrasound-assisted  liposuction cannula . Through liposuction, the fat sample is digested by enzymatic activities of  collagenase  or  trypsin  in  Dulbecco\u2019s modified Eagle's medium  (DMEM). The resultant tissue suspension undergoes incubation and agitation at around 37\u00a0\u00b0C and is filtered through a strainer to remove unnecessary  debris . The cell pallet left after  centrifugation  is the SVF, which is seeded on the plate after the second suspension with bovine calf serum, 1%  penicillin  or  streptomycin , and  L-glutamine . The adherent properties of ADSCs on the plate allow for their isolation, [ 12 ]  but due to the inconvenience of isolating the pure ADSCs, a cell-assisted lipo-transfer (CAL) is more commonly used. CAL transforms poor ADSCs into enriched ADSCs by mixing SVF isolate and aspirated fat. [ 13 ]  The efficacy of CAL was proven by the increased survival rate of autologous breast augmentation when introduced around 270 ml for each breast. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7823", "text": "Around 1.5 million women have breast implant surgeries per year, [ 15 ]  but the side effects can be severe and cause irreversible damage to the patient's body. The most well-known side effects are foreign body sensation,  calcification , fat cell  necrosis , capsular construction, rupture,  cysts  and some fat cells leaving the implanted area."}
{"_id": "WikiPedia_Hematology$$$corpus_7824", "text": "In most cases, calcification and cysts are the biggest threat of breast augmentation surgery. Fat stem cells that fail to pick up a new blood supply will die and be removed from the body by immune cells. However, if they are missed, the cluster will lead to calcification and cyst formation. These are visible on the breast as lump sometimes and are more dangerous when these dead cells are detected as cancer cells, which hinders an accurate diagnosis of  breast cancer . The calcified tissue will be diagnosed as a benign cancer and not cause any harm. However, if the tissue is severely damaged the entire breast needs to be removed. Once a patient is diagnosed with breast implant calcification, regular mammograms should be done to monitor the possible cancer development. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7825", "text": "Gornitsky  et al.  from McGill University conducted a  systematic review  of 4,577 patients who have received the facial fat transfer. The most prevalent side effects reported were  asymmetry , skin irregularities,  hypertrophy , prolonged  edema , and fat  necrosis . [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7826", "text": "The homing effect may have advantages in increasing the long-term survival of transferred fat, but concerns remain for patients with post-oncologic history, specifically breast cancer. It is more alarming since breast tumors are closely located with adipose tissue, as they develop a favorable  microenvironment  for cancer progression through homing and migration. [ 18 ]  There are cancer-associated  adipocytes  (CAAs) crucial for  metastasis  and the progression of tumors. Under normal conditions, the adipocytes are mature and they do not differentiate. However, when ADSCs migrate and circulate in blood vessels by the homing effect, it can result in the progression of tumor growth. Furthermore, the properties of migratory cells also promote tumor growth by secretion of trophic factors such as  adipokines  like  FGF ,  ILs  and  IGF-binding proteins ; this increases  vascularisation  as such oncogenic properties are unusual for other BM-MSCs or lung-derived MSDCs. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7827", "text": "The stem cell market has grown largely along with the increasing awareness of stem cells in regenerative medicine. The Google web search big data analysis showed that the terms  stem cell  facelift  and  stem cell breast augmentation  had 197,000 and 302,000 outcomes, respectively, according to the American Society of Plastic Surgeons. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7828", "text": "With the rising interest in stem cell cosmetic therapy, the adjacent figure demonstrates the content analysis on the 50 clinical websites that appeared on  Google  for \u201cstem cell therapy\u201d, \u201ctreatment\u201d or \u201cstem cell facelift\u201d in November 2013. The result showed that 90% of the clinics use autologous adult stem cells, 71% of clinics obtained stem cells from patient fat, 90% of procedures delivered cells through subcutaneous methods, and facial anti-ageing treatment was advertised the most in stem cell treatments as well as stem cell breast augmentation therapies. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7829", "text": "The International Association of Aesthetic Plastic Surgery announced the Korean plastic surgery market is estimated to be worth about $440 million as of 2017. It is a quarter of the world market, and the number of plastic surgeries per year ranked first (13.5 per 1,000 people per year). Korean stem cell markets formed a scale of $1.1 billion in 2016 and they are expected to grow to 26.67% annually by 2025 ($9.5 billion). [ 22 ] [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7830", "text": "In 2017 the government invested in the bio sector for the highest proportion for new drug development (13%), and only 4% on stem cells ($112 million). CartistemTM, Inc. Medipost published successfully developed stem cell-based degenerative knee cartilage therapy and has achieved more than 10 billion sales since 2017. [ 22 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7831", "text": "Behind the large stem cell cosmetic therapy market size of South Korea, non-specialists  practice without a license  in some clinics. According to the  National Statistical Office , the number of plastic surgeons was 1,924 in 2018, and the Korean Plastic Surgery Association estimates that non-specialists in cosmetic surgery will be about 10 times that of specialists."}
{"_id": "WikiPedia_Hematology$$$corpus_7832", "text": "Dr. Shin mentioned, \"There have been similar surgeries that advocate stem cell breast plastic surgery recently. When receiving stem cell breast surgery, patients need to check whether the doctor has officially proved and whether the hospital has stem cell researchers and high-quality equipment.\" [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7833", "text": "Studies have shown that diet is closely related to stem cell proliferation and performance. Among numerous chemicals that affect the entire stem cell differentiation and settlement process, it is shown that taking extra supplements such as below can help stem cells to function better."}
{"_id": "WikiPedia_Hematology$$$corpus_7834", "text": "The word \"syngenic\" or \"syngeneic\" (from the Greek word for a relative) means genetically identical, or sufficiently identical and immunologically compatible as to allow for transplantation. For example, it may be used for something transplanted from an  identical twin . When the cells are collected from the same patient on whom they will be used, a graft is called  autologous .  Syngeneic  refers to a graft transferred between genetically identical animals or people. [ 1 ]  A syngeneic graft is known as an  isograft . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7835", "text": "Related terms include: [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7836", "text": "Tranexamic acid  is a medication used to treat or prevent excessive  blood loss  from  major trauma ,  postpartum bleeding , surgery,  tooth removal ,  nosebleeds , and  heavy menstruation . [ 6 ] [ 7 ]  It is also used for  hereditary angioedema . [ 6 ] [ 2 ]  It is taken either  by mouth ,  injection into a vein , [ 6 ]  or by intramuscular injection."}
{"_id": "WikiPedia_Hematology$$$corpus_7837", "text": "Tranexamic acid is a synthetic  analog  of the  amino acid   lysine . It serves as an  antifibrinolytic  by reversibly binding four to five lysine receptor sites on  plasminogen . This decreases the conversion of plasminogen to plasmin, preventing  fibrin  degradation and preserving the framework of fibrin's matrix structure. [ 4 ]  Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue,  \u03b5-aminocaproic acid . [ citation needed ]  Tranexamic acid also directly inhibits the activity of plasmin with weak potency ( IC 50  = 87 mM), [ 8 ]  and it can block the active-site of  urokinase plasminogen activator  (uPA) with high specificity ( Ki  = 2 mM), one of the highest among all the  serine proteases . [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7838", "text": "Side effects are rare; [ 2 ]  they include changes in  color vision ,  seizures ,  blood clots , and  allergic reactions . [ 2 ]  Tranexamic acid appears to be safe for use during pregnancy and breastfeeding. [ 2 ] [ 10 ]  Tranexamic acid is an  antifibrinolytic  medication. [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7839", "text": "Tranexamic acid was first made in 1962 by Japanese researchers Shosuke and  Utako Okamoto . [ 12 ]  It is on the  World Health Organization's List of Essential Medicines . [ 13 ]  Tranexamic acid is available as a  generic drug . [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7840", "text": "Tranexamic acid is frequently used following major trauma. [ 15 ]  Tranexamic acid is used to prevent and treat blood loss in a variety of situations, such as dental procedures, heavy menstrual bleeding, and surgeries with high risk of blood loss. [ 16 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7841", "text": "Tranexamic acid has been found to decrease the risk of death due to any cause in people who have significant bleeding due to  trauma . [ 18 ] [ 19 ] [ 20 ] [ 21 ]  It is most effective if taken within the first three hours following major trauma. [ 22 ]  It also decreases the risk of death if given within the first three hours of brain injury. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7842", "text": "Tranexamic acid is sometimes used to treat heavy menstrual bleeding. [ 17 ]  When taken by mouth it both safely and effectively treats regularly occurring heavy menstrual bleeding and improves quality of life. [ 4 ] [ 24 ] [ 25 ]  Another study demonstrated that the dose does not need to be adjusted in females who are between ages 12 and 16. [ 4 ]  In a 10-year study, tranexamic acid and other oral medicines (mefenamic acid) were found to be as effective as the  levonorgestrel intrauterine coil ; the same proportion of women had not had surgery for heavy bleeding and had similar improvements in their quality of life. [ 26 ] [ 27 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7843", "text": "Tranexamic acid is sometimes used (often in conjunction with  oxytocin ) to reduce bleeding after childbirth. [ 28 ]  Death due to  postpartum bleeding  is reduced in women receiving tranexamic acid. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7844", "text": "In the United States, tranexamic acid is FDA-approved for short-term use in people with severe bleeding disorders who are about to have dental surgery. [ 35 ]  Tranexamic acid is used for a short period before and after the surgery to prevent major blood loss and decrease the need for blood transfusions. [ 36 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7845", "text": "Tranexamic acid is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time; e.g., from acquired or inherited disorders. [ 37 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7846", "text": "In China, tranexamic acid is allowed in over-the-counter toothpaste, with six products using the drug. As of 2018 [update] , there are no limits on dosage, nor requirements for labeling the concentration. [ 38 ]  0.05% TXA in toothpaste is allowed OTC in Hong Kong. [ 39 ]  <5% TXA in over-the-counter toothpaste is first patented and marketed by  Lion Corporation  in Japan, [ 40 ]  where it is still sold. [ 41 ]  Presence of unauthorized TXA has led to the Canadian recall of a  Yunnan Baiyao  toothpaste in 2019. [ 42 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7847", "text": "There is not enough evidence to support the routine use of tranexamic acid to prevent bleeding in people with blood cancers. [ 43 ]  However, several trials are currently assessing this use of tranexamic acid. [ 43 ]  For people with inherited bleeding disorders (e.g.  von Willebrand's disease ), tranexamic acid is often given. [ 44 ]  It has also been recommended for people with acquired bleeding disorders (e.g.,  directly acting oral anticoagulants  (DOACs)) to treat serious bleeding. [ 45 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7848", "text": "The use of tranexamic acid, applied directly to the area that is bleeding or taken by mouth, appears useful to treat  nose bleeding  compared to packing the nose with cotton pledgets alone. [ 46 ] [ 47 ] [ 48 ]  It decreases the risk of rebleeding within 10 days. [ 49 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7849", "text": "Tranexamic acid can be used in skincare products as a cosmetic active to reduce the appearance of inflammation and hyperpigmentation. [ citation needed ]  Tranexamic acid is a  zwitterion  amino acid, and has a low permeability coefficient in the  stratum corneum . [ 50 ]  Tranexamic acid can be combined with penetration enhancers and microneedling to overcome this limitation. [ 51 ]  Cosmetic uses may also employ lipophilic derivatives of tranexamic acid (ester prodrugs like  Cetyl tranexamate mesylate ) that are not zwitterionic and thus have improved skin permeability. [ 52 ] [ 53 ] [ 54 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7850", "text": "Side effects are rare. [ 2 ]  Reported adverse events include  seizures , changes in  color vision ,  blood clots , and  allergic reactions  such as  anaphylaxis . [ 2 ]  Whether the risk of  venous thromboembolism  (blood clots) is increased is a matter of debate. The risk is mentioned in the product literature, [ 4 ]  and they were reported in  post marketing experience . [ 4 ]  Despite this, and the inhibitory effect of tranexamic acid on blood clot breakdown, large studies of the use of tranexamic acid have not shown an increase in the risk of venous or arterial thrombosis, [ 55 ] [ 56 ]  even in people who had previously experienced thrombosis under other circumstances. [ 56 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7851", "text": "Tranexamic acid was first synthesized in 1962 by Japanese researchers Shosuke and  Utako Okamoto . [ 12 ]  It is on the  World Health Organization's List of Essential Medicines . [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7852", "text": "Tranexamic acid is marketed in the US and Australia in tablet form as Lysteda [ 4 ]  and in Australia, Sweden [ 58 ]  and Jordan it is marketed in an  IV  form and tablet form as Cyklokapron, in the UK and Sweden [ 58 ]  as Cyclo-F. In the UK it is also marketed as Femstrual, in Asia as Transcam, in Bangladesh as Intrax & Tracid, in India as Pause, in Pakistan as Transamin, in Indonesia as Kalnex, in South America as Espercil, in Japan as Nicolda, in France, Poland, Belgium, and Romania as Exacyl and in Egypt as Kapron. In the Philippines, its capsule form is marketed as Hemostan and in Israel as Hexakapron. