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Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery. Blood transfusions may also be used to treat a severe anaemia or thrombocytopenia caused by a blood disease. People suffering from hemophilia or sickle-cell disease may require frequent blood transfusions.
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The first historical attempt at blood transfusion was described by the 15th-century chronicler Stefano Infessura. Infessura relates that, in 1492, as Pope Innocent VIII sank into a coma, the blood of three boys was infused into the dying pontiff (through the mouth, as the concept of circulation and methods for intravenous access did not exist at that time) at the suggestion of a physician. The boys were ten years old, and had been promised a ducat each. However, not only did the pope die, but so did the three children. Some authors have discredited Infessura\'s account, accusing him of anti-papalism.
With Harvey\'s re-discovery of the circulation of the blood (which was discoverd by Ibn al-Nafis in the 13th century), more sophisticated research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts on humans continued to have fatal results.
The first fully-documented human blood transfusion was administered by Dr. Jean-Baptiste Denys on June 15, 1667. He transfused the blood of a sheep into a 15-year old boy, who recovered. Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to small amount of blood that was actually transfused into these people. This allowed them to withstand the allergic reaction. Then, Denys performed several transfusions into Mr. Mauroy, who on the third account had died (read Blood and Justice). Much controversy surrounded his death and his wife was accused of his murder; it\'s likely that the transfusion caused his death.
Richard Lower examined 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. His newly devised instruments eventually led to actual transfusion of blood.
"Many of his colleagues were present. . . towards the end of February 1665 [when he] 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 of 1665 in the Society’s Philosophical Transactions. On 15 June 1667 Denys, then a professor in Paris, carried out the first transfusion between humans and claimed credit for the technique, but Lower’s priority cannot be challenged.
Six months later in London, Lower performed the first human transfusion in England, where he "superintended the introduction in his [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. Lower wanted to treat Coga several times, but his patient wisely refused. No more transfusions were performed. Shortly before, Lower had moved to London, where his growing practice soon led him to abandon research. [1]
The science of blood transfusion dates to the first decade of the 19th 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).
In 1818, Dr. James Blundell, a British obstetrician, performed the first successful transfusion of human blood, for the treatment of postpartum hemorrhage. He 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, Dr. Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented many instruments for the transfusion of blood. He made a substantial amount of money from this endeavour, roughly $50 million in real dollars (adjusted for inflation).[citation needed]
In 1840, at St. George\'s Hospital Medical School in London, Samuel Armstrong Lane, aided by Dr. Blundell, performed the first successful whole blood transfusion to treat hemophilia.
George Washington Crile is credited with performing the first surgery using a direct blood transfusion at the Cleveland Clinic.
While the first transfusions had to be made directly from donor to receiver before coagulation, in the 1910s 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 blood banks. The first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, who used sodium citrate as an anticoagulant. The first blood transfusion using blood that had been stored and cooled was performed on January 1,1916. Oswald Hope Robertson, a medical researcher and U.S. Army officer, is generally credited with establishing the first blood bank while serving in France during World War I.
The first academic institution devoted to the science of blood transfusion was founded by Alexander Bogdanov in Moscow in 1925. Bogdanov was motivated, at least in part, by a search for eternal youth, and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of whole blood.
In fact, following the death of Vladimir Lenin, Bogdanov was entrusted with the study of Lenin\'s brain, with a view toward resuscitating the deceased Bolshevik leader. Tragically, but perhaps not unforeseeably, Bogdanov lost his life in 1928 as a result of one of his experiments, when the blood of a student suffering from malaria and tuberculosis was given to him in a transfusion. Some scholars (e.g. Loren Graham) have speculated that his death may have been a suicide, while others attribute it to blood type incompatibility, which was still incompletely understood at the time.See Bernice Glatzer Rosenthal. New Myth, New World: From Nietzsche to Stalinism, Pennsylvania State University, 2002, ISBN 0-271-02533-6 pp. 161-162.
Following Bogdanov\'s lead, the Soviet Union set up a national system of blood banks in the 1930s. News of the Soviet experience traveled to America, where in 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the first hospital blood bank in the United States. In creating a hospital laboratory that preserved and stored donor blood, Fantus originated the term "blood bank". Within a few years, hospital and community blood banks were established across the United States.
In the late 1930s and early 1940s, Dr. Charles R. Drew\'s research led to the discovery that blood could be separated into blood plasma and red blood cells, and that the components could be frozen separately. Blood stored in this way lasted longer and was less likely to become contaminated.
Another important breakthrough came in 1939-40 when Karl Landsteiner, Alex Wiener, Philip Levine, and R.E. Stetson discovered the Rhesus blood group system, which was found to be the cause of the majority of transfusion reactions up to that time. Three years later, the introduction by J.F. Loutit and Patrick L. Mollison of acid-citrate-dextrose (ACD) solution, which reduces the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer term storage.
