Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis

Katharine Ker, Phil Edwards, Pablo Perel, Haleema Shakur, Ian Roberts, Katharine Ker, Phil Edwards, Pablo Perel, Haleema Shakur, Ian Roberts

Abstract

Objective: To assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients.

Design: Systematic review and meta-analysis.

Data sources: Cochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles.

Study selection: Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status.

Results: 129 trials, totalling 10,488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; P<0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; P<0.001). The effect of tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P = 0.11), stroke (1.14, 0.65 to 2.00; P = 0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P = 0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; P = 0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years.

Conclusions: Strong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4789921/bin/kerk002257.f1_default.jpg
Fig 1 Selection of trials for review
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4789921/bin/kerk002257.f2_default.jpg
Fig 2 Cumulative meta-analysis of the effect of tranexamic acid in surgery on risk of blood transfusion in adequately concealed trials
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4789921/bin/kerk002257.f3_default.jpg
Fig 3 Cumulative meta-analysis of the effect of tranexamic acid in surgery on risk of myocardial infarction in adequately concealed trials
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4789921/bin/kerk002257.f4_default.jpg
Fig 4 Cumulative meta-analysis of the effect of tranexamic acid in surgery on risk of death in adequately concealed trials
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4789921/bin/kerk002257.f5_default.jpg
Fig 5 Funnel plot with pseudo 95% confidence limits for meta-analysis on effect of tranexamic acid on risk of blood transfusion

References

    1. Crescenti A, Borghi G, Bignami E, Bertarelli G, Landoni G, Casiraghi GM, et al. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial. BMJ 2011;343:d5701.
    1. Henry DA, Moxey AJ, Carless PA, O’Connell D, McClelland B, Henderson KM, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2001;1:CD001886.
    1. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Wiley, 2008.
    1. Stata Statistical Software: Release 11. College Station, TX: StataCorp LP [program], 2009.
    1. Review Manager (RevMan) [Computer program] Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
    1. Alvarez JC, Santiveri FX, Ramos I, Vela E, Puig L, Escolano F. Tranexamic acid reduces blood transfusion in total knee arthroplasty even when a blood conservation program is applied. Transfusion 2008;48:519-25.
    1. Andreasen JJ, Nielsen C. Prophylactic tranexamic acid in elective, primary coronary artery bypass surgery using cardiopulmonary bypass. Eur J Cardiothorac Surg 2004;26:311-7.
    1. Armellin G, Casella S, Guzzinati S, Pasini L, Marcassa A, Giron G. Tranexamic acid in aortic valve replacement. J Cardiothorac Vasc Anesth 2001;15:331-5.
    1. Auvinen O, Baer GA, Nordback I, Saaristo J. Antifibrinolytic therapy for prevention of hemorrhage during surgery of the thyroid gland. Klin Wochenschr 1987;65:253-5.
    1. Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients. J Bone Joint Surg Br 1996;78:434-40.
    1. Benoni G, Fredin H, Knebel R, Nilsson P. Blood conservation with tranexamic acid in total hip arthroplasty: a randomized, double-blind study in 40 primary operations. Acta Orthop Scand 2001;72:442-8.
    1. Benoni G, Lethagen S, Nilsson P, Fredin H. Tranexamic acid, given at the end of the operation, does not reduce postoperative blood loss in hip arthroplasty. Acta Orthop Scand 2000;71:250-4.
    1. Blauhut B, Harringer W, Bettelheim P, Doran JE, Späth P, Lundsgaard-Hansen P. Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994;108:1083-91.
    1. Boylan JF, Klinck JR, Sandler AN, Arellano R, Greig PD, Nierenberg H, et al. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology 1996;85:1043-8; discussion 30A-31A.
    1. Brown RS, Thwaites BK, Mongan PD. Tranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: a double-blind, randomized, placebo-controlled trial. Anesth Analg 1997;85:963-70.
    1. Bulutcu FS, Ozbek U, Polat B, Yalçin Y, Karaci AR, Bayindir O. Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? Paediatr Anaesth 2005;15:41-6.
    1. Caglar GS, Tasci Y, Kayikcioglu F, Haberal A. Intravenous tranexamic acid use in myomectomy: a prospective randomized double-blind placebo controlled study. EurJ Obst, Gynecol, Reprod Biol 2008;137:227-31.
    1. Casati V, Bellotti F, Gerli C, Franco A, Oppizzi M, Cossolini M, et al. Tranexamic acid administration after cardiac surgery: a prospective, randomized, double-blind, placebo-controlled study. Anesthesiology 2001;94:8-14.
