Van Cott Elizabeth M, Roberts A Joshua, Dager William E
Department of Pathology GRJ235, Massachusetts General Hospital, Boston, Massachusetts.
Department of Pharmacy, University of California Davis Medical Center, Sacramento, California.
Semin Thromb Hemost. 2017 Apr;43(3):270-276. doi: 10.1055/s-0036-1597297. Epub 2017 Jan 4.
Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.
阿加曲班和比伐卢定是肠外直接凝血酶活性抑制剂，但与肝素不同的是，它们既能抑制可溶性凝血酶，也能抑制与凝块结合的凝血酶。这些药物发挥活性不需要抗凝血酶作为辅助因子。肠外直接凝血酶抑制剂（DTIs）可用于多种情况，包括肝素诱导的血小板减少症（HIT）或对肝素过敏，以及需要进行侵入性心血管介入治疗而需抗凝的患者。在没有器官系统功能衰竭的患者中，这两种药物的半衰期相对较短，通常通过持续输注给药。阿加曲班主要通过肝脏清除，而比伐卢定则通过凝血酶的蛋白水解裂解和肾脏清除机制共同清除。有几种实验室检测方法可用于监测DTIs的抗凝效果：活化部分凝血活酶时间（aPTT）和活化凝血时间（ACT）是最常用的检测方法，但有时凝血酶时间也可能有用。其他凝血检测方法，如稀释凝血酶时间（dTT）、发色抗IIa检测法和蛇静脉酶凝血时间（ECT）也可使用。DTIs的抗凝强度取决于使用指征。对于HIT患者，阿加曲班和比伐卢定的目标aPTT分别为患者基线值的1.5至3.0倍和1.5至2.5倍。经皮冠状动脉介入治疗期间使用的DTI抗凝作用可用ACT来测量。两种DTIs都可能因其血浆浓度导致国际标准化比值升高。本文将综述肠外DTIs的使用以及评估这些药物抗凝效果的相关实验室检测方法。
