Summary
Recent clinical studies have shown that the interruption of platelet function appears
to be effective for treatment of coronary occlusive diseases. For this purpose, a
Fab fragment of humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody
(YM 337) that exhibited an 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 technique allows real time visualization of the formation
of fluorescence-labeled platelet thrombi on a collagen surface in a parallel plate
flow chamber mounted on an epifluorescence microscope. The process of thrombus growth
was also recorded in video tape and subjected to computer-assisted image analysis.
We found that YM 337 displayed a high shear-preferential antiplatelet effect, while
ReoPro, a control anti-GP IIb/IIIa antibody, did not show such shear dependency. The
present findings therefore suggest that YM 337 might be a useful antiplatelet agent
which can block pathological thrombotic events occurring under high shear, such as
in coronary occlusive diseases.