title: A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction.
abstract: The patients with inherited bleeding diathesis related to quantitative, structural, and/or functional abnormalities of von Willebrand factor (vWF) are said to have von Willebrand's disease (vWD). We report here the clinical and laboratory features of a 50-year-old woman with a life-long history of excessive bleeding. Her particular laboratory data are factor VIII (FVIII) deficiency, subnormal bleeding time, and the presence of all plasma and platelet vWF multimers in normal amounts. Infused with FVIII/vWF concentrate, she showed a persistent increase in FVIII that led us to discard hemophilia A carrier or "acquired hemophilia" diagnoses. vWF devoid of FVIII purified from normal and patient's plasma by immunoaffinity on anti-vWF monoclonal antibody (MoAb) was immobilized onto polystyrene tubes that were further incubated with purified normal FVIII. The bound FVIII was evidenced using radiolabeled anti-FVIII MoAb. The data showed that the patient's vWF, in contrast to vWF purified from normal plasma, was unable to bind FVIII. Furthermore, no inhibitor of FVIII/vWF interaction was evidenced in incubating purified normal vWF with the patient's plasma before the addition of FVIII and anti-FVIII MoAb. These results support the concept that the bleeding diathesis of this patient appears to be due mainly to her abnormal vWF preventing FVIII/vWF interaction. This abnormality, which is not yet described in present classification of vWD, could be considered as a new variant of vWD.
authors.affiliation: Centre Régional de Transfusion Sanguine, CRTS, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Mazurier
authors.forename: J
authors.initials: J
authors.lastname: Dieval
authors.forename: S
authors.initials: S
authors.lastname: Jorieux
authors.forename: J
authors.initials: J
authors.lastname: Delobel
authors.forename: M
authors.initials: M
authors.lastname: Goudemand
mesh_terms: D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008875:Middle Aged; D011485:Protein Binding; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D014841:von Willebrand Factor; D005169:Factor VIII