Study of TTP: Incidence Rates and Risk Factors

描述（由申请方提供）：血栓性血小板减少性紫癜（TTP）是一种危及生命的疾病，其特征为包括微血管病性溶血性贫血（MAHA）、血小板减少症、神经系统症状、发热和肾功能不全在内的五种症状。TIP的诊断必须及时进行，因为这种情况如果不治疗，死亡率很高。及时治疗可大大降低死亡率，因此及时识别至关重要。TTP是一种罕见疾病，估计年发病率为每百万人3.7例，在女性中更常见。最近，TTP的年发病率增加了5至8倍，这是常用抗血小板药物治疗或常见介入手术（如动脉支架）后的并发症。 与其他罕见疾病一样，对TTP的发病机制、其在美国人群中的分布、风险因素和结局决定因素的理解存在重大差距。我们建议使用一项多中心病例对照研究来评估我们目前对美国成年人TTP知识的差距，该研究涉及TTP的危险因素。此外，我们提出了一套相互关联的转化基础科学研究，这可能有助于我们更好地理解为什么一些TTP患者死于这种疾病。本研究的主要目的是评价与使用抗血小板药物（噻吩并吡啶类、噻氯匹定和氯吡格雷，FDA被动监测项目MedWatch中确定的两种最常见的非移植TTP相关药物）相关的TTP事件风险。人们担心，在美国2%的人口使用的氯吡格雷与TTP之间存在因果关系。本研究设计了一项为期四年的病例对照研究来探讨这一具体问题。该研究的次要目的是检查可能的生物标志物作为与TIP事件后30天死亡率相关的预后因素，包括vWF切割金属蛋白酶的存在和活性以及内皮细胞凋亡的程度。 这些问题特别相关，因为TTP是一种严重且可能致命的综合征，并且在过去七十年中一直回避科学进步。我们的研究是独一无二的，将推动这一领域的科学知识。本研究结果将有助于医疗保健专业人员未来的临床行动和公共政策的决定。

DESCRIPTION (provided by applicant): Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by a pentad of symptoms including microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurologic symptoms, fever, and renal dysfunction. The diagnosis of TIP must be made in a timely manner because this condition carries with it a high mortality rate if untreated. Prompt therapy reduces substantially the mortality rate and therefore timely recognition is essential. TTP is a rare disease with an estimated annual incidence of 3.7 cases per million, and is more frequent among women. Recently, concerns have been raised that the annual incidence of TTP has increased 5 to 8 fold as a complication of therapy with commonly used antiplatelet drugs or following commonplace interventional procedures such as arterial stents. As with other rare diseases, there are significant gaps in the understanding of the pathogenesis of TTP, its distribution in the US population, risk factors, and determinants of outcome. We propose to evaluate gaps in our current knowledge of TTP among adults in the United States using a multi-center case-control study that addresses risk factors for TTP. In addition, we propose an interrelated set of translational basic science studies that may help improve our understanding of why some persons with TTP die from the illness. The primary objective of this study is to evaluate risk of incident TTP in relation to the use of antiplatelet drugs (the thienopyridines, ticlopidine and clopidogrel, the two most common non-transplant TTP-associated drugs identified in the FDA's passive surveillance program, MedWatch). Concern exists that there is a cause and effect relationship between clopidogrel, an agent that is used by two percent of the United States population, and TTP. A four year case control study is designed to investigate this specific question. The secondary objective of the study is to examine possible biologic markers as prognostic factors related to 30-day mortality following an incident TIP, including presence and activity of vWF cleaving metalloprotease, and degree of endothelial cell apoptosis. These issues are of particular relevance, as TTP is a serious and potentially fatal syndrome and has eluded scientific advances for the past seven decades. Our study is unique and will advance scientific knowledge in this area. The findings of this study would facilitate health care professional for future clinical actions and public policy decisions.