交感肾上腺激活和内皮病变是创伤中低凝性和高纤维蛋白溶解的驱动因素：一项对404例重伤患者的前瞻性观察研究。
Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients.
作者信息
Ostrowski Sisse R, Henriksen Hanne H, Stensballe Jakob, Gybel-Brask Mikkel, Cardenas Jessica C, Baer Lisa A, Cotton Bryan A, Holcomb John B, Wade Charles E, Johansson Pär I
机构信息
From the Section for Transfusion Medicine (S.R.O., H.H.H., J.S., M.G.-B., P.I.J.), Capital Region Blood Bank, Department of Anesthesia (J.S.), Center of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and Centre for Translational Injury Research (CeTIR) and Department of Surgery (J.C.C., L.A.B., B.A.C., J.B.H., C.E.W., P.I.J.), UT Health, University of Texas Health Science Center at Houston, Houston, Texas.
出版信息
J Trauma Acute Care Surg. 2017 Feb;82(2):293-301. doi: 10.1097/TA.0000000000001304.
BACKGROUND
One third of severely injured patients present with a laboratory-based diagnosis of coagulopathy. This study investigated clinical and biomarker profile of patients with rapid thrombelastography (rTEG) coagulopathy, hypothesizing that sympathoadrenal activation and endothelial damage were drivers of this condition.
METHODS
Prospective observational study of 404 trauma patients admitted to a Level 1 US Trauma Center. Patients with admission rTEG and plasma measurements of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial activation/damage (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin, nucleosomes) were included. Demography, injury type/severity, physiology, treatment, and inhospital mortality were recorded.
RESULTS
Patients had a median Injury Severity Score (ISS) of 17, 73% from blunt injury. One third (35%) of the patients had rTEG coagulopathy, which was associated with higher plasma adrenaline, syndecan-1, and nucleosomes (all <0.05), higher transfusion requirements and higher early (<24 hours, 9.3% vs. 2.5%) and late (28 days, 23.8% vs. 13.4%) mortality. By adjusted linear regression analyses, high plasma adrenaline, sVE-cadherin, and syndecan-1 (reflecting sympathoadrenal activation and endothelial cell junction and glycocalyx damage) along with male sex, high ISS, low platelet count and prehospital red blood cell transfusion were independently associated with hypocoagulable rTEG, whereas prehospital plasma and sE-selectin (reflecting endothelial activation) were independently associated with more hypercoagulable rTEG.
CONCLUSION
In this cohort of severely injured trauma patients, rTEG coagulopathy was associated with sympathoadrenal activation, endotheliopathy, and excess mortality. High adrenaline and biomarkers reflecting endothelial cell junction and glycocalyx damage were independently associated with hypocoagulability and hyperfibrinolysis. These findings support that sympathoadrenal activation and endotheliopathy contribute to trauma-induced coagulopathy and warrants further studies of endothelial repair management.
LEVEL OF EVIDENCE
Prognostic, Level III.
背景
三分之一的重伤患者经实验室诊断存在凝血病。本研究调查了快速血栓弹力图（rTEG）凝血病患者的临床和生物标志物特征，假设交感肾上腺激活和内皮损伤是导致这种情况的原因。
方法
对入住美国一级创伤中心的404例创伤患者进行前瞻性观察研究。纳入入院时进行rTEG检查以及血浆儿茶酚胺（肾上腺素、去甲肾上腺素）和反映内皮激活/损伤的生物标志物（多配体蛋白聚糖-1、血栓调节蛋白、可溶性E选择素、可溶性血管内皮钙黏蛋白、核小体）检测的患者。记录人口统计学资料、损伤类型/严重程度、生理指标、治疗情况及住院死亡率。
结果
患者的损伤严重程度评分（ISS）中位数为17，73%为钝性损伤。三分之一（35%）的患者存在rTEG凝血病，这与血浆肾上腺素、多配体蛋白聚糖-1和核小体水平升高（均P<0.05）、输血需求增加以及早期（<24小时，9.3%对2.5%）和晚期（28天，23.8%对13.4%）死亡率升高相关。通过校正线性回归分析，血浆肾上腺素、可溶性血管内皮钙黏蛋白和多配体蛋白聚糖-1水平升高（反映交感肾上腺激活以及内皮细胞连接和糖萼损伤）以及男性、高ISS、低血小板计数和院前红细胞输血与rTEG低凝独立相关，而院前血浆和可溶性E选择素水平升高（反映内皮激活）与rTEG高凝独立相关。
结论
在这组重伤创伤患者中，rTEG凝血病与交感肾上腺激活、内皮病变和过高死亡率相关。高肾上腺素以及反映内皮细胞连接和糖萼损伤的生物标志物与低凝性和高纤溶独立相关。这些发现支持交感肾上腺激活和内皮病变促成创伤性凝血病，值得进一步研究内皮修复管理。
证据水平
预后性研究，三级。
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