title: Do incident and recurrent venous thromboembolism risks truly differ between heterozygous and homozygous Factor V Leiden carriers? A retrospective cohort study.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Hematology, Department of Medicine Mayo Clinic, Rochester, MN, USA. Electronic address: PerezBotero.Juliana@mayo.edu.
authors.forename: J
authors.initials: J
authors.lastname: Perez Botero
authors.affiliation: Division of Hematology, Department of Medicine Mayo Clinic, Rochester, MN, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Ormsby
authors.affiliation: Division of Hematology, Department of Medicine Mayo Clinic, Rochester, MN, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Ashrani
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: McBane
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Wysokinski
authors.affiliation: Division of Hematology, Department of Medicine Mayo Clinic, Rochester, MN, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Patnaik
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Lewis
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Grill
authors.affiliation: Division of Hematology, Department of Medicine Mayo Clinic, Rochester, MN, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Pruthi
authors.affiliation: Division of Hematology, Department of Medicine Mayo Clinic, Rochester, MN, USA; Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Heit
mesh_terms: D000328:Adult; D000368:Aged; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics*; D014481:United States; D054556:Venous Thromboembolism / Q000150:complications / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V
keywords: Activated protein C resistance; Factor V Leiden; Pulmonary embolism; Thrombophilia; Venous thrombosis