Inhibition of Fibrinogen Binding to Platelets by MK-852, a New GPIIb/IIIa Antagonist

Abstract

MK-852 is a newly developed low molecular weight inhibitor of fibrinogen binding to platelets. Platelet aggregation and adhesion of platelets to damaged vessel walls are critical events in haemostasis, and uncontrolled aggregation may cause arterial thrombus formation. Depending on the location of the occluded vessel, this may result in unstable angina, myocardial infarction or stroke. Platelet aggregation requires binding of fibrinogen to the GPIIb/IIIa receptor on the platelet surface. Thus, inhibitors of fibrinogen binding to the receptor may constitute an efficient way of preventing thrombus formation.

We have used flow cytometry and FITC-labelled chicken anti-human fibrinogen antibodies to study the in vitro inhibitory effects of MK-852 on fibrinogen binding to platelets. We show that MK-852 is a very efficient fibrinogen receptor antagonist in vitro. Flow cytometry is well suited for clinical use and may be used to monitor treatment with MK-852 or other fibrinogen receptor antagonists.