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CC BY-NC-ND 4.0 · J Neuroanaesth Crit Care 2019; 06(03): 257-266
DOI: 10.1055/s-0039-1693083
Review Article
Indian Society of Neuroanaesthesiology and Critical Care

Tranexamic Acid in Neuroanesthesia and Neurocritical Care: Time for Its Critical Appraisal

Bhavna Hooda
1   Department of Anaesthesiology and Critical Care, Army Hospital Research & Referral, New Delhi, India
,
Radhakrishnan Muthuchellappan
2   Department of Neuroanaesthesia and Neurocritical Care, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
› Institutsangaben
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Publikationsverlauf

Received: 05. Februar 2019

Accepted after revision: 22. April 2019

Publikationsdatum:
26. Juli 2019 (online)

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Abstract

There is a renewed interest in the use of antifibrinolytics, especially tranexamic acid (TxA), in varied clinical settings such as trauma, perioperative bleeding, cardiac surgery, and multilevel spine instrumentation procedures. Because of its prothrombotic potential, the use of TxA in neurosurgical disorders has not gained popularity since this subset of the population is more prone to developing thromboembolic complications. However, recent studies have shown that TxA reduces blood loss, reduces the need for allogeneic blood transfusion, and is associated with minimal side effects. In this narrative review, Google Scholar, PubMed, and EMBASE databases were searched to identify publications relevant to the current use of TxA in varied neurosurgical and critical care settings. These publications were analyzed, and a summary of the findings and the role of future research on this drug are presented in this review.

Keywords

tranexamic acid - traumatic brain injury - intracerebral hemorrhage - chronic subdural hematoma - subarachnoid hemorrhage - perioperative period
 