    1. Casati V, Della Valle P, Benussi S, Franco A, Gerli C, Baili P, et al. Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: comparison between on-pump and off-pump techniques. J Thorac Cardiovasc Surg 2004;128:83-91.
    1. Casati V, Sandrelli L, Speziali G, Calori G, Grasso MA, Spagnolo S. Hemostatic effects of tranexamic acid in elective thoracic aortic surgery: a prospective, randomized, double-blind, placebo-controlled study. J Thorac Cardiovasc Surg 2002;123:1084-91.
    1. Castelli G, Vogt E. [Result of an antifibrinolytic treatment using tranexamic acid for the reduction of blood-loss during and after tonsillectomy]. [German]. Schweiz Med Wochenschr 1977;107:780-4.
    1. Chauhan S, Bisoi A, Kumar N, Mittal D, Kale S, Kiran U, et al. Dose comparison of tranexamic acid in pediatric cardiac surgery. Asian Cardiovasc Thorac Ann 2004;12:121-4.
    1. Chauhan S, Bisoi A, Modi R, Gharde P, Rajesh MR. Tranexamic acid in paediatric cardiac surgery. Indian J Med Res 2003;118:86-9.
    1. Chauhan S, Das SN, Bisoi A, Kale S, Kiran U. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 2004;18:141-3.
    1. Chen CC, Wang CC, Wang CP, Lin TH, Lin WD, Liu SA. Prospective, randomized, controlled trial of tranexamic acid in patients who undergo head and neck procedures. Otolaryngol Head Neck Surg 2008;138:762-7.
    1. Choi WS, Irwin MG, Samman N. The effect of tranexamic acid on blood loss during orthognathic surgery: a randomized controlled trial. J Oral Maxillofac Surg 2009;67:125-33.
    1. Claeys MA, Vermeersch N, Haentjens P. Reduction of blood loss with tranexamic acid in primary total hip replacement surgery. Acta Chir Belg 2007;107:397-401.
    1. Coffey A, Pittmam J, Halbrook H, Fehrenbacher J, Beckman D, Hormuth D. The use of tranexamic acid to reduce postoperative bleeding following cardiac surgery: a double-blind randomized trial. Am Surg 1995;61:566-8.
    1. Corbeau JJ, Monrigal JP, Jacob JP, Cottineau C, Moreau X, Bukowski JG, et al. [Comparison of effects of aprotinin and tranexamic acid on blood loss in heart surgery]. [French]. Ann Fr Anesth Reanim 1995;14:154-61.
    1. Dadure C, Sauter M, Bringuier S, Bigorre M, Raux O, Rochette A, et al. Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology 2011;114:856-61.
    1. Dalmau A, Sabaté A, Acosta F, Garcia-Huete L, Koo M, Sansano T, et al. Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation. Anesth Analg 2000;91:29-34.
    1. Demeyere R, Bosteels A, Arnout J, Gasthuisberg UV. Comparison of the effects of tranexamic acid, aprotinin and placebo on blood conservation, fibrinolysis and platelet function with extensive heart surgery. Crit Care 2006;10(suppl 1).
    1. Diprose P, Herbertson MJ, O’Shaughnessy D, Deakin CD, Gill RS. Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage. Br J Anaesth 2005;94:271-8.
    1. Dryden PJ, O’Connor JP, Jamieson WR, Reid I, Ansley D, Sadeghi H, et al. Tranexamic acid reduces blood loss and transfusion in reoperative cardiac surgery. Can J Anaesth 1997;44:934-41.
    1. Durán de la Fuente P, García-Fernández J, Pérez-López C, Carceller F, Gilsanz Rodríguez F. [Usefulness of tranexamic acid in cranial remodeling surgery]. Rev Esp Anestesiol Reanim 2003;50:388-94.
    1. Ekbäck G, Axelsson K, Ryttberg L, Edlund B, Kjellberg J, Weckström J, et al. Tranexamic acid reduces blood loss in total hip replacement surgery. Anesth Analg 2000;91:1124-30.
    1. Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine 2008;33:2577-80.
    1. Engel JM, Hohaus T, Ruwoldt R, Menges T, Jürgensen I, Hempelmann G. Regional hemostatic status and blood requirements after total knee arthroplasty with and without tranexamic acid or aprotinin. Anesth Analg 2001;92:775-80.
    1. Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: a multi-center, randomized trial. Eur J Obstetr Gynecol Reprod Biol 2004;112:154-7.
