Limited usefulness of the PFA-100™ for the monitoring of ADP receptor antagonists–in vitro experience

Abstract

We have evaluated the usefulness of the PFA-100™ system (collagen/ADP and collagen/epinephrine cartridges) to assess the in vitro effects of a few platelet function inhibitors: Aspisol^® (60 μg/ml), 4-[4-[4-(aminoiminomethyl]-1-piperazinyl]-1-piperidineactetic acid, hydrochloride trihydrate (GR144053F, fibrinogen receptor antagonist, 100 nM), adenosine-3′,5′-diphosphate (A3P5P, P2Y₁ ADP receptor antagonist, 500 μM) and Bis[(adenosine-5′-O-phosphorodithioyl) methylene]-phosphinic acid (APTMPA, P2Y₁₂ ADP receptor antagonist, 500 μM) on platelet function, as compared with the other commonly used diagnostic technique, a whole blood electrical aggregometry (20 μM ADP-or 0.5 mM arachidonic acid). The in vitro studies were carried out on a group of 38 subjects. Whereas all the examined platelet antagonists and inhibitors almost completely blocked the 20 mM ADP-or 0.5 mM arachidonic acid-induced (in the case of acetylsalicylic acid) whole blood aggregation, only two inhibitors (Aspisol^® and GR144053F) remained effective in a significant prolongation of the PFA-100™ occlusion time. Otherwise, using the PFA-100™ system we were not able to detect the inhibitory actions of ADP receptor antagonists–P2Y₁ and P2Y₁₂. Our findings point to a limited usefulness of the PFA-100™ system for the monitoring of the effectiveness of ADP receptor antagonists. The outcomes of this study show that platelet aggregometry in whole blood is characterised by the highest sensitivity in the monitoring of the investigated blood platelet inhibitors.