  • References

  • 1 Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs 1999; 57 (06) 1005-1032
    CrossrefPubMedGoogle Scholar
  • 2 Schloss B, Gulati P, Yu L. et al. Impact of aprotinin and renal function on mortality: a retrospective single center analysis. J Cardiothorac Surg 2011; 6: 103
    CrossrefPubMedGoogle Scholar
  • 3 Mullan S, Dawley J. Antifibrinolytic therapy for intracranial aneurysms. J Neurosurg 1968; 28 (01) 21-23
    CrossrefPubMedGoogle Scholar
  • 4 Kassell NF, Torner JC, Jane JA, Haley Jr EC, Adams HP. The international cooperative study on the timing of aneurysm surgery. Part 2. Surgical results. J Neurosurg 1990; 73 (01) 37-47
    CrossrefPubMedGoogle Scholar
  • 5 Shakur H, Roberts I, Bautista R. et al; CRASH-2 trial 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 (9734) 23-32
    CrossrefPubMedGoogle Scholar
  • 6 CRASH-2 Collaborators, Intracranial Bleeding Study. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 2011; 343: d3795
    CrossrefPubMedGoogle Scholar
  • 7 Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev 2015; 29 (01) 17-24
    CrossrefPubMedGoogle Scholar
  • 8 Henry DA, Carless PA, Moxey AJ. et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011: CD001886
    PubMedGoogle Scholar
  • 9 Okamoto S, Sato S, Takada Y, Okamoto U. An active stereo-isomer (trans-form) of AMCHA and its antifibrinolytic (antiplasminic) action in vitro and in vivo. Keio J Med 1964; 13: 177-185
    CrossrefPubMedGoogle Scholar
  • 10 Melander B, Gliniecki G, Granstrand B, Hanshoff G. Biochemistry and toxicology of amikapron; the antifibrinolytically active isomer of AMCHA. (A comparative study with. ∊-aminocaproic acid). Acta Pharmacol Toxicol (Copenh) 1965; 22 (04) 340-352
    PubMedGoogle Scholar
  • 11 Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. J Clin Pathol Suppl (R Coll Pathol) 1980; 14: 41-47
    PubMedGoogle Scholar
  • 12 Andersson L, Nilsson IM, Niléhn JE, Hedner U, Granstrand B, Melander B. Experimental and clinical studies on AMCA, the antifibrinolytically active isomer of p-aminomethyl cyclohexane carboxylic acid. Scand J Haematol 1965; 2 (03) 230-247
    PubMedGoogle Scholar
  • 13 Horrow JC, Van Riper DF, Strong MD, Grunewald KE, Parmet JL. The dose-response relationship of tranexamic acid. Anesthesiology 1995; 82 (02) 383-392
    CrossrefPubMedGoogle Scholar
  • 14 Ker K, Prieto-Merino D, Roberts I. Systematic review, meta-analysis and meta-regression of the effect of tranexamic acid on surgical blood loss. Br J Surg 2013; 100 (10) 1271-1279
    CrossrefPubMedGoogle Scholar
  • 15 Grassin-Delyle S, Theusinger OM, Albrecht R. et al. Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis. Anaesthesia 2018; 73 (06) 719-729
    CrossrefPubMedGoogle Scholar
  • 16 Nishida T, Kinoshita T, Yamakawa K. Tranexamic acid and trauma-induced coagulopathy. J Intensive Care 2017; 5: 5
    CrossrefPubMedGoogle Scholar
  • 17 Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003; 54 (06) 1127-1130
    CrossrefPubMedGoogle Scholar
  • 18 Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma 2006; 60 (06) Suppl S3-S11
    CrossrefPubMedGoogle Scholar
  • 19 Raza I, Davenport R, Rourke C. et al. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost 2013; 11 (02) 307-314
    CrossrefPubMedGoogle Scholar
  • 20 Roberts I, Shakur H, Afolabi A. et al; CRASH-2 collaborators. 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 (9771) 1096-1101.e2
    CrossrefPubMedGoogle Scholar
  • 21 Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study. Arch Surg 2012; 147 (02) 113-119
    PubMedGoogle Scholar
  • 22 Ker K, Roberts I, Shakur H, Coats TJ. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev 2015; 5 (05) CD004896
    PubMedGoogle Scholar
  • 23 Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron FX, Roberts I. Antifibrinolytic Trials Collaboration. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet 2018; 391 (10116) 125-132
    CrossrefPubMedGoogle Scholar
  • 24 Roberts I, Kawahara T. Proposal for the Inclusion of Tranexamic Acid (Antifibrinolytic-lysine Analogue) in the WHO Model List of Essential Medicines. Geneva, Switzerland: World Health Organization; 2010
    Google Scholar
  • 25 Nakae R, Takayama Y, Kuwamoto K, Naoe Y, Sato H, Yokota H. Time course of coagulation and fibrinolytic parameters in patients with traumatic brain injury. J Neurotrauma 2016; 33 (07) 688-695
    CrossrefPubMedGoogle Scholar
  • 26 Epstein DS, Mitra B, O'Reilly G, Rosenfeld JV, Cameron PA. Acute traumatic coagulopathy in the setting of isolated traumatic brain injury: a systematic review and meta-analysis. Injury 2014; 45 (05) 819-824
    CrossrefPubMedGoogle Scholar
