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,  ε-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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


Tranexamic acid might alleviate  neuroinflammation  in some experimental settings. [ 63 ]


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 ]


Tentative evidence supports the use of tranexamic acid in  hemoptysis . [ 65 ] [ 66 ]


In  hereditary angioedema [ 67 ]


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 ]


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 ]


In  hyphema : tranexamic acid is effective in reducing the risk of secondary hemorrhage outcomes in people with traumatic hyphema. [ 72 ]


In  liver  resection: tranexamic acid did not reduce bleeding or transfusions but did increase complications. [ 73 ]


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 .


Transfusional hemosiderosis can cause  cardiac arrhythmia  and  cardiomyopathy . [ 1 ]


Transfusional hemosiderosis is a potential side effect of frequent  blood transfusions . [ 2 ]  These may be given for a number of conditions, including:


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 ]


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 ]


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 ]


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 ]


Ted DeVita  died of transfusional iron overload from too many  blood transfusions . [ citation needed ]


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 ]


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 ]


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 ]
There 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:


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 ]


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:


TPs collaborate with department heads and senior management to facilitate mandatory and non-mandatory staff education/training consistent with regulatory requirements/recommendations.


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:


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.


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.” 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:


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 ]


The TP role demands highly skilled and component health care professionals. Typical PT skills/abilities are:


Information to build a business case and on TP activities. [ 9 ]


James Challan provided a classic description of a TP : [ 3 ]


"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."


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.


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).


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.


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 ]


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 ]


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:


HIV–the virus that causes  AIDS –is 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 ]


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 .


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.


This section describes TTs involving  parasites  and specific  bacteria .


Babesia microti  is transmitted by ixodes ticks and causes  babesiosis . Transfusion-associated babesiosis has been documented. [ 2 ] [ 3 ]


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 ]


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 ]


The management of TACO includes immediate discontinuation of the transfusion, supplemental oxygen if needed, and medication to remove excess fluid. [ 8 ]


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 ]


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 ]


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 ]


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 ]


The National Healthcare Safety Safety Network division of the  Centers for Disease Control and Prevention  (CDC) released an updated criteria table in 2021: [ 11 ]


Patients diagnosed with TACO should have at least 1 of the following two characteristics within 12 hours after the transfusion was ended:


Along with:


TACO can be categorized by severity: [ 11 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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.


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 ]


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 ]


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 ]


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 ]


Other symptoms can include cough, abdominal pain, dyspnea and vomiting. [ 5 ]


Laboratory findings include  pancytopenia , marrow aplasia, abnormal  liver enzymes , and electrolyte imbalance (when diarrhea is present). [ citation needed ]


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 ]


In 2023, the first case of fetal-induced GvHD was reported in the New England Journal of Medicine. [ 6 ]


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 ]


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 ]


The incidence of TA-GvHD in immunocompromised patients receiving blood transfusions is estimated to be 0.1–1.0%, and mortality around 80–90%. 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 ]


The most common  causes of death  in TA-GvHD are infections and hemorrhages secondary to pancytopenia and liver dysfunction. [ citation needed ]


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 ]


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 ]


Delayed TRALI occurs 6 to 72 hours after transfusion completion. It is associated with a higher rate of  mortality . [ 4 ]


The cause of TRALI is currently not fully understood. 80–85% 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 ]


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 ]


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 ]


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–antibody 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 6–9%. [ 18 ]


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 ]


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 ]


The condition occurs when the vein–artery  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 ]


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.


Around 5–15% of identical twin fetuses will go on to develop TTTS. [ 2 ]  The condition was first described by German  obstetrician   Friedrich Schatz  in 1875. [ 6 ]


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–artery connection, this can cause blood flow to become unbalanced. [ 4 ]


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 ]


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 ]


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 ]


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 ]


A staging system is commonly used to classify the severity of TTTS. [ 7 ]


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.


Stage II : In addition to the description above, the ultrasound is not able to identify the bladder in the donor twin.


Stage III : In addition to the characteristics of Stages I and II, there is abnormal blood flow in the umbilical cords of the twins.


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).


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.


The Quintero staging does not provide information about prognosis, and other staging systems have been proposed. [ 8 ]


Various treatments exist for TTTS.


