title: The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis.
abstract: BACKGROUND
  The factor V Leiden mutation is a genetic defect associated with an increased incidence of venous thromboembolism. When the incidence of venous thromboembolism in relatives of patients known to have the mutation outweighs the disadvantages of prophylactic strategies, family screening may be necessary.
  
  
  OBJECTIVE
  To determine the incidence of venous thromboembolism in first-degree relatives of symptomatic carriers of the factor V Leiden mutation.
  
  
  METHODS
  Retrospective blinded study.
  
  
  METHODS
  University hospitals.
  
  
  METHODS
  437 first-degree relatives of 112 heterozygous propositi and 30 relatives of 6 homozygous propositi.
  
  
  METHODS
  Before DNA testing, information on previous venous thromboembolism and concomitant risk factors was obtained. Relatives with and without the FV: Q506 mutation were compared.
  
  
  RESULTS
  The annual incidence of thromboembolism in relatives of heterozygous propositi was 0.45% (95% CI, 0.28% to 0.61%) in those with the mutation and 0.10% (CI, 0.02% to 0.19%) in those without the mutation (relative risk, 4.2 [CI, 1.8 to 9.9]). Among carriers, the incidence increased from 0.25% (CI, 0.12% to 0.49%) in the 15- to 30-year-old age group to 1.1% (CI, 0.24% to 3.33%) in persons older than 60 years of age. Half of the episodes of venous thromboembolism occurred spontaneously, 20% were related to surgery, and 30% were associated with pregnancy or use of oral contraceptives.
  
  
  CONCLUSIONS
  The observed low annual risk for venous thromboembolism in persons carrying the factor V Leiden mutation does not seem to outweigh the risks for bleeding associated with coumarin prophylaxis or justify discouragement of the use of oral contraceptives. A general policy of screening the families of all patients with the factor V Leiden mutation does not seem to be indicated. The observations in this moderate-size, retrospective study need to be confirmed by prospective follow-up studies.
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Middeldorp
authors.forename: C M
authors.initials: CM
authors.lastname: Henkens
authors.forename: M M
authors.initials: MM
authors.lastname: Koopman
authors.forename: E C
authors.initials: EC
authors.lastname: van Pampus
authors.forename: K
authors.initials: K
authors.lastname: Hamulyák
authors.forename: J
authors.initials: J
authors.lastname: van der Meer
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D005165:Factor V / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011336:Probability; D012189:Retrospective Studies; D013923:Thromboembolism / Q000235:genetics*; D013924:Thrombophlebitis / Q000235:genetics*
chemical_list: D005165:Factor V