Tranexamic Acid: Mechanism of Action and Clinical Indications
Tranexamic acid (TXA) is a synthetic lysine analogue that acts as an antifibrinolytic by competitively inhibiting plasminogen activation and preventing plasmin from binding to fibrin, thereby preserving and stabilizing fibrin's matrix structure to reduce bleeding.1
Mechanism of Action
- TXA occupies the lysine receptor binding sites of plasmin for fibrin, preventing binding to fibrin monomers, thus preserving and stabilizing the fibrin clot 1
- The antifibrinolytic effects are mediated by reversible interactions at multiple binding sites within plasminogen, with highest affinity for the lysine site involved in fibrin binding 1
- TXA has a plasma half-life of approximately 2 hours, with more than 95% excreted unchanged in urine 1
- Antifibrinolytic concentrations remain in tissues for about 17 hours and in serum for 7-8 hours 1
Primary Clinical Indications
Trauma-Related Hemorrhage
- Recommended for trauma patients who are bleeding or at risk of significant hemorrhage 2
- Should be administered as early as possible, ideally within 3 hours of injury 2
- Standard dosing: 1g loading dose over 10 minutes, followed by 1g infusion over 8 hours 2
- Pre-hospital administration should be considered to ensure early treatment 2, 3
- Early administration (≤1 hour from injury) significantly reduces mortality due to bleeding 2
Traumatic Brain Injury
- Reduces risk of head injury-related death when administered within 3 hours, particularly in mild to moderate TBI 2
- Most beneficial in patients with smaller baseline bleed volumes 2
Hemophilia
- FDA-approved for short-term use (2-8 days) in hemophilia patients to reduce or prevent hemorrhage during and following tooth extraction 1
Other Evidence-Based Uses
- Postpartum hemorrhage 4, 5
- Menorrhagia 4
- Surgical bleeding in various procedures (cardiac, orthopedic, abdominal, urologic, cesarean section) 4, 6
- Can reduce major bleeding by approximately 25% in surgical settings 6
Important Clinical Considerations
Timing of Administration
- Effectiveness decreases by 10% for every 15-minute delay in administration 3
- Administration after 3 hours post-injury may increase risk of death due to bleeding 2
Safety Profile
- Generally well-tolerated with most adverse reactions considered mild to moderate 7
- No significant increase in thrombotic events in trauma patients 2
- Potential increased risk of venous thrombosis in patients with gastrointestinal bleeding 5
- Higher doses associated with increased risk of seizures, particularly in cardiac surgery 2, 7
Dosing in Special Populations
- Dose adjustment needed in patients with renal impairment as blood levels increase with decreased renal function 1
Contraindications/Cautions
- Not recommended for spontaneous intracranial bleeding, subarachnoid hemorrhage, or gastrointestinal bleeding due to lack of evidence of benefit 8
TXA has become a cornerstone therapy for hemorrhage control across multiple clinical scenarios, with strongest evidence supporting its use in trauma, postpartum hemorrhage, and surgical bleeding when administered early after onset of bleeding.