title: Differential inhibitory effects of platelet glycoprotein IIb/IIIa antagonists on aggregation induced by procoagulant agonists.
abstract: BACKGROUND
  In addition to mediating the final common pathway of aggregation, the glycoprotein (GP) IIb/IIIa receptor participates in the activation of coagulation on the platelet surface. High-affinity conformation of GP IIb/IIIa in response to collagen-induced inside-out signalling seems to be mediated by GP VI(-FcRgamma) and reinforced by release of soluble mediators.
  
  
  METHODS
  We assessed the effects of the three currently available GP IIb/IIIa antagonists--abciximab, tirofiban and eptifibatide--on platelet aggregation induced by various procoagulant and GP VI-related agonists, i.e. collagen-related peptide (CRP), convulxin and collagen fibrils, in PPACK-anticoagulated platelet-rich plasma.
  
  
  RESULTS
  At concentrations that equally inhibited 80% of ADP-induced maximal aggregation abciximab-inhibited GP VI-mediated platelet responses to CRP or convulxin significantly more than the low-molecular-weight antagonists (CRP: abciximab 75+/-18%, tirofiban 41+/-7% and eptifibatide 41+/-6%; convulxin: abciximab 90+/-6%, tirofiban 64+/-20%, eptifibatide 61+/-14%, p<0.01 for all). In contrast, aggregation induced by collagen was equally abolished with all antagonists under the similar conditions. During CRP- or convulxin-triggered platelet activation, inhibition of fibrin polymerisation with GPRP potentiated the antiaggregatory effects of tirofiban and eptifibatide to reach that of abciximab. GPRP as such did not affect platelet aggregation.
  
  
  CONCLUSIONS
  GP IIb/IIIa antagonists exhibit distinct inhibition profiles in platelet aggregation, depending on fibrin polymerization and calcium. Specifically, the ability of procoagulant platelet agonists to expose pre-activated and ligand-bound GP IIb/IIIa from the internal pool seems important.
authors.affiliation: Wihuri Research Institute and Department of Hematology, Coagulation Disorders, Helsinki Central University Hospital, 00029-HUS Helsinki, Finland.
authors.forename: Sorella
authors.initials: S
authors.lastname: Ilveskero
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
mesh_terms: D000077284:Abciximab; D000244:Adenosine Diphosphate / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002097:C-Reactive Protein / Q000737:chemistry; D002850:Chromatography, Gel; D003029:Coagulants / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D000077542:Eptifibatide; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D015233:Models, Statistical; D010455:Peptides / Q000494:pharmacology; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D003029:Coagulants; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D014443:Tyrosine; D000244:Adenosine Diphosphate; D003094:Collagen; D002097:C-Reactive Protein; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab