Tranexamic Acid

Tranexamic acid is a synthetic antifibrinolytic that stops clot from breaking down. It lowers death from bleeding in trauma and in postpartum haemorrhage when given early, and it reduces blood loss in surgery, heavy menstrual bleeding, nose bleeding, and dental procedures in bleeding disorders. It is cheap and widely available in East Africa. Clots can form, so it is avoided in active thromboembolism. Giving the intravenous product into the spinal canal by mistake is fatal.

Classification. Antifibrinolytic; synthetic lysine analogue.

Mechanism. Blocks the lysine binding sites on plasminogen, preventing plasmin from attaching to fibrin and breaking down the clot.

Pharmacodynamics. Onset within minutes IV; it keeps fibrinolysis suppressed for 6 to 8 hours.

Pharmacokinetics. Oral bioavailability about 34%, unaffected by food. Half life about 2 hours. About 95% excreted unchanged by the kidneys. Low protein binding. Enters breast milk in tiny amounts.

Major trauma with significant bleeding, adult. 1 g IV over 10 minutes within 3 hours of injury, then 1 g IV over 8 hours.

Postpartum haemorrhage, adult. 1 g IV over 10 minutes (about 1 mL/minute) as soon as possible and within 3 hours of birth; give a second 1 g dose if bleeding continues after 30 minutes or restarts within 24 hours.

Heavy menstrual bleeding, adult. 1 g orally three times daily (maximum 4 g/day) for up to 4 days, starting when bleeding begins.

Bleeding in surgery, adult. 10 to 15 mg/kg IV before the incision, repeated every 6 to 8 hours, or 1 g IV before and a second 1 g IV dose after surgery in orthopaedic procedures.

Dental extraction in haemophilia, adult. 10 mg/kg IV before the procedure; then 25 mg/kg orally three times daily for 2 to 8 days; or mouthwash 4.8% (10 mL for 2 minutes, four times daily).

Epistaxis, adult. 500 mg orally three times daily for 5 days or topical 1 mL of the IV solution on a pledget.

Hereditary angioedema, adult. 1 to 1.5 g orally two to three times daily.

Children. 10 mg/kg IV (maximum 1 g) before the incision, or 10 mg/kg two to three times daily; in trauma 15 mg/kg IV (maximum 1 g) then 2 mg/kg/hour for 8 hours.

Kidney impairment (serum creatinine). 120 to 249 micromol/L: 15 mg/kg twice daily; 250 to 500 micromol/L: 15 mg/kg once daily; above 500 micromol/L: 7.5 mg/kg once daily.

Contraindications. Active venous or arterial thromboembolism; subarachnoid haemorrhage; severe kidney impairment without dose reduction; history of seizures (relative); hypersensitivity; intrathecal or epidural injection.

Warnings. Seizures at high doses (cardiac surgery); thrombosis; visual changes (stop and examine); haematuria from the upper urinary tract (clot colic and obstruction); accumulation in kidney impairment; colour vision defects; wrong route errors (the vial is stored near spinal anaesthetics, so check twice).

Adverse effects. Nausea, vomiting, diarrhoea, dizziness, hypotension with rapid IV injection, seizures, thromboembolic events, allergic reaction.

Interactions. Combined oral contraceptives: increased thrombosis risk. Prothrombin complex concentrates, factor concentrates: caution. Thrombolytics: opposed effect.

Special groups.

• Pregnancy: used in postpartum haemorrhage; use in the first trimester only when benefit outweighs risk.

• Breastfeeding: acceptable.

• Patients of African ancestry: no dose change.

• Older adults: check kidney function.

• Kidney impairment: serum creatinine 120 to 249 micromol/L, 15 mg/kg twice daily; 250 to 500 micromol/L, 15 mg/kg once daily; above 500 micromol/L, 7.5 mg/kg once daily.

• Liver impairment: no adjustment.

Formulations. Tablets 500 mg; injection 100 mg/mL (500 mg/5 mL and 1 g/10 mL); mouthwash 4.8%.

Administration. IV slowly (no faster than 1 mL/minute, or over 10 minutes for 1 g) or dilute in 0.9% sodium chloride or 5% glucose for infusion. Oral with or without food. Never give intrathecally.

Baseline. Haemoglobin, creatinine, history of thrombosis or seizures, pregnancy status, vision.

Monitoring. Bleeding and blood pressure; creatinine in prolonged courses; signs of thrombosis; vision; seizures.

Stopping. Stop when bleeding is controlled or at the end of the planned course; no taper.

Common prescribing errors. Giving it too late (benefit falls by about 10% for each 15 minutes of delay); giving it too fast IV; wrong route; full dose in kidney impairment; use in active thrombosis; using the heavy menstrual bleeding dose in a patient on combined contraceptives without review.