University Heart Center Freiburg Bad Krozingen, Department of Cardiology and Angiology II, Bad Krozingen, Germany.
University Heart Center Freiburg Bad Krozingen, Department of Cardiology and Angiology II, Bad Krozingen, Germany.
J Am Coll Cardiol. 2016 Jul 19;68(3):286-293. doi: 10.1016/j.jacc.2016.04.056.
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.
The authors sought to determine the extent to which parameters describing reticulated platelets can predict antiplatelet response to thienopyridine loading compared with established predictors.
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.
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.
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).
先前的数据表明，网织血小板会显著影响噻吩吡啶类药物的抗血小板反应。目前尚不清楚是否可以通过描述网织血小板的参数来预测噻吩吡啶类药物的抗血小板反应。
作者旨在确定描述网织血小板的参数在多大程度上可以预测噻吩吡啶类药物负荷后抗血小板反应，与既定的预测因素相比。
本研究将 300 名择期接受冠状动脉支架置入术的患者随机分为氯吡格雷 600mg、普拉格雷 30mg 或普拉格雷 60mg 负荷剂量组。在负荷前（固有血小板反应性）和负荷后第 1 天，通过阻抗聚集法评估二磷酸腺苷（ADP）诱导的血小板反应性。通过自动化全血流式细胞术评估网织血小板的多个参数：绝对幼稚血小板计数（IPC）、幼稚血小板分数和高荧光幼稚血小板分数。
网织血小板的每个参数与 ADP 诱导的血小板反应性均显著相关（所有 3 个参数的 p 值均<0.01）。在包含所有 3 个参数的多变量模型中，只有 IPC 仍然是血小板反应性的显著预测因素（p<0.001）。在调整每个参数以包括已知的治疗后血小板反应性预测因素（包括细胞色素 P450 2C19（CYP2C19）多态性、年龄、体重指数、糖尿病和固有血小板反应性）的模型中，仅 IPC 仍然是独立的预测因素（p=0.001）。在该模型中，IPC 是噻吩吡啶类药物治疗后血小板反应性的最强独立预测因子，其次是固有血小板反应性。
IPC 是噻吩吡啶类药物治疗抗血小板反应的最强独立血小板计数衍生预测因子。鉴于其易于获得，以及与包括 CYP2C19*2 多态性在内的已知预测因子相比，与治疗后血小板反应性的相关性更强，IPC 可能成为噻吩吡啶类药物抗血小板反应的首选预测因子。（在选择性支架植入期间氯吡格雷诱导的血小板抑制程度对临床事件发生率的影响-高级负荷策略[ExcelsiorLOAD]；DRKS00006102）。
