What is the mechanism of action (MOA) of Tranexa (Tranexamic acid)?

Mechanism of Action of Tranexamic Acid (Tranexa)

Tranexamic acid is a synthetic lysine amino acid derivative that inhibits fibrinolysis by competitively binding to lysine receptor sites on plasminogen, preventing its binding to fibrin and thus preserving and stabilizing fibrin's matrix structure. 1

Primary Mechanism

Tranexamic acid works through several specific mechanisms:

• Plasminogen inhibition: It binds to lysine binding sites on plasminogen molecules, inhibiting the conversion of plasminogen to plasmin 1

• Fibrin preservation: By occupying the lysine receptor binding sites of plasmin for fibrin, it prevents plasmin from binding to fibrin monomers, thus preserving the fibrin clot 1

• Multiple binding interactions: The antifibrinolytic effects are mediated by reversible interactions at multiple binding sites within plasminogen:

  • 4-5 low-affinity lysine binding sites (Kd = 750 μmol/L)
  • 1 high-affinity binding site (Kd = 1.1 μmol/L) 1

• Displacement mechanism: Saturation of the high-affinity binding site displaces plasminogen from the surface of fibrin, preventing fibrin matrix dissolution even if plasmin is formed 1

Pharmacokinetics

• Distribution: Initial volume of distribution is 9-12 liters with minimal plasma protein binding (approximately 3%) 1

• Elimination: After IV administration, shows triexponential decay with terminal half-life of about 2 hours 1

• Excretion: Primarily eliminated unchanged through renal excretion (>95% excreted in urine as unchanged drug) 1

  • 90% of the drug is excreted within 24 hours after IV administration 1
  • Dose adjustment is required in patients with renal impairment 1

Clinical Applications

Tranexamic acid is effective in various bleeding conditions due to its antifibrinolytic properties:

• Trauma: Reduces mortality when administered within 3 hours of injury in bleeding trauma patients 2

• Postpartum hemorrhage: WHO strongly recommends early use (within 3 hours of birth) for women with clinically diagnosed postpartum hemorrhage 2

• Surgical bleeding: Reduces blood loss in various surgical procedures 2

Important Considerations

• Timing is critical: Maximum benefit is achieved when administered early (within 3 hours of bleeding onset) 2

• Dosing: Standard dosing is 1g loading dose over 10 minutes followed by 1g infused over 8 hours 2

• Contraindications: Use with caution in patients with renal impairment and avoid in disseminated intravascular coagulation 3

• Safety profile: Generally well-tolerated with no significant increase in thrombotic events in clinical trials 2

Clinical Pearls

• Tranexamic acid remains active in tissues for about 17 hours and in serum for 7-8 hours 1

• It does not affect platelet count, coagulation time, or various coagulation factors at therapeutic concentrations 1

• In trauma patients, limiting use only to those with confirmed hyperfibrinolysis would result in many preventable deaths - early administration to all bleeding trauma patients is recommended 4