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7853", "text": "The US Food and Drug Administration (FDA) approved tranexamic acid oral tablets (brand name Lysteda) for the treatment of heavy menstrual bleeding in November 2009. [ 4 ] [ 59 ] [ 60 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7854", "text": "In March 2011, the status of tranexamic acid for the treatment of  heavy menstrual bleeding  was changed in the UK, from POM (Prescription only Medicines) to P (Pharmacy Medicines) [ 61 ]  and became available  over the counter  in UK pharmacies under the brand names of Cyklo-F and Femstrual. [ 62 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7855", "text": "Tranexamic acid might alleviate  neuroinflammation  in some experimental settings. [ 63 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7856", "text": "Tranexamic acid can be used in case of postpartum hemorrhage; it can decrease the risk of death due to bleeding by one third according to the WHO. [ 64 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7857", "text": "Tentative evidence supports the use of tranexamic acid in  hemoptysis . [ 65 ] [ 66 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7858", "text": "In  hereditary angioedema [ 67 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7859", "text": "In  hereditary hemorrhagic telangiectasia : tranexamic acid has been shown to reduce the frequency of  epistaxis  in patients with severe and frequent nosebleed episodes from hereditary hemorrhagic telangiectasia. [ 68 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7860", "text": "In  melasma : tranexamic acid is sometimes used in skin whitening as a topical agent, injected into a lesion, or taken by mouth, both alone and as an adjunct to laser therapy; as of 2017 its safety seemed reasonable but its efficacy for this purpose was uncertain because there had been no large scale randomized controlled studies nor long term follow-up studies. [ 69 ] [ 70 ]  It is allowed as a  quasi-drug  for skin whitening in Japan. [ 71 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7861", "text": "In  hyphema : tranexamic acid is effective in reducing the risk of secondary hemorrhage outcomes in people with traumatic hyphema. [ 72 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7862", "text": "In  liver  resection: tranexamic acid did not reduce bleeding or transfusions but did increase complications. [ 73 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7863", "text": "Transfusional hemosiderosis  is the accumulation of  iron  in the body due to frequent  blood transfusions . Iron accumulates in the  liver  and  heart , but also  endocrine organs . Frequent blood transfusions may be given to many patients, such as those with  thalassemia ,  sickle cell disease ,  leukemia ,  aplastic anemia , or  myelodysplastic syndrome , among others. It is diagnosed with a blood  transferrin  test and a  liver biopsy . It is treated with  venipuncture ,  erythrocytapheresis , and iron  chelation therapy ."}
{"_id": "WikiPedia_Hematology$$$corpus_7864", "text": "Transfusional hemosiderosis can cause  cardiac arrhythmia  and  cardiomyopathy . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7865", "text": "Transfusional hemosiderosis is a potential side effect of frequent  blood transfusions . [ 2 ]  These may be given for a number of conditions, including:"}
{"_id": "WikiPedia_Hematology$$$corpus_7866", "text": "Hemoglobin , the oxygen-carrying molecule in a  red blood cell , contains iron. The body has limited ways to store and remove iron.  When red blood cells (RBCs) die, they are consumed by  macrophages . Transfused RBCs have shorter lifespans that native ones, so they die and are consumed more frequently by the macrophages, which causes the latter to die from excess iron which is then released into the blood. [ 2 ]  Therefore, with frequent blood transfusions, iron builds up in the body over time. [ 2 ]  This can enter the  liver ,  heart ,  pancreas , and  endocrine organs . [ 2 ]  Free iron increases the production of  oxygen radicals  (mostly  hydroxyl radicals ) that cause damage to cells (particularly their  DNA ). [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7867", "text": "Transfusional hemosiderosis can be inferred with a blood  transferrin  test. Blood  ferritin  may be increased with a number of other conditions, so is less reliable for diagnosis. [ 4 ]  A  liver biopsy  may be used, which is the most accurate diagnostic technique. [ 4 ]  The level of siderosis seen in a liver biopsy can be graded by severity. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7868", "text": "Transfusional hemosiderosis is treated with a number of therapies.  Venipuncture  ( phlebotomy ) removes  blood .  Erythrocytapheresis  filters  red blood cells  from the blood.  Chelation therapy  removes iron from the blood. [ 5 ]  This involves delivering iron  chelating agents  such as  deferoxamine ,  deferiprone  or  deferasirox . [ 5 ]  If iron overload has caused damage to end-organs, this is generally irreversible and may require  transplantation . [ clarification needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7869", "text": "Transfusion hemosiderosis can cause permanent damage to tissues that may lead to death. [ 2 ]  Tissue damage can remain even after chelation therapy. [ 2 ]  Outcomes are usually worse in patients who require blood transfusions compared to those who can have alternative therapies. [ 2 ]   Cardiomyopathy  and  cardiac arrhythmia  are often a cause of death. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7870", "text": "Ted DeVita  died of transfusional iron overload from too many  blood transfusions . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7871", "text": "There are more than 100 different titles that are used as another name to Transfusion Practitioner (TP). The most common titles used include Transfusion Practitioner, Haemovigilance Officer, Transfusion Safety Officer, Transfusion Nurse,  Patient Blood Management  (PBM) Practitioner, and PBM Nurse. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7872", "text": "The role of the TP has a long history with roles being in place since late 1990's and early 2000's in countries such as United Kingdom (UK), Australia, United States of America and Canada. [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]  A range of healthcare professionals from various clinical specialities undertakes the TP role. Many have a nursing, midwifery or scientific qualification, although, in some countries, medical officers undertake aspects of the role. [ 8 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7873", "text": "It is a specialist role focusing on patient safety through best practice and appropriate use of blood and blood products. Much of the work of TPS centres on aligning practices with local, national, or international standards and guidelines. [ 8 ] \nThere are many activities that comprise the TP role and some or all of these may be within TPs position (job) descriptions depending on the area they work, and the strategic direction of the organisation they work in. [ 9 ] [ 3 ]  TP activities aim to increase awareness and knowledge to improve clinical decision making and enhance practice. Transfusion practice require a multidisciplinary approach and TPs are seen as the link between different health professionals and departments, such as clinical and laboratory colleagues, as well as patients. [ 8 ] [ 10 ] [ 11 ]  To comply with governance, regulations and mandatory standards many organisations have established Blood Management Committees or Hospital Transfusion Committees. A TPs responsibilities include risk management, surveillance of appropriate use, coordinating patient blood  management strategies, blood waste minimisation and investigation and analysis of events. These committees ideally include multidisciplinary membership, and provide support, guidance, and endorsement of the TP activities. The TP plays an essential role in supporting the work of the committee. [ 8 ] [ 10 ] [ 6 ]  Transfusion Practitioners improve transfusion practice by promoting safe transfusion practice in a variety of ways. [ 5 ] [ 11 ]  Activities of the TP may include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7874", "text": "Haemovigilance is the set of surveillance procedures that monitors, reports, investigates, and analyses adverse events related to transfusion. It covers the entire blood transfusion chain, from blood donation and processing of blood and its components, through to their provision and transfusion to patients. These reporting systems play a fundamental role in enhancing patient safety by learning from failures and then putting system changes in place to prevent them in the future. The TP's involvement in haemovigilance within the hospital setting, starts with education of those involved in the transfusion process so they can recognise, manage, and report reactions. The TPs roles ensures clinical transfusion incidents, transfusion reactions, specimen labelling errors are investigated and report data to haemovigilance governance programmes (e.g.  SHOT  in the UK). By conducting process reviews and communicating directly with the relevant colleagues and patients, the TP can provide essential details that are needed to complete investigations. This information can assist with determining the transfusion reaction type and recommendations for future transfusion plans for the patient, or the implementation of corrective and preventative measures. National haemovigilance schemes e.g.  SHOT  provide the TP with a resource for educating clinical colleagues on transfusion safety and recommendations for best practice. [ 12 ] [ 13 ] [ 14 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7875", "text": "Developing and implementing blood management/transfusion related education sessions/programs is an important aspect of the TP role. Education can be targeted for the appropriate clinical groups (nursing, medical and allied health professionals) highlighting and promoting evidence-based practice change or national and international recommendations.  TPs act as a resource regarding transfusion and PBM information for all staff involved in the transfusion process. They develop, deliver, evaluate, and revise transfusion-practice/PBM educational content based on evidence-based practice and national/international recommendations. Education topics include, but are not limited to:"}
{"_id": "WikiPedia_Hematology$$$corpus_7876", "text": "TPs collaborate with department heads and senior management to facilitate mandatory and non-mandatory staff education/training consistent with regulatory requirements/recommendations."}
