Mechanism of Tranexamic Acid Action on the Endometrium
Tranexamic acid reduces menstrual bleeding by inhibiting fibrinolytic enzymes directly within the endometrial tissue, specifically decreasing tissue plasminogen activator activity and plasminogen activator inhibitor-1 levels, which stabilizes the fibrin clot matrix during menstruation. 1
Direct Endometrial Effects
Tranexamic acid significantly decreases endometrial tissue plasminogen activator (tPA) activity and antigen levels at the local tissue level, which is the primary mechanism responsible for reducing menstrual blood loss. 1
The drug also reduces plasminogen activator inhibitor-1 (PAI-1) antigen levels in the endometrium, contributing to its antifibrinolytic effect during menstruation. 1
These local endometrial changes result in a 58% reduction in measured menstrual blood loss in women with dysfunctional uterine bleeding. 1
Systemic Antifibrinolytic Mechanism
Tranexamic acid is a synthetic lysine derivative that reversibly binds to plasminogen, blocking the lysine receptor binding sites and preventing plasmin from binding to fibrin monomers. 2
By occupying the high-affinity lysine binding site on plasminogen (Kd = 1.1 μmol/L), tranexamic acid displaces plasminogen from the fibrin surface, thereby preserving and stabilizing the fibrin matrix structure. 2
Although plasmin may still form through conformational changes in plasminogen, the drug prevents binding to and dissolution of the fibrin matrix, which is critical during menstruation when fibrinolytic activity is naturally elevated. 2
Clinical Relevance for Menorrhagia
The antifibrinolytic concentration of tranexamic acid remains in different tissues for approximately 17 hours and in serum for 7-8 hours, providing sustained effect throughout the menstrual period. 2
Women with dysfunctional uterine bleeding have increased fibrinolytic activity in menstrual fluid, making them particularly responsive to tranexamic acid's local endometrial effects. 1
Clinical trials demonstrate that tranexamic acid reduces menstrual blood loss by 34-59% over 2-3 cycles, which correlates directly with its inhibition of endometrial fibrinolytic enzymes. 3, 4
Important Clinical Considerations
Tranexamic acid does not affect platelet count, coagulation time, or various coagulation factors in concentrations up to 10 mg/mL, meaning its effect is purely antifibrinolytic rather than procoagulant. 2
The drug's mechanism is localized to areas of active bleeding where fibrinolysis is occurring, which explains why it effectively reduces menstrual bleeding without causing systemic thrombotic complications in most patients. 3, 4
Endometrial biopsies taken 24-36 hours after menstruation onset show measurable decreases in fibrinolytic enzyme activity following tranexamic acid treatment, confirming direct tissue-level action. 1