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
Open Access
- 26 April 2010
- journal article
- retracted article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 95 (9), 1563-1571
- https://doi.org/10.3324/haematol.2010.021923
Abstract
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.This publication has 45 references indexed in Scilit:
- Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasmaJournal of Thrombosis and Haemostasis, 2010
- Protein S enhances the tissue factor pathway inhibitor inhibition of factor Xa but not its inhibition of factor VIIa–tissue factorJournal of Thrombosis and Haemostasis, 2008
- Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivationBlood, 2008
- The association between protein S levels and anticoagulant activity of tissue factor pathway inhibitor type 1Journal of Thrombosis and Haemostasis, 2008
- Differential effects of high prothrombin levels on thrombin generation depending on the cause of the hyperprothrombinemiaJournal of Thrombosis and Haemostasis, 2007
- Molecular diversity and thrombotic risk in protein S deficiency: The PROSIT studyHuman Mutation, 2005
- Effect of oral contraceptives on the anticoagulant activity of protein S in plasmaThrombosis and Haemostasis, 2005
- The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general populationBritish Journal of Haematology, 2004
- Study of a protein S gene polymorphism at DNA and mRNA level in a family with symptomatic protein S deficiencyBritish Journal of Haematology, 1993
- Recurrent Venous Thromboembolism in Patients with a Partial Deficiency of Protein SThe New England Journal of Medicine, 1984