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

• Published in: British journal of haematology 2005-03, Vol.128 (5), p.703-710
• Main Authors: Brouwer, Jan‐Leendert P., Veeger, Nic J. G. M., Schaaf, Wim van der, Kluin‐Nelemans, Hanneke C., Meer, Jan van der
• Format: Article
• Language: English
• Subjects: absolute risk; Adolescent; Adult; Aged; Arterial Occlusive Diseases - blood; Arterial Occlusive Diseases - etiology; Arterial Occlusive Diseases - genetics; arterial thrombosis; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cohort Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Hematologic and hematopoietic diseases; Hematology; Humans; Incidence; Male; Medical sciences; Middle Aged; Platelet diseases and coagulopathies; Proportional Hazards Models; Protein S - analysis; Protein S deficiency; Protein S Deficiency - classification; Protein S Deficiency - complications; Protein S Deficiency - genetics; Risk; Statistics, Nonparametric; Thromboembolism - blood; Thromboembolism - etiology; Thromboembolism - genetics; thrombophilia; venous thrombosis; Venous Thrombosis - blood; Venous Thrombosis - etiology; Venous Thrombosis - genetics
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2005.05371.x

Summary 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.