Blood transfusion: Difference between revisions

Blood transfusion
Blood transfusion
	Plastic bag with 0.5 - 0.7 liters containing packed red blood cells in citrate, phosphate, dextrose, and adenine (CPDA) solution
ICD-9-CM	99.0
MeSH	D001803
OPS-301 code	8-80
MedlinePlus	000431
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Blood transfusion is generally the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of 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.^[1] This is in part due to the increasing evidence that there are cases where patients have worse outcomes when transfused.^[2] One may consider transfusion for people with symptoms of cardiovascular disease such as chest pain or shortness of breath.^[1] Globally around 85 million units of red blood cells are transfused in a given year.^[1] 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.^[3] 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.

Pre-transfusion procedures

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 donation

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.

Processing and testing of blood products after donation

Template:Globalize/US

photograph of a bag containing one unit of fresh frozen plasma — A bag containing one unit of fresh frozen plasma

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.

All donated blood is tested for infections^{[citation needed]}. The current protocol tests donated blood for HIV-1, HIV-2, HTLV-1, HTLV-2, Hepatitis B, Hepatitis C, Syphilis (Treponema pallidum), Chagas disease (Trypanosoma cruzi), and West Nile Virus. In addition, platelet products are also tested for bacterial infections due to its higher inclination for contamination due to storage at room temperature. Presence of Cytomegalovirus (CMV) is also tested because of risk to certain immunocompromised recipients if given, such as those with organ transplant or HIV. However, not all blood is tested for CMV because only a certain amount of CMV-negative blood needs to be available to supply patient needs. Other than positivity for CMV, any products tested positive for infections are not used.
All donated blood is also tested for ABO and Rh groups, along with the presence of any red blood cell antibodies.
Leukoreduction is the removal of white blood cells by filtration. Leukoreduced blood products are less likely to cause HLA alloimmunization (development of antibodies against specific blood types), febrile non-hemolytic transfusion reaction, cytomegalovirus infection, and platelet-transfusion refractoriness.
Pathogen Reduction treatment that involves, for example, the addition of riboflavin with subsequent exposure to UV light has been shown to be effective in inactivating pathogens (viruses, bacteria, parasites and white blood cells) in blood products.^[4]^[5]^[6] By inactivating white blood cells in donated blood products, riboflavin and UV light treatment can also replace gamma-irradiation as a method to prevent graft-versus-host disease (TA-GvHD).^[7]^[8]^[9]

Compatibility testing

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.^[10] 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.^[11]

If there is no antibody present, an immediate spin crossmatch or computer assisted crossmatch is performed where the recipient serum and donor serum 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.

Neonatal transfusion

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.^[12] 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:

"Top-up" transfusions, to replace losses due to investigational losses and correction of anemia.
Exchange (or partial exchange) transfusions are done for removal of bilirubin, removal of antibodies and replacement of red cells (e.g., for anemia secondary to thalassemias and other hemoglobinopathies).^[13]

Procedures

Massive transfusion protocol

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.^[14] Typically higher ratios of fresh frozen plasma and platelets are given relative to packed red blood cells.^[14]

Epidemiology

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.^[15]

Adverse effects

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.^[16] In the UK this data is collected by a charity called SHOT (Serious Hazards Of Transfusion).^[17]

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.^[18] 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.^[19] 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.

Immunologic reaction

Acute hemolytic reactions occur with transfusion of red blood cells, and occurs in about 0.016 percent of transfusions, with about 0.003 percent being fatal.^{[citation needed]} This is due to destruction of donor erythrocytes by preformed recipient antibodies. Most often this occurs due to clerical errors or improper typing and crossmatching. Symptoms include fever, chills, chest pain, back pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop in blood pressure. When suspected, transfusion should be stopped immediately, and blood sent for tests to evaluate for presence of hemolysis. Treatment is supportive. Kidney injury may occur due to the effects of the hemolytic reaction (pigment nephropathy).

Delayed hemolytic reactions occur more frequently (about 0.025 percent of transfusions) and are due to the same mechanism as in acute hemolytic reactions. However, the consequences are generally mild and a great proportion of patients may not have symptoms. However, evidence of hemolysis and falling hemoglobin levels may still occur. Treatment is generally not needed, but due to the presence of recipient antibodies, future compatibility may be affected.

Febrile nonhemolytic reactions are due to recipient antibodies to donor white blood cells, and occurs in about 7% of transfusions. This may occur after exposure from previous transfusions. Fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. This is a reason for the now-widespread use of leukoreduction - the filtration of donor white cells from red cell product units.

Allergic reactions may occur when the recipient has preformed antibodies to certain chemicals in the donor blood, and does not require prior exposure to transfusions. Symptoms include urticaria, pruritus, and may proceed to anaphylactic shock. Treatment is the same as for any other type 1 hypersensitivity reactions. A small population (0.13%) of patients are deficient in the immunoglobin IgA, and upon exposure to IgA-containing blood, may develop an anaphylactic reaction.

Posttransfusion purpura is a rare complication that occurs after transfusion containing platelets that express a surface protein HPA-1a. Recipients who lack this protein develop sensitization to this protein from prior transfusions, and develop thrombocytopenia about 7–10 days after subsequent transfusions. Treatment is with intravenous immunoglobulin, and recipients should only receive future transfusions with washed cells or HPA-1a negative cells.

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.^[20] 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%.^[21] Although the cause of TRALI is not clear, it has been consistently associated with anti-HLA antibodies. Because these types of antibodies are commonly formed during pregnancy, several transfusion organisations have decided to use only plasma from men for transfusion.^[22] TRALI is typically associated with plasma components rather than packed red blood cells (RBCs), though there is some residual plasma in RBC units.^[22]

Infection

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.^[23] 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.

Inefficacy

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.^[24] Although some of the biochemical changes are reversible after the blood is transfused,^[25] the biomechanical changes are less so,^[26] and rejuvenation products are not yet able to adequately reverse this phenomenon.^[27] 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.^[28]^[29] Studies have not been consistent on answering this question,^[30] 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).^[31] However, all of these criteria are applied in a universal manner that does not account for differences among units of product.^[32] 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.^[33] 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^[34] and erythrocyte fragility (mechanical).^[35]

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,^[19] along with the increasing view that many transfusions are inappropriate or use too many RBC units.^[36]^[37] 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.^[38]

Other

Transfusion-associated volume overload is a common complication simply due to the fact that blood products have a certain amount of volume. This is especially the case in recipients with underlying cardiac or kidney disease. Red cell transfusions can lead to volume overload when they must be repeated due to insufficient efficacy (see above). Plasma transfusion is especially prone to causing volume overload due to its hypertonicity.

Hypothermia can occur with transfusions with large quantities of blood products which normally are stored at cold temperatures. Core body temperature can go down as low as 32 °C and can produce physiologic disturbances. Prevention should be done with warming the blood to ambient temperature prior to transfusions.

Transfusions with large amounts of red blood cells, whether due to severe hemorrhaging and/or transfusion inefficacy (see above), can lead to an inclination for bleeding. The mechanism is thought to be due to disseminated intravascular coagulation, along with dilution of recipient platelets and coagulation factors. Close monitoring and transfusions with platelets and plasma is indicated when necessary.

Metabolic alkalosis can occur with massive blood transfusions due to the breakdown of citrate stored in blood into bicarbonate

Hypocalcemia can also occur with massive blood transfusions due to the complex of citrate with serum calcium

Blood doping is often used by athletes, drug addicts or military personnel for reasons such as to increase physical stamina, to fake a drug detection test or simply to remain active and alert during the duty-times respectively. However a lack of knowledge and insufficient experience can turn a blood transfusion into a sudden death. For example, when individuals run the frozen blood sample directly in their veins this cold blood rapidly reaches the heart, where it disturbs the heart's original pace leading to cardiac arrest and sudden death.

History

Early attempts with animal blood

World War II Russian syringe for direct inter-human blood transfusion

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.

Jean-Baptiste Denys

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.^[39] He transfused the blood of a sheep into a 15-year-old boy, who survived the transfusion.^[40] 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.^[41] In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood, who on the third account died.^[42] 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.^[41] 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

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.^{[citation needed]}

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.^[43]

Early efforts to transfuse human blood

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.^[44] He made a substantial amount of money from this endeavour, roughly $2 million ($50 million real dollars).^{[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 haemophilia.

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?]^[45]

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.

Development of blood banking

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.^[46] 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.^{[citation needed]} 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.^[47]

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.^[48]

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).

