全球精选文摘 - 利用临床和遗传药理学数据估计华法林剂量

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利用临床和遗传药理学数据估计华法林剂量

Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data

The International Warfarin Pharmacogenetics Consortium 2009/8/14 20:26:54

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N Engl J Med, 2009,

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Background:
Genetic variability among patients plays an important role in determining the dose of warfarin that should be used when oral anticoagulation is initiated, but practical methods of using genetic information have not been evaluated in a diverse and large population. We developed and used an algorithm for estimating the appropriate warfarin dose that is based on both clinical and genetic data from a broad population base.

Methods:
Clinical and genetic data from 4043 patients were used to create a dose algorithm that was based on clinical variables only and an algorithm in which genetic information was added to the clinical variables. In a validation cohort of 1009 subjects, we evaluated the potential clinical value of each algorithm by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable therapeutic dose; we also evaluated other clinically relevant indicators.

Results:
In the validation cohort, the pharmacogenetic algorithm accurately identified larger proportions of patients who required 21mg of warfarin or less per week and of those who required 49mg or more per week to achieve the target international normalized ratio than did the clinical algorithm (49.4% vs. 33.3%, P<0.001, among patients requiring ≤21mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring ≥49mg per week).

Conclusions:
The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach. The greatest benefits were observed in the 46.2% of the population that required 21mg or less of warfarin per week or 49mg or more per week for therapeutic anticoagulation.

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病例分析 [栏目介绍]

呼吸急促伴精神状态改变——《西氏内科学》病例

摘自：《西氏内科学》，第23版

患者男性，36岁，幼年有吸入性肺损伤史，因呼吸急促和精神状态改变来我院就诊。患者睡眠和运动时，吸氧流量基值为2 L/min，每天均进行肺功能康复训练。患者居住在美国中西部，入院5天前曾离家乘船来这里看望其兄弟。入院前一天，患者呼吸急促加剧，自觉发热并注意到其慢性咳嗽稍加重，但痰液无变化。当天晚上，家人注意到患者更加急躁并有点偏执。由于症状加重，患者于次日送我院就诊。

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