C7E3 Fab inhibits low shear flow modulated platelet adhesion to endothelium and surface-adsorbed fibrinogen by blocking platelet GP IIb/IIIa as well as endothelial vitronectin receptor - Results from patients with acute myocardial infarction and healthy controls

The c7E3 Fab reduces ischemic complications in patients undergoing high-ris k coronary angioplasty or atherectomy. The present study investigated how c 7E3 Fab inhibition of the platelet receptor glycoprotein IIb/IIIa and the e ndothelial vitronectin receptor affected platelet adhesion to endothelium a nd surface adsorbed fibrinogen under flow conditions. Platelet adhesion was examined using a stagnation point flow device with sh ear stress and shear rates up to 2.2 dynes/cm(2) and 170 s(-1), respectivel y. Ex vivo adhesion was compared between two groups of patients with acute myocardial infarction (AMI) treated with angioplasty and stent implantation and a group of healthy controls. Only one AMI group received c7E3 Fab ther apy. Patients in both groups were administered acetyl salicylic acid (ASA) and heparin. In AMI patients c7E3 Fab reduced platelet adhesion to adsorbed fibrinogen by 79% compared to AMI patients without c7E3 Fab treatment and by 74% compared to healthy controls. Thirty hours after termination of c7E3 Fab infusion adhesion had slightly recovered with an inhibition of 61% and 52% still present, respectively. Additionally, in vitro platelet adhesion to intact endothelium and to adsorbed fibrinogen was measured during superf usion with ADP stimulated platelet rich plasma of healthy controls to which c7E3 Fab was added ata final concentration fc of 20 mu g/ml. In spite of A DP stimulation c7E3 Fab completely blocked platelet adhesion to adsorbed fi brinogen and, moreover, to intact endothelium. Preincubation of endothelial cells with c7E3 (fc = 20 mu g/ml) blocked adhesion of ADP-stimulated plate lets by approximately 50%. Apart from the inhibition of platelet aggregation, c7E3 Fab added in vitro and given therapeutically in patients effectively blocks platelet adhesion to components of the injured as well as intact vessel wall under stagnation point flow conditions.