Venous thromboembolism in patients with isolated moderate to severe traumatic brain injury

Background. Traumatic brain injury (TBI) remains a big problem of modern neurosurgery, accompanied by high rates of disability and lethality. Venous thromboembolism (VTE) including venous thrombosis and pulmonary embolism (PE) plays a significant role in the structure of mortality in this pathology. Regimens and schemes of pharmacological prevention of VTE in TBI as well as corresponding preventative measures are not yet determined completely.

Aim. To identify the frequency of VTE in patients with isolated moderate and severe TBI, and to evaluate the results of prevention and treatment of these complications in patients of this category.

Materials and methods. Over a 3‑year period (from 2020 to 2023) 73 patients with isolated moderate and severe TBI (51 men and 22 women, mean age 61.0 ± 13.0 years) were treated in the V. M. Buyanov City Clinical Hospital. Of these, 31 patients received only conservative therapy, and 42 patients underwent surgery (craniotomy with hematoma removal, closed external hematoma drainage, and installation of intracranial pressure sensor). Ultrasound examination of the lower limb veins was performed at patient admission, then every 7 days until discharge from the hospital. Pharmacological prevention of VTE using low molecular weight heparin in non‑surgical patients was started after 1–2 days if computed tomography of the brain 24 h after admission showed no negative hematoma dynamics. Surgical patients were prescribed preventive medications 24 h after surgery if computed tomography confirmed intracranial hemostasis.

Results. Venous thrombosis was detected in 22 (30.1 %) of 73 patients. PE complicated the underlying disease in 1 (1.4 %) case and was non‑fatal. There was no fatal PE in the study group. An increase of the initial intracranial hematoma volume occurred in 3 (4.1 %) patients, in 2 (2.8 %) patients the recurrence of hemorrhage occurred before the beginning of heparin administration, and in 1 (1.4 %) case against the background of therapeutic doses of anticoagulants prescribed for venous thrombosis. In the majority of cases (82.0 %; 18 of 22 patients) thromboses were localized in deep veins of the lower leg and were asymptomatic. Intrahospital mortality was 23.3 % (17 patients), all lethal outcomes were due to the course of traumatic brain disease.

Conclusion. VTE is a frequent complication of TBI with intracranial hemorrhage. Regular ultrasound diagnostics makes it possible to diagnose asymptomatic distal venous thrombosis in a timely manner and to prescribe therapeutic doses of low molecular weight heparin in time which in turn allows to avoid fatal PE. Currently, there are no clear domestic recommendations for the prevention and, most importantly, for the treatment of these complications in patients with isolated moderate and severe TBI, which requires further active study of this problem.

1. Bervitskiy A.V., Guzhin V.E., Moisak G.I. et al. Thromboembolic complications in neurosurgery: solutions at the boundaries of possible and necessary (review). Neyrokhirurgiya = Russian Journal of Neurosurgery 2020;22(4):112–22. (In Russ.). DOI: 10.17650/1683-3295-2020-22-4-112-122

2. Meyer R.M., Larkin M.B., Szuflita N.S. et al. Early venous thromboembolism chemoprophylaxis in combat-related penetrating brain injury. J Neurosurg 2017;126(4):1047–55. DOI: 10.3171/2016.4.JNS1610

3. Ng I.C., Barnes C., Biswas S. et al. When is it safe to resume anticoagulation in traumatic brain injury? Curr Opin Anaesthesiol 2022;35(2):166–71. DOI: 10.1097/ACO.0000000000001117

4. Rivas L., Vella M., Ju T. et al. Early chemoprophylaxis against venous thromboembolism in patients with traumatic brain injury. Am Surg 2022;88(2):187–93. DOI: 10.1177/0003134820983171

5. Senko I.V., Krylov V.V., Dashyan V.G., Grigoriev I.V. Surgical treatment of distal cerebral aneurysms. Neyrokhirurgiya = Russian Journal of Neurosurgery 2022;24(3):12–22. (In Russ.). DOI: 10.17650/1683-3295-2022-24-3-12-22

6. Khripun A.I., Pryamikov A.D., Mironkov A.B. et al. Venous thromboembolic complications in patients with intracerebral hemorrhage. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova = S.S. Korsakov’s Journal of Neurology and Psychiatry 2021;121(8–2): 41–6. (In Russ.). DOI: 10.17116/jnevro202112108241

7. Khaldi A., Helo N., Schneck M.J., Origitano T.C. Venous thromboembolism: deep venous thrombosis and pulmonary embolism in a neurosurgical population. J Neurosurg 2011;114(1):40–6. DOI: 10.3171/2010.8.JNS10332

8. Meskhiya N.Sh. Experience of surgical treatment of patients with severe traumatic brain injury. Neyrokhirurgiya = Russian Journal of Neurosurgery 2022;24(1):45–54. (In Russ.). DOI: 10.17650/1683-3295-2022-24-1-45-54

9. Byrne J.P., Witiw C.D., Schuster J.M. et al. Association of venous thromboembolism prophylaxis after neurosurgical intervention for traumatic brain injury with thromboembolic complications, repeated neurosurgery, and mortality. JAMA Surg 2022;157(3):e215794. DOI: 10.1001/jamasurg.2021.5794

10. Hubbard W.B., Dong J.-F., Cruz M.A., Rumbaut R.E. Links between thrombosis and inflammation in traumatic brain injury. Thromb Res 2021;198:62–71. DOI: 10.1016/j.thromres.2020.10.041

