I can tell you that many things can alter the metabolism of coumadin such as diet and other medications. Coumadin blocks the action of enzymes which utilize vitamin K in the vitamin K cycle which is responsible for generating clotting factors. The blood becomes “thinner” because there are less of these functional clotting factors due to the action of coumadin.

Therefore, we must assume that vitamin K supplements will also interact with coumadin. It is best for your wife to talk to her physician that is prescribing coumadin about any supplements before starting on them.

There is a website I often use when I want to read about a medication- http://www.rxlist.com. It lists some technical details about the medicine but also gives information on interactions and warnings. There is also the very dense package insert for the drug- which if you can make out the very tiny letters can give some additional information about the drug.

results should be coming down the pipeline in the next few months including preliminary results from a pilot RCT for a genotype based dosing regimen vs clinically based dosing.

for now- a decrease in major events has not been shown but trials are being developed to study this

Anyway, I think it looks good.

Time with INR>3 as a surrogate – seems very sound.

All is well.

Now if I could just figure out the magic dosing regimen from the publication…

http://www.nature.com/clpt/journal/vaop/ncurrent/pdf/6100316a.pdf

To my knowledge this is the only prospective study yet to be published. (Of course, I didn’t see this one come out… On my really fast read, I didn’t see that they referenced any prospective studies) It is a pretty strong publication. Unfortunately, it was underpowered to determine if dosing based on genotype gives a decrease in MAJOR bleeding events (they only had one and it was secondary to angiodysplasia – as you point out). I’m not sure that the minor bleeds even reached significance -it certainly wasn’t presented as such: 12% vs 3% out of 90 ish. What’s that? 3 vs 11? Seems like it may be close

HOWEVER, it uses an INR > 3 as a surrogate and the numbers look really good. If an individual is dosed based on genotype, then they spend a lot less time with an INR > 3 (and less time with an INR 3 and time to therapeutic INR are good indicators of propensity for major bleed – then all is well.

A prospective trial to read on this topic is
Y Caraco, S Blotnik, and M Muskat Clinical and Pharmacology and Therapeutics Sep 12 2007- Pubmed still calls this epub ahead of print
if you have any issues let me know if I can help

They gave a control group the normal dosing algorithm and a control group a genotype based algorithm (for CYP2C9 only). Both groups had similar proportions of patients with a wild type (non-variant) allele and homozygous and heterozygous CYP2C9 variant alleles.

The genotype based dosing was associated with a longer time to reach therapeutic INR but less time outside the therapeutic range ie more stable dose.

During the study, there were 15 bleeding episodes (14 minor events, 1 major event) with a 12.2% incidence in the control group versus 3.2% incidence in the genotype based dosing group. The major bleeding event occurred at an INR of 1.74 (nontherapeutic) and had angiodysplasia found in a colonoscopy which was felt to be the cause of the bleeding event.

The three patients in the genotype based group who had an adverse event were wild type genotype (ie did not have the variant allele associated with bleeding). Seven of the control group (normal algorithm) carried a variant allele. Bleeding for control patients coincided with INR above the therapeutic range.

OK this was long winded but I was attempting to address some of PathDoc15′s questions–the answer to them all are probably still “?”-this is still under study. Still need more information from trials-
I am still looking for papers on this any other suggestions?

But what this trial seems to point to is that genotype based dosing does not prevent all bleeding episodes–but it does seem to help with achieving a stable INR in patients prone to instability and thus curtailing/controlling the presence of very high INR which is associated with bleeding.