    1. Garneti N, Field J. Bone bleeding during total hip arthroplasty after administration of tranexamic acid. J Arthroplasty 2004;19:488-92.
    1. Gill JB, Chase E, Rosenstein AD. The use of tranexamic acid in revision total hip arthroplasty: a pilot study. Curr Orthop Pract 2009;20:152-6.
    1. Gobbur VR, Reddy SV, Bijapur UJ. Efficacy of tranexamic acid in reducing blood loss during lower segment caesarean section. 54th All India Congress of Obstetrics and Gynaecology; 5-9 Jan, 2011; Hyderabad, Andhra Pradesh, India. 2011:92.
    1. Gohel M, Patel P, Gupta A, Desai P. Efficacy of tranexamic acid in decreasing blood loss during and after cesarean section: a randomized case controlled prospective study. J Obstetr Gynaecol India 2007;57:228-30.
    1. Goobie SM, Meier PM, Pereira LM, McGowan FX, Prescilla RP, Scharp LA, et al. Efficacy of tranexamic acid in pediatric craniosynostosis surgery: a double-blind, placebo-controlled trial. Anesthesiology 2011;114:862-71.
    1. Good L, Peterson E, Lisander B. Tranexamic acid decreases external blood loss but not hidden blood loss in total knee replacement. Br J Anaesth 2003;90:596-9.
    1. Greiff G, Stenseth R, Wahba A, Videm V, Lydersen S, Irgens W, et al. Tranexamic acid reduces blood transfusions in elderly patients undergoing combined aortic valve and coronary artery bypass graft surgery: a randomized controlled trial. J Cardiothorac Vasc Anesth 2012;26:232-8.
    1. Grundsell H, Larsson G, Bekassy Z. Use of an antifibrinolytic agent (tranexamic acid) and lateral sutures with laser conization of the cervix. Obstet-Gynecol 1984;64:573-6.
    1. Gungorduk K, Yildirim G, Asicioglu O, Gungorduk OC, Sudolmus S, Ark C. Efficacy of intravenous tranexamic acid in reducing blood loss after elective cesarean section: a prospective, randomized, double-blind, placebo-controlled study. Am J Perinatol 2011;28:233-40.
    1. Hardy JF, Bélisle S, Dupont C, Harel F, Robitaille D, Roy M, et al. Prophylactic tranexamic acid and epsilon-aminocaproic acid for primary myocardial revascularization. Ann Thorac Surg 1998;65:371-6.
    1. Hiippala S, Strid L, Wennerstrand M, Arvela V, Mäntylä S, Ylinen J, et al. Tranexamic acid (Cyklokapron) reduces perioperative blood loss associated with total knee arthroplasty. Br J Anaesth 1995;74:534-7.
    1. Hiippala ST, Strid LJ, Wennerstrand MI, Arvela JV, Niemelä HM, Mäntylä SK, et al. Tranexamic acid radically decreases blood loss and transfusions associated with total knee arthroplasty. Anesth Analg 1997;84:839-44.
    1. Horrow JC, Hlavacek J, Strong MD, Collier W, Brodsky I, Goldman SM, et al. Prophylactic tranexamic acid decreases bleeding after cardiac operations. J Thorac Cardiovasc Surg 1990;99:70-4.
    1. Horrow JC, Van Riper DF, Strong MD, Brodsky I, Parmet JL. Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery. Circulation 1991;84:2063-70.
    1. Horrow JC, Van Riper DF, Strong MD, Grunewald KE, Parmet JL. The dose-response relationship of tranexamic acid. Anesthesiology 1995;82:383-92.
    1. Husted H, Blønd L, Sonne-Holm S, Holm G, Jacobsen TW, Gebuhr P. Tranexamic acid reduces blood loss and blood transfusions in primary total hip arthroplasty: a prospective randomized double-blind study in 40 patients. Acta Orthopaed Scand 2003;74:665-9.
    1. Isetta C, Guinness TK, Samat C, Paolini G, Lugrin D, Sanchez B, et al. Antifibrinolytic treatment and homologeous transfusion in cardiac surgery. Eur Heart Surg 1993;14(Suppl):424.
    1. Jansen AJ, Andreica S, Claeys M, D’Haese J, Camu F, Jochmans K. Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty. Br J Anaesth 1999;83:596-601.
    1. Jares M, Vanek T, Straka Z, Brucek P. Tranexamic acid reduces bleeding after off-pump coronary artery bypass grafting. J Cardiovasc Surg 2003;44:205-8.
