Epistemis

Tranexamic Acid

  • Antifibrinolytics

Synthetic Fibrinolysis Inhibitor (e.g. *Amchafibrin*).

Mechanism

Mechanism of Action

Tranexamic acid is a synthetic amino acid derived from aminomethylcyclohexanecarboxylic acid that acts by inhibiting the physiological dissolution of fibrin clots.

Molecular Mechanism of Fibrin Stabilization

1. Plasminogen and active plasmin are anchored to fibrin networks by specific lysine-rich domains ("Kringle" domains).
2. Tranexamic Acid is a synthetic structural analogue of the amino acid lysine.
3. It binds competitively and highly selectively to the lysine binding sites located on the plasminogen molecule, blocking the interaction of the enzyme with the lysine of fibrin.
4. This interaction prevents the activation of plasminogen and the enzymatic action of free plasmin on stable fibrin bonds.
5. The net result is the stabilization of the pre-existing hemostatic clot, reducing blood loss in hemorrhage foci without altering the extrinsic or intrinsic coagulation cascade.

Pharmacokinetics

Pharmacokinetics

  • Routes of administration: Slow intravenous, oral, topical.
  • Bioavailability (F): Orally it is approximately 35% to 50%, not being altered by the presence of food.
  • Distribution: Excellent tissue diffusion; It rapidly penetrates synovial fluid, bronchial mucus, saliva and seminal fluid. It crosses the blood-brain barrier, reaching therapeutic concentrations in the cerebrospinal fluid. The apparent volume of distribution is about 9 to 12 L.
  • Metabolism: Negligible metabolism, less than 3% of the total dose.
  • Excretion: Predominantly unchanged renal excretion by direct glomerular filtration (> 95% of the intravenous dose is actively eliminated in urine).
  • Half-life (t1/2): Approximately 2 to 3 hours in subjects with preserved renal function. It is significantly prolonged in severe renal failure.

Indicators and dose

Indications

  • Prevention and treatment of bleeding associated with generalized or local hyperfibrinolysis (digestive, gynecological bleeding such as severe primary or IUD-induced menorrhagia).
  • Reduction in mortality from hemorrhagic shock in patients with severe trauma with significant active bleeding in the first 3 hours post-event (CRASH-2 trial protocol).
  • Prevention of bleeding and reduction of transfusion requirements in major orthopedic (hip/knee) or aortocoronary bypass surgery.
  • Refractory postpartum hemorrhage (WOMAN trial).
  • Off-label use: Adjuvant treatment in refractory epistaxis (topical use), chronic recurrent hereditary angioedema and cutaneous melasma (low doses).

Precision Renal Dosing and Adjustment

  • Standard hemostatic treatment: 1 g to 1.5 g orally every 8 hours; or 1 g slowly intravenously administered at a minimum interval of 10 to 15 minutes (avoid rapid infusion due to risk of transient severe hypotension).
  • Trauma Protocol (CRASH-2): 1 g IV infused over 10 minutes (started within the first 3 hours of injury), followed by a continuous infusion of 1 g IV regulated over an 8-hour interval.
  • Mandatory renal adjustment according to serum creatinine or ClCr:
Creatinine Clearance (ClCr)Intravenous Dose of Tranexamic AcidDose Frequency
> 50 mL/min10 mg/kg to 15 mg/kgEvery 8 hours (standard dose)
30 - 50 mL/min10 mg/kgEvery 12 hours
10 - 29 mL/min10 mg/kgEvery 24 hours
< 10 mL/min5 mg/kgEvery 24 to 48 hours (or avoid use)

Pregnancy and Breastfeeding

FDA Category B. It freely crosses the placenta, reaching similar concentrations in the umbilical cord. Although there are no teratogenic effects reported in preclinical trials, its administration should be reserved exclusively for severe obstetric hemorrhages where the direct therapeutic benefits far exceed the risks of the maternal-fetal binomial. It is minimally excreted in breast milk and is compatible with low-risk breastfeeding.

Security

Contraindications

Absolute
  • Hypersensitivity to tranexamic acid.
  • Personal history or active suspicion of acute venous or arterial thrombosis (DVT, PE, ischemic stroke or active coronary artery thrombosis).
  • Active subarachnoid hemorrhage due to risk of induction of reactive ischemic vasospasm and cerebral edema.
  • Severe non-dialyzed renal failure (due to critical risk of systemic accumulation and neurotoxicity).
  • History of recurrent seizures of any etiology.
Relative
  • Macroscopic upper tract uria (high risk of acute ureteral obstruction due to intraluminal coagulation in the renal pelvis).
  • Concomitant use of combined oral hormonal contraceptives.

Adverse Effects (ADR)

  • Seizures: Severe ADR, typically associated with the administration of high intravenous doses (> 2-3 g) or after cardiac bypass surgery. Tranexamic acid acts as an antagonist of gamma-aminobutyric acid (GABA-A) and glycine receptors in the cerebral cortex, inducing neuronal hyperexcitability and generalized clonic seizures.
  • Transient visual alterations: Chromatopsia or blurred vision; The drug should be discontinued if they persist or worsen.
  • Gastrointestinal effects: Mild nausea, vomiting, and diarrhea (mainly oral).
  • Low-frequency arterial or venous thrombotic events.

Interactions

Avoid combined administration with recombinant active factor VIIa or prothrombin complex concentrates due to increased synergistic risk of induction of massive thrombosis. Simultaneous use with combined oral hormonal contraceptives exponentially increases the prothrombotic potential.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousAlteplase (rt-PA) / Tenecteplase
System
Hematology
Cluster
Antifibrinolytics
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