{"_id": "WikiPedia_Hematology$$$corpus_7877", "text": "Surveillance is often achieved through audits which helps to identify gaps in practice, compliance to standards and guidelines and staff knowledge deficits. Data collection through audit supports governance and practice improvement, where the results can be used to consolidate practice or drive change as required. The TP plays an important role in auditing and reporting to the blood management committee (or equivalent) to develop locally agreed action plans to implement quality improvements arising from audits. The TP liaison role between departments and clinical specialties helps them to facilitate and manage improvements/change involving and engaging appropriate stakeholders. [ 3 ] [ 10 ]  TPs participate in local, regional or national audits. Audit activities may include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7878", "text": "An example from the UK is the National Comparative Audit of Blood Transfusion (NCABT), which is a programme of clinical audits that look at the use and administration of blood and blood components in the National Health System (NHS) and independent hospitals in the UK. [ 15 ]  This audit programme's objectives are to provide evidence that blood is being prescribed and used appropriately and administered safely. It also highlights where practice is deviating from the guidelines and how this might affect patient outcomes. Data collection for these audits can be undertaken by a variety of health care professionals within the participating organisations, however the majority of the data collection and data submission is undertaken by the TP."}
{"_id": "WikiPedia_Hematology$$$corpus_7879", "text": "Patient blood management is a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood, while promoting patient safety and empowerment.\u201d TP's can play an active role in helping to establish and embed PBM practices to improve patient and safety outcomes. [ 16 ]  Some PBM practices activities that TPs could undertake include:"}
{"_id": "WikiPedia_Hematology$$$corpus_7880", "text": "The broad reach of the TP allows them to develop constructive working relationships with the many clinical users of blood products and assists with the implementation of PBM programmes. [ 3 ] [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7881", "text": "The TP role demands highly skilled and component health care professionals. Typical PT skills/abilities are:"}
{"_id": "WikiPedia_Hematology$$$corpus_7882", "text": "Information to build a business case and on TP activities. [ 9 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7883", "text": "James Challan provided a classic description of a TP : [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7884", "text": "\"She is a seemingly arbitrary woman, this TP, because she knows what she is talking about better than anyone else. She is a philosopher and a metaphysician; she has, I believe, an absolutely open mind. This, with an iron nerve, a temper of the ice-brook, and indomitable resolution, self-command, and toleration exalted from virtues to blessings, and the kindliest and truest heart that beats, these form her equipment for the noble work that she is doing for mankind, work both in theory and practice, for her views are as wide as her all-embracing sympathy.\""}
{"_id": "WikiPedia_Hematology$$$corpus_7885", "text": "A  transfusion transmitted infection  (TTI) is a  virus ,  parasite , or other potential  pathogen  that can be transmitted in  donated blood  through a  transfusion  to a recipient. The term is usually limited to known pathogens, but also sometimes includes agents such as  simian foamy virus  which are not known to cause disease."}
{"_id": "WikiPedia_Hematology$$$corpus_7886", "text": "Preventing the spread of these diseases by blood transfusion is addressed in several ways. In many cases, the blood is tested for the pathogen, sometimes with several different methodologies. Donors of blood are also screened for signs and symptoms of disease and for activities that might put them at risk for infection. If a local supply is not safe, blood may be imported from other areas.  Human immunodeficiency virus  (HIV) leads to the most well-known of the transfusion transmitted diseases,  acquired immune deficiency syndrome  (AIDS)."}
{"_id": "WikiPedia_Hematology$$$corpus_7887", "text": "Blood that is processed into medications by  fractionation  is treated in a multi-step process called  pathogen inactivation  that is analogous to  pasteurization : it destroys most viruses and bacteria in the blood. Donors are still screened and tested."}
{"_id": "WikiPedia_Hematology$$$corpus_7888", "text": "Many of these viruses are controlled through laboratory screening tests.  These fall into three basic varieties:  antibody tests ,  nucleic acid tests  (NAT), and surrogate tests.  Antibody tests look for the  immune system 's response to the infection.  Nucleic acid tests look for the genetic material of the virus itself.  The third variety are tests that are not specific to the disease but look for other related conditions. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7889", "text": "High risk activities for transfusion transmitted infections vary, and the amount of caution used for screening donors varies based on how dangerous the disease is.  Most of the viral diseases are spread by either  sexual contact  or by contact with blood, usually either  drug use , accidental  needle  injuries among health care workers, unsterilized  tattoo  and  body piercing  equipment, or through a blood transfusion or transplant.  Other  vectors  exist. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7890", "text": "Whether a donor is considered to be at \"too high\" of a risk for a disease to be allowed to donate is sometimes controversial, especially for sexual contact.  High risk sexual activity usually includes:"}
{"_id": "WikiPedia_Hematology$$$corpus_7891", "text": "HIV\u2013the virus that causes  AIDS \u2013is the most well-known of the transfusion-transmitted infections because of high-profile cases such as  Ryan White , a  haemophiliac  who was infected through  factor VIII , a blood-derived medicine used to treat the disease. Another person who died of medically acquired HIV/AIDS was Damon Courtenay, who died in 1991 due to a bad batch of factor VIII. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7892", "text": "The standard test for HIV is an  enzyme immunoassay  test that reacts with  antibodies  to the virus.  This test has a  window period  where a person will be infected but not yet have an immune response.  Other tests are used to look for donors during this period, specifically the  p24 antigen  test and  nucleic acid testing ."}
{"_id": "WikiPedia_Hematology$$$corpus_7893", "text": "In addition to the general risk criteria for viruses, blood donors are sometimes excluded if they have lived in certain parts of  Africa  where  subtypes of HIV  that are not reliably detected on some tests are found, specifically HIV group O.  People who have been in  prison  for extended periods are also excluded for HIV risk."}
{"_id": "WikiPedia_Hematology$$$corpus_7894", "text": "This section describes TTs involving  parasites  and specific  bacteria ."}
{"_id": "WikiPedia_Hematology$$$corpus_7895", "text": "Babesia microti  is transmitted by ixodes ticks and causes  babesiosis . Transfusion-associated babesiosis has been documented. [ 2 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7896", "text": "In  transfusion medicine ,  transfusion-associated circulatory overload  (aka  TACO ) is a  transfusion reaction  (an  adverse effect  of  blood transfusion ) resulting in signs or symptoms of excess fluid in the circulatory system ( hypervolemia ) within 12 hours after transfusion. [ 2 ]  The symptoms of TACO can include shortness of breath ( dyspnea ), low blood oxygen levels ( hypoxemia ), leg swelling ( peripheral edema ), high blood pressure ( hypertension ), and a high heart rate ( tachycardia ). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7897", "text": "It can occur due to a rapid transfusion of a large volume of  blood  but can also occur during a single red blood cell transfusion (about 15% of cases). [ 2 ]  It is often confused with  transfusion-related acute lung injury  (TRALI), another transfusion reaction. The difference between TACO and TRALI is that TRALI only results in symptoms of respiratory distress while TACO can present with either signs of respiratory distress, peripheral leg swelling, or both. [ 4 ]  Risk factors for TACO are diseases that increase the amount of fluid a person has, including liver, heart, or kidney failure, as well as conditions that require many transfusions. High and low extremes of age are a risk factor as well. [ 5 ] [ 6 ] [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7898", "text": "The management of TACO includes immediate discontinuation of the transfusion, supplemental oxygen if needed, and medication to remove excess fluid. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7899", "text": "The primary symptoms of TACO are signs of respiratory distress (shortness of breath, low oxygen levels in the blood) along with signs of excess fluid within the circulatory system (leg swelling, high blood pressure, and an elevated heart rate). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7900", "text": "On physical exam, patients may present with crackles when listening to the lungs, a  murmur  (S-3 murmur) when listening to the heart, leg swelling, and distended veins in the neck ( jugular venous distension ). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7901", "text": "Risk factors that can promote the development of TACO include conditions that predispose individuals to excess fluid in the circulatory system ( liver failure  causing low levels of protein in the blood ( hypoalbuminemia ), [ 5 ]   heart failure , [ 6 ] [ 7 ]   renal insufficiency , [ 6 ] [ 7 ]  or  nephrotic syndrome [ 7 ] ), conditions that place increased stress on the respiratory system ( lung disease [ 6 ] ), and conditions necessitating large volume transfusions ( severe anemia [ 6 ] ). Age has also been found to be a risk factor where individuals less than 3 years old and over 60 years old are at increased risk. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7902", "text": "In addition, the risk of TACO increases as the number of units of blood products transfused increases. [ 9 ]  Table 1 shows the volume transfused with each blood product. Multiple blood products and blood products with larger volumes increase the risk for TACO. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7903", "text": "The National Healthcare Safety Safety Network division of the  Centers for Disease Control and Prevention  (CDC) released an updated criteria table in 2021: [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7904", "text": "Patients diagnosed with TACO should have at least 1 of the following two characteristics within 12 hours after the transfusion was ended:"}
{"_id": "WikiPedia_Hematology$$$corpus_7905", "text": "Along with:"}
{"_id": "WikiPedia_Hematology$$$corpus_7906", "text": "TACO can be categorized by severity: [ 11 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7907", "text": "TACO and  transfusion-related acute lung injury  (TRALI) are both complications following a transfusion, and both can result in respiratory distress. [ 2 ]  TACO and TRALI are often difficult to distinguish in the acute situation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7908", "text": "Assessing fluid status is key in differentiating between the two. In TACO, the patient will always have a positive  fluid balance  and will often present with hypertension, jugular venous distension, elevated BNP, peripheral edema, and will respond well to  diuretics . In contrast, TRALI is not associated with fluid overload and the patient may have a positive, even, or net fluid balance. Patients with TRALI often present with hypotension, no signs of right-heart fluid overload, normal BNP, and lack of clinical improvement in response to diuretics. [ 12 ] [ 13 ] [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7909", "text": "Other causes of edema that can promote a volume-overloaded state and predispose individuals to TACO include: heart failure, renal insufficiency, nephrotic syndrome, cirrhosis, and chronic venous insufficiency. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7910", "text": "The development of TACO is thought to be due to a 2-hit mechanism. [ 15 ]  The first hit is the state of the patient and the second hit is the blood transfusion itself. A patient may be receiving blood due to any number of causes and may have heart or kidney dysfunction which can lead to excess fluid. Upon transfusion of the blood product, the patient is overwhelmed by the excess fluid and develops symptoms related to volume overload. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7911", "text": "The clinical symptoms from TACO are due to an excess of fluid within the circulatory system. As a result, there is increased pressure within the circulatory system, resulting in fluid moving into the surrounding tissues. [ 4 ]  In the lungs, the extra fluid accumulates into the air sacs within the lung, causing difficulties in oxygen getting into the blood. This results in low blood oxygen levels and shortness of breath. In the arms and legs, the fluid accumulates in the tissues, causing swelling. This is most prominent in the legs due to the effects of gravity. Conditions that predispose to increased hydrostatic pressure (heart failure and renal insufficiency) or decreased oncotic pressure (liver failure, malnutrition, nephrotic syndrome) places individuals at increased risk for TACO. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7912", "text": "Transfusion associated circulatory overload is prevented by avoiding unnecessary transfusions by following strict criteria necessitating blood transfusion, closely monitoring patients receiving transfusions, and transfusing smaller volumes of blood at a slower rate. Blood products are typically transfused at 2.0 to 2.5 ml/kg per hour but can be reduced to 1.0 ml/kg per hour for individuals at increased risk for TACO. [ 16 ]  Patients susceptible to volume overload (e.g., renal insufficiency or heart failure) may be pre-treated with a diuretic either during or immediately following transfusion to reduce the overall net fluid balance. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7913", "text": "If TACO is suspected, the transfusion is stopped immediately and the patient is sat upright to prevent the fluid from backing up into the lungs. Treatment is two-fold: respiratory support and removal of excess fluid. [ 8 ]  Patients with respiratory distress and/or hypoxemia are given supplemental oxygen or ventilatory support (through non-invasive or mechanical ventilation, if needed). To remove the excess fluid, patients are given diuretic therapy and their urine output is closely monitored to quantitate the amount removed."}
