Acquired von Willebrand's disease caused by a monoclonal antibody.
A 67-year-old man with malignant lymphoma and acquired von Willebrand's disease is described. His bleeding symptoms started late in life and at this time a monoclonal IgGK serum protein was found. He had a prolonged bleeding time, decreased platelet adhesiveness, low values for factor VIII clotting activity (VIII:C), factor VIII related antigen (VIIIR:Ag) and ristocetin co-factor activity (VIII:Rcof). Infusion of factor VIII concentrates (fraction I-0) did not correct the abnormalities. No inhibitory activity in vitro of the patient's plasma or IgG fraction could be demonstrated against VIII:C, VIIIR:Ag and VIII:Rcof. In order to demonstrate an antibody that binds factor VIII without inhibiting its biological activities in vitro, advantage was taken of the fact that staphylococcal protein A strongly binds the Fc part of IgG molecules. Addition of staphylococci to mixtures of patient IgG and a factor VIII preparation resulted in removal of all factor VIII activities (VIII:C, VIIIR:Ag, VIII:Rcof) from the supernatant at sedimentation of the bacteria. The active binding principle was the M-component, i.e. probably a monospecific antibody molecule. We hypothesize that the complex is formed in vivo and eliminated at an accelerated rate.
D000368:Aged; D001666:Binding Sites, Antibody; D001780:Blood Coagulation Tests; D005169:Factor VIII / Q000032:analysis / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G / Q000302:isolation & purification; D008223:Lymphoma / Q000097:blood / Q000150:complications / Q000276:immunology*; D008297:Male; D013205:Staphylococcal Protein A / Q000276:immunology; D013274:Stomach Neoplasms / Q000097:blood / Q000150:complications / Q000276:immunology*; D014842:von Willebrand Diseases / Q000097:blood / Q000209:etiology* / Q000276:immunology
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D005169:Factor VIII