In asymptomatic patients with heterozygous factor V Leiden, heterozygous prothrombin gene mutation, protein C deficiency, and protein S deficiency, the absolute risk of VTE each year is approximately equal to the yearly risk of major bleeding on anticoagulation, and prophylaxis is not recommended for routine use when these mutations are discovered due to a family history of thrombosis [60]. This evidence concerns the gene PROS1 and hyperinsulinemic hypoglycemia, familial, 4.