Abstract
Tranexamic acid, a synthetic derivative of the amino acid lysine, is an antifibrinolytic agent that acts by binding to plasminogen and blocking the interaction of plasmin (ogen) with fibrin, thereby preventing dissolution of the fibrin clot. Tranexamic acid (Transamin®) is indicated in Japan for use in certain conditions with abnormal bleeding or bleeding tendencies in which local or systemic hyperfi-brinolysis is considered to be involved. This article reviews the efficacy and tolerability of tranexamic acid in conditions amenable to antifibrinolytic therapy and briefly overviews the pharmacological properties of the drug.
In large, randomized controlled trials, tranexamic acid generally significantly reduced perioperative blood loss compared with placebo in a variety of surgical procedures, including cardiac surgery with or without cardiopulmonary bypass, total hip and knee replacement and prostatectomy. In many instances, tranexamic acid also reduced transfusion requirements associated with surgery. It also reduced blood loss in gynaecological bleeding disorders, such as heavy menstrual bleeding, postpartum haemorrhage and bleeding irregularities caused by contraceptive implants. Tranexamic acid significantly reduced all-cause mortality and death due to bleeding in trauma patients with significant bleeding, particularly when administered early after injury. It was also effective in traumatic hyphaema, gastrointestinal bleeding and hereditary angioneurotic oedema. While it reduces rebleeding in subarachnoid haemorrhage, it may increase ischaemic complications. Pharmacoeconomic analyses predicted that tranexamic acid use in surgery and trauma would be very cost effective and potentially life saving.
In direct comparisons with other marketed agents, tranexamic acid was at least as effective as e-aminocaproic acid and more effective than desmopressin in surgical procedures. It was more effective than desmopressin, etamsylate, flurbiprofen, mefenamic acid and norethisterone, but less effective than the levonorgestrel-releasing intra-uterine device in heavy menstrual bleeding and was as effective as prednisolone in traumatic hyphaema.
Tranexamic acid was generally well tolerated. Most adverse events in clinical trials were of mild or moderate severity; severe or serious events were rare. Therefore, while high-quality published evidence is limited for some approved indications, tranexamic acid is an effective and well tolerated antifibrinolytic agent.
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Various sections of the manuscript reviewed by: V. Casati, Clinica San Gaudenzio (Policlinico di Monza Group), Division of Cardiovascular Anaesthesia and Intensive Care, Novara, Italy; W. Dietrich, Institute for Research in Cardiac Anesthesia, Munich, Germany; A.-S. Ducloy-Bouthors, Pole d’Anesthésie-Réanimation, CHU Lille, Lille, France; S.M. Elwatidy, Division of Neurosurgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia; M.R. Farrokhi, Shiraz Neurosciences Research Center, Neurosurgery Department, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran; K. Hekmat, Department of Thoracic and Cardiovascular Surgery, University of Cologne, Cologne, Germany; J. Wong, Department of Anesthesia, University Health Network, Toronto Western Hospital and University of Toronto, Toronto, ON, Canada; P.J. Zufferey, Department of Anaesthesiology and Intensive Care, University Hospital of Saint-Étienne, Saint-Étienne, France.
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Sources: Medical literature (including published and unpublished data) on ‘tranexamic acid’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE and EMBASE search terms were ‘tranexamic acid’ and (‘blood loss’ or ‘bleeding’ or ‘menorrhagia’ or ‘epistaxis’ or ‘surgery’ or ‘angioneurotic edema’ or ‘angioneurotic oedema’ or ‘angioedema’ or ‘cancer’ or ‘neoplasm’ or ‘neoplasms’ or ‘leukemia’ or ‘leukaemia’ or ‘surgical blood loss’ or ‘blood transfusion’). Searches were last updated 23 February 2012.
Selection: Studies in patients who received tranexamic acid for the treatment of conditions involving hyperfibrinolysis. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Tranexamic acid, blood loss prevention, haemostasis, pharmacodynamics, pharmacokinetics, pharmacoeconomics, therapeutic use, tolerability.
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McCormack, P.L. Tranexamic Acid. Drugs 72, 585–617 (2012). https://doi.org/10.2165/11209070-000000000-00000
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DOI: https://doi.org/10.2165/11209070-000000000-00000