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

  • Dominique Meyer
    Correspondence
    Reprint requests: Dominique Meyer, M.D., Department of Molecular Immunology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Rd., La Jolla, Calif. 92037.
    Affiliations
    From the Institut de Pathologie Cellulaire (INSERM U. 143), Hôpital de Bicêtre, Paris, France

    From the Research Institute of Scripps Clinic, La Jolla, Calif., USA
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  • Bernadette Obert
    Affiliations
    From the Institut de Pathologie Cellulaire (INSERM U. 143), Hôpital de Bicêtre, Paris, France

    From the Research Institute of Scripps Clinic, La Jolla, Calif., USA
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  • Genevieve Pietu
    Affiliations
    From the Institut de Pathologie Cellulaire (INSERM U. 143), Hôpital de Bicêtre, Paris, France

    From the Research Institute of Scripps Clinic, La Jolla, Calif., USA
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  • J.Maurice Lavergne
    Affiliations
    From the Institut de Pathologie Cellulaire (INSERM U. 143), Hôpital de Bicêtre, Paris, France

    From the Research Institute of Scripps Clinic, La Jolla, Calif., USA
    Search for articles by this author
  • Theodore S. Zimmerman
    Affiliations
    From the Institut de Pathologie Cellulaire (INSERM U. 143), Hôpital de Bicêtre, Paris, France

    From the Research Institute of Scripps Clinic, La Jolla, Calif., USA
    Search for articles by this author
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      Abstract

      Recent studies have provided substantial evidence that F.VIII/vWF exists not only as a polymer of ~ 1 × 106 MW composed of 230,000 MW subunits but is further organized into a multimeric series (1 to 20 × 106 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.

      Abbreviations:

      molecular weight (MW), factor VIII/von Willebrand factor (F.VIII/vWF), factor VIII procoagulant activity (VIII:C), ristocetin cofactor activity (VIIIR:RCo), factor VIII-related antigen (VIIIR:Ag), von Willebrand's disease (vWD), immunoglobulin G (IgG), sodium dodecyl sulfate (SDS), phenylmethylsulfonylfluoride (PMSF), immunoradiometric assay (IRMA), phosphate saline buffer (PBS), immunoglobulin M (IgM), counterimmunoelectrophoresis (CIE), void volume (Vo)
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