J Haem Pract 2016; 3(2):1 - 4. doi: 10.17225/jhp00089

Authors: Daniel Hart, Saket Badle

Daniel Hart
The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, QMUL, UK

Saket Badle
The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry, QMUL, UK. Email: Saket.Badle@


Tranexamic acid (TXA) is a synthetic antifibrinolytic drug used widely used to control bleeding complications in a wide variety of clinical situations. Soon after its development in the 1960s it found use in treatment of women with menorrhagia, and in inherited bleeding disorders. Subsequently it was used in surgery and with proven efficacy to reduce transfusion requirements and bleeding complications. Recent meta-analysis have provided further evidence of efficacy and safety. Tranexamic acid is now on the World Health Organization’s (WHO) list of essential drugs, and is the focus of ongoing worldwide trials. Similarly, there is increasing evidence base in both congenital and acquired bleeding disorders. We present a clinical narrative of the antifibrinolytic system and associated drugs to accompany the pharmacy review by Chaplin et al, with the aim of highlighting the evolution of TXA use in bleeding disorders over recent decades.




  1. Reiner, Alexander Paul et al. The fibrinolytic system in man. Critical Reviews in Oncology / Hematology , Volume 2 , Issue 1 , 33 - 81
  2. Raza I, Davenport R, Rourke C, et al. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost 2013; 11(2): 307-14.
  3. Okamoto S. Plasmin and antiplasmin. Their pathologic physiology. Keio J Med 1959; 8: 211-7.
  4. Okamoto S, Okamoto U. Amino-methyl-cyclohexane-carboxylic acid: AMCHA: a new potent inhibitor of fibrinolysis. Keio J Med 1962; 11: 105-15.
  5. Shakur H, Elbourne D, Gülmezoglu M, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 2010, 11: 40.
  6. Dewan Y, Komolafe EO, Mejía-Mantilla JH, et al. CRASH-3 – tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo controlled trial. Trials 2012; 13: 87.
  7. Roberts I, Coats T, Edwards P, et al. HALT-IT – tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial. Trials 2014; 15: 450.
  8. Roberts I, Shakur H, Afolabi A, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011; 377: 1096-101.
  9. Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376: 23-32.
  10. Rea CJ, Foley JH, Ingerslev J, Sørensen B. Factor XIII combined with recombinant factor VIIa: a new means of treating severe hemophilia A. J Thromb Haemost 2011; 9: 510-6.
  11. Rea CJ, Foley JH, Okaisabor O, Sørensen B. FXIII: mechanisms of action in the treatment of hemophilia A. J Thromb Haemost 2014; 12: 159-68.
  12. Brummel-Ziedins KE, Branda RF, Butenas S, Mann KG. Discordant fibrin formation in hemophilia. J Thromb Haemost 2009; 7: 825-32.
  13. Foley JH, Nesheim ME, Rivard GE, Brummel-Ziedins KE. Thrombin activatable fibrinolysis inhibitor activation and bleeding in haemophilia A. Haemophilia 2012; 18: e316-22.
  14. Hvas A-M, Sørensen HT, Norengaard L, Christiansen K, Ingerslev J, Sørensen B. Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A. J Thromb Haemost 2007; 5: 2408-14..
  15. Bisordi MV. Peanut flour in haemophilia. Lancet 1964; 2: 476.
  16. Bruster H. Klin Wochenschr 1961; 39: 1145.
  17. Verstraete M, Ruys CA. Double-blind experiments on the effect of a peanut extract on the bleeding incidence in 92 haemophiliacs. Br Med J 1967; 4: 453-6.
  18. Bennett AE, Ingram GI, Inglish PJ. Antifibrinolytic treatment in haemophilia: a controlled trial of prophylaxis with tranexamic acid. Br J Haematol 1973 ;24(1): 83-8.
  19. Ingram GI, Inglish PJ, Bennet AE. Tranexamic acid for prophylaxis in haemophilia. J Clin Pathol 1972 ; 25(7): 629.
  20. Gordon AM, McNicol GP, Dubber AHC, McDonald GA, Douglas AS. Clinical trial of epsilon-aminocaproic acid in severe haemophilia. Br Med J 1965; 1(5451): 1632-5.
  21. Hermans C, Altisent C, Batorova A, et al. Replacement therapy for invasive procedures in patients with haemophilia: literature review, European survey and recommendations. Haemophilia 2009; 15: 639-58.
  22. Schulman S, Loogna J, Wallensten R. Minimizing factor requirements for surgery without increased risk. Haemophilia 2004; 10(Suppl. 4): 35-40
  23. Tavenner RW. Use of tranexamic acid in control of haemorrhage after extraction of teeth in haemophilia and Christmas disease. Br Med J 1972;2(5809): 314-5.
