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von Willebrand factor (vWF) consists of a series of multimers of 270,000 mol. wt. subunits. Ristocetin cofactor activity (vWF:RCo) and capacity of binding to platelets of vWF are associated with large multimers, and Type IIA von Willebrand's disease (vWD) is characterized by lack of the large multimers. The significance of multimeric structure in relation to vWF function remains unclear. We obtained a monoclonal antibody (MAb) to human vWF which inhibited ristocetin-induced platelet aggregation. This antibody proved to bind preferentially to larger multimers by the finding that the MAb-conjugated Sepharose adsorbed large multimers of vWF from cryoprecipitates, leaving small multimers unadsorbed. vWF:Ag levels of noraml subjects determined by ELISA using the MAb correlated well with those by ELISA using polyclonal antibody (PAb) to vWF. When the plasma from patients with Type IIA vWD and platelet type vWD were examined, the values obtained by the MAb ELISA had a good correlation with vWF:RCo, but were lower than the values obtained by the PAb ELISA. In gel filtration of factor VIII concentrate, vWF:Ag detected by the MAb and vWF:RCo were present in the void volume and large size fractions, whereas vWF:Ag detectable with PAb appeared broadly from the void volume to smaller size fractions. The MAb inhibited ristocetin-dependent binding of vWF to platelets, but did not affect ADP-induced binding of vWF to platelets. These findings suggest that the large multimers have a function-associated specific structure which is absent in the small multimers, and the MAb will be useful for the investigation of multimer-function relationship of vWF.

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