The introduction of citrate as an anticoagulant for transfusion and of glucose as a red cell preservative.
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Biomedical subjects
Publications and source records attributed to P L Mollison.
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Blood transfusion became a relatively safe and practicable procedure following the discovery in 1900 of blood groups and the realization early in the first World War that citrate was a safe and effective anticoagulant. Transfusion may elicit the formation of antibodies in the recipient due to "foreign" antigens on the donor's red cells, white cells, or platelets. Application of the methods of molecular biology has characterized the antigens concerned and the genes that determine them. The concept of transfusing whole blood to remedy a deficiency of any constituent, for example, platelets, has been superseded by the idea of transfusing only that component of blood which is needed. Many viruses, for example, hepatitis viruses and human immunodeficiency viruses, can be transmitted by transfusion. The high degree of success in preventing their transmission is a scientific triumph.
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Two human monoclonal antibodies, one IgG3 and one IgG1, with anti-Rh D specificity, were tested for their ability to clear red cells. Samples of red cells from 12 D-positive subjects were sensitised in vitro with various amounts of antibody, the number of antibody molecules bound to the cells was estimated, and the cells were reinjected into the donor's circulation. Both antibodies mediated clearance but substantially fewer IgG3 than IgG1 antibody molecules were required to produce a given rate of clearance. The IgG3 antibody was slightly more effective than polyclonal anti-D, as judged by comparison with previously published results. Since there is believed to be an association between the rate of red cell clearance by anti-D and the ability of the antibody to suppress D immunisation, the IgG3 monoclonal antibody may prove suitable for the immunoprophylaxis of Rh D haemolytic disease.
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Investigations on six males with naturally occurring Rh antibodies are described. In two subjects in whom the antibody (one anti-E and one anti-D) could be detected only by a two-stage papain technique, the survival of incompatible red cells was normal. In the remaining four subjects, the antibodies (two anti-E and two anti-D) could be detected by the indirect antiglobulin test and, in these, incompatible red cells were destroyed at an accelerated rate; in two of the subjects, 75-99% of the cells were cleared within 24 h; in the other two, 50% of the cells were cleared within 24 h and the remaining cells were cleared far more slowly. All six antibodies were mainly or wholly IgG; a clear-cut immune response was observed in only one case.
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Examination of death certificates and the clinical notes of the patients concerned showed that the number of deaths from rhesus (D) haemolytic disease in England and Wales was 44 and 34 during 1982 and 1983, respectively, a substantial decrease from the figure of 106 for 1977. Of the 78 women whose infants died in 1982 and 1983, 49 had not received anti-Rh immunoglobulin after previous pregnancies with Rh positive infants; most of these deaths would presumably have been prevented had postnatal anti-Rh immunoglobulin been given. In 13 women anti-D was detected during, or immediately after, a first pregnancy, and in 15 women rhesus immunisation developed despite administration of anti-Rh immunoglobulin postnatally. One or two apparent failures of treatment may have been due to underdosage, but it must be concluded that about one third of the deaths in 1982 and 1983 could have been prevented only by giving anti-Rh immunoglobulin antenatally as well as postnatally.