High sCD40L levels early after trauma are associated with enhanced shock, sympathoadrenal activation, tissue and endothelial damage, coagulopathy and mortality
High sCD40L levels early after trauma are associated with enhanced shock, sympathoadrenal activation, tissue and endothelial damage, coagulopathy and mortality
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DOI：
10.1111/j.1538-7836.2011.04589.x
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发表时间：
2012-02-01
影响因子：
10.4
通讯作者：
Ostrowski, S. R.
中科院分区：
文献类型：
--
作者：
Johansson, P. I.;Sorensen, A. M.;Ostrowski, S. R.
.背景资料：严重损伤激活交感肾上腺、止血和炎症系统，但不适应的反应可能导致不良结局。可溶性CD 40 L是一种血小板源性介质，其将炎症、止血和血管功能障碍联系起来。目的：探讨创伤患者血清可溶性CD 40 L水平与组织损伤、休克、凝血功能障碍及死亡率的关系。方法：一项前瞻性的观察性研究，80例创伤患者入住一级创伤中心。记录人口统计学、生物化学、损伤严重度评分（ISS）和30天死亡率的数据，并分析入院血浆/血清中sCD 40 L和反映交感肾上腺激活的生物标志物（肾上腺素、去甲肾上腺素）、组织/内皮细胞/糖萼损伤（组蛋白复合DNA片段[hcDNA]、膜联蛋白V、血栓调节蛋白和多配体蛋白聚糖-1）、凝血激活/抑制（PF1.2、TAT复合物、抗凝血酶、蛋白C、活化蛋白C、sEPCR、TFPI、血管性血友病因子[VWF]、纤维蛋白原和因子[F] XIII）、纤维蛋白溶解（D-二聚体、组织纤溶酶原激活物[tPA]和纤溶酶原激活物抑制剂-1 [派-1]）和炎症（白细胞介素-6 [IL-6]和sC 5 b-9）。我们比较了按sCD 40 L中位数水平分层的患者，并研究了sCD 40 L对死亡率的预测价值。结果如下：高循环sCD 40 L与增强的组织和内皮损伤（ISS、hcDNA、Annexin V、syndecan-1和sTM）、休克（pH、标准碱过量）、交感肾上腺激活（肾上腺素）和凝血病（由凝血酶生成减少（PF1.2）、纤溶亢进（D-二聚体）、活化部分凝血活酶时间（APTT）增加和炎症（IL-6）证明）相关（均P < 0.05）。多元线性回归分析显示，较高的ISS（P = 0.017）、肾上腺素（P = 0.049）和血小板计数（P = 0.012）以及较低的pH值（P = 0.002）与较高的sCD 40 L相关。高循环sCD 40 L（比值比[OR] 1.84 [95% CI 1.053.23]，P = 0.034）、高年龄（P = 0.002）和低院前格拉斯哥昏迷评分（GCS）（P = 0.002）是死亡率增加的独立预测因素。结论：创伤患者早期sCD 40 L水平升高反映了组织损伤、休克、凝血功能障碍和交感肾上腺激活，并可预测死亡率。由于sCD 40 L具有促炎活性并激活内皮，因此sCD 40 L可能参与创伤诱导的内皮损伤和凝血障碍。
. Background: Severe injury activates the sympathoadrenal, hemostatic and inflammatory systems, but a maladapted response may contribute to a poor outcome. Soluble CD40L is a platelet-derived mediator that links inflammation, hemostasis and vascular dysfunction. Objectives: To investigate the association between the sCD40L level and tissue injury, shock, coagulopathy and mortality in trauma patients. Methods: A prospective, observational study of 80 trauma patients admitted to a Level I Trauma Center. Data on demography, biochemistry, Injury Severity Score (ISS) and 30-day mortality were recorded and admission plasma/serum analyzed for sCD40L and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments [hcDNA], Annexin V, thrombomodulin and syndecan-1), coagulation activation/inhibition (PF1.2, TAT-complex, antithrombin, protein C, activated protein C, sEPCR, TFPI, von Willebrand factor [VWF], fibrinogen and factor [F] XIII), fibrinolysis (D-dimer, tissue plasminogen activator [tPA] and plasminogen activator inhibitor-1 [PAI-1]) and inflammation (interleukin-6 [IL-6] and sC5b-9). We compared patients stratified by median sCD40L level and investigated predictive values of sCD40L for mortality. Results: High circulating sCD40L was associated with enhanced tissue and endothelial damage (ISS, hcDNA, Annexin V, syndecan-1 and sTM), shock (pH, standard base excess), sympathoadrenal activation (adrenaline) and coagulopathy evidenced by reduced thrombin generation (PF1.2), hyperfibrinolysis (D-dimer), increased activated partial thromboplastin time (APTT) and inflammation (IL-6) (all P < 0.05). A higher ISS (P = 0.017), adrenaline (P = 0.049) and platelet count (P = 0.012) and lower pH (P = 0.002) were associated with higher sCD40L by multivariate linear regression analysis. High circulating sCD40L (odds ratio [OR] 1.84 [95% CI 1.053.23], P = 0.034), high age (P = 0.002) and low Glasgow Coma Score (GCS) pre-hospital (P = 0.002) were independent predictors of increased mortality. Conclusions: High early sCD40L levels in trauma patients reflect tissue injury, shock, coagulopathy and sympathoadrenal activation and predict mortality. As sCD40L has pro-inflammatory activity and activates the endothelium, sCD40L may be involved in trauma-induced endothelial damage and coagulopathy.