Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit

A Secondary Analysis of a Randomized Clinical Trial

Shimena R. Li, MD; Francis Guyette, MD, MPH; Joshua Brown, MD, MSc; Mazen Zenati, MD, MPH, PhD; Katherine M. Reitz, MD, MSc; Brian Eastridge, MD; Raminder Nirula, MD, MPH; Gary A. Vercruysse, MD; Terence O'Keeffe, MD; Bellal Joseph, MD; Matthew D. Neal, MD; Brian S. Zuckerbraun, MD; Jason L. Sperry, MD, MPH


Annals of Surgery. 2021;274(3):419-426. 

In This Article

Abstract and Introduction


Objective: We sought to characterize the timing of administration of prehospital tranexamic acid (TXA) and associated outcome benefits.

Background: TXA has been shown to be safe in the prehospital setting post-injury.

Methods: We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1 hour (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1 hour (DELAYED). We included patients with a shock index of >0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships.

Results: EARLY and DELAYED patients had similar demographics, injury characteristics, and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N = 238, log-rank chi-square test, 4.99; P = 0.03) with no separation for DELAYED patients (N = 238, log-rank chi-square test, 0.04; P = 0.83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.19–0.65, P = 0.001] with no independent survival benefit found in DELAYED patients (HR 1.00, 95% CI 0.63–1.60, P = 0.999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo.

Conclusions: Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirements.


Hemorrhage remains a leading cause of preventable death in both civilian and military injured patients.[1–6] A recent call for zero preventable deaths by the National Academies of Sciences, Engineering, and Medicine focuses on strategies to mitigate the physiologic consequences of hemorrhagic shock.[7] In addition to early balanced transfusion of blood components or whole blood transfusion, resuscitative adjuncts including tranexamic acid (TXA) improve survival after a patient has arrived at definitive care.[8–13] The timing of TXA administration during the in-hospital phase of care is important and associated with differential efficacy and safety outcomes.[8,14] More recent clinical trials following traumatic injury verified the importance of the timing of intervention and the significance of the prehospital environment to maximize benefit for the injured patient at risk of hemorrhage.[15–17]

Recent randomized clinical trials demonstrate the safety of prehospital TXA across a spectrum of injury types and severity.[18,19] These types of prehospital clinical trials following injury commonly require broad, pragmatic inclusion criteria with limited exclusion criteria due to the complexity of environment where enrollment occurs. Due to these factors, the most appropriate injured patient population and the timing of prehospital TXA administration to maximize outcome benefits remain poorly characterized.

Our objective is to characterize the timing of prehospital TXA administration relative to the time of injury and associations with differential outcome benefits. We hypothesized that early prehospital TXA administration is associated with efficacy and safety benefits as compared to delayed prehospital TXA administration.