VON WILLEBRAND FACTOR AND THE PATHOPHYSIOLOGY OF TTP

该项目是调查人员之间的合作安排，这些调查人员 积极参与动脉范型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)。这个 调查人员可以接触到TTP患者和临床相关患者 3家大型公立、私立和公立医院的症状 人口中心。尽管地理位置不同，但调查人员 有一个紧密的、富有成效的工作联系。他们还开发了一种 与参与研究的医生的临床研究互动网络 在美国其他地区护理这些患者。该项目的重点是 血管性血友病因子(VWF)多聚体在病理生理中的作用 复发和非复发类型的TTP。两者之间的联系 血浆vWF多聚体异常及其他与临床相关的疾病 TTP(例如，溶血性尿毒症综合征)以及异常vWF形式之间的关系 前列环素(PGI2)生产和稳定方面的缺陷也将 接受检查。实验工作包括：测试系统的开发 用于急性TTP；鉴定血液中存在的“vWF辅因子” 急性TTP发作；异常大的分离和特征 血管内皮细胞产生的VWF多聚体 慢性复发性TTP患者的分离和特征 正常冷冻上清液中的“异常大的vWF转化活性”；以及 对TTP复发形式是一种疾病的假设的评价 异常的免疫调节。我们期待更有效的预防和 TTP的治疗将从拟议的工作中出现。我们预计， 研究结果将为常见动脉血栓形成的研究提供参考。 累及冠状动脉或脑血管区域的疾病 发行量。我们也期待我们的研究结果将使 TTP及相关疾病的可能分子水平。

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.