Utility of PFA-100® closure time vs. optical aggregometry in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in vitro

BACKGROUND: Closure time measured by a platelet function analyser (PFA-100) was examined for its usefulness in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in vitro, and was compared to optical platelet aggregometry. METHODS: Three known glycoprotein IIb/IIIa antagonists [H-Arg-Gly-Asp-Ser-OH (RGDS), tirofiban and eptifibatide] and six new peptidomimetic glycoprotein IIb/IIIa antagonists (DKT-59, DPS-172, SMA-101, SMA-104, SMA-179 and SKN-191) were assessed. The concentration of antagonist which doubled closure time in collagen/ADP and collagen/epinephrine cartridges (IC200) or decreased ADP- or collagen-induced platelet aggregation by 50% (IC50) was used to assess the efficacy of the glycoprotein IIb/IIIa antagonist in inhibiting platelet function. RESULTS: IC200 for collagen/ADP and collagen/epinephrine closure times and IC50 for ADP- and collagen-induced platelet aggregation were highly associated (correlation coefficients 0.97-1.00, all p<0.001). Therefore, according to both methods, the most efficient glycoprotein IIb/IIIa antagonist was tirofiban (IC200=0.030-0.034 micromol/L, IC50=0.005-0.027 micromol/L) and the least efficient was RGDS (IC200=875-1100 micromol/L, IC50=124-377 micromol/L; all data are means), while the new peptidomimetic glycoprotein IIb/IIIa antagonists exhibited intermediate efficacies. CONCLUSIONS: Closure time represents a fast, simple and sensitive method of assessing glycoprotein IIb/IIIa antagonism in vitro, is comparable to optical aggregometry, and suitable for testing larger numbers of glycoprotein IIb/IIIa antagonists.