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Utility of PFA-100® closure time vs. optical aggregometry in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in vitro
Published/Copyright:
October 31, 2007
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.
Keywords: closure time; glycoprotein IIb/IIIa antagonist; peptidomimetic; platelet aggregation; platelet function analyser
Received: 2007-5-16
Accepted: 2007-7-23
Published Online: 2007-10-31
Published in Print: 2007-11-01
©2007 by Walter de Gruyter Berlin New York
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Keywords for this article
closure time;
glycoprotein IIb/IIIa antagonist;
peptidomimetic;
platelet aggregation;
platelet function analyser
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