Blood transfusion

Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery. Blood transfusions may also be used to treat a severe anaemia or thrombocytopenia caused by a blood disease.

Early attempts
The first historical attempt at blood transfusion was described by the 15th-century chronicler Stefano Infessura. Infessura relates that, in 1492, as Pope Innocent VIII sank into a coma, the blood of three boys was infused into the dying pontiff's veins at the suggestion of a physician. The boys were ten years old, and had been promised a ducat each. All three died. Roman Catholic authors take pains to discredit Infessura's account, accusing him of anti-papalism.



With Harvey's discovery of the circulation of the blood, more sophisticated research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts on humans continued to have fatal results.

The first fully-documented human blood transfusion was administered by Dr. Jean-Baptiste Denys on June 15, 1667. He transfused the blood of a sheep into a 15-year old boy (the boy later died, and Denys was accused of murder).

The first successes
The science of blood transfusion dates to the first decade of the 19th century, with the discovery of distinct blood types leading to the practice of mixing some blood from the donor and the receiver before the transfusion (an early form of cross-matching).

In 1818, Dr. James Blundell, a British obstetrician, performed the first successful transfusion of human blood, for the treatment of postpartum hemorrhage. He used the patient's husband as a donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Dr. Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented many instruments for the transfusion of blood. He made a substantial amount of money from this endeavour, roughly $50 million in real dollars.

In 1840, at St. George's Hospital Medical School in London, Samuel Armstrong Lane, aided by Dr. Blundell, performed the first successful whole blood transfusion to treat hemophilia.

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 anticoagulants and refrigerating the blood it was possible to store it for some days, thus opening the way for blood banks. The first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, who used sodium citrate as an anticoagulant. The first blood transfusion using blood that had been stored and cooled was performed on January 1,1916. Oswald Hope Robertson, a medical researcher and U.S. Army officer, is generally credited with establishing the first blood bank while serving in France during World War I.

The first academic institution devoted to the science of blood transfusion was founded by Alexander Bogdanov in Moscow in 1925. Bogdanov was motivated, at least in part, by a search for eternal youth, and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of whole blood.

In fact, following the death of Vladimir Lenin, Bogdanov was entrusted with the study of Lenin's brain, with a view toward resuscitating the deceased Bolshevik leader. Tragically, but perhaps not unforeseeably, Bogdanov lost his life in 1928 as a result of one of his experiments, when the blood of a student suffering from malaria and tuberculosis was given to him in a transfusion. Some scholars (e.g. Loren Graham) have speculated that his death may have been a suicide, while others attribute it to blood type incompatibility, which was still incompletely understood at the time.

The modern era
Following Bodganov's lead, the Soviet Union set up a national system of blood banks in the 1930's. 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 1930's and early 1940's, Dr. Charles Drew's research led to the discovery that blood could be separated into blood plasma and red blood cells, and that the components could be frozen separately. Blood stored in this way lasted longer and was less likely to become contaminated.

Another important breakthrough came in 1939-40 when Karl Landsteiner, Alex Wiener, Philip Levine, and R.E. Stetson discovered the Rhesus blood group system, which was found to be the cause of the majority of transfusion reactions up to that time. Three years later, the introduction by J.F. Loutit and Patrick L. Mollison of acid citrate dextrose (ACD) solution, which reduces the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer term storage.

Carl Walter and W.P. Murphy, Jr., introduced the plastic bag for blood collection in 1950. Replacing breakable glass bottles with durable plastic bags allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood. Further extending the shelf life of stored blood was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks.

Compatibility
Great care is taken in cross-matching to ensure that the recipient's immune system will not attack the donor blood. In addition to the familiar human blood types (A, B, AB and O) and Rh factor (positive or negative) classifications, other minor red cell antigens are known to play a role in compatibility. These other types can become increasingly important in people who receive many blood transfusions, as their bodies develop increasing resistance to blood from other people via a process of alloimmunization.

Screening for infection
A number of infectious diseases (such as HIV, syphilis, hepatitis B and hepatitis C, among others) can be passed from the donor to recipient. This has led to strict human blood transfusion standards in developed countries. Standards include screening for potential risk factors and health problems among donors by determining donor hemoglobin levels, adminstering a set of standard oral and written questions to donors, and laboratory testing of donated units for infection. The lack of such standards in places like rural China, where desperate villagers donated plasma for money and had others' red blood cells reinjected, has produced entire villages infected with HIV.

As of mid-2005, all donated blood in the United States is screened for the following infectious agents:
 * HIV-1 and HIV-2
 * Human T-lymphotropic virus (HTLV-1 and HTLV-2)
 * Hepatitis C virus
 * Hepatitis B virus
 * West Nile virus
 * Treponema pallidum (the causative agent of syphilis)

When a person's need for a transfusion can be anticipated, as in the case of scheduled surgery, autologous donation can be used to protect against disease transmission and eliminate the problem of blood type compatibility.