    1. Jimenez JJ, Iribarren JL, Lorente L, Rodriguez JM, Hernandez D, Nassar I, et al. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial. Crit Care (Lond) 2007;11:R117.
    1. Johansson T, Pettersson LG, Lisander B. Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients. Acta Orthopaed 2005;76:314-9.
    1. Kakar PN, Gupta N, Govil P, Shah V. Efficacy and safety of tranexamic acid in control of bleeding following TKR: a randomized control trial. Indian J Anaesth 2009;53:667-71.
    1. Karski J, Djaiani G, Carroll J, Iwanochko M, Seneviratne P, Liu P, et al. Tranexamic acid and early saphenous vein graft patency in conventional coronary artery bypass graft surgery: a prospective randomized controlled clinical trial. J Thorac Cardiovasc Surg 2005;130:309-14.
    1. Karski JM, Teasdale SJ, Norman P, Carroll J, VanKessel K, Wong P, et al. Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial. J Thorac Cardiovasc Surg 1995;110:835-42.
    1. Kaspar M, Ramsay MA, Nguyen AT, Cogswell M, Hurst G, Ramsay KJ. Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation. Anesth Analg 1997;85:281-5.
    1. Katoh J, Tsuchiya K, Sato W, Nakajima M, Iida Y. Additional postbypass administration of tranexamic acid reduces blood loss after cardiac operations. J Thorac Cardiovasc Surg 1997;113:802-4.
    1. Katsaros D, Petricevic M, Snow NJ, Woodhall DD, Van Bergen R. Tranexamic acid reduces postbypass blood use: a double-blinded, prospective, randomized study of 210 patients. Ann Thorac Surg 1996;61:1131-5.
    1. Kazemi SM, Mosaffa F, Eajazi A, Kaffashi M, Besheli LD, Bigdeli MR, et al. The effect of tranexamic acid on reducing blood loss in cementless total hip arthroplasty under epidural anesthesia. Orthopedics 2010;33:17.
    1. Klinck JR, Boylan JF, Sandler AN, Greig PD, Roger S, Nierenberg H, et al. Tranexamic acid prophylaxis during liver transplantation: a randomized controlled trial [abstract]. Hepatology 1993;18:728.
    1. Kojima T, Gando S, Morimoto Y, Mashio H, Goda Y, Kawahigashi H, et al. Systematic elucidation of effects of tranexamic acid on fibrinolysis and bleeding during and after cardiopulmonary bypass surgery. Thromb Res 2001;104:301-7.
    1. Kuitunen A, Hiippala S, Vahtera E, Rasi V, Salmenperä M. The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery. Acta Anaesth Scand 2005;49:1272-9.
    1. Kuitunen AH, Suojaranta-Ylinen RT, Kukkonen SI, Niemi TT. Tranexamic acid does not correct the haemostatic impairment caused by hydroxyethyl starch (200 kDa/0.5) after cardiac surgery. Blood Coagul Fibrinolysis 2006;17:639-45.
    1. Kulkarni AP, Chaukar MS, Patil V, Divatia J. Does tranexamic acid administration reduce blood loss during head and neck surgery? A prospective randomized double-blind study. ASA Abstracts 2011:A484.
    1. Later AF, Maas JJ, Engbers FH, Versteegh MI, Bruggemans EF, Dion RA, et al. Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial. Eur J Cardiothorac Surg 2009;36:322-9.
    1. Leelahanon S, Singhatanadgige S, Luengtaviboon K, Cheanvechai C, Benjacholamas V, Namchaisiri J, et al. Can tranexamic acid improve post cardiopulmonary bypass hemostasis? a double-blind prospective randomized placebo-controlled study. Thai J Surg 2002;23:138.
    1. Lemay E, Guay J, Côté C, Roy A. Tranexamic acid reduces the need for allogenic red blood cell transfusions in patients undergoing total hip replacement. Can J Anaesth 2004;51:31-7.
    1. Lin PC, Hsu CH, Chen WS, Wang JW. Does tranexamic acid save blood in minimally invasive total knee arthroplasty? Clin Orthop Relat Res 2011;469:1995-2002.
    1. Macgillivray RG, Tarabichi SB, Hawari MF, Raoof NT. Tranexamic acid to reduce blood loss after bilateral total knee arthroplasty a prospective, randomized double blind study. J Arthroplasty 2011;26:24-8.
    1. Maddali MM, Rajakumar MC. Tranexamic acid and primary coronary artery bypass surgery: a prospective study. Asian Cardiovasc Thorac Ann 2007;15:313-9.
