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Warfarin use leads to larger intracerebral hematomas

From the Departments of Neurology (M.L.F., M.H., D.K., B.K., P.K., C.J.M., J.P.B., D.W.), Emergency Medicine (B.S., O.A.), and Environmental Health (P.S.), University of Cincinnati Academic Health Center; and University of Cincinnati College of Medicine (H.T.), OH.

Address correspondence and reprint requests to Dr. Matthew L. Flaherty, Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson St., Room 2316, PO Box 670525, Cincinnati, OH 45267-0525 matthew.flaherty{at}uc.edu

Background: Among patients with intracerebral hemorrhage (ICH), warfarin use before onset leads to greater mortality. In a retrospective study, we sought to determine whether warfarin use is associated with larger initial hematoma volume, one determinant of mortality after ICH.

Methods: We identified all patients hospitalized with ICH in the Greater Cincinnati region from January through December 2005. ICH volumes were measured on the first available brain scan by using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine whether international normalized ratio (INR) influenced initial ICH volume after adjusting for other factors, including age, race, sex, antiplatelet use, hemorrhage location, and time from stroke onset to scan.

Results: There were 258 patients with ICH, including 51 patients taking warfarin. In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category (INR <1.2, 13.4 mL; INR 1.2–2.0, 9.3 mL; INR 2.1–3.0, 14.0 mL; INR >3.0, 33.2 mL; p = 0.10). In the model, compared with patients with INR <1.2, there was no difference in hematoma size for patients with INR 1.2–2.0 (p = 0.25) or INR 2.1–3.0 (p = 0.36), but patients with INR >3.0 had greater hematoma volume (p = 0.02). Other predictors of larger hematoma size were ICH location (lobar compared with deep cerebral, p = 0.02) and shorter time from stroke onset to scan (p < 0.001).

Conclusion: Warfarin use was associated with larger initial intracerebral hemorrhage (ICH) volume, but this effect was only observed for INR values >3.0. Larger ICH volume among warfarin users likely accounts for part of the excess mortality in this group.

GLOSSARY: AAICH = anticoagulant-associated intracerebral hemorrhage; GERFHS = Genetic and Environmental Risk Factors for Hemorrhagic Stroke; HR = hazard ratio; ICH = intracerebral hemorrhage; INR = international normalized ratio; IVH = intraventricular hemorrhage.

Supported in part by the National Institute of Neurological Disorder and Stroke (R-01-NS 36695) and a University of Cincinnati College of Medicine Medical Student Summer Research Fellowship.

Disclosure: M.L.F. has received compensation for activities with Novo Nordisk and provided a grand rounds presentation sponsored by an unrestricted educational grant from PhotoThera, Inc. J.P.B. has received compensation for activities with Ono Pharmaceuticals, Novo Nordisk, and Boehringer-Ingelheim. He was a member of the steering committee for trials of activated recombinant factor VII for treatment of acute intracerebral hemorrhage. He has received financial support/grant support from EKOS Corporation, AstraZeneca, and Genentech. B.K. has received honoraria from Boehringer-Ingelheim and Sanofi-Bristol Myers Squibb. D.K. has received honoraria from Boehringer-Ingelheim. The remaining authors have no disclosures.

Received May 13, 2007. Accepted in final form May 23, 2008.

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