How does Tranexamic acid (TXA) work?

From the Guidelines

Tranexamic acid (TXA) works by preventing blood clots from breaking down, which helps control bleeding, and it is recommended to be administered as soon as possible to the trauma patient who is bleeding or at risk of significant bleeding at a loading dose of 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 h 1.

Mechanism of Action

TXA functions as an antifibrinolytic agent by binding to plasminogen and blocking its conversion to plasmin, the enzyme responsible for dissolving blood clots. By inhibiting this process, TXA stabilizes existing clots and prevents excessive bleeding.

Dosage and Administration

The typical dose for trauma patients is 1 gram over 10 minutes, followed by another 1 gram over 8 hours, though dosing may vary by indication. For oral use in menorrhagia, the typical dose is 1300 mg three times daily for up to 5 days during menstruation.

Timing of Administration

TXA is most effective when given early after bleeding begins, ideally within 3 hours for trauma patients.

Side Effects

Side effects are generally mild but can include nausea, vomiting, and rarely, thromboembolic events.

Clinical Evidence

The CRASH-2 trial 1 and other studies have shown that early administration of TXA can reduce the risk of death due to bleeding in trauma patients. A meta-analysis of 216 trials (125,550 participants) found no evidence of an increased risk of thromboembolic complications associated with the use of TXA, supporting the general safety of the drug 1.

Key Points

• TXA should be administered as soon as possible to trauma patients who are bleeding or at risk of significant bleeding.
• The recommended dose is 1 g infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 h.
• TXA is most effective when given early after bleeding begins, ideally within 3 hours for trauma patients.
• Side effects are generally mild, but rare thromboembolic events can occur.

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 the dissolution of hemostatic fibrin by plasmin, which is achieved through the occupation of lysine receptor binding sites on plasmin. This prevents plasmin from binding to fibrin monomers, thereby preserving and stabilizing the fibrin matrix structure. The antifibrinolytic effects of TXA are mediated by reversible interactions at multiple binding sites within plasminogen 2.

• Key mechanism: Inhibition of fibrin dissolution by plasmin
• Main effect: Preservation and stabilization of fibrin matrix structure
• Mediated by: Reversible interactions at multiple binding sites within plasminogen

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 inhibits plasminogen activation and fibrinolysis, which contributes to its effectiveness in reducing blood loss 4.

Effective Concentration

• TXA concentrations between 10 and 15 mg/l result in substantial inhibition of fibrinolysis, although concentrations between 5 and 10 mg/l are partly inhibitory 5.
• A formulation of TXA that disperses the drug in blood and wounds can reach systemic concentrations of approximately 6 mg/L within the first hour 6.

Clinical Applications

• TXA is effective in reducing perioperative blood loss compared with placebo in a variety of surgical procedures, including cardiac surgery, total hip and knee replacement, and prostatectomy 3.
• TXA also reduces blood loss in gynaecological bleeding disorders, such as heavy menstrual bleeding, postpartum haemorrhage, and bleeding irregularities caused by contraceptive implants 3.
• TXA reduces all-cause mortality and death due to bleeding in trauma patients with significant bleeding, particularly when administered early after injury 7.

Administration Routes

• Intravenous TXA reduces death due to bleeding in patients with trauma and postpartum haemorrhage 5.
• Topical TXA formulated with self-propelling particles can inhibit fibrinolysis more effectively and may have advantages in prehospital trauma care for penetrating injury 6.