PLATELET ANTIGENS AND PLATELET ACTIVATION

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We have developed several methods to study platelet activation ex vivo and in vitro. These studies were made possible by the development and implementation of techniques to isolate platelets from human blood without inducing platelet activation or secretion. We have developed nine monoclonal antibodies that react only with activated platelets. Our results have shown that in some forms of von Willebrand's disease, platelet activation is present and causes thrombocytopenia. In patients with arteriosclerotic heart disease, platelet activation is increased after exercise. This finding suggests that some endotoxin, spontaneous platelet activation or enhances agonist-induced platelet activation is not observed. Exercise in individuals with minor or mild atherosclerosis does not induce platelet activation. We have identified patients with paroxysmal nocturnal hemoglobinuria (PNM) platelet activation. The activation was shown by release of alpha granule protein and increased fibrinogen binding to the platelet surface. New evidence of coagulation activation was observed. These findings suggest that platelet activation may be the primary mechanism of venous thrombosis in PNH. Studies to test this hypothesis are being implemented.