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Blood transfusion is generally the process of receiving blood products into one's circulation intravenously. 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, white blood cells, plasma, clotting factors, and platelets.
Units of packed red blood cells are typically only recommended when either a patient's hemoglobin level falls below 10g/dL or hematocrit falls below 30%; recently, this 'trigger' level has been decreased to 7-8g/dL, as a more restrictive strategy has been shown to have better patient outcomes. This is in part due to the increasing evidence that there are cases where patients have worse outcomes when transfused. One may consider transfusion for people with symptoms of cardiovascular disease such as chest pain or shortness of breath. Globally around 85 million units of red blood cells are transfused in a given year. In cases where patients have low levels of hemoglobin but are cardiovascularly stable, parenteral iron is increasingly a preferred option based on both efficacy and safety. Other blood products are given where appropriate, such as clotting deficiencies.
When a patient's own blood is salvaged and reinfused during a surgery (e.g. using a cell salvage machine such as a Cell Saver), this can be considered a form of autotransfusion (and thus a form of transfusion) even though no "blood product" is actually created. Before this was possible, autotransfusion had referred only to pre-donating one's own blood autologously, which still occurs as well.
Before a blood transfusion is given, there are many steps taken to ensure quality of the blood products, compatibility, and safety to the recipient.
Blood transfusions typically use sources of blood: one's own (autologous transfusion), or someone else's (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 intravenously and collecting it with an anticoagulant. In developed 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. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction. In developing countries the donor is sometimes specifically recruited by or for the recipient, typically a family member, and the donation occurs immediately before the transfusion.
|The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. (June 2011)|
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, platelets, 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. 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 a 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. 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. A direct antiglobulin test (Coombs test) is also performed as part of the antibody investigation.
If there is no antibody present, an immediate spin crossmatch or computer assisted crossmatch is 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 and the unit should not be transfused.
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 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.
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. Most guidelines recommend the provision of CMV-negative blood components and not simply leukoreduced components for newborns or low birthweight infants in whom the immune system is not fully developed. These specific requirements place additional restrictions on blood donors who can donate for neonatal use. vnv Neonatal transfusions typically fall into one of two categories:
A massive transfusion protocol is typically defined as when it is anticipated that more than ten units of packed red blood cells will be needed. Typically higher ratios of fresh frozen plasma and platelets are given relative to packed red blood cells.
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.
In the same way that the safety of pharmaceutical products are overseen by pharmacovigalence, the safety of blood and blood products are 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. In the UK this data is collected by a charity called SHOT (Serious Hazards Of Transfusion).
Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is also increasing focus (and controversy) on complications arising directly or indirectly from potential quality degradation during storage. Overall, adverse events from transfusions in the US account for about $17 Billion - and in effect add more to the cost of each transfusion than acquisition and procedure costs combined. While some complication risks depend on patient status or specific transfusion quantity involved, a baseline risk of complications simply increases in direct proportion to the frequency and volume of transfusion.
On rare occasion, blood products are contaminated with bacteria. This can result in life-threatening infection, also known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions. It is important to note that 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 when exceeding 5 days. Sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and from containers. Contaminating organisms vary greatly, and include skin flora, gut flora, or 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 1980s, the transmission of HIV during transfusion has dropped dramatically. Prior testing of donor blood only included testing for antibodies to HIV. However, due to 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. Although some of the biochemical changes are reversible after the blood is transfused, the biomechanical changes are less so, and rejuvenation products are not yet able to adequately reverse this phenomenon. There has been increasing 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. Studies have not been consistent on answering this question, with some showing that older blood is indeed less effective but with others showing no such difference; these developments are being closely followed by hospital blood bankers - who are the physicians, typically pathologists, who collect and manage inventories of tranfusable 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). However, all of these criteria are applied in a universal manner that does not account for differences among units of product. 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 (of course, 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. 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 and erythrocyte fragility (mechanical).
Many physicians have adopted a so-called "restrictive protocol" - whereby transfusion is held to a minimum - due in part to the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions, along with the increasing view that many transfusions are inappropriate or use too many RBC units. Of course, restrictive protocol is not an option with some especially vulnerable patients who may require the best possible efforts to rapidly restore tissue oxygenation.
Although tranfusions of platelets are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern.
Beginning with Harvey's experiments with circulation of the blood, 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.
