Published Online
on November 22, 2006

A more recent version of this article appeared on January 1, 2007

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Submitted on April 10, 2006
Revised on August 9, 2006
Accepted on August 22, 2006

Asymptomatic Hemorrhage After Thrombolysis May Not Be Benign. Prognosis by Hemorrhage Type in the Canadian Alteplase for Stroke Effectiveness Study Registry

Imanuel Dzialowski MD^*; J. H. Warwick Pexman MD, FRCR; Philip A. Barber MB, ChB, FRCPC; Andrew M. Demchuk MD, FRCPC; Alastair M. Buchan MB, FRCP(UK); Michael D. Hill MD, MSc, FRCPC; on behalf of the CASES Investigators

From the Departments of Clinical Neurosciences (I.D., J.H.W.P., P.A.B., A.M.D., M.D.H.), Calgary Stroke Program, and the Department of Medicine (M.D.H.), Department of Community Health Science, University of Calgary, Calgary, Canada; the Department of Gerontology (A.M.B.), University of Oxford, Oxford, England; and the Department of Neurology (I.D.), University of Dresden, Dresden, Germany.

^* To whom correspondence should be addressed. E-mail: imanuel.Dzialowski{at}neuro.med.tu-dresden.de.

Background and Purpose--There is ongoing controversy about the impact of hemorrhagic transformation after thrombolysis on long-term functional outcome. We sought to study the relation between the type of hemorrhagic transformation on CT scans and functional outcome.

Methods--Data were obtained from the Canadian Alteplase for Stroke Effectiveness Study. This study was established as a registry to prospectively collect data for acute stroke patients receiving intravenous alteplase within 3 hours from stroke onset between February 1999 and June 2001. Follow-up was completed at 90 days, and good functional outcome was defined as a modified Rankin Scale score of 0 or 1. Copies of head CT scans obtained at 24 to 48 hours after starting treatment were read in consensus by a central reading panel consisting of 1 neuroradiologist and 1 stroke neurologist. According to European Cooperative Acute Stroke Study criteria, hemorrhagic transformation was classified as none, hemorrhagic infarction (HI-1 and HI-2), or parenchymal hematoma (PH-1 and PH-2). We compared outcome across groups and performed a multivariable analysis including previously determined important predictors of good outcome in acute ischemic stroke.

Results--From 1135 patients enrolled at 60 centers across Canada, 954 follow-up CT scans were assessable. We observed some hemorrhagic transformation in 259 of 954 (27.1%) patients (110 HI-1, 57 HI-2, 48 PH-1, and 44 PH-2). Proportions of patients with good outcome were 41% with no hemorrhagic transformation, 30% with HI-1, 17% with HI-2, 15% with PH-1, and 7% with PH-2 (P<0.0001, ² test). After adjustment for age, baseline serum glucose, baseline Alberta Stroke Program Early CT score, and baseline National Institutes of Health Stroke Scale score, HI-1 was not a predictor of outcome. However, HI-2 (odds ratio=0.38, 95% CI=0.17 to 0.83), PH-1 (odds ratio=0.32, 95% CI=0.12 to 0.80), and PH-2 (odds ratio=0.14, 95% CI=0.04 to 0.48) were all negative predictors of outcome.

Conclusions--The likelihood of a poor outcome after thrombolysis was proportional to the extent of hemorrhage on CT scans. HI grades of hemorrhagic transformation may not be benign.

Key words: acute stroke • intracranial hemorrhage • thrombolysis • thrombolytic treatment

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