What is the dosage and usage of tranexamic acid for preventing or treating excessive blood loss?

Tranexamic Acid Dosing and Usage

Tranexamic acid should be administered at 1 gram IV over 10 minutes within 3 hours of bleeding onset for trauma and postpartum hemorrhage, followed by 1 gram infused over 8 hours for trauma, with timing being absolutely critical as benefit decreases by 10% for every 15-minute delay and the drug may cause harm if given beyond 3 hours. 1, 2

Critical Timing Considerations

• Do not administer tranexamic acid if more than 3 hours have elapsed since bleeding onset in trauma or postpartum hemorrhage—beyond this window, the drug increases risk of harm rather than providing benefit. 2
• Clinical diagnosis should suffice to initiate treatment; do not delay administration while waiting for laboratory confirmation or other interventions, as this reduces effectiveness. 2, 3
• The therapeutic window is narrow and time-sensitive, with efficacy declining progressively after injury or bleeding onset. 2, 3

Postpartum Hemorrhage (>500 mL vaginal delivery or >1000 mL cesarean)

• First dose: 1 gram IV over 10 minutes as soon as possible within 3 hours of birth. 1, 3
• Second dose: 1 gram IV if bleeding continues after 30 minutes OR if bleeding stops but restarts within 24 hours of the first dose. 1, 3
• The American College of Obstetricians and Gynecologists recommends tranexamic acid as part of standard treatment packages, not reserved as rescue therapy when uterotonics fail. 3
• Do not withhold the second dose if bleeding persists or recurs—this is part of the standard protocol. 2, 3

Major Trauma (including mild to moderate TBI)

• Loading dose: 1 gram IV over 10 minutes within 3 hours of injury. 1, 2
• Maintenance: 1 gram IV infused over 8 hours OR 2 grams IV over 20 minutes as single bolus within 3 hours. 1, 2
• Pediatric trauma: 15 mg/kg loading dose (maximum 1 gram) over 10 minutes, followed by 2 mg/kg/hour infusion until bleeding controlled. 1, 2

Major Surgery

Non-Cardiac Surgery

• 1 gram IV over 10 minutes prior to skin incision and again at end of surgery. 1

Cardiac Surgery

• 50-100 mg/kg IV over 30 minutes after induction of anesthesia. 1
• Maximum total dose should not exceed 100 mg/kg, especially in patients over 50 years of age, due to risk of neurotoxicity at higher doses. 4

Orthopedic Surgery

• 1 gram IV over 10 minutes prior to skin incision. 1
• Alternative validated regimen: 10-15 mg/kg bolus followed by 1-5 mg/kg/hour infusion (the Horrow regimen achieves therapeutic plasma levels of 10 μg/mL needed to inhibit fibrinolysis). 5, 2

Heavy Menstrual Bleeding (Oral Formulation)

• 3.9 grams daily (typically 1.3 grams three times daily) for up to 5 days during menstruation. 2, 6
• Treatment reduces menstrual blood loss by 26-60% and is more effective than NSAIDs, etamsylate, or luteal phase progestins. 6, 7
• The levonorgestrel-releasing intrauterine system is more effective than tranexamic acid but may cause amenorrhea and intermenstrual bleeding that some patients find unacceptable. 6, 7

Hemophilia-Related Dental Procedures (FDA-Approved Indication)

• Before extraction: 10 mg/kg IV immediately before tooth extraction. 8
• After extraction: 10 mg/kg IV 3-4 times daily for 2-8 days. 8
• Infuse no more than 1 mL/minute to avoid hypotension. 8

Renal Impairment Dosing Adjustments

• Serum creatinine 1.36-2.83 mg/dL (120-250 micromol/L): 10 mg/kg twice daily. 8
• Serum creatinine 2.83-5.66 mg/dL (250-500 micromol/L): 10 mg/kg once daily. 8
• Serum creatinine >5.66 mg/dL (>500 micromol/L): 10 mg/kg every 48 hours OR 5 mg/kg every 24 hours. 8
• Dose reduction applies to all indications in patients with renal dysfunction. 5, 3

Absolute Contraindications

• Active intravascular clotting or thromboembolic disease. 8
• History of thrombosis or thromboembolism (considered contraindication in the United States). 2, 3, 8
• Subarachnoid hemorrhage—tranexamic acid may cause cerebral edema and cerebral infarction in this population. 8
• Severe hypersensitivity to tranexamic acid. 8

Critical Safety Warnings

• Avoid concomitant use with pro-thrombotic agents including Factor IX concentrates, anti-inhibitor coagulant concentrates, and hormonal contraceptives, as this increases thrombotic risk. 2, 8
• FOR INTRAVENOUS USE ONLY—inadvertent intrathecal administration has caused seizures and cardiac arrhythmias. 8
• Tranexamic acid should be used with extreme caution in patients taking oral contraceptives due to compounded thrombotic risk. 5
• Discontinue tranexamic acid 5 days before high bleeding risk procedures or surgery in confined spaces. 5

Gastrointestinal Bleeding

• Not recommended for gastrointestinal bleeding. 1
• While older literature suggested benefit in upper GI bleeding with mortality reductions of 5-54%, current guidelines do not recommend its use in this setting. 1, 9

Administration Considerations

• Infusion rate should not exceed 1 mL/minute to prevent hypotension. 8
• May be mixed with electrolyte solutions, carbohydrate solutions, amino acid solutions, and dextran solutions; heparin may be added. 8
• Should NOT be mixed with blood or penicillin-containing solutions. 8
• Diluted mixture may be stored up to 4 hours at room temperature. 8

Mechanism and Pharmacokinetics

• Tranexamic acid is a synthetic lysine analogue that competitively inhibits plasminogen and plasmin, preventing fibrin degradation and stabilizing blood clots. 5, 3, 10
• Plasma half-life is approximately 120 minutes, requiring multiple daily doses or continuous infusion to maintain therapeutic levels. 5
• Therapeutic plasma concentration of 10 μg/mL is required to inhibit fibrinolysis effectively. 5, 2