Survival benefit of prehospital TXA in fibrinolytic shutdown: Insights from two prospective trauma trials

BACKGROUND: Fibrinolytic phenotypes have been implicated in postinjury pathophysiology and outcomes. While prehospital tranexamic acid (TXA) administration has demonstrated survival benefits, the interaction between TXA administration and distinct fibrinolytic profiles remains poorly defined. METHODS: We analyzed data from a harmonized dataset combining 2 prospective trials evaluating prehospital TXA use in trauma (Prehospital Tranexamic Acid Use for Traumatic Brain Injury and the Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial). Patients were stratified by initial thromboelastographic (TEG) LY30 into fibrinolytic shutdown (<0.9%), hyperfibrinolysis (>3%), and physiological fibrinolysis (0.9–3%). The primary outcome was 30-day mortality. Secondary outcomes included 24-hour mortality and adverse events. Multivariable regression adjusted for TXA administration, fibrinolysis phenotypes, age, mechanism of injury, injury severity score, and shock index on presentation to the hospital. RESULTS: Among 1,249 patients, 30-day mortality was 14.5% in the fibrinolytic shutdown group, 6.7% in the hyperfibrinolysis group, and 6.5% in the physiological fibrinolysis group. After multivariable regression, hyperfibrinolysis was associated with increased risk of death (HR 2.87; 95% CI: 1.10–7.53; p 0.03). Patients with fibrinolytic shutdown who were randomized to TXA had decreased risk of death (HR 0.32; 95% CI: 0.11–0.91; p =0.03). CONCLUSIONS: This multitrial analysis revealed greater statistically significant differences between fibrinolytic phenotypes than analysis of each trial alone. Fibrinolytic phenotypes were independently associated with mortality. Fibrinolytic shutdown in patients randomized to receive TXA was associated with lower risk of death. These findings support the relevance of fibrinolysis profiling during early trauma care and underscore the need for larger studies to further elucidate the prognostic and therapeutic implications in trauma. LEVEL OF EVIDENCE: II (Subanalysis of Randomized Controlled Trials).