Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure
Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure
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DOI：
10.1182/blood-2005-03-1087
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发表时间：
2006-01-15
期刊：
影响因子：
20.3
通讯作者：
Sakata, Y
中科院分区：
文献类型：
--
作者：
Ono, T;Mimuro, J;Sakata, Y
血栓性血小板减少性紫癜（TTP）患者存在ADAMTS 13缺陷，ADAMTS 13基因的遗传缺陷或抗ADAMTS 13的自身抗体被认为是TTP发生的原因。研究继发性ADAMTS 13缺陷在其他疾病状态中的临床相关性和机制。除TTP外，ADAMTS 13水平在脓毒症诱导的弥散性血管内凝血（DIC）患者中严重降低。ADAMTS 13活性水平低于20%的患者发生急性肾功能衰竭和血肌酐水平（发生率：41.2%;肌酐：160 +/- 150 μ M [1.81 +/- 1.70 mg/dL]）（P < .05）显著高于ADAMTS 13活性水平高于20%的患者（发病率，15.4%;肌酸酐，84 +/- 67 μ M [0.95 +/- 0.76 mg/dL]）（P < .01）。此外，在51例ADAMTS 13活性水平低于20%的患者中，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患者的血浆中发现了低分子量形式的ADAMTS 13，这表明ADAMTS 13的缺乏部分是由蛋白酶切割以及肝脏合成减少引起的。这些数据表明，严重的继发性ADAMTS 13缺乏可能与脓毒症诱导的DIC相关，并可能导致肾衰竭的发展。
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 mu M [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 mu M [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.