Beginning with
William Harvey's experiments on the circulation of blood, recorded 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.
Early attempts Animal blood pioneered the first blood transfusion from animal to human in 1665 at the
Royal Society. Working at the
Royal Society in the 1660s, the physician
Richard Lower began examining 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. The new instruments he was able to devise enabled him to perform the first reliably documented successful transfusion of blood in front of his distinguished colleagues from the Royal Society. According to Lower's account, "...towards the end of February 1665 [I] 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|[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. The first blood transfusion from animal to human was administered by
Jean-Baptiste Denys, eminent physician to
King Louis XIV of France, on June 15, 1667. He transfused the blood of a
sheep into a 15-year-old boy, who survived the transfusion. Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to the small amount of blood that was actually transfused into these people. This allowed them to withstand the
allergic reaction. Denys's third patient to undergo a blood transfusion was Swedish Baron
Gustaf Bonde. He received two transfusions. After the second transfusion Bonde died. In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood. On the third account Mauroy died. Six months later in London, Lower performed the first human transfusion of animal blood in Britain, where he "superintended the introduction in [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. Coga received 20 shillings () to participate in the experiment. Lower went on to pioneer new devices for the precise control of blood flow and the transfusion of blood; his designs were substantially the same as modern
syringes and
catheters. These early experiments with animal blood provoked a heated controversy in Britain and France.
Human blood successfully transfused human blood in 1818. 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 James Blundell made efforts to treat
hemorrhage by transfusion of human blood using a syringe. In 1818, after experiments with animals, he performed the first successful transfusion of human blood to treat
postpartum hemorrhage at Guy's Hospital in London. Blundell used the patient's husband as a donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented a number of instruments for the transfusion of blood. He made a substantial amount of money from this endeavour, roughly $2 million ($50 million
real dollars). In 1840,
Samuel Armstrong Lane, aided by Blundell, performed the first successful whole blood transfusion to treat
haemophilia at
St George's Hospital Medical School in London. However, early transfusions were risky and many resulted in the death of the patient. By the late 19th century, blood transfusion was regarded as a risky and dubious procedure, and was largely shunned by the medical establishment. Work to emulate James Blundell continued in Edinburgh. In 1845 the
Edinburgh Journal described the successful transfusion of blood to a woman with severe uterine bleeding. Subsequent transfusions were successful with patients of
James Young Simpson, after whom the
Simpson Memorial Maternity Pavilion in Edinburgh was named. Various isolated reports of successful transfusions emerged towards the end of the 19th century. The largest series of early successful transfusions took place at the
Edinburgh Royal Infirmary between 1885 and 1892. Edinburgh later became the home of the first blood donation and blood transfusion services. Landsteiner discovered that adverse effects arise from mixing blood from two incompatible individuals. He found that mixing incompatible types triggers an immune response and the red blood cells clump. The immunological reaction occurs when the receiver of a blood transfusion has antibodies against the donor blood cells. The
destruction of red blood cells releases free
hemoglobin into the bloodstream, which can have fatal consequences. Landsteiner's work made it possible to determine blood group and allowed blood transfusions to take place much more safely. For his discovery he won the Nobel Prize in Physiology and Medicine in 1930;
many other blood groups have been discovered since.
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.
Jan Janský also discovered the human blood groups; in 1907 he classified blood into four groups: I, II, III, IV. His nomenclature is still used in Russia and in states of the former USSR, in which blood types O, A, B, and AB are respectively designated I, II, III, and IV. American physician
William Lorenzo Moss's (1876–1957) developed a blood typing technique in 1910 (popularly known as Moss system of blood typing) that was widely used until
World War II. The Moss technique also used Roman numerals using I, II, III, IV to correspond to AB, A, B, and O respectively; a potentially dangerous overlap with Janský's classification.
William Stewart Halsted (1852–1922), an American surgeon, performed one of the first blood transfusions in the United States. He had been called to see his sister after she had given birth. He found her moribund from blood loss, and in a bold move withdrew his own blood, transfused his blood into his sister, and then operated on her to save her life.
Blood banks in WWI (
2nd from right) overseeing one of the first safe and effective blood transfusions in 1914 While the first transfusions had to be made directly from donor to receiver before
coagulation, 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 the development of
blood banks.
