EFFECTS OF DDAVP INFUSION ON FVIII/vWF IN THREE CASES OF ACQUIRED TYPE II VON WILLEBRAND'S DISEASE

The response to a single intravenous infusion of DDAVP (0.4 μg/kg) was studied in 3 patients with acquired type II von Willebrand's disease associated with monoclonal gammopathy (2 cases) or chronic lymphocytic leukaemia (1 case). The Simplate bleeding time (BT) was prolonged to 10-26 min, FVIII:C, vWF:Ag (ELISA) and vWF:RiCof activities were respectively decreased to 0.15-0.48, 0.18-0.30 and 0.06-0.48 U/ml. Circulating inhibitor to FVIII/vWF were demonstrated in the 3 cases. Plasma vWF multimeric analysis was performed by SDS-agarose, electrophoresis and densitometric patterns were recorded. In that way, each well-separated multimeric unit can be expressed as a percentage of the total area under the curve representing the total vWF. Whereas the large (slower-moving) multimers (numbered 6 and more) represented 52.8-63.2 % of the total vWF in normal plasma (n = 9), they could account only for 12.5-28.7 % of the total vWF in the patients' plasma. In addition, a progressive decrease in the relative intensity of the multimers as their size increased, in a similar manner as is seen in type lie vWD, was demonstrated. The triplet structure seen in normal plasma was undetectable in 2 patients but present in the 3rd one.

Following infusion of DDAVP, the prolonged BT was normalized for 2 hr in 2 patients and transiently shortened in the 3rd one. FVIII:C, vWF:Ag and vWF:RiCof activities were increased to normal levels and remained higher than 0.5 U/ml for respectively 4-24 hr, 3-13 hr and 2-4.5 hr. The multimeric pattern could be considered as completely normalized in 2 patients and greatly improved in the 3rd one. The triplet structure was apparent in the 3 cases. The vWF multimeric structure returned to the preinfusion pattern by 5 hr in 2 patients and approximately 10 hr in the last one. These results demonstrate that endothelial cells from these patients are able to synthesize and release vWF with a full complement of multimers. Furthermore they show that the loss of the larger vWF multimers occurs after vWF has been released into the circulation.