What is the use and dosage of Tranexamic acid (TXA) in clinical scenarios?

Tranexamic Acid: Clinical Uses and Dosing Guidelines

Tranexamic acid (TXA) is strongly recommended for early administration in trauma-related bleeding, postpartum hemorrhage, and surgical procedures with significant bleeding risk, with specific dosing regimens tailored to each clinical scenario.

Mechanism of Action

• TXA is a synthetic lysine analogue that competitively inhibits plasminogen activation, preventing fibrinolysis and stabilizing blood clots 1
• It has a plasma half-life of approximately 120 minutes and is distributed throughout all tissues 2

Major Clinical Indications and Dosing

Trauma-Related Hemorrhage

• For trauma patients with significant bleeding or at risk of hemorrhage: administer 1 g IV over 10 minutes, followed by 1 g IV over 8 hours 2
• TXA must be given within 3 hours of injury, as effectiveness decreases by 10% for every 15-minute delay 2
• No benefit is observed when administered beyond 3 hours post-injury, and late administration may be potentially harmful 2
• Consider administration en route to hospital for optimal timing 2

Postpartum Hemorrhage

• For clinically diagnosed postpartum hemorrhage: administer 1 g IV over 10 minutes within 3 hours of birth 2
• Give a second dose of 1 g IV if bleeding continues after 30 minutes or restarts within 24 hours 2
• Indicated for all cases of postpartum hemorrhage (>500 mL after vaginal birth or >1000 mL after cesarean section, or any blood loss compromising hemodynamic stability) 2
• Should be given regardless of bleeding cause (uterine atony, genital tract trauma, etc.) 2

Hemophilia and Dental Procedures

• For patients with hemophilia undergoing tooth extraction: administer 10 mg/kg IV immediately before extraction 3
• Infuse at no more than 1 mL/minute to avoid hypotension 3
• Continue with 10 mg/kg IV 3-4 times daily for 2-8 days post-extraction 3

Menorrhagia

• TXA is effective for reducing menstrual blood loss in women with menorrhagia 1
• Use with caution in patients taking oral contraceptives due to increased thrombotic risk 4

Dosage Adjustments for Renal Impairment

• TXA is primarily excreted by the kidneys, requiring dose adjustment in renal dysfunction 4, 3
• Recommended dosing based on serum creatinine levels 3:
  • 1.36-2.83 mg/dL: 10 mg/kg twice daily
  • 2.83-5.66 mg/dL: 10 mg/kg daily

  • 5.66 mg/dL: 10 mg/kg every 48 hours or 5 mg/kg every 24 hours

Contraindications and Precautions

• Absolute contraindications 3:

  • Subarachnoid hemorrhage (risk of cerebral edema and infarction)
  • Active intravascular clotting
  • Disseminated intravascular coagulation (DIC)
  • Severe hypersensitivity to TXA or its ingredients

• Use with caution in 4, 3:

  • Patients with history of thromboembolic disease
  • Patients taking prothrombotic medications
  • Patients with massive hematuria (risk of ureteric obstruction)
  • Renal dysfunction (increased risk of neurotoxicity and ocular toxicity)

Administration Considerations

• TXA is for intravenous use only; serious adverse reactions including seizures and cardiac arrhythmias have occurred with inadvertent intrathecal administration 3
• For IV infusion, TXA may be mixed with most solutions (electrolyte, carbohydrate, amino acid, and dextran solutions) 3
• Do not mix with blood or solutions containing penicillin 3
• If surgery is planned, consider discontinuing TXA 5 days before high bleeding risk procedures or surgery in confined spaces 4

Efficacy and Safety Profile

• TXA reduces mortality in trauma patients with bleeding by approximately 15% when given within 3 hours 2, 5
• In postpartum hemorrhage, early TXA administration reduces death due to bleeding by about 31% 6
• Despite theoretical concerns, clinical trials have not demonstrated increased risk of thrombotic events with appropriate TXA use 2, 6
• Most common adverse effects include nausea, vomiting, diarrhea, and dizziness 3