Tranexamic acid: A clinical review

Anaesthesiology Intensive Therapy

Volumn 47, Issue 4, 2015, Pages 339-350

  Ng, William ^a   Jerath, Angela ^a,b   Wasowicz, Marcin ^a,b  

^a TORONTO GENERAL HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Anesthesia; Antifibrinolytic; Blood conservation; Tranexamic acid

Indexed keywords

TRANEXAMIC ACID; ANTIFIBRINOLYTIC AGENT;

ARTICLE; DRUG EFFICACY; DRUG MECHANISM; DRUG USE; GASTROINTESTINAL SYMPTOM; GYNECOLOGY; HEART SURGERY; HUMAN; INJURY; LIVER SURGERY; NEUROSURGERY; OBSTETRICS; ORTHOPEDIC SURGERY; SEIZURE; SKIN ALLERGY; THROMBOEMBOLISM; VISUAL DISORDER; BLOOD LOSS, SURGICAL; GENERAL SURGERY;

ANTIFIBRINOLYTIC AGENTS; BLOOD LOSS, SURGICAL; GENERAL SURGERY; HUMANS; TRANEXAMIC ACID;

EID: 84942903836     PISSN: 16425758     EISSN: 17312531     Source Type: Journal    
DOI: 10.5603/AIT.a2015.0011     Document Type: Article

References (159)

1. Karkouti K, Wijeysundera DN, Yau TM et al.: The independent association of massive blood loss with mortality in cardiac surgery. Transfusion 2004; 44: 1453-1462.
2. Karkouti K, Beattie WS, Dattilo KM et al.: A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion 2006; 46: 327-338.
3. Henry DA, Carless PA, Moxey AJ et al.: Anti-fibrinolytic use for minimising perioperative allogeneic blood Transfusion Cochrane database Syst Rev 2011; 3: CD001886.
4. Ortmann E, Besser MW, Klein AA: Antifibrinolytic agents in current anaesthetic practice. Br J Anaesth 2013; 111: 549-563. doi:10.1093/bja/aet154.
5. Ker K, Roberts I: Tranexamic acid for surgical bleeding. BMJ 2014; 349: g4934. doi: 10.1136/bmj.g4934.
6. Pfizer Canada Inc. Cyklokapron® - Product monograph [Internet]. Kirkland: Pfizer Canada Inc; 2013 p. 1-22. Available from: http://www.pfizer.ca/en/our-products/products/monograph/195;11.12.2014.
7. Dunn CJ, Goa KL: Tranexamic acid. Drugs 1999; 57: 1005-1032.
8. McCormack PL: Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs 2012; 72: 585-617. doi: 10.2165/11209070-000000000-00000.
9. Harker LA, Malpass TW, Branson HE, Hessel II EA, Slichter SJ: Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood 1980; 56: 824-834.
10. De Haan J, Van Oeveren W: Platelets and soluble fibrin promote plasminogen activation causing downregulation of platelet glycoprotein Ib/IX complexes: protection by aprotinin. Thromb Res 1998; 92: 171-179.
11. Kucuk O, Kwaan HC, Frederickson J, Wade L, Green D: Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation. Am J Hematol 1986; 23: 223-229.
12. Khuri SF, Valeri CR, Loscalzo J et al.: Heparin causes platelet dysfunction and induces fibrinolysis before cardiopulmonary bypass. Ann Thorac Surg 1995; 60: 1008-1014.
13. Soslau G, Horrow J, Brodsky I: Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol 1991; 38: 113-119.
14. Jimenez JJ, Iribarren JL, Lorente L 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 2007; 11: R117.
15. Jiménez JJ, Iribarren JL, Brouard M et al.: Safety and effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial. J Cardiothorac Surg 2011; 6: 138.
16. Schöchl H, Frietsch T, Pavelka M, Jámbor C: Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma 2009; 67: 125-131. doi: 10.1097/TA.0b013e31818b2483.
