This research proposal focused on the human platelet and its interaction with human antibody and complement in immunohematologic disorders. The mechanisms of these interactions will be examined, as wll as their modification by physiologic regulatory systems and by pharmacologic agents. Platelets will be isolated from normal bolunteers and from patients with immune platelet disorders. The amount of platelet-associated antibody (immunoglobulin class and IgG subclass), C3 fragment and regulatory protein 1H will be quantitated and correlated with clinical course, response to therapy and platelet function. A detailed study of immune thrombocytopenia in pregnancy will be undertaken, as well as an analysis of the platelet Fc receptor and the role of corticosteroid therapy. These studies should be of diagnostic and therapeutic importance in the problematic setting of potential neonatal thrombocytopenia. A detailed study of corticosteroids and steroid analogues will be undertaken in an in vivo animal model and in an in vitro human model in order to identify potentially more therapeutically potent agents with minimal side effects. The effect of classic and alternative complement pathway activation and the role of the C3b inactivator system and the human macrophage in platelet function, alteration and subcellular damage will also be assessed, as well as the modification of these interactions by antiplatelet agents and steriod analogues. Complement-platelet interactions may lead to a paradoxial predisposition to thrombosis. The nature of the complement-platelet interaction in patients with heparin induced thrombocytopenia, the lupus inhibitor, PNH and immune hemolysis with thrombosis will be studied, as well as the modification of this interaction by the C3b inactivator system and pharmacologic agents. Alterations of platelet function which could lead to thrombosis will also be explored. A detailed analysis of the interaction of antibody and complement with platelets should help to define the pathogenesis of qualitative and quantitative platelet abnormalities in immunohematologic disease and help to delineate the rationale for pharmacologic interaction.
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