{"_id": "WikiPedia_Hematology$$$corpus_7914", "text": "The reported incidence of TACO is difficult to determine as many cases may be undetected but its incidence is estimated at 1% of all individuals receiving transfusion, with hospitalized patients being at increased risk. [ 17 ] [ 18 ]  TACO is the most commonly reported cause of transfusion-related death and major morbidity in the UK, [ 2 ]  and second most common cause in the USA. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7915", "text": "Death from pulmonary edema as the result of circulatory overload following transfusion was reported as early as 1936. [ 20 ]  However, the term 'transfusion associated circulatory overload' was not coined until the 1990s when it was seen as a separate complication following blood transfusion. [ 21 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7916", "text": "Transfusion-associated graft-versus-host disease  ( TA-GvHD ) is a rare complication of  blood transfusion , in which the immunologically competent donor  T lymphocytes  mount an immune response against the recipient's lymphoid tissue. [ 1 ]  These donor lymphocytes engraft, recognize recipient cells as foreign and mount an immune response against recipient tissues. [ 2 ]  Donor lymphocytes are usually identified as foreign and destroyed by the recipient's immune system. However, in situations where the recipient is severely immunocompromised, or when the donor and recipient  HLA  type is similar (as can occur in directed donations from first-degree relatives), the recipient's immune system is not able to destroy the donor lymphocytes. This can result in transfusion associated graft-versus-host disease. This is in contrast with organ/tissue transplant associated  GvHD , where matching HLA reduces the incident of the complication. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7917", "text": "The clinical presentation is the same as  GvHD  occurring in other settings, such as bone marrow transplantation. TA-GvHD can develop two days to six weeks after the transfusion. [ 4 ]  Typical symptoms include: [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7918", "text": "Other symptoms can include cough, abdominal pain, dyspnea and vomiting. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7919", "text": "Laboratory findings include  pancytopenia , marrow aplasia, abnormal  liver enzymes , and electrolyte imbalance (when diarrhea is present). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7920", "text": "TA-GvHD can be suspected from a  biopsy  of the affected skin or liver, [ 4 ]  and established by  HLA  analysis of the circulating lymphocytes. This testing can identify circulating lymphocytes with a different HLA type than the tissue cells of the host. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7921", "text": "In 2023, the first case of fetal-induced GvHD was reported in the New England Journal of Medicine. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7922", "text": "Prevention includes  gamma   irradiation  of the lymphocyte-containing blood components such as red blood cells, platelets and granulocytes. Irradiated blood components should be issued in the following situations: [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7923", "text": "Treatment is supportive. No available form of therapy has proven effective in treating TA-GvHD and it is fatal in more than 90% of cases. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7924", "text": "The incidence of TA-GvHD in immunocompromised patients receiving blood transfusions is estimated to be 0.1\u20131.0%, and mortality around 80\u201390%. Mortality is higher in TA-GvHD than in GvHD associated with  bone marrow transplantation , where the  engrafted  lymphoid cells in the  bone marrow  are of donor origin (in autotransplant) and therefore the immune reaction is not directed against them. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7925", "text": "The most common  causes of death  in TA-GvHD are infections and hemorrhages secondary to pancytopenia and liver dysfunction. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7926", "text": "Transfusion-related acute lung injury  ( TRALI ) is the serious  complication  of  transfusion  of  blood products  that is characterized by the rapid onset of excess fluid in the  lungs . [ 1 ]  It can cause dangerous drops in the supply of  oxygen  to body tissues. Although changes in transfusion practices have reduced the incidence of TRALI, it was the leading cause of transfusion-related deaths in the  United States  from fiscal year 2008 through fiscal year 2012. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7927", "text": "It is often impossible to distinguish TRALI from  acute respiratory distress syndrome  (ARDS). The typical  presentation  of TRALI is the sudden development of  shortness of breath , severe  hypoxemia  (O 2  saturation <90% in room air),  low blood pressure , and  fever  that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours. Although low blood pressure is considered one of the important signs for diagnosing TRALI, in some cases  high blood pressure  can occur. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7928", "text": "Delayed TRALI occurs 6 to 72 hours after transfusion completion. It is associated with a higher rate of  mortality . [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7929", "text": "The cause of TRALI is currently not fully understood. 80\u201385% of cases are thought to be  immune  mediated. [ 5 ] [ 6 ]   Antibodies  directed toward  human leukocyte antigens  (HLA) or human  neutrophil  antigens (HNA) have been implicated, with transfused antibodies shown to bind antigens expressed on pulmonary endothelial cells to initiate acute inflammation in the lungs. [ 7 ] [ 8 ]  Women who are  multiparous  (have carried more than one pregnancy to  viable gestational age ) develop these antibodies through exposure to fetal blood; transfusion of blood components obtained from these donors is thought to carry a higher risk of inducing immune-mediated TRALI. [ 6 ]  Previous transfusion or  transplantation  can also lead to donor sensitization. To be at risk of TRALI via this mechanism, the blood recipient must  express  the specific HLA or neutrophil receptors to which the implicated donor has formed antibodies. A two-hit hypothesis has been suggested [ 9 ]  wherein pre-existing pulmonary pathology (i.e., the first-hit) leads to localization of neutrophils to the pulmonary microvasculature. The second hit occurs when the aforementioned antibodies are transfused and attach to and activate neutrophils, leading to release of  cytokines  and  vasoactive  substances that induce non-cardiac  pulmonary edema . [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7930", "text": "A proposed mechanism for non-antibody-mediated TRALI involves the accumulation of bioactive lipids in stored blood components ( red cells ,  platelets , or  plasma ) that are capable of priming neutrophils. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7931", "text": "TRALI is typically associated with plasma products such as  fresh frozen plasma . TRALI can also occur in recipients of  packed red blood cells , whether adult or pediatric patients. [ 11 ]   Due to the higher risk of TRALI resulting from donations by females, the  AABB  (formerly the American Association of Blood Banks) has recommended that those blood components with a high volume of plasma not be used for transfusion, but for further processing into other  therapeutic  products. [ 12 ]  To mitigate the risk of TRALI, female donors are excluded from fresh frozen plasma donation in Germany as of 2009 if they have a history of pregnancy and there are no HLA/HNA screening results available, which has resulted in a significant reduction of TRALI reports. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7932", "text": "In TRALI, first-hit risk factors include long-term excessive alcohol use, shock, liver surgery, current smoking, higher peak airway pressure while undergoing mechanical ventilation, positive intravascular fluid balance, low levels of  interleukin-10 , and systemic  inflammation . Systemic inflammation may be reflected in the plasma cytokine profiles but also via increased levels of  C-reactive protein  (CRP), an  acute-phase protein  that rapidly increases during acute infections and inflammation and is widely used clinically as a  biomarker  of inflammation. CRP has been shown to be elevated in TRALI patients and, in a mouse  model , to functionally enable the first hit in the development of TRALI by increasing the accumulation in the lungs of a neutrophil  homologous  to  interleukin-8 . Another factor that can predispose patients to TRALI is pre-existing lung injury, which causes white blood cells to localize in the lungs' blood vessels. [ 14 ]  The second hit in TRALI may be conveyed by anti-leukocyte antibodies or other factors present in the transfusion product. In approximately 80% of cases, anti-HLA class I or II or anti-HNA antibodies are implicated as involved in triggering TRALI, although that figure may be even higher depending on the detection methods used. In the remaining 20% of TRALI cases, non\u2013antibody factors or biological response modifiers are suggested to contribute the second hit, and these may possibly include lipid mediators,  extracellular vesicles , and aged blood cells. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7933", "text": "TRALI is defined as an  acute lung injury  that is temporally related to a blood transfusion; specifically, it occurs within the first six hours following a transfusion. [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7934", "text": "It is typically associated with plasma components such as platelets and fresh frozen plasma, though cases have been reported with packed red blood cells since there is some residual plasma in the packed cells. [ 12 ]  Incidents have also been reported with other blood products including \" cryoprecipitate ,  granulocytes ,  intravenous immune globulin ,  allogeneic  and  autologous  stem cells\". [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7935", "text": "It is a diagnosis upon examination of clinical manifestations that appear within 6 hours of transfusion, such as acute respiratory distress, tachypnea, hypotension, cyanosis, and dyspnea. TRALI is an uncommon syndrome, that is due to the presence of leukocyte antibodies in transfused plasma. It is believed to occur in approximately one in every 5000 transfusions. [ 3 ]  Leukoagglutination and pooling of granulocytes in the recipient's lungs may occur, with release of the contents of leukocyte granules, and resulting injury to cellular membranes, endothelial surfaces, and potentially to lung parenchyma. In most cases leukoagglutination results in mild dyspnea and pulmonary infiltrates within about 6 hours of transfusion, and spontaneously resolves. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7936", "text": "Occasionally more severe lung injury occurs as a result of this phenomenon and  acute respiratory distress syndrome  (ARDS) results. Leukocyte filters may prevent TRALI for those patients whose lung injury is due to leukoagglutination of the donor white blood cells, but because most TRALI is due to donor antibodies to leukocytes, filters are not helpful in TRALI prevention. Transfused plasma (from any component source) may also contain antibodies that cross-react with platelets in the recipient, producing usually mild forms of posttransfusion purpura or platelet aggregation after transfusion. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7937", "text": "Another nonspecific form of immunologic transfusion complication is mild to moderate immunosuppression consequent to transfusion. This effect of transfusion is not completely understood, but appears to be more common with cellular transfusion and may result in both desirable and undesirable effects. Mild immunosuppression may benefit organ transplant recipients and patients with autoimmune diseases; however, neonates and other already immunosuppressed hosts may be more vulnerable to infection, and cancer patients may possibly have worse outcomes postoperatively. