Skip to main content

Advertisement

SpringerLink
Log in

Warfarin and Statins are Associated with Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background and purpose

Despite extensive studies of supratentorial intracerebral hemorrhage (ICH), limited data are available on determinants of hematoma volume in infratentorial ICH. We therefore aimed to identify predictors of infratentorial ICH volume and to evaluate whether location specificity exists when comparing cerebellar to brainstem ICH.

Methods

We undertook a retrospective analysis of 139 consecutive infratentorial ICH cases (95 cerebellar and 44 brainstem ICH) prospectively enrolled in a single-center study of ICH. ICH volume was measured on the CT scan obtained upon presentation to the Emergency Department using an established computer-assisted method. We used linear regression to identify determinants of log-transformed ICH volume and logistic regression to evaluate their role in surgical evacuation.

Results

Median ICH volumes for all infratentorial, cerebellar, and brainstem ICH were nine [interquartile range (IQR), 3–23], ten (IQR, 3–25), and eight (IQR, 3–19) milliliters, respectively. Thirty-six patients were on warfarin treatment, 31 underwent surgical evacuation, and 65 died within 90 days. Warfarin was associated with an increase in ICH volume of 86 % [β = 0.86, standard error (SE) = 0.29, p = 0.003] and statin treatment with a decrease of 69 % (β = −69, SE = 0.26, p = 0.008). Among cerebellar ICH subjects, those on warfarin were five times more likely to undergo surgical evacuation (OR = 4.80, 95 % confidence interval 1.63–14.16, p = 0.005).

Conclusions

Warfarin exposure increases ICH volume in infratentorial ICH. Further studies will be necessary to confirm the inverse relation observed between statins and ICH volume.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993;24:987–93.

    Article  PubMed  CAS  Google Scholar 

  2. Dahdaleh NS, Dlouhy BJ, Viljoen SV, et al. Clinical and radiographic predictors of neurological outcome following posterior fossa decompression for spontaneous cerebellar hemorrhage. J Clin Neurosci. 2012;19:1236–41.

    Article  PubMed  Google Scholar 

  3. Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology. 2008;71:1084–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Ricard G, Garant M-P, Carrier N, Leblanc N, Boulanger J-M. Statins may increase intracerebral hemorrhage volume. Can J Neurol Sci. 2010;37:791–6.

    PubMed  Google Scholar 

  5. Lou M, Al-Hazzani A, Goddeau RP Jr, Novak V, Selim M. Relationship between white-matter hyperintensities and hematoma volume and growth in patients with intracerebral hemorrhage. Stroke. 2010;41:34–40.

    Article  PubMed  Google Scholar 

  6. Lee S-H, Kim BJ, Roh J-K. Silent microbleeds are associated with volume of primary intracerebral hemorrhage. Neurology. 2006;66:430–2.

    Article  PubMed  Google Scholar 

  7. Biffi A, Sonni A, Anderson CD, et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol. 2010;68:934–43.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Heros RC. Cerebellar hemorrhage and infarction. Stroke. 1982;13:106–9.

    Article  PubMed  CAS  Google Scholar 

  9. Firsching R, Huber M, Frowein RA. Cerebellar haemorrhage: management and prognosis. Neurosurg Rev. 1991;14:191–4.

    Article  PubMed  CAS  Google Scholar 

  10. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007;38:2001–23.

    Article  PubMed  Google Scholar 

  11. Biffi A, Battey TW, Ayres AM, et al. Warfarin-related intraventricular hemorrhage imaging and outcome. Neurology. 2011;77:1840–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Wojcik NC, Huebner WW, Jorgensen G. Strategies for using the National Death Index and the Social Security Administration for death ascertainment in large occupational cohort mortality studies. Am J Epidemiol. 2010;172:469–77.

    Article  PubMed  Google Scholar 

  13. Goldstein JN, Fazen LE, Snider R, et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology. 2007;68:889–94.

    Article  PubMed  CAS  Google Scholar 

  14. Rosand J, Hylek EM, O’Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology. 2000;55:947–51.

    Article  PubMed  CAS  Google Scholar 

  15. Takeuchi S, Suzuki G, Takasato Y, et al. Prognostic factors in patients with primary brainstem hemorrhage. Clin Neurol Neurosurg. 2012. http://www.sciencedirect.com/science/article/pii/S0303846712004477. Accessed 7 Nov 2012.

