Typically not. The two alleles you mention are sometimes tested as a guide for determining initial dose for Warfarin. They may or may not be tested (usually not) for anyone on Warfarin, FVL-positive or otherwise.

http://knol.google.com/k/testing-of-vkorc1-and-cyp2c9-alleles-to-guide-warfarin-dosing

Testing for the two alleles is of most value in the days and weeks immediately succeeding an event when the individual's therapeutic Warfarin dose is being sought. Most practitioners still use a form of trial-and-error starting from a low dose and then slowly building up.

The variant for FVL is far different and is known by several names.
http://en.wikipedia.org/wiki/Factor_V_Leiden

The way most genetic tests work is that each one is ordered and billed as a separate line item, so if it is not specifically requested then the test is not run. Each individual test runs in the low $100s.

A more typical battery that a hematologist would order is FVL and Factor II, and even then as part of the decision to continue or cease the drug at a time that is several weeks or months out. Since those tests are genetic, Warfarin does not interfere. Most other hemo tests require leaving Warfarin for some period of time.

More2be

Thanks for your reply. Here's just a bit of what I found:


"In recent years, researchers also have learned that two genes can have an effect on a
persons response to warfarin. The first gene, called cytochrome p-450 family 2
subfamily C polypeptide 9 enzyme (CYP2C9), influences how the body processes, or
metabolizes, warfarin. The second gene, called vitamin K epoxide reductase complex
1 (VKORC1), influences how effectively the drug interacts with the body to prevent
blood clotting."

And

"Specifically, the COAG trial will analyze two
genes called CYP2C9 and VKORC1. Both genes have been shown in previous
research to influence individual response to warfarin therapy."

[The above is from the FAQ page about a large NIH study which started enrollment in 2009--- started in 2 years and finished in about 3.5 years----- so it's still ongoing.]

A Medscape article states:

"CYP2C9*1 metabolizes warfarin normally, CYP2C9*2 reduces warfarin metabolism by 30%, and CYP2C9*3 reduces warfarin metabolism by 90%. Because warfarin given to patients with *2 or *3 variants will be metabolized less efficiently, the drug will remain in circulation longer, so lower warfarin doses will be needed to achieve anticoagulation."

Simplified (for my mind :)) there are people whose metabolism would be reduced by 30 to 90 percent. Which may account for why so many have a difficult time staying with-in range.

When pharmacogenetics becomes more readily accepted some of the 'guess work' may be eliminated. (Then a long wait until the insurance companies accept it.) Until then I'll stick with Coumadin----- but since my secondary insurance will pay for almost everything, maybe I can talk my doctor into a test. Might be interesting (or not).

Warfarin (brand Coumadin) has been around for 60 years and has prolonged a lot of lives, but it is still considered an inconvenience as well as a risk to find and monitor its effects from one individual to the next. Certain aspects of it, such as frequent self-testing, make the process safer, less cumbersome, and less expensive. In its early days it was common to keep therapy down to three months just because the long-term risks were not known. Testing for the two alleles, where and when ordered, could be but one more tool to ease the process.

What a lot of people have been hoping for is an alternative to Warfarin that takes out the testing and monitoring altogether. So far Dabigatran (Pradaxa) shows the most promise.

Cost benefits is one of the concerns regarding genetic testing for warfarin/coumadin patients presently along with the need for larger studies.

I think it would be great to have prior knowledge of how a person will fare on Coumadin in order to better manage their anticoagulation. During the late 2006 to 2008 timeframe, pharmacogenetics was a hot topic in the anticoagulation community. But as I mentioned above, cost of testing was the issue which became problematic as did conflicting studies.

Here is a study in 2009 which, though reporting further studies would be needed, the researchers found no benefit in testing:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669873/

I think Clot Connect has a well written article discussing the Pro's and Con's; though it was written in 2007 (before either of the articles I mention above):

http://www.clotcare.com/warfaringenetictesting.aspx

Retirednavy, mabe you can inlighten me on the subject of calcium buildup in arteries while I am on coumadin. I am 73 and already have moderate calcium buildup in my arteries. Since I had unprovoked PE's and a DVT my GP is saying I should be on Coumadin for life. I do have afib but it is well controlled and I haven't had an event since last summer. I have read that K7 can help direct the calcium into your bones rather than arteries. But I am not supposed to take that. what is your opinion?

