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

Eur J Intern Med. 2016 May:30:77-81. doi: 10.1016/j.ejim.2016.02.023. Epub 2016 Mar 9.

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. 42.9years; 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 >6months 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.

Keywords: Activated protein C resistance; Factor V Leiden; Pulmonary embolism; Thrombophilia; Venous thrombosis.

MeSH terms

  • Adult
  • Aged
  • Factor V / genetics*
  • Female
  • Heterozygote*
  • Homozygote*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Thrombophilia / genetics*
  • United States
  • Venous Thromboembolism / complications
  • Venous Thromboembolism / genetics*
  • Venous Thrombosis / genetics*

Substances

  • factor V Leiden
  • Factor V

Supplementary concepts

  • Thrombophilia, hereditary