Carl Walter and W.P. Murphy, Jr., introduced the plastic bag for blood collection in 1950. Replacing breakable glass bottles with durable plastic bags allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood. Further extending the shelf life of stored blood was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks.
Great care is taken in cross-matching to ensure that the recipient\'s immune system will not attack the donor blood. In addition to the familiar human blood types (A, B, AB and O) and Rh factor (positive or negative) classifications, other minor red cell antigens are known to play a role in compatibility. These other types can become increasingly important in people who receive many blood transfusions, as their bodies develop increasing resistance to blood from other people via a process of alloimmunization.
The key importance of the Rh group is its role in the Hemolytic Disease of the Newborn (HDN). When an Rh negative mother carries a positive foetus, she can become immunised against the Rh antigen. This usually is not important during that pregnancy, but in the following pregnancies she can develop an anamnesic response to the Rh antigen. IgG antibodies produced in that moment can cross the placental barrier and attack the foetal red cells. This can induce varying degrees of anemia in the foetus, whit hiperbilirubinemia, organ malfunction, etc. Bilirubin deposition in the cerebral basal ganglia (kernicterus)can lead to severe mental damage. Severe cases of HDN were mortal. HDN prevention started in the 60\'s when it was noted children of pregnant women who had received anti Rh immunoglobulin did not develop the disease. From then on, Rh negative pregnant women receive immunoglobulin doses at several moments during pregnancy and after childbirth if the baby is Rh positive. Besides, women in fertile age are never transfused Rh positive blood. Thus, HDN due to Rh antibodies has practically disappeared in developed countries.
Other red cell antigens can also cause HDN, but Rh group antigens are the most common cause.
A number of infectious diseases (such as HIV, syphilis, hepatitis B and hepatitis C, among others) can be passed from the donor to recipient. This has led to strict human blood transfusion standards in developed countries. Standards include screening for potential risk factors and health problems among donors by determining donor hemoglobin levels, administering a set of standard oral and written questions to donors, and laboratory testing of donated units for infection. The lack of such standards in places like rural China, where desperate villagers donated plasma for money and had others\' red blood cells reinjected, has produced entire villages infected with HIV.
As of mid-2005, all donated blood in the United States is screened for the following infectious agents:American Association of Blood Banks. Standards for Blood Banks and Transfusion Services, 18th ed. American Association of Blood Banks, Bethesda, MD.
When a person\'s need for a transfusion can be anticipated, as in the case of scheduled surgery, autologous donation can be used to protect against disease transmission and eliminate the problem of blood type compatibility.
Donated blood is usually subjected to processing after it is collected, to make it suitable for use in specific patient populations. Examples include:
To ensure the safety of blood transfusion to pediatric patients, hospitals are taking additional precaution to avoid infection and prefer to use specially tested pediatric blood units that are guaranteed negative for Cytomegalovirus. It is uncertain whether leukodepletion can be adequate for the prevention of CMV, and therefore most guidelines recommend the provision of CMV-negative blood components for newborns or low birthweight infants in whom the immune system is not fully developed.Red blood cell transfusions in newborn infants: Revised guidelines. Canadian Paediatric Society (CPS). Retrieved on 2007-02-02. These specific requirements place additional restrictions on blood donors who can donate to babies. Red cells transfusions are usually top-up transfusions, exchange transfusions, partial exchange transfusions. Top-up transfusions are for investigational losses and correction of mild degrees of anemias, up to 5-15 ml/kg. Exchange transfusions are done for correction of anemia, removal of bilirubin, removal of antibodies and replacement of red cells. Ideally plasma-reduced red cells that are not older than 5 days are used.Component therapy. KM Radhakrishnan , Srikumar Chakravarthi , S Pushkala, J Jayaraju. Indian J Pediatr. 2003 Aug ;70 (8):661-6 14510088[2]
The terms type and screen are used for the testing that (1) determines the blood group (ABO compatibility) and (2) checks for alloantibodies.Blood Processing. University of Utah. Available at: http://library.med.utah.edu/WebPath/TUTORIAL/BLDBANK/BBPROC.html. Accessed on: December 15, 2006. It takes about 45 minutes to complete (depending on the method used). The blood bank technologist also checks for special requirements of the patient (eg. need for washed, irradiated or CMV negative blood) and the history of the patient to see if they have a previously identified antibody.
