Tranexamic Acid Infusion in Traumatic Brain Injury
Tranexamic acid should be administered in patients with traumatic brain injury, particularly those with mild-to-moderate TBI, using a 1-g loading dose over 10 minutes followed by 1-g infusion over 8 hours, initiated as early as possible and within 3 hours of injury. 1
Evidence-Based Recommendation
The most recent high-quality guidelines from the Association of Anaesthetists (2025) clearly state that tranexamic acid reduces mortality in patients with mild-to-moderate traumatic brain injury when administered within 3 hours of injury. 1 This recommendation is supported by the European Society of Intensive Care Medicine (2021), which provides a conditional recommendation for TXA use in TBI patients, acknowledging that while TXA does not reduce all-cause mortality across all TBI severities, it may reduce head-injury associated death in specific populations. 1
Patient Selection Algorithm
Appropriate candidates for TXA:
- Patients with mild-to-moderate TBI (GCS >3) 1
- Patients without bilateral unreactive pupils at baseline 1
- Patients presenting within 3 hours of injury 1, 2
- Patients with or without concomitant extracranial trauma 1
Patients unlikely to benefit:
- Severe TBI with GCS of 3 1
- Bilateral unreactive pupils at baseline 1
- Presentation beyond 3 hours post-injury (may increase mortality risk) 3
Dosing Protocol
Standard regimen:
- Loading dose: 1 g IV over 10 minutes 1, 3
- Maintenance: 1 g IV over 8 hours 1, 3
- Timing: Administer as soon as possible, ideally within 3 hours of injury 1, 2
Critical timing considerations:
- Effectiveness decreases by approximately 10% for every 15-minute delay in administration 3
- Early treatment (≤1 hour from injury) significantly reduces mortality due to bleeding 3
- Administration after 3 hours may increase risk of death due to bleeding 3
Evidence Quality and Nuances
The CRASH-3 trial (2019), the largest and most definitive study with 12,737 patients, demonstrated that TXA reduces head injury-related death when excluding patients with severe TBI (GCS 3 or bilateral unreactive pupils): risk ratio 0.89 (95% CI 0.80-1.00). 2 The effect was most pronounced in mild-to-moderate TBI (RR 0.78,95% CI 0.64-0.95) but not in severe TBI (RR 0.99,95% CI 0.91-1.07). 2
A 2024 network meta-analysis suggested that a 2-g bolus of TXA may be superior to the standard 1-g bolus followed by 1-g maintenance regimen, showing lower mortality (RR 1.44,95% CI 1.02-2.03 favoring 2-g bolus). 4 However, this finding comes from limited data and requires further validation before changing established protocols.
Safety Profile
No increased thrombotic risk:
- No significant increase in vascular occlusive events (stroke, MI, venous thromboembolism) 1, 2
- Risk of seizures similar to placebo (RR 1.09,95% CI 0.90-1.33) 2
- Higher doses may increase seizure risk in other populations (cardiac surgery), but standard TBI dosing appears safe 3
Implementation Considerations
Do not delay for diagnostic testing:
- Administer TXA empirically before viscoelastic testing results, as point-of-care measurements have varying sensitivity for hyperfibrinolysis 1
- Early empiric use is more important than waiting for laboratory confirmation 1
Polytrauma patients:
- TXA is indicated for trauma patients with or without TBI, supporting its use while the full extent of injuries is being assessed 1
- The same dosing regimen applies regardless of concomitant injuries 1
Common Pitfalls to Avoid
- Delaying administration beyond 3 hours significantly reduces effectiveness and may increase mortality 3
- Withholding TXA in severe TBI: While benefit is primarily in mild-to-moderate TBI, patients often have mixed injury patterns requiring assessment; early administration is reasonable in polytrauma 1
- Assuming prehospital administration is always superior: While early treatment is critical, evidence for very early prehospital administration remains limited 1
- Using alternative dosing without evidence: Stick to the validated 1-g/1-g regimen unless participating in clinical trials 1, 3