    1. Malhotra R. The use of tranexamic acid to reduce blood loss in primary cementless total hip arthroplasty. Eur J Orthop Surg Traumatol 2011;21:101-4.
    1. Mansour EE, Mustafa B. Aprotinin versus tranexamic acid in patients receiving aspirin and undergoing off-pump coronary artery bypass. Egypt J Anaesth 2004;20:229-36.
    1. McConnell JS, Shewale S, Munro NA, Shah K, Deakin AH, Kinninmonth AW. Reduction of blood loss in primary hip arthroplasty with tranexamic acid or fibrin spray. Acta Orthop 2011;82:660-3.
    1. Mehr-Aein A, Davoodi S, Madani-Civi M. Effects of tranexamic acid and autotransfusion in coronary artery bypass. Asian Cardiovasc Thoracic Ann 2007;15:49-53.
    1. Menichetti A, Tritapepe L, Ruvolo G, Speziale G, Cogliati A, Di Giovanni C, et al. Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: aprotinin vs tranexamic acid vs epsilon aminocaproic acid. J Cardiovasc Surg 1996;37:401-7.
    1. Miller RA, May MW, Hendry WF, Whitfield HN, Wickham JE. The prevention of secondary haemorrhage after prostatectomy: the value of antifibrinolytic therapy. Br J Urol 1980;52:26-8.
    1. Misfeld M, Dubbert S, Eleftheriadis S, Siemens HJ, Wagner T, Sievers HH. Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations. Ann Thorac Surg 1998;66:792-9.
    1. Molloy DO, Archbold HA, Ogonda L, McConway J, Wilson RK, Beverland DE. Comparison of topical fibrin spray and tranexamic acid on blood loss after total knee replacement: a prospective, randomised controlled trial. J Bone Joint Surg Br 2007;89:306-9.
    1. Moret F, Flo A, Escudero A, Masso E, Munoz S, Ruyra X, et al. Tranexamic acid reduces postoperative bleeding but not allogeneic transfusion requirements in valve replacement cardiac surgery. Transfus Altern Transfus Med 2006;8(suppl 1):93.
    1. Movafegh A, Eslamian L, Dorabadi A. Effect of intravenous tranexamic acid administration on blood loss during and after cesarean delivery. Int J Gynaecol Obstet 2011;115:224-6.
    1. Murphy GJ, Mango E, Lucchetti V, Battaglia F, Catapano D, Rogers CA, et al. A randomized trial of tranexamic acid in combination with cell salvage plus a meta-analysis of randomized trials evaluating tranexamic acid in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg 2006;132:475-80, 80.e1-8.
    1. Neilipovitz DT, Murto K, Hall L, Barrowman NJ, Splinter WM. A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. Anesth Analg 2001;93:82-7.
    1. Niskanen RO, Korkala OL. Tranexamic acid reduces blood loss in cemented hip arthroplasty: a randomized, double-blind study of 39 patients with osteoarthritis. Acta Orthopaed 2005;76:829-32.
    1. Nuttall GA, Oliver WC, Ereth MH, Santrach PJ, Bryant SC, Orszulak TA, et al. Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding. Anesthesiology 2000;92:674-82.
    1. Oertli D, Laffer U, Haberthuer F, Kreuter U, Harder F. Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer. Br J Surg 1994;81:856-9.
    1. Orpen NM, Little C, Walker G, Crawfurd EJ. Tranexamic acid reduces early post-operative blood loss after total knee arthroplasty: a prospective randomised controlled trial of 29 patients. Knee 2006;13:106-10.
    1. Ozal E, Kuralay E, Bingöl H, Cingöz F, Ceylan S, Tatar H. Does tranexamic acid reduce desmopressin-induced hyperfibrinolysis? J Thorac Cardiovasc Surg 2002;123:539-43.
    1. Penta de Peppo A, Pierri MD, Scafuri A, De Paulis R, Colantuono G, Caprara E, et al. Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs. Tex Heart Inst J 1995;22:231-6.
    1. Pfizer. Study of tranexamic acid for the reduction of blood loss in patients undergoing surgery for long bone fracture. 2011. .
    1. Pinosky ML, Kennedy DJ, Fishman RL, Reeves ST, Alpert CC, Ecklund J, et al. Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. J Cardiac Surg 1997;12:330-8.
    1. Pleym H, Stenseth R, Wahba A, Bjella L, Karevold A, Dale O. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Anesth Analg 2003;96:923-8.
    1. Pugh SC, Wielogorski AK. A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth 1995;9:240-4.
    1. Rannikko A, Pétas A, Taari K. Tranexamic acid in control of primary hemorrhage during transurethral prostatectomy. Urology 2004;64:955-8.
