title: Distinct yet complementary mechanisms of heparin and glycoprotein IIb/IIIa inhibitors on platelet activation and aggregation: implications for restenosis during percutaneous coronary intervention.
abstract: OBJECTIVE
  To study the effect of unfractionated heparin (UFH) versus low molecular weight heparin (LMWH) in combination with glycoprotein (Gp) IIb/IIIa blockers on platelet activation and aggregation.
  
  
  METHODS
  Washed platelets were stimulated with thrombin in the presence or absence of UFH (monoparin), LMWH (enoxaparin), and a Gp IIb/IIIa blocker (abciximab, eptifibatide, or tirofiban).
  
  
  RESULTS
  Although Gp IIb/IIIa antagonists blocked the final common pathway of thrombin induced platelet aggregation, UFH and LMWH were better at blocking upstream platelet activation. UFH was significantly more effective than LMWH at inhibiting P selectin expression (p = 0.001) and platelet derived growth factor release from thrombin activated platelets (p = 0.012).
  
  
  CONCLUSIONS
  UFH and LMWH exert complementary effects to Gp IIb/IIIa blockers by inhibiting afferent pathways of platelet activation. Coadministration of heparin with Gp IIb/IIIa blockers provides improved protection against persistent platelet activation, thereby improving outcome after percutaneous coronary intervention. Judging from these data, UFH may be more effective in this regard than LMWH, at least in vitro. The use of LMWH in preference to UFH during percutaneous coronary intervention, although initially attractive, may inadequately protect against platelet activation despite the presence of Gp IIb/IIIa blockers.
authors.affiliation: British Heart Foundation Cardiovascular Medicine and Cardiac Surgery Unit, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane road, London W12 0NN, UK. j.day@imperial.ac.uk
authors.forename: J R S
authors.initials: JR
authors.lastname: Day
authors.forename: I S
authors.initials: IS
authors.lastname: Malik
authors.forename: A
authors.initials: A
authors.lastname: Weerasinghe
authors.forename: M
authors.initials: M
authors.lastname: Poullis
authors.forename: I
authors.initials: I
authors.lastname: Nadra
authors.forename: D O
authors.initials: DO
authors.lastname: Haskard
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
authors.forename: R C
authors.initials: RC
authors.lastname: Landis
mesh_terms: D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology*; D023903:Coronary Restenosis / Q000097:blood; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology; D000077542:Eptifibatide; D005434:Flow Cytometry; D006490:Hemostatics / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000494:pharmacology*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D017984:Enoxaparin; D006490:Hemostatics; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D014443:Tyrosine; D006493:Heparin; D013917:Thrombin; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab