Tranexamic Acid Dosing in Trauma: CRASH-2 Trial Evidence
Recommended Dose and Administration
Administer tranexamic acid 1 gram intravenously over 10 minutes as a loading dose, followed by 1 gram infused over 8 hours, starting as early as possible and absolutely within 3 hours of injury. 1, 2
Critical Timing Considerations
The effectiveness of tranexamic acid is highly time-dependent based on CRASH-2 trial findings:
- Treatment within 1 hour of injury: Reduces bleeding-related mortality by 32% (5.3% vs 7.7% placebo; RR 0.68,95% CI 0.57-0.82) 1, 3
- Treatment between 1-3 hours: Still beneficial but less effective, reducing bleeding deaths by 21% (4.8% vs 6.1% placebo; RR 0.79) 1, 3
- Treatment after 3 hours: May actually increase risk of bleeding death by 44% (4.4% vs 3.1% placebo; RR 1.44) and should NOT be administered 1, 3
Effectiveness decreases by 10% for every 15-minute delay in administration, making pre-hospital administration strongly recommended. 4, 2
Patient Selection
Administer to all trauma patients who are bleeding or at risk of significant hemorrhage, regardless of:
The CRASH-2 trial enrolled 20,211 adult trauma patients and demonstrated an overall mortality reduction from 16.0% to 14.5% (RR 0.91,95% CI 0.85-0.97), preventing one death for every 67 patients treated. 6, 7
Pre-Hospital Administration
Protocols should consider administering the first 1 gram loading dose en route to the hospital to ensure treatment begins within the critical first hour. 1 This recommendation stems from the dramatic loss of benefit with delayed administration and the finding that only 40% of preventable deaths occur in the highest-risk patient group. 1
Safety Profile
- No increased thrombotic risk: The CRASH-2 trial showed lower rates of myocardial infarction with tranexamic acid compared to placebo 1
- Seizure risk: Higher doses (beyond the standard regimen) are associated with increased seizure risk, particularly in cardiac surgery patients 1, 4
- Hypotension: Rapid intravenous bolus can cause hypotension 7
Common Pitfalls to Avoid
- Delaying administration while awaiting laboratory confirmation of hyperfibrinolysis: This wastes precious time and would result in thousands of avoidable deaths 8
- Restricting use only to massive transfusion protocols: All bleeding trauma patients should receive tranexamic acid, not just those with the most severe hemorrhage 1
- Administering after 3 hours: This is potentially harmful and contraindicated 1, 2
- Waiting until hospital arrival: Pre-hospital administration should be standard practice 1, 2