Study of TTP: Incidence Rates and Risk Factors

描述（由申请人提供）：血栓性血小板减少性紫癜（TTP）是一种危及生命的疾病，其特征是五种症状，包括微血管病性溶血性贫血（MAHA）、血小板减少、神经系统症状、发烧和肾功能障碍。TIP的诊断必须及时做出，因为如果不治疗，这种疾病的死亡率很高。及时治疗可大大降低死亡率，因此及时识别至关重要。TTP是一种罕见的疾病，估计年发病率为每百万人3.7例，在女性中更为常见。最近，TTP的年发病率增加了5 - 8倍，这是常用抗血小板药物治疗或常规介入手术（如动脉支架）的并发症。

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.