PLATELETS AND BLOOD FLOW IN SICKLE CELL DISEASE

    Project: Research project

    Project Details

    Description

    Vascular occlusive events account for much of the morbidity and mortality in patients with sickle cell disease. The pathogenesis of these vaso- occlusive events remains ill-defined and the subject of much speculation. The focus of this research proposal will be the role of platelet activation and platelet-erythrocyte aggregates in vaso-occlusive events. We hypothesize the following: 1) There is baseline platelet activation in patients with sickle cell disease which increases during vaso-occlusive crisis, 2) increased platelet activation is negatively correlated with blood flow in the microvasculature, 3) circulating platelet-erythrocyte aggregates (PEA) are present in patients with sickle cell disease and increase during vaso-occlusive events and, 4) platelet-erythrocyte aggregation is mediated by thrombospondin and fibronectin. Using fluorescent-labeled antibodies to activation-dependent and -independent platelet antigens, red cell antigens, and flow cytometry, longitudinal studies of patients with sickle cell disease will be done to determine the degree of platelet activation and platelet-erythrocyte aggregate formation and their relation to clinical events. Platelet activation and PEA will be correlated with blood flow as measured by computer-assisted intravital microscopy of the bulbar conjunctiva. The role of fibronectin and thrombospondin in PEA formation will be studied by the incubation of platelets and red cells from patients and normals, in the presence and absence of antibodies to these adhesive proteins or their receptors. These data will fill gaps in the knowledge of the degree arid persistence of platelet activation, microcirculatory blood flow abnormalities, and platelet-red cell interactions in sickle call patients.
    StatusFinished
    Effective start/end date7/13/956/30/00

    Funding

    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health

    ASJC

    • Medicine(all)

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