Tranexamic acid in patients with traumatic brain injury: Is there benefit in patients with fibrinolytic shutdown?

Abstract

Tranexamic acid (TXA) is widely used in patients with traumatic brain injury (TBI). However, its pharmacology suggests differences in effectiveness should exist based on fibrinolytic phenotype, particularly fibrinolytic shutdown. This study examined whether fibrinolytic shutdown is associated with increased mortality in TBI and whether TXA retains its benefit in this subgroup. This retrospective cohort study included TBI patients who had thromboelastography (TEG) upon presentation at three affiliated trauma centers. Patients were excluded if they received TXA before TEG, had TXA >3 hours postadmission, Glasgow Coma Score (GCS)=3 and a nonreactive pupil or a nonsurvivable injury. The primary endpoint was all-cause mortality, either in-hospital or in-hospice, up to 28 days. Patients were stratified by fibrinolytic phenotype: shutdown (LY30<0.5%), physiologic (0.5-7.7%), or hyperfibrinolytic (>7.7%) and TXA receipt. Univariate and multivariate analyses were performed. Of 394 patients (mean age 64±21 y; 56% ground-level falls; 74% mild TBI), fibrinolytic shutdown predominated [72% (n=285)], followed by physiologic [27% (n=107)], and hyperfibrinolysis [0.5% (n=2)]. Unadjusted mortality was 16% with shutdown versus 9.2% without (p=0.090). After controlling for age, ISS, GCS, multicompartmental head injury, neurosurgical intervention, and TXA, there was no association between shutdown phenotype and mortality [OR (95% CI) =1.37 (0.62-3.05)]. In patients with fibrinolytic shutdown, unadjusted mortality was lower in patients who received TXA [12% (24/196) vs. 24% (21/89), p=0.015]. After controlling for age, ISS, GCS, multicompartmental head injury, and neurosurgical intervention, mortality remained lower [OR (95% CI)=0.36 (0.16-0.77)]. In patients without fibrinolytic shutdown, no difference in mortality was noted [TXA, 9.6% (7/73) vs. no TXA, 8.3% (3/36), p=1.00]. These results did not change after controlling for the above confounders [OR (95% CI)=0.96 (0.16-5.78)]. TXA remained associated with lower mortality in TBI patients with fibrinolytic shutdown, despite pharmacologic expectations. Fibrinolytic shutdown was not independently associated with higher mortality. These findings support early TXA administration without delaying treatment for TEG interpretation. (J Trauma Acute Care Surg 2026;00:000-000 Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.). Therapeutic/Care Management; Level IV.