11. Taylor A., Martinez-Quinones P., Huang E. et al. Effective use of weight-based enoxaparin for deep vein thrombosis chemoprophylaxis in patients with traumatic brain injury. Am J Surg 2022;223(1):146–50. DOI: 10.1016/j.amjsurg.2021.07.030

12. Hachem L.D., Mansouri A., Scales D.C. et al. Anticoagulant prophylaxis against venous thromboembolism following severe traumatic brain injury: a prospective observational study and systematic review of the literature. Clin Neurol Neurosurg 2018;175:68–73. DOI: 10.1016/j.clineuro.2018.09.032

13. Seifi A., Dengler B., Martinez P., Godoy D.A. Pulmonary embolism in severe traumatic brain injury. J Clin Neurosci 2018;57:46–50. DOI: 10.1016/j.jocn.2018.08.042

14. Silva V.T., Iglesio R., Paiva W.S. et al. Deep vein thrombosis prophylaxis in patients with traumatic brain injury. Acta Med Port 2015;28(2):250–5. DOI: 10.20344/amp.5470

15. Scudday T., Brasel K., Webb T. et al. Safety and efficacy of prophylactic anticoagulation in patients with traumatic brain injury. J Am Coll Surg 2011;213(1):148–53; discussion 153–4. DOI: 10.1016/j.jamcollsurg.2011.02.027

16. Al-Mufti F., Mayer S.A. Neurocritical care of acute subdural hemorrhage. Neurosurg Clin N Am 2017;28(2):267–8. DOI: 10.1016/j.nec.2016.11.009

17. Foreman P.M., Schmalz P.G., Griessenauer C.J. Chemoprophylaxis for venous thromboembolism in traumatic brain injury: a review and evidence-based protocol. Clin Neurol Neurosurg 2014;123:109–16. DOI: 10.1016/j.clineuro.2014.05.017

18. Mesa Galan L.A., Egea-Guerrero J.J., Quintana Diaz M., VilchesArenas A. The effectiveness and safety of pharmacological prophylaxis against venous thromboembolism in patients with moderate to severe traumatic brain injury: а systematic review and meta-analysis. J Trauma Acute Care Surg 2016;81(3):567–74. DOI: 10.1097/TA.0000000000001134

19. Bervitskiy A.V., Guzhin V.E., Moisak G.I. et al. Results of early administration of low molecular weight heparin for prevention of venous thromboembolism after removal of brain tumors. Neyrokhirurgiya = Russian Journal of Neurosurgery 2021;23(3): 30–8. (In Russ.). DOI: 10.17650/1683-3295-2021-23-3-30-38

20. Khripun A.I., Pryamikov A.D., Mironkov A.B. et al. Venous thromboembolic complications in patients with subarachnoid hemorrhage following cerebral aneurysm rupture. Flebologiya = Phlebology 2022;16(4):289–95. (In Russ.). DOI: 10.17116/flebo202216041289

21. Du M., Zhang Q.H., Tang R. et al. Prognostic significance of plasma insulin level for deep venous thrombosis in patients with severe traumatic brain injury in critical care. Neurocrit Care 2023;38(2):263–78. DOI: 10.1007/s12028-022-01588-y

22. Huijben J.A., Pisica D., Ceyisakar I. et al. Pharmaceutical venous thrombosis prophylaxis in critically ill traumatic brain injury patients. Neurotrauma Rep 2022;2(1):4–14. DOI: 10.1089/neur.2021.0037

23. Yang T., Wei G., Zhu C., Pan A. [Incidence and risk factor analysis of deep venous thrombosis in patients with severe traumatic brain injury (In Chines)]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019;31(2):182–6. DOI: 10.3760/cma.j.issn.2095-4352.2019.02.012

24. Abdel-Aziz H., Dunham C.M., Malik R.J., Hileman B.M. Timing for deep vein thrombosis chemoprophylaxis in traumatic brain injury: an evidence-based review. Crit Care 2015;19(1):96. DOI: 10.1186/s13054-015-0814-z

25. Minshall C.T., Eriksson E.A., Leon S.M. et al. Safety and efficacy of heparin or enoxaparin prophylaxis in blunt trauma patients with a head abbreviated injury severity score >2. J Trauma 2011;71(2):396–9; discussion 399–400. DOI: 10.1097/TA.0b013e31822734c9

26. Byrne J.P., Mason S.A., 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(4):621–31. DOI: 10.1016/j.jamcollsurg.2016.06.382

27. Jamous M.A. The Safety of early thromboembolic prophylaxis in closed traumatic intracranial hemorrhage. Open Access Emerg Med 2020;14(12):81–5. DOI: 10.2147/OAEM.S239881

28. Benjamin E., Recinos G., Aiolfi A. et al. Pharmacological thromboembolic prophylaxis in traumatic brain injuries: low molecular weight heparin is superior to unfractionated heparin. Ann Surg 2017;266(3):463–9. DOI: 10.1097/SLA.0000000000002359

29. Dudley R.R., Aziz I., Bonnici A. et al. Early venous thromboembolic event prophylaxis in traumatic brain injury with low-molecular-weight heparin: risks and benefits. J Neurotrauma 2010;27(12):2165–72. DOI: 10.1089/neu.2010.1366

30. Skrifvars M.B., Bailey M., Presneill J. et al. Venous thromboembolic events in critically ill traumatic brain injury patients. Intensive Care Med 2017;43(3):419–28. DOI: 10.1007/s00134-016-4655-2

31. Moore M., Goldin Y., Patel H., Greenwald B.D. Low vitamin D level is associated with acute deep venous thrombosis in patients with traumatic brain injury. Brain Sci 2021;11(7):849. DOI: 10.3390/brainsci11070849