Evaluation of a protocol for early detection of delayed brain hemorrhage in head injured patients on warfarin

  • Jing Li Huang
  • Theo A. Woehrle
  • Pat Conway
  • Catherine A. McCarty
  • Madeline M. Eyer
  • Steven D. Eyer
Original Article



In 2007, Essentia Health St. Mary’s Medical Center (SMMC), a Level II trauma center in northeastern Minnesota, implemented a protocol for patients who presented with blunt head trauma and were receiving warfarin for anticoagulation. The purpose of this study was to determine the incidence and risk factors of early delayed, warfarin-associated intracranial hemorrhage (ICH).


Adult patients with signs and symptoms of head injury on warfarin who were admitted by protocol to SMMC between March 2007 and June 2015 were included. Patients were observed for neurologic change and received a follow-up head CT scan within 24 h after an initial negative scan.


Among the 232 episodes of care studied, there were 204 patients. The average age was 71; 51% of patients were female. Most patients presented with Glasgow Coma Scale score of 15 and had signs of head trauma. The majority of patients (63%) had a therapeutic International Normalized Ratio (INR) for their indicated condition, but 19% of patients had a supratherapeutic INR and 19% had a subtherapeutic INR. The incidence of early delayed ICH was 1.7%; none of these cases required operative intervention or were fatal.


For patients who were anticoagulated with warfarin and had sustained minor traumatic brain injury, implementation of our protocol showed low incidence of early delayed ICH in the first 24 h. We believe withholding warfarin for several days and careful follow-up regarding its resumption is warranted, especially in the setting of supratherapeutic INR.


Traumatic brain injury Warfarin Delayed hemorrhage 



The project was funded in part by a Grant from Essentia Health Duluth Clinic Foundation.

Author contributions

JLH assisted with data collection, data analysis, and manuscript preparation. TAW assisted with literature search and manuscript preparation. PC assisted with the data analysis, interpretation, and manuscript preparation. CAM acquired funding, supervised staff, and assisted with manuscript preparation. MME assisted with data collection. SDE conceived the study, assisted with data collection and interpretation, and manuscript preparation. All authors reviewed and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

No conflicts of interests to declare: this research was funded in part by a Grant from Essentia Health Duluth Clinic Foundation.


