Interpreting high levels of unfolded Von Willebrand Factor in patients with the antiphospholipid syndrome

Abstract

Introduction: Unfolded Von Willebrand Factor (VWF) is increased in thrombotic pathologies such as myocardial infarction. Unfolded VWF mediates the binding of platelets without the need for collagen. β₂-glycoprotein I (β₂-GPI) is a natural inhibitor of the platelet-VWF interaction. The antiphospholipid syndrome (APS) is associated with thrombosis, with an important pathophysiological role of auto-antibodies directed against β₂-GPI.

Methods: (Unfolded) VWF levels were studied in normal controls (n=93), APS patients (n=64), non-APS thrombosis patients (n=39) and non-APS auto-immune disease (AID) patients (n=49.

Results: Unfolded VWF levels were respectively, 53%, 50% and 36% higher in APS patients, non-APS thrombosis patients and AID patients, compared to normal controls (p<0.0001). Unfolded VWF levels above the 90^th percentile in normal controls were associated with an odds of APS (OR: 8.51; CI:3.26 - 22.2; p<0.001), compared to ORs of non-APS thrombosis (OR:5.87; CI:2.07 - 16.7, p=0.001) and AID (OR:3.71; CI:1.40 - 9.87; p=0.009).

Discussion: We found that APS patients have high levels of unfolded VWF in their circulation. In APS, auto-antibodies against-β2-GPI may interfere with the β2-GPI-mediated inhibition of VWF-platelet interaction. Therefore, the higher unfolded VWF levels in APS could in part explain the association of APS and thrombotic complications.

Keywords: VWF pro-peptide; Von Willbrand Factor; antiphospholipid syndrome; thrombosis; unfolded VWF.