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 ]


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 ]


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 ]


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 6–7% risk of cerebral palsy and average delivery occurring at 32–33 weeks' gestation. [ 5 ]


Twin anemia–polycythemia sequence  (TAPS) may occur after laser surgery for TTTS (post-laser form). The spontaneous form of TAPS complicates approximately 3–5% of monochorionic twin pregnancies, whereas the post-laser form occurs in 2–13% 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 ]


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 ]


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 ]


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 33–39 weeks of gestation at delivery. [ 15 ] [ 16 ]


Some women choose to have an  abortion  of both fetuses as the health of both fetuses is impacted by TTFS. [ 13 ]


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 × 0.33 × 0.66 × 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 ]


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—instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made. [ 6 ]


TTTS was first described by a German  obstetrician ,  Friedrich Schatz , in 1875. Once defined by neonatal parameters—differences in birth weight and cord hemoglobin at the time of delivery—TTTS 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 ]


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 ]


Arnault Tzanck  (May 1, 1886 – 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 ]


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 ]


This biography related to medicine in France is a  stub . You can help Wikipedia by  expanding it .


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 ]


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 ]


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 ]


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 ] : 696   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 ]


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 ] : 981   In addition, the expression of Vel is very weak on fetal red blood cells – particularly in children who are heterozygous for Vel. [ 8 ]


Autoimmune hemolytic anemia  (a condition in which patients produce antibodies against antigens on their own red blood cells, leading to hemolysis) [ 9 ] : 956   involving auto-anti-Vel has been reported. [ 8 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 .


Vitalant is the nation’s 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.


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.


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’s 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 ]


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—whose predecessor, the Irwin Memorial Blood Bank, was founded in 1941 as the first community blood bank in the United States [ 5 ] [ 6 ] —and 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.


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 ]


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.


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 ]


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 ]


In neonates, transfusion has been associated with an increased risk of serious side effects [ 5 ] [ 6 ]  including:


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 ]


Once red blood cells have been washed, they can only be kept for up to a day. [ 7 ]


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 ]


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 °C). [ 3 ] [ 5 ] [ 7 ]  The blood is typically combined with an  anticoagulant  and  preservative  during the collection process. [ 8 ]


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 ]


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 ]


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 ]


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’s 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 ]


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 ]


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.


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 ]


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.


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 ]


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.


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.


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.


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.


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 μm; human 7.2 μm), 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 ]


Transfusion of canine blood into domestic cats was performed historically and continues to be performed in some countries. [ 4 ]


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 ]


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 ]


The  XG antigen  is a  red blood cell  surface  antigen  discovered in 1962. [ 1 ]  by researchers at the  MRC Blood Group Unit . [ 2 ]


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 ]


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 .


The Kx antigen plays a role in matching blood for  blood transfusions . [ citation needed ]


Mutation of XK protein may lead to  McLeod syndrome , [ 1 ]  a multi-system disorder characterized by  hemolytic anemia ,  myopathy ,  acanthocytosis , and  chorea . [ 2 ]


XK is located on the  X chromosome  (cytogenetic band Xp21.1) and absence of the XK protein is an  X-linked disease . [ 3 ]


XK is a  membrane transport  protein of unknown action. [ 4 ]


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 ]


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 ]


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 ]


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 ]


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 20–60 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 ]


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 ]


In February 2019 the FDA issued a warning about companies offering young blood transfusions stating:


"simply put, we’re 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 ]


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 ]


On February 19, 2019, Ambrosia announced it stopped testing the treatment, responding to concerns from the FDA. [ 20 ]


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 ]


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 ]   Participation in the trial is free of charge to the patients. [ 25 ]   This trial has been promoted by Bill Faloon, who founded the Life Extension Foundation. [ 2 ] [ 27 ]   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 ]   Dr. 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 ]


An organization called the Young Blood Institute has also run trials; these, however, involved exchange only of  blood plasma . [ 28 ]


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 .


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.

A bandage is in place over the phlebotomy site.


The needle is removed and pressure is applied over the venipuncture site, then a bandage is placed for the next couple of hours.


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.


Blood fills the collection bag by gravity in a few minutes.

The sealed plastic collection bag contains a blood preservative.


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.


The disinfectant is applied to the area around the vein to be used.


The site for drawing blood is selected and disinfected. A prominent vein has been chosen for the venipuncture site.


The donor sits in a reclining chair. An inflatable cuff on the arm is used to check blood pressure and to maintain venous filling.


The blood is drawn into a capillary tube which is then spun in the small centrifuge (seen in the background) to determine the hematocrit.


A fingerstick is made to obtain a drop of blood to test the hematocrit.


The donor is interviewed and a questionnaire is filled out.