纤溶酶血栓弹力描记术快速识别大出血、死亡和纤维蛋白溶解亢进风险的创伤患者：解决氨甲环酸国际争论的诊断工具？

Plasmin thrombelastography rapidly identifies trauma patients at risk for massive transfusion, mortality, and hyperfibrinolysis: A diagnostic tool to resolve an international debate on tranexamic acid?

机构信息

From the Koch Institute for Integrative Cancer Research (C.D.B., S.D., M.B.Y.), Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge; Division of Acute Care Surgery and Critical Care (C.D.B., M.B.Y.), Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Surgery (H.B.M., N.V., A.S., E.E.M.), University of Colorado Denver, Denver, Colorado; Ernest E. Moore Shock and Trauma Center (J.C., E.E.M.), Denver Health Medical Center; and Department of Radiology (M.P.C.), University of Colorado Denver, Denver, Colorado.

出版信息

J Trauma Acute Care Surg. 2020 Dec;89(6):991-998. doi: 10.1097/TA.0000000000002941.

DOI:10.1097/TA.0000000000002941

PMID:33230046

Abstract

BACKGROUND

Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis.

METHODS

Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%).

RESULTS

Plasmin TEG provided results faster than all other assays (4.7 ± 2.5-9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1-58.1 minutes; p < 0.001). Plasmin TEG-positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708).

CONCLUSION

Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy.

LEVEL OF EVIDENCE

Diagnostic test, level V.

摘要

背景

通过血栓弹性描记术（TEG）测量的纤维蛋白溶解抑制剂（DFI）耗竭和高纤维蛋白溶解的创伤患者用氨甲环酸（TXA）获得血凝块强度，但 TEG 结果需要近一个小时。我们旨在开发一种测定法，即纤溶酶 TEG（P-TEG），以更快速地对大量输血（MT）、死亡率和高纤维蛋白溶解的风险进行分层。

方法

评估了 148 名创伤患者的 TEG 测定法，不使用外源性添加剂（快速/原生）、使用外源性纤溶酶（P-TEG）或组织型纤溶酶原激活剂（tPA TEG）。使用的纤溶酶剂量不会影响健康对照者 30 分钟时的最大振幅后（LY30）的纤溶酶溶解，但与原生 TEG 相比，会缩短反应时间（R 时间）（P-TEG R 时间<原生 TEG R 时间被认为是 P-TEG 阴性）。如果 P-TEG R 时间大于或等于原生 TEG R 时间，则认为患者是 P-TEG 阳性。确定了每种测定法预测 MT、死亡率和（高纤维蛋白溶解的）风险的能力。使用 χ 和曼-惠特尼 U 检验分别比较分类和连续变量。结果以中位数±四分位距或 n（%）表示。

结果

纤溶酶 TEG 提供的结果比所有其他测定法都快（4.7±2.5-9.1 分钟），大约比快速-TEG（rTEG）LY30 快 11 倍（54.2±51.1-58.1 分钟；p<0.001）。纤溶酶 TEG 阳性患者的 MT 发生率高 4 倍（30%比 7%；p=0.0015），其受试者工作特征曲线下面积为 0.686（p=0.028），24 小时死亡率高 4 倍（33.3%比 7.8%；p=0.0177），30 天死亡率高 2 倍（35%比 16.4%；p=0.0483），DFI 发生率高 5 倍（55%比 18%；p<0.001），D-二聚体呈升高趋势（19.9 比 3.3μg/mL；p=0.14）。纤溶酶 TEG 与 rTEG LY30 7.6%的纤维蛋白溶解阈值相关（p=0.04），但与 3%的纤维蛋白溶解阈值不相关（p=0.40）。纤溶酶 TEG 在 DFI 方面表现最佳，阳性预测值为 58%，阴性预测值为 81%。当与 tPA TEG 达到最大振幅的时间结合时，P-TEG 在预测 MT 方面优于 rTEG LY30（受试者工作特征曲线下面积，0.811 比 0.708）。

结论

在 5 分钟内，P-TEG 可以对 MT、死亡率和高纤维蛋白溶解风险最高的患者进行分层。与 tPA TEG 达到最大振幅的时间综合后，P-TEG 在预测 MT 方面优于 rTEG LY30，速度快 4 倍（12.7 比 54.1 分钟）。P-TEG 的快速结果可能对那些选择性使用氨甲环酸以最大限度地提高氨甲环酸时间依赖性疗效的人有用。