VON WILLEBRAND FACTOR AND THE PATHOPHYSIOLOGY OF TTP

该项目是研究人员之间的合作安排， 活跃于典型动脉的临床和基础研究工作 血栓性疾病，血栓性血小板减少性紫癜（TTP）。 的 研究人员可以接触TTP患者和临床相关患者 综合征在公立，私立和政府医院的3大 人口中心。 虽然地理位置不同，但调查人员 有一个紧密的、富有成效的工作关系。 他们还开发了一种 临床研究网络与参与的医生互动， 在美国其他地区照顾这些病人。该项目的重点是 血管性血友病因子（vWF）多聚体在病理生理学中的作用 复发性和非复发性TTP的区别 之间的关联 血浆vWF多聚体异常和其他临床相关疾病 TTP（例如，溶血性尿毒症综合征），以及异常vWF形式之间 前列环素（PGI 2）产生和稳定的缺陷也会 接受检查。 实验工作包括：开发了测试系统 用于急性TTP;在急性TTP期间鉴定血液中存在的“vWF辅因子” 急性TTP发作;异常大TTP的分离和表征 vWF多聚体由内皮细胞产生，并在血浆中发现， 慢性复发性TTP患者; 正常冷冻上清液中“异常大的vWF转化活性”;和 对TTP复发形式是一种 异常的免疫调节 我们希望更有效的预防和 TTP的治疗将从所提出的工作中出现。 我们预计 结果将适用于研究常见的动脉血栓形成 涉及冠状动脉或脑血管区域的疾病 流通 我们还希望我们的研究结果将使 可能的分子水平上的TTP和相关疾病。

This project is a collaborative arrangement among investigators who are active in clinical and basic research work on the paradigm arterial thrombotic disease, thrombotic thrombocytopenic purpura (TTP). The investigators have access to patients with TTP and clinically related syndromes in the public, private and government hospitals of 3 large population centers. Although geographically separate, the investigators have a close, productive working association. They also have developed a network of clinical research interactions with physicians involved in the care of these patients in other parts of the U.S.A. The project is focused on the role of von Willebrand factor (vWF) multimers in the pathophysiology of relapsing and non-relapsing types of TTP. The association between plasma vWF multimer abnormalities and other disorders clinically related to TTP (e.g., the hemolytic-uremic syndrome), and between abnormal vWF forms and defects in prostacyclin (PGI2) production and stabilization will also be examined. The experimental work includes: development of a test system for acute TTP; identification of a "vWF cofactor" present in blood during acute TTP episodes; isolation and characterization of the unusually large vWF multimers produced by endothelial cells and found in the plasma of chronic relapsing TTP patients; isolation and characterization of the "unusually large vWF converting activity" in normal cryosupernatant; and evaluation of the hypothesis that the relapsing form of TTP is a disease of aberrant immune regulation. We expect that more effective prophylaxis and therapy for TTP will emerge from the work proposed. We anticipate that the results will be applicable to the study of common arterial thrombotic disorders involving regions of the coronary or cerebrovascular circulation. We also expect that the results of our study will make possible molecular level on TTP and related disorders.