  • 27 Kurland D, Hong C, Aarabi B, Gerzanich V, Simard JM. Hemorrhagic progression of a contusion after traumatic brain injury: a review. J Neurotrauma 2012; 29 (01) 19-31
    CrossrefPubMedGoogle Scholar
  • 28 Juratli TA, Zang B, Litz RJ. et al. Early hemorrhagic progression of traumatic brain contusions: frequency, correlation with coagulation disorders, and patient outcome: a prospective study. J Neurotrauma 2014; 31 (17) 1521-1527
    CrossrefPubMedGoogle Scholar
  • 29 Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emerg Med 2013; 13: 20
    CrossrefPubMedGoogle Scholar
  • 30 Dewan Y, Komolafe EO, Mejía-Mantilla JH, Perel P, Roberts I, Shakur H. CRASH-3 Collaborators. 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
    CrossrefPubMedGoogle Scholar
  • 31 Mahmood A, Roberts I, Shakur H. A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]). Trials 2017; 18 (01) 330
    CrossrefPubMedGoogle Scholar
  • 32 Napolitano LM. Prehospital tranexamic acid: what is the current evidence?. Trauma Surg Acute Care Open 2017; 2 (01) e000056
    CrossrefPubMedGoogle Scholar
  • 33 Davis SM, Broderick J, Hennerici M. et al; Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006; 66 (08) 1175-1181
    CrossrefPubMedGoogle Scholar
  • 34 Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke 1996; 27 (10) 1783-1787
    CrossrefPubMedGoogle Scholar
  • 35 Law ZK, Meretoja A, Engelter ST. et al. Treatment of intracerebral haemorrhage with tranexamic acid—a review of current evidence and ongoing trials. Eur Stroke J 2017; 2 (01) 13-22
    PubMedGoogle Scholar
  • 36 Al-Shahi SalmanR, Law ZK, Bath PM, Steiner T, Sprigg N. Haemostatic therapies for acute spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev 2018; 4: CD005951
    PubMedGoogle Scholar
  • 37 Sprigg N, Flaherty K, Appleton JP. et al; TICH-2 Investigators. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet 2018; 39110135: 2107-2115
    PubMedGoogle Scholar
  • 38 Broderick JP. Haemostatic treatment for intracerebral haemorrhage. Lancet 2018; 39110135: 2081-2082
    PubMedGoogle Scholar
  • 39 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 (04) 519-524
    PubMedGoogle Scholar
  • 40 Ito H, Saito K, Yamamoto S, Hasegawa T. Tissue-type plasminogen activator in the chronic subdural hematoma. Surg Neurol 1988; 30 (03) 175-179
    CrossrefPubMedGoogle Scholar
  • 41 Saito K, Ito H, Hasegawa T, Yamamoto S. Plasmin-alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor in chronic subdural hematoma. J Neurosurg 1989; 70 (01) 68-72
    CrossrefPubMedGoogle Scholar
  • 42 Kageyama H, Toyooka T, Tsuzuki N, Oka K. Nonsurgical treatment of chronic subdural hematoma with tranexamic acid. J Neurosurg 2013; 119 (02) 332-337
    CrossrefPubMedGoogle Scholar
  • 43 Tanweer O, Frisoli FA, Bravate C. et al. Tranexamic acid for treatment of residual subdural hematoma after bedside twist-drill evacuation. World Neurosurg 2016; 91: 29-33
    CrossrefPubMedGoogle Scholar
  • 44 Stary JM, Hutchins L, Vega RA. Tranexamic acid for recurring subdural hematomas following surgical evacuation: a clinical case series. J Neurol Surg A Cent Eur Neurosurg 2016; 77 (05) 422-426
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 45 Holl DC, Volovici V, Dirven CMF. et al; Dutch Chronic Subdural Hematoma Research Group (DSHR). Pathophysiology and nonsurgical treatment of chronic subdural hematoma: from past to present to future. World Neurosurg 2018; 116: 402-411.e2
    CrossrefPubMedGoogle Scholar
  • 46 Naidech AM, Janjua N, Kreiter KT. et al. Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage. Arch Neurol 2005; 62 (03) 410-416
    CrossrefPubMedGoogle Scholar
  • 47 Germans MR, Coert BA, Vandertop WP, Verbaan D. Time intervals from subarachnoid hemorrhage to rebleed. J Neurol 2014; 261 (07) 1425-1431
    CrossrefPubMedGoogle Scholar
  • 48 Fodstad H, Nilsson IM. Coagulation and fibrinolysis in blood and cerebrospinal fluid after aneurysmal subarachnoid haemorrhage: effect of tranexamic acid (AMCA). Acta Neurochir (Wien) 1981; 56 (01) (02) 25-38
    CrossrefPubMedGoogle Scholar
  • 49 Fodstad H. Tranexamic acid (AMCA) in aneurysmal subarachnoid haemorrhage. J Clin Pathol Suppl (Roy Coll Path) 198014 (Suppl. 22) 68-73
    PubMedGoogle Scholar
  • 50 Maurice-Williams RS. Prolonged antifibrinolysis: an effective non-surgical treatment for ruptured intracranial aneurysms?. BMJ 1978; 16118: 945-947
    PubMedGoogle Scholar
  • 51 Roos Y. STAR Study Group. Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. Neurology 2000; 54 (01) 77-82
    CrossrefPubMedGoogle Scholar
  • 52 Roos YB, Rinkel GJ, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2003; (02) CD001245
