title: No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors: D J
authors: DJ
authors: Groeneveld
authors: T
authors: T
authors: van Bekkum
authors: K L
authors: KL
authors: Cheung
authors: R J
authors: RJ
authors: Dirven
authors: G
authors: G
authors: Castaman
authors: P H
authors: PH
authors: Reitsma
authors: B
authors: B
authors: van Vlijmen
authors: J
authors: J
authors: Eikenboom
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004338:Drug Combinations; D005169:Factor VIII / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D013997:Time Factors; D056729:von Willebrand Disease, Type 3 / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D014841:von Willebrand Factor / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
chemical_list: D000017:ABO Blood-Group System; D015415:Biomarkers; D004338:Drug Combinations; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: ABO blood-group system; blood group antigens; type 3 VWD; von Willebrand disease; von Willebrand factor