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THU0278 Increased Platelet Aggregation by Von Willebrand Factor Activity Correlates with anti-dsDNA Antibody Levels and Acute Phase Reactants in Patients with Systemic Lupus Erythematosus
  1. J. Nossent1,2,
  2. W. Raymond2,
  3. G.Ø. Eilertsen1
  1. 1Department of Clinical Medicine, UiT The Artic University of Norway, Tromsø, Norway
  2. 2School of Medicine & Pharmacology, University of Western Australia, Perth, Australia

Abstract

Background Von Willebrand Factor (vWF) typically is released in response to endothelial damage or dysfunction to promote thrombus formation. In Systemic Lupus Erythematosus (SLE) patients vWF protein levels (vWF:Ag) predict cardiovascular events [1], but endothelial dysfunction in SLE is an incompletely understood multifactorial process [2].

Objectives To investigate whether vWF functional activity (VWF:RCo) is related to clinical disease activity, markers of inflammation, vascular risk factors and events in SLE.

Methods A cross sectional study in patients (n=90) that fulfilled ACR classification criteria for SLE and had detailed clinical information and serology collected at an extended outpatient visit. VWF functional activity was determined by ristocetin induced platelet aggregation (vWF:RCo), while vWF protein level was measured by turbidimetric assay (vWF:Ag). Variables included in this study were: SLEDAI2K; SLICC-DI; immunosuppressive drug usage (n=33); anticoagulant therapy (n=33); antiphospholipid antibody status (aPL) and syndrome (APS) and levels for anti-dsDNA Ab, B-cell activating factor (BAFF), IL-6 and TNFα, acute phase reactants and plasma Factor VIII [3, 4].

Results Platelet aggregation by vWF was significantly higher in SLE patients compared to healthy controls (n=10) (median vWF:RCo, 123% vs 78%, p=0.004) as were vWF:Ag levels (142% vs 107%, p=0.001). VWF:RCo correlated with levels of ESR (Rs 0.332, p=0.01), anti-dsDNA Ab (Rs 0.26, p=0.02), LDH (Rs 0.26, p=0.016), ceruloplasmin (Rs 0.367, p<0.01), C1-inhibitor (Rs 0.24, p=0.02), total cholesterol (Rs 0.23, p=0.03) and correlated inversely to transferrin (Rs -.317, p<0.01). VWF:RCo levels were unrelated to SLEDAI2K, CRP and IL-6 or TNFα levels and were not significantly different in patients with a previous cardiovascular event, vasculitis, antiphospholipid Ab, or in current smokers.

Conclusions The association between vWF dependent platelet aggregation, acute phase proteins and increased anti-dsDNA antibody levels suggest that anti-dsDNA Ab mediated inflammation contributes to endothelial dysfunction in SLE.

  1. Curiel RV, et al. Von Willebrand factor, red cell fragmentation, and disease activity in systemic lupus erythematosus. HSS journal: The Musculoskeletal Journal of Hospital for Special Surgery 2008;4:170–4

  2. de Leeuw K, et al. Traditional and non-traditional risk factors contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus. Lupus 2006;15:675–82

  3. Ibanez D, Gladman D & Urowitz M. Summarizing disease features over time: II. Variability measures of SLEDAI-2K. The Journal of Rheumatology 2007;34:336–40

  4. Gladman DD, et al. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for Systemic Lupus Erythematosus International Comparison. The Journal of Rheumatology 2000;27:373–6

Disclosure of Interest None declared

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