    1. Reid RW, Zimmerman AA, Laussen PC, Mayer JE, Gorlin JB, Burrows FA. The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 1997;84:990-6.
    1. Risch A, Dorscheid E, Stein G, Seyfert UT, Grundmann U. [The effect of aprotinin and tranexamic acid on fibrinolysis and thrombin generation during cardiopulmonary bypass]. [German]. Anaesthesist 2000;49:279-85.
    1. Rybo G, Westerberg H. The effect of tranexamic acid (AMCA) on postoperative bleeding after conization. Acta Obstetr Gynecol Scand 1972;51:347-50.
    1. Sadeghi M, Mehr-Aein A. Does a single bolus dose of tranexamic acid reduce blood loss and transfusion requirements during hip fracture surgery? A prospective randomized double blind study in 67 patients. Acta Med Iranica 2007;45:437-42.
    1. Santos AT, Kalil RA, Bauemann C, Pereira JB, Nesralla IA. A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting. Braz J Med Biol Res 2006;39:63-9.
    1. Sekhavat L, Tabatabaii A, Dalili M, Farajkhoda T, Tafti AD. Efficacy of tranexamic acid in reducing blood loss after cesarean section. J Matern Fetal Neonatal Med 2009;22:72-5.
    1. Sethna NF, Zurakowski D, Brustowicz RM, Bacsik J, Sullivan LJ, Shapiro F. Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology 2005;102:727-32.
    1. Shore-Lesserson L, Reich DL, Vela-Cantos F, Ammar T, Ergin MA. Tranexamic acid reduces transfusions and mediastinal drainage in repeat cardiac surgery. Anesth Analg 1996;83:18-26.
    1. Sorin A, Claeys MA, Jansen A, D’Haese J, Camu F. Reduction of blood loss by tranexamic acid in total knee replacement. J Bone Joint Surg Br 1999;81-B(suppl.II):234.
    1. Speekenbrink RG, Vonk AB, Wildevuur CR, Eijsman L. Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary bypass grafting. Ann Thorac Surg 1995;59:438-42.
    1. Taghaddomi RJ, Mashhadinezhad H, Attar ARS, Peivandi A. The effect of intravenous tranexamic acid on blood loss in lumbar hernial disc resection under inhalation and total intravenous anesthesia. Iran Red Crescent Med J 2009;11:265-70.
    1. Taghaddomi RJ, Mirzaee A, Attar AS, Shirdel A. Tranexamic acid reduces blood loss in off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2009;23:312-5.
    1. Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. J Bone Joint Surg Br 2001;83:702-5.
    1. Tsutsumimoto T, Shimogata M, Ohta H, Yui M, Yoda I, Misawa H. Tranexamic acid reduces perioperative blood loss in cervical laminoplasty: a prospective randomized study. Spine (Phila Pa 1976) 2011;36:1913-8.
    1. Uozaki Y, Watanabe G, Kotou K, Ueyama K, Doi Y, Misaki T. Effect of tranexamic acid on blood loss reduction after cardiopulmonary bypass. Jap J Thorac Cardiovasc Surg 2001;49:273-8.
    1. Vanek T, Jares M, Fajt R, Straka Z, Jirasek K, Kolesar M, et al. Fibrinolytic inhibitors in off-pump coronary surgery: a prospective, randomized, double-blind TAP study (tranexamic acid, aprotinin, placebo). Eur J Cardiothorac Surg 2005;28:563-8.
    1. Veien M, Sørensen JV, Madsen F, Juelsgaard P. Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized, controlled study. Acta Anaesth Scand 2002;46:1206-11.
    1. Wang G, Xie G, Jiang T, Wang Y, Wang W, Ji H, et al. Tranexamic acid reduces blood loss after off-pump coronary surgery: a prospective, randomized, double-blind, placebo-controlled study. Anesth Analg 2011; published online 7 Jul.
    1. Wei M, Jian K, Guo Z, Wang L, Jiang D, Zhang L, et al. Tranexamic acid reduces postoperative bleeding in off-pump coronary artery bypass grafting. Scand Cardiovasc J 2006;40:105-9.
    1. Wong J, El Beheiry H, Rampersaud YR, Lewis S, Ahn H, De Silva Y, et al. Tranexamic acid reduces perioperative blood loss in adult patients having spinal fusion surgery. Anesth Analg 2008;107:1479-86.
