This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (74)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Thrombolysis  • Adverse Effects  • Alert me on articles by topic

Jonathan Rosand, MD; Mark H. Eckman, MD; Katherine A. Knudsen, BA; Daniel E. Singer, MD; Steven M. Greenberg, MD, PhD

Arch Intern Med. 2004;164:880-884.

Background  Warfarin sodium is highly effective for prevention of embolic stroke, particularly in nonvalvular atrial fibrillation, but its expected benefit can be offset by risk of intracerebral hemorrhage (ICH). We studied the determinants of ICH outcome to quantify the independent effect of warfarin.

Methods  Consecutive patients with supratentorial ICH treated in a tertiary care hospital with a neurointensive care unit were prospectively identified during a 7-year period, and data on hemorrhage location, clinical characteristics, and warfarin use were collected. Independent predictors of 3-month mortality were determined using multiple logistic regression analysis.

Results  Of 435 consecutive patients aged 55 years or older, 102 (23.4%) were taking warfarin at the time of ICH. Three-month mortality was 25.8% for those not taking warfarin and 52.0% for those taking warfarin. Independent predictors of death were warfarin use (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3-3.8), age 70 years or older (OR, 2.4; 95% CI, 1.4-4.0), and presence of diabetes mellitus (OR, 1.8; 95% CI, 1.0-3.3). Although 68.0% of all warfarin-related hemorrhages occurred at an international normalized ratio (INR) of 3.0 or less, increasing degrees of anticoagulation were strongly associated with increasing risk of death compared with no warfarin use.

Conclusions  Patients taking warfarin had a doubling in the rate of intracerebral hemorrhage mortality in a dose-dependent manner. The data suggest that careful control of the INR, already known to limit the risk of warfarin-related ICH, may also limit its severity.

From the Neurology Clinical Trials Unit, Department of Neurology (Drs Rosand and Greenberg and Ms Knudsen), and Department of Medicine (Dr Singer), Massachusetts General Hospital, Boston; and Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio (Dr Eckman). Dr Singer has received research support and honoraria for lectures from DuPont Pharma, now Bristol-Myers Squibb, manufacturer of Coumadin brand warfarin sodium.

RELATED LETTERS

The Prognostic Impact of Oral Anticoagulant Treatment in Patients With Intracerebral Hemorrhage
Ulrich Thiem, Christoph Friedrich, Gerd Deutschinoff, and Ludger Pientka
Arch Intern Med. 2004;164(22):2504-2505.
EXTRACT | FULL TEXT  

The Prognostic Impact of Oral Anticoagulant Treatment in Patients With Intracerebral Hemorrhage—Reply
Jonathan Rosand and Steven M. Greenberg
Arch Intern Med. 2004;164(22):2505.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Experimental Model of Warfarin-Associated Intracerebral Hemorrhage
Foerch et al.
Stroke 2008;39:3397-3404.
ABSTRACT | FULL TEXT  

Patient-Specific Decision-Making for Warfarin Therapy in Nonvalvular Atrial Fibrillation: How Will Screening With Genetics and Imaging Help? * Supplemental Appendix
Eckman et al.
Stroke 2008;39:3308-3315.
ABSTRACT | FULL TEXT  

Hematoma Growth in Oral Anticoagulant Related Intracerebral Hemorrhage
Cucchiara et al.
Stroke 2008;39:2993-2996.
ABSTRACT | FULL TEXT  

Predictors of Outcome in Warfarin-Related Intracerebral Hemorrhage
Zubkov et al.
Arch Neurol 2008;65:1320-1325.
ABSTRACT | FULL TEXT  

Warfarin use leads to larger intracerebral hematomas
Flaherty et al.
Neurology 2008;71:1084-1089.
ABSTRACT | FULL TEXT  

Modifiable risk factors for intracerebral hemorrhage: Study of anticoagulated patients
Fric-Shamji et al.
cfp 2008;54:1138-1139.e4.
ABSTRACT | FULL TEXT  

Prediction of Functional Outcome in Patients With Primary Intracerebral Hemorrhage: The FUNC Score
Rost et al.
Stroke 2008;39:2304-2309.
ABSTRACT | FULL TEXT  

The Genetic Architecture of Intracerebral Hemorrhage
Rost et al.
Stroke 2008;39:2166-2173.
ABSTRACT | FULL TEXT  

Use of Anticoagulation in Elderly Patients with Atrial Fibrillation Who Are at Risk for Falls
Garwood and Corbett
The Annals of Pharmacotherapy 2008;42:523-532.
ABSTRACT | FULL TEXT  

Surgical Treatment of Atrial Fibrillation
Voeller et al.
Card Surg Adult 2008;3:1375-1394.
FULL TEXT  

REPRINT: 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: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
Broderick et al.
Circulation 2007;116:e391-e413.
ABSTRACT | FULL TEXT  

