Duke University, Durham, North Carolina.
Hofstra North Shore/LIJ School of Medicine at Lenox Hill Hospital, Manhasset, New York.
JACC Cardiovasc Interv. 2014 Dec;7(12):1333-51. doi: 10.1016/j.jcin.2014.06.014.
Direct oral anticoagulants (DOACs) are approved for multiple thromboembolic disorders and provide advantages over existing agents. As with all anticoagulants, management protocols for the eventuality of bleeding are important. Randomized phase III studies generally show that DOACs have a similar risk of clinically relevant bleeding compared with standard anticoagulants, with reductions in major bleeding in some cases. This may be particularly important in patients with atrial fibrillation, for whom the rate of intracranial hemorrhage was approximately halved with DOACs compared with warfarin. Conversely, the risk of gastrointestinal bleeding may be increased. Specific patient characteristics, such as renal impairment, comedications, and particular aspects of each drug, including the proportion eliminated by the kidneys, must be taken into account when assessing the risk of bleeding. Although routine coagulation monitoring of DOACs is not required, it may be useful under some circumstances. Of the traditional clotting assays, a sensitive and calibrated prothrombin time may be useful for detecting the presence or absence of clinically relevant factor Xa inhibitor concentrations (rivaroxaban or apixaban), but specific anti-factor Xa assays can measure drug levels quantitatively. For dabigatran, the results of an activated partial thromboplastin time test may exclude a clinically relevant pharmacodynamic effect, but a calibrated dilute thrombin time assay can be used for quantification of drug levels. In the event of mild or moderate bleeding, normal hemostatic support measures are recommended. For life-threatening bleeding, use of nonspecific prohemostatic agents may be considered, although clinical evidence is scarce. Specific antidotes are in development.
直接口服抗凝剂（DOACs）获批用于多种血栓栓塞性疾病，并具有优于现有药物的优势。与所有抗凝剂一样，针对出血事件的管理方案非常重要。随机 III 期研究通常表明，DOACs 与标准抗凝剂相比，具有相似的临床相关出血风险，某些情况下大出血减少。这在房颤患者中可能尤为重要，与华法林相比，DOACs 使颅内出血的发生率降低了约一半。相反，胃肠道出血的风险可能增加。在评估出血风险时，必须考虑特定的患者特征，如肾功能不全、合并用药以及每种药物的特定方面，包括通过肾脏消除的比例。尽管不需要常规监测 DOACs 的凝血情况，但在某些情况下可能有用。在传统的凝血检测中，敏感和校准的凝血酶原时间可能有助于检测是否存在或不存在具有临床意义的因子 Xa 抑制剂浓度（利伐沙班或阿哌沙班），但特定的抗因子 Xa 检测可以定量测量药物水平。对于达比加群，活化部分凝血活酶时间试验的结果可能排除了具有临床意义的药效学效应，但可以使用校准稀释凝血酶时间试验来定量药物水平。在出现轻度或中度出血的情况下，建议采用常规止血支持措施。对于危及生命的出血，可以考虑使用非特异性促凝剂，尽管临床证据很少。特定的解毒剂正在开发中。
