University of California (UC) Davis Medical Center, Sacramento, CA 95817, USA.
Am J Health Syst Pharm. 2013 May 15;70(10 Suppl 1):S21-31. doi: 10.2146/ajhp130042.
To describe a process for prompt evaluation and management- including reversal of the effects of warfarin and target-specific oral anticoagulants-of patients with or at high risk for bleeding during oral anticoagulant therapy or when such therapy is interrupted for an urgent invasive procedure or surgery.
The use of pharmacologic interventions for anticoagulant reversal may depend on the measured level of anticoagulation, time since the last anticoagulant dose, target level of coagulation, reliability of laboratory tests of coagulation, severity of or risk for bleeding, the agents' mechanism of action and pharmacokinetics, and pharmacodynamics of the reversal agent. The patient's age, weight, renal function, comorbid conditions, and other drug therapy, as well as the risk for thromboembolism and other adverse effects of the reversal therapies, also enter into therapeutic decisions. Hemodialysis may be used to remove the direct thrombin (factor IIa) inhibitor dabigatran and reverse its anticoagulant effects. Limited experience with clotting factor concentrates suggests that activated prothrombin complex concentrate may be useful for reversing the anticoagulant effects of dabigatran. The activity of oral factor Xa inhibitors (i.e., rivaroxaban and apixaban) is higher up the common pathway of the coagulation cascade and thus may be easier to reverse than that of direct thrombin inhibitors. Additional clinical experience is needed to identify the optimal reversal agents, dosage, and impact on thrombosis or bleeding outcomes for both classes of agents.
A comprehensive plan individualized to each agent should be developed to promptly reverse the effects of oral anticoagulants and optimize outcomes in patients with bleeding or an urgent need for surgery.
描述一种针对口服抗凝治疗期间或因紧急侵入性操作或手术而中断抗凝治疗时发生或有出血高风险患者的即时评估和管理方法,包括华法林和靶向口服抗凝剂作用的逆转。
抗凝逆转的药物干预可能取决于抗凝的检测水平、最后一次抗凝剂给药后的时间、凝血的目标水平、凝血实验室检测的可靠性、出血的严重程度或风险、药物的作用机制和药代动力学、以及逆转药物的药效动力学。患者的年龄、体重、肾功能、合并症和其他药物治疗情况,以及血栓栓塞和逆转治疗其他不良影响的风险,也会影响治疗决策。血液透析可用于清除直接凝血酶(因子 IIa)抑制剂达比加群并逆转其抗凝作用。有限的凝血因子浓缩物经验表明,活化的凝血酶原复合物浓缩物可能有助于逆转达比加群的抗凝作用。口服 Xa 因子抑制剂(即利伐沙班和阿哌沙班)的活性在上游凝血级联的共同途径中更高,因此可能比直接凝血酶抑制剂更容易逆转。需要更多的临床经验来确定这两类药物的最佳逆转药物、剂量以及对血栓形成或出血结局的影响。
应针对每种药物制定个体化的综合计划,以便迅速逆转口服抗凝剂的作用,优化出血或紧急手术患者的结局。