Proteolytic degradation of von Willebrand factor after DDAVP administration in normal individuals

Abstract

The infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) in normal individuals is followed by an increase in factor VIII/von Willebrand factor (vWF) in plasma, by an increase in intensity of all sizes of multimers, and by the appearance of larger multimers of vWF than those seen in the resting state. Since the larger multimers are rapidly cleared and proteolysis is known to cause disaggregation of large multimers, we evaluated the degree of vWF proteolysis after DDAVP administration. DDAVP was infused into eight normal adult volunteers, and the relative proportions of the intact 225 kilodalton (kDa) subunit and the 189, 176, and 140 kDa vWF fragments were compared before and at different times after DDAVP infusion. The relative proportion of the 176 kDa fragment was increased, whereas that of the other species was decreased, thereby indicating that proteolytic fragmentation had occurred. However, plasmin did not appear to be responsible because the vWF fragments characteristically produced by this enzyme could not be detected. Concomitant analysis of vWF multimeric structure showed that these changes were accompanied by an increase in the relative proportion of the satellite bands, which suggests that they were proteolytically generated. Proteolysis may explain, at least in part, rapid clearance of larger vWF multimers released by DDAVP.

Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity

“…Not only are immediate alterations in circulating VWF apparent, but also the UL‐VWF concatemers continue to circulate 24 hours after admission, suggesting insufficient clearance mechanisms for the degree of injury. This time frame demonstrates a significant difference from past reports investigating clearance mechanisms of endothelial VWF release; namely, that VWF exhibited a return to homeostasis within 4 hours after administration of DDAVP (desmopressin), a vasopressin analog that induces VWF secretion . After injury, this rapid clearance is not seen.…”

Heightened proteolysis of the von Willebrand factor subunit in patients with von Willebrand disease hemizygous or homozygous for the C2362F mutation

“…Proteolytic degradation of plasma VWF occurs physiologically in normal individuals and is enhanced by the administration of desmopressin (Zimmerman et al, 1986;Battle et al, 1987). Proteolysis is heightened in patients with type 2A and 2B VWD, in whom larger VWF multimers are absent in plasma, whereas proteolysis is minimal in other variants (Zimmerman et al, 1986).…”

von Willebrand factor‐collagen binding activity is increased in newborns and infants

“…However, it is of interest that a disproportionate increase in vWF:CBA compared with the corresponding vWF:Ag and vWF:RiCof has been shown recentlyin plasma of adult patients with von Willebrand's disease following infusion of 1 -deamino-8-D-arginine vasopressin (DDAVP) (19). These results suggest that the increased ability of vWF to interact with collagen in normal newborns and after DDAVP infusion may be related to the presence of structurally distinct vWF present in the circulation, as shown by the increased intensity of vWF protomer in newborn plasma, increased intensity of multimer satelite bands in plasma after DDAVP and the presence of the haemostatically highly effective, ultra-large molecular weight vWF multimers (6,10,(20)(21)(22).…”