title: Clinical features of thrombophilia in families with gene defects in protein C or protein S combined with factor V Leiden.
abstract: Twenty-nine clinically well-characterized, symptomatic index patients, 15 with protein C and 14 with protein S deficiency, in whom the genetic defect had been identified, were investigated for the presence of factor V Leiden. In six of 15 (40%) propositi with protein C and four of 14 (29%) with protein S deficiency, factor V Leiden was present. The age at first thrombosis was significantly lower (P < 0.001) in the ten propositi with a combined genetic defect (mean age 18.4 +/- 6.6 years) than in those with a single defect (mean age 32.6 +/- 10.4 years). Spontaneous occurrence, recurrence and site of thrombosis were similar in propositi with the single and the combined defect. Family studies led to the identification of a combined defect in 18 individuals from 11 families (11 propositi and 29 relatives), seven subjects had no abnormality, and in 15 a single defect was found. In individuals with a combined defect, thrombosis-free survival time was significantly shorter than in individuals with a single defect, even after exclusion of index patients. None of the seven individuals without genetic abnormality had experienced thrombosis. Our findings indicate a higher risk for development of thrombosis in individuals with a combined defect compared with those with a single defect.
authors.affiliation: Department of Internal Medicine, University Vienna Medical School, Wien, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Mustafa
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: C
authors.initials: C
authors.lastname: Rintelen
authors.forename: P A
authors.initials: PA
authors.lastname: Kyrle
authors.forename: P
authors.initials: P
authors.lastname: Knöbl
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
mesh_terms: D000293:Adolescent; D000328:Adult; D001778:Blood Coagulation Disorders / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011486:Protein C / Q000235:genetics; D020151:Protein C Deficiency; D017293:Protein S / Q000235:genetics; D018455:Protein S Deficiency / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D019851:Thrombophilia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011486:Protein C; D017293:Protein S; C095381:factor V Leiden; D005165:Factor V