17. Hess JR, Brohi K, Dutton RP et al.: The coagulopathy of trauma: a review of mechanisms. J Trauma 2008; 65: 748-754. doi: 10.1097/TA.0b013e3181877a9c.
18. Levrat a, Gros A, Rugeri L et al.: Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients. Br J Anaesth 2008; 100: 792-797. doi: 10.1093/bja/aen083.
19. Kutcher ME, Cripps MW, McCreery RC et al.: Criteria for empiric treatment of hyperfibrinolysis after trauma. J Trauma Acute Care Surg 2012; 73: 87-93. doi: 10.1097/TA.0b013e3182598c70.
20. Melissari E, Scully MF, Paes T, Kakkar VV: The influence of LMW heparin on the coagulation and fibrinolytic response to surgery. Thromb Res 1985; 37: 115-126.
21. Özal EE, Kuralay E, Bingöl H, Cingöz F, Ceylan S, Tatar H: Does tranexamic acid reduce desmopressin-induced hyperfibrinolysis? J Thorac Cardiovasc Surg 2002; 123: 539-543.
22. Ker K, Edwards P, Perel P, Shakur H, Roberts I: Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012; 344: e3054. doi: 10.1136/bmj.e3054.
23. Mangano DT, Tudor IC, Dietzel C: The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354: 353-365.
24. Mangano DT, Miao Y, Vuylsteke A et al.: Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA 2007; 297: 471-479.
25. Fergusson DA, Hébert PC, Mazer CD et al.: A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 2008; 358: 2319-2331. doi: 10.1056/NEJMoa0802395.
26. Ferraris VA, Brown JR, Despotis GJ et al.: 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91: 944-982. doi: 10.1016/j.athoracsur.2010.11.078.
27. Beattie WS, Karkouti K: The post-BART anti-fibrinolytic dilemma? J Cardiothorac 2011; 25: 3-5. doi: 10.1053/j.jvca.2010.11.018.
28. Karkouti K, Wijeysundera DN, Yau TM, McCluskey SA, Tait G, Beattie WS: The risk-benefit profile of aprotinin versus tranexamic acid in cardiac surgery. Anesth Analg 2010; 110: 21-29. doi: 10.1213/ANE.0b013e3181c0ea6d.
29. Laupacis A, Fergusson D: Drugs to minimize perioperative blood loss in cardiac surgery. Anesth Analg 1997; 85: 1258-1267.
30. Henry DA, Carless PA, Moxey AJ et al.: Anti-fibrinolytic use for minimising perioperative allogeneic blood Transfusion Cochrane database Syst Rev 2007; 4: CD001886.
31. Henry D, Carless P: The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. Can Med Assoc J 2009; 180: 183-194. doi: 10.1503/cmaj.081109.
32. 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 Cardio-thoracic Surg 2010; 37: 1375-1383. doi: 10.1016/j.ejcts.2009.11.055.
33. Armellin G, Vinciguerra A, Bonato R, Pittarello D, Giron GP: Tranexamic acid in primary CABG surgery: high vs low dose. Minerva Anestesiol 2004; 70: 97-107.
34. Dhir A: Antifibrinolytics in cardiac surgery. Ann Card Anaesth 2013; 16: 117-125 doi: 10.4103/0971-9784.109749.
35. Horrow JC, Van Riper DF, Strong MD, Grunewald KE, Parmet JL: Dose response of tranexamic acid. Anesthesiology 1995; 82: 383-392.
36. Nuttall GA, Gutierrez MC, Dewey JD et al.: A preliminary study of a new tranexamic acid dosing schedule for cardiac surgery. J Cardiothorac Vasc Anesth 2008; 22: 230-235. doi: 10.1053/j.jvca.2007.12.016.
37. Dowd NP, Karski JM, Cheng DC et al.: Pharmacokinetics of tranexamic acid during cardiopulmonary bypass. Anesthesiology 2002; 97: 390-399.