Processing of blood prior to transfusion
Donated blood is sometimes subjected to processing after it is collected, to make it suitable for use in specific patient populations. Examples of post-donation processing include:
 * Leukoreduction, or the removal of stray white blood cells from the blood product by filtration. Leukoreduced blood is less likely to cause alloimmunization (development of antibodies against specific blood types), and less likely to cause febrile transfusion reactions. Also, leukoreduction greatly reduces the chance of cytomegalovirus (CMV) transmission. Leukoreduced blood is appropriate for:
 * Chronically transfused patients
 * Potential transplant recipients
 * Patients with previous febrile nonhemolytic transfusion reactions
 * CMV seronegative at-risk patients for whom seronegative components are not available
 * Irradiation. In patients who are severely immunosuppressed and at risk for transfusion-associated graft-versus-host disease, transfused red cells may be subjected to irradiation with at least 2500 Gy to prevent the donor T lymphocytes from dividing in the recipient. Irradiated blood products are appropriate for:
 * Patients with hereditary immune deficiencies
 * Patients receiving blood transfusions from relatives in directed-donation programs
 * Patients receiving large doses of chemotherapy, undergoing stem cell transplantation, or with AIDS (controversial).
 * CMV screening. Cytomegalovirus, or CMV, is a virus which infects white blood cells. Many people are asymptomatic carriers. In patients with signficant immune suppression (eg recipients of stem cell transplants) who have not previously been exposed to CMV, blood products that are CMV-negative are preferred. Leukoreduced blood products can substitute for CMV-negative products, since the removal of white blood cells removes the source of CMV transmission (see leukoreduction above).

Procedure
Blood transfusions can be grouped into two main types depending on their source:
 * Homologous transfusions, or transfusions using the stored blood of others.
 * Autologous transfusions, or transfusions using one's own stored blood.

Blood can only be administered intravenously. It therefore requires the insertion of a cannula of suitable caliber. Before the blood is administered, the personal details of the patient are matched with the blood to be transfused, to minimize risk of transfusion reactions. With the recognition that clerical error (eg administering the wrong unit of blood) is a signficant source of transfusion reactions, attempts have been made to build redundancy into the matching process that takes place at the bedside.

A unit (up to 500 ml) of blood is typically administered over 4 hours. In patients at risk of congestive heart failure, many doctors administer furosemide to prevent fluid overload. Acetaminophen and/or an antihistamine such as diphenhydramine are sometimes given before the transfusion to prevent a transfusion reaction.

Blood donation
Blood is most commonly donated as whole blood by inserting a catheter into a vein and collecting it in a plastic bag (mixed with anticoagulant) via gravity. Collected blood is then separated into components to make the best use of it. Aside from red blood cells, plasma, and platelets, the resulting blood component products also include albumin protein, clotting factor concentrates, cryoprecipitate, fibrinogen concentrate, and immunoglobulins (antibodies). Red cells, plasma and platelets can also be donated individually via a more complex process called apheresis.

Donations are usually anonymous to the recipient, but products in a blood bank are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction.

Contraindications to being a blood donor
Blood donation centers in different countries may have different guidelines about who can serve as a blood donor. Common contraindications to being a blood donor include:
 * previous malaria or hepatitis
 * a history of intravenous drug abuse
 * donors who have received human-derived pituitary hormones
 * donors with high-risk sexual behaviour (variably defined)
 * donors who have previously been transfused (12-month min. deferral)

For the donor
Donating whole blood at a modern, well-run blood collection center is safe. The biggest risk is probably that of vasovagal syncope, or "passing out". A large study, involving 194,000 donations during a one-year period at an urban blood center, found 178 cases of syncope, for an incidence of 0.09%. Only 5 of these incidents required emergency room attention, and there was only one long-term complication. The best defense, as a donor, is being well-hydrated and remaining at the donation center for 10-15 minutes after finishing your donation, to make sure you are feeling well. Other risks to donors noted in one study included: Note that none of these were severe enough to require medical attention in this study. Overall, blood donation is very safe. There is no risk of acquiring an infection at a modern, well-run blood donation center.
 * Bruise at the needle site — 23 percent
 * Sore arm — 10 percent
 * Hematoma at needle site — 2 percent
 * Sensory changes in the arm used for donation (eg, burning pain, numbness, tingling) — 1 percent
 * Fatigue — 8 percent
 * Vasovagal symptoms — 5 percent
 * Nausea and vomiting — 1 percent

Donation of blood products via apheresis is a more invasive and complex procedure and can entail additional risks, although this procedure is, overall, still very safe for the donor.

