Abstract

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 μmol/L, IC₅₀=0.005–0.027 μmol/L) and the least efficient was RGDS (IC₂₀₀=875–1100 μmol/L, IC₅₀=124–377 μmol/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.

Clin Chem Lab Med 2007;45:1542–8.