Racial/Ethnic Differences in the Risk of Intracranial Hemorrhage Among Patients With Atrial Fibrillation
Shen et al.
J Am Coll Cardiol 2007;50:309-315.
ABSTRACT | FULL TEXT  

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: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
Broderick et al.
Stroke 2007;38:2001-2023.
ABSTRACT | FULL TEXT  

Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage
Goldstein et al.
Neurology 2007;68:889-894.
ABSTRACT | FULL TEXT  

Intracerebral Hemorrhage: Introduction
Greenberg
Stroke 2007;38:746-747.
FULL TEXT  

Determinants of Outcome in Anticoagulation-Associated Cerebral Hematoma Requiring Emergency Evacuation
Rabinstein and Wijdicks
Arch Neurol 2007;64:203-206.
ABSTRACT | FULL TEXT  

The increasing incidence of anticoagulant-associated intracerebral hemorrhage
Flaherty et al.
Neurology 2007;68:116-121.
ABSTRACT | FULL TEXT  

Cost-Effectiveness of Recombinant Activated Factor VII in the Treatment of Intracerebral Hemorrhage
Earnshaw et al.
Stroke 2006;37:2751-2758.
ABSTRACT | FULL TEXT  

Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP.
Lee et al.
Neurology 2006;67:1272-1274.
ABSTRACT | FULL TEXT  

Is "compassionate use" compassionate?: rFVIIa for intracerebral hemorrhage.
Greenberg
Neurology 2006;67:934-935.
FULL TEXT  

Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study
Viswanathan et al.
Brain 2006;129:2375-2383.
ABSTRACT | FULL TEXT  

Pretreatment With Antiplatelet Agents Is Not Independently Associated With Unfavorable Outcome in Intracerebral Hemorrhage
Foerch et al.
Stroke 2006;37:2165-2167.
ABSTRACT | FULL TEXT  

Hematoma Growth and Outcome in Treated Neurocritical Care Patients With Intracerebral Hemorrhage Related to Oral Anticoagulant Therapy: Comparison of Acute Treatment Strategies Using Vitamin K, Fresh Frozen Plasma, and Prothrombin Complex Concentrates
Huttner et al.
Stroke 2006;37:1465-1470.
ABSTRACT | FULL TEXT  

Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage
Wong and Toyoda
Neurology 2006;66:1610-1611.
FULL TEXT  

Long-term mortality after intracerebral hemorrhage
Flaherty et al.
Neurology 2006;66:1182-1186.
ABSTRACT | FULL TEXT  

Aspirin-Use Before ICH: A Potentially Treatable Iatrogenic Coagulopathy?
Tuhrim
Stroke 2006;37:4-5.
FULL TEXT  

Timing of Fresh Frozen Plasma Administration and Rapid Correction of Coagulopathy in Warfarin-Related Intracerebral Hemorrhage
Goldstein et al.
Stroke 2006;37:151-155.
ABSTRACT | FULL TEXT  

Regular Aspirin-Use Preceding the Onset of Primary Intracerebral Hemorrhage is an Independent Predictor for Death
Saloheimo et al.
Stroke 2006;37:129-133.
ABSTRACT | FULL TEXT  

Intracerebral Hemorrhage Associated With Oral Anticoagulant Therapy: Current Practices and Unresolved Questions
Steiner et al.
Stroke 2006;37:256-262.
ABSTRACT | FULL TEXT  

Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage
Toyoda et al.
Neurology 2005;65:1000-1004.
ABSTRACT | FULL TEXT  

Avoiding Central Nervous System Bleeding During Antithrombotic Therapy: Recent Data and Ideas
Hart et al.
Stroke 2005;36:1588-1593.
ABSTRACT | FULL TEXT  

Recombinant Factor VIIa in the Treatment of Non-Hemophiliac Bleeding
Lam and Sims-McCallum
The Annals of Pharmacotherapy 2005;39:885-891.
ABSTRACT | FULL TEXT  

The Prognostic Impact of Oral Anticoagulant Treatment in Patients With Intracerebral Hemorrhage--Reply
Rosand and Greenberg
Arch Intern Med 2004;164:2505-2505.
FULL TEXT  

The Prognostic Impact of Oral Anticoagulant Treatment in Patients With Intracerebral Hemorrhage
Thiem et al.
Arch Intern Med 2004;164:2504-2505.
FULL TEXT  

Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation
Fang et al.
ANN INTERN MED 2004;141:745-752.
ABSTRACT | FULL TEXT  

Managing Complications of Anticoagulant Therapy
Smythe et al.
Journal of Pharmacy Practice 2004;17:327-346.
ABSTRACT  

Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage
Flibotte et al.
Neurology 2004;63:1059-1064.
ABSTRACT | FULL TEXT  

JournalScan
Malik
Heart 2004;90:826-826.
FULL TEXT