Abstract:
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.
摘要:
直接口服抗凝剂(DOAC)代表了新一代药物,已越来越多地用于预防和治疗血栓栓塞状态。根据抗凝血作用机制,DOAC分为两组:凝血酶直接抑制剂(达比加群)和活化因子X直接抑制剂(FXa)(利伐沙班,阿哌沙班,edoxaban,betrixaban).与维生素K拮抗剂相比,DOAC在起效方面是优越的,药代动力学和药效学特性和固定的日剂量,无需常规凝血监测。尽管有这些优势,在某些临床条件下,应进行DOAC的实验室测量。尽管DOAC对筛查止血测定有影响(凝血酶原时间,PT;活化部分凝血活酶时间,aPTT;和凝血酶时间,TT),这些测试不适用于定量药物水平。因此,特定的定量方法(LC-MS/MS作为所有DOAC的黄金标准方法,达比加群的凝血和显色测定,和具有FXa抑制剂的药物特异性校准物的显色抗Xa测定法)应仅用于确定DOACs浓度。这篇综述的目的是介绍DOAC实验室评估的所有方面,包括预分析,整个测试过程中的分析和分析后因素,特别强调可用的特定定量方法来测量流通中的DOAC。