Military use of tranexamic acid in combat trauma: Does it matter?

Background: Tranexamic acid (TXA) has been previously reported to have a mortality benefit in civilian and combat-related trauma, and was thus added to the Joint Theater Trauma System Damage Control Resuscitation Clinical Practice Guideline. As part of ongoing system-wide performance improvement, the use of TXA has been closely monitored. The goal was to evaluate the efficacy and safety of TXA use in military casualties and provide additional guidance for continued use.
Methods: A total of 3,773 casualties were included in this retrospective, observational study of data gathered from a trauma registry. The total sample, along with three subsamples for massive transfusion patients (n = 784), propensity-matched sample (n = 1,030), and US/North Atlantic Treaty Organization (NATO) military (n = 1,262), was assessed for administration of TXA and time from injury to administration of TXA. Outcomes included mortality and occurrence of pulmonary embolism and deep vein thrombosis. Multivariable proportional hazards regression models with robust standard error estimates were used to estimate hazard ratios (HR) for assessment of outcomes while controlling for covariates.
Results: Results of univariate and multivariate analyses of the total sample (HR, 0.97; 95% confidence interval [CI], 0.62-1.53; p = 0.86), massive transfusion sample (HR, 0.84; 95% CI, 0.46-1.56; p = 0.51), propensity-matched sample (HR, 0.68; 95% CI, 0.27-1.73; p = 0.34), and US/NATO military sample (HR, 0.76; 95% CI, 0.30-1.92; p = 0.48) indicate no statistically significant association between TXA use and mortality. Use of TXA was associated with increased risk of pulmonary embolism in the total sample (HR, 2.82; 95% CI, 2.08-3.81; p < 0.001), massive transfusion sample (HR, 3.64; 95% CI, 1.96-6.78; p = 0.003), US/NATO military sample (HR, 2.55; 95% CI, 1.73-3.69; p = 0.002), but not the propensity-matched sample (HR, 3.36; 95% CI, 0.80-14.10; p = 0.10). TXA was also associated with increased risk of deep vein thrombosis in the total sample (HR, 2.00; 95% CI, 1.21-3.30; p = 0.02) and US/NATO military sample (HR, 2.18; 95% CI, 1.20-3.96; p = 0.02).
Conclusion: In the largest study on TXA use in a combat trauma population, TXA was not significantly associated with mortality, due to lack of statistical power. However, our HR estimates for mortality among patients who received TXA are consistent with previous findings from the CRASH-2 trial. At the same time, continued scrutiny and surveillance of TXA use in military trauma, specifically for prevention of thromboembolic events, is warranted.
Level of Evidence: Therapeutic, level IV.