Mechanism of Tranexamic Acid in Bleeding
Tranexamic acid (TXA) is a synthetic lysine analogue that prevents bleeding by competitively blocking plasminogen's lysine-binding sites, thereby inhibiting the conversion of plasminogen to plasmin and preventing the enzymatic breakdown of fibrin clots. 1
Molecular Mechanism
TXA works through reversible interactions at multiple binding sites within the plasminogen molecule:
High-affinity binding: TXA saturates the high-affinity lysine binding site (Kd = 1.1 μmol/L) on plasminogen, which is the site involved in plasminogen's binding to fibrin. 1
Displacement from fibrin: By occupying this high-affinity site, TXA displaces plasminogen from the surface of fibrin, preventing plasmin formation at the clot site. 1
Low-affinity sites: Native plasminogen also contains 4-5 additional lysine binding sites with lower affinity for TXA (Kd = 750 μmol/L), which contribute to the overall antifibrinolytic effect. 1
Dual inhibition at high concentrations: At higher concentrations, TXA not only competitively blocks plasminogen activation but also noncompetitively inhibits plasmin itself, providing additional protection against fibrin degradation. 2
Clinical Effect on Hemostasis
The net result is preservation and stabilization of fibrin's matrix structure:
Prevention of clot dissolution: By blocking plasmin's access to fibrin monomers, TXA prevents the enzymatic breakdown of hemostatic fibrin clots that have already formed. 1, 3
No effect on clot formation: TXA does not influence platelet count, coagulation time, or various coagulation factors in concentrations up to 10 mg/mL, meaning it does not enhance clot formation—only prevents clot breakdown. 1
Prolongation of thrombin time: At therapeutic concentrations (1-10 mg/mL), TXA prolongs thrombin time as a pharmacodynamic effect. 1
Therapeutic Concentration
The effective antifibrinolytic concentration of TXA is well-established:
Target concentration: In vitro studies demonstrate that 10-15 mg/L is required to substantially inhibit fibrinolysis, though concentrations of 5-10 mg/L provide partial inhibition. 4, 5
Tissue distribution: Antifibrinolytic concentrations remain in tissues for approximately 17 hours and in serum for 7-8 hours after administration. 1
Important Caveats
TXA's mechanism creates specific clinical considerations:
Contraindication in DIC: Because TXA prevents breakdown of clots, it is contraindicated in disseminated intravascular coagulation (DIC), where it may worsen the condition by inhibiting the breakdown of widespread pathological clots. 4
Time-dependent efficacy in trauma: The drug's effectiveness depends critically on timing—it reduces bleeding mortality when given within 3 hours of injury but paradoxically increases bleeding death when given after 3 hours, likely because established clots need to be remodeled at that stage. 6
Renal excretion: TXA is primarily eliminated unchanged via glomerular filtration (>95% urinary excretion), with a plasma half-life of approximately 2 hours, requiring dose adjustment in renal impairment to avoid accumulation and toxicity. 1