With Harvey's re-discovery of the circulation of the blood (which was discovered by Ibn al-Nafis in the 13th century), more sophisticated research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts on humans continued to have fatal results.
The first fully-documented human blood transfusion was administered by Dr. Jean-Baptiste Denis, eminent physician to King Louis XIV of France, on June 15, 1667. He transfused the blood of a sheep into a 15-year old boy, who recovered. Denis 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. In the winter of 1667, Denis performed several transfusions on Antoine Mauroy with calf's blood, who on the third account had died. Much controversy surrounded his death and his wife was accused for causing his death; it is likely that the transfusion caused his death. Even though it was later determined that Mauroy actually died from arsenic poisoning, Denis' experiments with animal blood provoked a heated controversy in France. Finally, in 1670 the procedure was banned. In time, the British Parliament and even the pope followed suit. Blood transfusions fell into obscurity for the next 150 years.
"Many of his colleagues were present. . . towards the end of February 1665 [when he] selected one dog of medium size, opened its jugular vein, and drew off blood, until . . . its strength was nearly gone . . . Then, to make up for the great loss of this dog by the blood of a second, I introduced blood from the cervical artery of a fairly large mastiff, which had been fastened alongside the first, until this latter animal showed . . . it was overfilled . . . by the inflowing blood." After he "sewed up the jugular veins," the animal recovered "with no sign of discomfort or of displeasure."
Lower had performed the first blood transfusion between animals. He was then "requested by the Honorable [Robert] Boyle . . . to acquaint the Royal Society with the procedure for the whole experiment," which he did in December of 1665 in the Society’s Philosophical Transactions. On 15 June 1667 Denys, then a professor in Paris, carried out the first transfusion between humans and claimed credit for the technique, but Lower’s priority cannot be challenged.
Six months later in London, Lower performed the first human transfusion in Britain, where he "superintended the introduction in his [a patient’s] arm at various times of some ounces of sheep’s blood at a meeting of the Royal Society, and without any inconvenience to him." The recipient was Arthur Coga, "the subject of a harmless form of insanity." Sheep’s blood was used because of speculation about the value of blood exchange between species; it had been suggested that blood from a gentle lamb might quiet the tempestuous spirit of an agitated person and that the shy might be made outgoing by blood from more sociable creatures. Lower wanted to treat Coga several times, but his patient wisely refused. No more transfusions were performed. Shortly before, Lower had moved to London, where his growing practice soon led him to abandon research.
In 1818, Dr. James Blundell, a British obstetrician, performed the first successful blood 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 (about $2 million in 1827) real dollars (adjusted for inflation).
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.
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. 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 transfused per year in the United States.
Great care is taken in cross-matching to ensure that the recipient's immune system will not attack the donor blood. In addition to the familiar human blood types (A, B, AB and O) and Rh factor (positive or negative) classifications, other minor red cell antigens are known to play a role in compatibility. These other types can become increasingly important in people who receive many blood transfusions, as their bodies develop increasing resistance to blood from other people via a process of alloimmunization.
The key importance of the Rh group is its role in Hemolytic disease of the fetus and newborn. When an Rh negative mother carries a positive fetus, she can become immunized against the Rh antigen. This usually is not important during that pregnancy, but in the following pregnancies she can develop an immune response to the Rh antigen. The mother's immune system can attack the baby's red cells through the placenta. Mild cases of HDFN can lead to disability but some severe cases are fatal. Rh-D is the most commonly involved red cell antigen in HDFN, but other red cell antigens can also cause the condition. The "positive" or "negative" in heard blood types such as "O positive" is the Rh-D antigen.
HDN prevention started in the 1960s when it was noted children of pregnant women who had received anti Rh immunoglobulin did not develop the disease. From then on, Rh negative pregnant women receive immunoglobulin doses at several moments during pregnancy and after childbirth if the baby is Rh positive. In current practice, Rh negative women of fertile age will not receive a transfusion of Rh positive blood except in desperate situations when nothing else is available.
Among the diseases than can be transmitted via transfusion are:
As of mid-2005, all donated blood in the United States is screened for HIV, Hepatitis B and C, HTLV-1 and 2, West Nile Virus, and Treponema pallidum. Blood which tests positive for any of the diseases it is tested for is discarded.
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. "Directed" donations from donors known to the recipient were a common practice during the initial years of HIV. These kinds of donations are still common in developing countries.
