Elizabeth R Maginot, Hunter B Moore, Ernest E Moore, Isabella M Bernhardt, Trace B Moody, Collin M White, Halima Siddiqui, Flobater I Gawargi, Reynold Henry, James G Chandler, Angela Sauaia, Christopher D Barrett
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We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.</p><p><strong>Methods: </strong>Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval. Plasminogen activator inhibitor-1 activity, A2AP, PAP, and tPA-PAI-1 complex as well as tPA activity were measured. Data were analyzed using Spearman's correlations and analysis of variance.</p><p><strong>Results: </strong>The median age was 34 years, 75% were male, and the New Injury Severity Score was 14. Mortality was 25%, and 23% required a massive transfusion. There was a significant negative correlation between PAI-1 activity and A2AP with tPA-TEG LY30 (r = -0.77, p < 0.0001 and r = -0.62, p < 0.0001). There was a significant positive correlation between PAP complex and tPA-TEG LY30 (r = 0.74, p < 0.0001). There was no correlation between any fibrinolytic analyte and rTEG LY30. When stratified by phenotype, patients with hypofibrinolysis and nonpathologic fibrinolysis had higher active PAI-1 (p < 0.05) and A2AP levels (p < 0.05), lower PAP (p < 0.05), and tPA-PAI-1 complex (p < 0.05). Tissue-plasminogen activator activity was higher in hyperfibrinolysis relative to the other three groups (p < 0.05).</p><p><strong>Conclusion: </strong>Tissue-plasminogen activator-TEG LY30 more accurately reflects fibrinolysis phenotypes in trauma patients than conventional TEG methods. This provides an explanation for tPA-TEG's superior performance over rTEG in predicting clinical outcomes.</p><p><strong>Level of evidence: </strong>Basic Science; N/A.</p>","PeriodicalId":17453,"journal":{"name":"Journal of Trauma and Acute Care Surgery","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured.\",\"authors\":\"Elizabeth R Maginot, Hunter B Moore, Ernest E Moore, Isabella M Bernhardt, Trace B Moody, Collin M White, Halima Siddiqui, Flobater I Gawargi, Reynold Henry, James G Chandler, Angela Sauaia, Christopher D Barrett\",\"doi\":\"10.1097/TA.0000000000004526\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Tissue-plasminogen activator-challenged thromboelastography (tPA-TEG) predicts massive transfusion and mortality better than conventional rapid thromboelastography (rTEG), with little concordance between their lysis values (LY30). We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.</p><p><strong>Methods: </strong>Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval. Plasminogen activator inhibitor-1 activity, A2AP, PAP, and tPA-PAI-1 complex as well as tPA activity were measured. Data were analyzed using Spearman's correlations and analysis of variance.</p><p><strong>Results: </strong>The median age was 34 years, 75% were male, and the New Injury Severity Score was 14. Mortality was 25%, and 23% required a massive transfusion. There was a significant negative correlation between PAI-1 activity and A2AP with tPA-TEG LY30 (r = -0.77, p < 0.0001 and r = -0.62, p < 0.0001). There was a significant positive correlation between PAP complex and tPA-TEG LY30 (r = 0.74, p < 0.0001). There was no correlation between any fibrinolytic analyte and rTEG LY30. When stratified by phenotype, patients with hypofibrinolysis and nonpathologic fibrinolysis had higher active PAI-1 (p < 0.05) and A2AP levels (p < 0.05), lower PAP (p < 0.05), and tPA-PAI-1 complex (p < 0.05). Tissue-plasminogen activator activity was higher in hyperfibrinolysis relative to the other three groups (p < 0.05).</p><p><strong>Conclusion: </strong>Tissue-plasminogen activator-TEG LY30 more accurately reflects fibrinolysis phenotypes in trauma patients than conventional TEG methods. 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引用次数: 0