The modern era

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.^[49]^[50]

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.^[51]

Ethical issues

Religious

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.^[52]

Between animals

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.

Blood substitutes

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.

Alternative treatment options

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^[53]^[54] In these cases parenteral iron is recommended.

References

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^ Villanueva, C; Colomo, A; Bosch, A; Concepción, M; Hernandez-Gea, V; Aracil, C; Graupera, I; Poca, M; Alvarez-Urturi, C; Gordillo, J; Guarner-Argente, C; Santaló, M; Muñiz, E; Guarner, C (2013). "Transfusion strategies for acute upper gastrointestinal bleeding". The New England journal of medicine. 368 (1): 11–21. doi:10.1056/NEJMoa1211801. PMID 23281973.
^ Gasche, C; Berstad, A; Befrits, R; Beglinger, C; Dignass, A; Erichsen, K; Gomollon, F; Hjortswang, H; Koutroubakis, I; Kulnigg, S; Oldenburg, B; Rampton, D; Schroeder, O; Stein, J; Travis, S; Van Assche, G (2007). "Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases" (PDF). Inflammatory bowel diseases. 13 (12): 1545–53. doi:10.1002/ibd.20285. PMID 17985376.
^ Hardwick, CC; Herivel, TR; Hernandez, SC; Ruane, PH; Goodrich, RP (2004). "Separation, Identification and Quantification of Riboflavin and Its Photoproducts in Blood Products Using High-Performance Liquid Chromatography With Fluorescence Detection: A Method to Support Pathogen Reduction Technology". Photochemistry and Photobiology. 80 (3): 609–615. doi:10.1562/0031-8655(2004)080<0609:TNSIAQ>2.0.CO;2. ISSN 0031-8655. PMID 15382964.
^ Mirasol Clinical Evaluation Study Group; Folléa, G.; Bardiaux, L.; Boiron, J.-M.; Lafeuillade, B.; Debost, M.; Lioure, B.; Harousseau, J-L.; Tabrizi, R.; Cahn, J.-Y.; Michallet; Ambruso, D.; Schots, R.; Tissot, J.-D.; Sensebé, L.; Kondo, T.; McCullough, J.; Rebulla, Paolo; Escolar, Gines; Mintz, P.; Heddle; Goodrich, R.P.; Bruhwyler, J.; Le, C.; Cook, R.J.; Stouch, B. (2010). "A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology". Transfusion. 50 (11): 2362–75. doi:10.1111/j.1537-2995.2010.02694.x. PMID 20492615.
^ Goodrich, RP; Edrich, RA; Li, J; Seghatchian, J (2006). "The Mirasol PRT system for pathogen reduction of platelets and plasma: An overview of current status and future trends". Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 35 (1): 5–17. doi:10.1016/j.transci.2006.01.007. PMID 16935562.
^ Fast, LD; Dileone, G; Cardarelli, G; Li, J; Goodrich, R (2006). "Mirasol PRT Treatment of Donor White Blood Cells Prevents the Development of Xenogeneic Graft-Versus-Host Disease in Rag2-/-γc-/- Double Knockout Mice". Transfusion. 46 (9): 1553–1560. doi:10.1111/j.1537-2995.2006.00939.x. PMID 16965583.
^ Fast, LD; Dileone, G; Marschner, S (2011). "Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation". Transfusion. 51 (7): 1397–404. doi:10.1111/j.1537-2995.2010.02984.x. PMID 21155832.
^ Reddy, Heather L.; Dayan, Anthony D.; Cavagnaro, Joy; Gad, Shayne; Li, Junzhi; Goodrich, Raymond P. (2008). "Toxicity Testing of a Novel Riboflavin-Based Technology for Pathogen Reduction and White Blood Cell Inactivation". Transfusion Medicine Reviews. 22 (2): 133–53. doi:10.1016/j.tmrv.2007.12.003. PMID 18353253.
^ Blood Processing. University of Utah. Available at: http://library.med.utah.edu/WebPath/TUTORIAL/BLDBANK/BBPROC.html. Accessed on: December 15, 2006.
^ Harmening, D. (1999). Modern Blood Banking and Transfusion Practices (4th ed.). Philadelphia: F. A. Davis. ISBN 0-8036-0419-X.
^ "Red blood cell transfusions in newborn infants: Revised guidelines". Canadian Paediatric Society (CPS). Retrieved 2007-02-02.
^ KM Radhakrishnan, Srikumar Chakravarthi, S Pushkala, J Jayaraju (2003 Aug). "Component therapy". Indian J Pediatr. 70 (8): 661–6. doi:10.1007/BF02724257. PMID 14510088. {{cite journal}}: Check date values in: |date= (help)CS1 maint: multiple names: authors list (link)
^ ^a ^b Cherkas, David (2011). "Traumatic Hemorrhagic Shock: Advances In Fluid Management". Emergency Medicine Practice. 13 (11). {{cite journal}}: Unknown parameter |month= ignored (help)
^ Pfuntner A., Wier L.M., Stocks C. Most Frequent Procedures Performed in U.S. Hospitals, 2011. HCUP Statistical Brief #165. October 2013. Agency for Healthcare Research and Quality, Rockville, MD. [1].
^ "WHO | Haemovigilance". Who.int. 2013-06-25. Retrieved 2013-12-11.
^ "Welcome to the website for SHOT, the United Kingdom's independent, - Serious Hazards of Transfusion : Serious Hazards of Transfusion". Shotuk.org. 2010-03-11. Retrieved 2013-12-11.
^ Wang SS. What's the Shelf Life of Blood? Focus on Whether Older Donations Impair Recovery of Transfusion Recipients. The Wall Street Journal. 2009 Dec. 1.
^ ^a ^b Shander, A; Hofmann, A; Gombotz, H; Theusinger, OM; Spahn, DR (2007). "Estimating the cost of blood: Past, present, and future directions". Best practice & research. Clinical anaesthesiology. 21 (2): 271–89. PMID 17650777.
^ 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. doi:10.1046/j.1537-2995.1997.37797369448.x. PMID 9225936.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Popovsky M, Chaplin H, Moore S (1992). "Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy". Transfusion. 32 (6): 589–92. doi:10.1046/j.1537-2995.1992.32692367207.x. PMID 1502715.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^a ^b Win N, Chapman CE, Bowles KM, Green A, Bradley S, Edmondson D, Wallis JP (2008). "How much residual plasma may cause TRALI?". Transfusion Medicine. 18 (5): 276–280. doi:10.1111/j.1365-3148.2008.00885.x. PMID 18937733.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Blajchman M (2002). "Incidence and significance of the bacterial contamination of blood components". Dev Biol (Basel). 108 (2): 59–67. PMID 12220143.
^ Zubair, AC (2010). "Clinical impact of blood storage lesions". American journal of hematology. 85 (2): 117–22. doi:10.1002/ajh.21599. PMID 20052749.
^ Heaton, A; Keegan, T; Holme, S (1989). "In vivo regeneration of red cell 2,3-diphosphoglycerate following transfusion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells". British journal of haematology. 71 (1): 131–6. PMID 2492818.
^ Frank, SM; Abazyan, B; Ono, M; Hogue, CW; Cohen, DB; Berkowitz, DE; Ness, PM; Barodka, VM (2013). "Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration". Anesthesia and analgesia. 116 (5): 975–81. doi:10.1213/ANE.0b013e31828843e6. PMC 3744176. PMID 23449853.
^ [2]^{[dead link]}
^ http://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/
^ Wang, Shirley S. (2009-12-01). "What's the Shelf Life of Blood?". The Wall Street Journal.
^ Aubron, Cécile; Nichol, Alistair; Cooper, D Jamie; Bellomo, Rinaldo (2013). "Age of red blood cells and transfusion in critically ill patients". Annals of Intensive Care. 3 (1): 2. doi:10.1186/2110-5820-3-2. PMC 3575378. PMID 23316800.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Hod, EA; Zhang, N; Sokol, SA; Wojczyk, BS; Francis, RO; Ansaldi, D; Francis, KP; Della-Latta, P; Whittier, S; Sheth, S; Hendrickson, JE; Zimring, JC; Brittenham, GM; Spitalnik, SL (2010). "Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation". Blood. 115 (21): 4284–92. doi:10.1182/blood-2009-10-245001. PMC 2879099. PMID 20299509.
^ Hess, JR; Biomedical Excellence for Safer Transfusion (BEST) Collaborative (2012). "Scientific problems in the regulation of red blood cell products". Transfusion. 52 (8): 1827–35. doi:10.1111/j.1537-2995.2011.03511.x. PMID 22229278.
^ Pape, A; Stein, P; Horn, O; Habler, O (2009). "Clinical evidence of blood transfusion effectiveness". Blood Transfusion. 7 (4): 250–258. doi:10.2450/2008.0072-08. PMC 2782802.
^ Burns, JM; Yang, X; Forouzan, O; Sosa, JM; Shevkoplyas, SS (2012). "Artificial microvascular network: A new tool for measuring rheologic properties of stored red blood cells". Transfusion. 52 (5): 1010–23. doi:10.1111/j.1537-2995.2011.03418.x. PMID 22043858.
^ Raval, JS; Waters, JH; Seltsam, A; Scharberg, EA; Richter, E; Daly, AR; Kameneva, MV; Yazer, MH (2010). "The use of the mechanical fragility test in evaluating sublethal RBC injury during storage". Vox sanguinis. 99 (4): 325–31. doi:10.1111/j.1423-0410.2010.01365.x. PMID 20673245.
^ [3]^{[dead link]}
^ "College of American Pathologists - Easy does it-showing caution with RBC transfusions". Cap.org. Retrieved 2013-12-11.
^ Devine, DV; Serrano, K (2010). "The platelet storage lesion". Clinics in laboratory medicine. 30 (2): 475–87. doi:10.1016/j.cll.2010.02.002. PMID 20513565.
^ "The First Blood Transfusion?". Heart-valve-surgery.com. 2009-01-03. Retrieved 2010-02-09.
^ "This Month in Anesthesia History". Retrieved 2009-06-15.
^ ^a ^b "Red Gold . Innovators & Pioneers . Jean-Baptiste Denis". PBS. Retrieved 2010-02-09.
^ Klein, Harvey G; Anstee, David J, eds. (2005). Mollison's Blood Transfusion in Clinical Medicine. doi:10.1002/9780470986868. ISBN 9780470986868""{{cite book}}: CS1 maint: postscript (link) p.406
^ Felts, John H. (2000). "Richard Lower: Anatomist and Physiologist". Annals of Internal Medicine. 132 (5): 420–3. doi:10.7326/0003-4819-132-5-200003070-00023. PMID 10691601.
^ Ellis, H. Surgical Anniversaries: James Blundell, pioneer of blood transfusion British Journal of Hospital Medicine, August 2007, Vol 68, No 8.
^ Nathoo, N; Lautzenheiser, FK; Barnett, GH (2009). "The first direct human blood transfusion: The forgotten legacy of George W. Crile". Neurosurgery. 64 (3 Suppl): ons20–6, discussion ons26–7. doi:10.1227/01.NEU.0000334416.32584.97. PMID 19240569.
^ Gordon, Murray B. (1940). "Effect of External Temperature on Sedimentation Rate of Red Blood Corpuscles". Journal of the American Medical Association. 114 (16). doi:10.1001/jama.1940.02810160078030.
^ "Red Gold: the Epic Story of Blood". PBS.
^ Bernice Glatzer Rosenthal. New Myth, New World: From Nietzsche to Stalinism, Pennsylvania State University, 2002, ISBN 0-271-02533-6 pp. 161-162.
^ Boyan, CP; Howland, WS (1963). "Cardiac arrest and temperature of bank blood". JAMA : the journal of the American Medical Association. 183: 58–60. PMID 14014662.
^ Rupreht, J (1985). Anaesthesia: essays on its history. Springer-Verlag. pp. 99–101. ISBN 3-540-13255-4. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Laura Landro (2007-01-10). "New rules may shrink ranks of blood donors". Wall Street Journal.
^ http://www.jw.org/en/publications/books/blood/how-can-blood-save-your-life/
^ Goddard, A. F.; James, M. W.; McIntyre, A. S.; Scott, B. B.; British Society of Gastroenterology (2011). "Guidelines for the management of iron deficiency anaemia". Gut. 60 (10): 1309–16. doi:10.1136/gut.2010.228874. PMID 21561874.
^ Transfusion Medicine Reviews, Vol 0, No 0 (Month), 2011: pp 1-15.e53

