Glycan structures at N1515 and N1574 in the A2 domain influence LRP1-mediated clearance. Recent studies have shown that macrophage LRP1 plays an important role in regulating in vivo clearance of VWF. Moreover, RAP prolongs VWF survival in vivo predominantly by inhibiting this macrophage LRP1 mediated clearance. To investigate whether the effect of VWF glycans on macrophage-mediated clearance were modulated via LRP1, clearance studies for wild type rVWF and glycan variants N1515Q and N1574Q were repeated in VWF^−/− mice in the presence or absence of the LRP1 antagonist RAP. Blood was collected at 3 and 10 minutes after injection, and data are graphed as percentage residual VWF relative to the amount injected (*P < .05, **P < .01, and ***P < .001; ns, not significant).