Kitajima Isao
Rinsho Byori. 2016 Aug;64(8):972-979.
Vitamin K antagonists such as warfarin, which inhibit vitamin K-dependent clotting factors II, VII, IX, and X, have been the only available oral anticoagulants for more than 50 years. Direct oral anticoagulants (DOACs), including direct anti-Xa and a thrombin inhibitor, have been introduced and provide advantages over warfarin. DOACs are rapidly-acting, target-specific anticoagulants that inhibit both free and bound activated serine proteases, unlike heparin that can inhibit only free proteases. The FXa inhibitors (Rivaroxaban, Apixaban, Edoxaban) bind directly to the catalytic site of FXa and inhibit both free and prothrombinase-bound FXa. The thrombin inhibitor (Dabigatran), designed to occupy and inactivate the serine proteolytic pocket of thrombin, prevents thrombin from acting on fibrinogen to produce fibrin. Although routine coagulation mon- itoring of DOACs is not required, it may be useful under some circumstances. Several reports have de- scribed the effect of DOACs on routine assays including the APTT and PT. Dabigatran will interfere with most APTT-based and some PT-based assays, which means that laboratory testing will lead to results that are not representative of the physiologic effects. Rivaroxaban and edoxaban prolong the PT to a greater extent than APTT, and these agents may interfere with PT-based factor activity assays (FVII, X, V, and II) causing factitiously low activities. Also discussed are the use of drug-specific assays and alternative meth- ods to determine the relative drug concentration, such as evaluating drug calibrators in APTT and PT assays. The actual drug concentration may be required for specific patients, such as those with deterioration of the renal function, before surgical interventions, bleeding or thrombotic episodes, and suspected overdoses, and to control adherence to therapy. The need to assess DOACs in emergent situations as well as their impact on routine and special coagulation assays has created challenges in most laboratories. [Review] '.
维生素K拮抗剂，如华法林，可抑制维生素K依赖的凝血因子II、VII、IX和X，50多年来一直是唯一可用的口服抗凝剂。直接口服抗凝剂（DOACs），包括直接抗Xa因子药物和凝血酶抑制剂，已被引入并具有优于华法林的优点。DOACs是快速起效的、靶向特异性抗凝剂，可抑制游离和结合的活化丝氨酸蛋白酶，这与只能抑制游离蛋白酶的肝素不同。FXa抑制剂（利伐沙班、阿哌沙班、依度沙班）直接结合到FXa的催化位点，抑制游离和凝血酶原酶结合的FXa。凝血酶抑制剂（达比加群）旨在占据并灭活凝血酶的丝氨酸蛋白水解口袋，防止凝血酶作用于纤维蛋白原产生纤维蛋白。虽然不需要对DOACs进行常规凝血监测，但在某些情况下可能会有用。几份报告描述了DOACs对包括活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）在内的常规检测的影响。达比加群会干扰大多数基于APTT的检测和一些基于PT的检测，这意味着实验室检测结果将不能代表其生理效应。利伐沙班和依度沙班使PT延长的程度大于APTT，并且这些药物可能会干扰基于PT的因子活性检测（FVII、X、V和II），导致人为的低活性。还讨论了使用药物特异性检测和替代方法来确定相对药物浓度，例如在APTT和PT检测中评估药物校准物。对于特定患者，如肾功能恶化患者、手术干预前、出血或血栓形成发作时以及疑似药物过量时，可能需要实际药物浓度，以控制治疗依从性。在紧急情况下评估DOACs及其对常规和特殊凝血检测的影响，给大多数实验室带来了挑战。[综述]
