England at about the same time [26, 27]. Subjects were protected from Rh immunization if they were given either Rh‐positive red cells coated with anti‐Rh or anti‐Rh followed by Rh‐positive red cells. Subsequent studies established that administration of anti‐Rh in the form of Rh immune globulin could prevent Rh immunization, and thus almost eliminate HDN. Currently, control of HDN is a public health measure similar to ensuring proper immunization programs for susceptible persons.
1.10 Coombs and antiglobulin serum
In 1908, Moreschi [28] is said to have described the antiglobulin reaction. The potential applicability of this in the detection of human blood groups was not appreciated until 1945, when Coombs, Mourant, and Race [29] published their work on studies of the use of rabbit antibodies against human IgG to detect IgG‐coated red cells. Red cells were incubated with human sera containing antibodies against red cell antigens and washed, and the rabbit anti‐human sera were used to demonstrate the presence of bound IgG by causing agglutination of the red cells. The availability of anti‐human globulin serum made it possible to detect IgG red cell antibodies when the antibody did not cause direct agglutination of the cells. Thus, red cells coated with anti‐IgG red cell antibodies could be easily detected, and the era of antibody screening and crossmatching was born. This greatly improved the safety of blood transfusion and also led to the discovery of many red cell antigens and blood groups.
1.11 Plasma and the blood program during World War II
Techniques for collection, storage, and transfusion of whole blood were not well developed during the 1930s. The outbreak of World War II added further impetus to the development of methods to store blood for periods longer than a few days. Although the method of blood anticoagulation was known by the mid‐1920s, red blood cells hemolyzed after storage in sodium citrate for 1 week. This limitation also slowed the development of blood transfusion. Although it was also known that the hemolysis could be prevented by the addition of dextrose, the practical value of this important observation was not recognized for more than a quarter of a century. Anticoagulant preservative solutions were developed by Mollison [30] in Great Britain. However, when the glucose–citrate mixtures were autoclaved, the glucose caramelized, changing the color of the solution to various shades of brown. The addition of citric acid eliminated this problem and also extended the storage time of blood to 21 days. The advance of World War II also brought an understanding of the value of plasma in patients with shock [31, 32]. In the early 1940s, Edwin J. Cohn, PhD, a Harvard biochemist, developed methods for the continuous flow separation of large volumes of plasma proteins [33, 34]. This made possible during World War II the introduction of liquid and lyophilized plasma and human albumin as the first‐line management of shock. Initial work using plasma for transfusion was carried out by John Elliott [31, 32]. This combination of technological and medical developments made it possible for Charles R. Drew to develop the “Plasma for Britain” program [35].
1.12 Plastic bags and blood components
One of the next major developments in blood banking was the discovery and patenting of the plastic blood container by Carl Walter in 1950. This made possible the separation of whole blood and the creation of blood component therapy. Dr. Walter’s invention was commercialized by the Baxter Corporation. The Fenwal division later became a freestanding company; the “‐wal” of “Fenwal” represents Dr. Walter’s name. The impact of the introduction of multiple connected plastic containers and the separation of whole blood into its components also began to generate enormous amounts of recovered plasma, which made possible the development of large‐scale use of coagulation factor VIII concentrates.
1.13 Cryoprecipitate and factor VIII
In 1965, Dr. Judith Pool reported that if fresh frozen plasma was allowed to thaw at refrigerator temperatures, precipitate remained that contained most of the coagulation factor VIII from the original fresh frozen plasma [36]. This made it possible for the first time to administer large doses of factor VIII in a concentrated form to patients with hemophilia and opened an era in which the bleeding diathesis could be effectively managed. A few years later, reports began to appear describing the use of a concentrated factor VIII prepared using the plasma fractionation technique developed by Edwin Cohn [33]. This further simplified the management of hemophilia because the ability to store the factor VIII concentrates in home refrigerators enabled the development of home treatment programs involving prophylactic or immediate self‐administration of factor VIII.
1.14 Red cell preservation
The role of 2,3‐diphosphoglycerate in oxygen transport by red cells was discovered in the mid‐1960s [37, 38]. It had been known previously that this compound was better maintained at higher pH, whereas adenosine triphosphate, which appeared to be involved in red cell survival, was maintained better at a lower pH. The addition of adenine was shown to improve adenosine triphosphate maintenance and prolong red cell survival and storage for transfusion [39]. The next major advance in red cell preservation was the development of preservative solutions designed to be added after removal of most of the original anticoagulated plasma, thus further extending the storage period of red cells [40].
1.15 Leukocyte antigens and antibodies
In 1926, Doan [41] described the sera of some individuals that caused agglutination of the leukocytes from others. Subsequent studies established the presence of leukocyte antibodies, the presence of these antibodies in the sera of polytransfused patients, the occurrence of white cell agglutinins in response to fetomaternal immunization, and the alloimmune and autoimmune specificities associated with these antibodies. These studies, along with studies of the murine histocompatibility system, led to the description of the major histocompatibility system (human lymphocyte antigens) [42] in humans and the understanding that there are separate antigenic specificities limited to neutrophils as well [43]. These studies also defined the causative role of leukocytes in febrile nonhemolytic transfusion reactions [44]. Strategies were sought to prevent these reactions by removing the leukocytes from blood [45, 46], one of the first methods being reported by Fleming [46], who discovered penicillin.
1.16 Platelet collection, storage, and transfusion
The relationship between bleeding and thrombocytopenia had been known for some time, but the development of the plastic bag system for blood collection made platelets available for transfusion. Several years of work by many investigators—predominantly at the National Cancer Institute during the 1960s—developed the methods for preparing platelets and established that platelet transfusion to patients with thrombocytopenia reduced mortality from hemorrhage [47]. Initially, platelets had to be transfused within a few hours after the whole blood was collected, and thus large‐scale application in the general medical care setting was impractical. The seminal report by Murphy and Gardner [48] showing that room temperature allowed platelets to be stored for several days revolutionized platelet transfusion therapy.
1.17 Apheresis
Plastic bags were used to remove whole blood, separate the plasma from the red cells, retain the plasma, and return the red cells, thus making it possible to obtain substantial amounts of plasma from one donor [49]. This initiated the concept of attempting to obtain only selected portions of whole blood to collect larger amounts of plasma or cells. The centrifuge developed by Cohn for plasma fractionation was modified by Jack Latham and became a semiautomated system for plasmapheresis [50] and subsequently was used for platelet collection as well [51, 52]. At the National Institutes of Health Clinical Center, an IBM engineer worked with hematologists to develop a centrifuge that enabled collection of platelets or granulocytes from a continuous flow of blood through the instrument [53, 54]. Later versions of these instruments have become widely used for plateletpheresis and leukophoresis.