    PubMedGoogle Scholar
  • 53 Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg 2002; 97 (04) 771-778
    CrossrefPubMedGoogle Scholar
  • 54 Baharoglu MI, Germans MR, Rinkel GJE. et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2013; 8 (08) CD001245
    PubMedGoogle Scholar
  • 55 Gaberel T, Magheru C, Emery E, Derlon JM. Antifibrinolytic therapy in the management of aneurismal subarachnoid hemorrhage revisited. A meta-analysis. Acta Neurochir (Wien) 2012; 154 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 56 Ross J, Al-Shahi SalmanR. The frequency of thrombotic events among adults given antifibrinolytic drugs for spontaneous bleeding: systematic review and meta-analysis of observational studies and randomized trials. Curr Drug Saf 2012; 7 (01) 44-54
    CrossrefPubMedGoogle Scholar
  • 57 Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G. European Stroke Organization. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis 2013; 35 (02) 93-112
    CrossrefPubMedGoogle Scholar
  • 58 Connolly ES, Rabinstein AA, Carhuapoma JR. et al. American Heart Association Stroke Council, Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2012; 43 (06) 1711-1737
    CrossrefPubMedGoogle Scholar
  • 59 Diringer MN, Bleck TP, Claude III HemphillJ. et al; Neurocritical Care Society, Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care 2011; 15 (02) 211-240
    CrossrefPubMedGoogle Scholar
  • 60 Germans MR, Post R, Coert BA, Rinkel GJ, Vandertop WP, Verbaan D. Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial. Trials 2013; 14: 143
    CrossrefPubMedGoogle Scholar
  • 61 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
    CrossrefPubMedGoogle Scholar
  • 62 Tsuda H, Oka K, Noutsuka Y, Sueishi K. Tissue-type plasminogen activator in patients with intracranial meningiomas. Thromb Haemost 1988; 60 (03) 508-513
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 63 Palmer JD, Francis JL, Pickard JD, Iannotti F. The efficacy and safety of aprotinin for hemostasis during intracranial surgery. J Neurosurg 2003; 98 (06) 1208-1216
    CrossrefPubMedGoogle Scholar
  • 64 Bharath K, Bhagat H, Mohindra S. Use of tranexamic acid as a rescue measure to achieve hemostasis after massive blood loss in a pediatric neurosurgical patient. J Neurosurg Anesthesiol 2011; 23 (04) 376-377
    CrossrefPubMedGoogle Scholar
  • 65 Vel R, Udupi BP, Satya PrakashMVS, Adinarayanan S, Mishra S, Babu L. Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients. Saudi J Anaesth 2015; 9 (01) 42-48
    CrossrefPubMedGoogle Scholar
  • 66 Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci 2017; 41: 132-138
    CrossrefPubMedGoogle Scholar
  • 67 Mebel D, Akagami R, Flexman AM. Use of tranexamic acid is associated with reduced blood product transfusion in complex skull base neurosurgical procedures: a retrospective cohort study. Anesth Analg 2016; 122 (02) 503-508
    CrossrefPubMedGoogle Scholar
  • 68 Möller H, Hedlund R. Instrumented and noninstrumented posterolateral fusion in adult spondylolisthesis–a prospective randomized study: part 2. Spine 2000; 25 (13) 1716-1721
    CrossrefPubMedGoogle Scholar
  • 69 Sokolowski MJ, Garvey TA, Perl II J. et al. Prospective study of postoperative lumbar epidural hematoma: incidence and risk factors. Spine 2008; 33 (01) 108-113
    CrossrefPubMedGoogle Scholar
  • 70 Wong J, El Beheiry H, Rampersaud YR. et al. Tranexamic acid reduces perioperative blood loss in adult patients having spinal fusion surgery. Anesth Analg 2008; 107 (05) 1479-1486
    CrossrefPubMedGoogle Scholar
  • 71 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 (24) 2577-2580
    CrossrefPubMedGoogle Scholar
  • 72 Farrokhi MR, Kazemi AP, Eftekharian HR, Akbari K. Efficacy of prophylactic low dose of tranexamic acid in spinal fixation surgery: a randomized clinical trial. J Neurosurg Anesthesiol 2011; 23 (04) 290-296
    CrossrefPubMedGoogle Scholar
  • 73 Li G, Sun TW, Luo G, Zhang C. Efficacy of antifibrinolytic agents on surgical bleeding and transfusion requirements in spine surgery: a meta-analysis. Eur Spine J 2017; 26 (01) 140-154
    CrossrefPubMedGoogle Scholar
  • 74 Colomina MJ, Koo M, Basora M, Pizones J, Mora L, Bagó J. Intraoperative tranexamic acid use in major spine surgery in adults: a multicentre, randomized, placebo-controlled trial. Br J Anaesth 2017; 118 (03) 380-390
    CrossrefPubMedGoogle Scholar
  • 75 Kozek-Langenecker SA, Afshari A, Albaladejo P. et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30 (06) 270-382
    CrossrefPubMedGoogle Scholar
  • 76 Ipema HJ, Tanzi MG. Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures. Ann Pharmacother 2012; 46 (01) 97-107