38. Sigaut S, Tremey B, Ouattara A: Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology 2014; 2: 590-600. doi: 10.1097/ALN.0b013e3182a443e8.
39. Weber CF, Görlinger K, Byhahn C et al.: Tranexamic acid partially improves platelet function in patients treated with dual antiplatelet therapy. Eur J Anaesthesiol 2011; 28: 57-62. doi: 10.1097/EJA.0b013e32834050ab.
40. Schouten ES, van de Pol AC, Schouten ANJ, Turner NM, Jansen NJG, 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: 182-190. doi: 10.1097/PCC.0b013e3181956d61.
41. Shimizu K, Toda Y, Iwasaki T et al.: Effect of tranexamic acid on blood loss in pediatric cardiac surgery: a randomized trial. J Anesth 2011; 25: 823-830. doi: 10.1007/s00540-011-1235-z.
42. Giordano R, Palma G, Poli V et al.: Tranexamic acid therapy in pediatric cardiac surgery: a single-center study. Ann Thorac Surg 2012; 94: 1302-1306. doi: 10.1016/j.athoracsur.2012.04.078.
43. Faraoni D, Willems A, Melot C, De Hert S, Van der Linden P: Efficacy of tranexamic acid in paediatric cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg 2012; 42: 781-786. doi: 10.1093/ejcts/ezs127.
44. Goobie SM, Meier PM, Sethna NF et al.: Population pharmacokinetics of tranexamic acid in paediatric patients undergoing craniosynostosis surgery. Clin Pharmacokinet 2013; 52: 267-276. doi: 10.1007/s40262-013-0033-1.
45. Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP: The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesth Analg 2013; 117: 767-772. doi: 10.1213/ANE.0b013e3182a22258.
46. Faraoni D, Goobie SM: New insights about the use of tranexamic acid in children undergoing cardiac surgery: from pharmacokinetics to pharmacodynamics. Anesth Analg 2013; 117: 760-762. doi: 10.1213/ANE.0b013e3182a22278.
47. Faraoni D, Goobie SM: The efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery: a systematic review of the literature. Anesth Analg 2014; 118: 628-636. doi: 10.1213/ANE.0000000000000080.
48. 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. doi: 10.1002/14651858.CD006883.pub2.
49. 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: 82-87.
50. 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: 727-732.
51. Xu C, Wu A, Yue Y: Which is more effective in adolescent idiopathic scoliosis surgery: batroxobin, tranexamic acid or a combination? Arch Orthop Trauma Surg 2012; 132: 25-31. doi: 10.1007/s00402-011-1390-6.
52. Basta MN, Stricker PA, Taylor JA: A systematic review of the use of antifibrinolytic agents in pediatric surgery and implications for craniofacial use. Pediatr Surg Int 2012; 28: 1059-1069. doi: 10.1007/s00383-012-3167-6.
53. Holcomb JB: Tranexamic acid in elective craniosynostosis surgery: it works, but how? Anesthesiology 2011; 114: 737-738. doi: 10.1097/ALN.0b013e3182110083.
54. Goobie SM, Meier PM, Pereira LM et al.: Efficacy of tranexamic acid in pediatric craniosynostosis surgery: a double-blind, placebo-controlled trial. Anesthesiology 2011; 114: 862-871. doi: 10.1097/ALN.0b013e318210fd8f.
55. Dadure C, Sauter M, Bringuier S et al.: Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology 2011; 114: 856-861. doi: 10.1097/ALN.0b013e-318210f9e3.
56. 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: 687-696. doi: 10.1016/j.thromres.2008.09.015.
57. Poeran J, Rasul R, Suzuki S et al.: Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. BMJ 2014; 349: g4829. doi: 10.1136/bmj.g4829.
58. 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. doi: 10.1302/0301-620X.93B1.24984.
59. 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: 1577-1585. doi: 10.1302/0301-620X.93B12.26989.
60. Klenerman L, Chakrabarti R, Mackie I: Changes in haemostatic system after application of a tourniquet. Lancet 1977; 970-972.
