Patients with antineutrophil cytoplasmic antibodies associated vasculitis in remission are hypercoagulable

J Rheumatol. 2013 Dec;40(12):2042-6. doi: 10.3899/jrheum.130200. Epub 2013 Oct 15.

Abstract

Objectives: The risk of venous thromboembolism (VTE) is increased in patients with antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides (AAV) as compared to healthy subjects. The mechanisms underlying this increased occurrence of VTE are not completely understood. We hypothesize that AAV patients in remission are more procoagulant than healthy controls.

Methods: Patients with AAV in remission and no VTE for the last 6 months were included. Patients with severe renal impairment (serum creatinine > 250 μmol/l) were excluded. Age and sex matched healthy controls were included. The endogenous thrombin potential (ETP) was determined together with hemostatic variables: fibrinogen, D-dimers, factor VIII (FVIII), tissue factor pathway inhibitor (TFPI), protein C, and free protein S.

Results: Thirty-one patients were included. In 27 patients not taking anticoagulants, ETP was measured and found to be elevated: 137.1% as compared to a median of 90.0% for healthy controls (p < 0.01). Fibrinogen and D-dimer levels were not elevated in patients (median 3.5 g/l and 279 μg/l, respectively). FVIII and TFPI levels were also significantly increased in patients as compared to healthy controls (159% vs 137%; 122.5% vs 101%, respectively), whereas protein C and free protein S levels were not elevated (126.5% vs 118.6% and 124.6% vs 118.3%, respectively).

Conclusion: Patients with AAV in remission are more procoagulant than healthy controls, as indicated by an increased ETP. The increased FVIII level measured in these patients suggests persistence of endothelial activation and/or dysfunction. This endothelial dysfunction may cause a continuous low-grade procoagulant state.

Keywords: ANCA ASSOCIATED VASCULITIS; ENDOGENOUS THROMBIN POTENTIAL; THROMBOSIS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / epidemiology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology*
  • Antibodies, Antineutrophil Cytoplasmic / blood
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Factor VIII / immunology
  • Factor VIII / metabolism
  • Female
  • Fibrin Fibrinogen Degradation Products / immunology
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinogen / immunology
  • Fibrinogen / metabolism
  • Follow-Up Studies
  • Humans
  • Lipoproteins / immunology
  • Lipoproteins / metabolism
  • Male
  • Middle Aged
  • Protein C / immunology
  • Protein C / metabolism
  • Protein S / immunology
  • Protein S / metabolism
  • Remission Induction
  • Risk Factors
  • Thrombin / immunology
  • Thrombin / metabolism
  • Thrombophilia / blood
  • Thrombophilia / epidemiology
  • Thrombophilia / immunology*
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / immunology*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Fibrin Fibrinogen Degradation Products
  • Lipoproteins
  • Protein C
  • Protein S
  • fibrin fragment D
  • lipoprotein-associated coagulation inhibitor
  • F8 protein, human
  • Factor VIII
  • Fibrinogen
  • Thrombin