Some blood banks routinely leukoreduce all collected blood. There is some evidence that this reduces the risk of CJD transmission.
A positive screen warrants an antibody panel/investigation. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for commonly encountered and clinically significant alloantibodies. Donor cells may have homozygous (e.g. K+k-), heterozygous (K+k+) expression or no expression of various antigens (K-k+). The phenotypes of all the donor cells being tested are shown in a chart. The patient's serum is tested against the various donor cells using an enhancement method, eg Gel or LISS. Based on the reactions of the patient's serum against the donor cells, a pattern will emerge to confirm the presence of one or more antibodies. Not all antibodies are clinically significant (i.e. cause transfusion reactions, HDN, etc). Once the patient has developed a clinically significant antibody it is vital that the patient receive antigen negative phenotyped red blood cells to prevent future transfusion reactions. A direct antiglobulin test (DAT) is also performed as part of the antibody investigation.
Once the type and screen has been completed, potential donor units will be selected based on compatibility with the patient's blood group, special requirements (eg CMV negative, irradiated or washed) and antigen negative (in the case of an antibody). If there is no antibody present or suspected, the immediate spin or CAC (computer assisted crossmatch) method may be used.
In the immediate spin method, two drops of patient serum are tested against a drop of 3-5% suspension of donor cells in a test tube and spun in a serofuge. Agglutination or hemolysis in the test tube is a positive reaction and the unit should not be transfused.
If 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.
If there is no time the blood is called "uncross-matched blood". Uncross-matched blood is O-positive or O-negative. O-negative is usually used for children and women of childbearing age. It is preferable for the laboratory to obtain a pre-transfusion sample in these cases so a type and screen can be performed to determine the actual blood group of the patient and to check for alloantibodies.
Donor units of blood must be kept refrigerated to prevent bacterial growth and to slow cellular metabolism. The transfusion must begin within 30 minutes after the unit has been taken out of controlled storage.
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. Clerical error is a significant source of transfusion reactions and attempts have been made to build redundancy into the matching process that takes place at the bedside.
A unit (up to 500 ml) is typically administered over 4 hours. In patients at risk of congestive heart failure, many doctors administer a diuretic to prevent fluid overload, a condition called Transfusion Associated Circulatory Overload or TACO. Acetaminophen and/or an antihistamine such as diphenhydramine are sometimes given before the transfusion to prevent other types of transfusion reactions.
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 immediately before the transfusion.
There are risks associated with receiving a blood transfusion, and these must be balanced against the benefit which is expected. The most common adverse reaction to a blood transfusion is a febrile non-hemolytic transfusion reaction, which consists of a fever which resolves on its own and causes no lasting problems or side effects.
Hemolytic reactions include chills, headache, backache, dyspnea, cyanosis, chest pain, tachycardia and hypotension.
Blood products can rarely be contaminated with bacteria; the risk of severe bacterial infection and sepsis is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions.
There is a risk that a given blood transfusion will transmit a viral infection to its recipient. As of 2006, the risk of acquiring hepatitis B via blood transfusion in the United States is about 1 in 250,000 units transfused, and the risk of acquiring HIV or hepatitis C in the U.S. via a blood transfusion is estimated at 1 per 2 million units transfused. These risks were much higher in the past before the advent of second and third generation tests for transfusion transmitted diseases. The implementation of Nucleic Acid Testing or "NAT" in the early 00's has further reduced risks, and confirmed viral infections by blood transfusion are extremely rare in the developed world.
Transfusion-associated acute lung injury (TRALI) is an increasingly recognized adverse event associated with blood transfusion. TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension, which may occur as often as 1 in 2000 transfusions. 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%.. Although the cause of TRALI is not clear, it has been consistently associated with anti HLA antibodies. Because anti HLA strongly correlate with pregnancy, several transfusion organisations (Blood and Tissues Bank of Cantabria, Spain, National Health Service in Britain) have decided to use only plasma from men for transfusion.
Other risks associated with receiving a blood transfusion include volume overload, iron overload (with multiple red blood cell transfusions), transfusion-associated graft-vs.-host disease, anaphylactic reactions (in people with IgA deficiency), and acute hemolytic reactions (most commonly due to the administration of mismatched blood types).
The rare and experimental practice of inter-species blood transfusions is a form of xenograft.
A number of blood substitutes are currently in the clinical evaluation stage. Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in emergency medicine and in pre-hospital EMS care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results. Hemopure, a hemoglobin-based therapy, is approved for use in South Africa.