Venous thromboembolic sequel of head injury: A narrative review


1 Centro de Investigaciones Biomédicas, Cartagena Neurotrauma Research Group Research Line, Faculty of Medicine, University of Cartagena, Cartagena de Indias, Colombia

2 Department of Community Medicine, MGM Medical College and LSK Hospital, Kishanganj, Bihar, India

3 Department of Biochemistry, Kolkata Medical College, Kolkata, West Bengal, India

4 Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

5 Neurosurgery-Critical Care, Red Latino, Organizacion Latinoamericana de Trauma y Cuidado Neurointensivo, Bogota, Colombia

6 Department of Neurosurgery, Narayana Medical College Hospital, Nellore, Andhra Pradesh, India


In this systematic review, we detailed the current understanding and controversies on venous thromboembolism as the sequel following traumatic brain injury (TBI). The review was conducted on the literature survey to find the thromboembolic morbidities in TBI patients. This review presented the thromboembolic sequel of patients with TBI by a comprehensive focused assembly of research publications by searching various resources. A search strategy with specific inclusion criteria was performed in PubMed, Cochrane, Web of Science, and the WHO Global Health Library. TBI is related with the incremental presence of spectrum of thromboembolic disorders from primary and secondary injuries by the significant increases in the concentrations of the initiating factors of the coagulation cascade. The incidences of thromboembolism vary on factors like the severity of TBI, methods of prophylaxis used or the processes to diagnose embolic involvement. The most effective time for the initiation of antithrombotic therapy chemoprophylaxis should be initiated after 24 h or after 72 h in patients with brain trauma is still a controversial issue. Patients with brain injury are at increased risk for thromboembolism for which prophylaxis and timely management are highly recommended, and this should be available in all levels of care.


