Skip to main content

Advertisement

Log in

Tranexamic acid in Neurosurgery: a controversy indication—review

  • Review
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Tranexamic acid (TXA) is one of the measures indicated to reduce bleeding and the need for volume replacement. However, data on risks and benefits are controversial. This study analyzes the effectivity and risks of using tranexamic acid in neurosurgery. We selected articles, published from 1976 to 2019, on the PubMed, EMBASE, Science Direct, and The Cochrane Database using the descriptors: “tranexamic acid,” “neurosurgery,” “traumatic brain injury,” “subdural hemorrhage,” “brain aneurysm,” and “subarachnoid hemorrhage.” TXA can reduce blood loss and the need for blood transfusion in trauma and spinal surgery. Despite the benefits of TXA, moderate-to-high doses are potentially associated with neurological complications (seizures, transient ischemic attack, delirium) in adults and children. In a ruptured intracranial aneurysm, the use of TXA can considerably reduce the risk of rebleeding, but there is weak evidence regarding its influence on mortality reduction. The TXA use in brain surgery does not present benefit. However, this conclusion is limited because there are few studies. TXA in neurosurgeries is a promising method for the maintenance of hemostasis in affected patients, mainly in traumatic brain injury and spinal surgery; nevertheless, there is lack of evidence in brain and vascular surgeries. Many questions remain unanswered, such as how to determine the dosage that triggers the onset of associated complications, or how to adjust the dose for chronic kidney disease patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Udupi B, Siva Satya Prakash M, Adinarayanan S, Mishra S, Babu L, Vel R (2014) Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients. Saudi J Anaesth 9:42. https://doi.org/10.4103/1658-354x.146304

    Article  Google Scholar 

  2. Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R (2017) Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci 41:132–138. https://doi.org/10.1016/j.jocn.2017.02.053

    Article  CAS  PubMed  Google Scholar 

  3. Choi HY, Hyun SJ, Kim KJ, Jahng TA, Kim HJ (2017) Effectiveness and safety of tranexamic acid in spinal deformity surgery. J Korean Neurosurg Soc 60:75–81. https://doi.org/10.3340/jkns.2016.0505.004

    Article  PubMed  Google Scholar 

  4. Seddighi A, Nikouei A, Seddighi A, Zali A, Tabatabaei S, Yourdkhani F, Naimian S, Razavian I (2015) The role of tranexamic acid in prevention of hemorrhage in major spinal surgeries. Asian J Neurosurg 12:501–505. https://doi.org/10.4103/1793-5482.165791

    Article  Google Scholar 

  5. Meneghini L, Zadra N, Aneloni V, Metrangolo S, Faggin R, Giusti F (2003) Erythropoietin therapy and acute preoperative normovolaemic haemodilution in infants undergoing craniosynostosis surgery. Paediatr Anaesth 13:392–396

    Article  Google Scholar 

  6. Paulo D, Semonche A, Choudhry O, Al-Mufti F, Prestigiacomo CJ, Roychowdhury S, Nanda A, Gupta G (2019) History of hemostasis in neurosurgery. World Neurosurg 124:237–250. https://doi.org/10.1016/j.wneu.2018.12.015

    Article  Google Scholar 

  7. Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A (2008) Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery. Spine (Phila Pa 1976) 33:2577–2580. https://doi.org/10.1097/brs.0b013e318188b9c5

    Article  Google Scholar 

  8. Cheriyan T, Maier SP, Bianco K, Slobodyanyuk K, Rattenni RN, Lafage V, Schwab FJ, Lonner BS, Errico TJ (2015) Efficacy of tranexamic acid on surgical bleeding in spine surgery: a meta-analysis. Spine J 15:752–761. https://doi.org/10.1016/j.spinee.2015.01.013

    Article  PubMed  Google Scholar 

  9. Ng WCK, Jerath A, Wasowicz M (2015) Tranexamic acid: a clinical review. Anestezjol Intens Ter 47:339–350. https://doi.org/10.5603/ait.a2015.0011

