Tranexamic Acid

To prevent bleeding due to fibrinolysis after surgery or trauma (cardiac surgery with and without cardiopulmonary bypass; liver transplantation; orthopedic surgery including spine; GU surgery; peripartum hemorrhage). Bleeding can be diagnosed clinically or via lab tests (prolonged thrombin time, reduced fibrinogen levels, increased d -dimer levels, classic teardrop shape on thromboelastography).

Antifibrinolytic choice in cardiac surgery has shifted from aprotinin to TXA and epsilon-aminocaproic acid (ɛ-ACA) owing to the concern that aprotinin may be associated with an increased risk of cardiovascular or cerebrovascular events, renal dysfunction, or renal failure.

TXA in 6% hydroxyethyl starch 130/0.4 prime solution decreases blood loss and chest tube drainage in CABG with no renal or postop complications.

The reduction of blood loss in orthopedic surgery is of great importance, especially in hip or knee arthroplasty and spinal surgery. TXA administered at 10–15 mg/kg IV reduces blood loss, reduces relative risk of transfusion, and poses no increased risk of thromboembolism.

Effective in reducing periop blood loss and transfusion requirements in neonates and children undergoing craniosynostosis reconstruction surgery and repair of congenital heart defects.

TXA application in trauma is supported by firm clinical evidence. IV loading of 1 g TXA within 8 h of trauma then followed by IV infusion of 1 g TXA over 8 h significantly reduced all-cause mortality and death due to bleeding.

PPH is a major cause of maternal mortality. TXA is used as a complement to uterotonics and appears to be a promising drug for the prevention and treatment of PPH after both vaginal and cesarean delivery.

Used to reduce placental bleeding and conization of the cervix.

For short-term use (2–8 d) in pts with hemophilia or von Willebrand disease to reduce or prevent hemorrhage and to reduce the need for replacement therapy during and following tooth extraction.

To treat primary menorrhagia, gastric and intestinal hemorrhage, urinary tract bleeding, recurrent epistaxis, and hereditary angioneurotic edema. The drug also inhibits induced hyperfibrinolysis during thrombolytic treatment with plasminogen activators.

Used in pts with hemophilia or those receiving anticoagulation who are about to undergo oral surgery.

Side effects: N/V, diarrhea, and abdominal pain are the most common adverse effects (in approximately 30% of pts with oral use).

Giddiness has been reported.

Hypotension (if the drug is injected too rapidly).

Potential for thrombotic complications secondary to the inhibition of fibrinolysis

A synthetic lysine analogue. Prevents plasmin formation and therefore fibrinolysis by occupying plasminogen’s lysine-binding site for fibrin.

Has a structure similar to that of lysine and reversibly binds to lysine-binding sites for fibrin on plasminogen, thereby blocking the binding of plasminogen to fibrin. Plasminogen activators are located on the fibrin clot. Without localized binding of plasminogen to fibrin, it cannot be converted to plasmin.

Because fibrinolysis requires plasminogen (and plasmin) binding to fibrin, fibrinolysis is inhibited.

A competitive inhibitor of plasminogen activation and, at much higher concentrations, a noncompetitive inhibitor of plasmin. Suppresses fibrinolysis by inhibiting activation of plasminogen.

Other antifibrinolytic medications incl ɛ-ACA (lysine analogue) and aprotinin (serine protease inhibitor).

Reductions in mortality rates with TXA doses of 4.5–6 g daily for 5–7 d (in most studies) produced statistical significance between TXA and placebo.

TXA was associated with reductions in mortality of 5–54% in pts with upper GI bleeding compared with placebo. Meta-analysis indicated a reduction of 40%.

Administered either PO at 25 mg/kg every 6–8 h or IV at 10 mg/kg every 6–8 h beginning on the d prior to surgery.

In adults, the minimum concentration of TXA necessary to completely prevent fibrinolysis is 17.5 ug/mL.

In children aged 2 d-4 y, body weight is less accurate at predicting the distribution and elimination of TXA. Dosing is recommended by age rather than body weight. Other factors that do not affect the distribution and elimination of TXA in children are body surface area, pump prime volume, ultrafiltrate volume, and body temperature.

Neonatal plasma requires a significantly lower concentration of TXA than adult plasma.

In neonates the minimum concentration of TXA to completely prevent fibrinolysis is 6.54 μg/mL.

Absorption after oral use is 30–50%; bioavailability is not affected by food.

An antifibrinolytic concentration of drug remains in serum up to 7–8 h.

The protein binding to plasminogen is approximately 3% at therapeutic plasma levels; it does not bind to serum albumin.

The half-time of elimination when administered orally is 120 min.

Urinary excretion is the main route of elimination via glomerular filtration.

Overall renal clearance is equal to overall plasma clearance, and >90% of the dose is excreted unchanged in 24 h.

Pts with renal insufficiency should have their doses reduced according to creatinine clearance. Only a small fraction of TXA is metabolized.

TXA is 6–10 times more potent in terms of binding to plasminogen/plasmin than ɛ-ACA.

Concurrent administration of heparin does not influence the activity of TXA.

Pharmacokinetic properties: Maximum plasma concentrations of TXA can be attained within 3 h after an oral dose. Elimination after IV administration is triexponential, and over 95% of each dose is eliminated unchanged in the urine.