Department of Laboratory Medicine, Hongcheon Asan Hospital, Gangwon, Korea.
Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, Korea.
J Clin Lab Anal. 2019 Jun;33(5):e22869. doi: 10.1002/jcla.22869. Epub 2019 Mar 12.
Apixaban and rivaroxaban are approved for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and embolic stroke in atrial fibrillation (AF) patients. The aim of this study was to find appropriate methods of monitoring the anticoagulant effects of are direct oral anticoagulants (DOACs) and establish on-therapy ranges using conventional tests.
A total of 184 samples were collected from 91 patients receiving DOACs. Concentrations of apixaban and rivaroxaban in plasma were accessed by an anti-factor Xa chromogenic assay. PT, APTT, antithrombin, D-dimer, dRVVT screen/confirm, FDP, and fibrinogen levels were measured. On-therapy ranges were calculated by substituting previously reported trough plasma concentrations of DOACs.
Anti-factor Xa chromogenic assay-based DOACs levels were 26.0-279.5 (115.9 ± 56.5) ng/mL for apixaban at 2.5 mg BID, 19.9-565.1 (205.3 ± 162.4) ng/mL for apixaban at 5 mg BID, 2.3-395.3 (205.3 ± 162.4) ng/mL for rivaroxaban at 15 mg OD, 3.6-494.8 (119.6 ± 95.1) ng/mL for rivaroxaban at 20 mg OD, and 9.6-431.4 (140.8 ± 113.6) ng/mL for rivaroxaban at 15 mg BID. PT (%), antithrombin, and dRVVT confirm tests showed good correlation with plasma apixaban levels. Plasma rivaroxaban concentrations were correlated well with PT (sec), PT (%),and dRVVT confirm results. On-therapy ranges established for dRVVT confirm test by linear regression were as follows: 1.32-1.52 for apixaban 2.5 mg BID, 1.12-1.75 for apixaban 5 mg BID, 1.11-1.78 for rivaroxaban 15 mg OD, 1.09-1.64 for rivaroxaban 20 mg OD, and 1.22-1.81 for rivaroxaban 20 mg BID.
Apixaban concentrations were well correlated with PT (%), antithrombin, and dRVVT confirm test. Rivaroxaban concentrations showed good correlation with PT (sec), PT (%), and dRVVT confirm test.
阿哌沙班和利伐沙班获批用于预防和治疗深静脉血栓（DVT）、肺栓塞（PE）和房颤（AF）患者的栓塞性卒中。本研究旨在寻找合适的方法来监测直接口服抗凝剂（DOACs）的抗凝效果，并使用常规检测方法建立治疗范围内的浓度。
共收集了 91 例接受 DOAC 治疗的患者的 184 份样本。采用抗因子 Xa 显色法检测阿哌沙班和利伐沙班的血浆浓度。检测凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、抗凝血酶、D-二聚体、dRVVT 筛查/确认、纤维蛋白原降解产物（FDP）和纤维蛋白原水平。通过替代先前报道的 DOAC 谷浓度计算治疗范围内的浓度。
基于抗因子 Xa 显色法的 DOAC 水平，阿哌沙班 2.5mg BID 组为 26.0-279.5（115.9±56.5）ng/mL，阿哌沙班 5mg BID 组为 19.9-565.1（205.3±162.4）ng/mL，利伐沙班 15mg OD 组为 2.3-395.3（205.3±162.4）ng/mL，利伐沙班 20mg OD 组为 3.6-494.8（119.6±95.1）ng/mL，利伐沙班 15mg BID 组为 9.6-431.4（140.8±113.6）ng/mL。PT（%）、抗凝血酶和 dRVVT 确认试验与血浆阿哌沙班水平具有良好的相关性。血浆利伐沙班浓度与 PT（sec）、PT（%）和 dRVVT 确认结果具有良好的相关性。通过线性回归为 dRVVT 确认试验建立的治疗范围内的浓度如下：阿哌沙班 2.5mg BID 组为 1.32-1.52，阿哌沙班 5mg BID 组为 1.12-1.75，利伐沙班 15mg OD 组为 1.11-1.78，利伐沙班 20mg OD 组为 1.09-1.64，利伐沙班 20mg BID 组为 1.22-1.81。
阿哌沙班浓度与 PT（%）、抗凝血酶和 dRVVT 确认试验具有良好的相关性。利伐沙班浓度与 PT（sec）、PT（%）和 dRVVT 确认试验具有良好的相关性。
