title: Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.
abstract: Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.
authors.affiliation: Christian Stratz, MD, University Heart Center Freiburg · Bad Krozingen, Department of Cardiology and Angiology II, Suedring 15, 79189 Bad Krozingen, Germany, Tel.: +49 7633 402 0, Fax: +49 7633 402 2489, E-mail: christian.stratz@universitaets-herzzentrum.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Stratz
authors.forename: Thomas
authors.initials: T
authors.lastname: Nührenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Amann
authors.forename: Marco
authors.initials: M
authors.lastname: Cederqvist
authors.forename: Pascal
authors.initials: P
authors.lastname: Kleiner
authors.forename: Christian M
authors.initials: CM
authors.lastname: Valina
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.forename: Willibald
authors.initials: W
authors.lastname: Hochholzer
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors; D010976:Platelet Count; D000068799:Prasugrel Hydrochloride / Q000494:pharmacology*; D058924:Thienopyridines / Q000494:pharmacology*; D013988:Ticlopidine / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D058924:Thienopyridines; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Immature platelets; clopidogrel; platelet reactivity; prasugrel; reticulated platelets