MULTIMERIC STRUCTURE OF FACTOR-VIII-VON WILLEBRAND FACTOR IN VON WILLEBRANDS DISEASE

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 95  (4) , 590-602
Abstract
Recent studies have provided substantial evidence that F VIII/vWF [factor VIII/von Willebrand factor] exists not only as a polymer of .apprx. 1 .times. 106 MW composed of 230,000 MW subunits but is further organized into a multimeric series (1 to 20 .times. 106 MW). With an immunologic technique to isolate F VIII/vWF directly from small volumes of plasma of patients with vWD [von Willebrand''s disease], relative distribution and concentration of individual multimeric sets was examined by agarose gel electrophoresis in the presence of SDS [sodium dodecyl sulfate]. In classical vWD (type I) with decreased VIIIR:RCo [ristocetin cofactor activity], 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 and 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 2 major types of vWD: reduced synthesis in type I and polymerization defect with resultant lack of VIIIR:RCo in type II.