The first fully documented human blood transfusion was administered by Dr. Jean-Baptiste Denys, eminent physician to King Louis XIV of France, on June 15, 1667. He transfused the blood of a sheep into a 15-year-old boy, who survived the transfusion. 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' third patient to undergo a blood transfusion was Swedish Baron Gustaf Bonde. He received two transfusions. After the second transfusion Bonde died. In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood, who on the third account died. Much controversy surrounded his death. Mauroy's wife asserted Denys was responsible for her husband's death; she was accused as well, though it was later determined that Mauroy actually died from arsenic poisoning, Denys' experiments with animal blood provoked a heated controversy in France. Finally, in 1670 the procedure was banned. In time, the British Parliament and the Vatican followed suit. Blood transfusions fell into obscurity for the next 150 years.
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 1665 in the Society's Philosophical Transactions.
Six months later in London, Lower performed the first human transfusion of animal blood in Britain. At a meeting of the Royal Society, Lower stated he had "superintended the introduction in [a patient's] arm at various times of some ounces of sheep's blood at , 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 refused. No more transfusions were performed. Shortly before, Lower had moved to London, where his growing practice soon led him to abandon research.
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).
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 following 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. He made a substantial amount of money from this endeavour, roughly $2 million ($50 million real dollars).
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.[when?]
Early transfusions were risky and many resulted in the death of the patient. It was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer. Mixing blood from two incompatible individuals can lead to an immune response, and the destruction of red blood cells releases free hemoglobin into the bloodstream, which can have fatal consequences. Karl Landsteiner discovered that when incompatible types are mixed, the red blood cells clump, and that this immunological reaction occurs when the receiver of a blood transfusion has antibodies against the donor blood cells. His work made it possible to determine blood type and allowed a way for blood transfusions to be carried out much more safely. For this discovery he was awarded the Nobel Prize in Physiology and Medicine in 1930, and many other blood groups have been discovered since.
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, though this was a diluted solution of blood. The Argentine doctor Luis Agote used a much less diluted solution in November of the same year. Both used sodium citrate as an anticoagulant. The First World War acted as a catalyst for the rapid development of blood banks and transfusion techniques. The first blood transfusion using blood that had been stored and cooled was performed on January 1, 1916. Geoffrey Keynes, a British surgeon, developed a portable machine that could store blood to enable transfusions to be carried out more easily. His work was recognized as saving thousands of lives during the war. 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. Bogdanov died 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 not completely understood at the time.
Today, Red Blood Cells (RBC) can be stored for up to 42 days / 6 weeks from the time of collection, assuming proper storage solutions and conditions. While this particular shelf life has little evidentiary basis and persists primarily for historical reasons, it remains the default metric in the absence of any direct means for measuring actual quality degradation of product units. Likewise, inventory is managed essentially on a "first-in-first-out" basis, due to the need to rely upon storage time as a rough indicator of quality (with many controversies surrounding the extent to which this is reliable).
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 plasma 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.
In the field of cancer surgery replacement of massive blood loss became a major problem. The cardiac arrest rate was high. In 1963, C. Paul Boyan and Willam Howland discovered that the temperature of the blood and the rate of infusion greatly affected survival rates, and introduced blood warming to surgery.
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.
As of 2006, there were about 15 million units of blood products transfused per year in the United States.
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—they believe that blood is sacred, the Bible says "abstain from blood" (Acts 15:28,29) they have also highlighted complications associated with transfusion.
Veterinarians also administer transfusions to other animals. Various species require different levels of testing to ensure a compatible match. For example, cats have 3 known blood types, 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.
Thus far, there are no available oxygen-carrying blood substitutes, which is the typical objective of a blood (RBC) transfusion; however, there are widely available non-blood volume expanders for cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood.
A number of blood substitutes have been explored (and still are), but thus far they all suffer from many challenges. Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in emergency medicine and in pre-hospital EMS care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results. Hemopure, a hemoglobin-based therapy, is approved for use in South Africa.
Although there are clinical situations where transfusion with red blood cells is the only clinically appropriate option, increasingly clinicians are looking at alternatives. This can be due to several reasons, such as patient safety, economic burden or scarcity of blood. Increasingly guidelines recommend blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia In these cases parenteral iron is recommended.
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