COMPARATIVE-STUDIES ON THE ANTIPLATELET EFFECTS OF A HUMANIZED ANTIPLATELET GLYCOPROTEIN IIB IIIA ANTIBODY (YM337) AND REOPRO UNDER FLOW CONDITIONS/

Recent clinical studies have shown that the interruption of platelet f unction appears to be effective for treatment of coronary occlusive di seases. For this purpose, a Fab fragment of humanized anti-platelet gl ycoprotein (GP) IIb/IIIa monoclonal antibody (YM 337) that exhibited a n in vivo antithrombotic effect without prolongation of bleeding time in monkeys was previously characterized. In this study, the effect of YM 337 under physiological flow conditions with high or low shear rate was evaluated. The antiplatelet effects of YM 337 under varying wall shear rates were examined with the whole blood flow system. This techn ique allows real time visualization of the formation of fluorescence-l abeled platelet thrombi on a collagen surface in a parallel plate flow chamber mounted on an epifluorescence microscope. The process of thro mbus growth was also recorded in video tape and subjected to computer- assisted image analysis. We found that YM 337 displayed a high shear-p referential antiplatelet effect, while ReoPro, a control anti-GP IIb/I IIa antibody, did not show such shear dependency, The present findings therefore suggest that YM 337 might be a useful antiplatelet agent wh ich can block pathological thrombotic events occurring under high shea r, such as in coronary occlusive diseases.