John Braxton Hicks was the first to experiment with chemical methods to prevent the coagulation of blood at
St Mary's Hospital, London in the late-19th century. His attempts, using
phosphate of soda, however, proved unsuccessful. The
Belgian doctor
Albert Hustin performed the first non-direct transfusion on March 27, 1914, though this involved a diluted solution of blood. The
Argentine doctor
Luis Agote used a much less diluted solution in November of the same year. Both used
sodium citrate as an anticoagulant. The
First World War (1914–1918) acted as a catalyst for the rapid development of blood banks and transfusion techniques.
Francis Peyton Rous and Joseph R. Turner at the
Rockefeller University (then The Rockefeller Institute for Medical Research) made the first important discoveries that blood typing was necessary to avoid blood clumping (coagulation) and blood samples could be preserved using chemical treatment. Their first report in March 1915 showed that gelatine, agar, blood serum extracts, starch and beef albumin proved to be useless preservatives. However, building on the same experiment, they discovered that a mixture sodium citrate and glucose (
dextrose) solution was a perfect preservative; as they reported in February issue of the
Journal of Experimental Medicine, the preserved bloods were just like fresh bloods and that they "function excellently when reintroduced into the body." Blood could be preserved for up to four weeks. An accompanying experiment using citrate-saccharose (sucrose) mixture was also a success which could maintain blood cells for two weeks. This use of citrate and sugars, sometimes known as Rous-Turner solution, was the foundation for the development of blood banks and improvement of transfusion method. Another discovery of Rous and Turner was the most critical step in the safety of blood transfusion. Rous was well aware that Landsteiner's concept of blood types had not yet found practical value, as he remarked: "The fate of Landsteiner's effort to call attention to the practical bearing of the group differences in human bloods provides an exquisite instance of knowledge marking time on technique. Transfusion was still not done because (until at least 1915), the risk of clotting was too great." In June 1915, they made a crucial report in the
Journal of the American Medical Association that agglutination could be avoided if the blood samples of the donor and recipient were tested before. Which they called a rapid and simple method for testing blood compatibility, sodium citrate was used to dilute the blood samples, and after mixing the recipient's and donor's blood in 9:1 and 1:1 parts, blood would either clump or remain watery after 15 minutes. According to their advice, blood without clumping "should always be chosen if possible." Canadian doctor and Lieutenant
Lawrence Bruce Robertson became instrumental in persuading the
Royal Army Medical Corps to adopt the use of blood transfusion at the
Casualty Clearing Stations for the wounded. In October 1915, Robertson performed his first wartime transfusion with a syringe to a patient who had multiple shrapnel wounds. He followed this up with four subsequent transfusions in the following months, and his success was reported to Sir
Walter Morley Fletcher, director of the
Medical Research Committee. Russian syringe for direct inter-human blood transfusion Robertson published his findings in the
British Medical Journal in 1916 and, with the help of a few like-minded individuals (including the eminent physician
Edward William Archibald), was able to persuade the British authorities of the merits of blood transfusion. Robertson went on to establish the first blood-transfusion apparatus at a Casualty Clearing Station on the
Western Front in the spring of 1917. Robertson did not test crossmatching so that one died of hemolysis in his 1916 transfusion, and three in 1917.
Oswald Hope Robertson, a medical researcher and
U.S. Army officer, was attached to the
RAMC in 1917, where he became instrumental in establishing the first blood banks in preparation for the anticipated
Third Battle of Ypres. He used sodium citrate as the anticoagulant; blood was extracted from punctures in the
vein and was stored in bottles at British and American Casualty Clearing Stations along the Front. Robertson also experimented with preserving separated
red blood cells in iced bottles. After providing a donor, Oliver set about organizing a system for the voluntary registration of blood donors at clinics around London, with Sir
Geoffrey Keynes appointed as a medical adviser. Volunteers were subjected to a series of physical tests to establish their
blood group. The
London Blood Transfusion Service was free of charge and expanded rapidly in its first few years of operation. By 1925 it was providing services for almost 500 patients; it was incorporated into the structure of the British Red Cross in 1926. Similar systems developed in other cities, including
Sheffield,
Manchester and
Norwich, and the service's work began to attract international attention. France, Germany, Austria, Belgium, Australia and Japan established similar services.
