Reduced plasma VWF levels in patients with low VWF are due to both decreased VWF synthesis/secretion and subtly enhanced VWF clearance. (A) Plasma FVIII:C levels were significantly reduced in patients with low VWF (n = 126, triangles) compared with normal controls (n = 40, circles) (mean FVIII:C levels 76 IU/dL vs 105 IU/dL; ****P < .0001). (B) FVIII:C/VWF:Ag ratios were significantly increased in LoVIC patients compared with controls (mean ratio 1.3 vs 1.07; ****P < .0001). (C) Plasma VWF:pp levels in LoVIC patients were not significantly different from those in normal controls (mean VWF:pp levels 91.6 U/dL vs 85.4 U/dL; P = .58). (D) VWF:pp/VWF:Ag ratios were significantly increased in LoVIC patients compared with controls (mean ratio 1.42 vs 0.95; **P < .01). Elevated VWF:pp/VWF:Ag ratios >3 (green dotted line) were identified in only 8 patients. Mean values for each group are indicated by a black line. In a subgroup of 40 LoVIC patients, plasma VWF:Ag (E) and VWF:RCo (F) levels were measured at baseline and subsequently repeated at 1 hour and 4 hours following intravenous DDAVP administration.