Warfarin in the NEJM and the Westchester WAG

In a brief clash of civilizations today, I happened to be reading the Westchester WAG in the physicians' lounge. What is the Westchester WAG? It is a swanky monthly publication put out to showcase the high and mighty in Westchester County, NY. Yes it is one of the most affluent counties in the country, yes so is Fairfield County CT oh wait....isn't that where you have offices Dr Sherpa? Yes.....I have one on Park Avenue as well so it should come as no surprise that I was reading the WAG....Well maybe it should since I am from a small town in Pennsylvania and from a humble middle class family.

While flipping through the swanky weddings I stumbled across an article written by Isadore Rosenfeld a physician reporter who also practices cardiology in New York City at Cornell. It's funny that he wrote about coumadin and risk for bleeding, simply because he was standing next to me in the Emergency Department a few months ago taking care of a patient of his. This patient had a significant bleed in his brain because his blood was too thin on coumadin.

But what stunned me was five seconds after I dropped the WAG I looked at NEJM Online. Guess what? The group from Vanderbilt released some of their data on the study of CYP 2C9 polymorphisms and VKORC1 polymorphisms. Truly amazing. Even more amazing is that when you ask an internist about this you may get "I think I read about that in the WAG"....

Why in the hell do upper class socialites get this information before Internists? I am so fired up about this that I am speechless (Almost). Even crazier is why most internists/cardiologists have no clue about these studies. I think that we must solve this problem before we get anywhere in genomic medicine/personalized medicine. How can we do this?As I sit on a conference call planning our presentation at the Association of Program Directors in Internal Medicine spring meeting and we all are asking the same question. I am working my tail of on these solutions.

What was neat in this clash of social groups is that I began to realize that the NYT is right. Especially after Amy Harmon published her article about the Russian who had 350k to burn. Next time you are looking for material Amy......give me a call! The rich will absolutely want this information and use it for better health (if they see us), the poor deserve these services but likely will not get them. As for my parents the middle class, good luck finding an internist who knows that CYP450 is more than one enzyme.

The Sherpa Says:

This NEJM data suggests that VKORC1 may be more strongly linked to INR variability than CYP 2C9. Something that was not so clear. Does this mean we only have to test for one of these genes? I doubt it. In fact this makes even more the case for testing both genes. Why? Because there a less people with SNPs in VKORC1 than in CYP2C9. And Lastly, what in the hell is wrong with medicine? How did we forget that science matters? We didn't, we just never thought that genetics mattered. Now it is too late for these physicians to learn a language....Maybe we need rosetta stone's help?

Warfarin rears its ugly head

I swear I have seen more intracerebral hemorrhages from Coumadin in the last year than in the any of the literature stating it's incidence. Last night I admitted an elderly gentleman who was in his usual state of health until he slipped on the ice and bumped his head. He then carried about his business for a day and a half. Then as he went to work his secretary noted him acting unusual.

When he showed up in my Emergency department, he had an INR of 9.4

For all of those who don't know what an INR is, 1.0-1.4 is normal. This is abnormal, big time.

He had traditionally been on a very low dose of coumadin (I.E. poor metabolizer) The problem was not that he just had very thin blood, the problem was the huge bleed he had in his brain!

What can we do about this problem? I have mentioned the future of coumadin therapy several times. I was just speaking to Dr Isadore Rosenfeld yesterday who pointed out to me that a recent study once again shows how beneficial Warfarin is in preventing strokes caused by a condition known as Atrial Fibrillation. The incidence of Atrial fibrillation increases as the population ages. Therefore, I am certain that we will begin to see more poor metabolizers and even more poor outcomes.

The Sherpa Says: On Coumadin? Mind your INR? Starting Coumadin? Get your metabolizer status checked! If you are in NYC or Greenwich come see us. Thank you to GTO for the early Christmas present....

I want my Genome!! What about your cholesterol?

Today I read something that blew me away! While Myriad is hammering away on NYC TV to get your BRCA test. 10-15% of all breast cancer patients have BRCA mutations in either 1 or 2. These tests cost over 3000 USD a piece, even worse, there are very few clinical changes that result from positivity of either mutation.

