Tranexamic acid (TXA), a synthetic lysine derivative that competitively blocks the lysine-binding sites on plasminogen, is an extensively studied and widely used pharmacologic intervention for perioperative bleeding. By preventing plasmin-mediated fibrin degradation, TXA stabilizes clot formation at the surgical site. A substantial body of research supports its efficacy in reducing intraoperative blood loss across multiple surgical settings, most notably orthopedic, cardiac, and obstetric surgery (McCormack, 2012).
A combined clinical practice guideline from AAHKS, AAOS, ASRA, the Hip Society, and the Knee Society concluded that intravenous, topical, and oral TXA all significantly reduce calculated blood loss and transfusion requirements in total joint arthroplasty compared with placebo, with intravenous and topical routes lowering transfusion risk by roughly 60–75% in total hip and knee arthroplasty (Fillingham et al., 2018). Notably, no single route of administration, nor higher or lower dosing, demonstrated clearly superior efficacy, and multiple doses conferred no additional benefit over a single dose. Administering TXA before surgical incision showed a modest advantage over post-incision dosing in reducing transfusion risk, though the evidence for this timing effect was only moderate in strength.
A meta-analysis of 73 randomized trials involving nearly 7,000 patients undergoing major orthopedic procedures found that intravenous TXA effectively reduced blood loss without increasing venous thromboembolic risk relative to controls (Franchini et al., 2018). In cardiac surgery performed with cardiopulmonary bypass, larger randomized trials have repeatedly shown that bolus and infusion regimens of TXA reduce postoperative blood loss and transfusion requirements compared with placebo, with efficacy generally comparable to that of aprotinin before its market withdrawal (McCormack, 2012). Additionally, a 2015 review concluded that TXA reduces the probability of receiving a blood transfusion across elective surgical populations by approximately one-third (Hunt, 2015).
The magnitude of TXA’s hemostatic effect appears to plateau at relatively modest doses. Early dose-ranging studies in cardiac surgery demonstrated that a loading dose of approximately 10 mg/kg followed by a low-dose maintenance infusion achieved maximal antifibrinolytic benefit, with no additional reduction in bleeding from higher doses (Hunt, 2015). This dose-ceiling effect has practical significance, since escalating doses have been associated with a higher incidence of postoperative seizures, particularly in cardiac surgical populations, without a corresponding gain in hemostatic efficacy.
Importantly, the efficacy of TXA in reducing intraoperative blood loss has not been consistently accompanied by a proportional reduction in clinical thromboembolic risk. Safety data remain more limited for patients with pre-existing thrombotic risk factors. Nonetheless, significant evidence supports TXA as a highly effective intervention for limiting intraoperative blood loss, with efficacy that is now considered well established rather than investigational.
References
- Fillingham, Y.A., Ramkumar, D.B., Jevsevar, D.S., Yates, A.J., Sayeed, S.A., Sah, A.P., Bini, S.A., Clarke, H.D., Schemitsch, E., Johnson, R.L., Memtsoudis, S., & Della Valle, C.J. (2018). Tranexamic acid in total joint arthroplasty: The endorsed clinical practice guides of the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, The Hip Society, and The Knee Society. Regional Anesthesia & Pain Medicine. https://doi.org/10.1136/rapm-2018-000024
- Franchini, M., Mengoli, C., Marietta, M., Marano, G., Vaglio, S., Pupella, S., Mannucci, P.M., & Liumbruno, G.M. (2018). Safety of intravenous tranexamic acid in patients undergoing major orthopaedic surgery: A meta-analysis of randomised controlled trials. Blood Transfusion, 16(1), 36–43. https://doi.org/10.2450/2017.0219-17
- Hunt, B.J. (2015). The current place of tranexamic acid in the management of bleeding. Anaesthesia, 70(Suppl. 1), 50–53. https://doi.org/10.1111/anae.12910
- McCormack, P.L. (2012). Tranexamic acid: A review of its use in the treatment of hyperfibrinolysis. Drugs, 72(5), 585–617. https://doi.org/10.2165/11209070-000000000-00000