  16. Matsukawa H, Shinoda M, Fujii M, et al. Relationships among hematoma diameter, location categorized by vascular territory, and 1-year outcome in patients with cerebellar hemorrhage. World Neurosurg. 2012;77:507–11.

    Article  PubMed  Google Scholar 

  17. Biffi A, Devan WJ, Anderson CD, et al. Statin use and outcome after intracerebral hemorrhage: case-control study and meta-analysis. Neurology. 2011;76:1581–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage a meta-analysis of 31 randomized controlled trials. Stroke. 2012;43:2149–56.

    Article  PubMed  CAS  Google Scholar 

  19. Fisher CM. Pathological observations in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol. 1971;30:536–50.

    Article  PubMed  CAS  Google Scholar 

  20. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009;8:453–63.

    Article  PubMed  CAS  Google Scholar 

  21. Serebruany VL, Malinin AI, Hennekens CH. Statins increase risk of hemorrhagic stroke by inhibition of the PAR-1 receptor. Cerebrovasc Dis. 2007;24:477–9.

    Article  PubMed  Google Scholar 

  22. Björkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004;24:806–15.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

All funding entities had no involvement in study design, data collection, analysis, interpretation, writing of the manuscript, and in the decision to submit for publication. The project described was supported by the National Institutes of Health—the National Institute of Neurological Disorders and Stroke (Grant Numbers R01NS073344, R01NS059727, 5K23NS059774) and the American Heart Association (Grant Number 0755984T). Dr. Brouwers was supported by the NIH-NINDS SPOTRIAS fellowship Grant P50NS061343. Dr. Anderson was supported by the American Brain Foundation.

Conflict of interest

The following authors “Guido J. Falcone, H. Bart Brouwers, Alessandro Biffi, Thomas W.K. Battey, Alison M. Ayres, Anastasia Vashkevich, Kristin M. Schwab, Natalia S. Rost, Anand Viswanathan” have stated that they have no conflict of interest.

Christopher D. Anderson: research Grant from the American Brain Foundation. Joshua N. Goldstein: research Grant NIH—NINDS, Consultant/advisory board CSL Behring. Steven M. Greenberg: research Grant NIH; Honoraria—Medtronic, Pfizer; Consultant/advisory board—Hoffman-La Roche, Janssen Alzheimer Immunotherapy, Bristol-Myers Squibb Company. Jonathan Rosand: research Grant NIH and American Heart Association.

Author information

Authors and Affiliations

  1. Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, CPZN-6818, Boston, MA, 02114, USA

    Guido J. Falcone, H. Bart Brouwers, Alessandro Biffi, Christopher D. Anderson, Thomas W. K. Battey, Natalia S. Rost & Jonathan Rosand

  2. Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Boston, MA, USA

    Guido J. Falcone, H. Bart Brouwers, Alessandro Biffi, Christopher D. Anderson, Thomas W. K. Battey, Alison M. Ayres, Anastasia Vashkevich, Kristin M. Schwab, Natalia S. Rost, Anand Viswanathan, Steven M. Greenberg & Jonathan Rosand

  3. Division of Neurocritical Care and Emergency Neurology Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Guido J. Falcone, H. Bart Brouwers, Alessandro Biffi, Christopher D. Anderson, Thomas W. K. Battey, Natalia S. Rost & Jonathan Rosand

  4. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA

    Guido J. Falcone, H. Bart Brouwers, Alessandro Biffi, Christopher D. Anderson, Thomas W. K. Battey, Natalia S. Rost & Jonathan Rosand

  5. Department of Epidemiology, Harvard School of Public Health, Boston, USA

    Guido J. Falcone

  6. Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA

    Joshua N. Goldstein

Authors
  1. Guido J. Falcone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Bart Brouwers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandro Biffi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher D. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas W. K. Battey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alison M. Ayres
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anastasia Vashkevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kristin M. Schwab
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Natalia S. Rost
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Joshua N. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Anand Viswanathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Steven M. Greenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jonathan Rosand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Rosand.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Falcone, G.J., Brouwers, H.B., Biffi, A. et al. Warfarin and Statins are Associated with Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage. Neurocrit Care 21, 192–199 (2014). https://doi.org/10.1007/s12028-013-9839-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-013-9839-9

Keywords

Search

Navigation