title: Acquired free protein S deficiency is associated with antiphospholipid antibodies and increased thrombin generation in patients with systemic lupus erythematosus.
abstract: In order to determine whether there is a relationship between acquired free protein S deficiency and increased thrombin generation, we performed a cross-sectional study of patients with systemic lupus erythematosus (SLE). Plasma samples were assayed for free protein S and were correlated to levels of prothrombin fragments (F1 + 2); an elevated level of F1 + 2 was used as a surrogate marker for a prothrombotic state. Assays for anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) were performed on two separate blood samples taken at least 3 months apart in order to detect the presence of antiphospholipid antibodies. Of the 36 subjects, 9 had reduced free protein S levels compared to 0 of 21 controls (P = 0.01) and the mean free protein S level was significantly lower in the SLE population than in controls (0.30 +/- 0.08 U/mL versus 0.43 +/- 0.10 U/mL, P < 0.001). Of the 24 subjects with antiphospholipid antibodies, 9 had reduced free protein S levels, compared to 0 of 12 subjects without antiphospholipid antibodies (P = .01). The mean F1 + 2 level was significantly higher in study subjects with reduced free protein S levels than in those with normal free protein S levels (1.22 +/- 0.50 nmol/L versus 0.78 +/- 0.27 nmol/L, P = 0.05). This study confirms an association between antiphospholipid antibodies and reduced free protein S levels and demonstrates that patients with SLE and acquired free protein S deficiency generate more thrombin than patients with SLE and normal free protein S levels. Further studies are needed to determine whether the thrombotic diathesis associated with the presence of antiphospholipid antibodies is directly caused by the concomitant presence of acquired free protein S deficiency.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: C
authors.initials: C
authors.lastname: Demers
authors.forename: P
authors.initials: P
authors.lastname: Brill-Edwards
authors.forename: R
authors.initials: R
authors.lastname: Bona
authors.forename: M
authors.initials: M
authors.lastname: Johnston
authors.forename: A
authors.initials: A
authors.lastname: Wong
authors.forename: J A
authors.initials: JA
authors.lastname: Denburg
mesh_terms: D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017293:Protein S / Q000378:metabolism; D018455:Protein S Deficiency / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000378:metabolism*; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D017152:Antibodies, Antiphospholipid; D017293:Protein S; D013917:Thrombin