DIATRIZOATE-CONTAINING CONTRAST-MEDIA INHIBIT PLATELET-AGGREGATION BY DISRUPTING FIBRINOGEN BINDING

Radiopaque contrast media have antiplatelet activities of varying potency. The effect of diatrizoate salts, components of many contrast agents, and of two contrast media (Hypaque-76 [Winthrop Pharmaceuticals] and iopamidol) on the binding of I-125-fibrinogen to activated platelets was examined. Diatrizoate salts inhibited I-125-fibrinogen binding with a 50% inhibitory concentration (IC50) of 12 mg/mL. In agreement with this finding, Hypaque-76 (diatrizoate sodium/meglumine) inhibited binding with an IC50 of 1.7% (vol/vol), equivalent to 12.9 mg/mL diatrizoate salts, lopamidol, which does not contain diatrizoate, was less effective (IC50 = 4.7%). Aggregation was inhibited in parallel with fibrinogen binding. The binding of monoclonal antibodies to glycoprotein IIb/IIa was intact at concentrations that inhibited fibrinogen binding. These findings suggest that fibrinogen itself, rather than expression of its receptor, is the primary target of the inhibition.