Transfusion Medicine. Jeffrey McCullough
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Key work in understanding the problems of using animal blood for human transfusions was provided by Ponfick and Landois [1]. They observed residues of lysed erythrocytes in the autopsy serum of a patient who died following transfusion of animal blood. They also noted pulmonary and serosal hemorrhages, enlarged kidneys, congested hemorrhagic livers, and bloody urine caused by hemoglobinuria and not hematuria when sheep’s blood was transfused to dogs, cats, or rabbits. Landois observed that human red cells would lyse when mixed in vitro with the sera of other animals. Thus, evidence mounted that interspecies transfusion was likely to cause severe problems in the recipient.
1.4 First transfusions in the United States
In the United States, transfusions were first used in the mid‐1800s, but it is not clear where they were first performed. They may have been done in New Orleans in about 1854 [2]. During the Civil War, the major cause of death was hemorrhage [10]. However, at that time blood transfusion had not been developed, and it appears to have been used in only two to four patients [2]. Two cases are described by Kuhns [10]. One was transfused at Louisville and one at Alexandria within about 10 days of each other. There is no evidence that the procedures were jointly planned or that the physicians involved communicated about them. In both cases, the patients improved following the transfusions [10].
1.5 The discovery of blood groups
The accumulating experiences began to make it clear that transfusions should be performed only between members of the same species. However, even within species, transfusions could sometimes be associated with severe complications. Because of this, and despite the experiences during the Civil War, few transfusions were carried out during the last half of the 1800s. The discovery of blood groups by Landsteiner [11] opened a new wave of transfusion activity. It had been known that the blood of some individuals caused agglutination of the red cells of others, but the significance of this was not appreciated until Landsteiner [11] in 1900 reported his studies of 22 individuals in his laboratory. He showed that the reactions of different combinations of cells and sera formed patterns and these patterns indicated three blood groups [11]. He named these blood groups A, B, and C (which later became group O). Apparently, none of the staff of Landsteiner’s laboratory had the less common group AB, but soon this blood group was reported by the Austrian investigators Decastello and Sturli [1]. Soon thereafter, several other nomenclature systems were proposed, and the American Medical Association convened a committee of experts who recommended a numerical nomenclature system [12] that never gained widespread use [11]. Others later demonstrated that the blood groups were inherited as independent Mendelian dominants, and that the phenotypes were determined by three allelic genes. Hektoen [13] of Chicago first advocated the use of blood grouping to select donors and recipients and to carry out transfusion, but it was Ottenberg [14] who put the theory into practice. These activities are the basis for the widely held belief that blood banking in the United States had its origins in Chicago.
1.6 Anticoagulation
Another factor that inhibited the use of transfusions during the late 1800s was blood clotting. Because of the inability to prevent clotting, most transfusions were given by direct methods. There were many devices for direct donor‐to‐recipient transfusion that incorporated valves, syringes, and tubing to connect the veins of donor and recipient [15].
Although there were many attempts to find a suitable anticoagulant, the following remarks must be prefaced by Greenwalt’s statement that “none of them could have been satisfactory or else the history of blood transfusion would have had a fast course” [1]. Two French chemists, Prévost and Dumas, found a method to defibrinate blood and observed that such blood was effective in animal transfusions [1]. Substances tested for anticoagulation of human blood include ammonium sulfate, sodium phosphate, sodium bicarbonate, ammonium oxalate and arsphenamine, sodium iodide, and sodium sulfate [16, 17]. The delays in developing methods to anticoagulate blood for transfusion are interesting because it was known in the late 1800s that calcium was involved in blood clotting and that blood could be anticoagulated by the addition of oxalic acid. Citrates were used for laboratory experiments by physiologists, and by 1915 several papers had been published describing the use of sodium citrate for anticoagulation for transfusions [1]. It is not clear who first used citrated blood for transfusion [1]. It could have been Lewisohn [18], Hustin, or Weil [19]. In 1955, Lewisohn received the Landsteiner award from the American Association of Blood Banks for his work in the anticoagulation of blood for transfusion.
1.7 Modern blood banking and blood banks
Major stimuli for developments in blood transfusion have come from wars. During World War I, sodium citrate was the only substance used as an anticoagulant. Early in the war, transfusions were vein to vein, but in 1917, Dr. Oswald Robertson of the U.S. Army Medical Corps devised a blood collection bottle and administration set similar to those used several decades later [1] and transfused several patients, some estimate hundreds of patients, with preserved blood [20].
Between World Wars I and II, there was increasing interest in developing methods to store blood in anticipation of rather than response to need. It has been suggested that the first “bank” where a stock of blood was maintained may have been in Leningrad in 1932 [1, 2]. A blood bank was established in Barcelona in 1936 because of the need for blood during the Spanish Civil War [21]. In the United States, credit for the establishment of the first blood bank for the storage of refrigerated blood for transfusion is usually given to Bernard Fantus at the Cook County Hospital in Chicago [22]. The blood was collected in sodium citrate and so it could be stored for only a few days. In England, blood donations were begun within days of the outbreak of WWII in 1939. The British established a Home Depot for collecting blood and shipped blood to Europe even during the Dunkirk campaign.
1.8 Cadaver blood
Cadavers served as another source of blood during the 1930s and later. Most of this work was done by Yudin [23] in the USSR. Following death, the blood was allowed to clot, but the clots lysed by normally appearing fibrinolytic enzymes, leaving liquid defibrinated blood.
The use of cadaver blood in the Soviet Union received much publicity and was believed by many to be the major source of transfusion blood there. Actually, not many more than 40,000 200‐mL units were used, and most of them at Yudin’s Institute [1]. In 1967, the procedure was quite complicated, involving the use of an operating room, a well‐trained staff, and extensive laboratory studies. This was never a practical or extensive source of blood.
1.9 The Rh blood group system and prevention of Rh immunization
In 1939, Levine, Newark, and Stetson [24] published in less than two pages in the Journal of the American Medical Association their landmark article, a case report describing hemolytic disease of the newborn (HDN) and the discovery of the blood group that later became known as the Rh system. A woman who delivered a stillborn infant received a transfusion of red cells from her husband because of intrapartum and postpartum hemorrhage. Following the transfusion, she had a severe reaction but did not react to subsequent transfusions from other donors. The woman’s serum reacted against her husband’s red cells, but not against the cells of the other donors. Levine, Newark, and Stetson postulated that the mother had become immunized by the fetus, who had inherited a trait from the father that the mother lacked. In a later report, they postulated that the antibody found in the mother and subsequently in many other patients was the same as the antibody Landsteiner and Wiener prepared by immunizing Rhesus monkeys [25]. This also began a long debate over credit for discovery of the Rh system.
During the early 1900s, immunologic studies had established that active immunization could be prevented by the presence of passive antibody. This strategy was applied to the prevention