Clinical use of tranexamic acid: evidences and controversies
Uso clínico do ácido tranexâmico: evidências e controvérsias
Maria J. Colomina, Laura Contreras, Patricia Guilabert, Maylin Koo, Esther Méndez, Antoni Sabate
Abstract
Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized.
Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.
Keywords
Resumo
O ácido tranexâmico (ATX) reduz significativamente a perda de sangue em uma ampla gama de procedimentos cirúrgicos e melhora as taxas de sobrevida em pacientes obstétricas e de trauma com sangramento grave. Embora atue principalmente como inibidor da fibrinólise, também tem efeito anti-inflamatório, podendo ajudar a atenuar a síndrome da resposta inflamatória sistêmica encontrada em alguns pacientes de cirurgia cardíaca. No entanto, a administração de altas doses de ATX tem sido associada a convulsões e outros efeitos adversos que aumentam o custo do atendimento, e a administração de ATX para reduzir o sangramento perioperatório precisa ser padronizada. O ácido tranexâmico é geralmente bem tolerado e a maioria das reações adversas são consideradas leves ou moderadas. Eventos graves são raros em ensaios clínicos, e revisões de literatura têm demonstrado que o ácido tranexâmico é seguro em diversos procedimentos cirúrgicos. No entanto, após muitos anos de experiência com ATX em vários campos, como cirurgia ortopédica, os médicos agora estão questionando se a dosagem, via e intervalo de administração atualmente usados e os métodos usados para controlar e analisar o mecanismo antifibrinolítico do ATX são realmente ideais. Essas questões precisam ser avaliadas e revisadas usando as evidências mais recentes para melhorar a segurança e a eficácia do ATX no tratamento de hemorragia e sangramento intracraniano em procedimentos como transplante de fígado, cirurgia cardíaca, trauma e obstétrica.
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References
1 J.B. Holcomb Multidisciplinary approach to the challenge of hemostasis Anesth Analg, 110 (2010), pp. 354-364
2 L. Tengborn, M. Blombäck, E. Berntorp Tranexamic acid - An old drug still going strong and making a revival Thromb Res, 135 (2015), pp. 231-242
3 T.D. Lloyd, G. Neal-Smith, J. Fennelly, et al. Peri-operative administration of tranexamic acid in lower limb arthroplasty: a multicentre, prospective cohort study Anaesthesia, 75 (2020), pp. 1050-1058
4 CRASH-2 trial collaborators, H. Shakur, I. Roberts, 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, 376 (2010), pp. 23-32
5 H. Shakur, I. Roberts, B. Fawole, et al. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial Lancet, 389 (2017), pp. 2105-2116
6 F. Monaco, P. Nardelli, L. Pasin, et al. Tranexamic acid in open aortic aneurysm surgery. A randomised clinical trial Br J Anaesth, 124 (2019), pp. 35-43
7 S.H. Mina, H.A. Garcia-Perdomo Effectiveness of tranexamic acid for decreasing bleeding in prostate surgery: a systematic review and meta-analysis Cent European J Urol, 71 (2018), pp. 72-77
8 A.R. Jadad, R.A. Moore, D. Carroll, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 17 (1996), pp. 1-12
9 Y.A. Fillingham, D.B. Ramkumar, D.S. Jevsevar, et al. The Efficacy of Tranexamic Acid in Total Knee Arthroplasty: A Network Meta-Analysis J Arthroplasty, 33 (2018) 3090–8.e1
10 Y.A. Fillingham, D.B. Ramkumar, D.S. Jevsevar, et al. The Efficacy of Tranexamic Acid in Total Hip Arthroplasty: A Network Meta-analysis J Arthroplasty, 33 (2018) 3083–9.e4
11 Y.A. Fillingham, D.B. Ramkumar, D.S. Jevsevar, et al. The Safety of Tranexamic Acid in Total Joint Arthroplasty: A Direct Meta-Analysis J Arthroplasty, 33 (2018) 3070–82.e1
12 Xu Sheng, Jerry Yongqiang Chen, Qishi Zheng, et al. The safest and most efficacious route of tranexamic acid administration in total joint arthroplasty: A systematic review and network meta-analysis Thromb Res, 176 (2019), pp. 61-66
13 Y.A. Fillingham, D.B. Ramkumar, D.S. Jevsevar, et al. Tranexamic Acid Use in Total Joint Arthroplasty: The Clinical Practice Guidelines Endorsed by the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society J Arthroplasty, 33 (2018), pp. 3065-3069
