We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Preserved thrombin-inducible platelet activation in thienopyridine-treated patients.
- Authors
Gremmel, Thomas; Kopp, Christoph W.; Seidinger, Daniela; Koppensteiner, Renate; Steiner, Sabine; Panzer, Simon
- Abstract
Background Abundant thrombin generation may be a major reason for subsequent thromboembolic events in patients with cardiovascular disease receiving dual antiplatelet therapy. We therefore investigated the susceptibility of thienopyridine responders and nonresponders to thrombin receptor-activating peptide ( TRAP)-6- and adenosine diphosphate ( ADP)-inducible platelet activation. Materials and methods Response to clopidogrel or prasugrel was determined by the vasodilator-stimulated phosphoprotein ( VASP) phosphorylation assay and multiple electrode aggregometry ( MEA) in 317 patients undergoing angioplasty and stenting for cardiovascular disease. Baseline, TRAP-6-, and ADP-inducible P-selectin expression, activated glycoprotein IIb/ IIIa ( GPIIb/ IIIa) and monocyte-platelet aggregate ( MPA) formation were measured as sensitive parameters of platelet activation. Results In patients with high on-treatment residual ADP-inducible platelet reactivity ( HRPR), baseline P-selectin expression, GPIIb/ IIIa and MPA formation were similar to those in patients without HRPR (all P > 0·05). After platelet activation with TRAP-6 or ADP, patients with HRPR by both assays exhibited significantly higher levels of P-selectin expression, GPIIb/ IIIa and MPA formation than patients with an adequate thienopyridine-mediated platelet inhibition (all P ≤ 0·02). However, high levels of TRAP-6-inducible P-selectin, GPIIb/ IIIa and MPA formation also occurred in 20·4%, 19·1% and 20·1% of the good responders by the VASP assay, and in 19·6%, 16·6% and 20·6% of the good responders by MEA, respectively. Conclusions Thienopyridine nonresponders are more susceptible to thrombin- and ADP-inducible platelet activation than patients with good platelet inhibition. However, even patients with adequate thienopyridine-mediated platelet inhibition often show a preserved responsiveness to thrombin. These patients may benefit from additional thrombin receptor blockage or inhibition of thrombin generation.
- Subjects
THROMBIN receptors; BLOOD platelet activation; PYRIDINE; CARDIOVASCULAR diseases; VASODILATOR-stimulated phosphoprotein; PLATELET aggregation inhibitors
- Publication
European Journal of Clinical Investigation, 2013, Vol 43, Issue 7, p689
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/eci.12094