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7938", "text": "The mainstay of therapy in TRALI is  supportive care . Oxygen supplementation is employed in all reported cases of TRALI, and 72% of patients require aggressive respiratory support.  To support blood pressure, intravenous administration of fluids, as well as  vasopressors , are essential. In treating TRALI,  diuretics  are to be avoided, although they are  indicated  in the management of  transfusion associated circulatory overload .  Corticosteroids  can be beneficial. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7939", "text": "The true incidence of TRALI is unknown because of the difficulty in making the diagnosis and because of underreporting. It is estimated to occur in 1:1300 to 1:5000 transfusions of plasma-containing products. TRALI is the leading reported cause of death related to transfusion in the United States; more than 20 cases were reported per year from 2003 to 2005. [ citation needed ]  The immune mediated form of TRALI occurs approximately once every 5000 transfusions and has a mortality of 6\u20139%. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7940", "text": "Transfusion-related immunomodulation  (TRIM) refers to the transient depression of the  immune system  following  transfusion  of blood products. This effect has been recognized in groups of individuals who have undergone  kidney transplantation  or have had multiple  miscarriages . [ 1 ]  Some research studies have shown that, because of this immune depression, blood transfusions increase the risk of infections and  cancer  recurrence. However, other studies have not shown these differences and the degree of impact transfusion has on infection and tumor recurrence is not well understood. [ 2 ]  The Blood Products Advisory Committee of the  Food and Drug Administration  recommends that all transfused blood products undergo  leukocyte reduction  in order to offset the contribution of donor white blood cells to immune suppression. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7941", "text": "Twin-to-twin transfusion syndrome  ( TTTS ), also known as  feto-fetal transfusion syndrome  ( FFTS ),  twin oligohydramnios-polyhydramnios sequence  ( TOPS ) and  stuck twin syndrome , is a complication of  monochorionic   multiple pregnancies  (the most common form of  identical twin  pregnancy) in which there is disproportionate blood supply between the  fetuses . This leads to unequal levels of  amniotic fluid  between each fetus and usually leads to death of the undersupplied twin and, without treatment, usually death or a range of  birth defects  or disabilities for a surviving twin, such as underdeveloped, damaged or missing limbs,  digits  or organs (including the brain), especially  cerebral palsy . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7942", "text": "The condition occurs when the vein\u2013artery  connections  within the fetuses' shared  placenta  allow the blood flow between each fetus to become progressively imbalanced. [ 4 ]  It usually develops between week 16 and 25 of pregnancy, during peak placental growth. The cause of the developmental effects on a surviving fetus may include  necrotic   embolisms  from a dead fetus,  low blood volume  due to pooling in the dead fetus or  velamentous cord insertion  (insertion of the umbilical cord into the  chorioamniotic membranes ). [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7943", "text": "The primary treatment of TTTS is  fetoscopy  and laser  ablation  of the interconnecting blood vessels to cut off the exchange of blood between the fetuses. This treatment is associated with an 85% survival rate of at least one fetus. [ 5 ]  Other treatments include periodic removal of amniotic fluid (serial  amniocentesis ), which is associated with a 66% survival rate of at least one fetus. Without treatment, there is an almost 100% mortality rate of one or all fetuses. [ 1 ]  Even with treatment, the condition is associated with  premature birth  and a risk of cerebral palsy in a surviving fetus."}
{"_id": "WikiPedia_Hematology$$$corpus_7944", "text": "Around 5\u201315% of identical twin fetuses will go on to develop TTTS. [ 2 ]  The condition was first described by German  obstetrician   Friedrich Schatz  in 1875. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7945", "text": "As a result of sharing a single placenta, the blood supplies of  monochorionic twin  fetuses can become connected, so that they share blood circulation: although each fetus uses its own portion of the placenta, the connecting blood vessels within the placenta allow blood to pass from one twin to the other. It is thought that most monochorionic placentae have these \"shared connections\" that cross the placenta, with the net flow volumes being equal between them. This state is sometimes referred to as \"flow balance\". When the placenta has deep vein\u2013artery connection, this can cause blood flow to become unbalanced. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7946", "text": "Depending on the number, type and direction of the interconnecting  blood vessels  ( anastomoses ), blood can be transferred disproportionately from one twin (the \"donor\") to the other (the \"recipient\"), due to a state of \"flow imbalance\" imparted by new blood vessel growth across the placental \"equator\", the line that divides each baby's proportion of the shared placenta. This state of transfusion causes the donor twin to have decreased blood volume, retarding the donor's development and growth, and also decreased  urinary  output, leading to a lower than normal level of  amniotic fluid  (becoming  oligohydramnios ). The blood volume of the recipient twin is increased, which can strain the fetus's heart and eventually lead to heart failure, and also higher than normal urinary output, which can lead to excess amniotic fluid (becoming  polyhydramnios ). The demise of the fetus is typically a result of  ischemia  related to the lack of blood flow. The lack of blood flow causes  bowel atresia , brain damage, and  kidney failure . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7947", "text": "TTTS usually develops during the period of peak placental growth, starting in week 16 and proceeding through week 25; after this point, the placenta's growth decelerates, essentially stopping just after week 30. While TTTS has occasionally been detected beyond this timepoint, it is thought that its occurrence beyond week 30 may be due to a placental  embolism  that upsets the flow balance of the shared connections between the babies. TTTS is potentially lethal to either or both twins, no matter when it is detected. However, when detected past week 25, emergency delivery may be considered to rescue the babies if the TTTS is severe. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7948", "text": "Other than requiring a monochorionic twin (or higher multiple) pregnancy, the underlying causes of TTTS are not known. It is not known to be hereditary or genetic. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7949", "text": "The fetal demise of one of the twins during the second trimester of a monochorionic pregnancy can result in serious complications to the surviving fetus. Complications include  gangrenous  limbs, hands and feet,  cerebral palsy  and IQ deficits,  constriction rings  of limbs and digits,  reduced digits , skin defects,  brain cysts ,  hydranencephaly , multicystic  encephalomalacia ,  microencephaly ,  renal agenesis  and bowel atresia. There are three hypotheses explaining these complications. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7950", "text": "A staging system is commonly used to classify the severity of TTTS. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7951", "text": "Stage I : A small amount of amniotic fluid (oligohydramnios) is found around the donor twin and a large amount of amniotic fluid (polyhydramnios) is found around the recipient twin."}
{"_id": "WikiPedia_Hematology$$$corpus_7952", "text": "Stage II : In addition to the description above, the ultrasound is not able to identify the bladder in the donor twin."}
{"_id": "WikiPedia_Hematology$$$corpus_7953", "text": "Stage III : In addition to the characteristics of Stages I and II, there is abnormal blood flow in the umbilical cords of the twins."}
{"_id": "WikiPedia_Hematology$$$corpus_7954", "text": "Stage IV : In addition to all of the above findings, the recipient twin has swelling under the skin and appears to be experiencing heart failure (fetal hydrops)."}
{"_id": "WikiPedia_Hematology$$$corpus_7955", "text": "Stage V : In addition to all of the above findings, one of the twins has died. This can happen to either twin. The risk to either the donor or the recipient is roughly equal & is quite high in Stage II or higher TTTS."}
{"_id": "WikiPedia_Hematology$$$corpus_7956", "text": "The Quintero staging does not provide information about prognosis, and other staging systems have been proposed. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7957", "text": "Various treatments exist for TTTS."}
{"_id": "WikiPedia_Hematology$$$corpus_7958", "text": "This is equivalent of zero intervention. It has been associated with almost 100% mortality rate of one or all fetuses. Exceptions to this include patients that are still in Stage 1 TTTS and are past 22 weeks' gestation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7959", "text": "This procedure involves removal of amniotic fluid periodically throughout the pregnancy under the assumption that the extra fluid in the recipient twin can cause preterm labor, perinatal mortality, or tissue damage. In the case that the fluid does not reaccumulate, the reduction of amniotic fluid stabilizes the pregnancy. Otherwise, the treatment is repeated as necessary. There is no standard procedure for how much fluid is removed each time. There is a danger that if too much fluid is removed, the recipient twin could die. This procedure is associated with a 66% survival rate of at least one fetus, with a 15% risk of cerebral palsy, and average delivery occurring at 29 weeks' gestation. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7960", "text": "This procedure involves the tearing of the dividing membrane between fetuses such that the amniotic fluid of both twins mixes, under the assumption that pressure is different in either amniotic sac and that its equilibration will ameliorate progression of the disease. It has not been proven that pressures are different in either amniotic sac. Use of this procedure can preclude use of other procedures as well as make difficult the monitoring of disease progression. In addition, tearing the dividing membrane has contributed to cord entanglement and demise of fetuses through physical complications. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7961", "text": "This procedure involves  endoscopic surgery  using laser to interrupt the vessels that allow exchange of blood between fetuses under the assumption that the unequal sharing of blood through these vascular communications leads to unequal levels of amniotic fluid. Each fetus remains connected to its primary source of blood and nutrition, the placenta, through the umbilical cord. This procedure is conducted once, with the exception of all vessels not having been found. The use of endoscopic instruments allows for short recovery time. This procedure has been associated with 85% survival rate of at least one fetus, with a 6\u20137% risk of cerebral palsy and average delivery occurring at 32\u201333 weeks' gestation. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7962", "text": "Twin anemia\u2013polycythemia sequence  (TAPS) may occur after laser surgery for TTTS (post-laser form). The spontaneous form of TAPS complicates approximately 3\u20135% of monochorionic twin pregnancies, whereas the post-laser form occurs in 2\u201313% of TTTS cases. [ 9 ] [ 10 ]  The pathogenesis of TAPS is based on the presence of few, minuscule arterio-venous (AV) placental anastomoses (diameter <1mm) [ 11 ]  allowing a slow transfusion of blood from the donor to the recipient and leading gradually to highly discordant Hb levels. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7963", "text": "A 2014 review found that laser coagulation resulted in fewer fetal and perinatal deaths than amnioreduction and septostomy, and recommended its use for all states of TTTS. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7964", "text": "Selective termination  of one of the fetuses is usually not considered until TTFS has reached either stage III or IV, [ 13 ]  and is indicated when the death of one twin is imminent, but the fetus is too premature to deliver, as the death of one twin will cause the death of the second twin due to the shared blood supply if not immediately delivered. