TY - JOUR AU - Elisabetta Castoldi, AU - Lisbeth F.A. Maurissen, AU - Daniela Tormene, AU - Luca Spiezia, AU - Sabrina Gavasso, AU - Claudia Radu, AU - Tilman M. Hackeng, AU - Jan Rosing, AU - Paolo Simioni, PY - 2010/08/31 Y2 - 2024/03/28 TI - Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency JF - Haematologica JA - haematol VL - 95 IS - 9 SE - Articles DO - 10.3324/haematol.2010.021923 UR - https://haematologica.org/article/view/5722 SP - 1563-1571 AB - Background Protein S, which circulates in plasma in both free and bound forms, is an anticoagulant protein that stimulates activated protein C and tissue factor pathway inhibitor. Hereditary type I protein S deficiency (low total and low free protein S) is a well-established risk factor for venous thrombosis, whereas the thrombosis risk associated with type III deficiency (normal total and low free protein S) has been questioned.Design and Methods Kaplan-Meier analysis was performed on 242 individuals from 30 families with protein S deficiency. Subjects were classified as normal, or having type I or type III deficiency according to their total and free protein S levels. Genetic and functional studies were performed in 23 families (132 individuals).Results Thrombosis-free survival was not different between type I and type III protein S-deficient individuals. Type III deficient individuals were older and had higher protein S, tissue factor pathway inhibitor and prothrombin levels than type I deficient individuals. Thrombin generation assays sensitive to the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S revealed similar hypercoagulable states in type I and type III protein S-deficient plasma. Twelve PROS1 mutations and two large deletions were identified in the genetically characterized families.Conclusions Not only type I, but also type III protein S deficiency is associated with a hypercoagulable state and increased risk of thrombosis. These findings may, however, be restricted to type III deficient individuals from families with mixed type I/III protein S deficiency, as these represented 80% of type III deficient individuals in our cohort. ER -