title: Factor V Leiden: an additional risk factor for thrombosis in protein S deficient families?
abstract: We recently reported a high prevalence of the FV Leiden mutation (R506Q, responsible for Activated Protein C resistance) among symptomatic protein C deficient probands (19%), and the involvement of the FV Leiden mutation in the expression of thrombophilia in six protein C deficient families. Here, we report the results of a similar study in protein S deficient probands and families. Among 16 symptomatic protein S deficient probands the prevalence of the FV Leiden mutation was high (38%). This high prevalence is significantly different from that in the normal population, and is probably caused by the selection of probands for familial thrombosis and protein S deficiency. In 4 families, the segregation of the FV Leiden mutation and the protein S deficiency could be studied. In sibships where both abnormalities were segregating, the percentage of symptomatic individuals with both abnormalities was 80%. Three of the seven subjects with only the FV Leiden mutation, and two out of the three subjects with only protein S deficiency had developed thrombosis. These results indicate that in the families presented here the combination of the FV Leiden mutation and the protein S deficiency is associated with a high risk for thrombosis. A reliable estimate of the penetrance of the single defects is not possible, because the number of individuals with a single defect is too low.
authors.affiliation: Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital, Leiden.
authors.forename: B P
authors.initials: BP
authors.lastname: Koeleman
authors.forename: D
authors.initials: D
authors.lastname: van Rumpt
authors.forename: K
authors.initials: K
authors.lastname: Hamulyák
authors.forename: P H
authors.initials: PH
authors.lastname: Reitsma
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015995:Prevalence; D018455:Protein S Deficiency / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V