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Glycoprotein IIb/IIIa and P2Y12 receptor antagonists yield additive inhibition of platelet aggregation, granule secretion, soluble CD40L release and procoagulant responses.
- Source :
-
Platelets [Platelets] 2005 Nov; Vol. 16 (7), pp. 398-407. - Publication Year :
- 2005
-
Abstract
- Glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists, including abciximab and tirofiban, are administered concurrently with clopidogrel, a P2Y12 antagonist, and aspirin in some patients undergoing percutaneous coronary intervention. We studied the effects of, and interactions between, abciximab, tirofiban, aspirin and the P2Y12 antagonist cangrelor on platelet aggregation, alpha and dense granule secretion and procoagulant responses in vitro. Blood was obtained from healthy volunteers. Platelet aggregation, dense granule secretion, alpha granule secretion (PAI-1 and soluble CD40 ligand levels) and procoagulant responses (annexin-V and microparticle formation) were assessed using collagen and thrombin receptor activating peptide (TRAP) as agonists. All the antagonists used singularly inhibited collagen-induced responses. Combinations of abciximab or tirofiban with aspirin and/or cangrelor gave additive inhibition with the greatest effect seen when abciximab or tirofiban was combined with both aspirin and cangrelor. Cangrelor inhibited TRAP-induced responses and, again, there was additive inhibition of these parameters when abciximab or tirofiban were combined with cangrelor. The GPIIb/IIIa receptor plays an important role in amplification of platelet activation such that there are important interactions between GPIIb/IIIa antagonists and inhibitors of both P2Y12 receptor activation and, to a lesser extent, thromboxane A2 generation. These interactions are likely to have important influences on the safety and efficacy of combination anti-platelet therapies.
- Subjects :
- Abciximab
Adenosine Monophosphate analogs & derivatives
Adenosine Monophosphate pharmacology
Antibodies, Monoclonal pharmacology
Aspirin pharmacology
Coagulants pharmacology
Humans
Immunoglobulin Fab Fragments pharmacology
Membrane Proteins metabolism
Plasminogen Activator Inhibitor 1 metabolism
Platelet Aggregation physiology
Platelet Glycoprotein GPIIb-IIIa Complex metabolism
Receptors, Purinergic P2 metabolism
Receptors, Purinergic P2Y12
Receptors, Thrombin metabolism
Tirofiban
Tyrosine analogs & derivatives
Tyrosine pharmacology
Blood Platelets drug effects
Blood Platelets metabolism
CD40 Ligand metabolism
Membrane Proteins antagonists & inhibitors
Platelet Aggregation drug effects
Platelet Aggregation Inhibitors pharmacology
Platelet Glycoprotein GPIIb-IIIa Complex antagonists & inhibitors
Purinergic P2 Receptor Antagonists
Secretory Vesicles metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0953-7104
- Volume :
- 16
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Platelets
- Publication Type :
- Academic Journal
- Accession number :
- 16236601
- Full Text :
- https://doi.org/10.1080/09537100500163226