1. Nyquist P, Bautista C, Jichici D, Burns J, Chhangani S, DeFilippis M, et al. Prophylaxis of venous thrombosis in neurocritical care patients: An evidence‑based guideline: A statement for healthcare professionals from the neurocritical care society. Neurocrit Care 2016;24:47‑60. 
2. Reiff DA, Haricharan RN, Bullington NM, Griffin RL, McGwin G Jr., Rue LW 3rd. Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 2009;66:1436‑40. 
3. DeMuro J, Hanna A. Prophylaxis of deep venous thrombosis in trauma patients: A review. J Blood Disord Transfus 2013; 4: 151. doi: 10.4172/2155- 9864.1000151. 
4. Ramnarain M. Thromboprophylaxis in Traumatic Brain Injury: University of Kwazulu‑Natal; 2011. 
5. American College of Surgeons Comittee on Trauma. ACS TQIP Best Practices in the Management of Traumatic Brain Injury. Chicago: American College of Surgeons; 2015. 
6. Kim L, Schuster J, Holena DN, Sims CA, Levine J, Pascual JL. Early initiation of prophylactic heparin in severe traumatic brain injury is associated with accelerated improvement on brain imaging. J Emerg Trauma Shock 2014;7:141‑8. 
7. Dudley RR, Aziz I, Bonnici A, Saluja RS, Lamoureux J, Kalmovitch B, et al. Early venous thromboembolic event prophylaxis in traumatic brain injury with low‑molecular‑weight heparin: Risks and benefits. J Neurotrauma 2010;27:2165‑72. 
8. FarooquiA, HiserB, Barnes SL, Litofsky NS. Safety and efficacy of early thromboembolism chemoprophylaxis after intracranial hemorrhage from traumatic brain injury. J Neurosurg 2013;119:1576‑82. 
9. Byrne JP, Mason SA, Gomez D, Hoeft C, Subacius H, Xiong W, et al. Timing of pharmacologic venous thromboembolism prophylaxis in severe traumatic brain injury: A propensity‑matched cohort study. J Am Coll Surg 2016;223:621‑31. 
10. Dengler BA, Mendez‑Gomez P, Chavez A, Avila L, Michalek J, Hernandez B, et al. Safety of chemical DVT prophylaxis in severe traumatic brain injury with invasive monitoring devices. Neurocrit Care 2016;25:215‑23.
11. Strollo BP, Bennett GJ, Chopko MS, Guo WA. Timing of venous thromboembolism chemoprophylaxis after traumatic brain injury. J Crit Care 2018;43:75‑80. 
12. Cupitt JM. Prophylaxis against thromboembolism in patients with traumatic brain injury: A survey of UK practice. Anaesthesia 2001;56:780‑85. 13. Lin W, Yang LK, Cai S, Zhu J, Feng Y, Yang L, et al. Cognitive function and biomarkers after traumatic brain injury: Protocol for a prospective inception cohort study. Asia Pac J Clin Trials Nervous Syst Dis 2016; 1:170. 
14. Vella MA, Crandall ML, Patel MB. Acute Management of Traumatic Brain Injury. Surg Clin North Am 2017;97:1015-30. 
15. Raychaudhuri R, Litofsky NS. Which traumatic brain injury patients should be treated with anticoagulants and when? Expert Rev Neurother2014;14:237‑9
16. Rabinowitz AR, Levin HS. Cognitive sequelae of traumatic brain injury. Psychiatr Clin North Am 2014;37:1‑11. 
17. Vincent AS, Roebuck‑Spencer TM, Cernich A. Cognitive changes and dementia risk after traumatic brain injury: Implications for aging military personnel. Alzheimers Dement 2014;10:S174‑87. 
18. Paydar S, Sabetian G, Khalili H, Fallahi J, Tahami M, Ziaian B, et al. Management of deep vein thrombosis (DVT) prophylaxis in trauma patients. Bull Emerg Trauma 2016;4:1‑7. 
19. Phelan HA. Pharmacologic venous thromboembolism prophylaxis after traumatic brain injury: A critical literature review. J Neurotrauma 2012;29:1821‑8. 
20. Zakrison TL, Pereira BM, Marttos AC Jr., Fraga GP, Nascimento B Jr., RizoliS. Venous thromboembolism prophylaxis in patients with traumatic brain injury. Rev Colégio Bras Cir 2012;39:553‑7. 
21. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80:6‑15. 
22. Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Results of meta‑analysis. Ann Surg 1988;208:227‑40. 
23. Heit JA, Mohr DN, Silverstein MD, Petterson TM, O’Fallon WM, Melton LJ 3rd. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: A population‑based cohort study. Arch Intern Med 2000;160:761‑8. 24. Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, et al. A comparison of low‑dose heparin with low‑molecular‑weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996;335:701‑7.
25. Kim J, Gearhart MM, Zurick A, Zuccarello M, James L, Luchette FA. Preliminary report on the safety of heparin for deep venous thrombosis prophylaxis after severe head injury. J Trauma 2002;53:38‑42. 
26. Merli GJ, Groce JB. Pharmacological and clinical differences between low‑molecular‑weight heparins: Implications for prescribing practice and therapeutic interchange. P T 2010;35:95‑105.
27. Lu JP, Knudson MM, Bir N, Kallet R, Atkinson K. Fondaparinux for prevention of venous thromboembolism in high‑risk trauma patients: A pilot study. J Am Coll Surg 2009;209:589‑94. 
28. Malinoski D, Jafari F, Ewing T, Ardary C, Conniff H, Baje M, et al. Standard prophylactic enoxaparin dosing leads to inadequate anti-Xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients. J Trauma 2010;68:874-80. 
29. Rutherford EJ, Schooler WG, Sredzienski E, Abrams JE, Skeete DA. Optimal dose of enoxaparin in critically ill trauma and surgical patients. J Trauma 2005;58:1167‑70. 
30. Costantini TW, Min E, Box K, Tran V, Winfield RD, Fortlage D, et al. Dose adjusting enoxaparin is necessary to achieve adequate venous thromboembolism prophylaxis in trauma patients. J Trauma Acute Care Surg 2013;74:128‑33. 
31. Lin H, Faraklas I, Saffle J, Cochran A. Enoxaparin dose adjustment is associated with low incidence of venous thromboembolic events in acute burn patients. J Trauma 2011;71:1557‑61. 
32. Koehler DM, Shipman J, Davidson MA, Guillamondegui O. Is early venous thromboembolism prophylaxis safe in trauma patients with intracranial hemorrhage. J Trauma 2011;70:324‑9. 
33. Schaible EV, Thal SC. Anticoagulation in patients with traumatic brain injury. Curr Opin Anaesthesiol 2013;26:529‑34. 
34. Levy AS, Salottolo K, Bar‑Or R, Offner P, Mains C, Sullivan M, et al. Pharmacologic thromboprophylaxis is a risk factor for hemorrhage progression in a subset of patients with traumatic brain injury. J Trauma 2010;68:886‑94. 35. Phelan HA, Eastman AL, Madden CJ, Aldy K, Berne JD, Norwood SH, et al. TBI risk stratification at presentation: A prospective study of the incidence and timing of radiographic worsening in the parkland protocol. J Trauma Acute Care Surg 2012;73:S122‑7. 
36. Pastorek RA, Cripps MW, Bernstein IH, Scott WW, Madden CJ, Rickert KL, et al. The parkland protocol’s modified Berne‑Norwood criteria predict two tiers of risk for