Acquired von Willebrand disease caused by an autoantibody selectively inhibiting the binding of von Willebrand factor to collagen

Blood. 1994 Nov 15;84(10):3378-84.

Abstract

An 82-year-old man with a low-grade malignant non-Hodgkin lymphoma and an IgG3 lambda monoclonal gammopathy presented a recently acquired bleeding tendency, characterized by recurrent epistaxis, easy bruising, and episodes of melena, requiring packed red blood cell transfusions. Coagulation studies showed a von Willebrand factor (vWF) defect (Ivy bleeding time, > 15 minutes; vWF antigen [vWF:Ag], 0.08 U/mL; ristocetin cofactor activity [vWF:RCoF], < 0.05 U/mL; collagen binding activity [vWF:CBA], 0.01 U/mL; absence of the high molecular weight multimers of vWF on multimeric analysis). Mixing experiments suggested the presence of an inhibitor directed against the vWF:CBA activity of vWF without significantly inhibiting the FVIII:C, vWF:Ag, and vWF:RCoF activities. The inhibitor was identified as an antibody of the IgM class by immunoabsorption of vWF and inhibitor-vWF complexes from the plasma of the patient. Subsequent immunoprecipitation experiments using recombinant fragments of vWF showed that the inhibitor reacted with both the glycoprotein Ib binding domain (amino acids [aa] 422-826) and the A3 (aa 909-1112) domain of vWF, but not with the A2 (aa 716-908) or D4 (aa 1183-1535) domains. We conclude that the IgM autoantibody inhibits the vWF:CBA activity by reacting with an epitope present on both the glycoprotein Ib and A3 domains of vWF.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autoantibodies / pharmacology
  • Cell Line
  • Collagen / metabolism*
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood*
  • Immunoglobulin G / classification
  • Immunoglobulin M / blood
  • Lymphoma, Non-Hodgkin / blood*
  • Lymphoma, Non-Hodgkin / complications
  • Lymphoma, Non-Hodgkin / immunology
  • Male
  • Paraproteinemias / blood*
  • Paraproteinemias / complications
  • Paraproteinemias / immunology
  • Peptide Fragments / metabolism
  • Protein Binding
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • von Willebrand Diseases / blood
  • von Willebrand Diseases / etiology*
  • von Willebrand Diseases / immunology
  • von Willebrand Factor / biosynthesis
  • von Willebrand Factor / metabolism*

Substances

  • Autoantibodies
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Peptide Fragments
  • Recombinant Proteins
  • von Willebrand Factor
  • Collagen