title: Difference in absolute risk of venous and arterial thrombosis between familial protein S deficiency type I and type III. Results from a family cohort study to assess the clinical impact of a laboratory test-based classification.
abstract: Hereditary protein S (PS) deficiency type I is an established risk factor for venous thromboembolism. Contradictionary data on type III deficiency suggests a difference in risk between both types. We studied 156 first degree relatives (90% of eligible relatives) from type I deficient probands (cohort 1) and 268 (88%) from type III deficient probands (cohort 2) to determine the absolute risk of venous and arterial thromboembolism. Annual incidences of venous thromboembolism were 1.47 and 0.17 per 100 person-years in deficient and non-deficient relatives in cohort 1 [relative risk (RR) 8.9; 95% confidence interval (CI) 2.6-30.0], and 0.27 vs. 0.24 in cohort 2 (RR 0.9; 95% CI 0.4-2.2). Type III deficiency was demonstrated in 20% of non-deficient relatives in cohort 1 and the annual incidence in this subgroup was 0.70 (RR 4.3;0.95-19.0). The cut-off level of free PS to identify subjects at risk was 30%, the lower limit of its normal range (65%). PS deficiency was not a risk factor for arterial thromboembolism. In conclusion, type I deficiency was found to be a strong risk factor for venous thromboembolism, in contrast with type III deficiency. This was because of lower free PS levels in type I deficient subjects and a free PS cut-off level far below the lower limit of its normal range.
authors.affiliation: Division of Haemostasis, Thrombosis and Rheology, Department of Haematology, University Hospital Groningen, 9713 GZ Groningen, The Netherlands. j.l.p.brouwer@int.azg.nl
authors.forename: Jan-Leendert P
authors.initials: JL
authors.lastname: Brouwer
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: Wim
authors.initials: W
authors.lastname: van der Schaaf
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017293:Protein S / Q000032:analysis; D018455:Protein S Deficiency / Q000145:classification* / Q000150:complications* / Q000235:genetics; D012306:Risk; D018709:Statistics, Nonparametric; D013923:Thromboembolism / Q000097:blood / Q000209:etiology* / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology* / Q000235:genetics
chemical_list: D017293:Protein S