819,821,822 Because most studies involved patients with SLE, lupus anticoagulant, or aCL, it is difficult to establish the value of anti- 2 GPI as an independent risk factor. Therefore, the clinical significance of these antibodies requires A prospective, observational study was performed to establish the incidence of first-time thromboem- bolic events in subjects with a high-risk aPL profile (positive lupus anticoagulant, positive aCL, and positive 2 The incidence of first thromboembolus was 5.3% annually com- pared with an annual rate of 1.9% in a study from the same group looking at subjects with only a single positive aPL test.824 Forty percent of thromboembolic events were stroke or TIA, and aspirin did not affect the incidence. Acquired Hypercoagulable State: Treatment for Primary Prevention of Stroke Adequately powered, controlled studies evaluating treatment of elevated aCL to prevent a first stroke are not available. In a subgroup analysis of the Physicians Health Study,818 aspirin every other day did not protect against venous throm- boembolism in 40- to 84-year-old men with moderate to high aCL titers. There is an ongoing primary prevention trial of warfarin therapy (INR, 2.0 2.5) to decrease thromboembolic events in patients with lupus and aPL.825 The Antiphospholipid Antibody Acetylsalicylic Acid (APLASA) study was a small, multicenter, double-blind, pla- cebo-controlled trial for the primary prevention of thrombosis in asymptomatic patients who were persistently aPL positive that compared low-dose aspirin (81 mg/d; n=48) with placebo (n=50) over an average follow-up of 2.30 0.95 years.816 The rates of acute thrombosis were 2.75 per 100 patient-years for the aspirin-treated subjects and 0 per 100 patient-years for placebo- sample size was relatively small; thus, the study insufficiently powered. 