| Title: |
Similar hypercoagulable state and thrombosis risk in type Iand type III protein S-deficient individuals from families with mixed type I/IIIprotein S deficiency. |
| Authors: |
SIMIONI, PAOLO; TORMENE, DANIELA; SPIEZIA, LUCA; GAVASSO, SABRINA; RADU, CLAUDIA-MARIA; MAURISSEN LF; HACKENG TM; ROSING J |
| Contributors: |
Simioni, Paolo; Maurissen, Lf; Tormene, Daniela; Spiezia, Luca; Gavasso, Sabrina; Radu, CLAUDIA-MARIA; Hackeng, Tm; Rosing, J |
| Publication Year: |
2010 |
| Collection: |
Padua Research Archive (IRIS - Università degli Studi di Padova) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
volume:95; firstpage:1563; lastpage:1571; numberofpages:9; journal:HAEMATOLOGICA; https://hdl.handle.net/11577/2427894 |
| Availability: |
https://hdl.handle.net/11577/2427894 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.15EB52C |
| Database: |
BASE |