14 J. Poeran, R. Rasul, S. Suzuki, 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, 349 (2014), p. g4829
15 M. Franchini, C. Mengoli, M. Marietta, et al. Safety of intravenous tranexamic acid in patients undergoing majororthopaedic surgery: a meta-analysis of randomised controlled trials Blood Transfus, 16 (2018), pp. 36-43
16 N. Tanaka, H. Sakahashi, E. Sato, et al. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee J Bone Joint Surg Br, 83 (2001), pp. 702-705
17 N. Imai, Y. Dohmae, K. Suda, et al. Tranexamic Acid for Reduction of Blood Loss During Total Hip Arthroplasty J Arthroplasty, 27 (2012), pp. 1838-1843
18 Y.A. Fillingham, D.B. Ramkumar, D.S. Jevsevar, et al. Tranexamic acid in total joint arthroplasty: the endorsed clinical practice guides of the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society Reg Anesth Pain Med, 44 (2019), pp. 7-11
19 R. Saravanan, R. Venkatraman, K. Karthik, et al. Efficacy of different doses and timing of tranexamic acid in major orthopedic surgeries: a randomized trial Rev Bras Anestesiol, 70 (2020), pp. 311-317
20 E. Souza Neto, G. Usandizaga Comparison of two doses of intra-articular tranexamic acid on postoperative bleeding in total knee arthroplasty: a randomized clinical trial Rev Bras Anestesiol, 70 (2020), pp. 318-324
21 M.J. Colomina, M. Koo, M. Basora, et al. Intraoperative tranexamic acid use in major spine surgery in adults: a multicentre, randomized, placebo-controlled trial Br J Anaesth, 118 (2017), pp. 380-390
22 A.A. Mosaad, M.H. Abd-, E.M. Abd-elazeem, et al. A Comparative Study between Prophylactic High Dose of Tranexamic Acid and Low Does Tranexamic Acid in Reducing Perioperative Blood Loss in Spine Surgery J Clin Anesth, 1 (2017), pp. 1-4
23 V.M. Lu, Y.-T. Ho, M. Nambiar, et al. The Perioperative Efficacy and Safety of Antifibrinolytics in Adult Spinal Fusion Surgery Spine, 43 (2018), pp. E949-E958
24 H. Lier, M. Maegele, A. Shander Tranexamic Acid for Acute Hemorrhage: A Narrative Review of Landmark Studies and a Critical Reappraisal of Its Use Over the Last Decade Anesth Analg, 129 (2019), pp. 1574-1584
25 R. Picetti, H. Shakur-Still, R.L. Medcalf, et al. What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies Blood Coagul Fibrinolysis, 30 (2019), pp. 1-10
26 Q.J. Yang, M. Kluger, K. Goryński, et al. Comparing early liver graft function from heart beating and living-donors: A pilot study aiming to identify new biomarkers of liver injury Biopharm Drug Dispos, 38 (2017), pp. 326-339
27 T.A. Eikebrokk, B.S. Vassmyr, K. Ausen, et al. Cytotoxicity and effect on wound re-epithelialization after topical administration of tranexamic acid BJS Open, 3 (2019), pp. 840-851
28 C. Xiao, S. Zhang, N. Long, et al. Is intravenous tranexamic acid effective and safe during hip fracture surgery? An updated meta-analysis of randomized controlled trials Arch Orthop Trauma Surg, 139 (2019), pp. 893-902
29 M. Heidet Tranexamic acid for acute traumatic hemorrhage in emergency medicine: why not, but… Eur J Emerg Med, 27 (2020), pp. 85-86
30 S. Roullet, S. Labrouche, C. Mouton, et al. Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation J Clin Pathol, 72 (2019), pp. 58-65
31 E. Abuelkasem, S. Lu, K. Tanaka, et al. Comparison between thrombelastography and thromboelastometry in hyperfibrinolysis detection during adult liver transplantation Br J Anaesth, 116 (2016), pp. 507-512
32 D. Bezinover, D. Dirkmann, J. Findlay Perioperative Coagulation Management in Liver Transplant Recipients Transplantation, 102 (2018), pp. 578-592
33 A. Steib, N. Gengenwin, G. Freys, et al. Predictive factors of hyperfibrinolytic activity during liver transplantation in cirrhotic patients Br J Anaesth, 73 (1994), pp. 645-648
34 A. Blasi, A. Sabate, J. Beltran, et al. Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment Vox Sang, 112 (2017), pp. 788-795
35 A. Sabate, A. Blasi, M. Costa, et al. Assessment of rotational thromboelastometry for the prediction of red blood cell requirements in orthotopic liver transplantation Minerva Anestesiol, 84 (2018), pp. 447-454
36 A. Sabate, R. Gutierrez, J. Beltran, et al. Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Am J Transplant, 16 (2016), pp. 2421-2429
