Clinical Pharmacy, Methodist University Hospital, Memphis, TN, USA.
Ann Pharmacother. 2013 Jun;47(6):e28. doi: 10.1345/aph.1R688.
To report a case of prolonged vomiting during warfarin therapy, leading to an elevated international normalized ratio (INR).
A 32-year-old female with a history of cyclic vomiting syndrome since early childhood and bilateral pulmonary emboli diagnosed 4 months prior to this acute event presented to the clinic for routine monitoring of warfarin therapy. The warfarin dose had been maintained at 35 mg/wk for 3½ months (INR 2-3.5), but it was increased to 37.5 mg/wk because the INR had trended down to the low goal range over the preceding month. At presentation, the patient reported a 15-day history of vomiting with minimal oral intake that required intravenous fluids to prevent dehydration. The INR was 4.7; warfarin was withheld, and oral vitamin K 5 mg as well as subcutaneous vitamin K 10 mg was administered the following day. The INR then decreased to 1.3. Therapy was transitioned to subcutaneous enoxaparin 1 mg/kg every 12 hours for the duration of the patient's anticoagulation therapy.
Multiple reports have demonstrated malabsorption of warfarin and decreased INR response in the presence of underlying gastrointestinal disease. Despite a prolonged episode of cyclic vomiting syndrome, our patient had an elevated INR. In normal circumstances, warfarin is rapidly absorbed from the gastrointestinal tract and reaches maximum serum concentrations in approximately 90 minutes. Studies have shown that although the presence of food does not affect overall absorption of the medication, it can decrease the rate of absorption. Our patient was vomiting 20-30 minutes after oral dose administration. Because the patient was not consuming food, absorption of warfarin was potentially prompt, thus contributing to the elevated INR. The variability of vitamin K in the diet also can have significant impact on the response to warfarin. Our patient's INR had been stable while she consumed 3 servings each week of foods rich in vitamin K. This consumption was abruptly discontinued with the onset of the cyclic vomiting syndrome. We believe that decreased intake and retention of oral vitamin K-containing foods from the diet due to the prolonged vomiting coupled with the rapid onset of absorption resulted in a notably increased INR and subsequent bruising in our patient.
In the presence of prolonged vomiting, warfarin therapy requires more frequent monitoring than usual to detect fluctuations in INR that may increase the risk of adverse events.
报告 1 例华法林治疗期间持续呕吐导致国际标准化比值（INR）升高的病例。
患者为 32 岁女性，自幼患有周期性呕吐综合征，4 个月前被诊断为双侧肺栓塞，此次因华法林治疗常规监测就诊。华法林剂量已维持 35 毫克/周 3 个半月（INR 2-3.5），但由于过去 1 个月 INR 呈下降趋势至低目标范围，因此增加至 37.5 毫克/周。就诊时，患者诉有 15 天的呕吐史，仅少量摄入食物，需静脉补液以防止脱水。INR 为 4.7；华法林被停用，次日给予口服维生素 K 5 毫克和皮下维生素 K 10 毫克。INR 随后降至 1.3。随后，患者接受皮下依诺肝素 1 毫克/公斤，每 12 小时 1 次，持续抗凝治疗。
多项报告表明，存在基础胃肠道疾病时，华法林吸收不良，INR 反应降低。尽管患者有反复发作的周期性呕吐综合征，但 INR 升高。在正常情况下，华法林从胃肠道迅速吸收，约 90 分钟达到血清峰值浓度。研究表明，尽管食物不影响药物的总体吸收，但可以降低吸收速度。患者在口服药物后 20-30 分钟呕吐。由于患者未进食，华法林吸收可能迅速，从而导致 INR 升高。饮食中维生素 K 的变异性也会对华法林的反应产生重大影响。患者每周摄入 3 份富含维生素 K 的食物时，INR 保持稳定。当周期性呕吐综合征发作时，这种摄入突然停止。我们认为，由于呕吐时间延长，饮食中口服含维生素 K 的食物摄入和保留减少，再加上吸收迅速，导致患者 INR 显著升高，随后出现瘀斑。
在持续呕吐的情况下，华法林治疗需要更频繁的监测，以发现 INR 的波动，这可能增加不良事件的风险。
