Do incident and recurrent venous thromboembolism risks truly differ between heterozygous and homozygous Factor V Leiden carriers? A retrospective cohort study

Abstract Introduction While Factor V Leiden ( F5 rs6025 A allele) is a known venous thromboembolism (VTE) risk factor, VTE risk among heterozygous vs. homozygous carriers is uncertain. Materials and methods In a retrospective cohort study of Mayo Clinic patients referred for genotyping between 1996 and 2013, we tested Factor V Leiden genotype as a risk factor for incident and recurrent VTE. Results Among heterozygous (n = 268) and homozygous (n = 111) carriers, the prevalence of VTE was 54% and 68%, respectively (p = 0.016). While mean patient age at first VTE event (43.9 vs. 42.9 years; p = 0.70) did not differ significantly, median VTE-free survival was modestly shorter for homozygous carriers (56.8 vs 59.5 years; p = 0.04). Sixty-nine (48%) and 31 (42%) heterozygous and homozygous carriers had ≥ 1 VTE recurrence (p = 0.42). In a multivariable model, idiopathic incident VTE and a second thrombophilia were associated with increased and anticoagulation duration > 6 months with reduced hazards of VTE recurrence; Factor V Leiden genotype was not an independent predictor of recurrence. Conclusions Aside from a higher VTE prevalence and modestly reduced VTE-free survival, VTE penetrance and phenotype severity did not differ significantly among homozygous vs. heterozygous carriers, suggesting that VTE prophylaxis and management should not differ by Factor V Leiden genotype.