External links

Transfusion, ISSN: 1537-2995 (electronic) 0041-1132 (paper)
Blood Groups and Red Cell Antigens. Free online book at NCBI Bookshelf ID: NBK2261
Blood Transfusion Indications, information provide by Maharashtra State Blood Transfusion Council.
Five Myths on Blood Transfusions, an information campaign by the New South Wales Government.
The Dangers of Illegal Blood Trade
Cochrane Injuries Group, publishes systematic reviews of interventions for traumatic injury, which include evaluations of blood and blood substitute transfusions

Template:Link FA Template:Link FA

[AABB2012-1] Carson, JL (2012 Mar 26). "Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB". Annals of internal medicine. doi:10.1059/0003-4819-156-12-201206190-00429. PMID 22454395. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[2] Villanueva, C; Colomo, A; Bosch, A; Concepción, M; Hernandez-Gea, V; Aracil, C; Graupera, I; Poca, M; Alvarez-Urturi, C; Gordillo, J; Guarner-Argente, C; Santaló, M; Muñiz, E; Guarner, C (2013). "Transfusion strategies for acute upper gastrointestinal bleeding". The New England journal of medicine. 368 (1): 11–21. doi:10.1056/NEJMoa1211801. PMID 23281973.

[3] Gasche, C; Berstad, A; Befrits, R; Beglinger, C; Dignass, A; Erichsen, K; Gomollon, F; Hjortswang, H; Koutroubakis, I; Kulnigg, S; Oldenburg, B; Rampton, D; Schroeder, O; Stein, J; Travis, S; Van Assche, G (2007). "Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases" (PDF). Inflammatory bowel diseases. 13 (12): 1545–53. doi:10.1002/ibd.20285. PMID 17985376.

[4] Hardwick, CC; Herivel, TR; Hernandez, SC; Ruane, PH; Goodrich, RP (2004). "Separation, Identification and Quantification of Riboflavin and Its Photoproducts in Blood Products Using High-Performance Liquid Chromatography With Fluorescence Detection: A Method to Support Pathogen Reduction Technology". Photochemistry and Photobiology. 80 (3): 609–615. doi:10.1562/0031-8655(2004)080<0609:TNSIAQ>2.0.CO;2. ISSN 0031-8655. PMID 15382964.

[5] Mirasol Clinical Evaluation Study Group; Folléa, G.; Bardiaux, L.; Boiron, J.-M.; Lafeuillade, B.; Debost, M.; Lioure, B.; Harousseau, J-L.; Tabrizi, R.; Cahn, J.-Y.; Michallet; Ambruso, D.; Schots, R.; Tissot, J.-D.; Sensebé, L.; Kondo, T.; McCullough, J.; Rebulla, Paolo; Escolar, Gines; Mintz, P.; Heddle; Goodrich, R.P.; Bruhwyler, J.; Le, C.; Cook, R.J.; Stouch, B. (2010). "A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology". Transfusion. 50 (11): 2362–75. doi:10.1111/j.1537-2995.2010.02694.x. PMID 20492615.

[6] Goodrich, RP; Edrich, RA; Li, J; Seghatchian, J (2006). "The Mirasol PRT system for pathogen reduction of platelets and plasma: An overview of current status and future trends". Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 35 (1): 5–17. doi:10.1016/j.transci.2006.01.007. PMID 16935562.

[7] Fast, LD; Dileone, G; Cardarelli, G; Li, J; Goodrich, R (2006). "Mirasol PRT Treatment of Donor White Blood Cells Prevents the Development of Xenogeneic Graft-Versus-Host Disease in Rag2-/-γc-/- Double Knockout Mice". Transfusion. 46 (9): 1553–1560. doi:10.1111/j.1537-2995.2006.00939.x. PMID 16965583.

[8] Fast, LD; Dileone, G; Marschner, S (2011). "Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation". Transfusion. 51 (7): 1397–404. doi:10.1111/j.1537-2995.2010.02984.x. PMID 21155832.

[9] Reddy, Heather L.; Dayan, Anthony D.; Cavagnaro, Joy; Gad, Shayne; Li, Junzhi; Goodrich, Raymond P. (2008). "Toxicity Testing of a Novel Riboflavin-Based Technology for Pathogen Reduction and White Blood Cell Inactivation". Transfusion Medicine Reviews. 22 (2): 133–53. doi:10.1016/j.tmrv.2007.12.003. PMID 18353253.

