Samuelson Bethany T, Cuker Adam, Siegal Deborah M, Crowther Mark, Garcia David A
Department of Medicine, Division of Hematology, University of Washington, Seattle, WA.
Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Chest. 2017 Jan;151(1):127-138. doi: 10.1016/j.chest.2016.08.1462. Epub 2016 Sep 13.
Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban.
PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results.
We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban.
An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available.
直接口服抗凝剂（DOACs）是大多数房颤和/或非癌症相关静脉血栓栓塞性疾病患者的首选治疗药物。虽然这些药物无需常规监测，但在特殊情况下可能需要评估抗凝效果。本综述的目的是系统总结关于达比加群、利伐沙班、阿哌沙班和依度沙班抗凝效果实验室评估的证据。
检索PubMed、Embase和Web of Science数据库，查找报告药物水平与凝血检测结果之间关系的研究。
我们确定了109项符合条件的研究：35项关于达比加群，50项关于利伐沙班，11项关于阿哌沙班，13项关于依度沙班。标准抗凝试验的性能因DOACs和试剂而异；大多数检测显示相关性不足，无法可靠评估DOACs的效果。稀释凝血酶时间（TT）检测在达比加群的一系列预期浓度范围内显示出线性相关性（r = 0.67 - 0.99），基于蛇毒凝血酶的检测也是如此。校准的抗Xa检测在利伐沙班、阿哌沙班和依度沙班的广泛浓度范围内显示出线性相关性（r = 0.78 - 1.00）。
一种能准确、精确测量任何DOAC的理想检测方法尚未广泛应用。我们建议用稀释TT或基于蛇毒凝血酶的检测来评估达比加群的抗凝效果，用针对直接Xa抑制剂的药物特异性校准物的抗Xa检测。在没有这些检测的情况下，评估达比加群时，推荐使用TT或活化部分凝血活酶时间（APTT）而非凝血酶原时间/国际标准化比值（PT/INR）；检测Xa抑制剂时，推荐使用PT/INR而非APTT。末次给药后的时间、药物相互作用的有无以及肾和肝功能应影响无法获得实验室检测结果患者的抗凝效果临床评估。
