Characterization of a new mode of defective ristocetin-induced platelet aggregation.

A patient with a reduced response to the platelet-aggregating agent ristocetin and a prolonged bleeding time was found to have an abnormally high level of vWf as measured by Laurell immunoelectrophoresis. Characterization of the patient's vWf by disc-gel electrophoresis and crossed immunoelectrophoresis showed it to be indistinguishable from vWf isolated from normal plasma. The specific activity of the purified vWf in supporting RIPA was the same for both patient and normal vWf. The diminished RIPA was therefore not due to decreased levels of vWf or the presence of a modified form of the vWf. The patient's platelet-poor plasma inhibited the ristocetin-induced platelet aggregating activity of normal PRP, indicating the presence of an inhibitor. Fractionation of the plasma by ion-exchange chromatography showed the inhibitory activity to be in the patient's gamma globulin fraction. The gamma globulin was not directed against either the patient's vWf or against the patient's platelets but appeared to interfere with RIPA by binding ristocetin.