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

Julius July, Raymond Pranata, Julius July, Raymond Pranata

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.

Keywords: Brain trauma; Coagulopathy; Thromboembolism; Tranexamic acid; Traumatic brain injury; Vascular occlusive events.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow diagram
Fig. 2
Fig. 2
Meta-analysis for tranexamic acid versus placebo. a demonstrated a lower mortality rate in TXA group. b showed hemorrhagic expansion was less in TXA group. Vascular occlusive events (Fig. 4c), defined as DVT + PE + stroke+MI was similar in both groups. Description = DVT: Deep Vein Thrombosis; MI: Myocardial Infarction; PE: Pulmonary Embolism; TXA: Tranexamic Acid
Fig. 3
Fig. 3
Risk of Bias Assessment. a showed Cochrane Risk of Bias Assessment for Randomized Controlled Trials. b and c showed funnel-plot analysis for mortality and hemorrhagic expansion respectively
Fig. 4
Fig. 4
Subgroup analysis for studies with low risk of bias. a demonstrated a lower mortality rate in TXA group. b showed hemorrhagic expansion was less in TXA group. Vascular occlusive events (c), defined as DVT + PE + stroke+MI was lower in TXA group. Description = DVT: Deep Vein Thrombosis; MI: Myocardial Infarction; PE: Pulmonary Embolism; TXA: Tranexamic Acid

References

    1. 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;130:1080–1097. doi: 10.3171/2017.10.JNS17352.
    1. 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. doi: 10.1016/S1474-4422(18)30415-0.
    1. 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. doi: 10.1186/1471-227X-9-15.
    1. 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;76:52–56. doi: 10.1016/j.resuscitation.2007.06.024.
    1. Harhangi BS, Kompanje EJO, Leebeek FWG, Maas AIR. Coagulation disorders after traumatic brain injury. Acta Neurochir. 2008;150:165–175. doi: 10.1007/s00701-007-1475-8.
    1. 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;67:959–967. doi: 10.1097/TA.0b013e3181ad5d37.
    1. 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;12:211–219. doi: 10.1007/s12028-009-9281-1.
    1. 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. doi: 10.1016/S0140-6736(16)00433-5.
    1. 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;45:719–726. doi: 10.1007/s00068-018-0974-z.
    1. 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. doi: 10.3310/hta17100.
    1. 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. doi: 10.1186/1471-227X-13-20.
    1. 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. doi: 10.1016/j.wneu.2017.10.075.
    1. 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;394:1713–1723. doi: 10.1016/S0140-6736(19)32233-0.
    1. 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. doi: 10.1016/j.cjtee.2016.02.005.
    1. May S. Prehospital tranexamic acid use for traumatic brain injury (TXA) 2019.
    1. Reed MR, Woolley LT. Uses of tranexamic acid. Contin Educ Anaesth Crit Care Pain. 2015;15:32–37. doi: 10.1093/bjaceaccp/mku009.
    1. Lier H, Maegele M, Shander A. Tranexamic acid for acute hemorrhage. Anesth Analg. 2019;129:1574–1584. doi: 10.1213/ANE.0000000000004389.
    1. 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;82:1080–1086. doi: 10.1097/TA.0000000000001445.
    1. 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;67:313–320. doi: 10.1538/expanim.17-0143.
    1. 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;17:2174–2187. doi: 10.1111/jth.14603.
    1. 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;36:3297–3308. doi: 10.1089/neu.2018.6030.
    1. 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–e670. doi: 10.1016/j.wneu.2019.01.145.
    1. 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;14:286–291. doi: 10.2174/1574887114666190620112829.
    1. 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. 10.2174/1574887114666191118111826.
    1. 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. 10.1007/s11239-019-02034-1.
    1. Levy JH. Antifibrinolytic therapy: new data and new concepts. Lancet. 2010;376:3–4. doi: 10.1016/S0140-6736(10)60939-7.
    1. Davies MJ. Coronary disease: the pathophysiology of acute coronary syndromes. Heart. 2000;83:361–366. doi: 10.1136/heart.83.3.361.
    1. 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. doi: 10.1155/2017/3039713.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel