Lenart-Migdalska Aleksandra, Drabik Leszek, Kaźnica-Wiatr Magdalena, Tomkiewicz-Pająk Lidia, Podolec Piotr, Olszowska Maria
Department of Cardiac and Vascular Diseases, Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, John Paul II Hospital, Cracow, Poland.
Department of Pharmacology, Jagiellonian University Medical College, Cracow, Poland.
Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620972467. doi: 10.1177/1076029620972467.
The prothrombotic state in patients with atrial fibrillation (AF) is related to endothelial injury, the activation of platelets and the coagulation cascade. We evaluated the levels of platelet- (CD42b) and endothelial-derived (CD144) microparticles in the plasma patients with non-valvular AF treated with dabigatran at the time of expected minimum and maximum drug plasma concentrations. Following that, we determined the peak dabigatran plasma concentration (c ). CD42b increased after taking dabigatran (median [IQR] 36.7 [29.4-53.3] vs. 45.6 [32.3-59.5] cells/µL; p = 0.025). The concentration of dabigatran correlated negatively with the post-dabigatran change in CD42b (ΔCD42b, r = -0.47, p = 0.021). In the multivariate model, the independent predictors of ΔCD42b were: c (HR -0.55; with a 95% confidence interval, CI [-0.93, -0.16]; p = 0.007), coronary artery disease (CAD) (HR -0.41; 95% CI [-0.79, -0.02]; p = 0.037) and peripheral artery disease (PAD) (HR 0.42; 95% CI [0.07, 0.74]; p = 0.019). CD144 did not increase after dabigatran administration. These data suggest that low concentrations of dabigatran may be associated with platelet activation. PAD and CAD have distinct effects on CD42b levels during dabigatran treatment.
心房颤动（AF）患者的血栓前状态与内皮损伤、血小板激活及凝血级联反应有关。我们评估了接受达比加群治疗的非瓣膜性AF患者在预期药物血浆浓度最低和最高时血浆中血小板源性（CD42b）和内皮源性（CD144）微粒的水平。随后，我们测定了达比加群的血浆峰值浓度（c）。服用达比加群后CD42b升高（中位数[四分位间距]36.7[29.4 - 53.3]对45.6[32.3 - 59.5]个细胞/µL；p = 0.025）。达比加群浓度与达比加群后CD42b的变化（ΔCD42b）呈负相关（r = -0.47，p = 0.021）。在多变量模型中，ΔCD42b的独立预测因素为：c（风险比-0.55；95%置信区间，CI[-0.93，-0.16]；p = 0.007）、冠状动脉疾病（CAD）（风险比-0.41；95%CI[-0.79，-0.02]；p = 0.037）和外周动脉疾病（PAD）（风险比0.42；95%CI[0.07，0.74]；p = 0.019）。服用达比加群后CD144未升高。这些数据表明，低浓度的达比加群可能与血小板激活有关。在达比加群治疗期间，PAD和CAD对CD42b水平有不同影响。
