Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Can J Cardiol. 2019 Jun;35(6):736-743. doi: 10.1016/j.cjca.2019.02.012. Epub 2019 Feb 27.
Conventional coagulation assays have poor sensitivity and specificity for assessing the anticoagulant effect of direct oral anticoagulants (DOACs). This study aimed to evaluate the causes and consequences of the excessive prolongation of coagulation time in patients with nonvalvular atrial fibrillation who receive DOACs.
We retrospectively analysed 1521 patients (age, 66 ± 12 years). The prothrombin time (PT) and activated partial thromboplastin time (APTT) were averaged if they were measured more than twice depending on the respective DOAC and dosage across individuals. Excessive coagulation time prolongation was defined as PT or APTT of >2 standard deviations over the median for each DOAC.
In all, 1913 DOAC cases were found. Excessive prolongation (EP), which was noted in 88 patients (5.8%), was found to be significantly associated with inappropriately high DOAC dosage and body weight (≤ 60 kg). During follow-up (median, 8.9 months), thromboembolisms developed in 10 patients (0.66%) and bleeding events in 85 (5.6%). Bleeding events were significantly higher in patients with excessive prolongation (EP group) than in those without (P = 0.013). Of the 53 patients in the EP group, 15 (28%) were positive for antiphospholipid antibodies, 6 (11%) had inappropriately high prescription dosages, 4 (8%) had coagulation factor deficiencies, and 3 (6%) had severe liver dysfunction.
Bleeding event rates were remarkably higher in patients receiving DOACs that caused EP of PT or APTT. Thus, following the current guidelines and administering the recommended dose of DOACs are fundamentally important. Patients with the body weight of <60 kg should be considered for dosage reduction or DOAC withdrawal.
传统凝血检测在评估直接口服抗凝剂（DOAC）的抗凝效果方面，灵敏度和特异性较差。本研究旨在评估服用 DOAC 的非瓣膜性房颤患者凝血时间过度延长的原因和后果。
我们回顾性分析了 1521 名患者（年龄 66±12 岁）。根据各自的 DOAC 和个体剂量，若两次以上测量凝血酶原时间（PT）和激活部分凝血活酶时间（APTT），则将其平均值。将超过每个 DOAC 中位数 2 个标准差的 PT 或 APTT 定义为凝血时间过度延长。
共发现 1913 例 DOAC 病例。88 例（5.8%）存在过度延长（EP），与 DOAC 剂量和体重（≤60kg）过高显著相关。在随访期间（中位数 8.9 个月），10 例（0.66%）发生血栓栓塞，85 例（5.6%）发生出血事件。EP 组出血事件发生率明显高于无 EP 组（P=0.013）。在 EP 组的 53 例患者中，15 例（28%）抗磷脂抗体阳性，6 例（11%）处方剂量过高，4 例（8%）凝血因子缺乏，3 例（6%）严重肝功能异常。
服用 DOAC 引起 PT 或 APTT 过度延长的患者出血事件发生率显著升高。因此，遵循现行指南和给予推荐剂量的 DOAC 至关重要。体重<60kg 的患者应考虑减少剂量或停用 DOAC。