    Article  Google Scholar 

  10. Lecker I, Orser BA, Mazer CD (2012) Saisir la chance de comprendre les antifibrinolytiques. Can J Anesth 59:1–5. https://doi.org/10.1007/s12630-011-9621-4

    Article  PubMed  Google Scholar 

  11. Goobie S (2013) The case for the use of tranexamic acid. Paediatr Anaesth 23:281–284. https://doi.org/10.1111/pan.12093

    Article  PubMed  Google Scholar 

  12. Pisklakov S, Ibrahim H, Huang L (2017) Tranexamic acid and major spine surgery: trends and controversies. J Surg Anesth 1:1–8

    Article  Google Scholar 

  13. Carabini LM, Moreland NC, Vealey RJ, Bebawy JF, Koski TR, Koht A, Gupta DK, Avram MJ, Zeeni C, Gould RW, Hemmer LB, Sugrue PA, McClendon J (2018) A randomized controlled trial of low-dose tranexamic acid versus placebo to reduce red blood cell transfusion during complex multilevel spine fusion surgery. World Neurosurg 110:e572–e579. https://doi.org/10.1016/j.wneu.2017.11.070

    Article  PubMed  Google Scholar 

  14. Mebel D, Akagami R, Flexman AM (2016) Use of tranexamic acid is associated with reduced blood product transfusion in complex skull base neurosurgical procedures: a retrospective cohort study. Anesth Analg 122:503–508. https://doi.org/10.1213/ANE.0000000000001065

    Article  CAS  PubMed  Google Scholar 

  15. Shi H, Ou Y, Jiang D, Quan Z, Zhao Z, Zhu Y (2017) Tranexamic acid reduces perioperative blood loss of posterior lumbar surgery for stenosis or spondylolisthesis a randomized trial. Med (US) 96:1–8. https://doi.org/10.1097/MD.0000000000005718

    Article  CAS  Google Scholar 

  16. Zhang F, Wang K, Li FN, Huang X, Li Q, Chen Z, Tang YB, Shen HX, Song QX (2014) Effectiveness of tranexamic acid in reducing blood loss in spinal surgery: a meta-analysis. BMC Musculoskelet Disord 15:1–9. https://doi.org/10.1186/1471-2474-15-448

    Article  CAS  Google Scholar 

  17. Shakeri M, Salehpour F, Shokouhi G, Aeinfar K, Aghazadeh J, Mirzaei F, Alavi SAN (2018) Minimal dose of tranexamic acid is effective in reducing blood loss in complex spine surgeries: a randomized double-blind placebo controlled study. Asian Spine J 12:484–489. https://doi.org/10.4184/asj.2018.12.3.484

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tsutsumimoto T, Shimogata M, Ohta H, Yui M, Yoda I, Misawa H (2011) Tranexamic acid reduces perioperative blood loss in cervical laminoplasty. Spine (Phila Pa 1976) 36:1913–1918. https://doi.org/10.1097/brs.0b013e3181fb3a42

    Article  Google Scholar 

  19. Raksakietisak M, Sathitkarnmanee B, Srisaen P, Duangrat T, Chinachoti T, Rushatamukayanunt P, Sakulpacharoen N (2015) Two doses of tranexamic acid reduce blood transfusion in complex spine surgery. Spine (Phila Pa 1976) 40:E1257–E1263. https://doi.org/10.1097/BRS.0000000000001063

    Article  Google Scholar 

  20. Colomina MJ, Koo M, Basora M, Pizones J, Mora L, Bagó J (2016) Intraoperative tranexamic acid use in major spine surgery in adults: a multicentre, randomized, placebo-controlled trial † †This Article is accompanied by Editorial Aew470. Br J Anaesth 118:380–390. https://doi.org/10.1093/bja/aew434

