What is tranexamic acid and what are its indications?

What is Tranexamic Acid and What is it Used For?

Tranexamic acid is a synthetic lysine analogue that works as an antifibrinolytic agent by competitively inhibiting plasmin and plasminogen, thereby preventing the breakdown of blood clots and reducing bleeding. 1, 2

Mechanism of Action

Tranexamic acid (trans-4-aminomethylcyclohexane-1-carboxylic acid) functions by binding to plasminogen and blocking its interaction with fibrin, which prevents dissolution of fibrin clots. 1, 3 The drug requires a concentration of approximately 10 μg/mL to effectively inhibit fibrinolysis. 1, 2 It is distributed throughout all tissues and has a plasma half-life of 120 minutes. 1

The antifibrinolytic mechanism makes TXA particularly effective in trauma-related bleeding where accelerated fibrinolysis contributes to ongoing hemorrhage, though the drug requires direct contact with the bleeding site or adequate systemic concentrations for effectiveness. 2

Primary Clinical Indications

Trauma and Major Hemorrhage

Tranexamic acid should be administered to all trauma patients who are bleeding or at risk of significant hemorrhage, with a loading dose of 1g IV over 10 minutes followed by 1g infusion over 8 hours, but only if treatment can be initiated within 3 hours of injury. 4

The landmark CRASH-2 trial involving over 20,000 patients demonstrated that TXA reduces all-cause mortality by 9% (relative risk 0.91) and bleeding-related death by 15% (relative risk 0.85). 4 Early administration (≤1 hour from injury) reduces bleeding death by 32% (relative risk 0.68), with efficacy decreasing by 10% for every 15-minute delay. 4 Administration after 3 hours may paradoxically increase bleeding death risk (relative risk 1.44). 4

Postpartum Hemorrhage

The World Health Organization strongly recommends early intravenous tranexamic acid (within 3 hours of birth) for all women with clinically diagnosed postpartum hemorrhage, regardless of whether bleeding is due to genital tract trauma or uterine atony. 4 A second dose of 1g IV should be administered if bleeding continues after 30 minutes or restarts within 24 hours. 4

Surgical Applications

Tranexamic acid is indicated for patients undergoing major surgery at high risk of significant bleeding, including cardiac surgery, orthopedic arthroplasty, and other major non-cardiac procedures. 4 A meta-analysis of 216 trials (125,550 participants) demonstrated safety and efficacy in reducing bleeding and transfusion requirements. 4

For orthopedic surgery, specifically femur fractures, TXA should be administered to all patients undergoing surgery, with 1 gram IV at the start of the surgical case prior to incision. 4

Hemophilia-Related Dental Procedures

The FDA-approved indication is for patients with hemophilia undergoing tooth extraction, using 10 mg/kg actual body weight IV before extraction, then 10 mg/kg 3-4 times daily for 2-8 days post-extraction. 5 Infusion should not exceed 1 mL/minute to avoid hypotension. 5

Other Indications

• Heavy menstrual bleeding: TXA reduces menstrual blood loss by 34-57.9% compared to placebo. 6
• Upper gastrointestinal bleeding (with caution): Meta-analysis showed 40% reduction in mortality, though high-dose IV TXA (≥4g/24h) should NOT be used in critically ill patients with GI bleeding due to increased DVT, PE, and seizure risk. 4
• Hereditary angioneurotic edema: Clinical benefit has been reported. 6

Standard Dosing Protocol

The evidence-based standard dosing regimen across most indications is 1g IV over 10 minutes (loading dose) followed by 1g infusion over 8 hours (maintenance). 1, 4 This regimen is derived from trauma guidelines and has been validated across surgical specialties. 4

For procedures expected to exceed 2-3 hours, the maintenance infusion should be continued. 4

Critical Contraindications

Absolute contraindications include: 5, 4

• Subarachnoid hemorrhage (risk of cerebral edema and infarction) 5
• Active intravascular clotting or disseminated intravascular coagulation (DIC) 5, 2
• Severe hypersensitivity reactions to tranexamic acid 5
• Concomitant use with activated prothrombin complex concentrate (aPCC) in acquired hemophilia 4

Relative contraindications requiring extreme caution: 4

• Massive hematuria (risk of ureteric obstruction from clot retention)
• Patients on oral contraceptive pills (increased thrombosis risk)
• Post-stroke patients

Renal Impairment Considerations

Tranexamic acid is renally excreted with approximately 90% recovered in urine within 24 hours, requiring dose adjustment in renal impairment to prevent drug accumulation and neurotoxicity. 4, 5 Creatinine clearance should be calculated before administration, with proportional dose reduction for any degree of renal impairment. 4

Safety Profile

No increased risk of arterial or venous thrombotic events has been demonstrated in over 8,000 patients receiving lysine analogues like tranexamic acid in appropriate bleeding scenarios. 4 A meta-analysis of 216 trials including 125,550 participants found no evidence of increased thromboembolic complications (risk difference = 0.001; 95% CI, -0.001 to 0.002; P = 0.49). 4

However, the HALT-IT trial demonstrated an almost two-fold rise in venous thrombo-embolic events when TXA was used in cirrhosis patients with suspected variceal hemorrhage. 4

Higher doses of TXA (≥4g/24h or >100mg/kg in cardiac surgery) are associated with increased seizure risk. 4

Key Clinical Pitfalls to Avoid

• Never delay TXA administration beyond 3 hours in acute bleeding scenarios - efficacy drops dramatically and harm may occur. 4
• Do not use TXA as a substitute for definitive bleeding control - it is an adjunct to surgical hemostasis, not a replacement. 4
• Avoid high-dose regimens (≥4g/24h) in critically ill patients with GI bleeding - increased thrombotic and seizure risk without mortality benefit. 4
• Always assess renal function before administration - failure to adjust dose in renal impairment leads to accumulation and toxicity. 4, 5
• FOR INTRAVENOUS USE ONLY - inadvertent neuraxial injection may result in seizures. 5