Title: Isolation of an Apparently Abnormal Von Willebrand Factor: Comparison with Plasma and Serum Von Willebrand Factor
Abstract: A patient with an extremely high level of von Willebrand factor (8X normal) failed to show any response to ristocetin with her platelet-rich plasma. The patient also had a long bleeding time and a large amount of a paraprotein. Using a washed platelet assay system and dilutions of her platelet-poor plasma, ristocetin-induced platelet aggregation activity could be recovered to 40% of normal. Purification of the von Willebrand factor from the patient’s plasma resulted in an increase in ristocetin-induced platelet aggregating activity associated with the von Willebrand factor. Electrophoretic comparison by SDS disc gel electrophoresis and crossed immunoelectrophoresis showed no differences between this patient’s von Willebrand factor and either purified normal plasma or serum von Willebrand factor. The patient’s plasma, following removal of the von Willebrand factor, inhibited ristocetin-induced platelet aggregation in normal platelet-rich plasma and in a washed platelet system using purified normal von Willebrand factor. These observations indicate the presence of an abnormal plasma protein which binds ristocetin and thereby inhibits platelet aggregation. Furthermore, the abnormal protein must interfere with the in vivo functions of the von Willebrand factor as witnessed by the increased bleeding time presented by the patient. This behavior is explained by a model system in which ristocetin mimics a structural component found in the lining of the vessel walls which is exposed by tissue injury. The abnormal plasma protein competes with the von Willebrand factor and interferes with von Willebrand dependent platelet adhesion. Supported by an NIH Research Career Development Award and the American Heart Association.