Acquired type II von Willebrand's disease: demonstration of a complexed inhibitor of the von Willebrand factor-platelet interaction and response to treatment.

An acquired von Willebrand's disease developed in two patients in association with a monoclonal gammopathy plus a Sjögren's syndrome and a chronic lymphocytic leukaemia (CLL). In both cases a plasma inhibitor to von Willebrand factor (vWf) was suspected and characterized after plasma gel filtration. The inhibitor was shown to be entirely complexed with vWf and was only demonstrated after complex dissociation by heating. The inhibitor was able to inhibit the binding of 125I-vWf to platelets in the presence of ristocetin in both cases and to thrombin-stimulated platelets in one case. In the two patients, the highest molecular weight multimers (HMWM) of vWf were absent when assessed by sodium dodecyl-sulphate agarose plasma electrophoresis. Intravenous infusion of 1-deamino-(8-D-arginine) vasopressin (DDAVP) resulted in the appearance of the HMWM in both cases and of the satellite bands of each multimer subunit which were lacking prior to the infusion in one patient. After transfusion of a VIII/vWf concentrate containing a significant amount of HMWM, there was a rapid plasma clearance of the vWf-related activities and of the HMWM when compared to that seen in a patient with type III constitutional vWD. We conclude that in the two patients studied the coagulation defect was related to the presence of a circulating inhibitor to vWf which could be responsible for the disappearance of the HMWM from plasma.