What is tranexamic acid?

What is Tranexamic Acid?

Tranexamic acid is a synthetic antifibrinolytic medication that prevents blood clot breakdown by blocking plasminogen's binding sites, thereby stabilizing fibrin and reducing bleeding in conditions involving excessive fibrinolysis. 1

Chemical Structure and Formulation

• Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, a synthetic derivative of the amino acid lysine, appearing as a white crystalline powder 1
• The intravenous formulation contains 100 mg tranexamic acid per mL in sterile water for injection, with a pH of 6.5 to 8.0 1

Mechanism of Action

• Tranexamic acid works by reversibly binding to plasminogen at multiple lysine receptor sites, preventing plasmin from binding to and dissolving fibrin clots 1
• The drug has particular affinity for plasminogen's high-affinity lysine binding site (Kd = 1.1 μmol/L), which is critical for plasminogen's attachment to fibrin 1
• An antifibrinolytic concentration of approximately 10 μg/mL is required to effectively inhibit fibrinolysis in patients with abnormal bleeding due to local or systemic hyperfibrinolysis 2, 3
• By occupying these binding sites, tranexamic acid displaces plasminogen from the fibrin surface, preventing the formation of plasmin and subsequent clot dissolution while preserving the fibrin matrix structure 1

Pharmacokinetics

• The initial volume of distribution is 9 to 12 liters, with only about 3% plasma protein binding at therapeutic levels 1
• The drug exhibits a triexponential decay pattern with a terminal elimination half-life of approximately 2 hours 1
• Tranexamic acid is primarily eliminated unchanged through the kidneys via glomerular filtration, with renal clearance equal to plasma clearance (110-116 mL/min) 1
• More than 95% of the dose is excreted unchanged in urine, with approximately 90% eliminated within 24 hours after intravenous administration 1
• An antifibrinolytic concentration remains in tissues for about 17 hours and in serum for 7-8 hours 1

FDA-Approved Indications

• Tranexamic acid is FDA-approved for patients with hemophilia undergoing tooth extraction, used for 2-8 days to reduce or prevent hemorrhage and decrease the need for replacement therapy 1

Evidence-Based Clinical Applications Beyond FDA Approval

• Postpartum hemorrhage: WHO 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
• Trauma-related bleeding: The American College of Critical Care recommends tranexamic acid for trauma patients who are bleeding or at risk of significant hemorrhage, with administration as early as possible within 3 hours of injury 5
• Surgical bleeding: Tranexamic acid reduces blood loss and transfusion requirements across multiple surgical specialties including cardiac surgery, orthopedic procedures, and gynecologic surgery 5, 6

Standard Dosing Protocol

• The evidence-based dosing regimen is 1 gram IV over 10 minutes (loading dose), followed by 1 gram infusion over 8 hours (maintenance dose) 4, 5
• For postpartum hemorrhage specifically, a second 1 gram dose should be given if bleeding continues after 30 minutes or restarts within 24 hours 4
• Dose adjustment is required in renal impairment, as tranexamic acid accumulates when kidney function is reduced 1, 5

Critical Timing Considerations

• Early administration (within 1 hour of bleeding onset) provides maximum benefit, reducing bleeding death by 32% in trauma patients 5
• Efficacy decreases by 10% for every 15-minute delay in administration 4, 5
• Administration after 3 hours may paradoxically increase the risk of death due to bleeding and should be avoided 5, 7

Safety Profile

• Large-scale meta-analyses involving over 125,550 participants demonstrate no increased risk of thromboembolic complications (myocardial infarction, stroke, DVT, pulmonary embolism) when used appropriately 5
• The most common adverse events are mild gastrointestinal symptoms including nausea, vomiting, and diarrhea 1, 6
• Higher doses (≥4g/24h) are associated with increased seizure risk, particularly in cardiac surgery 5

Absolute Contraindications

• Active intravascular clotting or disseminated intravascular coagulation (DIC), as inhibiting fibrinolysis in widespread clot formation can worsen the condition 5, 2, 3
• Severe hypersensitivity reactions to tranexamic acid 5
• Concomitant use with activated prothrombin complex concentrate (aPCC) in patients with acquired hemophilia 5

High-Risk Situations Requiring Caution

• Massive hematuria: Risk of ureteric obstruction from preventing clot breakdown in the urinary tract 5, 2
• Patients on oral contraceptive pills: Increased thrombosis risk when combined with hormonal contraceptives 5, 1
• Post-stroke patients: Thrombotic concerns warrant extreme caution 5
• High-dose use (≥4g/24h) in critically ill patients with gastrointestinal bleeding increases DVT, PE, and seizure risk without mortality benefit 5

Important Clinical Pitfalls

• Do not delay administration waiting for laboratory results or viscoelastic assessment, as early treatment is critical for efficacy 5
• Do not use tranexamic acid as a substitute for surgical hemostasis or definitive bleeding control measures 5
• Always assess renal function before dosing, as accumulation occurs in renal impairment requiring dose reduction 1, 5
• Advise patients to use non-hormonal contraceptive methods during treatment due to increased thrombotic risk with hormonal contraceptives 1