INVIVO EXPERIMENTS INDICATE THAT RELATIVELY HIGH PLATELET DEPOSITION IN VONWILLEBRANDS DISEASE VICENZA IS CAUSED BY NORMAL PLATELET-VWF LEVELS RATHER THAN BY HIGH VWF-MULTIMERS IN PLASMA

Von Willebrand's disease (vWD) 'Vicenza' is characterized by low plasma von Willebrand Factor antigen (vWF:Ag) and very low levels of Ristocetin Cofactor activity (RiCof). The hemorrhagic tendency in vWD 'Vicenza' is, however, mild and bleeding times in this rare vWD-subtype are only slightly prolonged(1). Larger than normal multimers of plasma-vWF and normal levels of platelet-vWF have both been suggested to compensate the defects that are normally present in vWD. To elucidate the mechanisms involved, whole blood of four patients with vWD 'Vicenza' was circulated through a rectangular perfusion chamber(2) with fibrillar collagen as adhesive surface. Under these conditions, both plasma and platelet vWF participate to platelet adhesion. Compared to perfusion results with blood of normal donors, platelet adhesion of 'Vicenza' patients was decreased. However, the Vicenza defect was less than was observed in parallel experiments with blood of vWD type 1 subtype platelet-low patients and blood of a severe vWD patient. Adhesion was not increased in perfusions with only plasma of the 'Vicenza' vWD - patients. Equal vWF:Ag concentrations of normal multimeric composition were just as effective as the high multimeric 'Vicenza' vWF. Therefore, the abnormal plasma-vWF in 'Vicenza' patients does not cause the relatively high adhesion obtained with whole blood. In contrast, platelets of vWD 'Vicenza' patients resuspended in human albumin solution (HAS) showed far better adhesion than (vWF-poor) platelets of a patient with severe vWD. The values were at least comparable and tended to be higher than those obtained with normal platelets or with platelets of patients with vWD type I subtype platelet normal. From these experiments, we conclude that in patients with vWD' Vicenza', normal levels of platelet-vWF largely compensate the adhesion defect which is expected from the low vWF:Ag levels in their plasma. Platelet-vWF in vWD-'Vicenza' as well as in vWD type I subtype platelet normal, strongly supports adhesion and is likely to explain the mild bleeding disorder of these patients. The additional presence of high multimeric vWF forms in the 'Vicenza' plasma does not increase adhesion at collagen.