title: Protein S type III deficiency is no risk factor for venous and arterial thromboembolism in 168 thrombophilic families: a retrospective study.
abstract: Free protein S rather than total protein S levels are currently measured to detect inherited protein S deficiency. Because type III (free protein S) deficiency is still not established as risk factor for thrombosis, we assessed the absolute risk of venous and arterial thromboembolism in a family cohort study. Annual incidences in first-degree relatives with and without protein S deficiency type III were compared. Probands had experienced thrombosis and had either the prothrombin G20210A mutation, increased factor VIII:C levels or hyperhomocysteinemia. Relatives were tested for these thrombophilic disorders and factor V Leiden. Levels of antithrombin, protein C, total and free protein S, and factor XI:C were additionally measured. Of 500 relatives enrolled, 105 were excluded from analysis because they could not be classified, due to acquired conditions. Protein S deficiency type III was demonstrated in 60/395 remaining relatives (15%). Other thrombophilic defects were equally distributed among deficient and non-deficient relatives. Annual incidences of venous thromboembolism were 0.28 per 100 person-years [95% confidence interval (CI), 0.09-0.66] in deficient relatives versus 0.20 per 100 person-years (95% CI, 0.12-0.30) in non-deficient relatives [hazard ratio, 1.4 (95% CI, 0.4-4.0)]. For arterial thromboembolism these values were 0.16 per 100 person-years (95% CI, 0.03-0.46) versus 0.10 per 100 person-years (95% CI, 0.05-0.19) [hazard ratio, 1.5 (95% CI, 0.3-6.0)]. These results suggest that protein S deficiency type III is not associated with an increased risk of either venous or arterial thromboembolism.
authors.affiliation: Department of Hematology, Division of Hemostasis, Thrombosis and Rheology, University Hospital, Groningen, The Netherlands.
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Libourel
authors.forename: Ivan
authors.initials: I
authors.lastname: Bank
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyàk
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011486:Protein C / Q000032:analysis; D018455:Protein S Deficiency / Q000097:blood* / Q000150:complications / Q000235:genetics; D011516:Prothrombin / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology / Q000235:genetics
chemical_list: D011486:Protein C; D011516:Prothrombin; D005169:Factor VIII