Department of Pharmacy, Rochester General Hospital, Rochester, NY, USA.
Ann Pharmacother. 2012 Apr;46(4):e10. doi: 10.1345/aph.1Q747. Epub 2012 Apr 10.
To report a case of dabigatran-induced overanticoagulation in a patient who developed acute renal failure and to inform health care providers of the need for appropriate patient selection and periodic monitoring of renal function in the elderly.
A 66-year-old woman treated with dabigatran for atrial fibrillation developed acute renal failure and upper gastrointestinal bleeding. She had been taking dabigatran 150 mg twice daily for 2 months, with intermittent renal insufficiency during the previous 6 months. On admission, laboratory values included serum creatinine 3.6 mg/dL, hematocrit 21%, and international normalized ratio greater than 10. She was treated with packed red blood cells, prothrombin complex concentrate, and multiple sessions of dialysis. There were no further bleeding events or additional transfusions for the remainder of the hospitalization. Her renal function never recovered and she remained hemodialysis-dependent. After a 47-day length of stay, she was transferred to a nursing home where she died 2 months later.
Renally eliminated drugs such as dabigatran place elderly patients at increased risk of drug accumulation and adverse drug events due to age-related decline in renal function. In a recent case series, dabigatran toxicity in the elderly with renal impairment was described with 1 fatal outcome. Recent literature, including the package insert, advises intermittent monitoring of renal function in the elderly and those with moderate renal impairment. Consideration should also include the appropriateness of dabigatran therapy in patients with fluctuating renal function. In our patient, the Naranjo probability scale indicated a probable cause between the bleeding event and dabigatran use.
Our case report, along with 2 other recent reports on dabigatran toxicity, illustrates the importance for appropriate patient selection and the need to periodically monitor renal function in elderly patients receiving dabigatran.
报告 1 例达比加群导致抗凝过度的病例，以提醒医护人员在为老年患者选择达比加群治疗时应注意适应证，并定期监测肾功能。
1 例 66 岁女性因心房颤动接受达比加群治疗，出现急性肾衰和上消化道出血。她接受达比加群 150mg，每日 2 次治疗已有 2 个月，此前 6 个月间间歇性肾功能不全。入院时，实验室检查示血肌酐 3.6mg/dL、血细胞比容 21%、国际标准化比值（INR）＞10。患者接受了红细胞悬液、凝血酶原复合物浓缩物输注及多次透析治疗。住院期间未再发生出血事件或需要进一步输血。她的肾功能未恢复，仍依赖血液透析。住院 47 天后，患者转至疗养院，2 个月后死亡。
达比加群等经肾脏清除的药物在老年患者中因肾功能随年龄增长而下降，药物蓄积和药物不良反应的风险增加。在最近的病例系列研究中，描述了肾功能不全的老年患者应用达比加群发生毒性的情况，其中 1 例死亡。最近的文献，包括药品说明书，建议对老年患者和中重度肾功能不全患者应间断监测肾功能。还应考虑到肾功能波动患者应用达比加群的适宜性。在我们的患者中，Naranjo 概率量表提示出血事件与达比加群使用之间可能存在因果关系。
我们的病例报告以及最近另外 2 例达比加群毒性报告均表明，在为老年患者选择达比加群治疗时应注意适应证，并且需要定期监测肾功能。