    1. Wu CC, Ho WM, Cheng SB, Yeh DC, Wen MC, Liu TJ, et al. Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a “blood transfusion”-free hepatectomy. Ann Surg 2006;243:173-80.
    1. Yang H, Zheng S, Shi C. [Clinical study on the efficacy of tranexamic acid in reducing postpartum blood lose: a randomized, comparative, multicenter trial]. Zhonghua Fu Chan Ke Za Zhi 2001;36:590-2.
    1. Yassen K, Bellamy MC, Sadek SA, Webster NR. Tranexamic acid reduces blood loss during orthotopic liver transplantation. Clin Transplant 1993;7:453-8.
    1. Yepes JF. Use of tranexamic acid during oral surgery in patients receiving anticoagulant therapy. (Abstract 56th Annual Meeting AAOM). Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:419.
    1. Zabeeda D, Medalion B, Sverdlov M, Ezra S, Schachner A, Ezri T, et al. Tranexamic acid reduces bleeding and the need for blood transfusion in primary myocardial revascularization. Ann Thorac Surg 2002;74:733-8.
    1. Zhang F, Gao Z, Yu J. [Clinical comparative studies on effect of tranexamic acid on blood loss associated with total knee arthroplasty]. [Chinese]. Chung-Kuo Hsiu Fu Chung Chien Wai Ko Tsa Chih 2007;21:1302-4.
    1. Zheng SR, Chi GZ. Effects of tranexamic acid on decreasing blood loss within two hours after delivery. A multicenter randomized comparative study. Blood 2000;96:846a.
    1. Zohar E, Ellis M, Ifrach N, Stern A, Sapir O, Fredman B. The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement. Anesth Analg 2004;99:1679-83.
    1. Zonis Z, Seear M, Reichert C, Sett S, Allen C. The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. J Thorac Cardiovasc Surg 1996;111:982-7.
    1. Zufferey PJ, Miquet M, Quenet S, Martin P, Adam P, Albaladejo P, et al. Tranexamic acid in hip fracture surgery: a randomized controlled trial. Br J Anaesth 2010;104:23-30.
    1. Aspirin and tranexamic acid for coronary artery surgery-ATACAS (ACTRN12605000557636) .
    1. Blood loss and transfusion requirement in infants treated with tranexamic acid (NCT01094977) .
    1. Fibrin glue or tranexamic acid for total knee arthroplasty-ATRHEMOS (NCT01306370) .
    1. Hemostatic and anti-inflammatory effects of ulinastatin and tranexamic acid in cardiopulmonary bypass cardiac surgery (NCT01060189) .
    1. Impact of tranexamic acid on red blood cell transfusion in spinal surgery (NCT01258010) .
    1. Tranexamic acid (TXA) versus epsilon aminocaproic acid (EACA) versus placebo for spine surgery (NCT00958581) .
    1. intravenous tranexamic acid and intraoperative visualization during functional endoscopic sinus surgery (NCT01111669) .
    1. Multicenter, randomized placebo-controlled clinical trial to evaluate the effect of perioperative use of tranexamic acid on transfusion requirements and surgical bleeding in major spine surgery (NCT01136590) .
    1. Non-idiopathic scoliosis treated with tranexamic acid (NCT01089140) .
    1. Search for optimum dose and timing of tranexamic acid administration in cardiac surgery with cardiopulmonary bypass (JPRN-UMIN000003327) .
    1. Tranexamic acid for craniofacial surgery (NCT00722436) .
    1. Tranexamic acid in surgery of advanced ovarian cancer (NCT00740116) .
    1. Tranexamic acid on blood loss and transfusion in cardiac surgery (NCT01060176) .
    1. Tranexamic acid versus placebo to reduce perioperative bleeding after major hepatectomy (NCT00657384) .
    1. Adler Ma SC, Brindle W, Burton G, Gallacher S, Hong FC, Manelius I, et al. Tranexamic acid is associated with less blood transfusion in off-pump coronary artery bypass graft surgery: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth 2011;25:26-35.
    1. Alshryda S, Sarda P, Sukeik M, Nargol A, Blenkinsopp J, Mason JM. Tranexamic acid in total knee replacement: a systematic review and meta-analysis. J Bone Joint Surg Br 2011;93:1577-85.
    1. Barrons RW, Jahr JS. A review of post-cardiopulmonary bypass bleeding, aminocaproic acid, tranexamic acid, and aprotinin. Am J Ther 1996;3:821-38.
