ROLE OF BLOOD/VESSEL WALL COMPONENTS IN THROMBOSIS

这项提案的总体目标是确定 血液中与血管相互作用的基本成分上的血流 在血栓形成过程中的表面。血小板和血小板的沉积 剥离血管内皮细胞的血管节段上的蛋白质物质 将在环状灌流系统中对衬里进行全面研究 在血管内遇到了一系列的剪切情况。全血将会是 通过各种技术制备：(1)在柠檬酸盐抗凝剂中，(2)天然的， 没有抗凝剂，(3)由各种细胞和 血液中的蛋白质组分，以及(4)重新钙化以允许激活 凝血系统的。这些血液会接触到各种类型的 血管节段：(1)储存在缓冲液中的兔、人和猪血管，(2) 新制备的血管，(3)用所选抗体处理的血管 内皮下层成分，以及(4)缺乏成分的血管，如 冯·威尔布兰德因子(VWF)。血管表面与表面的相互作用 纤维蛋白和血小板将使用形态计量学方法 评估。纤维蛋白原活化与血小板释放 血液中穿过血管节段的颗粒状物质 将通过放射免疫测定法进行测量，并与形态计量学相关 结果。 将特别强调调查冯·威勒布兰德的角色 与血小板与血小板相互作用有关的因子(VWF) 内皮下层与血管上血小板血栓的生长和稳定性 墙面利用了一组独特的患者，各种定义明确 VWD亚型。血流量对血浆VWF能力的影响 为了在血液中扩散，结合在内皮下表面并关联 具有血管壁的VWF将与其影响能力有关 血小板-内皮下相互作用。血小板的潜在重要性 血管性血友病因子在调节血小板-血小板聚集中的作用 通过使用不同水平的患者来评估内皮下层 血小板VWF与重症VWD患者输血后的研究 VWF。血管壁VWF多聚体的大小分布，它们的能力 内皮下层多聚体及其在血小板结合中的作用 还将对内皮下层进行研究。

The overall objective of this proposal is to determine the influence of blood flow on the basic components of blood which interact with vascular surfaces in the process of thrombosis. The deposition of platelets and proteinaceous material on vessel segments denuded of their endothelial lining will be investigated in an annular perfusion system under the full range of shear conditions encountered intravascularly. Whole blood will be prepared by various techniques: (1) in citrate anticoagulant, (2) native, without anticoagulant, (3) reconstituted with various cellular and proteinaceous fractions of blood, and (4) re-calcified to permit activation of the coagulation system. This blood will be exposed to various types of vascular segments: (1) rabbit, human and pig vessels stored in buffer, (2) freshly prepared vessels, (3) vessels treated with antibodies to selected elements of subendothelium, and (4) vessels deficient in components such as von Willebrand's factor (VWF). The interaction of the vessel surface with fibrin and platelets will be quantified using a morphometric means of evaluation. The activation of fibrinogen and the release of platelet granular material in the blood which has passed over the vascular segments will be measured by radio-immuno assay and correlated with the morphometric results. Special emphasis will be placed on investigating the role of von Willebrand factor (VWF) with respect to the interaction of platelets with subendothelium and the growth and stability of platelet thrombi on vessel walls utilizing a unique group of patients with various well-defined subtypes of VWD. The influence of blood flow on the ability of plasma VWF to diffuse through blood, bind at the subendothelial surface and associate with vessel wall VWF will be related to its ability to influence platelet-subendothelial interaction. The potential importance of platelet VWF in mediating the development of platelet-platelet aggregation on subendothelium will be assessed by using patients with varying levels of platelet VWF and by studying patients with severe VWD after transfusion of VWF. The size distribution of vessel wall VWF multimers, their ability to multimerize on subendothelium and their role in platelet binding to subendothelium will also be investigated.