Platelet activation markers during dual-antiplatelet therapy and after clopidogrel suspension in patients treated with drug-eluting stents

Objective. To assess platelet activation markers during dual-antiplatelet therapy (DAT) and after clopidogrel suspension in patients treated with drug-eluting stents (DES).
Background. Concerns have been raised regarding an increased thrombogenicity of DES after clopidogrel discontinuation.
Methods. We enrolled 48 patients electively treated with DES. Platelet activation markers (PAC-1, Tissue Factor [TF], P-selectin and percentage of total and TF-positive monocyte-platelet aggregates [MPA]) were assessed by whole-blood flow cytometry, and C-reactive protein (CRP), thrombin-antithrombin (TAT) and prothrombin activation fragment 1+2 (F1+2) plasma levels were measured during DAT (T0) and one (T1) and 6 months (T2) after clopidogrel suspension. As comparison, platelet activation was analyzed in 15 medically-treated (MT) stable angina patients.
Results. At T0, the number of circulating P-selectin-positive and TF-positive resting platelets was significantly higher in DES patients than in MT patients (~3 fold), while PAC-1 and MPA were comparable. The number of PAC-1- and P-selectin-positive platelets was also significantly higher at T1 and then tended to the levels of MT patients at T2. By contrast, TF-positive platelets further increased at T1 and remained significantly higher than in MT patients also at T2. No significant changes of MPA and CRP, F1+2 and TAT were found throughout the study.
Conclusions. Despite DAT, platelets in DES-treated patients show a hyperactive state, which further increases one month after clopidogrel withdrawal. Six months after clopidogrel withdrawal, P-selectin- and PAC-1-positive platelets tended to those found in MT patients, whereas TF positive platelets remained still significantly higher. This platelet behaviour may have implications for DES thrombosis.