Department of Internal Medicine, Riviera-Chablais Hospital, Rennaz, Switzerland.
Division of Haematology and Central Haematology Laboratory, CHUV Lausanne University Hospital, University of Lausanne (UNIL), Lausanne, Switzerland.
Hamostaseologie. 2020 Jun;40(2):184-200. doi: 10.1055/a-1113-0655. Epub 2020 May 26.
There is an increasing amount of literature on direct oral anticoagulant (DOAC) laboratory monitoring. The aims of the present review were to evaluate published data on monitoring DOACs, to provide clinical guidance on how to interpret results, and to summarize why, when, and how to monitor DOACs.
The publications screened for this review were obtained through a PubMed search for articles published in English or French before April 2019 that had the following as their main themes: DOAC monitoring, DOAC exposure-effect relationship, DOAC drug interactions, and pharmacokinetics and pharmacodynamics of DOACs.
DOACs show important inter- and intrapersonal concentration variability and a significant exposure-effect relationship. Concentrations out of the expected range have been shown to lead to an increased adverse event rate and a lower efficacy. No definitive therapeutic range exists for DOACs except for dabigatran for which trough levels of 40 to 200 ng/mL seem to be the consensus. Indications to monitor include suspected drug accumulation in special patient populations, suspected drug failure, and acute situations such as hemorrhagic or thrombotic events.
There is a likely benefit to monitor DOACs in order to improve their safety and efficacy but randomized controlled trials are required to determine the therapeutic range of these drugs and evaluate whether DOAC monitoring can improve outcomes in a clinical setting.
关于直接口服抗凝剂（DOAC）实验室监测的文献越来越多。本综述的目的是评估已发表的关于监测 DOAC 的数据，就如何解读结果提供临床指导，并总结为何、何时以及如何监测 DOAC。
通过在 PubMed 上搜索发表于 2019 年 4 月之前的英文或法文文献，筛选出本次综述的相关文献，这些文献的主题主要包括 DOAC 监测、DOAC 暴露-效应关系、DOAC 药物相互作用以及 DOAC 的药代动力学和药效学。
DOAC 显示出重要的个体间和个体内浓度变异性以及显著的暴露-效应关系。超出预期范围的浓度已被证明会导致不良事件发生率增加和疗效降低。除达比加群外，DOAC 目前尚无明确的治疗范围，达比加群的谷浓度似乎为 40 至 200ng/ml。需要监测的指征包括特殊患者人群中疑似药物蓄积、疑似药物失效以及出血或血栓形成等急性情况。
为了提高 DOAC 的安全性和疗效，对其进行监测可能是有益的，但需要开展随机对照试验来确定这些药物的治疗范围，并评估 DOAC 监测是否能改善临床环境中的结局。
