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

Q: What are the key findings of this study?

Factor V Leiden mutation was significantly associated with an increased risk of all-cause mortality (OR 1.423) compared to individuals without thrombophilia, particularly among young women.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Factor V Leiden mutation (n=483144). Intervention: Factor V Leiden mutation vs. No Factor V Leiden mutation. Primary outcome: All-cause mortality (OR 1.423, 95% CI 1.396-1.451, p=<0.001).

Q: What does this research mean for the field?

Factor V Leiden is significantly associated with increased all-cause mortality compared to individuals without thrombophilia, with the highest excess mortality observed among young females. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Moritz Hertel; Max Heiland; Susanne Nahles; Saskia Preissner; Robert Preissner

doi:10.1016/j.puhip.2026.100751

February 16, 2026Public Health in PracticeOpen Access

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

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Key result

Factor V Leiden mutation linked to ~42% higher all-cause mortality, particularly in young women.

OR 1.423
95% CI 1.396-1.451
P<0.001
n=483,144

Figures

Why the study?

Factor V Leiden increases the risk of venous thromboembolism, but its effect on all-cause mortality remains uncertain due to conflicting results from previous studies.

Does Factor V Leiden mutation increase the risk of all-cause mortality and venous thromboembolism in a large real-world population?

Study Design

Type

Cohort (n=483,144)

Multicenter

Yes

Structured PICO

Does Factor V Leiden mutation increase the risk of all-cause mortality and venous thromboembolism in a large real-world population?

P

Population

483,144 age-matched patients (mean age 49.8 years, 59.3% female) with and without the Factor V Leiden mutation, followed for 19 years using an international electronic health records database.

E

Exposure

Presence of Factor V Leiden (FVL) mutation (exposure group)

C

Comparator

Absence of Factor V Leiden (FVL) mutation (no thrombophilia), 1:1 propensity score-matched based on patient age

O

Outcome

All-cause mortality over a 19-year follow-up periodhard clinical

Main Result

Odds Ratio: 1.423 (95% CI 1.396–1.451)

Absolute Event Rate: 11.3% vs 8.2%

p-value: p=<0.001

In a large multinational real-world cohort, Factor V Leiden mutation was significantly associated with increased all-cause mortality, particularly among young women, highlighting its role as a potential independent mortality risk factor beyond venous thrombosis.

Limitations

Retrospective analysis based on electronic health records with possible residual confounding
Propensity score matching was limited to age, leaving unmeasured variables such as comorbidities, socioeconomic factors, or medication use
Selection bias due to inclusion based on FVL testing, as the control group may include undiagnosed carriers
Use of ICD-10 code I82 does not allow for differentiation between acute and chronic thrombotic events
Potential missed outcome events that occurred prior to the index encounter
Inability to adjust for ethnicity due to missing or inconsistently coded demographic information
Propensity score matching was limited to age; other unmeasured variables such as comorbidities, socioeconomic factors, or medication use could have influenced results
Selection bias as testing is typically performed in individuals with suspected thrombophilia
Use of ICD-10 code I82 to define thrombosis does not allow for differentiation between acute and chronic events
Potential missed outcome events prior to the index encounter and inability to adjust for ethnicity due to missing or inconsistently coded data

Implication

May inform mortality risk counseling for young women with Factor V Leiden; leaves open whether screening or intervention improves outcomes.

Abstract

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.

Discussion

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Cite This Study

Hertel et al. (2026) conducted a cohort in Factor V Leiden mutation (n=483,144). Factor V Leiden mutation vs. No Factor V Leiden mutation was evaluated on All-cause mortality (OR 1.423, 95% CI 1.396-1.451, p=<0.001). Factor V Leiden mutation was significantly associated with an increased risk of all-cause mortality (OR 1.423) compared to individuals without thrombophilia, particularly among young women.

synapsesocial.com/papers/6aa5374dbc2c7db7488e3593 https://doi.org/10.1016/j.puhip.2026.100751

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

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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