title: Quantification of abciximab-induced platelet inhibition is assay dependent: a comparative study in patients undergoing percutaneous coronary intervention.
abstract: BACKGROUND
  The best method for measuring the degree of platelet inhibition with glycoprotein (GP) IIb-IIIa antagonists during percutaneous coronary intervention (PCI) and the optimal degree of periprocedural inhibition is uncertain. Low molecular weight heparins have been reported to cause less platelet activation than unfractionated heparin. Therefore, compared with unfractionated heparin (UHF), a low molecular weight heparin could enhance measured platelet inhibition. In this study, we compared 3 methods of measuring platelet inhibition and investigated the effects of half doses of abciximab in combination with either UFH or the low molecular weight heparin dalteparin in patients undergoing PCI with planned abciximab administration.
  
  
  METHODS
  Abciximab-induced platelet inhibition was measured serially by means of 3 assays: 1) GP IIb-IIIa receptor occupancy, 2) binding of the activated GP IIb-IIIa-specific monoclonal antibody PAC1, and 3) agglutination of platelets with fibrinogen-coated beads (RPFA). Forty patients were randomly allocated to receive either UFH (70 U/kg) or dalteparin (60 IU/kg), followed by a half dose of abciximab (0.125 mg/kg) administered twice at 10-minute intervals. Assays were obtained 10 minutes after each half dose of abciximab and 8 to 10 and 24 hours after abciximab administration.
  
  
  RESULTS
  No differences between UFH and dalteparin were observed. At each time-point measured, the mean percent platelet inhibition as determined by means of the receptor occupancy assay and PAC1 binding assay was less than the degree of inhibition determined by means of the RPFA.
  
  
  CONCLUSIONS
  The results of targeted levels of platelet inhibition cannot be extrapolated between different clinical trials of GP IIb-IIIa antagonists unless the same assay is used. Dalteparin, compared with UFH, does not enhance platelet inhibition or receptor occupancy by abciximab, as demonstrated by means of 3 separate assays.
authors.affiliation: Center for Platelet Function Studies and Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. mark.furman@umassmed.edu
authors.forename: Mark I
authors.initials: MI
authors.lastname: Furman
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Lori A
authors.initials: LA
authors.lastname: Krueger
authors.forename: Michele N
authors.initials: MN
authors.lastname: Mueller
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Broderick
authors.forename: John F
authors.initials: JF
authors.lastname: Schneider
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Howard
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Fox
authors.forename: Marc R
authors.initials: MR
authors.lastname: Barnard
authors.forename: A L
authors.initials: AL
authors.lastname: Frelinger
authors.forename: Alan D
authors.initials: AD
authors.lastname: Michelson
mesh_terms: D000077284:Abciximab; D000789:Angina, Unstable / Q000097:blood / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology; D017985:Dalteparin / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin; D017985:Dalteparin; D000077284:Abciximab