37 J.F. Boylan, J.R. Klinck, A.N. Sandler, et al. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation Anesthesiology, 85 (1996), pp. 1043-1048 discussion 30A-31A
38 A. Dalmau, A. Sabaté, M. Koo, et al. Prophylactic use of Tranexamic Acid and Incidence of Arterial Thrombosis in Liver Transplantation Anesth Analg, 93 (2001), p. 516
39 A. Dalmau, A. Sabaté, M. Koo, et al. The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: A comparative study Liver Transplant, 10 (2004), pp. 279-284
40 A. Dalmau, A. Sabaté, F. Acosta, et al. Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation Anesth Analg, 91 (2000), pp. 29-34
41 N. Warnaar, S.V. Mallett, J.R. Klinck, et al. Aprotinin and the risk of thrombotic complications after liver transplantation: a retrospective analysis of 1492 patients Liver Transpl, 15 (2009), pp. 747-753
42 P.S. Myles, J.A. Smith, A. Forbes, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery N Engl J Med, 376 (2017), pp. 136-148
43 Q.J. Yang, A. Jerath, R.R. Bies, et al. 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, 36 (2015), pp. 294-307
44 N.S. Gerstein, J.K. Brierley, J. Windsor, et al. Antifibrinolytic Agents in Cardiac and Noncardiac Surgery: A Comprehensive Overview and Update J Cardiothorac Vasc Anesth., 31 (2017), pp. 2183-2205
45 Society of Thoracic Surgeons Blood Conservation Guideline Task Force VA, V.A. Ferraris, J.R. Brown, et al. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines Ann Thorac Surg, 91 (2011), pp. 944-982
46 A. Koster, D. Faraoni, J.H. Levy Antifibrinolytic Therapy for Cardiac Surgery Anesthesiology, 123 (2015), pp. 214-221
47 G.J.A.J.M. Kuiper, L.T. van Egmond, Y.M.C. Henskens, et al. Shifts of Transfusion Demand in Cardiac Surgery After Implementation of Rotational Thromboelastometry-Guided Transfusion Protocols: Analysis of the HEROES-CS (HEmostasis Registry of patiEntS in Cardiac Surgery) Observational, Prospective Open Cohort Datab J Cardiothorac Vasc Anesth, 33 (2019), pp. 307-317
48 S. Sigaut, B. Tremey, A. Ouattara, et al. Comparison of Two Doses of Tranexamic Acid in Adults Undergoing Cardiac Surgery with Cardiopulmonary Bypass Anesthesiology, 120 (2014), pp. 590-600
49 J.C. Horrow, D.F. Van Riper, M.D. Strong, et al. The dose-response relationship of tranexamic acid Anesthesiology, 82 (1995), pp. 383-392
50 B.K. Fiechtner, G.A. Nuttall, M.E. Johnson, et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass Anesth Analg, 92 (2001), pp. 1131-1136
51 N.P. Dowd, J.M. Karski, D.C. Cheng, et al. Pharmacokinetics of tranexamic acid during cardiopulmonary bypass Anesthesiology, 97 (2002), pp. 390-399
52 D.A. Fergusson, P.C. Hebert, C.D. Mazer, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery N Engl J Med, 358 (2008), pp. 2319-2331
53 S.R. Leal-Noval, M. Muñoz, M. Asuero, et al. The 2013 Seville Consensus Document on alternatives to allogenic blood transfusion. An update on the Seville Document Med Intensiva, 37 (2013), pp. 259-268
54 A.B. Goldstone, D.J. Bronster, A.C. Anyanwu, et al. Predictors and outcomes of seizures after cardiac surgery: a multivariable analysis of 2,578 patients Ann Thorac Surg, 91 (2011), pp. 514-518
55 V. Sharma, R. Katznelson, A. Jerath, et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients Anaesthesia, 69 (2014), pp. 124-130
56 R.A. Manji, H.P. Grocott, J. Leake, et al. Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors Can J Anaesth, 59 (2012), pp. 6-13
57 H. Takagi, T. Ando, T. Umemoto All-Literature Investigation of Cardiovascular Evidence (ALICE) group. Seizures associated with tranexamic acid for cardiac surgery: a meta-analysis of randomized and non-randomized studies J Cardiovasc Surg., 58 (2017), pp. 633-641
58 A.A. Klein, T. Collier, J. Yeates, et al. The ACTA PORT-score for predicting perioperative risk of blood transfusion for adult cardiac surgery Br J Anaesth, 119 (2017), pp. 394-401
59 PORT score for PeriOperative Risk of blood Transfusion in cardiac surgery by ACTA. Available at: https://qxmd.com/calculate/calculator_436/PORT-score-for-PeriOperative-Risk-of-blood-Transfusion-in-cardiac-surgery-by-ACTA. [accesed 20 June 2020].
