A combination of mul- tiple case-control studies demonstrated an 4.3-fold increased incidence of factor V Leiden in children with acute ischemic A meta-analysis of the association of factorV Leiden with ischemic stroke in adults 50 years of age showed a fixed-effect OR of 2.00 for the mutation. This association was even stronger (OR, 2.73; 95% CI, 1.98 3.75) in those patients with cryptogenic stroke in whom there is an increased suspi- cion of hypercoagulability; however, the estimated effect car- ries the risk of inflation by case selection bias.831 A combined retrospective and prospective multicenter study of cerebral venous thrombosis found that a hypercoagulable state was the most common predisposing factor, followed by pregnancy, malignancy, and homocysteinemia.832 These coag- ulopathies may therefore predispose to venous thromboem- bolism, including cerebral venous sinus thrombosis, but may only rarely be associated with ischemic stroke. A systematic review assessed the risk of thrombosis associ- ated with thrombophilia in 3 high-risk groups: women using oral estrogen preparations, women during pregnancy, and patients undergoing major orthopedic surgery.833 This is rele- vant for the primary prevention of cerebral venous thrombosis and ischemic stroke from paradoxical cerebral embolism in the setting of a PFO. The effectiveness of prophylactic treat- ments in preventing venous thromboembolism in these groups and the relative cost-effectiveness of universal and selec- tive venous thromboembolism history based screening for Meschia et al Guidelines for the Primary Prevention of Stroke 3795 thrombophilia compared with no screening were evaluated. Selective screening based on prior venous thromboembolism history was more cost-effective than universal screening. Inherited Hypercoagulable State: Treatment for Primary Prevention of Stroke There is very little evidence to guide the management of asymptomatic people with thrombophilia. 