title: Utility of PFA-100 closure time vs. optical aggregometry in assessing the efficacy of platelet membrane glycoprotein IIb/IIIa antagonists in vitro.
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 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.
authors.affiliation: Department of Vascular Diseases, University Medical Centre, Ljubljana, Slovenia. mojca.stegnar@kclj.si
authors.forename: Mojca
authors.initials: M
authors.lastname: Stegnar
authors.forename: Mojca
authors.initials: M
authors.lastname: Bozic
authors.forename: Marija Sollner
authors.initials: MS
authors.lastname: Dolenc
authors.forename: Petra Stefanic
authors.initials: PS
authors.lastname: Anderluh
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
mesh_terms: D000328:Adult; D019411:Clinical Laboratory Techniques; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex