Von Willebrand factor: gene dosage relationships and transfusion response in bleeder swine--a new bioassay.
Aggregation of human platelets by bovine plasma was recently recognized as a marker for the study of the antihemophilic and von Willebrand factors. A similar marker in porcine plasma is shown to be specific for the platelet-active von Willebrand factor of plasma, but not for the antihemophilic factor (factor VIII). A new quantitative assay for the von Willebrand factor is based on the dose-response relationship observed between the concentration of von Willebrand factor and platelet aggregation times determined macroscopically. Bleeder swine, homozygous for von Willebrand disease, had no detectable platelet aggregating activity, while heterozygotes, carriers of the disease, had reduced levels of approximately 50% of normal. Exact detection of non-obligate carriers, hitherto impossible, becomes readily feasible because of the gene dosage relationship to the von Willebrand factor plasma levels. Transfusion of bleeder swine with normal plasma results in an immediate post-transfusion rise of the von Willebrand factor, followed by a rapid falloff. At 24 hr post-transfusion, no von Willebrand factor is detectable at a time when the factor VIII response is at its maximum. The discordance in plasma levels of this platelet-active von Willebrand factor and factor VIII in carrier animals and in the bleeder animals after transfusion suggests a different molecular and genetic basis for these two biological activities.