| Author/Editor | Stegnar, M; Božič, M; Sollner-Dolenc, M; Štefanič-Anderluh, P; Kikelj, D | |
| Title | Utility of PFA-100((R)) closure time vs. optical aggregometry in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in vitro | |
| Type | članek | |
| Source | Clin Chem Lab Med | |
| Vol. and No. | Letnik 45, št. 11 | |
| Publication year | 2007 | |
| Volume | str. 1542-8 | |
| Language | eng | |
| Abstract | 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 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 (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/IIIa antagonist 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)=875-1100 mumol/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 numbers of glycoprotein IIb/IIIa antagonists. | |
| Descriptors | PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX PLATELET AGGREGATION COLLAGEN EPINEPHRINE DOSE-RESPONSE RELATIONSHIP, DRUG |