Sathanantham Vepusha, Alberio Lorenzo, Bovet Cédric, Fontana Pierre, Gerber Bernhard, Graf Lukas, Mendez Adriana, Sauter Thomas C, Schmidt Adrian, Studt Jan-Dirk, Wuillemin Walter A, Nagler Michael
Department of Clinical Chemistry, Inselspital, Bern University Hospital, 3010 Bern, Switzerland.
Service and Central Laboratory of Hematology, CHUV, Lausanne University Hospital, 1011 Lausanne, Switzerland.
Life (Basel). 2022 Jul 11;12(7):1027. doi: 10.3390/life12071027.
Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly. Citrated plasma samples were collected, and the Pefakit PiCT was utilized. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure drug concentrations. Cut-off levels were established using receiver-operating characteristics curves. We calculated sensitivities and specificities with respect to clinically relevant drug concentrations. Spearman's correlation coefficient between PiCT and drug concentrations was 0.85 in the case of rivaroxaban (95% CI 0.82, 0.88), 0.66 for apixaban (95% CI 0.60, 0.71), and 0.78 for edoxaban (95% CI 0.65, 0.86). The sensitivity to detect clinically relevant drug concentrations was 85.1% in the case of 30 µg L (95% CI 82.0, 87.7; specificity 77.9; 72.1, 82.7), 85.7% in the case of 50 µg L (82.4, 88.4; specificity 77.3; 72.5, 81.5), and 85.1% in the case of 100 µg L (80.9, 88.4; specificity 73.2%; 69.1, 76.9). In conclusion, the association of PiCT with DOAC concentrations was fair, and the majority of clinically relevant drug concentrations were correctly predicted.
凝血酶原酶诱导凝血时间（PiCT）被提议作为一种快速且经济的实验室检测方法，用于测定直接口服抗凝剂（DOAC）的药物水平。在一项纳入851例患者的前瞻性多中心横断面研究中，我们旨在研究PiCT在测定利伐沙班、阿哌沙班和依度沙班药物浓度方面的准确性，并评估是否能够正确预测临床相关药物水平。收集枸橼酸盐血浆样本，并使用Pefakit PiCT进行检测。采用超高效液相色谱 - 串联质谱法（LC-MS/MS）测定药物浓度。利用受试者工作特征曲线确定临界值水平。我们计算了与临床相关药物浓度相关的敏感性和特异性。利伐沙班的PiCT与药物浓度之间的Spearman相关系数为0.85（95%CI 0.82, 0.88），阿哌沙班为0.66（95%CI 0.60, 0.71），依度沙班为0.78（95%CI 0.65, 0.86）。检测临床相关药物浓度的敏感性在30 μg/L时为85.1%（95%CI 82.0, 87.7；特异性77.9；72.1, 82.7），50 μg/L时为85.7%（82.4, 88.4；特异性77.3；72.5, 81.5），100 μg/L时为85.1%（80.9, 88.4；特异性73.2%；69.1, 76.9）。总之，PiCT与DOAC浓度之间的相关性尚可，大多数临床相关药物浓度能够被正确预测。
