Factor V levels and risk of venous thrombosis: The MEGA case-control study

Background Blood coagulation levels are associated with risk of venous thrombosis (VT). The role of factor (F)V is ambiguous since it plays a dual role in coagulation: it has a procoagulant role when it serves as a cofactor for the activation of thrombin and it has an anticoagulant role by enhancing the inactivation of activated FVIII. Objectives To elucidate the association of FV levels with risk of VT. Patients/Methods We analyzed FV antigen levels in 2377 patients with VT and 2943 controls from the MEGA study. FV levels were categorized according using the 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of FV levels in controls as cut‐off points. Odds ratios (ORs) were estimated using logistic regression models and adjusted for age and sex, liver disease, FVIII levels, FV Leiden, and TFPI. Results The risk estimates were U‐shaped with increased ORs for the lowest (<0.57 U/dL) levels (OR 1.46; 95% CI 0.87‐2.43) as well as the highest (>1.22 U/dL) (OR 1.86; 95% CI 1.46‐2.37) levels as compared with the reference group (25th‐50th percentile). FVIII adjustment led to attenuation of the OR for high FV levels (OR 1.14; 95% CI 0.88‐1.48), with little change for low FV levels (OR 1.68; 95% CI 0.97‐2.91). Other adjustments had limited effects. Conclusions We found high FV levels to be associated with increased risk for VT, which was explained by concurrently raised FVIII levels. For low levels of factor V, the increased risk for VT could not be explained by the mechanisms we explored.