PLATELET ANTIGENS AND PLATELET ACTIVATION

血小板抗原和血小板激活

• 批准号: 2571413
• 负责人: H GRALNICK
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2571413
• 关键词: aplastic anemia; atherosclerosis; clinical research; endotoxins; exercise; granule; human subject; human tissue; method development; monoclonal antibody; paroxysmal nocturnal hemoglobinuria; phosphatidylinositols; platelet activation; platelets; thrombocytopenia; von Willebrand's disease

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 degree of platelet activation occurs in these patients after strenuous exercise. In volunteers receiving endotoxin, spontaneous platelet activation or enhanced 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 (PNH) platelet activation. The activation was determined 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. We have also identified modulation of alpha-granule proteins on platelets activated in vitro. In studies comparing patients with aplastic anemia, we were able to identify defects in the phosphatidylinositol anchors. Further studies are in progress.

我们已经开发了几种方法来研究血小板活化。 体内和体外。这些研究是由 血小板分离技术的发展与实现 从人类血液中提取，不会引起血小板活化或分泌。 我们已经研制出了九种只与 激活的血小板。我们的结果表明，在某些形式的 Von Willebrand病，血小板活化的存在和原因 血小板减少症。在动脉硬化性心脏病患者中， 运动后，血小板的活性会增加。这一发现 说明这些患者体内存在一定程度的血小板活化。 剧烈运动后的患者。在志愿者接待中 内毒素，自发的血小板激活或增强的激动剂- 未观察到诱导的血小板活化。个人锻炼 轻度或轻度动脉粥样硬化不会诱发血小板 激活。 我们已经确认了阵发性睡眠性血红蛋白尿患者。 (PNH)血小板活化。激活通过释放来确定。 α颗粒蛋白和增加的纤维蛋白原与 血小板表面。凝血激活的新证据是 观察到的。这些发现表明，血小板活化可能是 PNH静脉血栓形成的主要机制。测试这一点的研究 假说正在实施中。我们还发现了调制 在体外激活的血小板上的α颗粒蛋白。 在比较再生障碍性贫血患者的研究中，我们能够 确定磷脂酰肌醇锚定中的缺陷。进一步 研究正在进行中。