Curry Nicola S, Abu-Hanna Jeries, Morrow Gael B, Choudhury Robin, Laffan Michael
Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, Oxford University, Oxford.
Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, Oxford University, Oxford, UK; School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen.
Haematologica. 2025 Feb 1;110(2):414-424. doi: 10.3324/haematol.2024.285951.
Trauma-induced coagulopathy describes a complex set of coagulation changes affecting severely injured patients. The thrombomodulin-protein C axis is believed to be central to the evolution of trauma-induced coagulopathy. Soluble thrombomodulin (sTM) levels are elevated after injury. Our objectives were to explore whether sTM (at concentrations found in patients after injury) plays an important role in trauma-induced coagulopathy, and specifically to evaluate the effects of sTM and activated protein C (APC) on thrombin generation (TG) and clot lysis time (CLT). Plasma from healthy volunteers was spiked with rising concentrations of sTM and APC and the effects on TG and CLT were analyzed. Plasma samples from a cohort of trauma patients were evaluated using TG and CLT, and results correlated to clinical parameters and factor VIII, factor V, APC, sTM and fibrinolytic measures. Increasing sTM concentrations in volunteer plasma led to reductions in endogenous thrombin potential and prolongation of 50% CLT, in a dose-dependent manner. No effect on TG or CLT was seen with rising APC concentrations. In 91 trauma patients, higher sTM values were associated with greater, rather than reduced, endogenous thrombin potential (median 1,483 vs. 1,681 nM/min) and longer 50% CLT (41.9 vs. 54.0 mins). In conclusion, sTM concentrations, across ranges found after trauma, affect both TG and 50% CLT, unlike APC. Despite increased circulating sTM levels, the overriding dynamic coagulation effects seen after injury are: (i) accelerated TG and (ii) increased rates of fibrinolysis. We found no evidence for sTM as the major determinant of the coagulation changes seen in early trauma-induced coagulopathy.
创伤性凝血病描述了一组影响严重受伤患者的复杂凝血变化。血栓调节蛋白-蛋白C轴被认为是创伤性凝血病发展的核心。可溶性血栓调节蛋白（sTM）水平在受伤后会升高。我们的目的是探讨sTM（在受伤患者体内发现的浓度）是否在创伤性凝血病中起重要作用，特别是评估sTM和活化蛋白C（APC）对凝血酶生成（TG）和凝块溶解时间（CLT）的影响。向健康志愿者的血浆中加入浓度不断升高的sTM和APC，并分析其对TG和CLT的影响。使用TG和CLT对一组创伤患者的血浆样本进行评估，并将结果与临床参数以及因子VIII、因子V、APC、sTM和纤溶指标相关联。志愿者血浆中sTM浓度的增加导致内源性凝血酶潜力降低和50%CLT延长，呈剂量依赖性。随着APC浓度的升高，未观察到对TG或CLT有影响。在91例创伤患者中，较高的sTM值与更大而非降低的内源性凝血酶潜力（中位数1483对1681 nM/分钟）和更长的50%CLT（41.9对54.0分钟）相关。总之，与APC不同，创伤后发现的sTM浓度范围会影响TG和50%CLT。尽管循环中的sTM水平升高，但受伤后观察到的主要动态凝血效应是：（i）TG加速和（ii）纤溶速率增加。我们没有发现证据表明sTM是早期创伤性凝血病中所见凝血变化的主要决定因素。
