Tranexamic Acid

Mechanism

Pharmacological Class and Group

Synthetic antifibrinolytic hemostatic drug. Competitive inhibitor of plasminogen activation (synthetic analogue of the amino acid lysine).

Mechanism of Action

Tranexamic acid stops the degradation of the fibrin network of blood clots by blocking the anchoring sites of the enzyme plasmin:

Fibrin Clot Stabilization Mechanism

1. Covalent Binding to the Lysine Sites of Plasminogen: Binds selectively, competitively and reversibly to the lysine-binding "Kringle" structural domains of the plasminogen molecule and the active enzyme plasmin.

2. Blocking Fibrin Adhesion: By occupying these sites, it physically prevents plasminogen or plasmin from binding to the insoluble lysine residues of the fibrin mesh of the local hemostatic clot.

3. Inhibition of Fibrinolysis: Since active plasmin cannot anchor to fibrin, the hydrolytic degradation of the protein mesh by plasmin is completely stopped, preventing the dissolution of the newly formed clot:

Tranexamic Acid Binding of Plasmin to Fibrin Support of the local coagulation network

4. Reduction of the Vascular Inflammatory Response: By inhibiting the activation of plasmin, it indirectly decreases the activation of the complement cascade and the kinin system (bradykinin), limiting local vascular edema.

Pharmacokinetics

High Resolution Pharmacokinetics

• Oral Bioavailability: Moderate, between 30% and 50% after ingestion. It is not significantly altered by the consumption of common foods in the diet.
• Distribution: Rapid diffusion to the extravascular spaces and mucosa of the airway. It minimally crosses the blood-brain barrier with healthy meninges. Low binding to circulating plasma proteins (<3%, does not bind to albumin in a relevant way).
• Metabolism: Marginal hepatic metabolism (less than 5%), it is actively eliminated.
• Excretion: Predominant renal excretion (more than 95% of the absorbed drug is eliminated unchanged by glomerular filtration in the urine).
• Half-life (t_1/2): Plasma terminal elimination half-life of approximately 2 to 3 hours.

Indicators and dose

Clinical Indications and Off-Label Uses

• Refractory Previous or Posterior Epistaxis: Immediate topical treatment (using anterior nasal packing soaked in the injectable solution) or intravenous/oral systemic treatment in patients with persistent bleeding from the nasal passages refractory to cauterization of the vessels.
• Post-Adenotonsillectomy Hemorrhage (Tonsillectomy): Prevention and pharmacological control of intraoperative or late bleeding in the inflamed tonsillar bed (the oral cavity and saliva have high levels of tissue plasminogen activator, favoring rapid fibrinolysis).
• Major Endoscopic Nasosinusal Surgery (FESS): Reduction of local capillary bleeding in the intraoperative surgical field, facilitating the specialist's anatomical visualization and reducing intervention time.

Dosage and Clinical Adjustment

Management of Previous / Posterior Epistaxis:

• Emergency Local Topical Application: Soak a polyvinyl alcohol gauze or nasal plug with the solution of 500 mg to 1000 mg of pure tranexamic acid (1 or 2 injectable ampoules), introducing it firmly into the bleeding nostril for a minimum of 15-20 minutes.
• Adjuvant Systemic Route (Adults): 1 g (1000 mg) by slow intravenous route every 8 hours (diluted in 100 mL of SF, to be administered in 20 minutes), or 1 g to 1.5 g orally every 8 hours in stable phases for a period of 3 to 5 continuous days.

Surgical Prophylaxis in FESS (Adults):

• Administration of a single dose of 10 mg/kg to 15 mg/kg by slow intravenous route, administered 20 to 30 minutes prior to the start of the sinonasal surgical incision.

Mandatory Adjustment in Renal Failure:

• eGFR 30 to 50 mL/min/1.73 m²: Administer 50% of the recommended standard dose, or the usual dose divided every 12 hours instead of every 8 hours.
• eGFR 10 to 29 mL/min/1.73 m²: Administer 25% of the usual maintenance dose, or the standard dose divided every 24 hours.
• eGFR < 10 mL/min/1.73 m²: Contraindication for systemic use.

Security

Absolute and Relative Contraindications

Absolute Contraindications

• Known hypersensitivity to tranexamic acid or related compounds.
• History or presence of acute venous thromboembolism: Deep vein thrombosis (DVT), active pulmonary embolism or history of arterial thrombotic events (ischemic stroke, recent acute myocardial infarction).
• Presence of active subarachnoid hemorrhage (the drug can aggravate cerebral edema or induce vasospasm).
• Severe terminal chronic kidney disease without dialysis (extreme accumulation due to lack of clearance).

Relative Contraindications

• Moderate chronic kidney disease (requires proportional dose reduction based on serum creatinine).
• Concomitant use of combined hormonal contraceptives (estrogens synergistically increase the risk of systemic thromboembolism).

Adverse Effects (ADR) and Specific Toxicity

• Frequent (1%-10%): Transient gastrointestinal disorders after oral intake (nausea, vomiting, watery diarrhea, gastric heartburn), headache.
• Uncommon (0.1%-1%): Transient arterial hypotension (usually associated with a rapid intravenous infusion rate of the injectable ampoule), orthostatic dizziness, morbilliform skin rash.
• Rare (0.01%-0.1%): Systemic Thrombotic Events (deep vein thrombosis, lung embolism, acute retinal arterial occlusion), color vision alterations such as temporary chromatopsia.
• Very rare (<0.01%): Generalized seizures due to stimulation of cortical GABA receptors (associated with accidental massive overdoses).

Rapid Intravenous Infusion Alert: Avoid Sudden Hypotension

Rapid intravenous administration of tranexamic acid (as an undiluted direct bolus or in less than 5 minutes) can cause acute reflex systemic vasodilation, inducing a picture of profound severe arterial hypotension, dizziness, diaphoresis and transient syncope. The prescribed intravenous dose of tranexamic acid should always be diluted in 50-100 mL of sterile physiological solution or 5% dextrose, and administered as a slow intravenous infusion over a minimum period of 15 to 20 continuous minutes.

Drug Interactions of Clinical Relevance

• Prothrombin Concentrate Complex or Recombinant Factor VIIa: They drastically increase the systemic procoagulant potential, and can induce massive arterial or venous thrombotic events that are difficult to control.
• Combined Oral Contraceptives (High-Dose Estrogens): They synergistically increase the synthesis of hepatic coagulation factors, increasing the risk of thromboembolic events. Avoid prolonged systemic use of tranexamic acid.

Safety in Pregnancy and Breastfeeding

• Pregnancy: Compatible. It crosses the placental barrier reaching umbilical cord concentrations similar to maternal concentrations, but retrospective studies suggest reproductive safety. It is reserved exclusively for severe nasal or oropharyngeal hemorrhages that directly threaten the mother's stability.
• Breastfeeding: Compatible. It is excreted in human milk in extremely low concentrations (less than 1% of the maternal plasma dose), being considered of no risk to the infant.