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Clinical Chemistry 49: 575-580, 2003; 10.1373/49.4.575
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(Clinical Chemistry. 2003;49:575-580.)
© 2003 American Association for Clinical Chemistry, Inc.

Cleaved Protein S (PS), Total PS, Free PS, and Activated Protein C Cofactor Activity as Risk Factors for Venous Thromboembolism

Delphine Borgel1,a, Jean-Luc Reny2, David Fischelis1, Sophie Gandrille1, Joseph Emmerich2, Jean-Noël Fiessinger2 and Martine Aiach1

1 Service d’Hématologie Biologique A and
2 Service des Maladies Vasculaires, Hôpital Européen Georges Pompidou, AP-HP, Paris and INSERM 428, UFR de Pharmacie, Université Paris V, France.

aAddress correspondence to this author at: Service d’Hématologie Biologique A, Hôpital Européen Georges Pompidou, 75908 Paris Cedex 15, France. Fax 33-1-56-09-39-13; e-mail borgel{at}pharmacie.univ-paris5.fr.

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.

Conclusion: 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.




The following articles in journals at HighWire Press have cited this article:


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 J. Med. Genet.Home page
J Esparza-Gordillo, J M Soria, A Buil, J C Souto, L Almasy, J Blangero, S R de Cordoba, and J Fontcuberta
Genetic correlation between plasma levels of C4BP isoforms containing {beta} chains and susceptibility to thrombosis
J. Med. Genet., January 1, 2004; 41(1): e5 - 5.
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