Top

BMC Neurology

Published in:

01-12-2020 | Central Nervous System Trauma | Research article

Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials

Authors: Julius July, Raymond Pranata

Published in: BMC Neurology | Issue 1/2020

Abstract

Background

This systematic review and meta-analysis aimed to synthesize the latest evidence on the efficacy and safety of tranexamic acid (TXA) on traumatic brain injury (TBI).

Methods

We performed a systematic literature search on topics that compared intravenous TXA to placebo in patients with TBI up until January 2020 from several electronic databases.

Results

There were 30.522 patients from 7 studies. Meta-analysis showed that TXA was associated with reduced mortality (RR 0.92 [0.88, 0.97], p = 0.002; I²: 0%) and hemorrhagic expansion (RR 0.79 [0.64, 0.97], p = 0.03; I²: 0%). Both TXA and control group has a similar need for neurosurgical intervention (p = 0.87) and unfavourable Glasgow Outcome Scale (GOS) (p = 0.59). The rate for vascular occlusive events (p = 0.09), and its deep vein thrombosis subgroup (p = 0.23), pulmonary embolism subgroup (p = 1), stroke subgroup (p = 0.38), and myocardial infarction subgroup (p = 0.15) were similar in both groups. Subgroup analysis on RCTs with low risk of bias showed that TXA was associated with reduced mortality and hemorrhagic expansion. TXA was associated with reduced vascular occlusive events (RR 0.85 [0.73, 0.99], p = 0.04; I²: 4%). GRADE was performed for the RCT with low risk of bias subgroup, it showed a high certainty of evidence for lower mortality, less hemorrhage expansion, and similar need for neurosurgical intervention in TXA group compared to placebo group.

Conclusion

TXA was associated with reduced mortality and hemorrhagic expansion but similar need for neurosurgical intervention and unfavorable GOS. Vascular occlusive events were slightly lower in TXA group on subgroup analysis of RCTs with low risk of bias.

Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung Y-C, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2019;130:1080–97. https://doi.org/10.3171/2017.10.JNS17352.CrossRef

James SL, Theadom A, Ellenbogen RG, Bannick MS, Montjoy-Venning W, Lucchesi LR, et al. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2019;18:56–87. https://doi.org/10.1016/S1474-4422(18)30415-0.CrossRef

Perel P, Roberts I, Bouamra O, Woodford M, Mooney J, Lecky F. Intracranial bleeding in patients with traumatic brain injury: a prognostic study. BMC Emerg Med. 2009;9:15. https://doi.org/10.1186/1471-227X-9-15.CrossRefPubMedPubMedCentral

Zehtabchi S, Soghoian S, Liu Y, Carmody K, Shah L, Whittaker B, et al. The association of coagulopathy and traumatic brain injury in patients with isolated head injury. Resuscitation. 2008;76:52–6. https://doi.org/10.1016/j.resuscitation.2007.06.024.CrossRefPubMed

Harhangi BS, Kompanje EJO, Leebeek FWG, Maas AIR. Coagulation disorders after traumatic brain injury. Acta Neurochir. 2008;150:165–75. https://doi.org/10.1007/s00701-007-1475-8.CrossRefPubMed

Allard CB, Scarpelini S, Rhind SG, Baker AJ, Shek PN, Tien H, et al. Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage. J Trauma Inj Infect Crit Care. 2009;67:959–67. https://doi.org/10.1097/TA.0b013e3181ad5d37.CrossRef

Wafaisade A, Lefering R, Tjardes T, Wutzler S, Simanski C, Paffrath T, et al. Acute coagulopathy in isolated blunt traumatic brain injury. Neurocrit Care. 2010;12:211–9. https://doi.org/10.1007/s12028-009-9281-1.CrossRefPubMed

Gall L, Davenport R, Brohi K. Effect of early tranexamic acid on the coagulation system in patients with suspected traumatic haemorrhage: a prospective cohort study. Lancet. 2016;387:S46. https://doi.org/10.1016/S0140-6736(16)00433-5.CrossRef

Chakroun-Walha O, Samet A, Jerbi M, Nasri A, Talbi A, Kanoun H, 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;45:719–26. https://doi.org/10.1007/s00068-018-0974-z.CrossRefPubMed

10.

Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, 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;17:1–80. https://doi.org/10.3310/hta17100.CrossRefPubMedPubMedCentral

11.

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. https://doi.org/10.1186/1471-227X-13-20.CrossRefPubMedPubMedCentral

12.

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:e748–53. https://doi.org/10.1016/j.wneu.2017.10.075.CrossRefPubMed

13.

Crash T. 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. 2019;394:1713–23. https://doi.org/10.1016/S0140-6736(19)32233-0.CrossRef

14.

