Influence of the factor II G20210A variant or the factor V G1691A mutation on symptomatic recurrent venous thromboembolism in children: An international multicenter cohort study

Objective: To determine the relative importance of the factor (F) II G20210A or FV G1691A mutations as risk factors or predictors for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. Methods: In the present cohort, the rate of VTE recurrence and the time to recurrence in relation to FII, FV, age, and sex was determined in consecutively enrolled patients with VTE aged newborn to ≤18 years carrying the FII (n = 64) or FV (n = 194) mutation. 158 children with VTE without thrombophilia served as controls. Patients were followed for a median of 58 months. Data were pooled across participating sites to increase power and to enhance the generalizability of the data. Incidence rates were given as events per 1000 person-years. Results: Of the 416 children enrolled, 44 had recurrent VTE at a median of 12 months following VTE onset. The overall incidence rate of recurrence was 19.8, 57.9 in patients with the FII variant, 17.9 for FV carriers, and 11.8 in the control cohort. When comparing FII patients, FV children and the control cohort multivariate analysis (Cox regression) adjusted for age and sex showed that the FII variant (hazard ratio 2.6; 95% confidence interval 1.1-5.9) influenced the hazard for recurrent VTE. Conclusions: Based on multivariate analysis, the presence of the FII variant was associated with an increased risk of VTE recurrence.