Tranexamic Acid Timing and Mortality Impact After Trauma

Abstract

Study objective: Trauma resuscitation guidelines across the world have incorporated the administration of tranexamic acid (TXA) within 3 hours of injury. The 3-hour window was deduced from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial and has not been replicated. The aim of this study was to determine whether death within 28 days after trauma varied according to time from injury to the first TXA dose and, if so, precisely determine the therapeutic window.

Methods: This was an exploratory analysis of the Prehospital Tranexamic Acid for Severe Trauma (PATCH-Trauma) trial, which enrolled adults with major trauma and suspected trauma-induced coagulopathy. Eligible patients were randomized to receive either TXA (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1 g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. In this analysis, we examined the effect of time from injury to first treatment dose on death within 28 days utilizing a continuous scale with linear, first-degree fractional polynomial, and second-degree fractional polynomial functions of time from injury to first treatment dose. Further log-binomial regression analyses were performed in subgroups based on the information obtained from the previous step.

Results: The intention-to-treat study cohort comprised 1,287 patients, of which 635 had been allocated to the placebo arm and 652 to the TXA arm. The median time from injury to first treatment dose was 79 (interquartile range [IQR] 55 to 112) minutes. Risk of death within 28 days increased as the time to first dose of treatment increased, with benefit most pronounced up to 90 minutes. Beyond 90 minutes, the upper 95% confidence interval (CI) crossed the line of equivalence (risk ratio, 1). Administration of TXA within 90 minutes significantly reduced the risk of death within 28 days (67/393 [17%] in the TXA group versus 91/363 [25%] in placebo group; adjusted risk ratio 0.64, 95% CI 0.50 to 0.82), whereas administration beyond 90 minutes did not decrease mortality at 28 days (adjusted risk ratio 1.04, 95% CI 0.74 to 1.47).

Conclusion: The optimal therapeutic window for TXA after trauma may be within 90 minutes.

Keywords: Injury; Randomized controlled trial; Tranexamic acid; Trauma.