Skip to main content
  • A Systematic Review of the Risks and Benefits of Venous Thromboembolism Prophylaxis in Traumatic Brain Injury

    Final Number:

    Joseph Margolick; Charlotte Dandurand MD; David C Evans; Mypinder S Sekhon; Donald E G Griesdale; Peter A. Gooderham MD, BS; Morad Hameed

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of chemoprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the post-injury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion.

    Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were: studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers based on levels of evidence.

    Results: A total of 408 studies were screened. Forty-five studies were reviewed inentirety and 21 were included in the systematic review. There were 2 prospective randomized trials and 19 comparative studies. Eighteen total studies demonstrated that VTEp post injury in patients with stable head computed tomography scan (CT) does not lead to radiographic or clinical TBI progression. Fourteen studies demonstrated that VTEp administration specifically 24 – 72 hours post injury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive ICH. One study – a retrospective review of 1215 patients – suggested low molecular-weight-heparin (LMWH) is a risk factor for TBI progression. One retrospective review found unfractionated-heparin was associated with higher rates of TBI progression than LMWH. It is not yet clear what exactly constitutes a low risk TBI, but a recurring theme in the literature is that hemorrhagic expansion is associated with more severe TBI.

    Conclusions: Literature suggests that administering VTEp 48 hours post-injury may be safe for patients with low-hemorrhagic risk TBIs and stable injury on repeat imaging. A clinical practice guideline (CPG) was developed at our level-1 trauma center. Future research may focus on prospectively testing our CPG.

    Patient Care: Delaying or avoiding thromboprophylaxis in the TBI or multitrauma population can have devastating consequences such deep vein thrombosis and pulmonary embolism. It is recognized that the TBI population is heterogenous. A portion is considered low-risk for thromboprophylaxis initiation. This research aims at encouraging physicians, from neurosurgeons at tertiary center to physicians working in the rural community, to initiate thromboprophylaxis in adequate settings.

    Learning Objectives: By the conclusion of this session, participants should be able to : 1) Understand the diversity in TBI population 2) Identify low and high risk traumatic brain injuries in regards to thromboprophylaxis 2) Recognize the need to initiate thromboprophylaxis in multitrauma patients with low-risk traumatic brain injuries 3) Be familiar with the current literature in the choice of thromboprophylaxis agent 4) Recognize risk factors of TBI progression