61. Yang B, Li H, Wang D, He X, Zhang C, Yang P: Systematic review and meta-analysis of perioperative intravenous tranexamic acid use in spinal surgery. PLoS One 2013; 8: e55436. doi: 10.1371/journal.pone.0055436.
62. 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: 1913-1918. doi: 10.1097/BRS.0b013e-3181fb3a42.
63. Perel P, Ker K, Morales Uribe CH, Roberts I: Tranexamic acid for reducing mortality in emergency and urgent surgery. Cochrane database Syst Rev 2013; 1: CD010245. doi: 10.1002/14651858.CD010245.pub2.
64. Wong J, Abrishami A, El Beheiry H et al.: Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am 2010; 92: 2503-2513.
65. Baric D, Biocina B, Unic D et al.: Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg 2007; 31: 366-371; discussion 371.
66. Fawzy H, Elmistekawy E, Bonneau D, Latter D, Errett L: Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial. J Cardiothorac Surg 2009; 4: 25. doi: 10.1186/1749-8090-4-25.
67. Dell'Amore A, Caroli G, Nizar A et al.: Can topical application of tranexamic acid reduce blood loss in thoracic surgery? A prospective randomised double blind investigation. Heart Lung Circ 2012; 21: 706-710.
68. Nouraei M, Gholipour Baradari A, Ghafari R, Habibi MR, Emami Zeydi A, Sharifi N: Decreasing blood loss and the need for transfusion after CABG surgery: a double-blind randomized clinical trial of topical tranexamic acid. Turkish J Med Sci 2013; 43: 273-278.
69. Alshryda S, Mason J, Sarda P et al.: Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am 2013; 95: 1969-1974.
70. Alshryda S, Mason J, Vaghela M et al.: Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (TRANX-K). J Bone Joint Surg Am 2013; 95: 1961-1968.
71. Chang C-H, Chang Y, Chen DW, Ueng SWN, Lee MS: Topical tranexamic acid reduces blood loss and transfusion rates associated with primary total hip arthroplasty. Clin Orthop Relat Res 2014; 472: 1552-1557. doi: 10.1007/s11999-013-3446-0.
72. Zhang Y, Fu X, Liu W-X, Li Y-M, Ma X-L, Li Z-J: Safety and efficacy of intra-articular injection of tranexamic acid in total knee arthroplasty. Orthopedics 2014; 37: e775-e782. doi: 10.3928/01477447-20140825-53.
73. Albirmawy OA, Saafan ME, Shehata EM, Basuni AS, Eldaba AA: Topical application of tranexamic acid after adenoidectomy: a double-blind, prospective, randomized, controlled study. Int J Pediatr Otorhinolaryngol 2013; 77: 1139-1142.
74. Athanasiadis T, Beule AG, Wormald PJ: Effects of topical antifibrinolytics in endoscopic sinus surgery: a pilot randomized controlled trial. Am J Rhinol 2007; 21: 737-742. doi: 10.2500/ajr.2007.21.3097.
75. Sindet-Pedersen S, Ramström G, Bernvil S, Blombäck M: Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989; 320: 840-843.
76. Lee APH, Boyle CA, Savidge GF, Fiske J: Effectiveness in controlling haemorrhage after dental scaling in people with haemophilia by using tranexamic acid mouthwash. Br Dent J 2005; 198: 33-38; discussion 26.
77. Kaewpradub P, Apipan B, Rummasak D: Does tranexamic acid in an irrigating fluid reduce intraoperative blood loss in orthognathic surgery? A double-blind, randomized clinical trial. J Oral Maxillofac Surg 2011; 69: e186-e189. doi: 10.1016/j.joms.2010.11.041.
78. Panteli M, Papakostidis C, Dahabreh Z, Giannoudis PV: Topical tranexamic acid in total knee replacement: a systematic review and meta-analysis. Knee 2013; 20: 300-309. doi: 10.1016/j.knee.2013.05.014.
