RAPID AND SIMPLE PLATELET-FUNCTION ASSAY TO ASSESS GLYCOPROTEIN IIB IIIA RECEPTOR BLOCKADE/

Background The platelet glycoprotein (GP) IIb/IIIa receptor antagonist c7E3 Fab (abciximab; ReoPro) has been approved as an antithrombotic a gent, and other GP IIb/IIIa antagonists, including oral agents, are un der development. At present, there are no rapid and simple assays to m onitor GP IIb/IIIa receptor blockade. Methods and Results An assay was devised based on the ability of platelets in whole blood to rapidly a gglutinate fibrinogen-coated beads when stimulated with a peptide, (is o-S)FLLRN, that activates a platelet thrombin receptor but resists ina ctivation by plasma aminopeptidase M. Preincubation of normal blood wi th increasing concentrations of c7E3 Fab led to increasing inhibition of the assay, correlating with increased GP IIb/IIIa receptor blockade . Assay conditions wore chosen so that agglutination was inhibited at 2 minutes when >82% of the receptors were blocked. Similar results wer e obtained with the use of GP IIb/IIIa antagonists based on the argini nine-glycine-aspartic acid (RGD) cell-recognition sequence. Conclusion s A simple and rapid assay sensitive to GP IIb/IIIa receptor blockade has been developed that may be helpful in optimizing GP IIb/IIIa antag onist therapy.