Tranexamic Acid in Trauma: Evidence-Based Recommendations
Direct Recommendation
Administer tranexamic acid 1g IV over 10 minutes followed by 1g infusion over 8 hours to ALL trauma patients with significant bleeding or at risk of significant hemorrhage, ideally within 1 hour but no later than 3 hours post-injury. 1
Critical Time-Dependent Administration
The effectiveness of tranexamic acid is profoundly time-sensitive, with treatment benefit converting to potential harm beyond specific windows:
- Within 1 hour of injury: Maximum mortality reduction occurs, with bleeding deaths reduced by 32% (5.3% vs 7.7%; RR 0.68) 1, 2
- Between 1-3 hours: Moderate benefit persists, reducing bleeding deaths by 21% (4.8% vs 6.1%; RR 0.79) 1, 2
- After 3 hours: Treatment becomes potentially harmful, INCREASING death due to bleeding by 44% (4.4% vs 3.1%; RR 1.44) 1, 2
- Effectiveness decreases by 10% for every 15-minute delay in administration 1
Recent machine learning analysis of 28,448 trauma patients confirms the optimal treatment window is within 2 hours of injury, with benefits rapidly diminishing thereafter 3. The exception is severe traumatic brain injury (GCS < 9), where treatment benefits may extend beyond 2 hours 3.
Standard Dosing Protocol
The evidence-based regimen from the landmark CRASH-2 trial (20,211 patients) establishes:
This achieves therapeutic plasma levels of 10 μg/ml necessary to inhibit systemic fibrinolysis, with a plasma half-life of 120 minutes 1. Do not deviate from this protocol—higher doses increase seizure risk without additional benefit 1.
Mortality Benefit
Tranexamic acid demonstrates robust mortality reduction when administered appropriately:
- All-cause mortality: Reduced from 16.0% to 14.5% (RR 0.91,95% CI 0.85-0.97) 1, 4
- Death due to bleeding: Reduced from 5.7% to 4.9% (RR 0.85,95% CI 0.76-0.96) 1, 4
- 24-hour mortality: Reduced by 24% (OR 0.76,95% CI 0.65-0.88) 5
- Number needed to treat: 61 patients to prevent one death 5
Patient Selection: Broad Application Required
Do NOT restrict tranexamic acid to only massive transfusion protocols or highest-risk patients. 1 This is a critical implementation error that prevents the majority of preventable deaths:
- Only 40% of preventable deaths occur in the highest-risk group 1
- The proportional mortality reduction does not vary by baseline bleeding risk 6
- Far more low-risk trauma patients exist than high-risk patients, with substantial bleeding deaths occurring in the low-risk group 6
- Administer to ALL trauma patients with significant bleeding or at risk of significant hemorrhage 1
The treatment effect does not vary significantly by systolic blood pressure, Glasgow Coma Scale (except for timing considerations noted above), or type of injury 2.
Pre-Hospital Administration
Consider administering the first 1g loading dose en route to the hospital to ensure treatment within the critical time window 1. Pre-hospital administration is associated with reduced mortality compared to in-hospital administration 5. Intramuscular administration is well-tolerated and rapidly absorbed when IV access is challenging 6.
Safety Profile
Tranexamic acid demonstrates an exceptional safety profile in trauma:
- No increase in thrombotic events: Meta-analysis of 125,550 participants shows no increased risk of myocardial infarction, stroke, DVT, or pulmonary embolism 1
- Myocardial infarction rates were actually LOWER with tranexamic acid 1
- No evidence of increased vascular occlusive events (OR 0.96,95% CI 0.73-1.27) 5
Specific Contraindications in Trauma
Traumatic subarachnoid hemorrhage: Do not use tranexamic acid routinely in isolated traumatic SAH, as guidelines recommend against routine antifibrinolytic therapy due to lack of functional benefit despite reduced rebleeding 7. However, this differs from polytrauma with traumatic brain injury, where early tranexamic acid reduces deaths by approximately 20% 6.
Critical Implementation Pitfalls to Avoid
- Never delay administration beyond 3 hours—this converts benefit to harm 1, 2
- Do not restrict to massive hemorrhage protocols only—broader application prevents more deaths 1
- Do not use alternative routes without IV access unless intramuscular administration is necessary for pre-hospital treatment 6
- Do not exceed the CRASH-2 dosing protocol—higher doses increase seizure risk 1
- Do not wait for laboratory confirmation of bleeding—clinical diagnosis is sufficient 1
Renal Impairment Considerations
Tranexamic acid is renally excreted and accumulates in renal failure, requiring dose adjustment in severe renal impairment 8. However, in acute trauma with life-threatening bleeding, the standard dose should be administered immediately, with subsequent doses adjusted based on renal function assessment 8.
Cost-Effectiveness
Tranexamic acid demonstrates exceptional cost-effectiveness across all economic settings, with incremental cost per life-year gained of $48 in Tanzania, $66 in India, and $64 in the UK 1.