[uutah-10] Blood Processing. University of Utah. Available at: http://library.med.utah.edu/WebPath/TUTORIAL/BLDBANK/BBPROC.html. Accessed on: December 15, 2006.

[11] Harmening, D. (1999). Modern Blood Banking and Transfusion Practices (4th ed.). Philadelphia: F. A. Davis. ISBN 0-8036-0419-X.

[neonatal-CMV-12] "Red blood cell transfusions in newborn infants: Revised guidelines". Canadian Paediatric Society (CPS). Retrieved 2007-02-02.

[13] KM Radhakrishnan, Srikumar Chakravarthi, S Pushkala, J Jayaraju (2003 Aug). "Component therapy". Indian J Pediatr. 70 (8): 661–6. doi:10.1007/BF02724257. PMID 14510088. {{cite journal}}: Check date values in: |date= (help)CS1 maint: multiple names: authors list (link)

[EMB11-14] Cherkas, David (2011). "Traumatic Hemorrhagic Shock: Advances In Fluid Management". Emergency Medicine Practice. 13 (11). {{cite journal}}: Unknown parameter |month= ignored (help)

[15] Pfuntner A., Wier L.M., Stocks C. Most Frequent Procedures Performed in U.S. Hospitals, 2011. HCUP Statistical Brief #165. October 2013. Agency for Healthcare Research and Quality, Rockville, MD. [1].

[16] "WHO | Haemovigilance". Who.int. 2013-06-25. Retrieved 2013-12-11.

[17] "Welcome to the website for SHOT, the United Kingdom's independent, - Serious Hazards of Transfusion : Serious Hazards of Transfusion". Shotuk.org. 2010-03-11. Retrieved 2013-12-11.

[18] Wang SS. What's the Shelf Life of Blood? Focus on Whether Older Donations Impair Recovery of Transfusion Recipients. The Wall Street Journal. 2009 Dec. 1.

[Missingor-19] Shander, A; Hofmann, A; Gombotz, H; Theusinger, OM; Spahn, DR (2007). "Estimating the cost of blood: Past, present, and future directions". Best practice & research. Clinical anaesthesiology. 21 (2): 271–89. PMID 17650777.

[20] 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. doi:10.1046/j.1537-2995.1997.37797369448.x. PMID 9225936.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[21] Popovsky M, Chaplin H, Moore S (1992). "Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy". Transfusion. 32 (6): 589–92. doi:10.1046/j.1537-2995.1992.32692367207.x. PMID 1502715.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[Win_N,_Chapman_CE,_Bowles_KM,_Green_A,_Bradley_S,_Edmondson_D,_Wallis_JP_2008_276–280-22] Win N, Chapman CE, Bowles KM, Green A, Bradley S, Edmondson D, Wallis JP (2008). "How much residual plasma may cause TRALI?". Transfusion Medicine. 18 (5): 276–280. doi:10.1111/j.1365-3148.2008.00885.x. PMID 18937733.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[23] Blajchman M (2002). "Incidence and significance of the bacterial contamination of blood components". Dev Biol (Basel). 108 (2): 59–67. PMID 12220143.

[24] Zubair, AC (2010). "Clinical impact of blood storage lesions". American journal of hematology. 85 (2): 117–22. doi:10.1002/ajh.21599. PMID 20052749.

[25] Heaton, A; Keegan, T; Holme, S (1989). "In vivo regeneration of red cell 2,3-diphosphoglycerate following transfusion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells". British journal of haematology. 71 (1): 131–6. PMID 2492818.

[26] Frank, SM; Abazyan, B; Ono, M; Hogue, CW; Cohen, DB; Berkowitz, DE; Ness, PM; Barodka, VM (2013). "Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration". Anesthesia and analgesia. 116 (5): 975–81. doi:10.1213/ANE.0b013e31828843e6. PMC 3744176. PMID 23449853.

[27] [2]^{[dead link]}

[28] ttp://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/

[29] Wang, Shirley S. (2009-12-01). "What's the Shelf Life of Blood?". The Wall Street Journal.

[30] Aubron, Cécile; Nichol, Alistair; Cooper, D Jamie; Bellomo, Rinaldo (2013). "Age of red blood cells and transfusion in critically ill patients". Annals of Intensive Care. 3 (1): 2. doi:10.1186/2110-5820-3-2. PMC 3575378. PMID 23316800.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[31] Hod, EA; Zhang, N; Sokol, SA; Wojczyk, BS; Francis, RO; Ansaldi, D; Francis, KP; Della-Latta, P; Whittier, S; Sheth, S; Hendrickson, JE; Zimring, JC; Brittenham, GM; Spitalnik, SL (2010). "Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation". Blood. 115 (21): 4284–92. doi:10.1182/blood-2009-10-245001. PMC 2879099. PMID 20299509.

[32] Hess, JR; Biomedical Excellence for Safer Transfusion (BEST) Collaborative (2012). "Scientific problems in the regulation of red blood cell products". Transfusion. 52 (8): 1827–35. doi:10.1111/j.1537-2995.2011.03511.x. PMID 22229278.

[33] Pape, A; Stein, P; Horn, O; Habler, O (2009). "Clinical evidence of blood transfusion effectiveness". Blood Transfusion. 7 (4): 250–258. doi:10.2450/2008.0072-08. PMC 2782802.

[34] Burns, JM; Yang, X; Forouzan, O; Sosa, JM; Shevkoplyas, SS (2012). "Artificial microvascular network: A new tool for measuring rheologic properties of stored red blood cells". Transfusion. 52 (5): 1010–23. doi:10.1111/j.1537-2995.2011.03418.x. PMID 22043858.

[35] Raval, JS; Waters, JH; Seltsam, A; Scharberg, EA; Richter, E; Daly, AR; Kameneva, MV; Yazer, MH (2010). "The use of the mechanical fragility test in evaluating sublethal RBC injury during storage". Vox sanguinis. 99 (4): 325–31. doi:10.1111/j.1423-0410.2010.01365.x. PMID 20673245.

[36] [3]^{[dead link]}

[37] "College of American Pathologists - Easy does it-showing caution with RBC transfusions". Cap.org. Retrieved 2013-12-11.

[38] Devine, DV; Serrano, K (2010). "The platelet storage lesion". Clinics in laboratory medicine. 30 (2): 475–87. doi:10.1016/j.cll.2010.02.002. PMID 20513565.

[39] "The First Blood Transfusion?". Heart-valve-surgery.com. 2009-01-03. Retrieved 2010-02-09.

[anes-40] "This Month in Anesthesia History". Retrieved 2009-06-15.

[pbs.org-41] "Red Gold . Innovators & Pioneers . Jean-Baptiste Denis". PBS. Retrieved 2010-02-09.

[42] Klein, Harvey G; Anstee, David J, eds. (2005). Mollison's Blood Transfusion in Clinical Medicine. doi:10.1002/9780470986868. ISBN 9780470986868""{{cite book}}: CS1 maint: postscript (link) p.406

[43] Felts, John H. (2000). "Richard Lower: Anatomist and Physiologist". Annals of Internal Medicine. 132 (5): 420–3. doi:10.7326/0003-4819-132-5-200003070-00023. PMID 10691601.

[Ellis-44] Ellis, H. Surgical Anniversaries: James Blundell, pioneer of blood transfusion British Journal of Hospital Medicine, August 2007, Vol 68, No 8.

[45] Nathoo, N; Lautzenheiser, FK; Barnett, GH (2009). "The first direct human blood transfusion: The forgotten legacy of George W. Crile". Neurosurgery. 64 (3 Suppl): ons20–6, discussion ons26–7. doi:10.1227/01.NEU.0000334416.32584.97. PMID 19240569.

[46] Gordon, Murray B. (1940). "Effect of External Temperature on Sedimentation Rate of Red Blood Corpuscles". Journal of the American Medical Association. 114 (16). doi:10.1001/jama.1940.02810160078030.

[47] "Red Gold: the Epic Story of Blood". PBS.

[48] Bernice Glatzer Rosenthal. New Myth, New World: From Nietzsche to Stalinism, Pennsylvania State University, 2002, ISBN 0-271-02533-6 pp. 161-162.

[49] Boyan, CP; Howland, WS (1963). "Cardiac arrest and temperature of bank blood". JAMA : the journal of the American Medical Association. 183: 58–60. PMID 14014662.

[50] Rupreht, J (1985). Anaesthesia: essays on its history. Springer-Verlag. pp. 99–101. ISBN 3-540-13255-4. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[51] Laura Landro (2007-01-10). "New rules may shrink ranks of blood donors". Wall Street Journal.

