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

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. β ₂ -glycoprotein I (β ₂ -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 β ₂ -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.
Competing Interests: SH, RL-K, MN, and BL are employees of Synapse Research Institute, part of Diagnostica SAS. BL is an employee of Diagnostica Stago. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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