Pathogenesis of antibody-induced acquired von Willebrand Syndrome

A patient with clinical and laboratory evidence of von Willebrand syndrome is described in association with an IgG-kappa immunoglobulin and Bence-Jones proteinuria due to a probable lymphoproliferative disorder. He had a persistently prolonged bleeding time of greater than 20 minutes, factor VIII related antigen (VIII:R.Ag), factor VIII procoagulant activity (VIII:C) and factor VIII ristocetin co-factor (VIIIR:Rcof) below 10%. Following cryoprecipitate or high purity factor VIII concentrate infusion, he had the expected immediate rise in VIII:C, VIII:R.Ag, and VIIIR:Rcof, but there was a rapid decline in all three components within two hours. The larger forms of VIII:R.Ag were preferentially removed from the plasma, and this paralleled the fall in plasma VIIIR:Rcof level. However, no inhibitory activity could be demonstrated in vitro using the patient's plasma or IgG. Using protein A it was possible to demonstrate that his plasma or IgG bound factor VIII and that this complex retained its biological activity in vitro. It is postulated that the monoclonal IgG forms complexes with factor VIII in vivo and these are rapidly removed by the reticuloendothelial system (RES).