[52] ttp://www.jw.org/en/publications/books/blood/how-can-blood-save-your-life/

[53] Goddard, A. F.; James, M. W.; McIntyre, A. S.; Scott, B. B.; British Society of Gastroenterology (2011). "Guidelines for the management of iron deficiency anaemia". Gut. 60 (10): 1309–16. doi:10.1136/gut.2010.228874. PMID 21561874.

[54] Transfusion Medicine Reviews, Vol 0, No 0 (Month), 2011: pp 1-15.e53

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@@ Line 16: / Line 16: @@
 '''Blood transfusion''' is generally the process of receiving [[blood]] products into one's [[Circulatory system|circulation]] [[intravenous]]ly. Transfusions are used in a variety of 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]], [[blood plasma|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.<ref name=AABB2012>{{cite journal|last=Carson|first=JL|coauthors=Grossman, BJ, Kleinman, S, Tinmouth, AT, Marques, MB, Fung, MK, Holcomb, JB, Illoh, O, Kaplan, LJ, Katz, LM, Rao, SV, Roback, JD, Shander, A, Tobian, AA, Weinstein, R, Swinton McLaughlin, LG, Djulbegovic, B, for the Clinical Transfusion Medicine Committee of the, AABB|title=Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB.|journal=Annals of internal medicine|date=2012 Mar 26|pmid=22454395|doi=10.1059/0003-4819-156-12-201206190-00429}}</ref> This is in part due to the increasing evidence that there are cases where patients have worse outcomes when transfused.<ref>{{cite pmid|23281973}}</ref> One may consider transfusion for people with symptoms of [[cardiovascular disease]] such as chest pain or shortness of breath.<ref name=AABB2012/> Globally around 85 million units of red blood cells are transfused in a given year.<ref name=AABB2012/> 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.<ref>http://www.gasche.at/pdf/IBD_Journal_2007.pdf</ref> Other blood products are given where appropriate, such as clotting deficiencies.
+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.<ref name=AABB2012>{{cite journal|last=Carson|first=JL|coauthors=Grossman, BJ, Kleinman, S, Tinmouth, AT, Marques, MB, Fung, MK, Holcomb, JB, Illoh, O, Kaplan, LJ, Katz, LM, Rao, SV, Roback, JD, Shander, A, Tobian, AA, Weinstein, R, Swinton McLaughlin, LG, Djulbegovic, B, for the Clinical Transfusion Medicine Committee of the, AABB|title=Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB.|journal=Annals of internal medicine|date=2012 Mar 26|pmid=22454395|doi=10.1059/0003-4819-156-12-201206190-00429}}</ref> This is in part due to the increasing evidence that there are cases where patients have worse outcomes when transfused.<ref>{{cite journal|pmid=23281973|year=2013|last1=Villanueva|first1=C|last2=Colomo|first2=A|last3=Bosch|first3=A|last4=Concepción|first4=M|last5=Hernandez-Gea|first5=V|last6=Aracil|first6=C|last7=Graupera|first7=I|last8=Poca|first8=M|last9=Alvarez-Urturi|first9=C|last10=Gordillo|first10=J|last11=Guarner-Argente|first11=C|last12=Santaló|first12=M|last13=Muñiz|first13=E|last14=Guarner|first14=C|title=Transfusion strategies for acute upper gastrointestinal bleeding|volume=368|issue=1|pages=11–21|doi=10.1056/NEJMoa1211801|journal=The New England journal of medicine}}</ref> One may consider transfusion for people with symptoms of [[cardiovascular disease]] such as chest pain or shortness of breath.<ref name=AABB2012/> Globally around 85 million units of red blood cells are transfused in a given year.<ref name=AABB2012/> 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.<ref>{{Cite journal|url=http://www.gasche.at/pdf/IBD_Journal_2007.pdf|pmid=17985376|year=2007|last1=Gasche|first1=C|last2=Berstad|first2=A|last3=Befrits|first3=R|last4=Beglinger|first4=C|last5=Dignass|first5=A|last6=Erichsen|first6=K|last7=Gomollon|first7=F|last8=Hjortswang|first8=H|last9=Koutroubakis|first9=I|last10=Kulnigg|first10=S|last11=Oldenburg|first11=B|last12=Rampton|first12=D|last13=Schroeder|first13=O|last14=Stein|first14=J|last15=Travis|first15=S|last16=Van Assche|first16=G|title=Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases|volume=13|issue=12|pages=1545–53|doi=10.1002/ibd.20285|journal=Inflammatory bowel diseases}}</ref> 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.
@@ Line 37: / Line 37: @@
 *All donated blood is also tested for ABO and Rh groups, along with the presence of any red blood cell antibodies.
 *Leukoreduction is the removal of white blood cells by filtration. Leukoreduced blood products are less likely to cause HLA [[alloimmunization]] (development of antibodies against specific blood types), [[febrile non-hemolytic transfusion reaction]], [[cytomegalovirus infection]], and [[platelet-transfusion refractoriness]].
-*Pathogen Reduction treatment that involves, for example, the addition of [[riboflavin]] with subsequent exposure to [[UV light]] has been shown to be effective in inactivating pathogens (viruses, bacteria, parasites and white blood cells) in blood products.<ref>{{cite journal | doi = 10.1562/0031-8655(2004)080<0609:TNSIAQ>2.0.CO;2 | last1 = Hardwick | first1 = CC | last2 = Herivel | year = 2004 | first2 = TR | last3 = Hernandez | first3 = SC | last4 = Ruane | first4 = PH | last5 = Goodrich | first5 = RP | title = Separation, Identification and Quantification of Riboflavin  and Its Photoproducts in Blood Products Using High-Performance Liquid Chromatography With Fluorescence Detection: A Method to Support Pathogen Reduction Technology | url = | journal = [[Photochemistry and Photobiology]] | volume = 80 | issue = 3| pages = 609–615 | pmid = 15382964 | issn = 0031-8655 }}</ref><ref>The Mirasol Clinical Evaluation Study Group, “A Randomized Controlled Clinical Trial Evaluating the Performance and Safety of Platelets treated with Mirasol Pathogen Reduction Technology.” Transfusion 2010, in press</ref><ref>Goodrich RP, et al., “The Mirasol PRT System for Pathogen Reduction of Platelets and Plasma: An Overview of Current Status and Future Trends.” Transfusion and ApheresisScience2006a; 35 (1): 5-17.</ref> By inactivating white blood cells in donated blood products, [[Pathogen Reduction Using Riboflavin and UV Light|riboflavin and UV light treatment]] can also replace gamma-irradiation as a method to prevent graft-versus-host disease ([[TA-GvHD]]).<ref>{{cite journal | doi = 10.1111/j.1537-2995.2006.00939.x | last1 = Fast | first1 = LD | last2 = Dileone | year = 2006 | first2 = G | last3 = Cardarelli | first3 = G | last4 = Li | first4 = J | last5 = Goodrich | first5 = R | title = Mirasol PRT Treatment of Donor White Blood Cells Prevents the Development of Xenogeneic Graft-Versus-Host Disease in Rag2-/-γc-/- Double Knockout Mice | url = | journal = [[AABB|Transfusion]] | volume = 46 | issue = 9| pages = 1553–1560 | pmid = 16965583 }}</ref><ref>Fast LD, DiLeone G, Marschner S. (2010) Inactivation of human leukocytes in platelet products after pathogen reduction technology treatment in comparison to gamma-irradiation.  Transfusion, In press.</ref><ref>Reddy HL, et.al. , “Toxicity Testing of a Novel Riboflavin-Based Technology for Pathogen Reduction and White Blood Cell Inactivation.” Transfusion Medicine Reviews 2008; 22 (2): 133-153.</ref>
+*Pathogen Reduction treatment that involves, for example, the addition of [[riboflavin]] with subsequent exposure to [[UV light]] has been shown to be effective in inactivating pathogens (viruses, bacteria, parasites and white blood cells) in blood products.<ref>{{cite journal | doi = 10.1562/0031-8655(2004)080<0609:TNSIAQ>2.0.CO;2 | last1 = Hardwick | first1 = CC | last2 = Herivel | year = 2004 | first2 = TR | last3 = Hernandez | first3 = SC | last4 = Ruane | first4 = PH | last5 = Goodrich | first5 = RP | title = Separation, Identification and Quantification of Riboflavin  and Its Photoproducts in Blood Products Using High-Performance Liquid Chromatography With Fluorescence Detection: A Method to Support Pathogen Reduction Technology | url = | journal = [[Photochemistry and Photobiology]] | volume = 80 | issue = 3| pages = 609–615 | pmid = 15382964 | issn = 0031-8655 }}</ref><ref>{{Cite journal|pmid=20492615|year=2010|author1=Mirasol Clinical Evaluation Study Group|title=A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology|volume=50|issue=11|pages=2362–75|doi=10.1111/j.1537-2995.2010.02694.x|journal=Transfusion|last2=Folléa|first2=G.|last3=Bardiaux|first3=L.|last4=Boiron|first4=J.-M.|last5=Lafeuillade|first5=B.|last6=Debost|first6=M.|last7=Lioure|first7=B.|last8=Harousseau|first8=J-L.|last9=Tabrizi|first9=R.|last10=Cahn|first10=J.-Y.|last11=Michallet|last12=Ambruso|first12=D.|last13=Schots|first13=R.|last14=Tissot|first14=J.-D.|last15=Sensebé|first15=L.|last16=Kondo|first16=T.|last17=McCullough|first17=J.|last18=Rebulla|first18=Paolo|last19=Escolar|first19=Gines|last20=Mintz|first20=P.|last21=Heddle|last22=Goodrich|first22=R.P.|last23=Bruhwyler|first23=J.|last24=Le|first24=C.|last25=Cook|first25=R.J.|last26=Stouch|first26=B.}}</ref><ref>{{Cite journal|pmid=16935562|year=2006|last1=Goodrich|first1=RP|last2=Edrich|first2=RA|last3=Li|first3=J|last4=Seghatchian|first4=J|title=The Mirasol PRT system for pathogen reduction of platelets and plasma: An overview of current status and future trends|volume=35|issue=1|pages=5–17|doi=10.1016/j.transci.2006.01.007|journal=Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis}}</ref> By inactivating white blood cells in donated blood products, [[Pathogen Reduction Using Riboflavin and UV Light|riboflavin and UV light treatment]] can also replace gamma-irradiation as a method to prevent graft-versus-host disease ([[TA-GvHD]]).<ref>{{cite journal | doi = 10.1111/j.1537-2995.2006.00939.x | last1 = Fast | first1 = LD | last2 = Dileone | year = 2006 | first2 = G | last3 = Cardarelli | first3 = G | last4 = Li | first4 = J | last5 = Goodrich | first5 = R | title = Mirasol PRT Treatment of Donor White Blood Cells Prevents the Development of Xenogeneic Graft-Versus-Host Disease in Rag2-/-γc-/- Double Knockout Mice | url = | journal = [[AABB|Transfusion]] | volume = 46 | issue = 9| pages = 1553–1560 | pmid = 16965583 }}</ref><ref>{{Cite journal|pmid=21155832|year=2011|last1=Fast|first1=LD|last2=Dileone|first2=G|last3=Marschner|first3=S|title=Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation|volume=51|issue=7|pages=1397–404|doi=10.1111/j.1537-2995.2010.02984.x|journal=Transfusion}}</ref><ref>{{Cite journal|doi=10.1016/j.tmrv.2007.12.003|title=Toxicity Testing of a Novel Riboflavin-Based Technology for Pathogen Reduction and White Blood Cell Inactivation|year=2008|last1=Reddy|first1=Heather L.|last2=Dayan|first2=Anthony D.|last3=Cavagnaro|first3=Joy|last4=Gad|first4=Shayne|last5=Li|first5=Junzhi|last6=Goodrich|first6=Raymond P.|journal=Transfusion Medicine Reviews|volume=22|issue=2|pages=133–53|pmid=18353253}}</ref>
