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

BackgroundOne of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood groupO have similar to 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated. ObjectivesTo determine whether clearance of VWF is directly dependent on the presence of ABH antigens on VWF. MethodsThree type3 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 groupA, blood groupB, or blood groupO. ResultsIn mice, we found no difference in clearance rate between plasma-derived blood groupA, blood groupB and blood groupO VWF. Faster clearance of the blood groupO VWF present in Haemate-P infused in type3 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. ConclusionThere is no direct effect of ABH antigens on VWF in VWF clearance. We demonstrate that, in a direct comparison within one individual, blood groupO VWF is not cleared faster than blood groupA or blood groupB VWF. Clearance differences between blood groupO and non-blood groupO individuals may therefore be related to the blood group status of the individual rather than the ABH antigen loading on VWF itself.