[Increased von Willebrand activity of low molecular-weight factor VIII following binding to gold granules]

High molecular weight factor VIII was partially reduced with beta-mercaptoethanol. Disulfide reduction resulted in progressive dissociation of the multimeric protein with a concomitant decrease in von Willebrand activity. The binding of reduced small factor VIII oligomers to gold particles with an average diameter of 20--25 nm led to marked "activation" of their von Willebrand activity. A similar increase in activity was also observed following adsorption of native small molecular weight forms of factor VIII to gold granules. Binding of initially highly active high molecular weight factor VIII to gold granules resulted in inhibition of von Willebrand activity, probably by formation of superaggregates. The platelet aggregating function of factor VIII in the circulation appears to depend largely on the size of this multimeric protein, which must be in the range of several millions for its maximum expression.