What is the mechanism of action of Tranexamic Acid (TXA)?

From the Guidelines

Tranexamic acid (TXA) works by preventing blood clots from breaking down, which helps control bleeding, and it should be administered as soon as possible to the trauma patient who is bleeding or at risk of significant bleeding, ideally within 3 hours after injury. The mechanism of action of TXA involves competitively inhibiting the activation of plasminogen by binding to specific sites on both plasminogen and plasmin, preventing them from attaching to fibrin, which preserves existing clots and allows new ones to form more effectively at sites of injury 1.

Key Points

• TXA is an antifibrinolytic agent that blocks the conversion of plasminogen to plasmin, the enzyme responsible for dissolving blood clots.
• The recommended dose of TXA for trauma patients is a loading dose of 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 hours, and it should be administered as soon as possible, if feasible en route to the hospital, and within 3 h after injury 1.
• TXA is most effective when given early after injury or bleeding onset, and its administration should not await results from a viscoelastic assessment 1.
• The medication works quickly, with onset within minutes when given intravenously, making it valuable for acute bleeding situations in trauma, surgery, and obstetric emergencies.
• Side effects are generally mild but can include nausea, vomiting, and rarely, thromboembolic events.

Administration and Efficacy

• TXA should be administered to all patients with trauma and significant bleeding, not just those with major hemorrhage, as it has been shown to be efficacious and safe in trauma patients 1.
• The cost-effectiveness of TXA in trauma has been calculated in several countries, and it has been found to be a cost-effective treatment option 1.
• ε-aminocaproic acid is a potential alternative to TXA if TXA is not available, but it has a potency 10-fold weaker than that of TXA and must be administered by continuous infusion to maintain therapeutic drug levels 1.

From the FDA Drug Label

Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin’s matrix structure The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen.

Tranexamic acid (TXA) works by inhibiting fibrinolysis, which is the process of breaking down blood clots. It does this by:

• Occupying lysine receptor binding sites on plasmin, preventing it from binding to fibrin monomers
• Preserving and stabilizing fibrin's matrix structure, which helps to maintain the blood clot
• Mediating antifibrinolytic effects through reversible interactions at multiple binding sites within plasminogen 2

From the Research

Mechanism of Action

• Tranexamic acid (TXA) is an antifibrinolytic agent that acts by binding to plasminogen and blocking the interaction of plasmin(ogen) with fibrin, thereby preventing dissolution of the fibrin clot 3.
• TXA exerts its antifibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen molecules 4.
• By preventing the conversion of plasminogen to plasmin, TXA reduces the breakdown of fibrin clots and decreases bleeding 3, 4.

Clinical Applications

• TXA is effective in reducing bleeding in various surgical procedures, including cardiac surgery, orthopedic surgery, and gynecological surgery 3, 5.
• TXA is also effective in reducing bleeding in patients with menorrhagia, postpartum hemorrhage, and traumatic hyphaema 3, 5.
• TXA has been shown to reduce mortality in patients suffering from trauma and postpartum hemorrhage 3, 5.

Pharmacological Properties

• TXA is generally well tolerated, with most adverse events being mild or moderate in severity 3.
• The optimal dose and timing of TXA administration are still being studied, with some indications requiring further research 5, 6.
• TXA has been reported to have anti-inflammatory activity, protect endothelial and epithelial monolayers, stimulate mitochondrial respiration, and suppress melanogenesis 7.