Nature of von Willebrand factor: a new assay and a specific inhibitor.

Platelet-active "von Willebrand factor" is a poorly characterized activity of a plasma-protein macromolecular complex. A new simple assay for von Willebrand factor is based on the dose response relation of the factor and the ristocetin platelet aggregation time. This assay uses the "snowstorm" macroscopic endpoint. A multiply transfused subject with von Willebrand's disease was observed to have a circulating inhibitor that blocks normal ristocetin aggregation of platelets, but not ADP-, epinephrine-, or collagen-induced aggregation. The inhibitor was not adsorbed by normal platelets, and was stable to heating at 56 degrees for 30 min and to repeated freezings and thawings. This inhibitor also prevents action on human platelets by platelet-aggregating factor of bovine plasma, indicating this bovine factor activity is a function of von Willebrand factor. Three inhibitors were compared: (1) the von Willebrand factor inhibitor specifically blocked von Willebrand factor activity, (2) a human antibody from a hemophiliac inhibited only antihemophilic factor activity, and (3) a rabbit antiserum to a preparation of human antihemophilic factor inhibited both activities. The active site for von Willebrand factor on the macromolecular complex appears to be spaced some distance from the antihemophilic factor site.