    Article  CAS  Google Scholar 

  21. Yagi M, Hasegawa J, Nagoshi N, Iizuka S, Kaneko S, Fukuda K, Takemitsu M, Shioda M, MacHida M (2012) Does the intraoperative tranexamic acid decrease operative blood loss during posterior spinal fusion for treatment of adolescent idiopathic scoliosis? Spine (Phila Pa 1976) 37:16–20. https://doi.org/10.1097/BRS.0b013e318266b6e5

    Article  Google Scholar 

  22. Xue P, Yang J, Xu X, Liu T, Huang Y, Qiao F, Huang X (2018) The efficacy and safety of tranexamic acid in reducing perioperative blood loss in patients with multilevel thoracic spinal stenosis: a retrospective observational study. Med (US) 97. https://doi.org/10.1097/MD.0000000000013643

  23. Camille D, Gaëtan T, Vianney G, Solène V, Emmanuel F, Rémi G, Mourad O-S (2019) Blood loss and perioperative transfusions related to surgery for spinal tumors. Relevance of tranexamic acid. Neurochirurgie. 65:377–381. https://doi.org/10.1016/j.neuchi.2019.05.003

    Article  Google Scholar 

  24. Dadure C, Sauter M, Bringuier S, Bigorre M, Raux O, Rochette A, Canaud N, Capdevila X (2011) Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology 114:856–861. https://doi.org/10.1097/ALN.0b013e318210f9e3

    Article  CAS  PubMed  Google Scholar 

  25. Kurnik NM, Pflibsen LR, Do A, Bristol R, Singh DJ (2018) Craniosynostosis surgery and the impact of tranexamic acid dosing. J Craniofac Surg 29:96–98. https://doi.org/10.1097/SCS.0000000000004196

    Article  PubMed  Google Scholar 

  26. Huebner BR, Dorlac WC, Cribari C (2017) Tranexamic acid use in prehospital uncontrolled hemorrhage. Wilderness Environ Med 28:S50–S60. https://doi.org/10.1016/j.wem.2016.12.006

    Article  PubMed  PubMed Central  Google Scholar 

  27. Na HS, Shin HJ, Lee YJ, Kim JH, Koo KH, Do SH (2016) The effect of tranexamic acid on blood coagulation in total hip replacement arthroplasty: rotational thromboelastographic (ROTEM®) analysis. Anaesthesia 71:67–75. https://doi.org/10.1111/anae.13270

    Article  CAS  PubMed  Google Scholar 

  28. Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE (2013) Tranexamic acid in trauma. J Trauma Acute Care Surg 74:1575–1586. https://doi.org/10.1097/TA.0b013e318292cc54

    Article  PubMed  Google Scholar 

  29. Germans MR, Post R, Coert BA, Rinkel GJE, Vandertop WP, Verbaan D (2013) Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial. Trials 14:1–6. https://doi.org/10.1186/1745-6215-14-143

    Article  Google Scholar 

  30. Post R, Germans MR, Boogaarts HD, Ferreira Dias Xavier B, Van den Berg R, Coert BA, Vandertop WP, Verbaan D (2019) Short-term tranexamic acid treatment reduces in-hospital mortality in aneurysmal sub-arachnoid hemorrhage: a multicenter comparison study. PLoS One 14:1–9. https://doi.org/10.1371/journal.pone.0211868

    Article  CAS  Google Scholar 

  31. Baharoglu MI, Germans MR, Rinkel GJE, Algra A, Vermeulen M, van Gijn J, Roos YBWEM (2013) Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2013. https://doi.org/10.1002/14651858.CD001245.pub2

  32. Gaberel T, Magheru C, Emery E, Derlon JM (2012) Antifibrinolytic therapy in the management of aneurismal subarachnoid hemorrhage revisited. A meta-analysis. Acta Neurochir (Wien) 154:1–9. https://doi.org/10.1007/s00701-011-1179-y

    Article  Google Scholar 

  33. Roos YBWE, Beenen LFM, Groen RJM, Albrecht KW, Vermeulen M (1997) Timing of surgery in patients with aneurysmal subarachnoid haemorrhage: Rebleeding is still the major cause of poor outcome in neurosurgical units that aim at early surgery. J Neurol Neurosurg Psychiatry 63:490–493