Alexander Bogdanov founded an academic institution devoted to the science of blood transfusion 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. Bogdanov died in 1928 as a result of one of his experiments, when the blood of a student with
malaria and
tuberculosis was given to him in a transfusion. Following Bogdanov's lead, Vladimir Shamov and
Sergei Yudin in the
USSR pioneered the
transfusion of cadaveric blood from recently deceased donors. Yudin performed such a transfusion successfully for the first time on March 23, 1930, and reported his first seven
clinical transfusions with cadaveric blood at the Fourth Congress of
Ukrainian Surgeons at Kharkiv in September. However, this method was never used widely, even in the Soviet Union. Nevertheless, the Soviet Union was the first to establish a network of facilities to collect and store blood for use in transfusions at hospitals.
Frederic Durán-Jordà established one of the earliest blood banks during the
Spanish Civil War in 1936. Duran joined the Transfusion Service at the
Barcelona Hospital at the start of the conflict, but the hospital was soon overwhelmed by the demand for blood and the paucity of available donors. With support from the Department of Health of the
Spanish Republican Army, Duran established a blood bank for the use of wounded soldiers and civilians. The 300–400 mL of extracted blood was mixed with 10% citrate solution in a modified Duran Erlenmeyer flask. The blood was stored in a sterile glass enclosed under pressure at 2 °C. During 30 months of work, the Transfusion Service of Barcelona registered almost 30,000 donors, and processed 9,000 liters of blood. 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 setting up a hospital laboratory that preserved, refrigerated 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. Until the middle of World War II, the newly established US blood banks rejected African-American donors. During the war, Black people were allowed to donate blood, but the donated blood was labeled as being suitable only for transfusion into another person from the same race. Frederic Durán-Jordà fled to Britain in 1938 and worked with Dr
Janet Vaughan at the
Royal Postgraduate Medical School at Hammersmith Hospital to establish a system of national blood banks in London. With the outbreak of
war appearing imminent in 1938, the
War Office created the Army Blood Supply Depot (ABSD) in Bristol, headed by
Lionel Whitby and in control of four large blood-depots around the country. British policy through the war was to supply military personnel with blood from centralized depots, in contrast to the approach taken by the Americans and Germans where troops at the front were bled to provide required blood. The British method proved more successful in adequately meeting all requirements, and over 700,000 donors were bled over the course of the war. This system evolved into the
National Blood Transfusion Service established in 1946, the first national service to be implemented. Stories tell of
Nazis in Eastern Europe during World War II using captive children as repeated involuntary blood-donors.
Medical advances in
Sicily, 1943 Gordon R. Ward, writing in the correspondence columns of the
British Medical Journal, proposed the use of
blood plasma as a substitute for whole blood and for transfusion purposes as early as 1918. At the onset of
World War II, liquid plasma was used in Britain. A large project, known as "Blood for Britain", began in August 1940 to collect blood in
New York City hospitals for the export of plasma to
Britain. Following heavy casualties in the Battle of Dunkirk, the Blood Transfusion Association in New York City originated the campaign that was enlarged to the whole US by the
Red Cross, and was called the National Blood Programme. At the time, American physician
Edwin Cohn pioneered the process of
blood fractionation. He worked out the techniques for isolating the
serum albumin fraction of
blood plasma, which is essential for maintaining the
osmotic pressure in the
blood vessels, preventing their collapse. A
freeze-dried plasma package was developed by the Surgeons General of the Army and Navy, working with the
National Research Council, which reduced breakage and made transportation, packaging, and storage much simpler. oversaw the production of blood plasma for shipping to Britain during WW2. The resulting dried plasma package came in two tin cans containing 400 mL bottles. One bottle contained enough
distilled water to reconstitute the dried plasma contained within the other bottle. In about three minutes, the plasma would be ready to use and could stay fresh for around four hours.
Charles R. Drew was appointed medical supervisor, and he was able to transform the
test-tube methods into the first successful technique for mass production. Another important breakthrough came in 1937–40 when Karl Landsteiner (1868–1943), 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 reduced 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 made from
PVC 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, the replacement of massive blood-loss became a major problem. The cardiac-arrest rate was high. In 1963 C. Paul Boyan and William S. Howland discovered that the temperature of the blood and the rate of infusion greatly affected survival rates, and introduced blood warming to surgery. Further extending the shelf-life of stored blood up to 42 days was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks. about 15 million units of blood products were transfused per year in the United States. By 2013 the number had declined to about 11 million units, because of the shift towards
laparoscopic surgery and other surgical advances and studies that have shown that many transfusions were unnecessary. For example, the standard of care reduced the amount of blood transfused in one case from 750 to 200 mL. In 2019, 10,852,000 RBC units, 2,243,000 platelet units, and 2,285,000 plasma units were transfused in the United States. == Special populations ==