79. Abrishami A, Chung F, Wong J: Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis. Can J Anaesth 2009; 56: 202-212. doi: 10.1007/s12630-008-9038-x.
80. Mahaffey R, Wang L, Hamilton A, Phelan R, Arellano R: A retrospective analysis of blood loss with combined topical and intravenous tranexamic acid after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2013; 27: 18-22. doi: 10.1053/j.jvca.2012.08.004.
81. Spegar J, Vanek T, Snircova J et al.: Local and systemic application of tranexamic acid in heart valve surgery: a prospective, randomized, double blind LOST study. J Thromb Thrombolysis 2011; 32: 303-310. doi: 10.1007/s11239-011-0608-3.
82. 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 Elsevier Ltd 2010; 376: 23-32.
83. 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, 1101.e1-2. doi: 10.1016/S0140-6736(11)60278-X.
84. Moore HB, Moore EE, Gonzalez E et al.: Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy. J Trauma Acute Care Surg 2014; 77: 811-817; discussion 817. doi: 10.1097/TA.0000000000000341.
85. Meier K, Hoesch R: Antifibrinolytic Therapy in Intracranial Hemorrhage. Drug Dev Res 2013; 74: 478-484.
86. Roos YBWEM, Rinkel GJE, Vermeulen M, Algra A, van Gijn J: Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane database Syst Rev 2003; 2: CD001245.
87. Roos Y: Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. STAR Study Group. Neurology 2000; 54: 77-82.
88. Albuquerque FC: Rebleeding and its prevention after subarachnoid hemorrhage. World Neurosurg 2013; 79: 245-246. doi: 10.1016/j.wneu.2012.07.025.
89. Starke RM, Kim GH, Fernandez A et al.: Impact of a protocol for acute antifibrinolytic therapy on aneurysm rebleeding after subarachnoid hemorrhage. Stroke 2008; 39: 2617-2621. doi: 10.1161/STROKEAHA.107.506097.
90. Harrigan MR, Rajneesh KF, Ardelt AA, Fisher WS: Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus. Neurosurgery 2010; 67: 935-939; discussion 939-940.
91. Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson K-E: Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg 2002; 97: 771-778.
92. Larsen CC, Astrup J: Rebleeding after aneurysmal subarachnoid hemorrhage: A literature review. World Neurosurg 2013: 307-312. doi: 10.1016/j.wneu.2012.06.023.
93. Chwajol M, Starke RM, Kim GH, Mayer SA, Connolly ES: Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage. Neurocrit Care 2008; 8: 418-426.
94. Perel P, Al-Shahi Salman R, Kawahara T et al.: Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 2011; 343: d3795. doi: 10.1136/bmj.d3795.
95. Sprigg N, Renton CJ, Dineen RA, Kwong Y, Bath PMW: Tranexamic acid for spontaneous intracerebral hemorrhage: a randomized controlled pilot trial (ISRCTN50867461). J Stroke Cerebrovasc Dis 2014; 23: 1312-1318. doi: 10.1016/j.jstrokecerebrovasdis.2013.11.007.
96. Sprigg N: ISRCTN93732214: Tranexamic acid for IntraCerebral Haemorrhage (TICH-2). ISRCTN Registry 2013; http://www.isrctn.com/ISRCTN93732214; 15.12.2014.
97. Meretoja A, Churilov L, Campbell BCV et al.: The spot sign and tranexamic acid on preventing ICH growth-AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial. Int J Stroke 2014; 9: 519-524. doi: 10.1111/ijs.12132.
98. Steib A, Gengenwin N, Freys G, Boudjema K, Levy S, Otteni JC: Predictive factors of hyperfibrinolytic activity during liver transplantation in cirrhotic patients. Br J Anaesth 1994; 73: 645-648.
99. Segal H, Cottam S, Potter D, Hunt BJ: Coagulation and fibrinolysis in primary biliary cirrhosis compared with other liver disease and during orthotopic liver transplantation. Hepatology 1997; 25: 683-688.