    Article  CAS  Google Scholar 

  34. Fodstad H, Forssell A, Liliequist B, Schannong M (1981) Antifibrinolysis with tranexamic acid in aneurysmal subarachnoid hemorrhage: a consecutive controlled clinical trial. Neurosurgery 8:158–165. https://doi.org/10.1227/00006123-198102000-00004

    Article  CAS  PubMed  Google Scholar 

  35. Wijdicks EFM, Hasan D, Lindsay KW, Brouwers PJAM, Hatfield R, Murray GD, van Gijn J, Vermeulen M (1989) Short-term tranexamic acid treatment in aneurysmal subarachnoid hemorrhage. Stroke 20:1674–1679. https://doi.org/10.1161/01.STR.20.12.1674

    Article  CAS  PubMed  Google Scholar 

  36. Eastin TR, Snipes CD, Seupaul RA (2014) Are antifibrinolytic agents effective in the treatment of aneurysmal subarachnoid hemorrhage? Ann Emerg Med 64:658–659. https://doi.org/10.1016/j.annemergmed.2014.06.004

    Article  PubMed  Google Scholar 

  37. Hillman J, Fridriksson S, Nilsson O, Yu Z, Säveland H, Jakobsson K-E (2002) Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg 97:771–778

    Article  CAS  Google Scholar 

  38. Fodstad H, Nilsson IM (1981) Coagulation and fibrinolysis in blood and cerebrospinal fluid after aneurysmal subarachnoid haemorrhage: effect of tranexamic acid (AMCA). Acta Neurochir (Wien) 56:25–38. https://doi.org/10.1007/BF01400969

    Article  CAS  Google Scholar 

  39. Vermeulen M, Lindsay KW, Murray GD, Cheah F, Hijdra A, Muizelaar JP, Schannong M, Teasdale GM, Van Crevel H, Van Gijn J (1984) Antifibrinolytic treatment in subarachnoid hemorrhage. N Engl J Med 311:432–437. https://doi.org/10.1056/NEJM198408163110703

    Article  CAS  PubMed  Google Scholar 

  40. Chandra B (1978) Treatment of subarachnoid hemorrhage with tranexamic acid (a double-blind clinical trial). Stroke 9:105

    Google Scholar 

  41. Roos Y (2000) Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. Neurology 54:77–82. https://doi.org/10.1212/wnl.54.1.77

    Article  CAS  PubMed  Google Scholar 

  42. Moreira MM, Adry RAR d C, Pereira CU (2019) Características do Hematoma Epidural Contralateral após Craniectomia Descompressiva para Tratamento de Trauma Cranioencefálico Grave. Revisão Sistemática Jbnc - J Bras Neurocir 28:101–110. https://doi.org/10.22290/jbnc.v28i2.1681

    Article  Google Scholar 

  43. Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, Cook L, Kawahara T, Perel P, Prieto-Merino D, Ramos M, Cairns J, Guerriero C (2013) The CRASH-2 trial: A randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess (Rockv) 17:1–80. https://doi.org/10.3310/hta17100

    Article  CAS  Google Scholar 

  44. Roberts I, Edwards P, Prieto D, Joshi M, Mahmood A, Ker K, Shakur H (2017) Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms. Trials 18:1–6. https://doi.org/10.1186/s13063-016-1750-1

    Article  CAS  Google Scholar 

  45. Ebrahimi P, Mozaffari J, Bahrami R, Hanafi MG, Mousavinejad M (2019) Intravenous tranexamic acid for subdural and epidural intracranial hemorrhage: randomized, double-blind, placebo-controlled trial. Rev Recent Clin Trials 14. https://doi.org/10.2174/1574887114666190620112829

  46. Weng S, Wang W, Wei Q, Lan H, Su J, Xu Y (2019) Effect of tranexamic acid in patients with traumatic brain injury: a systematic review and meta-analysis. World Neurosurg 123:128–135. https://doi.org/10.1016/j.wneu.2018.11.214

