Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke

Background and ObjectivesPrior ischemic stroke is a risk factor for intracerebral hemorrhage (ICH) in patients taking warfarin, but the mechanism is not known. This study investigates radiographic and clinical characteristics of patients with warfarin-related ICH following ischemic stroke. Methods In this case-control study, the authors selected all patients with warfarin-related ICH and previous symptomatic ischemic stroke from a prospective cohort of consecutive patients with ICH. Control subjects were similarly aged patients with history of symptomatic stroke randomly chosen from an anticoagulant therapy unit. The 26 eligible ICH cases and 56 controls were compared for vascular risk factors, stroke characteristics, and extent of leukoaraiosis (graded in anterior and posterior brain regions on a validated scale of 0 to 4). Results The presence and severity of leukoaraiosis on CT scan correlated strongly with the occurrence of ICH. Leukoaraiosis was seen in 24 of 26 cases (92%) compared with 27 of 56 controls (48%), yielding an odds ratio of 12.9 (95% CI 2.8 to 59.8). Other clinical factors associated with ICH included an international normalized ratio >3.0, history of multiple previous strokes, and the presence of carotid artery stenosis. The relationship between leukoaraiosis and ICH persisted in multivariable analyses controlling for these risk factors as well as hypertension and diabetes mellitus. Conclusions Leukoaraiosis is an independent risk factor for warfarin-related ICH in survivors of ischemic stroke, including those in the commonly employed range of anticoagulation.

[1]  J. Halperin,et al.  Atrial fibrillation and stroke : concepts and controversies. , 2001, Stroke.

[2]  S. Greenberg,et al.  Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston Criteria , 2003, Current atherosclerosis reports.

[3]  J. Hirsh,et al.  Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. , 2001, Chest.

[4]  S. Greenberg,et al.  Warfarin-associated hemorrhage and cerebral amyloid angiopathy , 2000, Neurology.

[5]  J. Webster,et al.  Analysis of risk factors involved in oral-anticoagulant-related intracranial haemorrhages. , 2000, QJM : monthly journal of the Association of Physicians.

[6]  K. Furie,et al.  Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. , 2000, The New England journal of medicine.

[7]  J. Gorter,et al.  Major bleeding during anticoagulation after cerebral ischemia , 1999, Neurology.

[8]  F. Verheugt,et al.  A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin , 1997, Annals of neurology.

[9]  Vittorio Pengo,et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT) , 1996, The Lancet.

[10]  Bradley T. Hyman,et al.  Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy , 1996 .

[11]  David C. Anderson,et al.  Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. , 1996, Archives of internal medicine.

[12]  R. Hart,et al.  Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. , 1995, Stroke.

[13]  P. Koudstaal.  Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. , 1995, The New England journal of medicine.

[14]  G. Albers,et al.  Atrial fibrillation and stroke. Three new studies, three remaining questions. , 1994, Archives of internal medicine.

[15]  E. Hylek,et al.  Risk Factors for Intracranial Hemorrhage in Outpatients Taking Warfarin , 1994, Annals of Internal Medicine.

[16]  Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. , 1994, Archives of internal medicine.

[17]  Donald Martin,et al.  Risk Factors for Complications of Chronic Anticoagulation: A Multicenter Study , 1993, Annals of Internal Medicine.

[18]  David Lee Gordon,et al.  Classification of Subtype of Acute Ischemic Stroke: Definitions for Use in a Multicenter Clinical Trial , 1993, Stroke.

[19]  B. Norrving,et al.  Cost effectiveness of primary stroke prevention in atrial fibrillation: Swedish national perspective. , 1992, BMJ.

[20]  J. Olsson,et al.  Prognostic Parameters in Spontaneous Intracerebral Hematomas with Special Reference to Anticoagulant Treatment Subjects and Methods , 2022 .

[21]  P. Koudstaal,et al.  Grading white matter lesions on CT and MRI: a simple scale. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[22]  L Goldman,et al.  Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. , 1989, The American journal of medicine.

[23]  Daniel B Hier,et al.  Anticoagulant‐related intracerebral hemorrhage , 1985, Neurology.

[24]  K. Barron,et al.  Intracranial hemorrhage as a complication of anticoagulant therapy , 1959, Neurology.