Cimenti Christina, Koestenberger Martin, Leschnik Bettina, Haidl Harald, Muntean Wolfgang
Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis at the Department of Pediatrics, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Austria.
Thromb Res. 2007;119(3):361-7. doi: 10.1016/j.thromres.2006.03.004. Epub 2006 May 19.
Combinations of anticoagulants might be beneficial in some patients with sepsis, but most anticoagulants require specific clotting assays for monitoring. Thrombin generation assay, however, is a global function test of hemostasis.
We performed an in vitro investigation of the respective effects of recombinant human activated protein C (rhAPC) alone and in combination with either melagatran (a new direct thrombin inhibitor), unfractionated heparin (UH) or low molecular weight heparin (LMWH) in varying concentrations on the thrombin generation (TG) using the calibrated automated thrombography.
RhAPC, UH, LMWH and melagatran dose-dependently prolonged the lag time and the time to peak, and significantly suppressed the endogenous thrombin potential (ETP). Combined application of rhAPC with either melagatran, UH or LMWH induced an additive prolongation of the lag time; this effect was more pronounced in a combination of rhAPC with UH or LMWH.
In our in vitro study adding either melagatran, UH or LMWH augmented the capacity of rhAPC to suppress thrombin generation in human plasma. These findings suggest that patients with severe sepsis might benefit from a treatment with combinations of anticoagulant agents.
抗凝剂联合使用可能对某些脓毒症患者有益，但大多数抗凝剂需要特定的凝血检测来进行监测。然而，凝血酶生成检测是一种全面的止血功能检测。
我们使用校准自动血栓形成描记法，对重组人活化蛋白C（rhAPC）单独以及与不同浓度的美拉加群（一种新型直接凝血酶抑制剂）、普通肝素（UH）或低分子肝素（LMWH）联合使用时，对凝血酶生成（TG）的各自影响进行了体外研究。
rhAPC、UH、LMWH和美拉加群均剂量依赖性地延长了延迟时间和达到峰值的时间，并显著抑制了内源性凝血酶潜能（ETP）。rhAPC与美拉加群、UH或LMWH联合应用可导致延迟时间的相加性延长；这种效应在rhAPC与UH或LMWH联合使用时更为明显。
在我们的体外研究中，添加美拉加群、UH或LMWH可增强rhAPC抑制人血浆中凝血酶生成的能力。这些发现表明，严重脓毒症患者可能受益于抗凝剂联合治疗。