    CrossrefPubMedGoogle Scholar
  • 77 Winter SF, Santaguida C, Wong J, Fehlings MG. Systemic and topical use of tranexamic acid in spinal surgery: a systematic review. Global Spine J 2016; 6 (03) 284-295
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 78 Verma K, Kohan E, Ames CP. et al. A comparison of two different dosing protocols for tranexamic acid in posterior spinal fusion for spinal deformity: a prospective, randomized trial. Int J Spine Surg 2015; 9: 65
    CrossrefPubMedGoogle Scholar
  • 79 CYKLOKAPRON tranexamic acid injection. Antifibrinolytic agent. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019281s030lbl.pdf Accessed June 15, 2019
    PubMedGoogle Scholar
  • 80 Calapai G, Gangemi S, Mannucci C. et al. Systematic review of tranexamic acid adverse reactions. J Pharmacovigil 2015; 3: 171
    PubMedGoogle Scholar
  • 81 Thiagarajamurthy S, Levine A, Dunning J. Does prophylactic tranexamic acid safely reduce bleeding without increasing thrombotic complications in patients undergoing cardiac surgery?. Interact Cardiovasc Thorac Surg 2004; 3 (03) 489-494 [Internet]
    CrossrefPubMedGoogle Scholar
  • 82 Khaldi A, Helo N, Schneck MJ, Origitano TC. Venous thromboembolis deep venous thrombosis and pulmonary embolism in a neurosurgical population. J Neurosurg 2011; 114 (01) 40-46
    CrossrefPubMedGoogle Scholar
  • 83 Montroy J, Fergusson NA, Hutton B. et al. The safety and efficacy of lysine analogues in cancer patients: a systematic review and meta-analysis. Transfus Med Rev 2017; 31 (03) 141-148
    CrossrefPubMedGoogle Scholar
  • 84 Myles PS, Smith JA, Forbes A. et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 2017; 376 (02) 136-148
    CrossrefPubMedGoogle Scholar
  • 85 Pellegrini A, Giaretta D, Chemello R, Zanotto L, Testa G. Feline generalized epilepsy induced by tranexamic acid (AMCA). Epilepsia 1982; 23 (01) 35-45
    CrossrefPubMedGoogle Scholar
  • 86 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 (02) 124-130
    CrossrefPubMedGoogle Scholar
  • 87 Kratzer S, Irl H, Mattusch C. et al. Tranexamic acid impairs. γ-aminobutyric acid receptor type A-mediated synaptic transmission in the murine amygdala: a potential mechanism for drug-induced seizures?. Anesthesiology 2014; 120 (03) 639-649
    CrossrefPubMedGoogle Scholar
  • 88 Furtmüller R, Schlag MG, Berger M. et al. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. J Pharmacol Exp Ther 2002; 301 (01) 168-173
    CrossrefPubMedGoogle Scholar
  • 89 Lecker I, Wang DS, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors. J Clin Invest 2012; 122 (12) 4654-4666
    CrossrefPubMedGoogle Scholar
  • 90 Takagi H, Ando T, Umemoto T. 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 (Torino) 2017; 58 (04) 633-641
    PubMedGoogle Scholar
  • 91 Montes FR, Pardo DF, Carreño M, Arciniegas C, Dennis RJ, Umaña JP. Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: a case-control study. Ann Card Anaesth 2012; 15 (01) 6-12
    CrossrefPubMedGoogle Scholar
  • 92 Hui AC, Wong TY, Chow KM, Szeto CC. Multifocal myoclonus secondary to tranexamic acid. J Neurol Neurosurg Psychiatry 2003; 74 (04) 547
    CrossrefPubMedGoogle Scholar
  • 93 Merriman B, Mayson K, Sawka A, Akagami R, Flexman AM. Postoperative seizure in a neurosurgical patient: should tranexamic acid be on the differential?. Can J Anaesth 2013; 60 (05) 506-507
    CrossrefPubMedGoogle Scholar
  • 94 Moore HB, Moore EE, Liras IN. 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 2016; 222 (04) 347-355
    CrossrefPubMedGoogle Scholar
  • 95 Harvin JA, Peirce CA, Mims MM. et al. The impact of tranexamic acid on mortality in injured patients with hyperfibrinolysis. J Trauma Acute Care Surg 2015; 78 (05) 905-909 discussion909–911
    CrossrefPubMedGoogle Scholar
  • 96 Moore HB, Moore EE, Huebner BR. et al. Tranexamic acid is associated with increased mortality in patients with physiological fibrinolysis. J Surg Res 2017; 220: 438-443
    CrossrefPubMedGoogle Scholar
  • 97 Spinella PC, Bochicchio GV. Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI trial). Available at http://www.tampiti.wustl.edu Accessed April 16, 2016
    PubMedGoogle Scholar
  • 98 Iribarren JL, Jimenez JJ, Hernández D. et al. Postoperative bleeding in cardiac surgery: the role of tranexamic acid in patients homozygous for the 5G polymorphism of the plasminogen activator inhibitor-1 gene. Anesthesiology 2008; 108 (04) 596-602
    CrossrefPubMedGoogle Scholar
  • 99 Godier A, Hunt BJ. Plasminogen receptors and their role in the pathogenesis of inflammatory, autoimmune and malignant disease. J Thromb Haemost 2013; 11 (01) 26-34
    CrossrefPubMedGoogle Scholar