Béné Johana, Saïd Worighi, Rannou Marianne, Deheul Sylvie, Coupe Patrick, Gautier Sophie
Regional Center of Pharmacovigilance, Lille University Hospital Center, Lille, France.
Ann Pharmacother. 2012 Jun;46(6):e14. doi: 10.1345/aph.1Q705. Epub 2012 Jun 5.
To report rectal bleeding associated with hemostatic disorders in 2 elderly patients treated with dabigatran etexilate.
A 79-year-old woman (weight, 69 kg) was hospitalized in a gastroenterology unit for severe rectal bleeding. She had been treated for 2 months with dabigatran etexilate 110 mg twice daily for chronic atrial fibrillation. On admission, her creatinine clearance (CrCl) was 20.7 mL/min/1.73 m(2), prothrombin time (PT) less than 10% (reference range 70-130%), and international normalized ratio (INR) 14.5 (venous blood). Eleven days after admission, hematologic and renal function were normalized and rectal bleeding stopped. An 84-year-old man (weight, 71 kg) was admitted for rectal bleeding with acute renal failure and dehydration that began while he was treated with dabigatran etexilate 110 mg twice daily for atrial fibrillation. On admission, CrCl was 33.5 mL/min/1.73 m(2), PT 13%, and INR 7.53 (venous blood). Dabigatran etexilate was stopped on admission. At the end of the hospitalization, CrCl was 66.5 mL/min/1.73 m(2), PT 54%, and INR 1.53. In both cases, an objective causality assessment revealed that those adverse reactions were probably related to dabigatran etexilate.
In these 2 cases of rectal bleeding during dabigatran etexilate therapy, coagulation monitoring showed elevated PT and INR; neither patient had been exposed to vitamin K antagonists. These cases indicate the importance of PT and INR monitoring when using dabigatran etexilate, mainly in patients with a high risk of overdose, such as elderly patients or those with renal function impairment.
It is critical to identify and subsequently manage dabigatran etexilate toxicity because there is no specific antidote to reverse the drug's anticoagulant effects.
报告2例接受达比加群酯治疗的老年患者出现的与止血障碍相关的直肠出血情况。
一名79岁女性（体重69kg）因严重直肠出血入住胃肠病科。她因慢性房颤接受达比加群酯110mg每日两次治疗2个月。入院时，她的肌酐清除率（CrCl）为20.7mL/min/1.73m²，凝血酶原时间（PT）低于10%（参考范围70 - 130%），国际标准化比值（INR）为14.5（静脉血）。入院11天后，血液学和肾功能恢复正常，直肠出血停止。一名84岁男性（体重71kg）因直肠出血伴急性肾衰竭和脱水入院，其直肠出血在接受达比加群酯110mg每日两次治疗房颤期间开始。入院时，CrCl为33.5mL/min/1.73m²，PT为13%，INR为7.53（静脉血）。入院时停用达比加群酯。住院结束时，CrCl为66.5mL/min/1.73m²，PT为54%，INR为1.53。在这两个病例中，客观因果关系评估显示这些不良反应可能与达比加群酯有关。
在这2例达比加群酯治疗期间出现直肠出血的病例中，凝血监测显示PT和INR升高；两名患者均未使用过维生素K拮抗剂。这些病例表明在使用达比加群酯时进行PT和INR监测的重要性，主要针对有药物过量高风险的患者，如老年患者或肾功能损害患者。
识别并随后处理达比加群酯毒性至关重要，因为目前尚无特异性解毒剂来逆转该药物的抗凝作用。