 ===Compatibility testing===
@@ Line 79: / Line 79: @@
 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.<ref>{{cite web|url=http://www.who.int/bloodsafety/haemovigilance/en/ |title=WHO &#124; Haemovigilance |publisher=Who.int |date=2013-06-25 |accessdate=2013-12-11}}</ref> In the UK this data is collected by a [[Charitable organization|charity]] called SHOT (Serious Hazards Of Transfusion).<ref>{{cite web|url=http://www.shotuk.org/ |title=Welcome to the website for SHOT, the United Kingdom’s independent, - Serious Hazards of Transfusion : Serious Hazards of Transfusion |publisher=Shotuk.org |date=2010-03-11 |accessdate=2013-12-11}}</ref>
-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.<ref>Wang SS. What's the Shelf Life of Blood? Focus on Whether Older Donations Impair Recovery of Transfusion Recipients. The Wall Street Journal. 2009 Dec. 1.</ref> 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.<ref name="ReferenceA">Shander A, Hofmann A, Gombotz H, Theusinger OM, Spahn DR: Estimating the cost of blood: past, present, and future directions. Best Pract Res Clin Anaesthesiol; 2007; 21: 271-89.</ref>  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.
+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.<ref>Wang SS. What's the Shelf Life of Blood? Focus on Whether Older Donations Impair Recovery of Transfusion Recipients. The Wall Street Journal. 2009 Dec. 1.</ref> 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.<ref name="Missingor">{{Cite journal|pmid=17650777|year=2007|last1=Shander|first1=A|last2=Hofmann|first2=A|last3=Gombotz|first3=H|last4=Theusinger|first4=OM|last5=Spahn|first5=DR|title=Estimating the cost of blood: Past, present, and future directions|volume=21|issue=2|pages=271–89|journal=Best practice & research. Clinical anaesthesiology}}</ref>  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.
 ===Immunologic reaction===
@@ Line 107: / Line 107: @@
 '''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.<ref>Zubair AC: Clinical impact of blood storage lesions. Am J Hematol; 2010; 85: 117-22.</ref>  Although some of the biochemical changes are reversible after the blood is transfused,<ref>{{cite pmid|2492818}}</ref> the biomechanical changes are less so,<ref>Decreased Erythrocyte Deformability After Transfusion and the Effects of Erythrocyte Storage Duration Anesth Analg ANE.0b013e31828843e6; published ahead of print February 28, 2013.</ref> and rejuvenation products are not yet able to adequately reverse this phenomenon.<ref>[http://www.isb-isch2012.org/Poster/P32.htm ]{{dead link|date=December 2013}}</ref> 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.<ref>http://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/</ref><ref>{{cite news| url=http://online.wsj.com/article/SB10001424052748703939404574567771148801570.html | work=The Wall Street Journal | title=What's the Shelf Life of Blood? | first=Shirley S. | last=Wang | date=2009-12-01}}</ref> Studies have not been consistent on answering this question,<ref>{{cite web|url=http://www.annalsofintensivecare.com/content/3/1/2 |title=Full text &#124; Age of red blood cells and transfusion in critically ill patients |publisher=Annals of Intensive Care |date= |accessdate=2013-12-11}}</ref> 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 bank]]ers - who are the physicians, typically pathologists, who collect and manage inventories of tranfusable blood units.
+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.<ref>{{Cite journal|pmid=20052749|year=2010|last1=Zubair|first1=AC|title=Clinical impact of blood storage lesions|volume=85|issue=2|pages=117–22|doi=10.1002/ajh.21599|journal=American journal of hematology}}</ref>  Although some of the biochemical changes are reversible after the blood is transfused,<ref>{{cite journal|pmid=2492818|year=1989|last1=Heaton|first1=A|last2=Keegan|first2=T|last3=Holme|first3=S|title=In vivo regeneration of red cell 2,3-diphosphoglycerate following transfusion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells|volume=71|issue=1|pages=131–6|journal=British journal of haematology}}</ref> the biomechanical changes are less so,<ref>{{Cite journal|pmid=23449853|year=2013|last1=Frank|first1=SM|last2=Abazyan|first2=B|last3=Ono|first3=M|last4=Hogue|first4=CW|last5=Cohen|first5=DB|last6=Berkowitz|first6=DE|last7=Ness|first7=PM|last8=Barodka|first8=VM|title=Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration|volume=116|issue=5|pages=975–81|doi=10.1213/ANE.0b013e31828843e6|pmc=3744176|journal=Anesthesia and analgesia}}</ref> and rejuvenation products are not yet able to adequately reverse this phenomenon.<ref>[http://www.isb-isch2012.org/Poster/P32.htm ]{{dead link|date=December 2013}}</ref> 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.<ref>http://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/</ref><ref>{{cite news| url=http://online.wsj.com/article/SB10001424052748703939404574567771148801570.html | work=The Wall Street Journal | title=What's the Shelf Life of Blood? | first=Shirley S. | last=Wang | date=2009-12-01}}</ref> Studies have not been consistent on answering this question,<ref>{{cite journal|doi=10.1186/2110-5820-3-2|title=Age of red blood cells and transfusion in critically ill patients|year=2013|last1=Aubron|first1=Cécile|last2=Nichol|first2=Alistair|last3=Cooper|first3=D Jamie|last4=Bellomo|first4=Rinaldo|journal=Annals of Intensive Care|volume=3|pages=2|pmid=23316800|issue=1|pmc=3575378}}</ref> 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 bank]]ers - 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).<ref>{{cite web|url=http://bloodjournal.hematologylibrary.org/content/115/21/4284.long |title=Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation |publisher=Bloodjournal.hematologylibrary.org |date= |accessdate=2013-12-11}}</ref> However, all of these criteria are applied in a universal manner that does not account for differences among units of product.<ref>{{cite pmid|22229278}}</ref> 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''.<ref>{{cite web|author=USA |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782802/ |title=Clinical evidence of blood transfusion effectiveness |publisher=Ncbi.nlm.nih.gov |date=2013-08-12 |accessdate=2013-12-11}}</ref> 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]]<ref>Transfusion. 2012 May;52(5):1010-23. Artificial microvascular network: a new tool for measuring rheologic properties of stored red blood cells. Burns JM, Yang X, Forouzan O, Sosa JM, Shevkoplyas SS.</ref> and [[erythrocyte fragility]] (mechanical).<ref>Vox Sang. 2010 Nov;99(4):325-31. The use of the mechanical fragility test in evaluating sublethal RBC injury during storage.</ref>
+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).<ref>{{cite journal|pmid=20299509|year=2010|last1=Hod|first1=EA|last2=Zhang|first2=N|last3=Sokol|first3=SA|last4=Wojczyk|first4=BS|last5=Francis|first5=RO|last6=Ansaldi|first6=D|last7=Francis|first7=KP|last8=Della-Latta|first8=P|last9=Whittier|first9=S|last10=Sheth|first10=S|last11=Hendrickson|first11=JE|last12=Zimring|first12=JC|last13=Brittenham|first13=GM|last14=Spitalnik|first14=SL|title=Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation|volume=115|issue=21|pages=4284–92|doi=10.1182/blood-2009-10-245001|pmc=2879099|journal=Blood}}</ref> However, all of these criteria are applied in a universal manner that does not account for differences among units of product.<ref>{{cite journal|pmid=22229278|year=2012|last1=Hess|first1=JR|author2=Biomedical Excellence for Safer Transfusion (BEST) Collaborative|title=Scientific problems in the regulation of red blood cell products|volume=52|issue=8|pages=1827–35|doi=10.1111/j.1537-2995.2011.03511.x|journal=Transfusion}}</ref> 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''.<ref>{{cite journal|pmc=2782802|year=2009|last1=Pape|first1=A|last2=Stein|first2=P|last3=Horn|first3=O|last4=Habler|first4=O|title=Clinical evidence of blood transfusion effectiveness|volume=7|issue=4|pages=250–258|doi=10.2450/2008.0072-08|journal=Blood Transfusion}}</ref> 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]]<ref>{{Cite journal|pmid=22043858|year=2012|last1=Burns|first1=JM|last2=Yang|first2=X|last3=Forouzan|first3=O|last4=Sosa|first4=JM|last5=Shevkoplyas|first5=SS|title=Artificial microvascular network: A new tool for measuring rheologic properties of stored red blood cells|volume=52|issue=5|pages=1010–23|doi=10.1111/j.1537-2995.2011.03418.x|journal=Transfusion}}</ref> and [[erythrocyte fragility]] (mechanical).<ref>{{Cite journal|pmid=20673245|year=2010|last1=Raval|first1=JS|last2=Waters|first2=JH|last3=Seltsam|first3=A|last4=Scharberg|first4=EA|last5=Richter|first5=E|last6=Daly|first6=AR|last7=Kameneva|first7=MV|last8=Yazer|first8=MH|title=The use of the mechanical fragility test in evaluating sublethal RBC injury during storage|volume=99|issue=4|pages=325–31|doi=10.1111/j.1423-0410.2010.01365.x|journal=Vox sanguinis}}</ref>
-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,<ref name="ReferenceA"/> along with the increasing view that many transfusions are inappropriate or use too many RBC units.<ref>[http://www.patientsafetysummit.org/_assets/documents/Action%20Plan%20-%20RBC%20Overuse%20-%20January%2013,%202013.pdf ]{{dead link|date=December 2013}}</ref><ref>{{cite web|url=http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_today%2F0409%2F0409d_easy_does_it.html&_state=maximized&_pageLabel=cntvwr |title=College of American Pathologists - Easy does itï¿½showing caution with RBC transfusions |publisher=Cap.org |date= |accessdate=2013-12-11}}</ref>  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.
+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,<ref name="Missingor"/> along with the increasing view that many transfusions are inappropriate or use too many RBC units.<ref>[http://www.patientsafetysummit.org/_assets/documents/Action%20Plan%20-%20RBC%20Overuse%20-%20January%2013,%202013.pdf ]{{dead link|date=December 2013}}</ref><ref>{{cite web|url=http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_today%2F0409%2F0409d_easy_does_it.html&_state=maximized&_pageLabel=cntvwr |title=College of American Pathologists - Easy does it-showing caution with RBC transfusions |publisher=Cap.org |date= |accessdate=2013-12-11}}</ref>  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.<ref>{{cite pmid|20513565}}</ref>
