Optimal Timing of Resumption of Warfarin After Intracranial Hemorrhage

• Published in: Stroke (1970) Vol. 41; no. 12; pp. 2860 - 2866
• Main Authors: MAJEED, Ammar, KIM, Yang-Ki, ROBERTS, Robin S, HOLMSTRÖM, Margareta, SCHULMAN, Sam
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-12-2010
• Subjects: Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - therapeutic use; Biological and medical sciences; Brain Ischemia - epidemiology; Brain Ischemia - prevention & control; Cerebral Hemorrhage - chemically induced; Cohort Studies; Female; Fibrinolytic Agents - adverse effects; Fibrinolytic Agents - therapeutic use; Hematologic and hematopoietic diseases; Humans; International Normalized Ratio; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Neurology; Platelet diseases and coagulopathies; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Assessment; Stroke - epidemiology; Stroke - prevention & control; Time Factors; Vascular diseases and vascular malformations of the nervous system; Warfarin - administration & dosage; Warfarin - adverse effects; Warfarin - therapeutic use; Cerebral infarction; Stroke; Nervous system diseases; Warfarin; Coumarine derivatives; anticoagulation; Cardiovascular disease; Intracranial hemorrhage; Anticoagulant; Cerebral disorder; Vascular disease; Antivitamin K; Clinical management; management; Central nervous system disease; Brain ischemia; Cerebrovascular disease; ischemic stroke
• ISSN: 0039-2499; 1524-4628; 1524-4628
• DOI: 10.1161/strokeaha.110.593087

The optimum timing of resumption of anticoagulation after warfarin-related intracranial hemorrhage in patients with indication for continued anticoagulation is uncertain. We performed a large retrospective cohort study to obtain more precise risk estimates.
We reviewed charts of 2869 consecutive patients with objectively verified intracranial hemorrhage over 6 years at 3 tertiary centers. We calculated the daily risk of intracranial hemorrhage or ischemic stroke with and without resumption of warfarin; we focused on patients who survived the first week and had cardiac indication for anticoagulation or previous stroke. Using a Cox model, we estimated rates for these 2 adverse events in relation to different time points of resumed anticoagulation. The combined risk of either a new intracranial hemorrhage or an ischemic stroke was calculated for a range of warfarin resumption times.
We identified warfarin-associated intracranial hemorrhage in 234 patients (8.2%), of whom 177 patients (76%) survived the first week and had follow-up information available; the median follow-up time was 69 weeks (interquartile range [IQR] 19-144). Fifty-nine patients resumed warfarin after a median of 5.6 weeks (IQR 2.6-17). The hazard ratio for recurrent intracranial hemorrhage with resumption of warfarin was 5.6 (95% CI, 1.8-17.2), and for ischemic stroke it was 0.11 (95% CI, 0.014-0.89). The combined risk of recurrent intracranial hemorrhage or ischemic stroke reached a nadir if warfarin was resumed after approximately 10 to 30 weeks.
The optimal timing for resumption of warfarin therapy appears to be between 10 and 30 weeks after warfarin-related intracranial hemorrhage.