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7965", "text": "One procedure for selective reduction is  umbilical cord occlusion . This procedure involves the ligation or otherwise occlusion of one twin's umbilical cord to interrupt the exchange of blood between the fetuses. The procedure is typically offered in cases where one of the fetuses is presumed moribund and endangering the life or health of the other twin through resultant hypotension. [ 14 ]  Use of this treatment has decreased as TTTS is identified and treated in earlier stages and with better outcomes. When used, it is associated with an 85% survival rate of the remaining fetuses with 5% risk of cerebral palsy and a 33\u201339 weeks of gestation at delivery. [ 15 ] [ 16 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7966", "text": "Some women choose to have an  abortion  of both fetuses as the health of both fetuses is impacted by TTFS. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7967", "text": "Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births). The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS. By extrapolating the number of expected identical twins (about one-third) from annual multiple births, and the number of twins with monochorionic placentae (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 4,500 TTTS cases per year in the U.S. alone: 139,816 \u00d7 0.33 \u00d7 0.66 \u00d7 0.15 = 4,568 cases of TTTS per year in U.S. (involving more than 9,000 babies.) Since spontaneous pregnancy losses and terminations that occur prior to 20 weeks go uncounted by the C.D.C., this estimate of TTTS cases may be very conservative. Although infertility treatments have increased the rate of multiple birth, they have not appreciably diluted the expected incidence of identical twins. Studies show a higher rate of identical twins (up to 20 times with IVF) using these treatments versus spontaneous pregnancy rates. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7968", "text": "One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies, or 1 in 58 twin gestations. This distinction could be partly explained by the \"hidden mortality\" associated with MC multifetal pregnancies\u2014instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7969", "text": "TTTS was first described by a German  obstetrician ,  Friedrich Schatz , in 1875. Once defined by neonatal parameters\u2014differences in birth weight and cord hemoglobin at the time of delivery\u2014TTTS is now defined differently. Today, it is known that discordant fetal weights will most likely be a late manifestation, and fetal hemoglobin through cordocentesis is often equivalent in the twin pair even in severe TTTS. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7970", "text": "A painting known as the  De Wikkelkinderen  (The Swaddled Children), from 1617, is thought to represent a depiction of TTTS. [ 17 ]  The drawing shows twins that appear to be identical, but one is pale, while the other is red. Analysis of the family histories of the owners of the painting suggests that the twins did not survive to adulthood, although whether that is due to TTTS is uncertain. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7971", "text": "Arnault Tzanck  (May 1, 1886 \u2013 February 18, 1954) was a French physician and a pioneer of  blood transfusion . During the First World War, he was a doctor in the military ambulance where he realized the vital role of the blood transfusions. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7972", "text": "Arnault Tzanck's name is attached to an apparatus he invented that was widely used for transfusing blood in France between the wars, as well as a simple test he devised [ 2 ]  using the microscopic analysis of scrapings from skin cancer lesions, different ganglia, and some forms of dermatitis especially pemphigus. The Tzanck smear is still widely used as a test for herpes, among other diseases. [ 3 ]  A  deep learning  model was developed to analyze Tzanck smears and named after him as  TzanckNet . [ 4 ]  He also experimented with different methods of preserving blood and blood substitutes. Tzanck's most lasting contribution was in the organization of blood transfusion in France that eventually resulted in the creation of the Centre National de Transfusion Sanguine (National Blood Transfusion Center), which was established in 1949 with Tzanck as its first director. In the process, Tzanck educated a whole generation of serologists and immunologists, including  Jean Dausset ,  Marcel Bessis , and  Jean Pierre Soulier . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7973", "text": "This biography related to medicine in France is a  stub . You can help Wikipedia by  expanding it ."}
{"_id": "WikiPedia_Hematology$$$corpus_7974", "text": "The  Vel blood group  is a human  blood group  that has been implicated in  hemolytic transfusion reactions . [ 1 ]  The blood group consists of a single  antigen , the high-frequency  Vel antigen , which is expressed on the surface of  red blood cells . Individuals are typed as Vel-positive or Vel-negative depending on the presence of this antigen. The  expression  of the antigen in Vel-positive individuals is highly variable and can range from strong to weak. Individuals with the rare Vel-negative blood type develop  anti-Vel   antibodies  when exposed to Vel-positive blood, which can cause transfusion reactions on subsequent exposures. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7975", "text": "The Vel blood group is associated with the  SMIM1  gene, which is located in the 1p36 region of  chromosome 1 . [ 3 ] [ 4 ]  This gene produces small integral membrane protein 1, a  single-pass transmembrane protein  which carries the Vel antigen [ 2 ]  but whose structure and function are otherwise poorly understood. [ 5 ]  The Vel-negative phenotype is inherited in an  autosomal recessive  manner, being expressed by patients who are  homozygous  for a  deletion mutation  in the  coding region  of  SMIM1  which renders the gene  nonfunctional . [ 5 ] [ 6 ]  Patients who are  heterozygous  for this mutation, meaning inherited from only one parent, exhibit weakened Vel antigen expression. [ 7 ]   Missense mutations  at nucleotide position 152 can also result in a weak Vel phenotype, and various  single nucleotide polymorphisms  in the noncoding regions of  SMIM1  affect the strength of Vel antigen expression. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7976", "text": "The Vel-negative blood type is rare. The highest prevalence of Vel-negative blood has been reported in Sweden, where approximately 1 in 1200 individuals exhibit this  phenotype . [ 5 ]  Only about 1 in 3000 English people [ 8 ]  and 1 in 4000 Southern Europeans are Vel-negative, and much lower rates have been reported in people of African and Asian heritage. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7977", "text": "When exposed to Vel-positive blood through  transfusion  or  pregnancy , Vel-negative individuals can become  sensitized  and begin producing an anti-Vel antibody. If they are exposed to Vel-positive blood again, the anti-Vel antibody can bind to Vel-positive red blood cells and destroy them, causing  hemolysis . [ 2 ] [ 9 ] :\u200a696\u200a  Anti-Vel is a particularly dangerous antibody because it is able to activate the  complement system , which causes immediate and severe destruction of red blood cells. [ 10 ] [ 11 ]  Therefore, patients with anti-Vel should not be transfused with Vel-positive blood, as it can cause a serious  acute hemolytic transfusion reaction . [ 2 ] [ 8 ]  Finding compatible blood for Vel-negative patients is difficult due to the rarity of this blood type, [ 5 ]  and it may be necessary to perform  autologous blood donation  or to contact rare blood banks. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7978", "text": "Cases of anti-Vel causing  hemolytic disease of the newborn  (HDN) have been reported, but this is an unusual occurrence. [ 5 ] [ 8 ]  It is hypothesized that anti-Vel associated HDN is rare because the antibody is usually predominantly composed of  IgM immunoglobulin , which does not cross the  placenta  into the fetal circulation. [ 9 ] :\u200a981\u200a  In addition, the expression of Vel is very weak on fetal red blood cells \u2013 particularly in children who are heterozygous for Vel. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7979", "text": "Autoimmune hemolytic anemia  (a condition in which patients produce antibodies against antigens on their own red blood cells, leading to hemolysis) [ 9 ] :\u200a956\u200a  involving auto-anti-Vel has been reported. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7980", "text": "An individual's Vel blood type can be determined by  serologic methods , which use  reagents  containing anti-Vel antibodies to identify the antigen, or by  genetic testing . [ 5 ]  As of 2019, serologic testing for Vel is mainly performed using  polyclonal antibodies  isolated from the blood of patients with anti-Vel. However, this method is problematic because these antibodies are variable in quality and sometimes produce false negative results in patients with weak Vel expression; moreover, the reagent cannot be mass-produced. [ 5 ] [ 13 ]  In 2016, a recombinant  monoclonal antibody  against Vel was introduced [ 14 ]  and it has since been used to screen for Vel-negative blood donors in France. [ 5 ]   Genotyping  of  SMIM1  using  polymerase chain reaction  is another method that has been used to identify Vel-negative donors. [ 15 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7981", "text": "Anti-Vel is a mixture of  IgG  and  IgM  immunoglobulins and is able to activate  complement , which can cause hemolysis  in vitro  (i.e. during  compatibility testing ). [ 5 ] [ 16 ]  Anti-Vel can be mistaken for a typical  cold antibody  in compatibility testing if inappropriate techniques are used; this misidentification is dangerous, because such antibodies are usually clinically insignificant. [ 5 ] [ 12 ] [ 17 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7982", "text": "The Vel blood group was first described in 1952 by Sussman and Miller, [ 18 ]   who reported a case of a patient who had suffered a severe hemolytic reaction following a blood transfusion. [ 2 ]  The patient's  serum  was subsequently  crossmatched  against blood samples from 10,000 donors, and only five of them were found to be compatible, indicating that an antibody against a high-frequency antigen was present. [ 5 ]  This antigen was named  Vel  after the first patient. [ 1 ]  The authors also observed variable expression of the antigen: the patient's serum reacted less strongly with the blood of her children, who were presumably heterozygous for Vel, than with blood from unrelated donors. [ 5 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7983", "text": "In 1955, a further case was described  [ 19 ]  in which the blood of a woman who had suffered a transfusion reaction was incompatible with more than 1,000 donors, but not with the blood of the first Vel-negative patient. [ 5 ]  This patient's antibody was the first example of an anti-Vel that could hemolyze red blood cells  in vitro . [ 20 ]  Six other individuals from three generations of this woman's family were found to be Vel-negative, but they did not exhibit an anti-Vel antibody, demonstrating that anti-Vel is not naturally occurring. [ 2 ]  By 1962, 19 cases of anti-Vel and approximately 50 cases of Vel-negative patients had been described. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7984", "text": "Although the Vel blood group has been widely studied due to its significance in  transfusion medicine , its genetic and molecular basis remained unclear for several decades. [ 12 ] [ 14 ]  In 2013, two research groups simultaneously identified the  SMIM1  gene and its protein product as the determinants of the Vel blood group. [ 12 ] [ 3 ] [ 4 ]  The Vel blood group was officially recognized by the  International Society of Blood Transfusion  in 2016. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7985", "text": "Vitalant  (formerly  Blood Systems Inc. [ 1 ] ) is a  nonprofit  organization that collects blood from volunteer donors and provides  blood ,  blood products  and services across the  United States . It was founded in 1943 as the Salt River Valley Blood Bank in  Phoenix, Arizona ."}
{"_id": "WikiPedia_Hematology$$$corpus_7986", "text": "Vitalant is the nation\u2019s largest independent, nonprofit blood services provider exclusively focused on providing blood and comprehensive transfusion medicine services. [ 2 ]  The organization comprises a network of about 120 donation centers across the U.S. and are the sole blood provider to about 900 hospitals across the United States."}
{"_id": "WikiPedia_Hematology$$$corpus_7987", "text": "Vitalant is a founding member of the  Association for the Advancement of Blood & Biotherapies  (formerly known as the American Association of Blood Banks) and was involved in the creation of the  America's Blood Centers  consortium of nonprofit blood centers."}
