Section for Transfusion Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
J Trauma Acute Care Surg. 2012 Jul;73(1):60-6. doi: 10.1097/TA.0b013e31825b5c10.
There is emerging evidence that early trauma-induced coagulopathy (TIC) is mechanistically linked to disruption of the vascular endothelium and its glycocalyx, assessed by thrombomodulin and syndecan 1, respectively. This study evaluated if degradation of the endothelial glycocalyx and ensuing release of its heparin-like substances induce autoheparinization and thereby contributes to TIC.
Prospective observational study of 77 trauma patients admitted to a Level I trauma center having blood sampled at admission. Data on demography, hematology, Injury Severity Score, transfusion requirements, 30-day mortality, and thrombelastography (TEG, concurrent kaolin-activated/kaolin-heparinase-activated) were recorded. Retrospective analysis of plasma/serum for biomarkers reflecting endothelial glycocalyx and cell damage (syndecan 1, thrombomodulin), tissue injury (histone-complexed DNA fragments), sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/anticoagulation (prothrombin fragment 1+2, fibrinogen, von Willebrand factor, factor XIII, antithrombin, protein C, activated protein C, tissue factor pathway inhibitor), fibrinolysis (tissue-type plasminogen activator, plasminogen activator inhibitor 1) and inflammation (interleukin 6, terminal complement complex). Stratification of patients was according to the degree of TEG-measured heparinization.
Four patients (5.2%) displayed evidence of high-degree autoheparinization, and these patients had higher Injury Severity Score (median [interquartile range], 31 [26-37] vs. 17 [10-26]), increased glucose (median, 13.6 vs. 8.0 mmol/L), and lower hemoglobin level (median, 5.8 vs. 8.4 mmol/L) and received more transfusions during the first 1 hour (median, 5 vs. 0) and 24 hours (median, 10 vs. 0) (all p < 0.05). Importantly, patients with autoheparinization had fourfold higher syndecan 1 levels (median [interquartile range], 116 ng/mL [78-140 ng/mL] vs. 31 ng/mL [18-49 ng/mL]), and they had higher international normalized ratio (median, 1.4 vs. 1.1), thrombomodulin (median, 4.1 vs. 1.7 ng/mL) and interleukin 6 (median, 129 vs. 71 pg/mL) but lower protein C (85% vs. 109%) (all p < 0.05), indicating profound endothelial damage, coagulopathy and inflammation.
Five percent of the patients with trauma in the present study had evidence of acute endogenous coagulopathy with autoheparinization by TEG, which appeared mechanistically linked to endothelial glycocalyx degradation. Acute endogenous autoheparinization may contribute to TIC.
Prognostic study, level III.
越来越多的证据表明，早期创伤诱导的凝血病（TIC）与血管内皮及其糖萼的破坏有关，分别由血栓调节蛋白和 syndecan 1 评估。本研究评估了内皮糖萼的降解以及随之而来的肝素样物质的释放是否会诱导自身肝素化，从而导致 TIC。
对入住一级创伤中心的 77 名创伤患者进行前瞻性观察性研究，在入院时采集血液样本。记录人口统计学、血液学、损伤严重程度评分、输血需求、30 天死亡率和血栓弹性图（TEG，同时使用高岭土激活/高岭土肝素酶激活）的数据。对血浆/血清进行生物标志物的回顾性分析，这些生物标志物反映了内皮糖萼和细胞损伤（syndecan 1、血栓调节蛋白）、组织损伤（组蛋白结合的 DNA 片段）、交感肾上腺激活（肾上腺素、去甲肾上腺素）、凝血激活/抗凝（凝血酶原片段 1+2、纤维蛋白原、血管性血友病因子、因子 XIII、抗凝血酶、蛋白 C、活化蛋白 C、组织因子途径抑制剂）、纤维蛋白溶解（组织型纤溶酶原激活物、纤溶酶原激活物抑制剂 1）和炎症（白细胞介素 6、末端补体复合物）。根据 TEG 测量的肝素化程度对患者进行分层。
有 4 名患者（5.2%）表现出高程度的自身肝素化证据，这些患者的损伤严重程度评分更高（中位数[四分位距]，31[26-37] vs. 17[10-26]），血糖更高（中位数，13.6 vs. 8.0 mmol/L），血红蛋白水平更低（中位数，5.8 vs. 8.4 mmol/L），在第 1 小时（中位数，5 vs. 0）和第 24 小时（中位数，10 vs. 0）接受更多的输血（均 p<0.05）。重要的是，自身肝素化的患者 syndecan 1 水平高出四倍（中位数[四分位距]，116 ng/mL[78-140 ng/mL] vs. 31 ng/mL[18-49 ng/mL]），国际标准化比值（中位数，1.4 vs. 1.1）、血栓调节蛋白（中位数，4.1 vs. 1.7 ng/mL）和白细胞介素 6（中位数，129 vs. 71 pg/mL）更高，但蛋白 C 水平更低（85% vs. 109%）（均 p<0.05），表明存在严重的内皮损伤、凝血障碍和炎症。
本研究中，5%的创伤患者存在急性内源性凝血病伴 TEG 自身肝素化，这似乎与内皮糖萼降解有关。急性内源性自身肝素化可能导致 TIC。
预后研究，III 级。