For the recipient
There are risks associated with receiving a blood transfusion, and these must always be balanced against the benefit which is expected. Risks can include:
 * Febrile non-hemolytic transfusion reaction. This is the most common adverse reaction to a blood transfusion. Symptoms include fever and dyspnea 1 to 6 hours after receiving the transfusion. Such reactions are clinically benign, causing no lasting side effects or problems, but are unpleasant for the patient. Furthermore, they must be carefully differentiated from hemolytic transfusion reactions or infection (see below).
 * Viral infection. The risk of viral infection is a common concern when receiving a blood transfusion. As noted above, the blood supply in developed countries is carefully screened for a number of infectious agents, in addition to careful screening of donors themselves. Nonetheless, viral transmission has been documented, albeit extremely rarely. The risk for acquiring hepatitis B in the United States is about 1 in 250,000 units transfused, and the risk of acquiring HIV or hepatitis C via a blood transfusion is currently (as of 2006) estimated at 1 per 2 million units transfused. Bacterial infection is a much more common problem (see below)
 * Bacterial infection. Blood products can provide an excellent medium for bacteria, and can become contaminated after collection while they are being stored. The risk is highest with platelet transfusion, since platelets must be stored near room temperature and cannot be refrigerated. The risk of severe bacterial infection and sepsis is estimated (as of 2001) at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions.
 * Acute hemolytic reaction. This is a medical emergency resulting from rapid destruction (hemolysis) of the donor red blood cells by host antibodies. The most common cause is clerical error (i.e. the wrong unit of blood going to the wrong patient). The symptoms are fever and chills, sometimes with back pain and pink or red urine (hemoglobinuria). The major complication is that hemoglobin released by the destruction of red blood cells can cause acute renal failure.
 * Anaphylactic reaction. An anaphylactic (or severe allergic) reaction can occur at a rate of 1 per 30,000-50,000 transfusions. These reactions are most common in people with selective IgA deficiency (although this condition is often asymptomatic, and people may not know they have it until an anaphylactic reaction occurs). An anaphylactic reaction is a medical emergency, requiring prompt treatment, and may be life-threatening.
 * Transfusion-associated acute lung injury (TRALI). TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension. It may occur as often as 1 in every 2000 transfusions. 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%.
 * Volume overload. Patients with impaired cardiac function (eg congestive heart failure) can become volume-overloaded as a result of blood transfusion, leading to edema, dyspnea (shortness of breath), and orthopnea (shortness of breath while lying flat).
 * Iron overload. Each transfused unit of red blood cells contains approximately 250 mg of elemental iron. Since elimination pathways for iron are limited, a person receiving numerous red blood cell transfusions can develop iron overload, which can in turn damage the liver, heart, kidneys, and pancreas. The threshold at which iron overload becomes significant is somewhat unclear, but is likely around 12-20 units of red blood cells transfused.
 * Transfusion-associated graft-vs-host disease (GVHD). GVHD refers to an immune attack by transfused cells against the recipient. This is a common complication of stem cell transplantation, but an exceedingly rare complication of blood transfusion. It occurs only in severely immunosuppressed patients, primarily those with congenital immune deficiencies or hematologic malignancies who are receiving intensive chemotherapy. When GVHD occurs in association with blood transfusion, it is almost uniformly fatal. Transfusion-associated GVHD can be prevented by irradiating the blood products prior to transfusion (see Processing of blood products above).

Objections to blood transfusion
Objections to blood transfusions primarily come for two different reasons namely, medical reasons or religious reasons. Jehovah's Witnesses do so solely for religious reasons though they have been known to highlight possible complications in the administering of blood.

Jehovah's Witnesses believe that in the Bible blood is sacred to God representing life thus it must not be eaten but pour out (figuratively giving it back to God). They also state that blood was reserved for only one special use, the atonement for sins, leading up to Jesus' shed blood, thus when a Christian abstains from blood, he or she is in effect expressing faith that "only the shed blood of Jesus Christ can truly redeem him and save his life.-Ephesians 1:7" Therefore, they believe that when the New Testament says to “keep abstaining from ...blood” it means that Christians should, 'not take blood into their bodies at all.' This stance, over the years, on blood has been a source of controversy, as members have died due to loss of blood.

Animal blood transfusion
Veterinarians also administer transfusions to animals. Various species require different levels of testing to ensure a compatible match. For example, cats have 3 blood types, cattle have 11, dogs have 12, pigs 16 and horses have 34.

The rare and experimental practice of inter-species blood transfusions is a form of xenograft.

Blood transfusion substitutes
As of mid-2006, there are no clinically utilized oxygen-carrying blood substitutes for humans; however, there are widely available non-blood volume expanders and other blood-saving techniques. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the religious objections of Jehovah's Witnesses and others who have ethical objections to receiving transfused blood.

A number of blood substitutes are currently in the clinical evaluation stage. Most attempts to find a suitable alternative to blood thus farhave 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.