The RGD cyclic pentapetide, cilengitide, is a selective inhibitor of αvβ3 and 
αvβ5 integrins and was developed for antiangiogenic therapy. Since cilengitide 
interacts with platelet αIIbβ3 and platelets express αv integrins, the effect of 
cilengitide on platelet pro-coagulative response and adhesion is of interest. 
Flow-based adhesion assays were performed to evaluate platelet adhesion and 
rolling on von Willebrand factor (vWf), on fibrinogen and on human umbilical 
vein endothelial cells (HUVECs). Flow cytometry was used to detect platelet 
activation (PAC1) and secretion (CD62P) by cilengitide and light transmission 
aggregometry was used to detect cilengitide-dependent platelet aggregation. 
Cilengitide inhibited platelet adhesion to fibrinogen at concentrations above 
250 µM [which is the Cmax in human studies] and adhesion to vWf and HUVECs at 
higher concentrations under physiologic flow conditions. Platelet aggregation 
was already impaired at cilengitide concentrations >10 µM. Activation of αIIbβ3 
integrin was inhibited by 250 µM cilengitide, whereas platelet secretion was 
unaffected by cilengitide. No evidence of cilengitide-induced platelet 
activation was found at all tested concentrations (0.01-1500 µM). At higher 
concentrations, platelet activation was inhibited, predominantly due to αIIbβ3 
inhibition.