title: Cleaved protein S (PS), total PS, free PS, and activated protein C cofactor activity as risk factors for venous thromboembolism.
abstract: BACKGROUND
  Although hereditary protein S (PS) deficiency is clearly associated with venous thromboembolism (VTE), the importance of low PS concentrations as a risk factor for VTE in other patients is still a matter of debate. To clarify this issue, we designed a case-control study to evaluate the role of different molecular forms of plasma PS.
  
  
  METHODS
  We quantified plasma cleaved, total, and free PS and activated protein C (APC) cofactor activity in 87 VTE patients and 174 controls matched for age, sex, and hormonal treatment. Free PS was measured by ELISA or by enzyme-linked ligand sorbent assay (ELSA). Cleaved and total PS were measured by ELISA.
  
  
  RESULTS
  In controls, the mean (SD) concentration of circulating cleaved PS was 39 (14) nmol/L, corresponding to 10% (3.5%) of total PS. Concentrations of cleaved PS and total PS were not significantly different in patients with VTE compared with controls. However, in our population, low free PS measured by ELISA or ELSA, as well as APC cofactor activity values were significantly associated with VTE with odds ratios (95% confidence intervals) of 2.9 (1.3-6.3), 2.5 (1.1-5.6), and 2.9 (1.3-6.4), respectively, in multivariate analyses.
  
  
  CONCLUSIONS
  Phenotypic low PS detected by APC cofactor activity assay or by an assay specific for free PS should be considered a risk factor for VTE.
authors.affiliation: Service d'Hématologie Biologique A, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. borgel@pharmacie.univ-paris5.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Borgel
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Reny
authors.forename: David
authors.initials: D
authors.lastname: Fischelis
authors.forename: Sophie
authors.initials: S
authors.lastname: Gandrille
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Fiessinger
authors.forename: Martine
authors.initials: M
authors.lastname: Aiach
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D016022:Case-Control Studies; D015935:Complement C4b / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008297:Male; D011486:Protein C / Q000032:analysis* / Q000378:metabolism; D017293:Protein S / Q000032:analysis* / Q000378:metabolism; D018455:Protein S Deficiency; D012307:Risk Factors; D013923:Thromboembolism / Q000175:diagnosis*; D020246:Venous Thrombosis / Q000175:diagnosis*
chemical_list: D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D011486:Protein C; D017293:Protein S; D015935:Complement C4b