White R H, McKittrick T, Hutchinson R, Twitchell J
University of California, Davis.
Ann Intern Med. 1995 Jan 1;122(1):40-2. doi: 10.7326/0003-4819-122-1-199501010-00006.
To measure the rate of decrease of the international normalized ratio (INR) after temporary discontinuation of warfarin therapy.
Prospective evaluation of an outpatient cohort.
University medical center anticoagulation clinic.
22 patients receiving a fixed evening dose of warfarin for whom temporary discontinuation of therapy was deemed safe.
Serial plasma samples were drawn for INR measurements approximately 20, 65, 115, and 185 hours after patients received the last dose of warfarin. In five patients, INR was measured twice daily for 5 days.
For patients with a mean steady-state INR of 2.6, the mean INR 65 hours (2.7 days) after discontinuation of warfarin therapy was 1.6 (range, 1.11 to 2.16); 20 of 22 patients (91%) had an INR greater than 1.2. The mean INR 115 hours (4.7 days) after discontinuation of warfarin therapy was 1.1; 5 of 22 patients (23%) had an INR of 1.2 or greater. In 5 patients studied in detail, the INR decreased exponentially and had a half-life that ranged from 0.52 to 1.2 days; the onset of maximal decrease began 24 to 36 hours after discontinuation of warfarin therapy. In the total cohort, age was a significant (P < 0.005) independent predictor of smaller decreases in the INR between day 1 and day 3 (regression coefficient = -6.8% +/- 2%/2 days per decade of age; R2 = 0.34).
By simulating preoperative discontinuation of warfarin therapy, we found that the INR decreases exponentially, with wide interpatient variation in the rate of decrease. Age is associated with a slower rate of decrease. To be certain that the INR at the time of the surgery is less than 1.2, warfarin should be withheld for 96 to 115 hours (4 doses) in patients with a steady-state INR between 2.0 and 3.0. For patients with a higher steady-state INR, a longer wait is necessary.
测量华法林治疗暂时中断后国际标准化比值（INR）的下降速率。
对一组门诊患者进行前瞻性评估。
大学医学中心抗凝门诊。
22名接受固定晚间剂量华法林治疗且其治疗暂时中断被认为安全的患者。
在患者接受最后一剂华法林后约20、65、115和185小时采集系列血浆样本用于INR测量。在5名患者中，连续5天每天测量两次INR。
对于平均稳态INR为2.6的患者，华法林治疗中断65小时（2.7天）后的平均INR为1.6（范围为1.11至2.16）；22名患者中有20名（91%）的INR大于1.2。华法林治疗中断115小时（4.7天）后的平均INR为1.1；22名患者中有5名（23%）的INR为1.2或更高。在详细研究的5名患者中，INR呈指数下降，半衰期为0.52至1.2天；最大下降开始于华法林治疗中断后24至36小时。在整个队列中，年龄是第１天至第3天INR下降幅度较小的显著（P<0.005）独立预测因素（回归系数=-6.8%±2%/每十岁年龄2天；R2=0.34）。
通过模拟术前华法林治疗中断，我们发现INR呈指数下降，患者间下降速率差异很大。年龄与下降速率较慢有关。为确保手术时INR小于1.2，稳态INR在2.0至3.0之间的患者应停用华法林96至115小时（4剂）。对于稳态INR较高的患者，需要等待更长时间。
