Current Evidence and Future Directions of Tranexamic Acid Use, Efficacy, and Dosing for Major Surgical Procedures

Tranexamic acid: current use in obstetrics, major orthopedic, and trauma surgery

“…The protein binding of TXA is low (3%) with binding being predominantly to plasminogen. 10,11 Overall, TXA has been shown to have a favourable safety profile in non-cardiac surgery studies. Nevertheless, the use of TXA can theoretically promote thromboembolic events (i.e., deep vein thromboses, pulmonary emboli, myocardial infarction, stroke), though large clinical trials have shown that this adverse effect is not clinically significant in hospital, with the commonly used intravenous doses of 1-2 g. [12][13][14] The risk of administering TXA in patients with a history of thromboembolism or hypercoagulable state remains understudied.…”

“…Other adverse effects of TXA that are more commonly associated with oral administration, and less frequently seen by anesthesiologists, are gastrointestinal disturbance (nausea, dyspepsia, diarrhea) and headaches. 11 Seizures are a recognized, though rare, side effect of TXA administration. An estimated 10% of the TXA dose crosses the blood brain barrier, but this likely varies with changes in membrane permeability from trauma, cerebral emboli, and cardiopulmonary bypass.…”

Individualized Perioperative Antifibrinolytic Therapy: The Next Goal in Cardiac Surgery?

“…9 In the setting of cardiac surgery with CPB, TXA and EACA are thought to be equivalent in their general ability to reduce bleeding and transfusion requirements in adult cardiac surgery. 8,10 Despite having similar structures, mechanisms of action, and pharmacodynamics including intravenous application, renal elimination, and comparable plasma half-time of about 2-to-3 hours, 8,11 their relevant pharmacokinetics and dosing regimens differ. 8,10 Of note, TXA is thought to be about 6 to-10 times more potent on a molecular basis.…”

“…8,10 Of note, TXA is thought to be about 6 to-10 times more potent on a molecular basis. 2,8,11,12 Further, TXA is used more extensively worldwide than the earlier developed EACA. 13 EACA is approved in the United States and Canada alone, 8 but is being administered off-label in some pediatric cardiac surgery units in Europe.…”

“…19 In general, these dosing regimens aim for a target plasma TXA concentration during CPB of >10-to-20 mg/mL, which is thought to be associated with an inhibition of fibrinolysis of about 80%. 8,20 High-dose regimens, using up to 10 g of TXA, have been described 11,21 and result in TXA plasma concentrations of >100 mg/mL, which presumably must suppress any systemic fibrinolytic activity. 8,10 It is not fully clear whether high-dose regimens are clinically advantageous in reducing bleeding and transfusion of blood products; however, they obviously are associated with a higher risk of postoperative seizures.…”