100. Xia VW, Steadman RH: Antifibrinolytics in orthotopic liver transplantation: current status and controversies. Liver Transpl 2005; 11: 10-18.
101. Molenaar IQ, Warnaar N, Groen H, Tenvergert EM, Slooff MJH, Porte RJ: Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2007; 7: 185-194.
102. Dalmau A, Sabaté A, Koo M et al.: The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: a comparative study. Liver Transpl 2004; 10: 279-284.
103. Ickx BE, van der Linden PJ, Melot C et al.: Comparison of the effects of aprotinin and tranexamic acid on blood loss and red blood cell transfusion requirements during the late stages of liver transplantation. Transfusion 2006; 46: 595-605.
104. Gurusamy KS, Pissanou T, Pikhart H, Vaughan J, Burroughs AK, Davidson BR: Methods to decrease blood loss and transfusion requirements for liver transplantation. Cochrane database Syst Rev 2011; 12: CD009052. doi: 10.1002/14651858.CD009052.pub2.
105. Massicotte L, Denault AY, Beaulieu D, Thibeault L, Hevesi Z, Roy A: Aprotinin versus tranexamic acid during liver transplantation: impact on blood product requirements and survival. Transplantation 2011; 91: 1273-1278. doi: 10.1097/TP.0b013e-31821ab9f8.
106. Görlinger K. Coagulation management during liver transplantation. Hamostaseologie 2006; 26 (3 Suppl 1): S64-76.
107. Wu C-C, Ho W-M, Cheng S-B et al.: Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a "blood transfusion" - free hepatectomy. Ann Surg 2006; 243: 173-180.
108. 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.
109. Truong JL, Cyr DP, Lam-McCulloch J, Cleary SP, Karanicolas PJ: Consensus and controversy in hepatic surgery: a survey of Canadian surgeons. J Surg Oncol 2014; 110: 947-951. doi: 10.1002/jso.23748. Epub 2014 Aug 22.
110. Lumsden MA, Wedisinghe L: Tranexamic acid therapy for heavy menstrual bleeding. Expert Opin Pharmacother 2011; 12: 2089-2095. doi: 10.1517/14656566.2011.598857.
111. Lethaby A, Farquhar C, Cooke I: Antifibrinolytics for heavy menstrual bleeding. Cochrane database Syst Rev 2000; 4: CD000249.
112. Lukes AS, Moore KA, Muse KN et al.: Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol 2010; 116: 865-875. doi: 10.1097/AOG.0b013e3181f20177.
113. Winkler UH: The effect of tranexamic acid on the quality of life of women with heavy menstrual bleeding. Eur J Obstet Gynecol Reprod Biol 2001; 99: 238-243.
114. Edlund M, Andresson K, Rybo G, Lindoff C, Astedt B, Schoultz B: Reduction of menstrual blood loss in women suffering from idiopathic menorrhagia with a novel antifibrinolytic drug (Kabi 2161). BJOG An Int J Obstet Gynaecol 1995; 102: 913-917.
115. Novikova N, Hofmeyr GJ: Tranexamic acid for preventing postpartum haemorrhage. Cochrane database Syst Rev 2010; 7: CD007872.
116. 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: 590-592.
117. Gai M, Wu L, Su Q, Tatsumoto K: Clinical observation of blood loss reduced by tranexamic acid during and after caesarian section: a multi-center, randomized trial. Eur J Obstet Gynecol Reprod Biol 2004; 112: 154-157.
118. Peitsidis P, Kadir RA: Antifibrinolytic therapy with tranexamic acid in pregnancy and postpartum. Expert Opin Pharmacother 2011; 12: 503-516. doi: 10.1517/14656566.2011.545818.
119. 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 Obstet Gynecol India 2007; 57: 227-230.
120. 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: 72-75. doi: 10.1080/14767050802353580.
