Multimeric structure of factor VIII/von Willebrand factor in von Willebrand's disease.

Recent studies have provided substantial evidence that F. VIII/vWF exists not only as a polymer of approximately 1 x 10(6) MW composed of 230,000 MW subunits but is further organized into a multimeric series (1 to 20 x 10(6) MW). With an immunologic technique to isolate F.VIII/vWF directly from small volumes of plasma of patients with vWD, the relative distribution and concentration of individual multimeric sets was examined by agarose gel electrophoresis in the presence of SDS. In classical vWD (type I) with decreased VIIIR:RCo, the relative distribution of multimeric forms of FVIII/vWF was comparable to normal plasma but reduced in quantity. In "variants" of vWD (type II) with undetectable VIIIR:RCo, the larger multimer subsets were absent, and the smaller one present in relatively greater concentration. Large multimers as well as VIIIR:RCo were also lacking in F.VIII/vWF prepared from normal plasma cryosupernatant. These observations suggest the existence of different molecular abnormalities of F.VIII/vWF underlying the two major types of vWD: reduced synthesis in type I and polymerization defect with resultant lack of VIIIR:RCo in type II.