No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

J Thromb Haemost. 2015 Apr;13(4):592-600. doi: 10.1111/jth.12867. Epub 2015 Mar 11.

Abstract

Background: One of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood group O have ~ 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated.

Objectives: To determine whether clearance of VWF is directly dependent on the presence of ABH antigens on VWF.

Methods: Three type 3 von Willebrand disease (VWD) patients were infused with Haemate-P, and the relative loading of VWF with ABH antigens at different time points was measured. VWF-deficient mice were injected with purified plasma-derived human VWF obtained from donors with either blood group A, blood group B, or blood group O.

Results: In mice, we found no difference in clearance rate between plasma-derived blood group A, blood group B and blood group O VWF. Faster clearance of the blood group O VWF present in Haemate-P infused in type 3 VWD patients would have resulted in a relative increase in the loading of VWF with A and B antigens over time. However, we observed a two-fold decrease in the loading with A and B antigens in two out of three patients, and stable loading in the third patient.

Conclusion: There is no direct effect of ABH antigens on VWF in VWF clearance. We demonstrate that, in a direct comparison within one individual, blood group O VWF is not cleared faster than blood group A or blood group B VWF. Clearance differences between blood group O and non-blood group O individuals may therefore be related to the blood group status of the individual rather than the ABH antigen loading on VWF itself.

Keywords: ABO blood-group system; blood group antigens; type 3 VWD; von Willebrand disease; von Willebrand factor.

Publication types

  • Comparative Study

MeSH terms

  • ABO Blood-Group System / blood*
  • Animals
  • Biomarkers / blood
  • Drug Combinations
  • Factor VIII / administration & dosage
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • Time Factors
  • von Willebrand Disease, Type 3 / blood*
  • von Willebrand Disease, Type 3 / diagnosis
  • von Willebrand Disease, Type 3 / drug therapy
  • von Willebrand Factor / administration & dosage
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism*

Substances

  • ABO Blood-Group System
  • Biomarkers
  • Drug Combinations
  • factor VIII, von Willebrand factor drug combination
  • von Willebrand Factor
  • Factor VIII