Miyata Toshiyuki, Kokame Koichi, Banno Fumiaki
National Cardiovascular Center Research Institute, Osaka, Japan.
Curr Opin Hematol. 2005 Sep;12(5):384-9. doi: 10.1097/01.moh.0000169286.74464.3a.
Acquired or congenital deficiency in the plasma von Willebrand factor-cleaving protease ADAMTS13 causes life-threatening thrombotic thrombocytopenic purpura. This condition is characterized primarily by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by variable degrees of neurologic dysfunction, renal failure, and fever. Measurement of ADAMTS13 activity is important in the diagnosis of microangiopathies such as thrombotic thrombocytopenic purpura. This review introduces both established and emerging assays for ADAMTS13 activity, focusing on their impact on clinical practice.
Previously established assays are useful screening methods to identify suspected thrombotic thrombocytopenic purpura. Novel assays measuring ADAMTS13 activity using either recombinant peptides or synthetic substrates directly measure the activity quantitatively. These assays can also detect neutralizing autoantibodies in the plasma of patients with acquired ADAMTS13 deficiency. Although ADAMTS13 in control subjects exhibits a broad variation in activity, ranging from 30 to 200%, significant decreases in ADAMTS13 activity have been observed in several physiologic and pathologic conditions. A portion of thrombotic thrombocytopenic purpura patients, however, did not display severe ADAMTS13 deficiency, suggesting that as-yet-unidentified environmental or genetic factors may contribute to the etiology of thrombotic thrombocytopenic purpura.
New assays measuring ADAMTS13 activity will contribute significantly to the accurate diagnosis of microangiopathies, ultimately leading to improved clinical treatment of these diseases. These assays may also help to clarify the role of ADAMTS13 activity in additional thrombotic disorders, including disseminated intravascular coagulation, stroke, and myocardial infarction.
血浆血管性血友病因子裂解蛋白酶ADAMTS13的获得性或先天性缺乏会导致危及生命的血栓性血小板减少性紫癜。这种疾病主要特征为血小板减少和微血管病性溶血性贫血，并伴有不同程度的神经功能障碍、肾衰竭和发热。ADAMTS13活性的测定对于血栓性血小板减少性紫癜等微血管病的诊断很重要。本综述介绍了已有的和新出现的ADAMTS13活性检测方法，重点关注它们对临床实践的影响。
先前已有的检测方法是识别疑似血栓性血小板减少性紫癜的有用筛查手段。使用重组肽或合成底物测量ADAMTS13活性的新检测方法可直接定量测量活性。这些检测方法还能检测获得性ADAMTS13缺乏患者血浆中的中和性自身抗体。尽管健康对照者的ADAMTS13活性存在很大差异，范围在30%至200%之间，但在一些生理和病理情况下已观察到ADAMTS13活性显著降低。然而，一部分血栓性血小板减少性紫癜患者并未表现出严重的ADAMTS13缺乏，这表明尚未明确的环境或遗传因素可能有助于血栓性血小板减少性紫癜的病因。
测量ADAMTS13活性的新检测方法将对微血管病的准确诊断有显著贡献，最终改善这些疾病的临床治疗。这些检测方法还可能有助于阐明ADAMTS13活性在其他血栓性疾病中的作用，包括弥散性血管内凝血、中风和心肌梗死。
