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 ]


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 – 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.


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 ]


Skinks  in the genus  Prasinohaema  have green blood due to a buildup of the waste product  biliverdin . [ 37 ]


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 ]


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.


Other blood products administered  intravenously  are platelets, blood plasma, cryoprecipitate, and specific coagulation factor concentrates.


Many forms of medication (from  antibiotics  to  chemotherapy ) are administered intravenously, as they are not readily or adequately absorbed by the digestive tract.


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.


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.


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  blōþ ). There is no accepted  Indo-European  etymology. [ 41 ]


Robin Fåhræus  (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 ]


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 ]


The ABO blood group system was discovered in the year 1900 by  Karl Landsteiner .  Jan Janský  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.


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 ".


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.


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.


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:


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 ]


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 .


Among the  Germanic tribes , blood was used during their sacrifices; the  Blóts . 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  blóedsian  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 .
The  Ancient Greeks  believed that the blood of the gods,  ichor , was a substance that was poisonous to mortals.


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 ]


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 .


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.


At the  Council of Jerusalem , the  apostles  prohibited certain Christians from consuming blood – this is documented in Acts 15:20 and 29. This chapter specifies a reason (especially in verses 19–21): It was to avoid offending Jews who had become Christians, because the Mosaic Law Code prohibited the practice.


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).


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 ) .


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.


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 ]


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.


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 ]


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."


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.


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 ]


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.


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.


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.


Blood residue analysis is also a technique used in  archeology .


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.


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 .


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.


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.


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 ] : How often can I donate blood?


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 —or 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.


Charles Richard Drew  (1904–1950) 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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–Jakob disease  (vCJD). These questions vary from country to country. For example, while blood centers in  Québec  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 ]


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.


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 kg) or more for whole blood and platelet donation and at least 130 pounds (59 kg) (males) and at least 150 pounds (68 kg) (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 ]


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 ]


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 ]


Donated blood is tested by many methods, but the core tests recommended by the World Health Organization are these four: [ 46 ]


The WHO reported in 2006 that 56 out of 124 countries surveyed did not use these basic tests on all blood donations. [ 14 ]


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 ]


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 ]


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 ]


The amount of blood donated in one session – generally called a 'unit' – 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 460–500 ml range, [ 56 ] [ 57 ]  while those in the EU must be in the 400-500 ml range. [ 58 ]  Other countries have smaller units – 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.


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 ]


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 ]


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 ]


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 ]


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 .


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 ]


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 ]


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 ]


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 ]


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 .


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 ]


Donors are usually kept at the donation site for 10–15 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 ]


Donated plasma is replaced after 2–3 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 ]


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 ]


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 ]


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 ]
One 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


Red blood cells (RBC), the most frequently used component, have a shelf life of 35–42 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 ]


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 ]


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 26,000–28,000 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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,  Poznań '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 ]


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 ]


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 ]


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.


P a O 2  – Partial pressure of oxygen at sea level (160  mmHg  in the atmosphere, 21% of standard atmospheric pressure of 760 mmHg) in  arterial blood  is between 75 mmHg and 100 mmHg. [ 4 ] [ 5 ] [ 6 ]


P v O 2  – Oxygen tension in  venous blood  at sea level is between 30 mmHg and 40 mmHg. [ 6 ] [ 7 ]


Carbon dioxide is a by-product of food metabolism and in high amounts has toxic effects including:  dyspnea ,  acidosis  and  altered consciousness . [ 8 ]


P a CO 2  – Partial pressure of carbon dioxide at sea level in arterial blood is between 35 mmHg and 45 mmHg. [ 9 ]


P v CO 2  – Partial pressure of carbon dioxide at sea level in venous blood is between 40 mmHg and 50 mmHg. [ 9 ]


P a CO  – 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.


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 − 3  (and  lactate ) suggest to the health care practitioner which interventions, if any, should be made. [ 10 ] [ 11 ]


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 ]


This is an estimation and does not account for differences in temperature, pH and concentrations of 2,3 DPG. [ 13 ]


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 (6–8%; e.g.,  serum albumins ,  globulins , and  fibrinogen ), [ 2 ]   glucose ,  clotting factors ,  electrolytes  ( Na + ,  Ca 2+ ,  Mg 2+ ,  HCO 3 − ,  Cl − , 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 ]


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 kg/m 3  (1.025 g/ml). [ 8 ]   Blood serum  is blood plasma without clotting factors. [ 5 ]   Plasmapheresis  is a medical therapy that involves blood plasma extraction, treatment, and reintegration.


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 ]


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 ]


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 ]


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 ]


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 ]


Fibrinogen proteins make up most of the remaining proteins in the blood. Fibrinogens are responsible for clotting blood to help prevent blood loss. [ 17 ]


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 ]


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 ]


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 ]


Compared to serum, 15–20% 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 ]


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 ]


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 ]


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 ]


No anticoagulants are added to serum samples, which decreases the preparation cost of the samples relative to plasma samples. [ 26 ]


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 ]


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 (1514–1564). The discovery of fibrinogen by William Henson,  c.  1770 , [ 27 ]  made it easier to study plasma, as ordinarily, upon coming in contact with a foreign surface – something other than the vascular endothelium – 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 ]


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 ]


Dr. José Antonio Grifols Lucas, a scientist from Vilanova i la Geltrú, 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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 £200 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 ]


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 ]


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 ]


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 ]


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.


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.


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 ]


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 ]


It is unclear whether applying alcohol swab alone or alcohol swab followed by antiseptic is able to reduce contamination of donor's blood. [ 13 ]


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 ]


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 .


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.


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−k−). 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 ]


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 3–5% 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.


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.


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.


This chart shows possible matches in blood transfusion between donor and receiver using ABO and Rh system. The symbol   indicates compatibility.


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 ]


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 ]


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 ]


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.


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.


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.


Other rare transmissible infections include  hepatitis B ,  syphilis ,  Chagas disease ,  cytomegalovirus  infections (in immunocompromised recipients),  HTLV , and  Babesia .


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 – 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.


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 — 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  — who are the physicians, typically pathologists, who collect and manage inventories of transfusable blood units.


Certain regulatory measures are in place to minimize RBC storage lesion — 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 ]


Physicians have adopted a so-called "restrictive protocol" — whereby transfusion is held to a minimum — 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.


Although transfusions of platelets are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern. [ 63 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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".


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 ]


The first blood transfusion from animal to human was administered by Dr.  Jean-Baptiste Denys , eminent physician to  King Louis XIV  of France, on June 15, 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 .


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 ]


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 £217 in 2023) to participate in the experiment. [ 86 ]


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 ]


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 ]


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 ]


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 ]


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 ]


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.


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 ]


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 ]


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 ]


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 ]


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 ]


Jan Janský  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.


Dr. William Lorenzo Moss's (1876–1957) Moss-blood typing technique of 1910 was widely used until  World War II . [ 94 ] [ 95 ]


William Stewart Halsted , M.D. (1852–1922), 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 ]


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.


The  Belgian  doctor  Albert Hustin  performed the first non-direct transfusion on March 27, 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 ]


The  First World War  (1914–1918) 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 ]


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 ]


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 ]


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 ]


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 ]


Oswald Hope Robertson , a medical researcher and  U.S. Army  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.


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.
 [ 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 ]