Trauma induced coagulopathy (TIC) 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 TIC. 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 TIC, and specifically to evaluate the effect 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 analysed. Plasma samples from a cohort of trauma patients were evaluated using TG and CLT, and results correlated to clinical parameters and FVIII, FV, APC, sTM and fibrinolytic measures. Increasing sTM concentrations in volunteer plasma led to reductions in ETP and prolongation of 50% CLT times, 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, ETP (median 1483 vs. 1681 nM/min) and longer 50% CLT times (41.9 vs. 54.0 mins). In conclusion, sTM concentrations, across trauma ranges, impact both TG and 50% CLT times, unlike APC. Despite increased circulating sTM levels, the overriding dynamic coagulation effects seen after injury are: (a) accelerated thrombin generation and (b) increased rates of fibrinolysis. We find no evidence for sTM as the major determinant of the coagulation changes seen in early TIC.

中文翻译：

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可溶性血栓调节蛋白和活化蛋白 C 对创伤动态止血功能的影响：关注凝血酶生成和血栓溶解。


创伤诱发凝血病 (TIC) 描述了影响严重受伤患者的一系列复杂的凝血变化。血栓调节蛋白-蛋白 C 轴被认为是 TIC 演变的核心。受伤后可溶性血栓调节蛋白（sTM）水平升高。我们的目标是探索 sTM（在患者受伤后发现的浓度）是否在 TIC 中发挥重要作用，特别是评估 sTM 和活化蛋白 C (APC) 对凝血酶生成 (TG) 和血栓溶解时间 (CLT) 的影响）。健康志愿者的血浆中添加了浓度不断升高的 sTM 和 APC，并分析了其对 TG 和 CLT 的影响。使用 TG 和 CLT 评估一组创伤患者的血浆样本，结果与临床参数和 FVIII、FV、APC、sTM 和纤溶测量相关。志愿者血浆中 sTM 浓度的增加导致 ETP 减少并以剂量依赖性方式延长 50% CLT 时间。 APC 浓度升高对 TG 或 CLT 没有影响。在 91 名创伤患者中，较高的 sTM 值与较高而非减少的 ETP（中位数 1483 与 1681 nM/min）和较长的 50% CLT 时间（41.9 与 54.0 分钟）相关。总之，与 APC 不同，在整个创伤范围内，sTM 浓度都会影响 TG 和 50% CLT 时间。尽管循环 sTM 水平增加，但受伤后最重要的动态凝血效应是：（a）加速凝血酶生成和（b）纤维蛋白溶解率增加。我们没有发现任何证据表明 sTM 是早期 TIC 中凝血变化的主要决定因素。