Jokar A, Ahmadi K, Salehi T, Sharif-Alhoseini M, Rahimi-Movaghar V. The effect of tranexamic acid in traumatic brain injury: a randomized controlled trial. Chin J Traumatol. 2017;20:49–51. https://doi.org/10.1016/j.cjtee.2016.02.005.CrossRefPubMedPubMedCentral

15.

May S. Prehospital tranexamic acid use for traumatic brain injury (TXA); 2019. Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT01990768?term=NCT01990768&draw=2&rank=1&view=results. Accessed 1 Jan 2020.

16.

Reed MR, Woolley LT. Uses of tranexamic acid. Contin Educ Anaesth Crit Care Pain. 2015;15:32–7. https://doi.org/10.1093/bjaceaccp/mku009.CrossRef

17.

Lier H, Maegele M, Shander A. Tranexamic acid for acute hemorrhage. Anesth Analg. 2019;129:1574–84. https://doi.org/10.1213/ANE.0000000000004389.CrossRefPubMed

18.

Diebel LN, Martin JV, Liberati DM. Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model. J Trauma Acute Care Surg. 2017;82:1080–6. https://doi.org/10.1097/TA.0000000000001445.CrossRefPubMed

19.

Teng Y, Feng C, Liu Y, Jin H, Gao Y, Li T. Anti-inflammatory effect of tranexamic acid against trauma-hemorrhagic shock-induced acute lung injury in rats. Exp Anim. 2018;67:313–20. https://doi.org/10.1538/expanim.17-0143.CrossRefPubMedPubMedCentral

20.

Draxler DF, Daglas M, Fernando A, Hanafi G, McCutcheon F, Ho H, et al. Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis. J Thromb Haemost. 2019;17:2174–87. https://doi.org/10.1111/jth.14603.CrossRefPubMed

21.

Draxler DF, Awad MM, Hanafi G, Daglas M, Ho H, Keragala C, et al. Tranexamic acid influences the immune response, but not bacterial clearance in a model of post-traumatic brain injury pneumonia. J Neurotrauma. 2019;36:3297–308. https://doi.org/10.1089/neu.2018.6030.CrossRefPubMed

22.

Chan DYC, Tsang ACO, Li LF, Cheng KKF, Tsang FCP, Taw BBT, et al. 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. 2019;125:e665–70. https://doi.org/10.1016/j.wneu.2019.01.145.CrossRefPubMed

23.

Ebrahimi P, Mozafari J, Ilkhchi RB, Hanafi MG, Mousavinejad M. Intravenous tranexamic acid for subdural and epidural intracranial hemorrhage: randomized, double-blind, placebo-controlled trial. Rev Recent Clin Trials. 2019;14:286–91. https://doi.org/10.2174/1574887114666190620112829.CrossRefPubMed

24.

Mousavinejad M, Mozafari J, Ilkhchi RB, Hanafi MG, Ebrahimi P. Intravenous tranexamic acid for brain contusion with Intraparenchymal hemorrhage: randomized, double-blind, placebo-controlled trial. Rev Recent Clin Trials. 2019;14. https://doi.org/10.2174/1574887114666191118111826.

25.

Yu X, Wang J, Wang X, Xie L, Chen C, Zheng W. The efficacy and safety of tranexamic acid in the treatment of intertrochanteric fracture: an updated meta-analysis of 11 randomized controlled trials. J Thromb Thrombolysis. 2020. https://doi.org/10.1007/s11239-019-02034-1.

26.

Levy JH. Antifibrinolytic therapy: new data and new concepts. Lancet. 2010;376:3–4. https://doi.org/10.1016/S0140-6736(10)60939-7.CrossRefPubMed

27.

Davies MJ. Coronary disease: the pathophysiology of acute coronary syndromes. Heart. 2000;83:361–6. https://doi.org/10.1136/heart.83.3.361.CrossRefPubMedPubMedCentral

28.

Behravesh S, Hoang P, Nanda A, Wallace A, Sheth RA, Deipolyi AR, et al. Pathogenesis of thromboembolism and endovascular management. Thrombosis. 2017;2017:1–13. https://doi.org/10.1155/2017/3039713.CrossRef

Title: Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials
Authors: Julius July
Raymond Pranata
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Central Nervous System Trauma
Myocardial Infarction
Phlebothrombosis
Tranexamic Acid
Published in: BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-020-01694-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2020

Radiation-induced cavernous malformation after stereotactic radiosurgery for cavernous sinus meningioma: a case report

Two case reports of distal upper limb weakness following influenza-like illness: an emerging pattern of para-infectious myositis in adults

Restless abdomen: a spectrum or a phenotype variant of restless legs syndrome?

Severe pain-related adverse events of percutaneous dilatational tracheostomy performed by a neurointensivist compared with conventional surgical tracheostomy in neurocritically ill patients

Fulminant encephalopathy in a child with hyperferritinemic sepsis: a case report

Recurrence and retreatment of anterior communicating artery aneurysms after endovascular treatment: a retrospective study