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

The largest and highest-quality randomized trial evidence (CRASH-2) shows tranexamic acid reduces 28-day all-cause mortality and death due to bleeding in trauma patients with significant hemorrhage, particularly when given within 3 hours of injury, and this underpins current European trauma guideline dosing recommendations; smaller and prehospital trials (MATTERs, STAAMP) show mixed or reanalysis-dependent mortality signals.

Guideline recommendation

• The 2019 updated European guideline on management of major hemorrhage and coagulopathy after trauma recommends giving tranexamic acid early to bleeding trauma patients or those at risk of significant hemorrhage as a 1 g bolus within 3 h of injury followed by 1 g infusion over 8 h, citing a survival advantage demonstrated in large randomized controlled trials including CRASH-2.

Randomized trial evidence on mortality

• The CRASH-2 trial, a multicenter international RCT of trauma patients with systolic blood pressure lower than 90 mmHg and/or heart rate higher than 110 beats per minute or considered at risk of significant hemorrhage, randomized to tranexamic acid or placebo within 8 hours of injury, found a statistically significant 28-day mortality reduction with a relative risk of 0.91 (95%-CI 0.85–0.97; p = 0.0035), an absolute mortality reduction of 1.5% (95%-CI 0.5–2.5) from 16% to 14.5%, and a number needed to treat for benefit of 68 (95%-CI 40–206).
• A separate summary of CRASH-2 (20,211 adult trauma patients with or at risk of significant bleeding, randomized within 8 h of injury) reported 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 h of injury.
• The MATTERs trial (military trauma patients, all receiving blood transfusion) found an absolute mortality reduction of 6.7% with TXA (14.4% in TXA group versus 28.1% in no-TXA group; P = 0.004), with a number needed to treat of 1:7.
• A bayesian reanalysis of the STAAMP trial (903 patients) found the posterior probability that prehospital TXA was associated with reduced 30-day mortality ranged from 84% to 99%, including under a noninformative prior, whereas the original STAAMP trial analysis did not find a difference in mortality between TXA and placebo.

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
• The European Perspective on the Management of Acute Major Hemorrhage and Coagulopathy after Trauma: Summary of the 2019 Updated European Guideline — Journal of Clinical Medicine
• Recent advances in traumatic brain injury — Journal of Neurology
• Early Tranexamic Acid in Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials — Frontiers in Neurology

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