INR and the major influences

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Professional Dingbat
Nov 4, 2012
Queensland, OzTrayLeeYa
firstly, I'm sorry that this post has a bunch of acronyms in it, I'll try to inline clarify them.

We'd all love things to be simple ... however often they're not (hello Tax time forms). Despite knowing things are complex we always seek simplifications to make explaining things easier. These simplifications often make extending what we "know" dangerous because what we (think we) know is based on a simplification (or a dumbing down).

With respect to warfarin, at the root of it all is this point: we are not totally sure how warfarin acts. We have a lot of evidence, but we aren't totally sure. So like paracetamol we just don't know for sure.
NB from MIMS
Mechanism of action. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K[SUB]1[/SUB] epoxide.
So the following article is of benefit to read, it makes the case clear that while vitamin K is a factor the actions of the body to rid itself of warfarin is the most significant factor.
The article starts its abstract (the simple bit) with the following:
The considerable variability in the warfarin dose–response relationship between individuals, is explained mainly by genetic variation in its major metabolic (CYP2C9) and target (VKORC1) enzymes.
So knowing what are CYP2C9 and VKORC1 are key.
CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes (data only for antifungal).
The human gene VKORC1 encodes for the enzyme, Vitamin K epOxide Reductase Complex (VKORC) subunit 1
Now if you look at the "dosing calculator" here ( you'll see that it requires this as input (as well as your CYP2C9 genotypes

This is actually important but mostly never obtained because in the real world we can measure our INR and know the outcome.

What we can't know however is what the dietary effects on our VKORC actually is ... but we do know that many things inhibit it.

So accordingly I say that don't worry about your diet, only concern yourself with knowing your INR and making any changes to your dose to reflect what's happening (or in extreme cases stop drinking gallons of Grapefruit juice ;-)

Anyway, I strongly recommend you read that first article slowly and take it in. The advice is good: for instance:
Many patients on warfarin are vitamin K depleted as a result of routine instructions to restrict vitamin K intake in an attempt to achieve optimal therapeutic response. As described above, in vitamin K depleted patients, small changes in intake may be an important determinant of day to day variability in warfarin dose–response. Older recommendations for diets low in vitamin K as appropriate for warfarin treated patients [54] should now be considered outdated.
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