    References: References 1. Kim L, Holena D, Schuster J, Sims C, 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(3):141–17. 2. Schaible E-V, Thal SC. Anticoagulation in patients with traumatic brain injury. Current Opinion in Anaesthesiology. 2013 Oct;26(5):529–34. 3. Saiki RL. Current and evolving management of traumatic brain injury. Critical Care Nursing Clinics of North America. 2009 Dec;21(4):549–59. 4. Spyropoulos AC, Hussein M, Lin J, Battleman D. Rates of venous thromboembolism occurrence in medical patients among the insured population. Thromb Haemost. 2009 Sept;102:951-57. 5. Ekeh AP, Dominguez KM, Markert RJ, McCarthy MC. Incidence and risk factors for deep venous thrombosis after moderate and severe brain injury. The Journal of Trauma: Injury, Infection, and Critical Care. 2010;68(4):912-15. 6. Norwood SH, Berne JD, Rowe SA, Villarreal DH, Ledlie JT. Early Venous Thromboembolism prophylaxis with enoxaparin in patients with blunt traumatic brain injury. The Journal of Trauma: Injury, Infection, and Critical Care. 2008 Nov;65(5):1021–27. 7. Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. New England Journal of Medidicne. 1994 Dec 15;331(24):1601–6. 8. Phelan HA. Pharmacologic venous thromboembolism prophylaxis after traumatic brain injury: A Critical Literature Review. Journal of Neurotrauma. 2012 Jul;29(10):1821–28. 9. Gross AK, Norman J, Cook AM. Contemporary pharmacologic issues in the management of traumatic brain injury. Journal of Pharmacy Practice. 2010 Oct 4;23(5):425–40. 10. Saadeh Y, Gohil K, Bill C, Smith C, Morrison C, Mosher B, Schneider P, Stevens P, Kepros JP. Chemical venous thromboembolic prophylaxis is safe and effective for patients with traumatic brain injury when started 24 hours after the absence of hemorrhage progression on head CT. Journal of Trauma and Acute Care Surgery. 2012 Aug;73(2):426–30. 11. Reiff DA, Haricharan RN, Bullington NM, Griffin RL, McGwin G Jr, Rue LW III. Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. The Journal of Trauma: Injury, Infection, and Critical Care. 2009 May;66(5):1436–40. 12. Foreman PM, Schmalz PGR, Griessenauer CJ. Chemoprophylaxis for venous thromboembolism in traumatic brain injury: A review and evidence-based protocol. Clinical Neurology and Neurosurgery. 2014 Aug;123:109–16. 13. Praeger AJ, Westbrook AJ, Nichol AD, Wijemunige R, Davies AR, Lyon SM, Wills JL, Bailey M, Rosenfeld JV, Cooper JD. Deep vein thrombosis and pulmonary embolus in patients with traumatic brain injury: a prospective observational study. Critical Care and Resuscitation 2012 Mar 14(1):10-13. 14. Cherry RA, Nichols PA, Snavely TM, David MT, Lynch FC. Prophylactic inferior vena cava filters: do they make a difference in trauma patients? The Journal of Trauma: Injury, Infection, and Critical Care. 2008 Sept;65(3):544–48. 15. Velmahos GC, Kern J, Chan LS, Oder D, Murray JA, Shekelle P. Prevention of venous thromboembolism after injury: an evidence-based report--part II: analysis of risk factors and evaluation of the role of vena caval filters. The Journal of Trauma: Injury, Infection, and Critical Care. 2000 Jul;49(1):140–44. 16. Lu D, Mahmood A, Goussev A, Schallert T, Qu C, Zhang ZG, Li Y, Lu M, Chopp M. Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury. Journal of Neurosurgery. 2004 Nov;101(5): 813-21. 17. Jamjoom AAB, Jamjoom AB. Safety and efficacy of early pharmacological thromboprophylaxis in traumatic brain injury: systematic review and meta-analysis. Journal of Neurotrauma. 2013 Apr;30(7):503–11. 18. Tang ME, Lobel DA. Severe traumatic brain injury: maximizing outcomes. Mt Sinai Journal of Medicine. 2009 Apr;76(2):119–28. 19. Levy AS, Salottolo K, Bar-Or R, Offner P, Mains C, Sullivan M, Bar-Or D. Pharmacologic thromboprophylaxis is a risk factor for hemorrhage progression in a subset of patients with traumatic brain injury. The Journal of Trauma: Injury, Infection, and Critical Care. 2010 Apr;68(4):886–94. 20. Haddad SH, Arabi YM. Critical care management of severe traumatic brain injury in adults. