Does tranexamic acid reduce mortality in traumatic brain injury?

Pooled RCT evidence, dominated by CRASH-3, shows a modest overall mortality reduction with tranexamic acid in TBI (RR 0.92), but this benefit appears confined to mild-to-moderate TBI, with no benefit and possibly harm in severe TBI according to at least one cited study; the packet does not support a uniform mortality benefit across all TBI severities.

Randomized trial and meta-analysis evidence on mortality

• In a meta-analysis of six randomized controlled trials totaling 30073 patients, tranexamic acid decreased mortality compared with placebo (RR = 0.92; 95% CI, 0.87–0.96; p < 0.001), though it did not decrease disability, need for neurosurgery, vascular embolism, or stroke.
• The CRASH-3 trial, a randomised placebo-controlled trial, found the risk of death from head injury was reduced with tranexamic acid, particularly when patients with a Glasgow Coma Scale score of 3 and those with bilateral unreactive pupils at baseline were excluded, with no evidence of increased disability among survivors.
• A clinical practice guideline update reports that CRASH-3 found TXA significantly reduced mortality in patients with mild or moderate TBI but had no advantage in patients with severe TBI, with Brenner et al. obtaining similar results, whereas Bossers et al. (2021) found TXA administration was associated with increased mortality in patients with severe TBI.
• A narrative review states that the CRASH-3 trial provided evidence that early administration of TXA reduces head injury-related mortality specifically in patients with mild to moderate TBI.
• Two earlier small randomised trials of TXA in TBI (510 patients total) showed a statistically significant reduction in death on meta-analysis, but this was considered hypothesis-generating given the small sample size, requiring confirmation in larger trials such as CRASH-3.

Observational and mechanistic data

• A nested subgroup analysis of the CRASH-2 trial in patients with extracranial bleeding and TBI with abnormal CT findings found a non-significant trend toward reduced hemorrhage growth, ischaemic lesions, and mortality with TXA.
• A prospective cohort study (EpiC, South Africa) evaluated 7-day mortality using inverse probability treatment weighting in trauma patients with both non-head hemorrhage and TBI who received TXA within 3 hours post-injury versus those who did not, framed around the premise that TXA has been shown to reduce mortality from hemorrhage and TBI independently, though evidence in combined injury is described as sparse.

Sources

• Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial — Lancet (London, England)
• The effect of tranexamic acid in patients with TBI: a systematic review and meta-analysis of randomized controlled trials — Chinese Neurosurgical Journal
• 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
• A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan — Wellcome Open Research
• Recent advances in traumatic brain injury — Journal of Neurology
• Early and Ultraearly Administration of Tranexamic Acid in Traumatic Brain Injury: Our 8-Year-Long Clinical Experience — Emergency Medicine International
• Hemostatic Resuscitation in Trauma-Induced Coagulopathy: A Comprehensive Narrative Review — Medicina
• Prehospital coagulation management and fluid replacement therapy in patients with multiple and/or severe injuries – A systematic review and clinical practice guideline update — European Journal of Trauma and Emergency Surgery
• Tranexamic acid for neurological outcomes and mortality in adults with hemorrhagic acute brain injury: an updated systematic review and 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.