Thanks Dee

From http://www.clotcare.com/warfaringenetictesting.aspx

"In addition, the American Enterprise Institute-Brookings Joint Center (with input from the FDA) has published a document that reached some very impressive conclusions. Specifically, the report concludes:

"We estimate that formally integrating genetic testing into routine warfarin therapy could allow American warfarin users to avoid 85,000 serious bleeding events and 17,000 strokes annually. We estimate the reduced health care spending from integrating genetic testing into warfarin therapy to be $1.1 billion annually, with a range of about $100 million to $2 billion." (6)"


ClotCare, after a few paragraphs of explaining, in mostly plain language (thank you!), the potential benefits of using genetic testing for warfarin dosing, then issued this:

"Limitations & Risks of Genetic Testing for Warfarin Dosing

The use of genetic testing for warfarin dosing may have no significant benefit in practice and may significantly increase healthcare costs. Additionally, the misuse of genetic information may increase the risk of warfarin therapy."

"may increase healthcare costs". Granted---- the tests, I'm sure, will be expensive and I'm sure patents are being applied for now by the hundreds if not thousands.

But might that not be offset by fewer warfarin-dose caused strokes, bleeding events or even death----(which, morbidly enough, probably doesn't figure into the cost/benefit calculations)?

"The genetic tests in question cost approximately $250 per test or $500 for both tests. "

Yes, that's expensive but I've had to take tests that are even more expensive (for other conditions).

A colonoscopy costs in the neighborhood of $1000 (and usually more) were done every five years, I think. (The recommendations are for fewer now, I think). And they have to be repeated. A genetic test doesn't, since I doubt a persons' genetics changes. (grin)

(The bolding, below, is mine)

"if the patient has an early and rapid increase after starting a reasonable dose of warfarin, that patient is LIKELY to have the sensitive (AA) VKORC1 genotype. If the patient requires a prolonged period of time before the INR stabilizes, then that patient is LIKELY to have a CYP2C9 variant that leads to a slower rate of warfarin metabolism."

My personal opinion, and that's all this is, is that I'd prefer to KNOW those factors rather than have it guessed at. There might be other factors that cause those 'likely' effects.

"Misuse of Genetic Information May Increase the Risk of Warfarin Therapy"
" if the clinician relies too heavily on equation-based estimates of warfarin dosage, he/she may not follow the patient's INR as closely as he/she should."

Perhaps it's time for medical schools (and CME courses) to start educating future and present doctors on the 'wave of the future' about genetic testing?

"The bottom line is that genetic testing for warfarin dosing may hold promise, but its time has not yet arrived."

That article was written in 2007 and I'm guessing that genetic testing is getting closer and closer. I'll wait for it, impatiently, and hope that the doctor who treats me is much better 'educated' than the doctor who ignored all my symptoms and almost caused my death. But that's just my opinion.

Dee - In regards to the calcification issue, there was one study where high doses of Coumadin caused arterial calcification in rats but the amount of Warfarin was very high. It was also found that Vitamin K prevented the calcification.

There are not studies in human which indicate this to date.

Cave76, here is another interesting read:

http://www.ncbi.nlm.nih.gov/books/NBK52750/

As I said, I all for the testing. Genetics aside, there is another concern regarding the non-genetic factors which affect the effectiveness of Coumadin.

Retirednavy, thanks for the prompt reply. I will talk to my GP about the testing.
My INR was 1.7 for six weeks and last week jumped to 3. So now I have to go back to once a week testing.

Thanks so much Dee

retnav

Thanks for the new link (to Bookshelf). I look forward to reading them (and sequalae, links etc) but have to get going with my morning.

Good conversation!

BTW----- what criteria is used for inclusion in the Bookshelf? Do you know?

What a complicated mares nest of he said/he said about this issue (gene testing for controlling warfarin dosing better) in the literature. (grin)

One of the criticized points is the length of time to actually get the test done and then applied to the patient. That gene test is now performed within five hours now by some labs. With a click of the mouse it can be on the doctors iPad in a second.

Even if the test took the 30 days that have been mention somewhere in the lovely morass of articles----- wouldnt it be practical to start the patient on the current method of testing (blood stick for INR) while waiting for the genetic test results. (But I think that the genetic testing will be getting faster and faster)

Another point made against the use of genetic testing is the cost of the test. Not that expensive, as I pointed out, compared to a colonoscopy or a mammogram which have to be repeated.

The cost/benefit was also criticized by detractors----- but if they were comparing the cost of the test against the cost of what might be saved by fewer hospital bleeding events et al. thats apples and oranges.

