The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured

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

The tissue-plasminogen activator-challenged thromboelastography provides a comprehensive assessment of fibrinolysis in the severely injured

J Trauma Acute Care Surg. 2025 Jan 17. doi: 10.1097/TA.0000000000004526. Online ahead of print.

Authors

Elizabeth R Maginot¹, 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

Affiliation

¹ From the Division of Acute Care Surgery, Department of Surgery (E.R.M., T.B.M., C.M.W., H.S., R.H., C.D.B.), University of Nebraska Medical Center, Omaha, Nebraska; Department of Surgery (H.B.M.), AdventHealth Porter; Department of Surgery (E.E.M., J.G.C.), Ernest E Moore Shock Trauma Center at Denver Health, Denver; Department of Surgery (E.E.M.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Hunter College (I.M.B.), New York, New York; Sauaia Statistical Solutions, LLC (A.S.), Denver, Colorado; and Department of Cellular and Integrative Physiology (F.I.G., C.D.B.), University of Nebraska Medical Center, Omaha, Nebraska.

PMID: 39836091
DOI: 10.1097/TA.0000000000004526

Abstract

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.

Level of evidence: Basic Science; N/A.