+Although tranfusions of '''platelets''' are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern.<ref>{{cite journal|pmid=20513565|year=2010|last1=Devine|first1=DV|last2=Serrano|first2=K|title=The platelet storage lesion|volume=30|issue=2|pages=475–87|doi=10.1016/j.cll.2010.02.002|journal=Clinics in laboratory medicine}}</ref>
 ===Other===
@@ Line 136: / Line 136: @@
 ==== Jean-Baptiste Denys====
-The first fully documented human blood transfusion was administered by Dr. [[Jean-Baptiste Denys]], eminent physician to King Louis&nbsp;XIV of France, on June&nbsp;15, 1667.<ref>{{cite web|url=http://www.heart-valve-surgery.com/heart-surgery-blog/2009/01/03/first-blood-transfusion|title=The First Blood Transfusion? |publisher=Heart-valve-surgery.com |date=2009-01-03|accessdate=2010-02-09}}</ref> He transfused the blood of a [[sheep]] into a 15-year-old boy, who survived the transfusion.<ref name="anes">{{cite web |url=http://www.anesthesia.wisc.edu/AHA/Calendar/June.html |title= This Month in Anesthesia History|accessdate= 2009-06-15}}</ref> 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.<ref name="pbs.org">{{cite web|url=http://www.pbs.org/wnet/redgold/innovators/bio_denis.html |title=Red Gold . Innovators & Pioneers . Jean-Baptiste Denis |publisher=PBS |date= |accessdate=2010-02-09}}</ref> In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood, who on the third account died.<ref>"Mollison's Blood Transfusion in Clinical Medicine" by H.Klein, D. Anstee (2005), p.406</ref> 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.<ref name="pbs.org"/> 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.
+The first fully documented human blood transfusion was administered by Dr. [[Jean-Baptiste Denys]], eminent physician to King Louis&nbsp;XIV of France, on June&nbsp;15, 1667.<ref>{{cite web|url=http://www.heart-valve-surgery.com/heart-surgery-blog/2009/01/03/first-blood-transfusion|title=The First Blood Transfusion? |publisher=Heart-valve-surgery.com |date=2009-01-03|accessdate=2010-02-09}}</ref> He transfused the blood of a [[sheep]] into a 15-year-old boy, who survived the transfusion.<ref name="anes">{{cite web |url=http://www.anesthesia.wisc.edu/AHA/Calendar/June.html |title= This Month in Anesthesia History|accessdate= 2009-06-15}}</ref> 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.<ref name="pbs.org">{{cite web|url=http://www.pbs.org/wnet/redgold/innovators/bio_denis.html |title=Red Gold . Innovators & Pioneers . Jean-Baptiste Denis |publisher=PBS |date= |accessdate=2010-02-09}}</ref> In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood, who on the third account died.<ref>{{Cite book|doi=10.1002/9780470986868|postscript=""|title=Mollison's Blood Transfusion in Clinical Medicine|year=2005|editor1-last=Klein|editor1-first=Harvey G|editor2-last=Anstee|editor2-first=David J|isbn=9780470986868}} p.406</ref> 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.<ref name="pbs.org"/> 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====
@@ Line 145: / Line 145: @@
 Lower had performed the first blood transfusion between animals. He was then "requested by the Honorable [[Robert Boyle|[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.{{Citation needed|date=June 2009}}
-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.<ref>{{cite web|url=http://www.annals.org/cgi/reprint/132/5/420.pdf |title=Annals of Internal Medicine &#124; Richard Lower: Anatomist and Physiologist |publisher=Annals.org |date=2011-04-25 |accessdate=2012-06-24}}</ref>
+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.<ref>{{cite journal|doi=10.7326/0003-4819-132-5-200003070-00023|title=Richard Lower: Anatomist and Physiologist|year=2000|last1=Felts|first1=John H.|journal=Annals of Internal Medicine|volume=132|issue=5|pages=420–3|pmid=10691601}}</ref>
 ===Early efforts to transfuse human blood===
@@ Line 155: / Line 155: @@
 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 [[haemophilia]].
-[[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|date=May 2013}}<ref>Nathoo N, ''The first direct human blood transfusion: the forgotten legacy of George W. Crile.''. Neurosurgery. 2009 Mar;64(3 Suppl)</ref>
+[[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|date=May 2013}}<ref>{{Cite journal|pmid=19240569|year=2009|last1=Nathoo|first1=N|last2=Lautzenheiser|first2=FK|last3=Barnett|first3=GH|title=The first direct human blood transfusion: The forgotten legacy of George W. Crile|volume=64|issue=3 Suppl|pages=ons20–6; discussion ons26–7|doi=10.1227/01.NEU.0000334416.32584.97|journal=Neurosurgery}}</ref>
 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 [[hemolysis|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 [[ABO blood group system|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 [[human blood group systems|many other blood groups]] have been discovered since.
@@ Line 162: / Line 162: @@
 {{Main|Blood bank}}
 [[File:Agote 1a transfusión.jpg|thumb|Dr. [[Luis Agote]] (''2nd from right'') overseeing one of the first safe and effective blood transfusion in 1914]]
-While the first transfusions had to be made directly from donor to receiver before [[blood coagulation|coagulation]], in the 1910s it was discovered that by adding [[anticoagulant]] and [[refrigeration|refrigerating]] the blood it was possible to store it for some days, thus opening the way for [[blood bank]]s. The first non-direct transfusion was performed on March&nbsp;27, 1914 by the [[Belgium|Belgian]] doctor [[Albert Hustin]], though this was a diluted solution of blood.  The [[Argentina|Argentine]] doctor [[Luis Agote]] used a much less diluted solution in November of the same year.  Both used [[Monosodium citrate|sodium citrate]] as an anticoagulant.<ref>{{cite web|url=http://jama.ama-assn.org/content/114/16/1576.2|title=CITRATE METHOD OF BLOOD TRANSFUSION|author=R. Lewisohn|publisher=[[Journal of the American Medical Association]]}}</ref> 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&nbsp;1, 1916.{{citation needed|date=February 2013}} [[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|U.S.&nbsp;Army]] officer, is generally credited with establishing the first blood bank while serving in [[France]] during [[World War I|World War&nbsp;I]].<ref>{{cite web|url=http://www.pbs.org/wnet/redgold/history/timeline3.html|title=Red Gold: the Epic Story of Blood|publisher=PBS}}</ref>
+While the first transfusions had to be made directly from donor to receiver before [[blood coagulation|coagulation]], in the 1910s it was discovered that by adding [[anticoagulant]] and [[refrigeration|refrigerating]] the blood it was possible to store it for some days, thus opening the way for [[blood bank]]s. The first non-direct transfusion was performed on March&nbsp;27, 1914 by the [[Belgium|Belgian]] doctor [[Albert Hustin]], though this was a diluted solution of blood.  The [[Argentina|Argentine]] doctor [[Luis Agote]] used a much less diluted solution in November of the same year.  Both used [[Monosodium citrate|sodium citrate]] as an anticoagulant.<ref>{{cite journal|doi=10.1001/jama.1940.02810160078030|title=Effect of External Temperature on Sedimentation Rate of Red Blood Corpuscles|year=1940|last1=Gordon|first1=Murray B.|journal=Journal of the American Medical Association|volume=114|issue=16}}</ref> 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&nbsp;1, 1916.{{citation needed|date=February 2013}} [[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|U.S.&nbsp;Army]] officer, is generally credited with establishing the first blood bank while serving in [[France]] during [[World War I|World War&nbsp;I]].<ref>{{cite web|url=http://www.pbs.org/wnet/redgold/history/timeline3.html|title=Red Gold: the Epic Story of Blood|publisher=PBS}}</ref>
 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]].
@@ Line 180: / Line 180: @@
 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.<ref>{{cite pmid | 14014662}}</ref><ref>{{cite book | isbn = 3-540-13255-4 | last = Rupreht | first = J | coauthors = van Lieburg MJ; Lee JA; Erdman W | publisher = Springer-Verlag| year = 1985 | pages = 99–101 | title = Anaesthesia: essays on its history }}</ref>
+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.<ref>{{cite journal |pmid= 14014662 |year= 1963 |last1= Boyan |first1= CP |last2= Howland |first2= WS |title= Cardiac arrest and temperature of bank blood |volume= 183 |pages= 58–60 |journal= JAMA : the journal of the American Medical Association}}</ref><ref>{{cite book | isbn = 3-540-13255-4 | last = Rupreht | first = J | coauthors = van Lieburg MJ; Lee JA; Erdman W | publisher = Springer-Verlag| year = 1985 | pages = 99–101 | title = Anaesthesia: essays on its history }}</ref>
 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.
@@ Line 189: / Line 189: @@
 ===Religious===
-Objections to blood transfusions may arise for personal, medical, or religious reasons. For example, [[Jehovah's Witnesses]] [[Jehovah's Witnesses and blood transfusions|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. http://www.jw.org/en/publications/books/blood/how-can-blood-save-your-life/
+Objections to blood transfusions may arise for personal, medical, or religious reasons. For example, [[Jehovah's Witnesses]] [[Jehovah's Witnesses and blood transfusions|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.<ref>http://www.jw.org/en/publications/books/blood/how-can-blood-save-your-life/</ref>
 ==Between animals==
@@ Line 205: / Line 205: @@
 ==Alternative treatment options==
-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<ref>Gut. 2011 Oct;60(10):1309-16. doi: 10.1136/gut.2010.228874</ref><ref>Transfusion Medicine Reviews, Vol 0, No 0 (Month), 2011: pp 1-15.e53</ref> In these cases [[parenteral iron]] is recommended.
+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<ref>{{Cite journal|doi=10.1136/gut.2010.228874|title=Guidelines for the management of iron deficiency anaemia|year=2011|last1=Goddard|first1=A. F.|last2=James|first2=M. W.|last3=McIntyre|first3=A. S.|last4=Scott|first4=B. B.|journal=Gut|volume=60|issue=10|pages=1309–16|pmid=21561874|author5=British Society of Gastroenterology}}</ref><ref>Transfusion Medicine Reviews, Vol 0, No 0 (Month), 2011: pp 1-15.e53</ref> In these cases [[parenteral iron]] is recommended.
 ==See also==