60 A. Jerath, Q.J. Yang, K.S. Pang, et al. Tranexamic Acid Dosing for Cardiac Surgical Patients With Chronic Renal Dysfunction Anesth Analg, 127 (2018), pp. 1323-1332
61 R. Rossaint, B. Bouillon, V. Cerny, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition Crit Care, 20 (2016), p. 100
62 B.A. Cotton, M.A. Schreiber, E.E. Moore Tranexamic acid in trauma: how should we use it? J Trauma Acute Care Surg, 74 (2013), pp. 1575-1586
63 P. Stein, J.-D. Studt, R. Albrecht, et al. The Impact of Prehospital Tranexamic Acid on Blood Coagulation in Trauma Patients Anesth Analg, 126 (2018), pp. 522-529
64 M. Neeki, F. Dong, J. Toy, et al. Tranexamic Acid in Civilian Trauma Care in the California Prehospital Antifibrinolytic Therapy Study West J Emerg Med, 19 (2018), pp. 977-986
65 F.X. Guyette, J.B. Brown, M.S. Zenati, STAAMP Study Group Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury: A Double-blind, Placebo-Controlled, Randomized Clinical Trial JAMA Surg, 156 (2020), pp. 11-20
66 H. Lier, A. Shander Tranexamic acid: the king is dead, long live the king! Br J Anaesth, 124 (2020), pp. 659-662
67 P.F. Walker, S. Schobel, J.D. Caruso, et al. Trauma Embolic Scoring System in military trauma: a sensitive predictor of venous thromboembolism Trauma Surg Acute Care Open, 4 (2019), Article e000367
68 J.T. Howard, Z.T. Stockinger, A.P. Cap, et al. Military use of tranexamic acid in combat trauma: Does it matter? J Trauma Acute Care Surg, 83 (2017), pp. 579-588
69 L.R. Johnston, C.J. Rodriguez, E.A. Elster, et al. Evaluation of Military Use of Tranexamic Acid and Associated Thromboembolic Events JAMA Surg, 153 (2018), pp. 169-175
70 K.E. Adair, J.D. Patrick, E.J. Kliber, et al. TXA (Tranexamic Acid) Risk Evaluation in Combat Casualties (TRECC) Trauma Surg Acute Care Open, 5 (2020), Article e000353
71 S. Benipal, J.L. Santamarina, L. Vo, et al. Mortality and Thrombosis in Injured Adults Receiving Tranexamic Acid in the Post-CRASH-2 Era West J Emerg Med, 20 (2019), pp. 443-453
72 A. Gillissen, D. Henriquez, T. van den Akker, et al. The effect of tranexamic acid on blood loss and maternal outcome in the treatment of persistent postpartum hemorrhage: A nationwide retrospective cohort study PLoS One, 12 (2017) e0187555
73 M. Boutonnet, P. Abback, F. Le Saché, et al. Tranexamic acid in severe trauma patients managed in a mature trauma care system J Trauma Acute Care Surg, 84 (2018), pp. S54-S62
74 W. Hu, Y. Xin, X. Chen, et al. Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review CNS Drugs, 33 (2019), pp. 327-336
75 A. Bonet, Z. Madrazo, M. Koo, et al. Thromboelastometric Profile and Acute Coagulopathy of the Polytraumatized Patient: Clinical and Prognostic Implications Cir Esp, 96 (2018), pp. 41-48
76 H.B. Moore, E.E. Moore, I.N. Liras, et al. Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients J Am Coll Surg, 222 (2016), pp. 347-355
77 E.E. Moore, H.B. Moore, E. Gonzalez, et al. Postinjury fibrinolysis shutdown J Trauma Acute Care Surg, 78 (2015), pp. S65-S69
78 I. Raza, R. Davenport, C. Rourke, et al. The incidence and magnitude of fibrinolytic activation in trauma patients J Thromb Haemost, 11 (2013), pp. 307-314
