Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure
Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure
复制标题
DOI：
10.1160/th08-03-0161
复制
发表时间：
2009-02-01
影响因子：
6.7
通讯作者：
Loesche, Wolfgang
中科院分区：
文献类型：
--
作者：
Claus, Ralf A.;Bockmeyer, Clemens L.;Loesche, Wolfgang
测量了健康对照者和不同原因和严重程度的全身炎症患者的血浆中的血管性血友病因子（VWF）和相关参数以及调节其生物活性的蛋白酶活性，以检查这些措施对检测高度血栓形成状态（包括脓毒症后遗症之一的血栓性微血管病（TMA））的有效性。 VWF 的血浆水平随着全身炎症严重程度的增加而增加，这可能是由于内皮细胞的激活所致。与此同时，VWF 失活蛋白酶 ADAMTS 13 的蛋白水解活性随着炎症的严重程度而逐步下降，这强调了 VWF 触发内皮细胞血小板聚集随后形成 TMA 的作用。因此，炎症和脓毒症患者中 VWF 抗原水平和 ADAMTS13 活性的比率显着较高，表明该比率可能比单独的 VWF 多聚体分析更有助于诊断包括 TMA 在内的高度血栓形成状态。这些发现表明，ADAMTS13、VWF 和相关参数，即使采用组合方法，也可能有助于脓毒症相关血栓性微血管病患者的诊断和治疗监测。
Von Willebrand factor (VWF) and related parameters as well as the protease activity regulating its biological activity were measured in plasma of healthy controls and patients with different cause and severity of systemic inflammation to examine the efficacy of the measures to detect highly prothrombotic states including thrombotic microangiopathy (TMA), one of the sequelae of sepsis. Plasma levels of VWF increased with increasing severity of systemic inflammation, probably due to activation of the endothelium. In parallel, the proteolytic activity of VWF inactivating protease, ADAMTS 13, stepwise declined with the severity of inflammation, emphasizing the role of VWF-triggered platelet aggregation on the endothelium subsequently followed by development of TMA. As a consequence, the ratio of VWF antigen level and ADAMTS13 activity was significantly higher in patients with inflammation and sepsis, suggesting that this ratio might be more useful for the diagnosis of highly prothrombotic states including TMA than VWF multimer analysis alone. These findings suggest that ADAMTS13, VWF and related parameters, even in a combined approach, might be useful for the diagnosis and the therapeutic monitoring of patients with sepsis associated thrombotic microangiopathy.