{"_id": "WikiPedia_Hematology$$$corpus_7988", "text": "The  Vitalant Research Institute  (formerly Blood Systems Research Institute) is housed in San Francisco with a second campus in Denver. VRI is supported by grants from the  National Institute of Health  and has  collaborative partnerships  with major universities and medical centers such as the  University of California, San Francisco ,  University of Southern California ,  Children's National Medical Center ,  Emory University ,  Johns Hopkins University ,  Cornell University ,  University of Pittsburgh , Children\u2019s Medical Center, Oakland,  U.S. Department of Veteran Affairs ,  University of Massachusetts Medical School ,  Massachusetts General Hospital  and  Harvard Medical School  Partners AIDS Research Center. [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7989", "text": "The main blood bank that became United Blood Services was founded in 1943 as the Salt River Valley Blood Bank in  Phoenix, Arizona , by Opal Davis and Kitty Baldwin. Not long after its creation, parent company Blood Systems, Inc., was formed. [ 4 ]  Other blood banks that later became part of Blood Systems were founded in this same time period, including Blood Centers of the Pacific\u2014whose predecessor, the Irwin Memorial Blood Bank, was founded in 1941 as the first community blood bank in the United States [ 5 ] [ 6 ] \u2014and the Inland Northwest Blood Center (1945). [ 7 ]  Blood Systems was the first interstate blood bank, operating under multiple names; by 1967, it served 850 hospitals in 12 states. [ 8 ]  The youngest predecessor to Vitalant, LifeSource, was created in 1987 by the merger of the Blood Center of Northern Illinois with operations of the  American Red Cross  in the Chicago area. [ 9 ] [ 10 ]  The company grew through mergers with other blood centers."}
{"_id": "WikiPedia_Hematology$$$corpus_7990", "text": "On September 24, 2018, Blood Systems merged all of its existing brands under the Vitalant name. These included Lifeblood, Blood Centers of the Pacific, BloodSource, Bonfils Blood Center, Central Blood Bank, Community Blood Services, Inland Northwest Blood Center, LifeShare, LifeSource, and United Blood Services. [ 11 ] [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7991", "text": "Washed red blood cells  are  red blood cells  that have had most of the  plasma ,  platelets  and  white blood cells  removed and replaced with saline or another type of preservation solution. [ 1 ] [ 2 ]  The most common reason for using washed red blood cells in transfusion medicine is to prevent the recurrence of severe  allergic transfusion reactions  that do not respond to medical treatment. The usual cause of these allergic reactions is proteins in the donor plasma. [ 3 ]  These proteins are removed by the process of washing the red blood cells."}
{"_id": "WikiPedia_Hematology$$$corpus_7992", "text": "There are multiple methods of washing red cells. [ 2 ]  These can include automated or manual methods. They can use  centrifugation  or centrifugation-free methods. [ 2 ]  The red cells can be re-suspended in saline or other types of special preservative solutions for red cells, such as SAGM (saline, adenine, glucose and mannitol). [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7993", "text": "The most common reason for using washed red blood cells in transfusion medicine is to prevent the recurrence of severe  allergic transfusion reactions . The allergen is usually a protein in the plasma that is removed by the process of washing the red blood cells. Various proteins, such as antibodies directed against  IgA  or  haptoglobin  in people with IgA and haptoglobin deficiency, have been suggested to have a causal relationship with the allergic reaction. [ 4 ] [ 3 ]   Cytokines  and  chemokines , which accumulate during the storage of blood components, have also been suggested as causative agents. [ 3 ] [ 5 ]  However, the literature is scarce and conflicting, as passive infusion of anti-IgA antibodies in to recipients has not been found to cause an allergic reaction. [ 4 ] [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7994", "text": "In neonates, transfusion has been associated with an increased risk of serious side effects [ 5 ] [ 6 ]  including:"}
{"_id": "WikiPedia_Hematology$$$corpus_7995", "text": "Transfusion-related immune modulation  has been thought to be the underlying mechanism. [ 6 ]  Washing red cells has been thought to be one way of potentially decreasing the risk of theses transfusion-related side-effects. [ 6 ]  However, in neonates, there is insufficient evidence to say whether washing red cells has any effect. [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7996", "text": "Once red blood cells have been washed, they can only be kept for up to a day. [ 7 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7997", "text": "Whole blood  ( WB ) is human  blood  from a standard  blood donation . [ 1 ]  It is used in the treatment of  massive bleeding , in  exchange transfusion , and when people  donate blood to themselves (autologous transfusion) . [ 1 ] [ 2 ]  One unit of whole blood (approximately 450 mL) increases  hemoglobin  levels by about 10 g/L. [ 3 ] [ 4 ]   Cross matching  is typically done before the blood is given. [ 2 ] [ 5 ]  It is given by  injection into a vein . [ 6 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7998", "text": "Side effects include  red blood cell breakdown ,  high blood potassium ,  infection ,  volume overload ,  lung injury , and  allergic reactions  such as  anaphylaxis . [ 2 ] [ 3 ]  Whole blood is made up of  red blood cells ,  white blood cells ,  platelets , and  blood plasma . [ 3 ]  It is best within a day of collection; however, it can be stored for up to three weeks if refrigerated (1-6\u00a0\u00b0C). [ 3 ] [ 5 ] [ 7 ]  The blood is typically combined with an  anticoagulant  and  preservative  during the collection process. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_7999", "text": "The first transfusion of whole blood was in 1818; however, common use did not begin until the  First  and  Second World Wars . [ 5 ] [ 9 ]  It is on the  World Health Organization's List of Essential Medicines . [ 10 ] [ 11 ]  Whole blood is also used to make a number of  blood products  including  ed cell concentrates ,  platelet concentrates ,  cryoprecipitate , and  fresh frozen plasma . [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8000", "text": "Whole blood has similar risks to a transfusion of  red blood cells  and is typically  cross-matched  to avoid hemolytic  transfusion reactions . The use of whole blood is common in low- and middle-income countries. Over 40% of blood collected in low-income countries is administered as whole blood, and approximately a third of all blood collected in middle-income countries is administered as whole blood. [ 12 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8001", "text": "Whole blood is sometimes \"recreated\" from stored  red blood cells  and  fresh frozen plasma  (FFP) for neonatal transfusions. This is done to provide a final product with a very specific  hematocrit  (percentage of red cells) with  type O  red cells and  type AB  plasma to minimize the chance of complications. [ 13 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8002", "text": "Transfusion of whole blood is being used in the military setting and in the civilian setting, where it is being used in pre-hospital trauma care and in the setting of  massive transfusion  in the civilian setting. [ 14 ] [ 15 ] [ 16 ] [ 17 ]  Whole blood can be ABO-type specific when the recipient blood type is known. When the recipient\u2019s blood group is not known, particularly in pre-hospital transfusion, low-titer O universal donor whole blood (LTOWB) can be used; this requires that the donor plasma contains only low titers of anti-A and anti-B. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8003", "text": "Historically, blood was  transfused  as whole blood without further processing.  Most  blood banks  now split the whole blood into two or more components, [ 18 ]  typically  red blood cells  and a  plasma  component such as  fresh frozen plasma .  Platelets  for transfusion can also be prepared from a unit of whole blood, whereby 4 or 5 buffy coats are pooled to produce a platelet component.  Some blood banks have replaced this with platelets collected by  plateletpheresis  because whole blood platelets, sometimes called \"random donor\" platelets, must be pooled from multiple donors to get enough for an adult therapeutic dose. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8004", "text": "The collected blood is generally separated into components by one of three methods. A centrifuge can be used in a \"hard spin\" which separates whole blood into plasma and red cells or a \"soft spin\" which separates it into plasma, buffy coat (used to make platelets), and red blood cells. The third method is sedimentation: the blood simply sits overnight, and the red cells and plasma are separated by gravitational interactions, which is used predominantly in low-income countries."}
{"_id": "WikiPedia_Hematology$$$corpus_8005", "text": "Whole blood is typically stored under the same conditions as red blood cells and can be kept up to 35 days if collected with citrate-phosphate-dextrose-adenine-1 (CPDA-1) anticoagulant solution, or 21 days with other common anticoagulants such as citrate-phosphate-dextrose (CPD). [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8006", "text": "If the whole blood is used to make  platelets , it is kept at room temperature until the process is complete. Whole blood processing must be completed within 24 hours to minimize the warm storage of red cells in the unit."}
{"_id": "WikiPedia_Hematology$$$corpus_8007", "text": "Xenotransfusion  (from Greek  xenos-  'strange, foreign'), a form of  xenotransplantation , was initially defined as the  transfer of blood  from one species into the  veins  of another. [ 1 ]  In most cases, it is a transfer of blood between a non-human animal and a human. However, further experimentation has been done between various non-human animal species. This procedure can be performed without affecting the health of the donor, as only about 10% of their  blood volume  is used each time. [ 2 ]  Utilizing the unlimited blood supply from animal sources eliminates the risk of transmitting  infectious diseases  between humans. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8008", "text": "In 1658, Dom  Robert Desgabets , a French monk, introduced the idea of xenotransfusion at a scientific society meeting. This society later afforded the  French Academy of Sciences . [ 1 ]  Some ethical issues have been identified by the Ethics Committee of the International Xenotransplantation Association (IXA). [ 2 ]  For example, the IXA sets standards and regulations for those planning to orchestrate clinical xenotransplantation trials. [ 3 ]  The IXA has identified three major ethical areas that require adequate attention: favorable risk and benefit assessment supported by pre-clinical data, lack of alternative treatment for participants, and minimizing the risk of infection by ensuring the highest  biosafety  regulations are followed for selected animal donors. These are just a few examples of the ethics behind xenotransplantation."}
{"_id": "WikiPedia_Hematology$$$corpus_8009", "text": "The first recorded  blood transfusion  was performed between two dogs in 1665. [ 4 ]  On June 15, 1667,  Jean-Baptiste Denis , a French physician, and Paul Emmerez, a surgeon, performed the first documented xenotransfusion to humans. The transfusion occurred between a lamb and a 15-year-old boy. [ 1 ] [ 5 ]  Carotid artery blood from the lamb was introduced to a vein in the patient's inner elbow, and the procedure ultimately resulted in a successful recovery. [ 5 ]  Denis and Emmerez performed multiple xenotransfusions together. On June 24, 1667, the duo performed a transfusion on a young Swedish nobleman. [ 1 ]  When they arrived, the patient had already lost his ability to speak and was practically unconscious. Shortly after the transfusion began, the patient was able to speak again. His health was improving until his condition grew progressively worse. A second transfusion took place, but it was unsuccessful, and the patient died."}
{"_id": "WikiPedia_Hematology$$$corpus_8010", "text": "Richard Lower , an English physician, performed a similar procedure on November 23, 1667. [ 1 ] [ 5 ]  He successfully transfused the blood of a lamb to a 22-year-old man. [ 1 ]  In both cases, the whole blood of the lamb was directly introduced into the vein of the patient. The direct introduction of blood was due to a lack of knowledge in preventative blood coagulation techniques at the time."}
{"_id": "WikiPedia_Hematology$$$corpus_8011", "text": "After several xenotransfusion procedures, some successful some not, the  French Parliament  prohibited the practice of these transfusions in 1670. [ 5 ]  The  English Parliament , as well as the Pope, followed suit and prohibited the procedures shortly after."}