  1. 1.
    Faul M, Xu L, Wald MM, Coronado V, Dellinger AM. Traumatic brain injury in the United States: national estimates of prevalence and incidence, 2002–2006. Injury Prevent. 2010;16(Suppl 1):A268.CrossRefGoogle Scholar
  2. 2.
    Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008;7(8):728–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Marin JR, Weaver MD, Yealy DM, Mannix RC. Trends in visits for traumatic brain injury to emergency departments in the United States. JAMA. 2014;311(18):1917–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet. 2001;357(9258):771–2.CrossRefPubMedGoogle Scholar
  5. 5.
    Cohen DB, Rinker C, Wilberger JE. Traumatic brain injury in anticoagulated patients. J Trauma Acute Care Surg. 2006;60(3):553–7.CrossRefGoogle Scholar
  6. 6.
    Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality. J Trauma Acute Care Surg. 2005;59(5):1131–9.CrossRefGoogle Scholar
  7. 7.
    Mueller RL, Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89(1):432–49.CrossRefPubMedGoogle Scholar
  8. 8.
    Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest J. 2004;126(3_suppl):204S–33S.CrossRefGoogle Scholar
  9. 9.
    Shlevin EL, Lederer M. Uncontrollable hemorrhage after dicoumarol therapy with autopsy findings. Ann Intern Med. 1944;21(2):332–42.CrossRefGoogle Scholar
  10. 10.
    Stein SC, Young GS, Talucci RC, Greenbaum BH, Ross SE. Delayed brain injury after head trauma: significance of coagulopathy. Neurosurgery. 1992;30(2):160–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Itshayek E, Rosenthal G, Fraifeld S, Perez-Sanchez X, Cohen JE, Spektor S. Delayed posttraumatic acute subdural hematoma in elderly patients on anticoagulation. Neurosurgery. 2006;58(5):E851–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Menditto VG, Lucci M, Polonara S, Pomponio G, Gabrielli A. Management of minor head injury in patients receiving oral anticoagulant therapy: a prospective study of a 24-h observation protocol. Ann Emerg Med. 2012;59(6):451–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Peck KA, Sise CB, Shackford SR, Sise MJ, Calvo RY, Sack DI, Walker SB, Schechter MS. Delayed intracranial hemorrhage after blunt trauma: are patients on preinjury anticoagulants and prescription antiplatelet agents at risk? J Trauma Acute Care Surg. 2011;71(6):1600–4.CrossRefGoogle Scholar
  14. 14.
    Kaen A, Jimenez-Roldan L, Arrese I, Delgado MA, Lopez PG, Alday R, Alen JF, Lagares A, Lobato RD. The value of sequential computed tomography scanning in anticoagulated patients suffering from minor head injury. J Trauma Acute Care Surg. 2010;68(4):895–8.Google Scholar
  15. 15.
    Scantling D, Fischer C, Gruner R, Teichman A, McCracken B, Eakins J. The role of delayed head CT in evaluation of elderly blunt head trauma victims taking antithrombotic therapy. Eur J Trauma Emerg Surg. 2017;24:1–6.Google Scholar
  16. 16.
    Nishijima DK, Offerman SR, Ballard DW, Vinson DR, Chettipally UK, Rauchwerger AS, Reed ME, Holmes JF. Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury warfarin or clopidogrel use. Ann Emerg Med. 2012;59(6):460–8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    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. Eur J Neurol. 2014;21(7):1021–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Tomei G, Brambilla GL, Delfini R, Servadei F, Ambrosio A, Acampora S, Arienta C, Arista A, Armenise B, Montinaro A, Benericetti E. Guidelines for minor head injured patients’ management in adult age. J Neurosurg Sci. 1996;40(1):11–15.Google Scholar
  19. 19.
    Vos PE, Alekseenko Y, Battistin L, Ehler E, Gerstenbrand F, Muresanu DF, Potapov A, Stepan CA, Traubner P, Vécsei L, Von Wild K. Mild traumatic brain injury. Eur J Neurol. 2012;19(2):191–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Hodgkinson S, Pollit V, Sharpin C. Early management of head injury: summary of updated NICE guidance. BMJ. 2014; 348:g104.
  21. 21.
    New South Wales Institute of Trauma and Injury Management. Adult trauma clinical practice guidelines: initial management of closed head injury in adults. CPG 2nd editor. Revised November 2011. Accessed Nov 18 2016.
  22. 22.
    Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864–70.CrossRefPubMedGoogle Scholar
  23. 23.
    Kujovich JL. Factor v Leiden thrombophilia. Genet Med. 2011;13(1):1–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994;89(2):635–41.CrossRefPubMedGoogle Scholar
  25. 25.
    Cannegieter SC, Rosendaal FR, Wintzen AR, Van der Meer FJ, Vandenbroucke JP, Briet E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med. 1995;333(1):11–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Horton JD, Bushwick BM. Warfarin therapy: evolving strategies in anticoagulation. Am Fam Physician. 1999;59(3):635–46.PubMedGoogle Scholar
  27. 27.
    Nielsen PB, Larsen TB, Gorst-Rasmussen A, Skjoth F, Rasmussen LH, Lip GY. Intracranial hemorrhage and subsequent ischemic stroke in patients with atrial fibrillation. A national cohort study. Chest. 2015; 147(6):1651–8.CrossRefGoogle Scholar
  28. 28.
    Albrecht JS, Liu X, Baumgarten M, Langenberg P, Rattinger GB, Smith GS, Gambert SR, Gottlieb SS, Zuckerman IH. Benefits and risks of anticoagulation resumption following traumatic brain injury. JAMA Internal Med. 2014;174(8):1244–51.CrossRefGoogle Scholar
  29. 29.
    Kuramatsu JB, Gerner ST, Schellinger PD, Glahn J, Endres M, Sobesky J, Flechsenhar J, Neugebauer H, Jüttler E, Grau A, Palm F. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA. 2015;313(8):824–36.CrossRefPubMedGoogle Scholar
  30. 30.
    Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.CrossRefPubMedGoogle Scholar
  31. 31.
    Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;(361):1139–51.CrossRefPubMedGoogle Scholar
  32. 32.
    Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefPubMedGoogle Scholar
  33. 33.
    Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jing Li Huang
    • 1
  • Theo A. Woehrle
    • 2
  • Pat Conway
    • 2
  • Catherine A. McCarty
    • 2
    • 3
  • Madeline M. Eyer
    • 2
  • Steven D. Eyer
    • 4
  1. 1.University of MinnesotaMinneapolisUSA
  2. 2.Essentia Institute of Rural HealthDuluthUSA
  3. 3.University of Minnesota School of MedicineDuluthUSA
  4. 4.Essentia Health St. Mary’s Medical CenterDuluthUSA

Personalised recommendations