The stat that hit me like a punch in the nose was "80 per cent of women in the US between 18 and 44 don't know their cholesterol level" I couldn't believe it! This according to a recent survey by the Society for Women's Health Research (SWHR). This non-profit agency "encourages the study of sex differences between women and men that affect the prevention, diagnosis and treatment of disease".

This is what I find funny. A patented gene test can have a multi-million dollar ad campaign, but women's heart health gets barely a whisper. Despite heart disease being a much bigger killer in women. If you thought carrier status for breast cancer was a big deal. Having an elevated cholesterol is the closest thing to having a heart attack. Even worse, there are some simple preventative things you can do for cholesterol and it doesn't include surgery or medications.

So while we all bask in the glory of The Personal Genome Project and 23andMe, we need to get a grip. Just because you can get your genome sequenced, doesn't mean it will tell you your cholesterol level. Clinical acumen is what is required for personalized medicine, not technology alone.

The Sherpa says: According to this study "More than half of the women 18-44 surveyed were concerned about cholesterol, but the vast majority weren’t aware of their personal cholesterol level and one-quarter did not even know how cholesterol is tested" Why? Because we don't have Quest lab reps stopping by your PMDs office telling you that you MUST test women's cholesterol. That means asking your physician to check your cholesterol is up to you!

Send in the Clowns......

The Gene Genie is at Microbiology Bytes this week. The theme is bugs and beyond. It has been 7 genies since my hosting and the topics just keep getting better. I am so impressed by the set of links posted, from evolutionary bacteriology to pharmacogenomics there is a lot in the bottle this go 'round.

I have been moving off topic lately and I promise to start redirecting. I have been guiding your attention towards the business side simply because there are so many shenanigans out there. I firmly believe that the revolution known as personalized medicine will be manipulated, just as the "organic food" wave was. Pretty soon you have everything from organic food to organic car washes.

Perhaps the next move is Procter and Gamble releasing Genomically Targeted Food, personalized just for you. Where will this start? Not in your foods, but in Fido's. I have recently discovered from several sources, including I guy (venutre capitalist) who I bumped into waiting to buy power ball tickets, that there are several food manufacturers working on nutrigenomic cat, dog, and parakeet food!!!

All that glitters isn't gold and all that buy it aren't fools. They can be tremendously smart people that are duped by marketing. I ask that we all take a step back, take inventory and prepare for the avalanche of marketing about to hit the air waves.....From Myriad and Sheryl Crow to Puppy Chow...please don't dismiss Personalized Medicine as more of the same charlatanism. We have something revolutionary, it is a shame if we let the PR, Marketing, and VC fools run us into the ground for a cheap buck or two!

The Sherpa Says: Thanks for reading.....please stick to the trail and we will get there safe and sound, I promise. Oh and BTW, I am still awaiting Salugen's studies and data.

Coumadin and Buccal Swabs!!!

Prior to posting part 3 of the Brown conference I had to put Kimball Genetics on the Radar! The have devised a test to help with the scourge of Adverse Drug Reactions and Coumadin! Coumadin/Warfarin is designed to thin the blood and prevent clots causing stroke and pulmonary embolism. The test detects specific variations in the CYP2C9 and VKORC1 genes, the presence of which result in lower dose requirements for warfarin/coumadin. To help with implementation the nice people at Washington University, St Louis. The interactive website at warfarindosing.org has been developed by Brian F. Gage, MD,MSc, colleagues and is ideal for this purpose.

With every test their is the Good, The Bad, and the Ugly.

• The Bad? Turnaround time is a day. At the American College of Cardiology conference there was a claim of 1 hour turnaround time with an unspecified test!


• The Ugly? Will physicians know to advise patients of the familial implications of these tests? And will the 2 million plus people on coumadin be able to understand the counseling?


• The Good? This test is 99.9% sensitive and accounts for over 35% of coumadin metabolism variation

The Sherpa Says: I have to go tell it on the mountain....but I will be back to go over coumadin metabolism and this test in a finer detail. For now, hold tight and get some help with test interpretation if you plan to use it.