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Ideas and Opinions |

Should We Be Applying Warfarin Pharmacogenetics to Clinical Practice? No, Not Now

Michael H. Rosove, MD; and Wayne W. Grody, MD, PhD
[+] Article, Author, and Disclosure Information

From the University of California, Los Angeles, Los Angeles, California.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Michael H. Rosove, MD, 100 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90095; e-mail, mrosove@mednet.ucla.edu.

Current Author Addresses: Dr. Rosove: 100 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90095.

Dr. Grody: UCLA Center for the Health Sciences, 760 Westwood Plaza, Los Angeles, CA 90095.

Ann Intern Med. 2009;151(4):270-273. doi:10.7326/0003-4819-151-4-200908180-00009
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The U.S. Food and Drug Administration modified warfarin labeling in 2007 to suggest, but not mandate, pharmacogenetic testing. Genetic analysis is now commercially available. However, results predict only one third of all dosing variation, the value of testing in reducing bleeding and thrombosis rates remains unproved, and cost-effectiveness is not established. Careful consideration of clinical factors that influence dosing, conscientious prothrombin time monitoring, and sage dosage adjustment remain paramount in warfarin management. Further study is required before routine warfarin pharmacogenetic testing can be recommended.





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pharmacogenetics and clinical practice: time to reflect
Posted on August 19, 2009
pietro cavalli
servizio di genetica, azienda istituti ospitalieri, cremona, italy
Conflict of Interest: None Declared

The costs of genetic tests depend on type of procedure used, cost of labor involved in the procedure, number and size of genes being tested, searching for known or unknown mutations. Moreover, it should be underlined that the costs of a genetic test being done in a general laboratory greatly differs from the same test being done in a genetics lab. Commercially available kits are used in general laboratories, yet genetics labs often use different techniques such as real-time PCR, sequencing, and others.

The choice of what procedure being used greatly impacts on economic costs. A single SNP-based real-time PCR assay should be considered inexpensive, as its cost is less than 10 Euros, including DNA extraction. Sequencing a DNA fragment up to 500 bp costs about the same. If so, the economic costs of commercially available kits for warfarin pharmacogenetics(400 "“ 500 USD/patient) should be carefully compared with the costs of the same procedure performed in genetics labs, that can produce the same results at lowest costs (up to tenfold lower). Moreover, the choice of what and how many CYP2C9 and VKORC1 polymorphisms should be included in the analysis of warfarin pharmacogenetics depends on the allele frequency in different ethnic groups. As an example, heterozygous CYP2C9*3, that produces a 60% reduction in warfarin clearance can be found in 6-10% of whites and 0.5-1.5% in individuals of African origin, and CYP2C9*2 (15% reduction in warfarin clearance) can be found in 8-19% of whites and 0% of asian individuals (1,2,3). Therefore, CYP2C9 and VKORC1 genotyping should be done according to those considerations, and the performance of commercial kits in selected populations needs to be carefully assessed.

I agree with Rosove and Grody (4) that clinical considerations are of paramount importance in driving warfarin treatment, and that pharmacogenetics is still far from having a solid role in managing those patients. However, genetics tests might identify some patients at risk for serious bleeding complications, and it is not clear why genetic status should hardly be considered in clinical management. Genetic tests simply add more information to standard clinical evaluation and, from a Bayesian point of view, are associated with a more accurate clinical management. Moreover, the patient viewpoint should also be kept in mind, as individualizing therapy should be considered another key point to assess clinical appropriateness.


1. Takahashi H, Kashima T, Nomizo Y et Al. metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes. Clin Pharmacol Ther 1998;63:519-528

2. Steward DJ, Haining RL, Henne KR et Al. Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 1997;7:361-367

3. Adcock DM, Koftan C, Crisan D, Kiechle FL. Effect of polymorphisms in the Cytochrome P450 CYP2C9 gene on warfarin anticoagulation. Arch Pathol Lab Med 2004;128:1360-1363

4. Rosove MH, Grody WW. Should we be applying warfarin pharmacogenetics to clinical practice? No, not now. Ann Int med. 2009;151:270-273

Conflict of Interest:

None declared

Role of pharmacogenetic test kit for warfarin in developing countries
Posted on August 27, 2009
Udip Dahal
No Affiliation
Conflict of Interest: None Declared

The dose of warfarin we use in Nepal is primarily based on western literature although the build of general Nepalese people is smaller than those of western people.Interestingly, this drug seems to be more well tolerated than in the western population. I wonder whether commercially available warfarin pharmacogenetic test kits will ever be cost effective in a developing country like Nepal where infectious diseases still lead the overall mortality rate, but if they become available at subsidized costs then it will be of great value to find out the proper dose needed for patients in this part of the world.

Conflict of Interest:

None declared

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