Binding of quinine- and quinidine-dependent drug antibodies to platelets is mediated by the Fab domain of the immunoglobulin G and is not Fc dependent.

The antibody domain controlling reactions between platelet membranes and drug-dependent (dd) antibodies from patients with thrombocytopenia induced by cinchona alkaloids was studied using F(ab')2, Fab, and Fc fragments made from purified dd-IgG. By direct binding radioimmunoassay (RIA) measurements, 20,000 to 50,000 antibody molecules bound per platelet equivalent of purified platelet membranes at apparent saturation with three different antibodies. F(ab')2 and Fab fragments bound to platelet membranes drug dependently but Fc fragments did not. The ability of dd-IgG fragments to compete with intact IgG was quantitatively measured by RIA and by complement fixation. F(ab')2 and Fab competed with intact IgG at an 8:1 and greater than 50:1 molar ratio, respectively, in RIA, and at a 1.6-3:1 and 44-75:1 ratio, respectively, by complement fixation assays. Fc did not compete with IgG in either assay. We conclude that the Fab domain supports attachment of dd antibody to the platelet surface.