Hoppensteadt Debra, Tsuruta Kazuhisa, Hirman Joe, Kaul Inder, Osawa Yutaka, Fareed Jawed
Research Laboratories, Loyola University Chicago, Maywood, IL, USA
Asahi Kasei Pharma America Corporation, Waltham, MA, USA.
Clin Appl Thromb Hemost. 2015 Mar;21(2):120-7. doi: 10.1177/1076029613509476. Epub 2013 Nov 19.
Inflammatory mediators and hemostatic markers were evaluated in patients enrolled in a phase-2b study evaluating the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with sepsis and suspected disseminated intravascular coagulation (DIC). In contrast to controls, patients with sepsis and suspected DIC showed an increase in the circulating levels of inflammatory and fibrinolytic markers. The levels of procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), anaphylatoxin C5a, plasminogen activator inhibitor 1 (PAI-1), and myeloperoxidase were higher in the patients with sepsis and suspected DIC, whereas protein C (PrC) exhibited a significant decrease. When the patients with overt and nonovert DIC were compared, the PrC level was lower, and PCT, PAI-1, IL-6, and IL-10 levels were higher in the patients with overt DIC. These results indicate that inflammation is elevated in sepsis and suspected DIC, and inflammation, impairment of fibrinolysis, and overconsumption of PrC may play a key role in the pathogenesis of DIC.
在一项2b期研究中,对入组的脓毒症和疑似弥散性血管内凝血(DIC)患者的炎症介质和止血标志物进行了评估,该研究旨在评估重组血栓调节蛋白(ART-123)对脓毒症和疑似DIC患者的安全性和有效性。与对照组相比,脓毒症和疑似DIC患者的炎症和纤溶标志物循环水平升高。脓毒症和疑似DIC患者的降钙素原(PCT)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、过敏毒素C5a、纤溶酶原激活物抑制剂1(PAI-1)和髓过氧化物酶水平较高,而蛋白C(PrC)则显著降低。当比较显性和非显性DIC患者时,显性DIC患者的PrC水平较低,而PCT、PAI-1、IL-6和IL-10水平较高。这些结果表明,脓毒症和疑似DIC患者炎症水平升高,炎症、纤溶功能受损和PrC过度消耗可能在DIC发病机制中起关键作用。