{"_id": "WikiPedia_Hematology$$$corpus_8012", "text": "Xenotransfusion uses non-human animals to aid in the shortage of blood for  blood transfusion  in humans. Some scientists preliminarily favor  Sus scrofa domesticus  (pigs) as a source of blood after having tested many different animals in order to find the best candidate for a  blood donation . Pig  red blood cells  (pRBCs) show many characteristics similar to that of a human, including RBC diameters (pig 6 \u03bcm; human 7.2 \u03bcm), RBC counts (pig 5.7 to 6.9 million/ll; human 4.2 to 6.2 million/ll), and RBC average lifespan (human 86 days; pig 120 days). [ 6 ]  Current evidence shows that pRBCs will function normally in humans due to the relation between porcine  blood groups  and human  ABO group system . [ 7 ]  In addition, it is possible to produce pigs with type O blood and to genetically modify pigs to make their blood more compatible with humans.  Sus scrofa domesticus 's blood may be used to save lives and to increase blood quantity. The organism is kept alive and no serious harm is involved, similar to how blood is removed from humans. One article examining the ethics of xenotransfusion notes that only 10% of the animal's blood volume is used each time; therefore, it may be considered ethically acceptable to raise pigs for periodical blood collection as it does not damage the health of the animal. Likewise, using pRBCs on humans would not cause severe harm to human health. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8013", "text": "Transfusion of canine blood into domestic cats was performed historically and continues to be performed in some countries. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8014", "text": "Xenotransfusions have been performed on birds, though the procedure is only done to stabilize a bird in shock, due to  rejection  by the recipient bird's antibodies. [ 8 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8015", "text": "Xenotransfusion of bovine whole blood into domestic goats has been preliminarily investigated as a potential option for anemic goats. [ 9 ]  When comparing caprine-recipient bovine-donor cross matching a study found 11/15 caprine-bovine combinations compatible on both major and minor cross matching. [ 9 ] [ 10 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8016", "text": "The  XG antigen  is a  red blood cell  surface  antigen  discovered in 1962. [ 1 ]  by researchers at the  MRC Blood Group Unit . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8017", "text": "The PBDX gene that encodes the  antigen  is located on the  short arm  of the  X chromosome . [ 3 ] [ 4 ]  Since males normally have one X chromosome they are considered  hemizygotes . Since women have two copies of the gene and could be  heterozygotic  for the presence or absence of the functioning gene they could (through the process of  lyonisation )  express  the functioning  protein  on just some of their red blood cells. [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8018", "text": "XK  (also known as  Kell blood group precursor ) is a  protein  found on human  red blood cells  and other tissues which is responsible for the Kx  antigen  which helps determine a person's  blood type ."}
{"_id": "WikiPedia_Hematology$$$corpus_8019", "text": "The Kx antigen plays a role in matching blood for  blood transfusions . [ citation needed ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8020", "text": "Mutation of XK protein may lead to  McLeod syndrome , [ 1 ]  a multi-system disorder characterized by  hemolytic anemia ,  myopathy ,  acanthocytosis , and  chorea . [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8021", "text": "XK is located on the  X chromosome  (cytogenetic band Xp21.1) and absence of the XK protein is an  X-linked disease . [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8022", "text": "XK is a  membrane transport  protein of unknown action. [ 4 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8023", "text": "Young blood transfusion  refers to  transfusing blood  specifically from a young person into an older one with the intention of creating a health benefit. [ 1 ]  The efficacy and safety of young blood transfusions for anti-aging purposes remain a subject of debate in the scientific community, with limited clinical evidence in humans. [ 1 ] [ 2 ] [ 3 ]  There are also concerns of harm. [ 3 ]  While some preclinical studies on animals suggest potential benefits, there is a lack of robust clinical evidence to support its use in humans. [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ]  The U.S.  Food and Drug Administration , in 2019, cautioned \"consumers against receiving young donor plasma infusions\" stating that they are an \"unproven treatment\". [ 3 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8024", "text": "Experiments beginning in the 1950s in the  Cornell University  lab of  Clive McCay  on pairs of old and young rodents placed into  parabiosis  provided some evidence, albeit limited and \"largely anecdotal\", that the circulation of blood from young mice increased both the longevity and the tissue function of old mice. [ 10 ]  After decades in which relatively little work on parabiosis in aging was done, the work was revived by researchers at  Stanford University  and the  University of California at Berkeley . [ 10 ] [ 11 ]  Parabiosis experiments are difficult to generalize, as the circulatory systems of the mice are fully joined and it is unclear whether the benefits come from the sharing of blood or the older mouse's access to the younger mouse's organs. [ 1 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8025", "text": "A study conducted at UC Berkeley found that when delivered alone, blood from older mice was more inhibitory to the regenerative capacities of younger mice than blood from younger mice was beneficial to older ones, and that the benefit of young blood in older mice was less than had been observed when older mice were subjected to parabiosis. [ 12 ] [ 13 ]  Replacing plasma of old mice with saline and albumin from young mice was sufficient to rejuvenate brain, liver, and muscle. [ 13 ]  A 2020 review of plasma components that change with age identified several candidate anti-aging and pro-aging factors. [ 14 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8026", "text": "In experiments like this, researchers found that some of the parabiosed died quickly (11 out of 69 in one experiment) for reasons the scientists could not explain, but described as possibly some form of  immune rejection ; [ 10 ] [ 1 ]  most such cases were the young parabiont. [ 10 ]   Amy Wagers , a researcher who coauthored several mouse studies on young blood transfusion, has said that her papers do not provide a scientific basis for some of the existing human trials. [ 2 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8027", "text": "A review of studies on donor age for whole blood transfusions reported that blood from donors under the age of 20 years, when compared to donors aged 20\u201360 years, resulted in a modestly higher risk of death in the recipients. [ 15 ]  However, other studies have found no effect of age. [ 16 ] [ 17 ]  Research on blood transfusion outcomes has been complicated by the lack of careful characterization of the transfusion products that have been used in clinical trials; studies had focused on how storage methods and duration might affect blood, but not on the differences among lots of blood themselves. [ 18 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8028", "text": "Another approach to achieving \"younger\" blood is to rejuvenate blood-producing  stem cells  in the  bone marrow . A 2023 study reported that the existing rheumatoid arthritis drug  anakinra  blocked  IL-1B  in elderly mice and returned those cells to a more youthful state. [ 19 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8029", "text": "In February 2019 the FDA issued a warning about companies offering young blood transfusions stating:"}
{"_id": "WikiPedia_Hematology$$$corpus_8030", "text": "\"simply put, we\u2019re concerned that some patients are being preyed upon by unscrupulous actors touting treatments of plasma from young donors as cures and remedies. Such treatments have no proven clinical benefits for the uses for which these clinics are advertising them and are potentially harmful. There are reports of bad actors charging thousands of dollars for infusions that are unproven and not guided by evidence from adequate and well-controlled trials. The promotion of plasma for these unproven purposes could also discourage patients suffering from serious or intractable illnesses from receiving safe and effective treatments that may be available to them.\" [ 3 ] [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8031", "text": "A startup company, Ambrosia, has been selling \"young blood transfusions\" for $8,000 since 2016 framing it as a  clinical trial , to see if such transfusions lead to changes in the blood of recipients. [ 1 ] [ 21 ]  As of August 2017, 600 people had participated in the trial. [ 22 ]  The clinical trial has no  control arm  and so is neither randomized nor blind. As described, whole blood collected by blood banks that had passed its 42-day storage limit was centrifuged to remove cells, the resulting cell-free plasma pooled from several donations and intravenously transfused into recipients. [ 22 ]  The company was started by Jesse Karmazin, a medical school graduate without a license to practice medicine. [ 23 ]  David Wright is the licensed doctor overseeing the clinical trial; in his practice he administers intravenous treatments of vitamins and antibiotics for  nontraditional purposes  and was disciplined by the California Medical Board for the latter in 2015. Jonathan Kimmelman, a bioethicist from McGill University, suggests that Ambrosia is running this as a trial as they would be unable to get FDA approval to sell this treatment otherwise. [ 23 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8032", "text": "On February 19, 2019, Ambrosia announced it stopped testing the treatment, responding to concerns from the FDA. [ 20 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8033", "text": "Another company, Alkahest, was founded based on the Stanford rodent studies. As of 2017 it is collaborating with European pharmaceutical company  Grifols  to create a  blood plasma -based experimental  biologic  drug which they propose to test on people with  Alzheimer's . [ 21 ] [ 24 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8034", "text": "The Maharaj Institute led by Dr. Dipnarine Maharaj MD, a Florida licensed physician, is currently running a clinical trial to test whether using G-CSF (Granulocyte Colony Stimulating Factor) stem cell mobilized young blood plasma can treat symptoms of frailty in patients aged 55 to 95. [ 25 ] [ 26 ]  \u00a0Participation in the trial is free of charge to the patients. [ 25 ]  \u00a0This trial has been promoted by Bill Faloon, who founded the Life Extension Foundation. [ 2 ] [ 27 ] \u00a0 The trial has received FDA Investigational New Drug (IND) and IRB approval for a Phase I/Phase II clinical trial as a single-arm study without a control group, which is not uncommon for Phase I/Phase II studies. [ 25 ]  \u00a0Dr. Maharaj also has a program for hematopoietic progenitor stem cell and immune cell banking so that patients can preserve their cells for future use. [ 26 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8035", "text": "An organization called the Young Blood Institute has also run trials; these, however, involved exchange only of  blood plasma . [ 28 ]"}
{"_id": "WikiPedia_Hematology$$$corpus_8036", "text": "The  Yt antigen system  (also known as  Cartwright ) is present on the  membrane  of  red blood cells  and helps determine a person's  blood type . The antigens are found on the  protein   acetylcholinesterase , an  enzyme  which helps break down  acetylcholine . [ 1 ]  The Yt system features two alleles, Yt(a) and Yt(b).  Antibodies  against the Yt system can lead to  transfusion reactions  such as  hemolytic anemia ."}
{"_id": "blood_donation_clean$$$corpus_1", "text": "The donor drinks some liquid (here a tube of apple juice) to replace the lost volume, eats some cookies, and is on his way in about 10 minutes.\n\nA bandage is in place over the phlebotomy site."}
{"_id": "blood_donation_clean$$$corpus_2", "text": "The needle is removed and pressure is applied over the venipuncture site, then a bandage is placed for the next couple of hours."}
{"_id": "blood_donation_clean$$$corpus_3", "text": "Just after the bag has filled, blood from the line is taken to fill several collection tubes for further testing. A red top collection tube is being filled here."}
{"_id": "blood_donation_clean$$$corpus_4", "text": "Blood fills the collection bag by gravity in a few minutes.\n\nThe sealed plastic collection bag contains a blood preservative."}
{"_id": "blood_donation_clean$$$corpus_5", "text": "The needle used to draw the blood from the vein is gently inserted. The needle is attached to plastic tubing to conduct the blood to the collection bag."}
{"_id": "blood_donation_clean$$$corpus_6", "text": "The disinfectant is applied to the area around the vein to be used."}
{"_id": "blood_donation_clean$$$corpus_7", "text": "The site for drawing blood is selected and disinfected. A prominent vein has been chosen for the venipuncture site."}
{"_id": "blood_donation_clean$$$corpus_8", "text": "The donor sits in a reclining chair. An inflatable cuff on the arm is used to check blood pressure and to maintain venous filling."}
{"_id": "blood_donation_clean$$$corpus_9", "text": "The blood is drawn into a capillary tube which is then spun in the small centrifuge (seen in the background) to determine the hematocrit."}
{"_id": "blood_donation_clean$$$corpus_10", "text": "A fingerstick is made to obtain a drop of blood to test the hematocrit."}
{"_id": "blood_donation_clean$$$corpus_11", "text": "The donor is interviewed and a questionnaire is filled out."}