Newly Formed Reticulated Platelets Undermine Pharmacokinetically Short-Lived Antiplatelet Therapies.
Arterioscler Thromb Vasc Biol
; 37(5): 949-956, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-28279968
ABSTRACT
OBJECTIVE:
Aspirin together with thienopyridine P2Y12 inhibitors, commonly clopidogrel, is a cornerstone of antiplatelet therapy. However, many patients receiving this therapy display high on-treatment platelet reactivity, which is a major therapeutic hurdle to the prevention of recurrent thrombotic events. The emergence of uninhibited platelets after thrombopoiesis has been proposed as a contributing factor to high on-treatment platelet reactivity. Here, we investigate the influences of platelet turnover on platelet aggregation in the face of different dual-antiplatelet therapy strategies. APPROACH ANDRESULTS:
Traditional light transmission aggregometry, cytometry, advanced flow cytometric imaging, and confocal microscopy were used to follow the interactions of populations of platelets from healthy volunteers and patients with stable cardiovascular disease. Newly formed, reticulated platelets overproportionately contributed to, and clustered at, the core of forming aggregates. This phenomenon was particularly observed in samples from patients treated with aspirin plus a thienopyridine, but was absent in samples taken from patients treated with aspirin plus ticagrelor.CONCLUSIONS:
Reticulated platelets are more reactive than older platelets and act as seeds for the formation of platelet aggregates even in the presence of antiplatelet therapy. This is coherent with the emergence of an uninhibited subpopulation of reticulated platelets during treatment with aspirin plus thienopyridine, explained by the short pharmacokinetic half-lives of these drugs. This phenomenon is absent during treatment with ticagrelor, because of its longer half-life and ability to act as a circulating inhibitor. These data highlight the important influences of pharmacokinetics on antiplatelet drug efficacies, especially in diseases associated with increased platelet turnover.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Doença da Artéria Coronariana
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Inibidores da Agregação Plaquetária
/
Adenosina
/
Aspirina
/
Trombopoese
/
Tienopiridinas
/
Antagonistas do Receptor Purinérgico P2Y
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido