von Willebrand factor: evidence for variable clearance in vivo according to Y/C1584 phenotype and ABO blood group

Abstract

Background: The plasma von Willebrand factor (VWF) level (VWF:Ag) is known to correlate with the VWF Y/C1584 variation and with ABO blood group. The ratio of the VWF propeptide (VWFpp) to VWF:Ag and the ratio of coagulation factor VIII (FVIII:C) to VWF:Ag have previously been used as indicators of VWF clearance and/or secretion.

Objectives and methods: To investigate the mechanism underlying the relationship between VWF phenotype and VWF:Ag, the VWFpp/VWF:Ag ratio and FVIII:C/VWF:Ag ratio were determined for plasmas of phenotype Y/C1584, Y/Y1584, blood group O and blood group A (n = 50 for each set). The blood group O plasmas comprised two sets of 25 with low and high mean VWF levels (Low-O and High-O), respectively; similarly for group A (Low-A and High-A).

Results and conclusions: The VWFpp/VWF:Ag ratio was greater than 1 (unity) for Y/C1584 plasmas and significantly higher than for Y/Y1584 plasmas; however, the FVIII:C/VWF:Ag ratio was near unity for both and was not significantly different. These results are consistent with increased clearance for Y/C1584 VWF. Similarly, the VWFpp/VWF:Ag ratio and FVIII:C/VWF:Ag ratio in combination were consistent with increased VWF clearance in blood group O compared with blood group A, and in Low-O and Low-A, respectively, compared with High-O and High-A. The data indicate that in vivo C1584 and blood group O are associated with increased VWF clearance, and that clearance contributes to differing VWF level within a given blood group.