INTRODUCTION: 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. MATERIALS AND 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.
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INTRODUCTION: 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. MATERIALS AND 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.
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Authors: Volker Rudolph; Tanja K Rudolph; Francisco J Schopfer; Gustavo Bonacci; Denise Lau; Katalin Szöcs; Anna Klinke; Thomas Meinertz; Bruce A Freeman; Stephan Baldus Journal: J Pharmacol Exp Ther Date: 2008-08-13 Impact factor: 4.030
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