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.