Comparison of Immature Platelet Count to Established Predictors of Platelet Reactivity During Thienopyridine Therapy

• Published in: Journal of the American College of Cardiology Vol. 68; no. 3; pp. 286 - 293
• Main Authors: Stratz, Christian, MD, Bömicke, Timo, MD, Younas, Iris, MS, Kittel, Anja, PhD, Amann, Michael, MD, Valina, Christian M., MD, Nührenberg, Thomas, MD, Trenk, Dietmar, PhD, Neumann, Franz-Josef, MD, Hochholzer, Willibald, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.07.2016; Elsevier Limited
• Subjects: Acute coronary syndromes; Aged; Aspirin; Automation; Blood platelets; Blood Platelets - drug effects; Cardiology; Cardiovascular; Cardiovascular disease; clopidogrel; Coronary Artery Disease - blood; Coronary Artery Disease - drug therapy; Coronary Artery Disease - surgery; Dose-Response Relationship, Drug; Drug dosages; Female; Heart attacks; Humans; Internal Medicine; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation - drug effects; Platelet Count; prasugrel; Pyridines - administration & dosage; reticulated platelets; Stents; Studies; Treatment Outcome; Variables; Germany; clopidogrel; prasugrel; aggregation units; highly fluorescent immature platelet fraction; immature platelet fraction; hIPF; ADP; percutaneous coronary intervention; AU; adenosine diphosphate; immature platelet count; reticulated platelets; IPC; IPF
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2016.04.056

Abstract Background Previous data suggest that reticulated platelets significantly affect antiplatelet response to thienopyridines. It is unknown whether parameters describing reticulated platelets can predict antiplatelet response to thienopyridines. Objectives The authors sought to determine the extent to which parameters describing reticulated platelets can predict antiplatelet response to thienopyridine loading compared with established predictors. Methods This study randomized 300 patients undergoing elective coronary stenting to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg. Adenosine diphosphate (ADP)-induced platelet reactivity was assessed by impedance aggregometry before loading (intrinsic platelet reactivity) and again on day 1 after loading. Multiple parameters of reticulated platelets were assessed by automated whole blood flow cytometry: absolute immature platelet count (IPC), immature platelet fraction, and highly fluorescent immature platelet fraction. Results Each parameter of reticulated platelets correlated significantly with ADP-induced platelet reactivity (p < 0.01 for all 3 parameters). In a multivariable model including all 3 parameters, only IPC remained a significant predictor of platelet reactivity (p < 0.001). In models adjusting each of the 3 parameters for known predictors of on-treatment platelet reactivity including cytochrome P450 2C19 ( CYP2C19 ) polymorphisms, age, body mass index, diabetes, and intrinsic platelet reactivity, only IPC prevailed as an independent predictor (p = 0.001). In this model, IPC was the strongest predictor of on-treatment platelet reactivity followed by intrinsic platelet reactivity. Conclusions IPC is the strongest independent platelet count–derived predictor of antiplatelet response to thienopyridine treatment. Given its easy availability, together with its even stronger association with on-treatment platelet reactivity compared with known predictors, including the CYP2C19*2 polymorphism, IPC may become the preferred predictor of antiplatelet response to thienopyridine treatment. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate—Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102 )