Nakazawa Takafumi, Yamazaki Shingo, Uchida Masashi, Suzuki Takaaki, Nakamura Takako, Ohtsuka Masayuki, Ishii Itsuko
Division of Pharmacy, Chiba University Hospital, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, 260-8677, Japan.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba-Shi, Chiba, 260-8675, Japan.
Eur J Clin Pharmacol. 2023 Mar;79(3):437-443. doi: 10.1007/s00228-023-03459-7. Epub 2023 Feb 1.
A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin.
Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction.
Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR.
PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.
在使用华法林的患者发生胆道梗阻期间，经常观察到凝血酶原时间-国际标准化比值（PT-INR）显著延长。本研究的目的是确定使用华法林的患者在胆道梗阻期间与PT-INR延长相关的因素。
在44例使用华法林且发生胆道梗阻的患者中，我们回顾性调查了胆道梗阻前后的华法林剂量和实验室数据。主要结局是PT-INR变化（ΔPT-INR）与胆道梗阻前后实验室数据变化之间的关联。
胆道梗阻前PT-INR中位数为1.59（四分位间距1.38-1.95），梗阻期间为2.27（四分位间距1.60-3.49），表明梗阻期间有显著延长（P<0.001）。ΔPT-INR与总胆红素变化（ΔT-Bil；ρ=0.692，P<0.001）和结合胆红素变化（ΔC-Bil；ρ=0.731，P<0.001）呈强正相关。ΔPT-INR与白蛋白变化（ΔAlb；ρ=-0.371，P<0.05）呈弱负相关。当在多元线性回归分析中使用ΔPT-INR作为因变量时，ΔT-Bil、ΔC-Bil和ΔAlb与ΔPT-INR显著相关。
使用华法林的患者在胆道梗阻期间PT-INR延长，胆红素水平变化与ΔPT-INR相关。如果发生胆红素水平明显升高的胆道梗阻，检测PT-INR可使华法林治疗更安全。
