(Candidate?s abstract) Sickle cell disease affects approximately 50,000 African-Americans. The major clinical problems are the crises (painful episodes), associated with occlusion of small vessels by sickled red blood cells, by other cellular and vascular changes and by increased clotting activity. The cause of the hypercoagulable state is not clear. We will examine the effects of the strongly procoagulant vesicles, which are shed from sickle red cells, and relate the levels to clotting activity, to the presence or absence of crises as well as to severity of disease. Ten patients with Hb SS disease, 10 with Hb SC disease, 10 with sickle cell trait and 10 normal controls will be studied. Levels of circulating vesicles will be measured by a flow cytometric method recently developed in our group using annexin V-FITC labeled vesicles. The results would determine the contribution of the shed vesicles to the increased clotting activity, to the pathogenesis of the microvascular occlusion and crises as well as to disease severity and would be helpful for selection of patients for marrow transplantation, drug treatment or for other forms of treatment. The findings may also determine whether anticoagulation would be useful in management of the disease.