Genetic testing is already licensed in much of the world. Patents are extant and are continuing to be applied for; I wont bore you with those urls. (grin)
Europe is often in the forefront of many new technologies. I dont know why we lag so much---- but would like to think that its our FDA being extra-cautious and not awaiting the lobbyists to finish what they do.

I know that genetic testing is in our future. But until then I will have to be content with the old way.

When researching almost anything I follow the money. Business, stock market, patents, lobbying expenditures etc. Cui bono. Money talks and also makes policies, laws, guidelines.

Here's something to think about, from an investment site.

http://seekingalpha.com/article/311297-winners-in-the-shift-to-personalized-medicine#comments_header

(Dec 2011)
[pharmacogenetics, molecular medicine, personalized medicine and other names are the names of the future.]

"Personalized Medicine Tomorrow

PM is already here, but its clear its full impact is still in the future. Analysts have been trying to predict the timing of the great drive for personalized medicine. Not all personalized medicine plays can be made today; look for certain drivers to impact the industry. There will be huge catalysts for personalized medicine and opportunities to make well calculated bets on the industry.

The Catalyst: FDA Policy On MDx

Right now FDA categorizes Molecular Diagnostic tests (MDx) as medical devices under the subheading IVD. These tests are getting increasing complex and more difficult for the FDA to evaluate. The evaluation process needs to be driven by experts who understand the testing complexity. Advancing these test can be greatly helped by having a specific FDA branch for molecular testing. When its own branch is created and the FDA finally creates a section and policy for companion diagnostics, expect a huge drive in MDx."

"Diagnostics make 80 percent of the therapeutic decisions, but only represent 2 percent of the costs, according to a study by Lab Corp. Because of the increased importance of diagnostics to the health care system, reimbursement will shift from therapeutics to diagnostics."

"Beware of prognostics, rather than diagnostics, and one-trick ponies: Genomic Health (GHDX) and Myriad Genetics (MYGN) have diagnostics with a weak link to therapies (without the therapy, its just a prognostic) and are dependent on a market with one product that some experts believe is priced too high."


"large laboratory centers should also benefit. The cost saving paradigm will benefit lean and more efficiently run private testing centers. Automated molecular diagnostic devices will make these firms more productive. Many of tomorrows tests manufactured by some of the previously mentioned companies will be performed in places like Laboratory Corporation (LH), Quest Diagnostics (DGX) and Bio-reference laboratory (BRLI)."


"Big Pharma

Never underestimate the political power of Pharma. Pharma as a whole is one of the most well connected group in Washington with numerous lobbyists and insiders working around the clock to tweak public policy in its favor. Do not expect pharma to not fight for a continued high rate of reimbursement. Pharma will continue to try to influence public policy even if it means slowing the personalized medicine paradigm.

In Conclusion

Personalized Medicine is not a passing trend, but rather a paradigm that has always been in medicine and will continue to influence the health care sector. The value added to payers, patients, physicals makes it inevitable in health care today and tomorrow. Position portfolios accordingly knowing this trend is here and comes to develop."

I can't remember if many people on this forum take Plavix or not.
But genetic testing for CYP2C19 could possibly prevent some of the hazards from Plavix. (There's a black box warning for it now)

Perhaps another reason to have all genetic tests done, not just a few.

http://thechart.blogs.cnn.com/2010/03/12/fda-issues-new-warning-for-plavix/#comment-283259

FDA issues new warning for Plavix

A new boxed warning has been added to the anti-blood clotting drug Plavix by the Food and Drug Administration, who says the medication doesn't work well in people who have difficulty metabolizing the drug.

Plavix is used by patients with heart disease to help decrease risk of heart attack, stroke and death. It works on plateletsspecial blood cells that help blood clot to stop bleedingby preventing blood clots from forming.

Plavix needs to be activated by the liver enzyme, CYP2C19. Patients that have reduced liver enzyme function can't activate the drug making it less effective for them. They're called "poor metabolizers" and this puts them at greater risk of heart attack, stroke and death.

"We want to highlight this warning to make sure health care professionals use the best information possible to treat their patients," said Mary Ross Southworth, a clinical analyst in the Division of Cardiovascular and Renal Products in the FDA's Center for Drug Evaluation and Research.

The Agency says there are tests available to evaluate CYP2C19 and determine if you are a "poor metabolizer." They say patients should talk to their doctors to determine if they should stop taking the drug.