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thrombosis despite warfarin in the target INR range include increasing the intensity of warfarin anticoagulation to achieve a higher target INR (target INR, 2.5-3.5 or 3.0-4.0), switching from warfarin to therapeutic doses of unfractionated heparin or low-molecularweight heparin, or adding an antiplatelet agent to warfarin. Plasma exchange or intravenous immune globulin, particularly in patients with catastrophic APS, have also been suggested.73 CONCLUSIONS Since initial reports of an association between aCL and thrombosis and fetal death,74 much of the research has focused on the pathogenesis and clinical features of APS. Prospective studies on the optimal treatment of thrombosis in APS have focused primarily on venous thrombosis and ischemic stroke. The results of these studies indicate that patients with antiphospholipid antibodies and venous thrombosis should be treated with longterm (potentially indefinite) anticoagulation with warfarin administered to achieve an INR of 2.0 to 3.0. Either moderate-intensity warfarin or aspirin is acceptable for patients with antiphospholipid antibodies and a first episode of stroke. Prospective studies addressing the issue of primary antithrombotic prophylaxis in asymptomatic patients with antiphospholipid antibodies are in progress.75,76 These and other well-designed prospective studies are required to complete the understanding of the optimal treatment of patients with antiphospholipid antibodies and APS. Author Contributions: Dr Eikelboom had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Eikelboom. Acquisition of data: Lim, Eikelboom. Analysis and interpretation of data: Lim, Crowther, Eikelboom. Drafting of the manuscript: Lim, Eikelboom. Critical revision of the manuscript for important intellectual content: Crowther, Eikelboom. Study supervision: Eikelboom. Financial Disclosures: None reported. Funding/Support: No funding was received for this review. Dr Lim is the recipient of the International Society on Thrombosis and Haemostasis/SanofiAventis Clinical Research Fellowship. Dr Crowther is a Career Investigator of the Heart and Stroke Foun1056

dation of Canada. Dr Eikelboom holds a Tier II Canada Research Chair in Cardiovascular Medicine from the Canadian Institutes of Health Research.

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