    1. Brown JR, Birkmeyer NJ, O’Connor GT. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation 2007;115:2801-13.
    1. Cid J, Lozano M. Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials. Transfusion 2005;45:1302-7.
    1. Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D. Blood loss in major spine surgery: are there effective measures to decrease massive hemorrhage in major spine fusion surgery? Spine (Phila Pa 1976) 2010;35(suppl 9):S47-56.
    1. Erstad BL. Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery. Ann Pharmacother 2001;35:1075-84.
    1. Erstad BL. Systemic hemostatic medications for reducing surgical blood loss. Ann Pharmacother 2001;35:925-34.
    1. Fremes SE, Wong BI, Lee E, Mai R, Christakis GT, McLean RF, et al. Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding. Ann Thorac Surg 1994;58:1580-8.
    1. Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am 2008;90:2399-407.
    1. Gill JB, Rosenstein A. The use of antifibrinolytic agents in total hip arthroplasty: a meta-analysis. J Arthroplasty 2006;21:869-73.
    1. Guay J, de Moerloose P, Lasne D. Minimizing perioperative blood loss and transfusions in children. Can J Anaesth 2006;53(suppl 6):S59-67.
    1. Gurusamy KS, Li J, Sharma D, Davidson BR. Pharmacological interventions to decrease blood loss and blood transfusion requirements for liver resection. Cochrane Database Syst Rev 2009(4):CD008085.
    1. Ho KM, Ismail H. Use of intravenous tranexamic acid to reduce allogeneic blood transfusion in total hip and knee arthroplasty: a meta-analysis. Anaesth Intensive Care 2003;31:529-37.
    1. Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res 2009;123:687-96.
    1. Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy for fibroids. Cochrane Database Syst Rev 2009(3):CD005355.
    1. Laupacis A, Fergusson D. Drugs to minimize perioperative blood loss in cardiac surgery: meta-analyses using perioperative blood transfusion as the outcome. The International Study of Peri-operative Transfusion (ISPOT) Investigators. Anesth Analg 1997;85:1258-67.
    1. Levi M, Cromheecke ME, de Jonge E, Prins MH, de Mol BJ, Briet E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999;354:1940-7.
    1. Liu JM, Peng HM, Shen JX, Qiu GX. [A meta-analysis of the effectiveness and safety of using tranexamic acid in spine surgery]. Zhonghua Wai Ke Za Zhi 2010;48:937-42.
    1. Makwana J, Paranjape S, Goswami J. Antifibrinolytics in liver surgery. Indian J Anaesth 2010;54:489-95.
    1. Martin-Hirsch PP, Keep SL, Bryant A. Interventions for preventing blood loss during the treatment of cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2010(6):CD001421.
    1. Molenaar IQ, Warnaar N, Groen H, Tenvergert EM, Slooff MJ, Porte RJ. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2007;7:185-94.
    1. Ngaage DL, Bland JM. Lessons from aprotinin: is the routine use and inconsistent dosing of tranexamic acid prudent? Meta-analysis of randomised and large matched observational studies. Eur J Cardiothorac Surg 2010;37:1375-83.
    1. Novikova N, Hofmeyr GJ. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database Syst Rev 2010(7):CD007872.
    1. Schouten ES, van de Pol AC, Schouten AN, Turner NM, Jansen NJ, Bollen CW. The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: a meta-analysis. Pediatr Crit Care Med 2009;10:182-90.
    1. Sukeik M, Alshryda S, Haddad FS, Mason JM. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J Bone Joint Surg Br 2011;93:39-46.
    1. Tzortzopoulou A, Cepeda MS, Schumann R, Carr DB. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev 2008(3):CD006883.
    1. Umscheid CA, Kohl BA, Williams K. Antifibrinolytic use in adult cardiac surgery. Curr Opin Hematol 2007;14:455-67.
    1. Zhang H, Chen J, Chen F, Que W. The effect of tranexamic acid on blood loss and use of blood products in total knee arthroplasty: a meta-analysis. Knee Surg Sports Traumatol Arthrosc 2011; published online 8 Nov.
    1. Zufferey P, Merquiol F, Laporte S, Decousus H, Mismetti P, Auboyer C, et al. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology 2006;105:1034-46.
    1. Ioannidis JP, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA 2001;285:437-43.
    1. Loke YK, Derry S. Reporting of adverse drug reactions in randomised controlled trials—a systematic survey. BMC Clin Pharmacol 2001;1:3.
    1. The CRASH-2 Collaborators. 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.
    1. Myles PS, Smith J, Knight J, Cooper DJ, Silbert B, McNeil J, et al. Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) Trial: rationale and design. Am Heart J 2008;155:224-30.

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