RELATIONSHIPS BETWEEN COAGULATION AND THROMBOSIS

这一综合生化、生理和临床计划的目标是 是研究启动和调节组织的机制 凝血因子依赖的凝血途径在止血中的作用 病理状态。生物化学反应将在纯化和 血浆系统，利用活化肽释放分析来测量 凝血因子IX和X的激活以及凝血因子VII与凝血酶原活动度的比值 胺解活性与标记因子放射性分布的偶联 第七因子的措施激活。将作出重大努力 提纯一种先前未描述的等离子体材料，使用Xa因子， 抑制因子VIIa-组织因子的酶活性，并描绘 抑制作用的机制。第二个生化项目将集中在 激活因子VII。激活的程度将与 组织因子依赖的因子IX和X的激活率来确定 产生最小数量的因子VIIa是否能产生最大 因子IX和X的激活率。能力将被评估为 活化的血小板上的磷脂和未受干扰的磷脂 人内皮细胞支持因子Xa及其诱导的因子IXa 激活因子VII。第三个生化项目将集中在 凝血酶原因子VII与组织因子相互作用能力的研究 培养的人内皮细胞对因子IX的激活作用 和X.抗凝血酶III和上述血浆抑制材料 将包括在一些反应混合物中。在其他实验中， 将在孵化过程中加入越来越多的预制因子VIIa 与因子VII的混合物。生理实验将在 兔确定是输注组织因子还是注射内毒素 可以耗尽血浆中和所需的抑制物质 因子VIIa--组织因子。血浆抑制因子水平也将 在病人身上测量。血浆抑制因子的定量测定 就是为这些目的而设计的。其他临床项目将包括 研究(1)血小板因子V在心脏骤停止血中的作用 患者服用凝血因子V抗凝剂，(2) 抗凝血酶原抗体和狼疮抗凝剂，以及(3)诊断 遗传性蛋白C和血栓形成的技术和表现 蛋白质S缺乏。

The goal of this integrated biochemical, physiological and clinical program is to study mechanisms initiating and regulating the tissue factor-dependent pathway of blood coagulation during hemostasis and in pathologic states. Biochmical reactions will be studied in purified and plasma systems, utilizing activation peptide release assays to measure activation of factors IX and X and the ratio of factor VII clotting to amidolytic activity coupled with radioactivity profiles of labeled factor VII measure activation of factor VII. A major effort will be made to purify a previously undescribed plasma material that, with factor Xa, inhibits factor VIIa-tissue factor enzymatic activity and to delineate the mechanism of the inhibition. A second biochemical project will focus upon activation of factor VII. The extent of activation will be related to rates of tissue factor-dependent activation of factor IX and X to determine whether generation of minimal amounts of factor VIIa can yield maximum rates of activation of factors IX and X. The ability will be evaluated of phospholipid on activated platelets and of phospholipid on unperturbed human endothelial cells to support factor Xa and factor IXa-induced activation of factor VII. A third biochemical project will focus upon the ability of zymogen factor VII to interact with tissue factor formed on cultured human endothelial cells with resultant activation of factors IX and X. Antithrombin III and the above described plasma inhibitory material will be included in some reaction mixtures. In additional experiments, increasing amounts of preformed factor VIIa will be added to the incubation mixtures with factor VII. Physiologic experiments will be carried out in rabbits to determine if infusion of tissue factor or injection of endotoxin can deplete plasma of the inhibitory material required for neutralization of factor VIIa-tissue factor. Plasma inhibitory factor levels will also be measured in patients. A quantitative assay for plasma inhibitory factor has been designed for these purposes. Other clinical projects will include studies of (1) the importance of platelet factor V for hemostasis in patients with factor V anticoagulants, (2) the relation between antiprothrombin antibodies and the lupus anticoagulant, and (3) diagnostic techniques and manifestations of thrombosis in hereditary protein C and protein S deficiency.