Immature cell fractions after cessation of chronic P2Y₁₂-inhibition in patients with coronary artery diseases

Abstract

Changes in circulating cell populations may promote ischemic events that occur soon after discontinuation of P2Y₁₂-inhibition. The aim of the study was to track the course of thrombopoietic and erythropoietic cells in patients with coronary artery diseases (CAD) after planned and physician-driven cessation of chronic P2Y₁₂-inhibition (clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID). Cell fractions were determined in 62 patients at baseline (the last day of P2Y₁₂-inhibitor intake), on day-10, day-30, and day-180 thereafter. Immature platelet fraction (IPF), immature reticulocyte fraction (IRF), reticulocyte hemoglobin content (Ret-Hb) and red blood cell count (RBC) significantly increased from baseline to day-180 (IPF: p = .003; IRF: p = .013; Ret-Hb: p < .001; RBC: p = .044). Platelet count, leucocyte count and immature granulocyte fraction did not change over time (p = .561, p = .869, and p = .161, respectively). Fibrinogen levels significantly declined over time (p = .011), thrombopoietin levels increased in a non-significant manner (p = .379). We did not observe any significant interaction with choice of P2Y₁₂-inhibitor, therefore suggesting a drug class-effect. Our data shows, that discontinuation of dual antiplatelet therapy is associated with raised thrombopoietic and erythropoietic activity in the bone marrow, without significant upregulation of thrombopoietin. This provides further evidence for a direct stimulation of precursor cells by P2Y_12-inhibitors.

Keywords:

• Immature platelet fraction
• immature reticulocyte fraction
• P2Y₁₂-inhibitor
• prasugrel
• reticulated platelets
• ticagrelor

Disclosure Of Interest

The authors report no conflicts of interest and are fully responsible for the study design, conduction of the study, data analysis and manuscript preparation.

Additional information

Funding

This work was supported by the Medical Scientific Fund of the Mayor of the City of Vienna [under grant number 17092]; the Association for Research on Atherosclerosis, Thrombosis and Vascular Biology (ATVB) Vienna; and the Ludwig Boltzmann Cluster for Cardiovascular Research (Vienna, Austria).