摘要
背景：组织纤溶酶原激活物激发的血栓弹性成像（tPA-TEG）比传统的快速血栓弹性成像（rTEG）更能预测大量输血和死亡率，两者的溶解值（LY30）几乎没有一致性。我们假设主要的纤溶酶抑制剂纤溶酶原激活物抑制剂-1 （PAI-1）和α-2抗纤溶酶（A2AP），以及纤溶酶激活标志物（纤溶酶抗纤溶酶[PAP]， tPA-PAI-1复合物，tPA活性）与tPA-TEG和rTEG LY30的相关性更强，并且可以解释最近基于这两种TEG方法在创伤中发现的四种不同的纤溶表型。方法：56例成人外伤患者经机构审查委员会批准，在到达急诊科时进行tPA-TEG、rTEG和血浆检测。测定纤溶酶原激活物抑制剂-1活性、A2AP、PAP、tPA- pai -1复合物及tPA活性。数据分析采用Spearman相关和方差分析。结果：中位年龄34岁，男性占75%，新损伤严重程度评分为14分。死亡率为25%，23%的人需要大量输血。PAI-1活性、A2AP与tPA-TEG LY30呈显著负相关（r = -0.77, p < 0.0001; r = -0.62, p < 0.0001）。PAP复合物与tPA-TEG LY30呈显著正相关（r = 0.74, p < 0.0001）。任何纤溶分析物与rTEG LY30均无相关性。当按表型分层时，低纤溶和非病理性纤溶患者活性PAI-1和A2AP水平较高（p < 0.05）， PAP水平较低（p < 0.05）， tPA-PAI-1复合物水平较低（p < 0.05）。高纤溶组组织纤溶酶原激活物活性高于其他3组（p < 0.05）。结论：组织-纤溶酶原激活物-TEG LY30比常规TEG方法更准确地反映创伤患者的纤溶表型。这就解释了tPA-TEG在预测临床结果方面优于rTEG的原因。证据水平：基础科学；N/A。
The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured.
Background: Tissue-plasminogen activator-challenged thromboelastography (tPA-TEG) predicts massive transfusion and mortality better than conventional rapid thromboelastography (rTEG), with little concordance between their lysis values (LY30). We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.
Methods: Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval. Plasminogen activator inhibitor-1 activity, A2AP, PAP, and tPA-PAI-1 complex as well as tPA activity were measured. Data were analyzed using Spearman's correlations and analysis of variance.
Results: The median age was 34 years, 75% were male, and the New Injury Severity Score was 14. Mortality was 25%, and 23% required a massive transfusion. There was a significant negative correlation between PAI-1 activity and A2AP with tPA-TEG LY30 (r = -0.77, p < 0.0001 and r = -0.62, p < 0.0001). There was a significant positive correlation between PAP complex and tPA-TEG LY30 (r = 0.74, p < 0.0001). There was no correlation between any fibrinolytic analyte and rTEG LY30. When stratified by phenotype, patients with hypofibrinolysis and nonpathologic fibrinolysis had higher active PAI-1 (p < 0.05) and A2AP levels (p < 0.05), lower PAP (p < 0.05), and tPA-PAI-1 complex (p < 0.05). Tissue-plasminogen activator activity was higher in hyperfibrinolysis relative to the other three groups (p < 0.05).
Conclusion: Tissue-plasminogen activator-TEG LY30 more accurately reflects fibrinolysis phenotypes in trauma patients than conventional TEG methods. This provides an explanation for tPA-TEG's superior performance over rTEG in predicting clinical outcomes.
期刊介绍：
The Journal of Trauma and Acute Care Surgery® is designed to provide the scientific basis to optimize care of the severely injured and critically ill surgical patient. Thus, the Journal has a high priority for basic and translation research to fulfill this objectives. Additionally, the Journal is enthusiastic to publish randomized prospective clinical studies to establish care predicated on a mechanistic foundation. Finally, the Journal is seeking systematic reviews, guidelines and algorithms that incorporate the best evidence available.
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