Circulation. 2002;105:1679-1685
doi: 10.1161/01.CIR.0000012747.53592.6A
doi: 10.1161/01.CIR.0000012747.53592.6A
(Circulation. 2002;105:1679.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Markers of Increased Risk of Intracerebral Hemorrhage After Intravenous Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke in Clinical Practice
The Multicenter rt-PA Acute Stroke Survey
From the Stroke Unit, Department of Neurology, Chaim Sheba Medical Center, Tel Hashomer, Israel (D.T.); Comprehensive Stroke Center, University of Pennsylvania Medical Center, Philadelphia, Pa (S.E.K.); Foothills Hospital, Department of Clinical Neurosciences, Calgary, Canada (A.M.D.); Division of Epidemiology and Preventive Medicine, Sackler School of Medicine, Tel-Aviv, Israel (N.K-M.); Park Nicollet Neuroscience, St Louis Park, Minn (S.H.); Klinik für Neurologie der Universität zu Köln, Cologne, Germany (M.G.); and Mount Sinai School of Medicine, New York, NY (S.R.L).
Correspondence to David Tanne, MD, Stroke Unit, Department of Neurology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail tanne{at}post.tau.ac.il
Background— Intravenous recombinant tissue plasminogen activator (rtPA) is an effective therapy for acute ischemic stroke, but it is associated with risk of intracerebral hemorrhage (ICH). Our aim was to identify, in a large cohort of patients, readily available baseline factors that are associated with thrombolysis-related ICH.
Methods and Results— In a multicenter retrospective and prospective investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset, 72 patients (6%) developed symptomatic ICH and 86 additional patients (7%) had asymptomatic ICH identified on a routine follow-up CT. In analyses based on clinical variables alone, the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease, increasing stroke severity, advancing age, use of antiplatelet agents other than aspirin before stroke onset, and elevated pretreatment mean blood pressure. In additional analyses that incorporated baseline CT and laboratory findings (in a subset of patients), the main associations were early ischemic CT changes, in particular if exceeding one third of middle cerebral artery territory; increasing stroke severity; diabetes mellitus or elevated serum glucose; and lower platelet counts. Final independent attributes associated with parenchymatous hematoma, defined by purely radiologically based criteria, were similar to those of symptomatic ICH.
Conclusions— Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation.
Key Words: hemorrhage • plasminogen activators • stroke
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|
|
|
|
|
|
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|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
D. Tanne and Y. Schwammenthal Editorial Comment--Hyperglycemia and Early Reperfusion Therapy Stroke, May 1, 2003; 34(5): 1240 - 1241. [Full Text] [PDF]
|
|
|
|
|
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R. von Kummer Early Major Ischemic Changes on Computed Tomography Should Preclude Use of Tissue Plasminogen Activator Stroke, March 1, 2003; 34(3): 820 - 821. [Full Text] [PDF]
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