Katada Yoshiki, Nakagawa Shunsaku, Nishimura Akiko, Sato Yu-Ki, Taue Hiromi, Matsumura Katsuyuki, Yamazaki Kazuhiro, Minakata Kenji, Yano Ikuko, Omura Tomohiro, Imai Satoshi, Yonezawa Atsushi, Sato Yuki, Nakagawa Takayuki, Minatoya Kenji, Matsubara Kazuo
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
Eur J Clin Pharmacol. 2019 Apr;75(4):561-568. doi: 10.1007/s00228-018-2592-4. Epub 2018 Nov 21.
Warfarin shows large inter- and intra-individual variabilities in its pharmacokinetics and pharmacodynamics. Sufficient understanding of factors affecting the response to warfarin is necessary to achieve improved outcomes for warfarin therapy. In this study, we evaluated effects of fasting on the anticoagulant properties of warfarin.
We conducted a retrospective observational study involving a total of 58 patients, who received cardiovascular surgeries and subsequent warfarin therapy. The effect of dietary intake on the anticoagulant properties with warfarin was assessed by measurement of the international normalized ratio of prothrombin time (PT-INR): the anticoagulant activities of warfarin were expressed as the warfarin sensitivity index (WSI). Additionally, fluctuations in WSI during the study period were obtained as differences between the maximum and minimum WSI.
The maximum PT-INR and WSI values were significantly higher for patients who were fasting for different reasons during the postoperative period than those in the group without reduced dietary intake. The differences between maximum and minimum WSI in the fasting group significantly increased compared with those in the groups with moderate or no reduced dietary intake. Meanwhile, effects of other markers of clinical conditions including the baseline Child-Pugh score and Charlson Comorbidity Index on WSI were not significant.
Our results indicate that postoperative fasting was significantly associated with the anticoagulation activity of warfarin. In patients fasting for different reasons during the postoperative period, closer control of PT-INR values and warfarin adjustments may be required to avoid adverse effects such as bleeding in warfarin treatment.
华法林在药代动力学和药效学方面存在较大的个体间和个体内变异性。充分了解影响对华法林反应的因素对于改善华法林治疗效果至关重要。在本研究中，我们评估了禁食对华法林抗凝特性的影响。
我们进行了一项回顾性观察研究，共纳入58例接受心血管手术及后续华法林治疗的患者。通过测量凝血酶原时间国际标准化比值（PT-INR）来评估饮食摄入对华法林抗凝特性的影响：华法林的抗凝活性用华法林敏感性指数（WSI）表示。此外，研究期间WSI的波动通过最大和最小WSI之间的差值获得。
术后因不同原因禁食的患者，其最大PT-INR和WSI值显著高于饮食摄入量未减少组的患者。与饮食摄入量中度减少或未减少组相比，禁食组最大和最小WSI之间的差异显著增加。同时，包括基线Child-Pugh评分和Charlson合并症指数在内的其他临床状况指标对WSI的影响不显著。
我们的结果表明，术后禁食与华法林的抗凝活性显著相关。在术后因不同原因禁食的患者中，可能需要更密切地控制PT-INR值并调整华法林剂量，以避免华法林治疗中出现出血等不良反应。
