Clinical Significance of Vascular Occlusive Events following Moderate-to-Severe Traumatic Brain Injury: An Observational Cohort Study

Abstract

Preventing hemorrhage progression is a potential therapeutic opportunity in traumatic brain injury (TBI) management, but its use has been limited by fear of provoking vascular occlusive events (VOEs). However, it is currently unclear whether VOE actually affects outcome in these patients. The aim of this study was to determine incidence, risk factors, and clinical significance of VOE in patients with moderate-to-severe TBI. A retrospective observational cohort study of adults (≥15 years) with moderate-to-severe TBI was performed. The presence of a VOE during hospitalization was noted from hospital charts and radiological reports. Functional outcome, using the Glasgow Outcome Scale (GOS), was assessed at 12 months posttrauma. Univariate and multivariate logistic regressions were used for endpoint assessment. In total, 848 patients were included, with a median admission Glasgow Coma Scale of 7. A VOE was detected in 54 (6.4%) patients, of which cerebral venous thrombosis was the most common (3.2%), followed by pulmonary embolism (1.7%) and deep vein thrombosis (1.3%). Length of ICU stay (p < 0.001), body weight (p = 0.002), and skull fracture (p = 0.004) were independent predictors of VOE. VOE development did not significantly impact 12-month GOS, even after adjusting for potential confounders using propensity score matching. In conclusion, VOE in moderate-to-severe TBI patients was relatively uncommon, and did not affect 12-month GOS. This suggests that the potential benefit of treating bleeding progression might outweigh the risks of VOE.

Keywords

traumatic brain injury - head injury - neurotrauma - vascular occlusive event - pulmonary embolism - deep vein thrombosis - cerebral venous thrombosis

Note

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethical Approval

The study was approved by the Swedish Ethical Review Authority (Dnr: 2019-04476) who waived the need for informed consent.

Authors' Contributions

Study design: A.F.-S. Data collection: A.F-S., C.T., J.T. Statistical analysis: A.F.-S. Data interpretation: All authors. Draft of manuscript: A.F.-S. Critical revision and approval of manuscript: All authors. Study supervision: E.P.T., B.-M.B.

^* Shared last authorship.

Publikationsverlauf

Artikel online veröffentlicht:
06. Januar 2022

• References

• 1 Alahmadi H, Vachhrajani S, Cusimano MD. The natural history of brain contusion: an analysis of radiological and clinical progression. J Neurosurg 2010; 112 (05) 1139-1145
• 2 CRASH-3 Trial Collaborators. 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 (10210): 1713-1723
• 3 Xu X, Wang C, Wu Y. et al. Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice. Blood 2021; 137 (04) 544-555
• 4 Lawati KA, Sharif S, Maqbali SA. 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 (01) 14-27
• 5 Fletcher-Sandersjöö A, Thelin EP, Maegele M. et al. Time course of hemostatic disruptions after traumatic brain injury: a systematic review of the literature. Neurocrit Care 2021; 34 (02) 635-656
• 6 Reiff DA, Haricharan RN, Bullington NM, Griffin RL, McGwin Jr G, Rue III LW. Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 2009; 66 (05) 1436-1440
• 7 Byrne JP, Mason SA, Gomez D. et al. Timing of pharmacologic venous thromboembolism prophylaxis in severe traumatic brain injury: a propensity-matched cohort study. J Am Coll Surg 2016; 223 (04) 621-631.e5
• 8 Denson K, Morgan D, Cunningham R. et al. Incidence of venous thromboembolism in patients with traumatic brain injury. Am J Surg 2007; 193 (03) 380-383 , discussion 383–384
• 9 Ekeh AP, Dominguez KM, Markert RJ, McCarthy MC. Incidence and risk factors for deep venous thrombosis after moderate and severe brain injury. J Trauma 2010; 68 (04) 912-915
• 10 Farooqui A, Hiser B, Barnes SL, Litofsky NS. Safety and efficacy of early thromboembolism chemoprophylaxis after intracranial hemorrhage from traumatic brain injury. J Neurosurg 2013; 119 (06) 1576-1582
• 11 Praeger AJ, Westbrook AJ, Nichol AD. et al. Deep vein thrombosis and pulmonary embolus in patients with traumatic brain injury: a prospective observational study. Critical Care and Resuscitation 2012; 14: 10-13
• 12 Skrifvars MB, Bailey M, Presneill J. et al; EPO-TBI Investigators and the ANZICS Clinical Trials Group. Venous thromboembolic events in critically ill traumatic brain injury patients. Intensive Care Med 2017; 43 (03) 419-428
• 13 Bahloul M, Chelly H, Regaieg K. et al. Pulmonary embolism following severe traumatic brain injury: incidence, risk factors and impact outcome. Intensive Care Med 2017; 43 (09) 1433-1435
• 14 Seifi A, Dengler B, Martinez P, Godoy DA. Pulmonary embolism in severe traumatic brain injury. J Clin Neurosci 2018; 57: 46-50
• 15 Fletcher-Sandersjöö A, Tatter C, Tjerkaski J. et al. Clinical impact of hemorrhagic lesion progression following moderate-to-severe traumatic brain injury: an observational cohort study. 2021 (epub ahead of print)
• 16 Steyerberg EW, Mushkudiani N, Perel P. et al. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med 2008; 5 (08) e165 , discussion e165
• 17 Harrel Jr F. rms: Regression Modeling Strategies. R package version 6.2–0. 2021
• 18 Ho D, Imai K, King G, Stuart EA. MatchIt: Nonparametric preprocessing for parametric causal inference. J Stat Softw 2011; 42: 1-28
• 19 van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate imputation by chained equations in R. J Stat Softw 2011; 45: 1-67
• 20 Lu VM, Alvi MA, Rovin RA, Kasper EM. Clinical outcomes following early versus late pharmacologic thromboprophylaxis in patients with traumatic intracranial hemorrhage: a systematic review and meta-analysis. Neurosurg Rev 2020; 43 (03) 861-872
• 21 Dietch ZC, Petroze RT, Thames M, Willis R, Sawyer RG, Williams MD. The “high-risk” deep venous thrombosis screening protocol for trauma patients: Is it practical?. J Trauma Acute Care Surg 2015; 79 (06) 970-975 , discussion 975
• 22 Braithwaite I, Healy B, Cameron L, Weatherall M, Beasley R. Lower limb immobilisation and venous thromboembolism risk: combined case-control studies. Postgrad Med J 2017; 93 (1100): 354-359
• 23 Hotoleanu C. Association between obesity and venous thromboembolism. Med Pharm Rep 2020; 93 (02) 162-168
• 24 Blokhin IO, Lentz SR. Mechanisms of thrombosis in obesity. Curr Opin Hematol 2013; 20 (05) 437-444
• 25 Netteland DF, Mejlænder-Evjensvold M, Skaga NO, Sandset EC, Aarhus M, Helseth E. Cerebral venous thrombosis in traumatic brain injury: a cause of secondary insults and added mortality. J Neurosurg 2020; 134 (06) 1912-1920
• 26 Rivkin MA, Saraiya PV, Woodrow SI. Sinovenous thrombosis associated with skull fracture in the setting of blunt head trauma. Acta Neurochir (Wien) 2014; 156 (05) 999-1007 , discussion 1007
• 27 Schultz DJ, Brasel KJ, Washington L. et al. Incidence of asymptomatic pulmonary embolism in moderately to severely injured trauma patients. J Trauma 2004; 56 (04) 727-731 , discussion 731–733
• 28 Wilson JTL, Pettigrew LEL, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 1998; 15 (08) 573-585