Acquired free protein S deficiency is associated with antiphospholipid antibodies and increased thrombin generation in patients with systemic lupus erythematosus.

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.
AuthorsJ S Ginsberg, C Demers, P Brill-Edwards, R Bona, M Johnston, A Wong, J A Denburg
JournalThe American journal of medicine (Am J Med) Vol. 98 Issue 4 Pg. 379-83 (Apr 1995) ISSN: 0002-9343 [Print] UNITED STATES
PMID7709951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Antiphospholipid
  • Protein S
  • Thrombin
  • Adult
  • Aged
  • Antibodies, Antiphospholipid (blood)
  • Cross-Sectional Studies
  • Female
  • Humans
  • Lupus Erythematosus, Systemic (blood, complications, immunology, metabolism)
  • Male
  • Middle Aged
  • Protein S (metabolism)
  • Protein S Deficiency (blood, complications, immunology, metabolism)
  • Thrombin (biosynthesis)

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