A propensity score-matched study including 250,000 patients with Factor V Leiden shows significantly increased mortality in comparison with individuals without thrombophilia.

Background: Factor V Leiden (FVL) is a common inherited thrombophilia that increases the risk of venous thromboembolism (VTE). However, its effect on all-cause mortality remains uncertain, and previous studies yielded conflicting results. Objectives: To assess the association between FVL and all-cause mortality using a large international database, including age- and sex-stratified analyses. Study design: Retrospective propensity score-matched cohort study using real-world electronic health records. Methods: We analyzed electronic health records from the TriNetX Global Health Research Network, comparing 241,572 patients with FVL to 20,779,115 patients without thrombophilia. One-to-one propensity score matching for age was applied. Incidences of VTE and all-cause mortality were compared over a 19-year follow-up. Subgroup analyses were performed for female patients and three age categories: <20, 20-50, and >50 years. Results: FVL was significantly associated with both VTE (OR: 9.325; 95% CI: 9.109-9.546) and all-cause mortality (OR: 1.423; 95% CI: 1.396-1.451). The mortality risk was particularly elevated in young females (<20 years: OR: 9.681; 20-50 years: OR: 2.345) and attenuated in older females (>50 years: OR: 1.432). Kaplan-Meier analyses showed significantly reduced survival probabilities in FVL-positive patients across all subgroups. Conclusions: This large-scale real-world study indicates that FVL is not only a major risk factor for thrombosis but also associated with increased all-cause mortality-particularly among young women. These findings may have implications for screening and risk stratification in selected populations.