Antibody-Induced von Willebrand’s Disease. Dissociation of Factor VIII Molecular Complex Activities by the Autoantibody

Abstract

Acquired Von Willebrand’s disease is reported in a 16 year old girl with systemic lupus erythematosus. Routine coagulation studies showed a normal platelet count, prolonged bleeding time and abnormal glass bead retention. Factor VIII molecular complex respective activities were 8% for VIIIAHF and undetectable for VIIIVWF (Ristocetin aggregation of washed platelets) and VIIIAGN (electro-immunodiffusion).In vitro, the patient’s plasma exhibited an inhibitory activity against exogenous VIIIAGN and VIIIywF but did not neutralize VIIIAHF activity of control plasma, even after a 2 hour incubation at 37°C. This inhibitory activity was supported by the purified plasma IgG fraction. In vivo, following cryoprecipitate administration (20U. VIIIAHF/kg), only 50% of the infused VIIIAHF activity was recovered after 15 mn and the original level was reached 4 hours later. It was only observed a transient peak of VIIIVWF activity and VIIIAGN level did not increase at all after the infusion.After the start of immuno depressive therapy the three factor VIII related activities returned to normal level in the following order : VIIIAHF and VIIIVWF (9-12 days); VIIIAGN (3 weeks).These findings could be explained by the formation of a short-living cirulating immune complex between the antibody and the factor VIII molecular complex. In such an hypothesis the auto-antibody would respect the site of VIIIAHF activity and would mask the site reacting with anti VIIIAGN hetero antibodies.