Mechanism of Action of Tranexamic Acid
Tranexamic acid is a synthetic lysine derivative that competitively inhibits plasminogen activation, preventing its conversion to plasmin and thereby blocking the enzymatic breakdown of fibrin clots. 1
Molecular Mechanism
TXA works by reversibly binding to lysine binding sites on plasminogen molecules, physically blocking plasmin's ability to bind to and dissolve fibrin. 1, 2
Plasminogen contains 4-5 low-affinity lysine binding sites (Kd = 750 μmol/L) and one high-affinity binding site (Kd = 1.1 μmol/L) for TXA. 1
The high-affinity lysine site is critical because it mediates plasminogen's binding to fibrin—when TXA saturates this site, it displaces plasminogen from the fibrin surface. 1
Even if plasmin forms through conformational changes in plasminogen, TXA prevents it from binding to and dissolving the fibrin matrix, thereby preserving clot stability. 1, 3
Pharmacodynamic Effects
An antifibrinolytic concentration of approximately 10 μg/mL is required to effectively inhibit fibrinolysis, which is clinically relevant for patients with abnormal bleeding due to local or systemic hyperfibrinolysis. 4, 5
TXA at concentrations of 1-10 mg/mL prolongs thrombin time but does not affect platelet count, coagulation time, or various coagulation factors in whole blood. 1
The antifibrinolytic effect persists in different tissues for approximately 17 hours and in serum for 7-8 hours. 1
Clinical Relevance of the Mechanism
This antifibrinolytic mechanism makes TXA particularly effective in trauma-related bleeding, where accelerated fibrinolysis contributes to ongoing hemorrhage. 2, 4
The drug reduces blood loss by inhibiting the enzymatic breakdown of fibrin rather than by promoting clot formation, which explains its relatively favorable safety profile regarding thrombotic risk in most clinical contexts. 6, 7
TXA's mechanism requires direct contact with the bleeding site or adequate systemic concentrations—this is why timing of administration matters significantly, with efficacy declining after 3 hours post-injury when fibrinolysis is most active. 2
Important Mechanistic Cautions
TXA is absolutely contraindicated in disseminated intravascular coagulation (DIC) because inhibiting fibrinolysis in the setting of widespread clot formation can worsen the condition by preventing breakdown of pathologic clots. 4, 5
The mechanism also explains why TXA should not be used in massive hematuria—preventing clot breakdown in the urinary tract can cause ureteric obstruction. 5
Plasma protein binding is minimal (about 3%) and is fully accounted for by binding to plasminogen, with no albumin binding. 1
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