Tranexamic acid is associated with post-injury mortality in a resource-limited trauma system: Findings from the epidemiology and outcomes of prolonged trauma care cohort study

Background: Injury-related deaths claim millions of lives annually, with severe hemorrhage a leading cause. This study assesses tranexamic acid (TXA) administered within 3 h post-injury on mortality in trauma patients. Study Design And Methods: We conducted secondary database analysis of EpiC, a multicenter, prospective cohort of trauma patients in South Africa. We compared mortality between severely injured patients at risk for traumatic hemorrhage receiving TXA within 3 h post-injury versus untreated patients. Inverse probability of treatment weighting adjusted for confounders, and multivariate logistic regression assessed 24-h mortality, with extended secondary outcome analyses. Results: Of 3607 analyzed patients, 502 received TXA within 3 h. TXA reduced 24-h mortality by 38% (marginal odds ratio [mOR], 0.62; 95% confidence interval [CI], 0.49–0.78) versus untreated patients. Similar reductions were observed for longer-term mortality. Subgroup analyses revealed reduced mortality when TXA was given within 2 h post-injury (mOR, 0.57; 95% CI, 0.45–0.73), doses of 1 g of TXA within 3 h (mOR, 0.73; 95% CI, 0.56–0.94), and those with the highest risk of hemorrhage (mOR, 0.40; 95% CI, 0.30–0.53). The 24-h mortality reduction was significant for patients with penetrating injury (mOR, 0.58; 95% CI, 0.43–0.78) but not for blunt injury patients. Sensitivity analyses confirmed the robustness of these findings, with TXA consistently reducing mortality odds by 28%–39% across subgroups. Discussion: Early TXA administration significantly reduced mortality in trauma patients, especially with penetrating injuries and those with the highest risk of hemorrhage. One-gram dosing was as effective as higher doses, and mortality reduction was notable when TXA was given within 2 h post-injury. These findings support TXA use in resource-limited trauma protocols.