Ono Tomoko, Mimuro Jun, Madoiwa Seiji, Soejima Kenji, Kashiwakura Yuji, Ishiwata Akira, Takano Katsuhiro, Ohmori Tsukasa, Sakata Yoichi
Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Tochigi-ken 329-0498, Japan.
Blood. 2006 Jan 15;107(2):528-34. doi: 10.1182/blood-2005-03-1087. Epub 2005 Sep 27.
Deficiency of ADAMTS13 is found in patients with thrombotic thrombocytopenic purpura (TTP), and the genetic defects in the ADAMTS13 gene or the autoantibody against ADAMTS13 is thought to be responsible for the development of TTP. The clinical correlation and mechanisms of secondary ADAMTS13 deficiency in other disease states were investigated. In addition to TTP, ADAMTS13 levels were severely decreased in patients with sepsis-induced disseminated intravascular coagulation (DIC). The incidence of acute renal failure and serum creatinine levels in patients with ADAMTS13 activity levels lower than 20% (incidence, 41.2%; creatinine, 160 +/- 150 microM [1.81 +/- 1.70 mg/dL]) (P < .05) were significantly higher than they were in patients with ADAMTS13 activity levels higher than 20% (incidence, 15.4%; creatinine, 84 +/- 67 microM [0.95 +/- 0.76 mg/dL]) (P < .01). Additionally, unusually large von Willebrand factor multimers were detected in 26 (51.0%) of 51 patients with ADAMTS13 activity levels lower than 20%. Lower molecular weight forms of ADAMTS13 were found in the plasma of patients with sepsis-induced DIC, suggesting that the deficiency of ADAMTS13 was partially caused by its cleavage by proteases in addition to decreased synthesis in the liver. These data suggested that severe secondary ADAMTS13 deficiency can be associated with sepsis-induced DIC and may contribute to the development of renal failure.
血栓性血小板减少性紫癜（TTP）患者存在ADAMTS13缺乏，ADAMTS13基因的遗传缺陷或针对ADAMTS13的自身抗体被认为是TTP发病的原因。研究了其他疾病状态下继发性ADAMTS13缺乏的临床相关性及机制。除TTP外，脓毒症诱导的弥散性血管内凝血（DIC）患者的ADAMTS13水平也严重降低。ADAMTS13活性水平低于20%的患者（发生率为41.2%；肌酐为160±150μmol/L[1.81±1.70mg/dL]）（P<0.05）急性肾衰竭的发生率和血清肌酐水平显著高于ADAMTS13活性水平高于20%的患者（发生率为15.4%；肌酐为84±67μmol/L[0.95±0.76mg/dL]）（P<0.01）。此外，在51例ADAMTS13活性水平低于20%的患者中，有26例（51.0%）检测到异常大的血管性血友病因子多聚体。在脓毒症诱导的DIC患者血浆中发现了分子量较低形式的ADAMTS13，这表明ADAMTS13缺乏除了肝脏合成减少外，部分还由蛋白酶对其的裂解所致。这些数据表明，严重的继发性ADAMTS13缺乏可能与脓毒症诱导的DIC有关，并可能导致肾衰竭的发生。