A positive screen warrants an antibody panel/investigation. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for 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 enhancement method, eg Gel or LISS. 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 clinicially significant antibody it is vital that the patient receive antigen negative phenotyped red blood cells to prevent future transfusion reactions. A direct antiglobulin test (DAT) is also performed as part of the antibody investigation.D. Harmening, Modern Blood Banking and Transfusion Practices, 4th Ed. 1999
Once the type and screen has been completed, potential donor units will be selected based on compatibility with the patient\'s blood group, special requirements (eg CMV negative, irradiated or washed) and antigen negative (in the case of an antibody). If there is no current/historical antibody, the immediate spin or CAC (computer assisted crossmatch) method may be used.
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 in the test tube is a positive reaction and the unit should not be transfused.
If there is a current/historical antibody, potential donor units must first be screened for the antibody 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 of antibodies.
If there is no time the blood is called "uncross-matched blood". Uncross-matched blood is O-positive or O-negative. O-negative is usually 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.
Blood transfusions can be grouped into two main types depending on their source:
Donor units of blood must be kept refrigerated to prevent bacterial growth and to slow cellular metabolism. The transfusion must begin within 30 minutes after the unit has been taken out of controlled storage.
Blood can only be administered intravenously. It therefore requires the insertion of a cannula of suitable caliber.
Before the blood is administered, the personal details of the patient are matched with the blood to be transfused, to minimize risk of transfusion reactions. With the recognition that clerical error (eg administering the wrong unit of blood) is a significant source of transfusion reactions, attempts have been made to build redundancy into the matching process that takes place at the bedside.
A unit (up to 500 ml) is typically administered over 4 hours. In patients at risk of congestive heart failure, many doctors administer furosemide to prevent fluid overload. Acetaminophen and/or an antihistamine such as diphenhydramine are sometimes given before the transfusion to prevent a transfusion reaction.
Blood is most commonly donated as whole blood by inserting a catheter into a vein and collecting it in a plastic bag (mixed with anticoagulant) via gravity. Collected blood is then separated into components to make the best use of it. Aside from red blood cells, plasma, and platelets, the resulting blood component products also include 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.
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. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction.
Blood donation centers in different countries may have different guidelines about who can serve as a blood donor. Common contraindications to being a blood donor fall into two main groups: conditions which might cause a problem for the recipient and conditions which might cause a problem for the donor. A donor who is found ineligible is "deferred" from donation, though in some cases this may be a permanent deferral and the donor is not expected to return.
For recipient safety:
For donor safety:
Donating whole blood at a modern, well-run blood collection center is safe. The biggest risk is probably that of vasovagal syncope, or "passing out". A large study, involving 194,000 donations during a one-year period at an urban U.S. blood center, found 178 cases of syncope, for an incidence of 0.09%.Newman B, Graves S (2001). "A study of 178 consecutive vasovagal syncopal reactions from the perspective of safety.". Transfusion 41 (12): 1475-9. PMID 11778059. Only 5 of these incidents required emergency room attention, and there was one long-term complication. Most syncopal episodes occurred at the refreshment table following donation, leading the authors to recommend that donors spend at least 10 minutes at the refreshment table drinking fluids after donation. A Greek study of over 12,000 blood donors found an incidence of vasovagal events of 0.89%.Zervou E, Ziciadis K, Karabini F, Xanthi E, Chrisostomou E, Tzolou A (2005). "Vasovagal reactions in blood donors during or immediately after blood donation.". Transfus Med 15 (5): 389-94. PMID 16202053. Another study interviewed 1,000 randomly selected blood donors 3 weeks after donation, and found the following adverse effects:Newman B, Pichette S, Pichette D, Dzaka E (2003). "Adverse effects in blood donors after whole-blood donation: a study of 1000 blood donors interviewed 3 weeks after whole-blood donation.". Transfusion 43 (5): 598-603. PMID 12702180.
None of these were severe enough to require medical attention in this study. There is virtually no risk of acquiring an infection at a modern, well-run blood donation center.
Donation of blood products via apheresis is a more complex procedure and can entail additional risks, although this procedure is, overall, still very safe for the donor.
There are risks associated with receiving a blood transfusion, and these must be balanced against the benefit which is expected. The most common adverse reaction to a blood transfusion is a febrile non-hemolytic transfusion reaction, which consists of a fever which resolves on its own and causes no lasting problems or side effects.
Hemolytic reactions include chills, headache, backache, dyspnea, cyanosis, chest pain, tachycardia and hypotension.
Blood products can rarely be contaminated with bacteria; the risk of severe bacterial infection and sepsis is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions.Blajchman M. "Incidence and significance of the bacterial contamination of blood components.". Dev Biol (Basel) 108: 59-67. PMID 12220143.
