Margetić Sandra, Goreta Sandra Šupraha, Ćelap Ivana, Razum Marija
Department of Clinical Chemistry Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
Department of Biochemistry and Molecular Biology, University of Zagreb Faculty of Pharmacy and Biochemistry Croatia.
Acta Pharm. 2022 Oct 18;72(4):459-482. doi: 10.2478/acph-2022-0034. Print 2022 Dec 1.
Direct oral anticoagulants (DOACs) represent a new generation of drugs that have been increasingly used in the prevention and treatment of thromboembolic states. According to the mechanism of anticoagulant action, DOACs are divided into two groups: direct inhibitors of thrombin (dabigatran) and direct inhibitors of activated factor X (FXa) (rivaroxaban, apixaban, edoxaban, betrixaban). Compared to the vitamin K antagonists, DOACs are superior in terms of onset of action, pharmacokinetic and pharmacodynamics properties and fixed daily dose without the need for routine coagulation monitoring. Despite these advantages, there are clinical conditions in which laboratory measurement of DOACs should be performed. Although DOACs have an impact on screening haemostasis assays (prothrombin time, PT; activated partial thromboplastin time, aPTT; and thrombin time, TT), these tests are not appropriate for quantifying drug levels. Therefore, specific quantitative methods (LC-MS/MS as a gold standard method for all DOACs, coagulometric and chromogenic assays for dabigatran, and chromogenic anti-Xa assays with drug-specific calibrators for inhibitors of FXa) should only be used for determination of DOACs concentration. The aim of this review is to present all aspects of laboratory assessment of DOACs, including pre-analytical, analytical and post-analytical factors in the overall testing process with a special accent on the available specific quantitative methods for measurement of DOACs in circulation.
直接口服抗凝剂（DOACs）是新一代药物，已越来越多地用于预防和治疗血栓栓塞状态。根据抗凝作用机制，DOACs分为两组：凝血酶直接抑制剂（达比加群）和活化因子X（FXa）直接抑制剂（利伐沙班、阿哌沙班、依度沙班、贝曲沙班）。与维生素K拮抗剂相比，DOACs在起效时间、药代动力学和药效学特性以及固定每日剂量方面具有优势，无需常规凝血监测。尽管有这些优点，但在某些临床情况下仍应进行DOACs的实验室检测。虽然DOACs会影响筛查止血试验（凝血酶原时间，PT；活化部分凝血活酶时间，aPTT；以及凝血酶时间，TT），但这些试验不适用于定量药物水平。因此，特定的定量方法（液相色谱-串联质谱法作为所有DOACs的金标准方法、达比加群的凝固法和显色法以及使用药物特异性校准物的FXa抑制剂显色抗Xa法）仅应用于测定DOACs浓度。本综述的目的是介绍DOACs实验室评估的各个方面，包括整个检测过程中的分析前、分析和分析后因素，并特别强调循环中DOACs测量的可用特定定量方法。
