Etiology underlying reduced α(2-6)-linked sialylation in patients with low VWF. (A-B) To investigate the pathophysiology involved in the reduction in α(2-6)-linked sialylation on VWF in low-VWF patients. (A) Two subsets of low-VWF patients were defined with highest (blue) and lowest (red) levels of SNA binding (sialic acids) to VWF (n = 13-14 in each group). (B) Plasma neuraminidase activity was not significantly different between the 2 subgroups (ns = not significant). (C-D) To study endothelial cell sialylation of VWF in patients with low VWF, samples were collected from a subgroup (n = 23) of LoVIC patients immediately before and 1 hour after DDAVP administration. (C) All patients demonstrated significantly increased plasma VWF:Ag levels post-DDAVP (median, 61.2 vs 174.2 IU/dL; ***P < .001). (D) SNA binding to VWF secreted after DDAVP was significantly elevated compared with circulating steady-state plasma VWF (median, 87.3% vs 103.3%; **P < .01).