Cleaved protein S (PS), total PS, free PS, and activated protein C cofactor activity as risk factors for venous thromboembolism.
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.
Borgel
Delphine
D
Service d'Hématologie Biologique A, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. borgel@pharmacie.univ-paris5.fr
Reny
Jean-Luc
JL
Fischelis
David
D
Gandrille
Sophie
S
Emmerich
Joseph
J
Fiessinger
Jean-Noël
JN
Aiach
Martine
M
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*
D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D011486:Protein C; D017293:Protein S; D015935:Complement C4b