PMID- 16139336 OWN - NLM STAT- MEDLINE DCOM- 20070111 LR - 20181201 IS - 0049-3848 (Print) IS - 0049-3848 (Linking) VI - 118 IP - 3 DP - 2006 TI - 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. PG - 361-9 AB - 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. FAU - Keating, Friederike K AU - Keating FK AD - Cardiology Unit, Department of Medicine, University of Vermont/Fletcher Allen Health Care, 111 Colchester Avenue, Burlington, VT 05401, USA. friederike.keating@vtmednet.org FAU - Dauerman, Harold L AU - Dauerman HL FAU - Whitaker, Deborah A AU - Whitaker DA FAU - Sobel, Burton E AU - Sobel BE FAU - Schneider, David J AU - Schneider DJ LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20050901 PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Anticoagulants) RN - 0 (Drug Combinations) RN - 0 (Hirudins) RN - 0 (P-Selectin) RN - 0 (Peptide Fragments) RN - 0 (Peptides) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (Recombinant Proteins) RN - 9005-49-6 (Heparin) RN - NA8320J834 (Eptifibatide) RN - TN9BEX005G (bivalirudin) SB - IM MH - Anticoagulants/administration & dosage MH - Cells, Cultured MH - Drug Combinations MH - Eptifibatide MH - Female MH - Heparin/*administration & dosage MH - Hirudins/*administration & dosage MH - Humans MH - Leukocytes/drug effects/immunology MH - Male MH - Middle Aged MH - P-Selectin/*immunology MH - Peptide Fragments/*administration & dosage MH - Peptides/*administration & dosage MH - Platelet Aggregation/*drug effects/*immunology MH - Platelet Aggregation Inhibitors/administration & dosage MH - Recombinant Proteins/administration & dosage MH - Thrombosis/blood/*immunology/prevention & control EDAT- 2005/09/06 09:00 MHDA- 2007/01/12 09:00 CRDT- 2005/09/06 09:00 PHST- 2005/03/21 00:00 [received] PHST- 2005/07/16 00:00 [revised] PHST- 2005/07/22 00:00 [accepted] PHST- 2005/09/06 09:00 [pubmed] PHST- 2007/01/12 09:00 [medline] PHST- 2005/09/06 09:00 [entrez] AID - S0049-3848(05)00344-0 [pii] AID - 10.1016/j.thromres.2005.07.020 [doi] PST - ppublish SO - Thromb Res. 2006;118(3):361-9. doi: 10.1016/j.thromres.2005.07.020. Epub 2005 Sep 1.