Zheng X Long
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; email:
Annu Rev Med. 2015;66:211-25. doi: 10.1146/annurev-med-061813-013241.
Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.
在发现ADAMTS13之前的半个多世纪里，血栓性血小板减少性紫癜（TTP）的发病机制一直是个谜。ADAMTS13主要在肝脏合成，其主要功能是裂解锚定在内皮表面、循环系统以及血管损伤部位的血管性血友病因子（VWF）。由ADAMTS13基因突变或针对ADAMTS13的自身抗体导致的血浆ADAMTS13活性缺乏（<10%）会引起遗传性或获得性（特发性）TTP。在继发于造血祖细胞移植、感染和播散性恶性肿瘤的其他形式的血栓性微血管病或溶血尿毒综合征中，ADAMTS13活性通常正常或轻度降低（>20%）。血浆输注或置换至今仍是首选的初始治疗方法，但重组ADAMTS13和基因治疗等新型疗法正在研发中。此外，ADAMTS13缺乏已被证明是心肌梗死、中风、脑型疟疾和子痫前期发生的危险因素。