  24. Forbes CD, Barr RD, Reid G, Thomson C, Prentice CR, McNicol GP, Douglas AS. Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. Br Med J 1972 ;2(5809): 311-3.
  25. Walsh PN, Rizza CR, Evans BE, Aledort LM. The therapeutic role of epsilon-aminocaproic acid (EACA) for dental extractions in hemophiliacs. Ann N Y Acad Sci 1975; 240: 267-76.
  26. Walsh PN, Rizza CR, Matthews JM, et al. Epsilon-aminocaproic acid therapy for dental extractions in haemophilia and Christmas disease: a double blind controlled trial. Br J Haematol 1971; 20(5): 463-75.
  27. Sindet-Pedersen S, Stenbjerg S. Effect of local antifibrinolytic treatment with tranexamic acid in hemophiliacs undergoing oral surgery. J Oral Maxillofac Surg 1986; 44(9): 703-7.
  28. Waly NG. Local antifibrinolytic treatment with tranexamic acid in hemophilic children undergoing dental extractions. Egypt Dent J 1995; 41(1): 961-8.
  29. Nuvvula S, Gaddam KR, Kamatham R. Efficacy of tranexamic acid mouthwash as an alternative for factor replacement in gingival bleeding during dental scaling in cases of hemophilia: a randomized clinical trial. Contemp Clin Dent 2014; 5(1): 49-53.
  30. Laffan MA, Lester W, O’Donnell JS, et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol 2014; 167: 453-65.
  31. Davis A, Walsh M, McCarthy P, et al. Tranexamic acid without prophylactic factor replacement for prevention of bleeding in hereditary bleeding disorder patients undergoing endoscopy: a pilot study. Haemophilia 2013; 19: 583-9.
  32. Coppola A, Windyga J, Tufano A, Yeung C, Di Minno MN. Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery. Cochrane Database Syst Rev 2015; (2): CD009961.
  33. Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2014; (11): CD006640.
  34. van Galen KPM, Engelen ET, Mauser-Bunschoten EP, van Es RJ, Schutgens RE. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions. Cochrane Database Syst Rev 2015; (12): CD011385.
  35. Negrier C, Goudemand J, Sultan Y, Bertrand M, Rothschild C, Lauroua P. Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight Bypassing Activity. Thromb Haemost 1997; 77: 1113-9.
  36. Astermark J, Donfield SM, DiMichele DM et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood 2007; 109: 546-51 Epub 2006; doi 10.1182/blood-2006-04-01798.
  37. Dai L, Bevan D, Rangarajan S, Sørensen B, Mitchell M. Stabilization of fibrin clots by activated prothrombin complex concentrate and tranexamic acid in FVIII inhibitor plasma. Haemophilia 2011; 17: e944-8.
  38. Holmström M, Tran HT, Holme PA. Combined treatment with APCC (FEIBA®) and tranexamic acid in patients with haemophilia A with inhibitors and in patients with acquired haemophilia A – a two-centre experience. Haemophilia 2012; 18: 544-9.
  39. Tran HT, Sørensen B, Rea CJ, et al. Tranexamic acid as adjunct therapy to bypassing agents in haemophilia A patients with inhibitors. Haemophilia 2014; 20: 369-75.
  40. Kouides PA, Byams VR, Philipp CS, et al. Multisite management study of menorrhagia with abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral tranexamic acid. Br J Haematol 2009; 145: 212-20.
  41. Mohri H. High dose of tranexamic acid for treatment of severe menorrhagia in patients with von Willebrand disease. J Thromb Thrombolysis 2002; 14(3): 255-7.
  42. Rybo G. Tranexamic acid therapy: effective treatment in heavy menstrual bleeding: clinical update on safety. Therapeutic Advances 1991; 4: 1-8.
  43. Lindoff C, Rybo G, Astedt B. Treatment with tranexamic acid during pregnancy, and the risk of thrombo-embolic complications. Thromb Haemost 1993; 70(2): 238-40.
  44. Kadir RA, Lee CA, Sabin CA, Pollard D, Economides DL. Pregnancy in women with von Willebrand’s disease or factor XI deficiency. Br J Obstet Gynaecol 1998; 105(3): 314-21.
  45. Ducloy-Bouthors AS, Jude B, Duhamel A, et al. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care 2011; 15(2): R117.
  46. Lee CA, Chi C, Pavord SR, et al. The obstetric and gynaecological management of women with inherited bleeding disorders – review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors’ Organization. Haemophilia 2006; 12: 301-36.

The Journal of Haemophilia Practice is published by Haemnet.

Haemnet is a registered charity that brings together and gives a voice to haemophilia nurses, physiotherapists and allied health care professionals, providing forums for collaborative research, educational activities and support.