Tranexamic Acid (TXA) for Prophylactic Use in Severe Bleeding or Traumatic Injury
Tranexamic acid (TXA) is strongly recommended for prophylactic use in all cases of severe bleeding or traumatic injury, administered as soon as possible and ideally within 3 hours of injury at a loading dose of 1g infused over 10 minutes, followed by an intravenous infusion of 1g over 8 hours. 1, 2
Timing of Administration
The timing of TXA administration is critical:
- TXA should be administered as early as possible, ideally within the first hour after injury 2
- Treatment benefit decreases by approximately 10% for every 15-minute delay 2
- Administration within 1 hour shows the greatest benefit (32% relative risk reduction in death due to bleeding) 2
- TXA should not be delayed to await viscoelastic assessment results 1
- Administration after 3 hours may potentially increase mortality risk 2
Dosing Protocol
The standard dosing regimen is:
Dose Adjustments for Renal Impairment
For patients with renal insufficiency, dose adjustment is required 2:
| Creatinine Level | Recommended Dose |
|---|---|
| 1.36-2.83 mg/dL | 10 mg/kg twice daily |
| 2.83-5.66 mg/dL | 10 mg/kg once daily |
| >5.66 mg/dL | 10 mg/kg every 48 hours or 5 mg/kg every 24 hours |
Contraindications
TXA is contraindicated in patients with 2, 3:
- Active intravascular clotting
- Subarachnoid hemorrhage (risk of cerebral edema and infarction)
- Known thromboembolic disease
- History of thrombosis or intrinsic risk for thrombosis
- Severe hypersensitivity to tranexamic acid or any ingredients
Clinical Evidence Supporting Prophylactic Use
The recommendation for prophylactic TXA use in severe bleeding or traumatic injury is supported by high-quality evidence:
- The CRASH-2 trial demonstrated that TXA reduces all-cause mortality (14.5% vs 16.0%) and death due to bleeding (4.9% vs 5.7%) 2, 4
- A recent systematic review and bias-adjusted meta-analysis (2024) showed an 11% decrease in death risk at 1 month after TXA use (OR 0.89,95% CI 0.84 to 0.95) 5
- The number needed to treat is 61 to avoid one additional death 5
- Early treatment (within 3 hours) significantly reduces the risk of hemorrhage death 1, 2
Special Considerations
Traumatic Brain Injury (TBI)
- In the CRASH-3 trial, TXA reduced head injury-related death in mild and moderate head injury (RR 0.78,95% CI 0.64–0.95) but not in severe head injury 1
- TXA is cost-effective for patients with mild or moderate TBI 6
Pre-hospital Administration
- Pre-hospital TXA administration is associated with reduced mortality compared to in-hospital administration 5
- Patients receiving TXA within 1 hour of injury with a shock index <0.9 had a 65% lower likelihood of 30-day mortality 1
Potential Adverse Effects
While TXA is generally safe, clinicians should be aware of potential adverse effects:
- Most common: nausea, vomiting, diarrhea, allergic dermatitis, giddiness, hypotension 3
- Rare but serious: thromboembolic events, seizures, visual disturbances 3
- One study suggested an association between TXA and multiple organ failure in patients with fibrinolysis shutdown or hyperfibrinolysis phenotypes 7, but this finding has not altered guideline recommendations
Clinical Algorithm for TXA Administration in Trauma
- Assessment: Identify patients with severe bleeding or at risk of significant bleeding from traumatic injury
- Timing: Administer TXA as soon as possible, ideally within 1 hour and no later than 3 hours after injury
- Standard Dosing: 1g IV over 10 minutes, followed by 1g IV over 8 hours
- Monitor: Observe for adverse effects including thromboembolic events, seizures, and hypersensitivity reactions
- Avoid in patients with contraindications (active intravascular clotting, subarachnoid hemorrhage, history of thrombosis)
The evidence strongly supports the prophylactic use of TXA in all cases of severe bleeding or traumatic injury when administered within the appropriate timeframe and in the absence of contraindications.