Transmission of viral infection is a common concern with blood transfusion. As of 2006, the risk of acquiring hepatitis B via blood transfusion in the United States is about 1 in 250,000 units transfused, and the risk of acquiring HIV or hepatitis C in the U.S. via a blood transfusion is estimated at 1 per 2 million units transfused. These risks were much higher in the past before the advent of second and third generation tests for transfusion transmitted diseases. The implementation of Nucleic Acid Testing or "NAT" in the early 00\'s has further reduced risks, and confirmed viral infections by blood transfusion are extremely rare in the developed world.
Transfusion-associated acute lung injury (TRALI) is an increasingly recognized adverse event associated with blood transfusion. TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension, which may occur as often as 1 in 2000 transfusions.Silliman C, Paterson A, Dickey W, Stroneck D, Popovsky M, Caldwell S, Ambruso D (1997). "The association of biologically active lipids with the development of transfusion-related acute lung injury: a retrospective study.". Transfusion 37 (7): 719-26. PMID 9225936. Symptoms can range from mild to life-threatening, but most patients recover fully within 96 hours, and the mortality rate from this condition is less than 10%.Popovsky M, Chaplin H, Moore S. "Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy.". Transfusion 32 (6): 589-92. PMID 1502715. . Although the cause of TRALI is not clear, it has been consistently associated with anti HLA antibodies. Because anti HLA strongly correlate with pregnancy, several transfusion organisations (Blood and Tissues Bank of Cantabria, Spain, National Health Service in Britain) have decided to use only plasma from men for transfusion.
Other risks associated with receiving a blood transfusion include volume overload, iron overload (with multiple red blood cell transfusions), transfusion-associated graft-vs.-host disease, anaphylactic reactions (in people with IgA deficiency), and acute hemolytic reactions (most commonly due to the administration of mismatched blood types).
Scientists working at the University of Copenhagen reported in the journal Nature Biotechnology in April 2007 of discovering enzymes, which potentially enable blood from groups A, B and AB to be converted into group O. These enzymes do not affect the Rh group of the blood.Liu QP, Sulzenbacher G, Yuan H, Bennett EP, Pietz G, Saunders K, Spence J, Nudelman E, Levery SB, White T, Neveu JM, Lane WS, Bourne Y, Olsson ML, Henrissat B, Clausen H (2007). "Bacterial glycosidases for the production of universal red blood cells". Nat Biotechnol. PMID 17401360. BBC: Blood groups can be converted
Objections to blood transfusions may arise for personal, medical, or religious reasons. For example, Jehovah\'s Witnesses object to blood transfusion primarily on religious grounds, although they have also highlighted possible complications associated with transfusion.
Veterinarians also administer transfusions to animals. Various species require different levels of testing to ensure a compatible match. For example, cats have 3 blood types, cattle have 11, dogs have 12, pigs 16 and horses have 34. However, in many species (especially horses and dogs), cross matching is not required before the first transfusion, as antibodies against non-self cell surface antigens are not expressed constitutively - i.e. the animal has to be sensitized before it will mount an immune response against the transfused blood.
The rare and experimental practice of inter-species blood transfusions is a form of xenograft.
As of mid-2006, there are no clinically utilized oxygen-carrying blood substitutes for humans; however, there are widely available non-blood volume expanders and other blood-saving techniques. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah\'s Witnesses and others who have religious objections to receiving transfused blood.
A number of blood substitutes are currently in the clinical evaluation stage. Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in emergency medicine and in pre-hospital EMS care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results.
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This section may require cleanup to meet Wikipedia\'s quality standards. Please improve this article if you can (August 2007). |
As mentioned above, the major risks that the patient (donors and receivers) may have encountered are the transmission of HIV or hepatitis and immunological transfusion reactions. Most of these problems are risky possibilities and cannot always be effectively treated with appropriate medical care. In many cases, donors are either screened to reduce risks of these contaminations, the blood is tested, or both.
| Transfusion medicine | |
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| General concepts | Apheresis (Plasmapheresis, Plateletpheresis, Leukapheresis) - Blood transfusion - Coombs test - Cross-matching - Exchange transfusion - International Society of Blood Transfusion - Intraoperative blood salvage - ISBT 128 - Transfusion reactions |
| Human blood group systems - Blood type | ABO - Chido-Rodgers - Colton - Cromer - Diego - Dombrock - Duffy - Gerbich - GIL - Hh - Ii - Indian - JMH - Kell (Xk) - Kidd - Knops - Landsteiner-Weiner - Lewis - Lutheran - MNS - OK - P - Raph - Rh - Scianna - T-Tn - Xg - Yt |
| Blood products | Blood donation - Blood substitutes - Cryoprecipitate - Platelets - Plasma - Red blood cells |
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