Division of Hematology, Department of Medicine and Blood Research Center, University of North Carolina, Chapel Hill, NC, USA.
Department of Surgery, Mayo Clinic, Rochester, MN, USA.
Thromb Res. 2021 Aug;204:22-28. doi: 10.1016/j.thromres.2021.05.017. Epub 2021 May 31.
Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinolysis that could add novel insights into the frequency and mechanisms of fibrinolytic activation in trauma. Global fibrinolysis in plasma was assessed using a modified euglobulin clot lysis time (ECLT) assay in 171 major trauma patients and compared to commonly assessed analytes of fibrinolysis. The median ECLT in trauma patients was significantly shorter at 8.5 h (IQR, 1.3-19.5) compared to 19.9 h (9.8-22.6) in healthy controls (p < 0.0001). ECLT values ≤2.5th percentile of the reference range were present in 83 (48.5%) of trauma patients, suggesting increased fibrinolytic activation. Shortened ECLT values were associated with elevated plasmin-antiplasmin (PAP) complexes and free tissue plasminogen activator (tPA) levels in plasma. Sixteen (9.2%) individuals met the primary outcome for massive transfusion, here defined as the critical administration threshold (CAT) of 3 units of packed red cells in any 60-minute period within the first 24 h. In a univariate screen, plasma biomarkers associated with CAT included D-dimer (p < 0.001), PAP (p < 0.05), free tPA (p < 0.05) and ECLT (p < 0.05). We conclude that fibrinolytic activation, measured by ECLT, is present in a high proportion of trauma patients at presentation. The shortened ECLT is partially driven by high tPA levels and is associated with high levels of circulating PAP complexes. Further studies are needed to determine whether ECLT is an independent predictor of trauma outcomes.
纤溶系统的激活在创伤宿主反应中起着核心作用。在基线时,纤溶激活的程度存在显著异质性,通常通过全血血栓弹力图(TEG)进行评估。很少有研究关注纤溶的血浆标志物,这些标志物可能为创伤中纤溶激活的频率和机制提供新的见解。使用改良的优球蛋白溶解时间(ECLT)测定法评估了 171 例严重创伤患者的血浆整体纤溶情况,并与通常评估的纤溶分析物进行了比较。与健康对照组的 19.9 小时(9.8-22.6)相比,创伤患者的 ECLT 中位数明显缩短,为 8.5 小时(IQR,1.3-19.5)(p<0.0001)。在 83 例(48.5%)创伤患者中,ECLT 值≤参考范围的第 2.5 个百分位数,表明纤溶激活增加。缩短的 ECLT 值与血浆中纤溶酶-抗纤溶酶(PAP)复合物和游离组织型纤溶酶原激活剂(tPA)水平升高相关。16 例(9.2%)患者达到了大量输血的主要结局,这里定义为在最初 24 小时内的任何 60 分钟内,给予 3 个单位的浓缩红细胞的临界输注阈值(CAT)。在单变量筛查中,与 CAT 相关的血浆生物标志物包括 D-二聚体(p<0.001)、PAP(p<0.05)、游离 tPA(p<0.05)和 ECLT(p<0.05)。我们得出结论,在出现时,大量创伤患者存在纤溶激活,通过 ECLT 测量。缩短的 ECLT 部分由高水平的 tPA 驱动,并与循环 PAP 复合物的高水平相关。需要进一步的研究来确定 ECLT 是否是创伤结局的独立预测因子。