121. Gobbur V, Shiragur S, Jhanwar U, Tehalia M: Efficacy of tranexamic acid in reducing blood loss during lower segment caesarean section. Int J Reprod Contracept Obstet Gynecol 2014; 3: 414.
122. Ferrer P, Roberts I, Sydenham E, Blackhall K, Shakur H: Anti-fibrinolytic agents in post partum haemorrhage: a systematic review. BMC Pregnancy Childbirth 2009; 9: 29. doi: 10.1186/1471-2393-9-29.
123. Ducloy-Bouthors A-S, Jude B, Duhamel A et al.: High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care 2011; 15: R117. doi: 10.1186/cc10143.
124. Gungorduk K, Ascoʇlu O, Yldrm G, Ark C, Tekirdaʇ AÝ, Besmoglu B: Can intravenous injection of tranexamic acid be used in routine practice with active management of the third stage of labor in vaginal delivery? A randomized controlled study. Obstet Gynecol Surv 2013; 68: 673-675.
125. Gungorduk K, Yildirim G, Asicioglu O, Gungorduk Ozgu C, 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: 233-239. doi: 10.1055/s-0030-1268238.
126. Xu J, Gao W, Ju Y: Tranexamic acid for the prevention of postpartum hemorrhage after cesarean section: a double-blind randomization trial. Arch Gynecol Obstet 2013; 287: 463-468. doi: 10.1007/s00404-012-2593-y.
127. 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: 224-226. doi: 10.1016/j.ijgo.2011.07.015.
128. Sentürk MB, Cakmak Y, Yildiz G, Yildiz P: Tranexamic acid for cesarean section: a double-blind, placebo-controlled, randomized clinical trial. Arch Gynecol Obstet 2013; 287: 641-645. doi: 10.1007/s00404-012-2624-8.
129. Chan CC, Chan YY, Tanweer F: Systematic review and meta-analysis of the use of tranexamic acid in tonsillectomy. Eur Arch Otorhinolaryngol 2013; 270: 735-748. doi: 10.1007/s00405-012-2184-3.
130. Sheffer AL, Fearon DT, Austen KF, Rosen FS: Tranexamic acid: preoperative prophylactic therapy for patients with hereditary angioneurotic edema. J Allergy Clin Immunol 1977; 60: 38-40.
131. Laurberg G: Plasma kinin activation in tranexamic acid treated patients with hereditary angioneurotic edema. Arch Dermatol Res 1978; 262: 153-156.
132. Gluud LL, Klingenberg SL, Langholz E: Tranexamic acid for upper gastrointestinal bleeding. Cochrane database Syst Rev 2012; 1: CD006640.
133. Martí-Carvajal AJ, Solà I, Martí-Carvajal PI: Antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease. Cochrane database Syst Rev 2012; 9: CD006007. doi: 10.1002/14651858.CD006007.pub3.
134. Prutsky G, Domecq JP, Salazar CA, Accinelli R: Antifibrinolytic therapy to reduce haemoptysis from any cause. Cochrane database Syst Rev 2012; 4: CD008711. doi: 10.1002/14651858.CD008711.pub2.
135. Schlag M, Hopf R, Zifko U, Redl H: Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats. Acta Neurochir (Wien) 2002; 144: 63-69.
136. Pellegrini A, Giaretta D, Chemello R, Zanotto L, Testa G: Feline generalized epilepsy induced by tranexamic acid (AMCA). Epilepsia 1982; 23: 35-45.
137. Mohseni K, Jafari A, Nobahar MR, Arami A: Polymyoclonus seizure resulting from accidental injection of tranexamic acid in spinal anesthesia. Anesth Analg 2009; 108: 1984-1986. doi: 10.1213/ane.0b013e3181a04d69.
138. Sabzi F, Teimouri H, Zokai A: Myoclonus, seizure, and ventricular fibrillation after intrathecal injection of tranexamic acid. J Tehran Univ Hear Cent 2009; 4: 253-255.
