STUDIES OF HEMOSTASIS IN RENAL FAILURE

肾衰竭止血研究

• 批准号: 3353101
• 负责人: Harvey J. Weiss
• 金额: $ 13万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCI
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1989-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353101
• 关键词: arginine vasopressin; biophysics; blood coagulation disorders; blood coagulation tests; blood proteins; blood transfusion; cell adhesion; erythrocytes; fibrin; hemostasis; human subject; platelet aggregation; platelet disorder; platelet factor 4; prostacyclins; radioimmunoassay; radiotracer; renal failure; thrombosis; thromboxanes; uremias; vascular endothelium

The objectives are to investigate the pathogenesis of the bleeding diathesis in chronic renal failure (uremia) through studies on platelet function, primary hemostasis, and rheology in these patients. The specific aims are 1) to characterize more completely the nature and extent of the abnormalities of platelet function in platelets from uremic patients; 2) to examine in detail some of the biochemical pathways that are associated with platelet function as a means of probing the specific defects which may be responsible for the functional abnormalities. These studies will utilize techniques which have demonstrated, in patients with congenital platelet disorders, a variety of abnormalities in secretion-dependent and secretion-independent mechanisms and, in some cases, abnormalities in arachidonate and phospholipid metabolism; 3) to examine whether a defect in platelet interaction with subendothelium exists, utilizing an experimental model (for exposing subendothelium to anticoagulated blood under controlled shear conditions) which has been utilized to demonstrate abnormalities of platelet adhesion/thrombus formation in von Willebrand's disease and congenital platelet disorders, and to determine the basis for such a defect; 4) to study the mechanisms which may account for the findings in recent studies demonstrating a shortening of the bleeding time in uremic patients after transfusion of packed red cells by focusing on the question whether this effect is primarily due to physical properties of red cells in enhancing the diffusivity of platelets, or whether other possible effects of red cells in promoting hemostasis may also be involved; 5) to explore possible defects in the coagulation mechanism by studying platelet-vessel interaction, fibrin deposition, and fibrinopeptide A (FPA) production after exposure of subendothelium to directly sampled (non-anticoagulated) venous blood; 6) to utilize a recently developed technique for analyzing the primary arrest of bleeding through measurements of thromboxane B2 (TxB2), platelet factor 4 (PF4), FPA, and 6-keto-PGF-1Alpha in sequential samples of incisional blood obtained during performance of the bleeding time and, through these studies, to ascertain whether abnormalities of platelet function, prostacyclin (PGI2), arachidonate metabolism, and coagulation in uremia may be detected in vivo; 7) to study the effect of DDAVP on platelet adhesion and the role of large von Willebrand multimers during primary hemostasis.

目的是研究出血的发病机理 慢性肾功能衰竭（尿症）的素质通过血小板的研究 这些患者的功能，原发性止血和流变学。 具体 目的是1）更全面地表征 血小板功能异常在尿毒症患者的血小板中； 2）到 详细检查与某些与之相关的生化途径 血小板功能是探测可能是特定缺陷的一种手段 负责功能异常。 这些研究将利用 在先天性血小板患者中已经证明的技术 疾病，分泌依赖性的各种异常和 与分泌无关的机制，在某些情况下是异常的机制 蛛网酸和磷脂代谢； 3）检查是否存在缺陷 使用实验 模型（用于在受控下将下皮暴露于抗凝血液 剪切条件）已用于证明异常 Von Willebrand氏病的血小板粘附/血栓形成 先天性血小板疾病，并确定此类的基础 缺点; 4）研究可能解释发现的机制 最近的研究表明尿毒症的出血时间缩短 通过关注这个问题，将挤满红细胞输血后的患者 这种效应是否主要是由于红细胞在 增强血小板的扩散率，或者是否其他可能的影响 促进止血的红细胞也可能涉及； 5）探索 通过研究血小板血管的凝血机制可能缺陷 相互作用，纤维蛋白沉积和纤维蛋白肽A（FPA）产生 接触下皮暴露于直接采样（未期权）静脉 血; 6）利用最近开发的技术来分析 通过测量血栓烷B2（TXB2）的一级逮捕出血， 顺序样品中的血小板因子4（PF4），FPA和6-酮-PGF-1Alpha 在出血时间表现期间获得的切口血液 通过这些研究，以确定血小板异常是否 功能，前列环蛋白（PGI2），蛛形代谢和凝结 可以在体内检测到尿毒症； 7）研究DDAVP对血小板的影响 粘附和大型von Willebrand多聚体的作用 止血。