79 S. Grassin-Delyle, O.M. Theusinger, R. Albrecht, et al. Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis Anaesthesia, 73 (2018), pp. 719-729
80 P.C. Spinella, K.A. Thomas, I.R. Turnbull, TAMPITI Investigators The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial Front Immunol, 11 (2020), p. 2085
81 E.E. Moore, H.B. Moore, E. Gonzalez, et al. Rationale for the selective administration of tranexamic acid to inhibit fibrinolysis in the severely injured patient Transfusion, 56 (2016), pp. S110-S114
82 C. Longstaff Measuring fibrinolysis: from research to routine diagnostic assays J Thromb Haemost, 16 (2018), pp. 652-662
83 M. Muñoz, J. Stensballe, A.-S. Ducloy-Bouthors, et al. Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement Blood Transfus, 17 (2019), pp. 112-136
84 N. Novikova, G.J. Hofmeyr, C. Cluver Tranexamic acid for preventing postpartum haemorrhage Cochrane Database Syst Rev (2015), Article CD007872
85 A.S. Ducloy-Bouthors, A. Duhamel, E. Kipnis, et al. Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial Br J Anaesth, 116 (2016), pp. 641-648
86 M. Mirghafourvand, S. Mohammad-Alizadeh, F. Abbasalizadeh, et al. The effect of prophylactic intravenous tranexamic acid on blood loss after vaginal delivery in women at low risk of postpartum haemorrhage: a double-blind randomised controlled trial Aust N Z J Obstet Gynaecol, 55 (2015), pp. 53-58
87 N. Sujata, R. Tobin, R. Kaur, et al. Randomized controlled trial of tranexamic acid among parturients at increased risk for postpartum hemorrhage undergoing cesarean delivery Int J Gynaecol Obstet, 133 (2016), pp. 312-315
88 L. Sentilhes, N. Winer, E. Azria, et al. Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery N Engl J Med, 379 (2018), pp. 731-742
89 J.H. Levy, A. Koster, Q.J. Quinones, et al. Antifibrinolytic Therapy and Perioperative Considerations Anesthesiology, 128 (2018), pp. 657-670
90 P. Le Roux, D.K. Menon, G. Citerio Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine Neurocritical Care, 21 (2014), pp. S1-S26
91 R.M. Starke, G.H. Kim, A. Fernandez, et al. Impact of a protocol for acute antifibrinolytic therapy on aneurysm rebleeding after subarachnoid hemorrhage Stroke, 39 (2008)
92 M.R. Germans, R. Post, B.A. Coert, et al. Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial Trials, 14 (2013), p. 143
93 M.R. Harrigan, K.F. Rajneesh, A.A. Ardelt, et al. Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus Neurosurgery, 67 (2010), pp. 935-939 discussion 939–940
94 J. Hillman, S. Fridriksson, O. Nilsson, et al. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study J Neurosurg, 97 (2002), pp. 771-778
95 T. Anker-Møller, A. Troldborg, N. Sunde, et al. Evidence for the Use of Tranexamic Acid in Subarachnoid and Subdural Hemorrhage: A Systematic Review Semin Thromb Hemost, 43 (2017), pp. 750-758
96 T. Steiner, S. Juvela, A. Unterberg, et al. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage Cerebrovasc Dis, 35 (2013), pp. 93-112
97 N. Sprigg, K. Flaherty, J.P. Appleton, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial Lancet, 391 (2018), pp. 2107-2115
98 CRASH-3 trial collaborators Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial Lancet, 394 (2019), pp. 1713-1723
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