The frequency of anticardiolipin antibodies and genetic mutations associated with hypercoagulability among patients with Wegener's granulomatosis with and without history of a thrombotic event

Jodi K. Sebastian, Barbara Voetsch, John H. Stone, Zurina Romay-Penabad, Grace H. Lo, Nancy B. Allen, John C. Davis, Gary S. Hoffman, W. Joseph McCune, E. William St. Clair, Ulrich Specks, Robert Spiera, Joseph Loscalzo, Silvia Pierangeli, Peter A. Merkel

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Objective. Venous thrombotic events (VTE), including both deep venous thrombosis and pulmonary emboli, are now recognized as an important complication of Wegener's granulomatosis (WG), but the mechanism(s) of this occurrence is unclear. The frequency of anticardiolipin antibodies (aCL), anti- β2-glycoprotein antibodies (anti-β2-GP), and several genetic hypercoagulable factors were examined in a large cohort of patients with WG. Methods. One hundred eighty patients with active WG had serum and DNA samples collected upon entry into a clinical trial. Of the 180 patients, 29 patients had VTE - 13 before trial entry, 16 during trial. aCL (IgG, IgM, and IgA) and anti-β2-GP (IgG and IgM) were evaluated in 176 patients. Factor V Leiden (FVL), the prothrombin gene mutation (G20210A, PGM), and methylenetetrahydrofolate reductase (MTHFR) gene mutation were tested in the 29 patients with thrombotic events, and 36 patients without. Results. aCL occurred with increased frequencies in patients with WG when compared to the general population (1%-5%): 12% had aCL and 3% had anti-β2-GP. There was no difference in the prevalences of aCL or anti-β2-GP based on clotting status. The prevalence of the genetic hypercoagulable factors examined in patients with WG was comparable to the reported rates in the general population. Conclusion. Although the incidence of clinically significant VTE is increased in patients with WG, this increased risk is not explained by increased prevalences of aCL, anti-β2-GP, FVL, or mutations in PGM or MTHFR. These observations suggest a need to search for new genetic or acquired prothrombotic abnormalities to account for the increased thrombotic event rate in patients with active WG.

Original languageEnglish (US)
Pages (from-to)2446-2450
Number of pages5
JournalJournal of Rheumatology
Volume34
Issue number12
StatePublished - Dec 2007

Keywords

  • Anticardiolipin antibodies
  • Thrombotic events
  • Wegener's granulomatosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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    Sebastian, J. K., Voetsch, B., Stone, J. H., Romay-Penabad, Z., Lo, G. H., Allen, N. B., Davis, J. C., Hoffman, G. S., McCune, W. J., St. Clair, E. W., Specks, U., Spiera, R., Loscalzo, J., Pierangeli, S., & Merkel, P. A. (2007). The frequency of anticardiolipin antibodies and genetic mutations associated with hypercoagulability among patients with Wegener's granulomatosis with and without history of a thrombotic event. Journal of Rheumatology, 34(12), 2446-2450.