Comparing 24-hour mortality for plasma and tranexamic acid, alone and in combination, for traumatic hemorrhage: findings from a prospective, observational, multicenter cohort study in South Africa

Background: Hemorrhage is the leading cause of preventable deaths in injured persons. Blood products and timely surgical intervention are the mainstays of treatment, but they are often limited in resource-constrained settings. Both plasma (which expands volume and replaces clotting factors) and tranexamic acid (TXA, an anti-fibrinolytic) mitigate dangerous post-traumatic fibrinolysis and have practical advantages in resource-limited settings. We evaluate the relative mortality benefit of plasma, TXA, and their combination in traumatic hemorrhage. Materials and methods: This is a secondary analysis from a prospective multicenter cohort study of adult traumapatients in South Africa. We included patients with or at high risk of hemorrhage who survived to receive care in an ambulance or hospital between 2021 and 2024. Three treatment groups were compared: Plasma, TXA, and Plasma + TXA. A multivariable Cox proportional hazards model with inverse probability of treatment weighting, adjusting for demographic, anatomic, and physiologic factors, was used to assess 24-hour in-hospital mortality. Results: A total of 843 patients were included. Thirty-six percent received Plasma + TXA, 43% received Plasma, and 21% received TXA (reference group). The median age was 31 years, 86% had penetrating injuries, and 59% had severe anatomic injuries. Overall, 8.3% of patients died within 24 hours, and 13.2% died within 30 days. Plasma alone was associated with a 46% reduction in 24-hour mortality (adjusted hazard ratio [aHR] 0.54, 95% confidence interval [CI] 0.35–0.83). Plasma + TXA demonstrated a non-significant 28% reduction in 24-hour mortality (aHR 0.72, 95% CI 0.39–1.32). Subgroup analysis excluding fresh-frozen plasma showed a 38% mortality reduction for patients receiving freeze-dried plasma (FDP) alone at 24 hours (aHR 0.62, 95% CI 0.43–0.90) and a 42% reduction for FDP + TXA at 30-days (aHR 0.58, 95% CI 0.49–0.68). Conclusion: Plasma alone and Plasma + TXA were associated with reduced 24-hour mortality compared to TXA alone. FDP demonstrated a mortality-lowering benefit. This study contributes to the evidence supporting the use of plasma and TXA, individually or in combination, in resource-poor settings.