HEMORRHAGIC DISEASES

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Studies of the pathogenesis, diagnosis and treatment of hemorrhagic diseases are proposed, with emphasis on the following areas: Membrane platelet markers; immunologic and immunochemical studies: Membrane constitutents to which platelet antibodies bind and the mechanism of drug-antibody-platelet interaction in drug-induced immune thrombocytopenia will be characterized at a molecular level. The variable expression of HLA-A and B markers on platelets and its implications for platelet transfusion therapy will be explored. Immune disorders of platelets; immunologic aspects of platelet transfusion therapy: Studies will be conducted to improve the sensitivity and specificity of platelet antibody detection and measurement of platelet associated immunoglobulins. The relationship of previously undescribed, warm-reactive macroglobulin specific for an enzyme-activated site on normal platelets to the pathogenesis of autoimmune thrombocytopenic purpura of childhood will be defined. The natural history and response to therapy of neonatal alloimmune thrombocytopenic purpura and post-transfusion purpura will be further characterized. Studies to improve matching of platelets for alloimmunized thrombocytopenic patients and to define the importance of circulating immune complexes in the response to platelet transfusions will be conducted. Optimum conditions for isolation and short-term preservation of platelets: Methods to improve the quality of platelet concentrates will be sought with emphasis on the use of inhibitors of adenylate cyclase, the significance of activation of the endogenous, calcium-activated protease of platelets, and the mode of agitation during storage. The importance of leukocytes in platelet preservation will be further characterized. Human platelet heterogeneity: physiologic significance: Studies of the factors that determine buoyant density of human platelets, the relationship of buoyant density to platelet age, and the changes that occur in human platelets during the aging process will be conducted.