The rationale for monitoring platelet inhibition by
thienopyridines for the identification of patients at risk for future recurrent arterial
thrombosis or ischemic events is intensively discussed, as well as which monitoring systems are appropriate, robust and reliable. Flow cytometric measurement of phosphorylated VASP (
vasodilator-stimulated phosphoprotein), expressed as platelet reactivity index (PRI), is presently "the gold standard method" for evaluating P2Y(12) receptor inhibition. The PFA-100 system, a commercially available and clinically widely used platelet test system, is based on a different principle, not that of VASP phosphorylation. The aim of the present study was to compare the two methods and evaluate whether the conventional PFA-100
collagen/
ADP cartridge could be pharmacologically improved to enable its routine clinical use for detection of platelet P2Y(12) receptor inhibition. The effects of increasing concentrations of the competitive P2Y(12) receptor antagonist
cangrelor (AR-C69931MX) and the time-dependent effects of a single oral loading dose of
clopidogrel (600 mg) were analysed with human whole blood. P2Y(12) receptor inhibition was measured by the VASP/PRI assay and the PFA-100
collagen/
ADP cartridge system, with and without preincubation with the
prostacyclin analog
iloprost (Ilomedin). In vitro addition of
iloprost (0.5 nM) enabled PFA-100
collagen/
ADP cartridge system detection of P2Y(12) receptor inhibition in whole blood by
cangrelor in vitro or by
clopidogrel treatment of volunteers. The addition of a
prostacyclin analog facilitates PFA-100
collagen/
ADP system detection of P2Y(12) receptor inhibition, achieving a sensitivity similar to that of the VASP/PRI reference method. Future studies should now evaluate whether this modified PFA-100 system, like the VASP assay, is a reliable test system for monitoring P2Y(12) receptor inhibition under clinical conditions.