Vol 12, No 1 (2021)
Review paper
Published online: 2021-09-29

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Tranexamic acid for traumatic brain injury? Old drug raises new debate

Damian Palus1, Aleksandra Cegła1, Alan Majeranowski2, Andrzej Mital2, Michał Krakowiak3, Tomasz Szmuda3, Paweł Słoniewski3
Hematology in Clinical Practice 2021;12(1):1-7.


Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and young adults, but also an important medical problem concerning the older part of the population. TBI has an inauspicious prognosis and the mortality remains high, reaching up to 40% in severe injuries. Extensive research on treatment options that could minimize the mortality rate and the number of complications is ongoing and one of these options is tranexamic acid. One of the pathomechanisms of uncontrollable bleeding is hyperfibrinolysis, where the mechanisms controlling fibrinolysis are disrupted and cause it to become excessively intensified. Tranexamic acid (TXA) is an inhibitor of plasminogen and thus inhibits fibrinolysis. This paper aims to provide an overview of the current state of knowledge about tranexamic acid in traumatic brain injury. According to available, data pre-hospital intravenous tranexamic acid infusion administered early, within 3 hours from the injury, seems to reduce mortality in patients with mild to moderate traumatic brain injury, but in patients with severe TBI, this treatment could be associated with increased mortality. The use of TXA does not increase the risk of adverse events. Moreover, the safety of tranexamic acid has been confirmed and no correlation between the use of TXA and a higher incidence of thromboembolic events has been found. Current findings do not give a conclusive answer on the effectiveness of TXA in TBI. Large, international randomized clinical trials have to be performed to answer this question. Additionally, further studies in the use of TXA in TBI in the pediatric population are also needed.

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  1. Dewan MC, Rattani A, Gupta S, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018 [Epub ahead of print]: 1–18.
  2. Khellaf A, Khan DZ, Helmy A. Recent advances in traumatic brain injury. J Neurol. 2019; 266(11): 2878–2889.
  3. Mena JH, Sanchez AI, Rubiano AM, et al. Effect of the modified Glasgow Coma Scale score criteria for mild traumatic brain injury on mortality prediction: comparing classic and modified Glasgow Coma Scale score model scores of 13. J Trauma. 2011; 71(5): 1185–92; discussion 1193.
  4. Peeters W, van den Brande R, Polinder S, et al. Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien). 2015; 157(10): 1683–1696.
  5. McGinn MJ, Povlishock JT. Pathophysiology of traumatic brain injury. Neurosurg Clin N Am. 2016; 27(4): 397–407.
  6. Harhangi BS, Kompanje EJO, Leebeek FWG, et al. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien). 2008; 150(2): 165–75; discussion 175.
  7. Wafaisade A, Lefering R, Tjardes T, et al. Trauma Registry of DGU. Acute coagulopathy in isolated blunt traumatic brain injury. Neurocrit Care. 2010; 12(2): 211–219.
  8. Zhang J, Jiang R, Liu Li, et al. Traumatic brain injury-associated coagulopathy. J Neurotrauma. 2012; 29(17): 2597–2605.
  9. Hess JR, Brohi K, Dutton RP, et al. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008; 65(4): 748–754.
  10. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016; 41(1): 3–14.
  11. Levy JH, Koster A, Quinones QJ, et al. Antifibrinolytic therapy and perioperative considerations. Anesthesiology. 2018; 128(3): 657–670.
  12. Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev. 2015; 29(1): 17–24.
  13. McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012; 72(5): 585–617.
  14. Pabinger I, Fries D, Schöchl H, et al. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017; 129(9-10): 303–316.
  15. Picetti R, Shakur-Still H, Medcalf RL, et al. What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies. Blood Coagul Fibrinolysis. 2019; 30(1): 1–10.
  16. Eriksson O, Kjellman H, Pilbrant A, et al. Pharmacokinetics of tranexamic acid after intravenous administration to normal volunteers. Eur J Clin Pharmacol. 1974; 7(5): 375–380.
  17. Roberts I, Shakur-Still H, Aeron-Thomas A A. 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. The Lancet. 2019; 394(10210): 1713–1723.
  18. Roberts I, Shakur H, Coats T, et al. 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. 2013; 17(10): 1–79.
  19. Roberts I, Yates D, Sandercock P, et al. CRASH trial collaborators. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004; 364(9442): 1321–1328.
  20. Roberts I, Shakur H, Coats T, et al. 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. 2013; 17(10): 1–79.
  21. Roos YB, Rinkel GJE, Vermeulen M, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2000(2): CD001245.
  22. Perel P, Salman RAS, Constain A, et al. 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.
  23. Bossers SM, Loer SA, Bloemers FW, et al. BRAIN-PROTECT collaborators. Association between prehospital tranexamic acid administration and outcomes of severe traumatic brain injury. JAMA Neurol. 2021; 78(3): 338–345.
  24. Rowell SE, Meier EN, McKnight B, et al. Effect of out-of-hospital tranexamic acid vs placebo on 6-month functional neurologic outcomes in patients with moderate or severe traumatic brain injury. JAMA. 2020; 324(10): 961–974.
  25. Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, et al. Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emerg Med. 2013; 13: 20.
  26. Jokar A, Ahmadi K, Salehi T, et al. The effect of tranexamic acid in traumatic brain injury: a randomized controlled trial. Chin J Traumatol. 2017; 20(1): 49–51.
  27. Fakharian E, Abedzadeh-Kalahroudi M, Atoof F. Effect of tranexamic acid on prevention of hemorrhagic mass growth in patients with traumatic brain injury. World Neurosurg. 2018; 109: e748–e753.
  28. Chakroun-Walha O, Samet A, Jerbi M, et al. Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients. Eur J Trauma Emerg Surg. 2019; 45(4): 719–726.
  29. Ebrahimi P, Mozafari J, Ilkhchi RB, et al. Intravenous tranexamic acid for subdural and epidural intracranial hemorrhage: randomized, double-blind, placebo-controlled trial. Rev Recent Clin Trials. 2019; 14(4): 286–291.
  30. Mousavinejad M, Mozafari J, Ilkhchi RB, et al. Intravenous tranexamic acid for brain contusion with intraparenchymal hemorrhage: randomized, double-blind, placebo-controlled trial. Rev Recent Clin Trials. 2020; 15(1): 70–75.
  31. Lawati KAl, Sharif S, Maqbali SAl, et al. Efficacy and safety of tranexamic acid in acute traumatic brain injury: a systematic review and meta-analysis of randomized-controlled trials. Intensive Care Med. 2021; 47(1): 14–27.
  32. Yokobori S, Yatabe T, Kondo Y, et al. Japan Resuscitation Council (JRC) Neuroresuscitation Task Force and the Guidelines Editorial Committee. Efficacy and safety of tranexamic acid administration in traumatic brain injury patients: a systematic review and meta-analysis. J Intensive Care. 2020; 8: 46.
  33. Guo J, Gao X, Ma Y, et al. Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials. BMC Anesthesiol. 2019; 19(1): 129.

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