PLATELETS AND BLOOD FLOW IN SICKLE CELL DISEASE

血管闭塞事件是导致发病率和死亡率的主要原因。 在患有镰状细胞病的患者中。这些血管的发病机制-- 遮蔽性事件仍然定义不清，也是许多猜测的主题。 这项研究计划的重点将是血小板的作用 血管闭塞事件中的活化和血小板-红细胞聚集性。 我们假设如下：1)存在基线的血小板活化 在血管闭塞期间增加的镰状细胞病患者 危象，2)血小板活化增加与 微血管中的血流，3)循环中的血小板-红细胞 聚集体(PEA)存在于镰状细胞疾病患者和 在血管闭塞事件期间增加，4)血小板-红细胞 凝血酶原蛋白和纤维连接蛋白参与了凝集。vbl.使用 激活依赖和非激活的荧光标记抗体 纵向的血小板抗原、红细胞抗原和流式细胞术 将对镰状细胞病患者进行研究，以确定 血小板活化程度与血小板-红细胞聚集性 以及它们与临床事件的关系。血小板活化和PEA将是 与计算机辅助活体内测量的血流量相关 球结膜的显微镜检查。纤维粘连蛋白及其受体的作用 凝血酶敏感蛋白在PEA形成中的研究将通过孵育 患者和正常人的血小板和红细胞 缺乏对这些黏附蛋白或其受体的抗体。这些 数据将填补关于 血小板活化，微循环血流异常，以及 镰状呼唤患者中的血小板-红细胞相互作用。

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.