Increased expression of platelet P-selectin and formation of platelet-leukocyte aggregates in blood from patients treated with unfractionated heparin plus eptifibatide compared with bivalirudin.
BACKGROUND
Platelet-leukocyte aggregates have been implicated in atherogenesis. This study was designed to determine the influence in vivo of a direct thrombin inhibitor, bivalirudin, compared with unfractionated heparin (UFH) plus the GP IIb-IIIa inhibitor eptifibatide (E) on platelet reactivity, the formation of platelet-leukocyte aggregates, and leukocyte activation.


METHODS
Blood was taken before and after percutaneous coronary intervention (PCI) from 60 patients randomized to UFH+E (n=26) or bivalirudin (n=34). Platelet function and the formation in vivo of platelet-monocyte aggregates (PMA) and platelet-neutrophil aggregates (PNA) were assessed with the use of flow cytometry. Myeloperoxidase (MPO) elaborated during leukocyte activation was measured by ELISA.


RESULTS
Compared with those treated with bivalirudin, patients treated with UFH+E exhibited a 45% decrease in the capacity of platelets to bind fibrinogen (p=0.006) but a 2-fold increase in platelet surface expression of P-selectin (p=0.04) in samples taken from the coronary ostium before PCI. Platelet-leukocyte aggregation in vivo was greater (PMA=2-fold, p=0.04; PNA=3-fold, p=0.006) with UFH+E as was the concentration in blood of MPO (1.5-fold, p=0.007).


CONCLUSIONS
Increased platelet surface expression of P-selectin, augmented platelet-leukocyte aggregation in vivo, and consequent activation of leukocytes was seen before PCI in blood from patients treated with UFH+E compared with bivalirudin. Benefits associated with decreased platelet aggregation when PCI is performed with UFH plus GP IIb-IIIa inhibition may be partially offset by increased platelet-leukocyte aggregation.
Keating
Friederike K
FK
Cardiology Unit, Department of Medicine, University of Vermont/Fletcher Allen Health Care, 111 Colchester Avenue, Burlington, VT 05401, USA. friederike.keating@vtmednet.org
Dauerman
Harold L
HL
Whitaker
Deborah A
DA
Sobel
Burton E
BE
Schneider
David J
DJ
D000925:Anticoagulants / Q000008:administration & dosage; D002478:Cells, Cultured; D004338:Drug Combinations; D000077542:Eptifibatide; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D013927:Thrombosis / Q000097:blood / Q000276:immunology* / Q000517:prevention & control
D000925:Anticoagulants; D004338:Drug Combinations; D006629:Hirudins; D019007:P-Selectin; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D006493:Heparin; D000077542:Eptifibatide; C074619:bivalirudin