Antibody induced von Willebrand's disease: a newly defined inhibitor syndrome

Abstract

A patient is described with clinical and laboratory evidence of von Willebrand's disease (VWD) in association with lymphosarcoma. He consistently had a bleeding time of over 20 min; factor VIII coagulant activity (VIII(AHF)), factor VIII antigen (VIII(AGN), and von Willebrand factor (VIII(VWF) under 20%; and severe, diffuse hemorrhage. Following transfusion with cryoprecipitate, the patient had the expected rise in VIII(AGN) and VIII(AHF), but no secondary increment in VIII(AHF). The patient's plasma contained an inhibitor which prevented aggregation of normal platelets by ristocetin, but which did not interfere with the measurement of VIII(AGN) or inactivate VIII(AHF) activity. The inhibitor was present in serum heated at 56°C for 60 min, was present in a purified IgG fraction of serum, and was precipitated by anti human IgG. The antibody did not interact directly with washed platelets, but appeared to interact with that portion of the factor VIII protein that supports ristocetin aggregation (VIII(VWF)). The data provide the first explanation for the pathophysiology of the acquired von Willebrand's syndrome.