Utility of PFA-100((R)) closure time vs. optical aggregometry in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in vitro
Stegnar, Mojca ...
Background: Closure time measured by a platelet function analyser (PFA-100((R))) was examined for its usefulness in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in ...vitro, and was comparedto optical platelet aggregometry. Methods: Three known glycoprotein IIb/IIIa antagonists šH-Arg-Gly-Asp-Ser-OH (RGDS), tirofiban and eptifibatideđand 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 (IC(200)) or decreased ADP- or collagen-induced platelet aggregation by 50% (IC(50)) was used to assess the efficacy of the glycoprotein IIb/IIIa antagonist in inhibiting platelet function. Results: IC(200) for collagen/ADP and collagen/epinephrine closure times and IC(50) 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/IIIaantagonist was tirofiban (IC(200)=0.030-0.034 mumol/L, IC(50)=0.005-0.027 mumol/L) and the least efficient was RGDS (IC(200)=875-1100mumol/L, IC(50)=124-377 mumol/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 numbersof glycoprotein IIb/IIIa antagonists.
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