ORIGINAL ARTICLESTranexamic acid rapidly inhibits fibrinolysis, yet transiently enhances plasmin generation in vivoDraxler, Dominik F.a; Zahra, Saffanaha; Goncalves, Isaaca; Tran, Huyena; Hanafi, Gryseldaa; Ho, Heidia; Keragala, Charithani B.a; Ilich, Antonb; Key, Nigel S.b; Myles, Paul S.c,d; Medcalf, Robert L.aAuthor Information aAustralian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia bDivision of Hematology and Blood Research Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA cDepartment of Anaesthesiology and Perioperative Medicine, Alfred Hospital dDepartment of Anaesthesiology and Perioperative Medicine, Monash University, Melbourne, Victoria, Australia Correspondence to Dominik F. Draxler, MD, PhD, Inselspital, Universitatsspital Bern, Bern, Switzerland. E-mail: [email protected] Received 2 October, 2020 Revised 29 November, 2020 Accepted 2 December, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.bloodcoagulation.com). Blood Coagulation & Fibrinolysis: April 2021 - Volume 32 - Issue 3 - p 172-179 doi: 10.1097/MBC.0000000000001008 Buy SDC Metrics Abstract Tranexamic acid (TXA) is a lysine analogue that inhibits plasmin generation and has been used for decades as an antifibrinolytic agent to reduce bleeding. Recent reports have indicated that TXA can paradoxically promote plasmin generation. Blood was obtained from 41 cardiac surgical patients randomly assigned to TXA or placebo before start of surgery (preOP), at the end of surgery (EOS), then again on postoperative day 1 (POD-1) as well as POD-3. Plasma levels of tissue-type plasminogen activator (t-PA), urokinase (u-PA), the plasmin-antiplasmin (PAP) complex, as well as t-PA and u-PA-induced clot lysis assays were then determined. Clot lysis and PAP complex levels were also assessed in healthy volunteers before and at various time points after taking 1 g TXA orally. Surgery induced an increase in circulating t-PA, yet not u-PA at EOS. t-PA levels were unaffected by TXA; however, u-PA levels were significantly reduced in patients on POD-3. t-PA and u-PA-induced clot lysis were both inhibited in plasma from TXA-treated patients. In contrast, PAP complex formation, representing plasmin generation, was unexpectedly enhanced in the plasma of patients administered TXA at the EOS time point. In healthy volunteers, oral TXA effectively blocked fibrinolysis within 30 min and blockade was sustained for 8 h. However, TXA also increased PAP levels in volunteers 4 h after administration. Our findings demonstrate that TXA can actually augment PAP complex formation, consistent with an increase in plasmin generation in vivo despite the fact that it blocks fibrinolysis within 30 min. This may have unanticipated consequences in vivo. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.