In a nested case control study on venous thrombosis in this E+P trial, the WHI researchers reported the associations of genetic variants with thrombosis risk. They identified 147 women in the WHI study who developed thrombosis, and compared them to 513 controls. Factor V Leiden was associated with thrombosis risk, and appeared to lead to a further increased risk in combination with E+P; the prevalence of Factor V Leiden among cases and controls was 13.8 percent and 4.6 percent, respectively. Compared to women without Factor V Leiden and assigned to placebo, women with Factor V Leiden assigned to E+P had a 6.7-fold increased risk of thrombosis (95 percent CI 3.1 14.5). The prothrombin 20210A variant was not common enough to draw conclusions; prevalences were 3.6 percent and 4.2 percent for E+P and placebo, respectively. Factor V Leiden is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk of venous thromboembolism. Factor V Leiden, inactivated at a rate approximately ten times slower than normal factor V, increases a woman's risk for venous thrombosis. Prothrombin 20210A is associated with elevated prothrombin levels (plasma protein produced in the liver in the presence of vitamin K and converted into thrombin by the action of various activators in the clotting of blood) and an increased risk for venous thrombosis.