v t e Blood transfusion and transfusion medicine
Blood products	Whole blood Platelets Platelet transfusion Red blood cells Plasma Fresh frozen plasma PF24 Cryoprecipitate Cryosupernatant White blood cells Granulocyte transfusion Blood substitutes
General concepts	Blood bank Blood donation Blood management International Society of Blood Transfusion ISBT 128
Methods	Apheresis (plasmapheresis, plateletpheresis, leukapheresis) Exchange transfusion Intraoperative blood salvage
Tests	Blood compatibility testing Cross-matching Coombs test Kleihauer–Betke test Antibody elution Monocyte monolayer assay
Transfusion reactions and adverse effects	Transfusion hemosiderosis Transfusion related acute lung injury Transfusion associated circulatory overload Transfusion-associated graft versus host disease Febrile non-hemolytic transfusion reaction Hemolytic reaction acute delayed Serum sickness Transfusion transmitted infection
Blood group systems	Blood types ABO Secretor status Augustine CD59 Chido-Rodgers Colton Cromer Diego Dombrock Duffy Er FORS Gerbich GIL GLOB Hh Ii Indian JR JMH KANNO Kell (Xk) Kidd Knops Lan Lewis Lutheran LW MNS OK P1PK Raph Rh and RHAG Scianna Sid T-Tn Vel Xg Yt Other