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

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).

Keywords: clopidogrel; percutaneous coronary intervention; prasugrel; reticulated platelets.