Does tranexamic acid reduce mortality in traumatic brain injury?

The largest dedicated RCT (CRASH-3) and a pooled meta-analysis of six RCTs (30073 patients) both show tranexamic acid modestly reduces mortality in TBI overall, with the benefit concentrated in mild-to-moderate TBI; evidence in severe TBI is mixed, with at least one study reporting increased mortality in that subgroup.

Meta-analysis and RCT evidence on mortality benefit

• A meta-analysis of six randomized controlled trials totaling 30073 patients with TBI found tranexamic acid decreased mortality compared with placebo (RR = 0.92; 95% CI, 0.87–0.96; p < 0.001), though it did not reduce disability, need for neurosurgery, vascular embolism, or stroke.
• CRASH-3, a randomised, placebo-controlled trial, found reduced risk of death from head injury 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 prehospital systematic review and clinical practice guideline update reports that CRASH-3 found tranexamic acid significantly reduced mortality in patients with mild or moderate TBI but had no advantage in patients with severe TBI.
• A narrative review states that in traumatic brain injury, CRASH-3 provided evidence that early administration of tranexamic acid reduces head injury-related mortality in patients with mild to moderate TBI.
• Earlier pooled analysis of two small trials (510 patients total) showed a statistically significant reduction in death with tranexamic acid, but this evidence was considered hypothesis-generating and requiring confirmation in larger randomised trials.

Related mechanistic and extracranial bleeding context

• A nested study within CRASH-2 examining trauma patients with extracranial bleeding and TBI with abnormal CT brain findings found a non-significant trend toward reduction in hemorrhage growth, ischaemic lesions, and mortality with tranexamic acid.

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.