PROTEOLYTIC DEGRADATION OF VON WILLEBRAND FACTOR AFTER DDAVP ADMINISTRATION IN NORMAL INDIVIDUALS
The infusion of l-Deamino-8-D-Arginine Vasopressin (DDAVP) in normal individuals is followed by an increase in factor VIII/von Willebrand factor in plasma and by the appearance of larger multimers of von Willebrand factor (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. DDAVP was infused into eight normal adult volunteers and the relative proportions of the intact 225 kDa subunit and the 189, 176 and 140 kDa fragments were compared before and at different times after DDAVP infusion. The relative proportion of the 176 kDa fragment was increased while that of the other species was decreased, 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 suggesting that they were ptoteolytically generated. Proteolysis may explain, at least in part, rapid clearance of larger vWF multimers released by DDAVP.