warfarin dose

Volume 360:753-764 February 19, 2009 Number 8
Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data
The International Warfarin Pharmacogenetics Consortium


ABSTRACT

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 21 mg of warfarin or less per week and of those who required 49 mg 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 21 mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring 49 mg 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 21 mg or less of warfarin per week or 49 mg or more per week for therapeutic anticoagulation.



Source Information


Address reprint requests to the International Warfarin Pharmacogenetics Consortium at 300 Pasteur Dr., Ln. 301, Mailstop 5120, Stanford, CA 94305, or at iwpc@pharmgkb.org.


中研院研究》抗凝血劑 依基因精準抓劑量

【聯合報╱記者楊正敏／台北報導】
2009.02.20 02:19 am


中研院發展抗凝血劑劑量公式，李明達博士拿著基因鑑定套件，很快就驗出結果。
記者趙文彬／攝影
未來使用口服抗凝血劑「華法林」時，不必再為劑量頭痛了。中央研究院國家基因體鑑定中心參與的一項國際鉅型研究計畫，發展出「華法林」劑量公式，可依病人的基因型，精確算出藥量，減少藥物不良反應，有效預防心臟病或中風。

這項研究是由國科會基因體國家型計畫經費支持，中研院、長庚醫院等單位參與，研究成果獲刊登於醫學界權威期刊「新英格蘭醫學」，昨天全球同步發表。

中研院生醫所所長陳垣崇說，未來會在台灣進行「華法林」劑量公式的大型臨床試驗，從臨床治療上驗證公式的準確性，預計最快一年半後可以完成，屆時就能應用於臨床治療。

中研院基因體鑑定中心研究助技師李明達指出，華法林是目前世界上最被廣泛使用的口服抗凝血劑，可以用來預防深部靜脈栓塞、肺栓塞、缺血性冠狀動脈症狀。在台灣保守估算，每年約有三萬人，使用超過一千萬顆華法林。

他指出，華法林劑量很難掌控，且每個人的差異很大，劑量過多可能造成中風；過少會造成血栓塞。醫師多半只能按照病人的年紀、身高體重及經驗等判斷。

二○○五年陳垣崇帶領的團隊發現人體VKORC1基因上的基因型差異，影響人體對「華法林」劑量的需求，不知是否能運用在所有種族的人身上。

因此九國廿一個團隊展開合作研究，觀察五千七百位固定服「華法林」藥物的不同種族病患的醫療效果，先鑑定患者的基因型，再加上身高、體重、年齡等，發展出計算公式，可以精確預測適當劑量。

李明達說，中研院發展出快速基因型鑑定的套件，用現有的設備就能在三點五小時檢出患者的基因型。未來劑量公式也將網頁化，只要填進相關資訊與基因型，五秒內就能算出劑量。他指出，有這套公式，不僅能減少劑量不準造成的不良反應，更能提升治療品質，患者不必為了調藥到往返醫院，往個人化醫療再邁進一步。

【2009/02/20 聯合報】@ http://udn.com/

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http://content.nejm.org/cgi/content/full/360/7/711

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