Does tranexamic acid reduce mortality in trauma patients with significant hemorrhage?

The largest and highest-quality randomized trial evidence (CRASH-2) shows tranexamic acid modestly but significantly reduces 28-day mortality in trauma patients with significant hemorrhage when given within 8 hours of injury, with greatest benefit within 3 hours; a smaller military trial (MATTERs) reported a much larger absolute mortality benefit in transfusion-requiring casualties, though this is lower-certainty evidence.

CRASH-2: primary RCT evidence

• CRASH-2 also showed tranexamic acid significantly reduced death due to bleeding (RR = 0.85, 95% CI 0.76–0.96) and all-cause mortality (RR = 0.91, 95% CI 0.85–0.97), with no increase in vascular occlusive events, and the reduction in death due to bleeding was greatest when given within 3 hours of injury.
• A systematic review restricted to CRASH-2 as the only study meeting full-text screening criteria for this question rated the evidence quality as high per GRADE.

Military and observational data

• The MATTERs military trauma trial found an absolute mortality reduction of 6.7% (14.4% in the TXA group versus 28.1% in the no-TXA group; P = 0.004), with a number needed to treat of 1:7; all patients in this trial received blood transfusion, and TXA recipients required less blood product.
• Maximal mortality benefit from tranexamic acid in CRASH-2 was achieved when given within the first 3 hours of injury, but a subsequent study noted that most severely injured patients have fibrinolysis shutdown, suggesting tranexamic acid may have no effect in that subgroup, with greatest benefit likely in patients with increased clot lysis on thromboelastography.

Sources

• Blood Component Therapy and Coagulopathy in Trauma: A Systematic Review of the Literature from the Trauma Update Group — PLoS ONE
• Bayesian Statistics to Reanalyze Data From the STAAMP Trial — JAMA Network Open
• Association of Tranexamic Acid Administration With Mortality and Thromboembolic Events in Patients With Traumatic Injury — JAMA Network Open
• Tranexamic Acid (TXA) in Trauma Patients: Barriers to Use among Trauma Surgeons and Emergency Physicians — Emergency Medicine International
• Damage control resuscitation: a practical approach for severely hemorrhagic patients and its effects on trauma surgery — Journal of Intensive Care
• The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial — Frontiers in Immunology
• Mortality Benefit of Tranexamic Acid for Hemorrhage With Concurrent Traumatic Brain Injury: Outcomes From a Prospective Cohort Study in a High‐Trauma, Prolonged Care Setting — World Journal of Surgery
• Tranexamic acid for post-partum haemorrhage: What, who and when — Best Practice & Research. Clinical Obstetrics & Gynaecology

Decision support for clinicians, not medical advice. Answers are grounded in the published literature and every claim cites its source in the interactive view.