title: The GPIIb/IIIa antagonist eptifibatide markedly potentiates platelet-leukocyte interaction and tissue factor expression following platelet activation in whole blood in vitro.
abstract: Tissue factor (TF) is the most important initiator of intravascular coagulation. Activated platelets are able to adhere to leukocytes and this heterotypic cell-cell interaction results in a CD62P-dependent TF expression on monocytes. GPIIb/IIIa antagonists are inhibitors of the common pathway of platelet aggregation and they are widely used in patients with acute coronary syndromes undergoing coronary interventions. As GPIIb/IIIa antagonists do not prevent platelet activation we investigated the effect a GPIIb/IIIa antagonist, eptifibatide, on the formation of platelet-leukocyte conjugates and leukocyte TF expression. Flow cytometry was used to detect conjugates and TF. When platelets in citrated human blood were stimulated for 30 min with collagen there was a increase in the number of both neutrophils and monocytes with the platelet-specific antigen CD42a, indicating the formation of platelet-neutrophil (P/N) and platelet-monocyte (P/M) conjugates. P/M formation was associated with about a 2.5-fold increase in TF expression on monocytes, whereas P/N formation changed TF expression neutrophils only by about 10%. Eptifibatide enhanced dose-dependently (0.0625-1.5 microg/ml) both collagen-induced P/M formation and monocyte TF expression. Maximum enhancement by about 60 and 120%, respectively, was observed at 0.5 microg/ml eptifibatide. In contrast, eptifibatide had only a minor effect on P/N formation and no effect on neutrophil TF expression. The augmented P/M formation and monocyte TF expression in the presence of a GPIIb/IIIa antagonist may be relevant to the poor antithrombotic efficiency of oral GPIIb/IIIa antagonists as shown in recent large clinical trials.
authors.affiliation: Centre for Vascular Biology and Medicine, University Hospital Jena, Nordhäuser Str. 78, D-99089 Erfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Scholz
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Uta
authors.initials: U
authors.lastname: Temmler
authors.forename: Philip
authors.initials: P
authors.lastname: Bath
authors.forename: Stan
authors.initials: S
authors.lastname: Heptinstall
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lösche
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D000077542:Eptifibatide; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D003094:Collagen; D013925:Thromboplastin; D000077542:Eptifibatide