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Distinct yet complementary mechanisms of heparin and glycoprotein IIb/IIIa inhibitors on platelet activation and aggregation: implications for restenosis during percutaneous coronary intervention
  1. J R S Day1,*,
  2. I S Malik2,*,
  3. A Weerasinghe1,
  4. M Poullis1,
  5. I Nadra3,
  6. D O Haskard3,
  7. K M Taylor1,
  8. R C Landis3
  1. 1British Heart Foundation Cardiac Surgery Unit, The Hammersmith Hospital, London, UK
  2. 2Waller Department of Cardiology, St Mary’s Hospital, London, UK
  3. 3Cardiovascular Medicine Unit, The Hammersmith Hospital
  1. Correspondence to:
    Mr J R S Day
    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;


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.

  • ACS, acute coronary syndromes
  • ELISA, enzyme linked immunosorbent assay
  • ESSENCE, efficacy and safety of subcutaneous enoxaparin in non-Q wave coronary events
  • Gp, glycoprotein
  • LMWH, low molecular weight heparin
  • PAR, protease activated receptor
  • PCI, percutaneous coronary intervention
  • PDGF, platelet derived growth factor
  • POLONIA, Polish-American local Lovenox NIR assessment
  • PSGL, P selectin glycoprotein ligand
  • SYNERGY, superior yield of the new strategy of enoxaparin, revascularisation and glycoprotein IIb/IIIa inhibitors
  • TRAP, thrombin receptor activating peptide
  • UFH, unfractionated heparin

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  • * These authors contributed equally to the work