    Article  PubMed  Google Scholar 

  47. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer EAM, Ozier Y, Riddez L, Schultz A, Vincent JL, Spahn DR (2016) The European guideline on management of major bleeding and coagulopathy following trauma: Fourth edition. Crit Care 20:1–55. https://doi.org/10.1186/s13054-016-1265-x

    Article  Google Scholar 

  48. Crash T (2019) Articles Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury ( CRASH-3 ): a randomised. 6736

  49. Chan DYC, Tsang ACO, Li LF, Cheng KKF, Tsang FCP, Taw BBT, Pu JKS, Ho WWS, Lui WM, Leung GKK (2019) Improving survival with tranexamic acid in cerebral contusions or traumatic subarachnoid hemorrhage: univariate and multivariate analysis of independent factors associated with lower mortality. World Neurosurg 125:e665–e670. https://doi.org/10.1016/j.wneu.2019.01.145

    Article  PubMed  Google Scholar 

  50. El-Menyar A, Sathian B, Wahlen BM, Abdelrahman H, Peralta R, Al-Thani H, Rizoli S (2019) Prehospital administration of tranexamic acid in trauma patients: a 1:1 matched comparative study from a level 1 trauma center. Am J Emerg Med. 38:266–271. https://doi.org/10.1016/j.ajem.2019.04.051

    Article  PubMed  Google Scholar 

  51. Chakroun-Walha O, Samet A, Jerbi M, Nasri A, Talbi A, Kanoun H, Souissi B, Chtara K, Bouaziz M, Ksibi H, Rekik N (2018) Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients. Eur J Trauma Emerg Surg 45:1–8. https://doi.org/10.1007/s00068-018-0974-z

    Article  Google Scholar 

  52. Sponseller PD, Johnson CC, Nami N, Wetzler JA, Frank SM, Goobie SM, Johnson DJ (2016) High-dose versus low-dose tranexamic acid to reduce transfusion requirements in pediatric scoliosis surgery. J Pediatr Orthop 37:e552–e557. https://doi.org/10.1097/bpo.0000000000000820

    Article  Google Scholar 

  53. Martin K, Breuer T, Gertler R, Hapfelmeier A, Schreiber C, Lange R, Hess J, Wiesner G (2011) Tranexamic acid versus ε-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardio-thoracic Surg 39:892–897. https://doi.org/10.1016/j.ejcts.2010.09.041

    Article  Google Scholar 

  54. Ngaage DL, Bland JM (2010) 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 37:1375–1383. https://doi.org/10.1016/j.ejcts.2009.11.055

    Article  Google Scholar 

  55. Hariharan D, Mammi M, Daniels K, Petrucci K, Lamba N, Cerecedo-Lopez CD, Doucette J, Papatheodorou S, Hulsbergen A, Aglio LS, Smith TR, Mekary DR, Zaidi H (2019) The safety and efficacy of tranexamic acid in adult spinal deformity surgery: a meta-analysis. Value Health 22:S176. https://doi.org/10.1016/j.jval.2019.04.757

    Article  Google Scholar 

  56. Sharma V, Katznelson R, Jerath A, Garrido-Olivares L, Carroll J, Rao V, Wasowicz M, Djaiani G (2014) The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia 69:124–130. https://doi.org/10.1111/anae.12516

    Article  CAS  PubMed  Google Scholar 

  57. Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M (2010) High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg 110:350–353. https://doi.org/10.1213/ANE.0b013e3181c92b23

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nícollas Nunes Rabelo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, formal consent is not required.

Animal experiments

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Faria, J.L., da Silva Brito, J., Costa e Silva, L.T. et al. Tranexamic acid in Neurosurgery: a controversy indication—review. Neurosurg Rev 44, 1287–1298 (2021). https://doi.org/10.1007/s10143-020-01324-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-020-01324-0

Keywords

Navigation