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2012 Feb;20(1):12. 21. Depew AJ, Hu J, Nguyen A, Driessen N. Thromboembolic prophylaxis is blunt traumatic intracranial hemorrhage: A retrospective review. The American Surgeon 2008 Oct; 74(10):906-11. 22. Rogers FB, Cipolle MD, Velmahos G, Rzycki G, Luchette FA. Practice Management Guidelines for the Prevention of Venous Thromboembolism in Trauma Patients: The EAST Practice Management Guidelines Work Group. The Journal of Trauma: Injury, Infection and Critical Care 2002;53(1):142-64. 23. Gould MK. Prevention of VTE in Nonorthopedic Surgical Patients. Chest. 2012 Feb: 41(supplement 2):e227S–51. 24. Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, et al. Deep Vein Thrombosis Prophylaxis. Journal of Neurotrauma. 2007 May;24(supplement 1):S–32–S–36. 25. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart L. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews. 2015;4(1):1-9. 26. Phillips B, Ball C, Sackett D, Badenoch D, Straus S. Phillips: Oxford centre for evidence-based medicine.2009 [cited 2015 Sept 24] Available from: 27. Algattas H, Huang J. Traumatic brain injury pathophysiology and treatments: early, intermediate, and late phases post-injury. International Journal of Molecular Sciences. 2014 Jan;15(1):309–41. 28. Cowley NJ, da Silva EJ. Prevention of secondary brain injury following Head Trauma. Trauma. 2008 Jan 1;10(1):35–42. 29. Carlile M, Nicewander D, Yablon SA, Brown A, Brunner R, Burke D, Chae E, Englander J, Flanagan S, Hamond F, et al. Prophylaxis for venous thromboembolism during rehabilitation for traumatic brain injury: a multicenter observational study. The Journal of Trauma: Injury, Infection, and Critical Care. 2009 Dec;1–8. 30. Elliott B, Patel P, Matharu MS, Amos R, Machin S, Liu C, Greenwood R. Prophylaxis of venous thromboembolism during early inpatient rehabilitation after acquired brain injury: How guidelines change management. Disability and Rehabilitation. 2006 Jan;28(5):333–37. 31. Grenander A, Bredbacka S, Rydvall A, Aroch R, Edner G, Koskinen OD, Olivecron M. Antithrombin treatment in patients with traumatic brain injury. Journal of Neurosurgical Anesthesiology. 2001;13(1):49-56. 32. Vergouwen MDI, Roos Y, Kamphusien PW. Venous thromboembolism prophylaxis and treatment in patients with acute stroke and traumatic brain injury. Current Opinion in Critical Care. 2008;14:149-55. 33. Schoonman GG, Bakker DP, Jellema K. Low risk of late intracranial complications in mild traumatic brain injury patients using oral anticoagulation after an initial normal brain computed tomography scan: education instead of hospitalization. European Journal of Neurology. 2014 Mar;21(7):1021–5. 34. Petruska DA. Prophylactic Anticoagulation in Patients with Traumatic Brain Injury. Journal of the American College of Surgeons Letters. 2011 Dec;213(6):809. 35. Phelan H. Venous Thromboembolism after Traumatic Brain Injury. Seminars in Thrombosis and Hemostasis. 2013 Jun;39(5):541–48. 36. Cullen N, Bayley M, Bayona N, Hilditch M, Aubut J. Management of heterotopic ossification and venous thromboembolism following acquired brain injury. Brain Injury. 2007 Jan;21(2):215–30. 37. Carlile MC, Yablon SA, Mysiw WJ, Frol AB, Lo D, Diaz-Arrastia R Deep venous thrombosis management following traumatic brain injury: a practice survey of the traumatic brain injury model systems. 2006;21(6):483-90. 38. Cothren CC, Smith WR, Moore EE, Morgan SJ. Utility of once-daily dose of low-molecular-weight heparin to prevent venous thromboembolism in multisystem trauma patients. World Journal of Surgery. 2006 Dec;31(1):98–104. 39. Kwiatt ME, Patel MS, Ross SE, Lachant MT, MacNew HG, Ochsner MG, Norwood SH, Speier L, Kozar R, Gerber J, et al. . Is low-molecular-weight heparin safe for venous thromboembolism prophylaxis in patients with traumatic brain injury? A Western Trauma Association multicenter study. Journal of Trauma and Acute Care Surgery. 2012 Sep;73(3):625–28. 