139. Kaabachi O, Eddhif M, Rais K, Zaabar MA: Inadvertent intrathecal injection of tranexamic acid. Saudi J Anaesth 2011; 5: 90-92. doi: 10.4103/1658-354X.76504.
140. Manji RA, Grocott HP, Leake J et al.: Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. Can J Anaesth 2012; 59: 6-13. doi: 10.1007/s12630-011-9618-z.
141. Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M: High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg 2010; 110: 350-353. doi: 10.1213/ANE.0b013e3181c92b23.
142. Sharma V, Katznelson R, Jerath A et al.: The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia 2014; 69: 124-130. doi:10.1111/anae.12516.
143. Koster A, Börgermann J, Zittermann A, Lueth JU, Gillis-Januszewski T, Schirmer U: Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome. Br J Anaesth 2013; 110: 34-40. doi: 10.1093/bja/aes310.
144. Martin K, Breuer T, Gertler R et al.: Tranexamic acid versus ε-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardiothorac Surg 2011; 39: 892-897. doi: 10.1016/j.ejcts.2010.09.041.
145. Lecker I, Orser B a, Mazer CD: "Seizing" the opportunity to understand antifibrinolytic drugs. Can J Anaesth 2012; 59: 1-5. doi: 10.1007/s12630-011-9621-4.
146. Andersson L, Nilsoon IM, Colleen S, Granstrand JB, Melander B: Role of urokinase and tissue activator in sustaining bleeding and the management thereof with EACA and AMCA. Ann NY Acad Sci 1968; 146: 642-656.
147. Benoni G, Björkman S, Fredin H: Application of pharmacokinetic data from healthy volunteers for the prediction of plasma concentrations of tranexamic acid in surgical patients. Clin Drug Investig 1995; 10: 280-287.
148. Fiechtner BK, Nuttall GA, Johnson ME et al.: Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg 2001; 92: 1131-1136.
149. Andersson L, Eriksson O, Hedlund P-O, Kjellman H, Lindqvist B: Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases. Urol Res 1978; 6: 83-88.
150. Sharma V, Fan J, Jerath A et al.: Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass. Anaesthesia 2012; 67: 1242-1250. doi: 10.1111/j.1365-2044.2012.07266.x.
151. Yang QJ, Jerath A, Bies RR, Wasowicz M, Pang KS: Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment. Biopharm Drug Dispos 2015; 36: 294-307. doi: 10.1002/bdd.1941.
152. Ferring Pharmaceuticals. LYSTEDA TM (tranexamci acid) Tablets - PI. Parsippany: Ferring Pharmaceuticals; 2013. p. 1-20. Available from: http://lysteda.com/assets/pi-ferring2013.pdf; 7.12.2014.
153. Ma SCA, Brindle W, Burton G 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. doi: 10.1053/j.jvca.2010.08.012.
154. Ogawa S, Richardson JE, Sakai T, Ide M, Tanaka KA: High mortality associated with intracardiac and intrapulmonary thromboses after cardiopulmonary bypass. J Anesth 2012; 26: 9-19. doi: 10.1007/s00540-011-1253-x.
155. Sundström A, Seaman H, Kieler H, Alfredsson L: The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case-control study using the General Practice Research Database. BJOG 2009; 116: 91-97. doi: 10.1111/j.1471-0528.2008.01926.x.
156. Nardi K, Pelone G, Bartolo M et al.: Ischaemic stroke following tranexamic acid in young patients carrying heterozygosity of MTHFR C677T. Ann Clin Biochem 2011; 48: 575-578. doi: 10.1258/acb.2011.011101.
157. Dewan Y, Komolafe EO, Mejía-Mantilla JH, Perel P, Roberts I, Shakur H: 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.
158. Shakur H, Elbourne D, Gülmezoglu M et al.: Study protocol 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: 40-53.
159. Myles PS, Smith J, Knight J et al.: Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) Trial: rationale and design. Am Heart J 2008; 155: 224-230. doi: 10.1016/j.ahj.2007.10.003.