40. Minshall CT, Eriksson EA, Leon SM, Doben AR, McKinzie BP, Fakhry SM. Safety and efficacy of heparin or enoxaparin prophylaxis in blunt trauma patients with a Head Abbreviated Injury Severity Score >2. The Journal of Trauma: Injury, Infection, and Critical Care. 2011 Aug;71(2):396–400. 41. Lin M, Davis JV, Wong DT. Evaluation of heparin prophylaxis protocol on deep venous thrombosis and pulmonary embolism in traumatic brain injury. The American Surgeon. 2013 Oct; 79(10):1050-53. 42. Agnelli G, Piovella F, Buoncristiani P, Severi P, Pini M, D'Angelo A, Beltrametti C, Damiani M, Andrioli GC, Pugliese R, et al. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. New England Journal of Medicine. 1998 Jul;339(2):80–85. 43. Nathens AB, McMurray MK, Cuschieri J, Durr EA, Moore EE, Bankey PE, Freeman B, Harbrecht BG, Johnson JL, Minei JP, et al. The practice of venous thromboembolism prophylaxis in the major trauma patient. The Journal of Trauma: Injury, Infection, and Critical Care. 2007 Mar;62(3):557–63. 44. Farooqui A, Hiser B, Barnes SL, Litofsky NS. Safety and efficacy of early thromboembolism chemoprophylaxis after intracranial hemorrhage from traumatic brain injury. Journal of Neurosurgery. 2013 Nov;119:1576-82. 45. Scudday T, Brasel K, Webb T, Codner P, Somberg L, Weigelt J, Herrmann D. Safety and efficacy of prophylactic anticoagulation in patients with traumatic brain injury. Journal of the American College of Surgeons. 2011 Jul;213(1):148–53. 46. Kleindienst A, Harvey HB, Mater E, Bronst J, Flack J, Herenz K, Haupt WF, Schon R. Early antithrombotic prophylaxis with low molecular weight heparin in neurosurgery. Acta Neurochirugica. 2003 Dec;145(12):1085–91 47. Koehler DM, Shipman J, Davidson MA, Guillamondegui O. Is Early venous thromboembolism prophylaxis safe in trauma patients with intracranial hemorrhage. The Journal of Trauma: Injury, Infection, and Critical Care. 2011 Feb;70(2):324–29. 48. Nickele CM, Kamps TK, Medow JE. Safety of a DVT Chemoprophylaxis Protocol Following Traumatic Brain Injury: A Single Center Quality Improvement Initiative. Neurocrit Care. 2012 Oct 26;18(2):184–92. 49. Phelan HA, Wolf SE, Norwood SH, Aldy K, Brakenridge SC, Eastman AL, Madden CJ, Nakonezny PA, Yang L, Chason DP et al. A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury. Journal of Trauma and Acute Care Surgery. 2012 Dec;73(6):1434–41. 50. Salottolo K, Offner P, Levy AS, Mains CW, Slone DS, Bar-Or D. Interrupted Pharmocologic Thromboprophylaxis Increases Venous Thromboembolism in Traumatic Brain Injury. The Journal of Trauma: Injury, Infection, and Critical Care. 2011 Jan;70(1):19–26. 51. Callcut RA, Hanseman DJ, Solan PD, Kadon KS, Ingalls NK, Fortuna GR, Tsuei BJ, Robinson BRH. Early treatment of blunt cerebrovascular injury with concomitant hemorrhagic neurologic injury is safe and effective. Journal of Trauma. 2011 Sept; 72(2):338-46. 52. Dudley RR, Aziz I, Bonnici A, Saluja RS, Lamoureux J, Kalmovitch B, Gursahaney A, Razek T, Maleki M, Marcoux J. Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits. Journal of Neurotrauma. 2010 Dec;27(12):2165–72. 53. Norwood SH, McAuley CE, Berne JD, Van L Vallina, Kerns DB, Grahm TW, Short K, McLarty JW. Prospective evaluation of the safety of enoxaparin prophylaxis for venous thromboembolism in patients with intracranial hemorrhagic injuries. Archives of Surgery. 2002 Jun;137(6):696–702. 54. Kurtoglu M, Yanar H, Bilsel Y, Guloglu R, Kizilirmak S, Buyukkurt D, Granit V. Venous thromboembolism prophylaxis after head and spinal trauma: Intermittent pneumatic compression devices versus low molecular weight heparin. World Journal of Surgery. 2004 Aug;28(8):807–11. 55. 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. The Journal of Trauma: Injury, Infection and Critical Care. 2002;53(1):38-43. 56. Kelly J, Rudd A, Lewis RR, Hunt BJ. Screening for subclinical deep-vein thrombosis. QJM An International Journal of Medicine. 2001;94:511-19.

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy