How Warfarin works - good read

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TheGymGuy

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Warfarin decreases the hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, and X) and proteins C and S. It is metabolized by the hepatic p450 system, has a relatively long half-life, and requires several days for equilibration. There are many guidelines for maintaining safe and effective anticoagulation with warfarin for atrial fibrillation, DVT, pulmonary embolism, and other diseases.Systemic anticoagulation confers significant morbidity, from ecchymosis and epistaxis to intracranial bleeds and retroperitoneal hematomas. Every 0.5 increase in the INR doubles the risk of intracranial hemorrhage. It is important to remember the potential drug interactions between warfarin and other therapies we provide. This is especially true for the elderly and those with prior stroke or multiple comorbidities.Drugs that inhibit the p450 system will increase the anticoagulation effect of warfarin and vice versa. Patients taking antibiotics while on warfarin are six times more likely to develop an INR above 7.0 and associated morbidity. We must be careful with antibiotics in these patients.

Human P450 metabolism of warfarin: http://www.ncbi.nlm.nih.gov/pubmed/9014207
The Effect of Cytochrome P450 Metabolism on Drug Response, Interactions, and Adverse Effects: http://www.aafp.org/afp/2007/0801/p391.html


I spent another 2 hours reading up on clotting factors, etc., after I read this, but boy-oh-boy was this helpful.

Wanted to start sharing some of my research for the curious minds. Next up in my research is about accidental greens overload, how to prepare, etc., as well as alcohol consumption and accidental too many drinks scenario. Can these be planned for and if so how.


EDIT: Linking up 3 articles that I started which all talk about Vitamin K and/or Coumadin/Warfarin
1. Vitamin K links to USDA.gov: http://www.valvereplacement.org/forums/entry.php?61-Vitamin-K-links-to-USDA-gov
2. Great article on Vitamin K Supplementation and Anticoagulation Control: http://www.valvereplacement.org/for...K-Supplementation-and-Anticoagulation-Control
3. How Warfarin works - good read: http://www.valvereplacement.org/forums/showthread.php?40393-How-Warfarin-works-good-read
 
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Somehow I think I'm far more likely to accidently have to many drinks than I am to accidently have to much spinach. Looking forward to your findings and thanks for doing the research.
 
I think the thing with drinking is probably a bit overblown -- unless you're talking about wine. There's a substance in wine that CAN have an impact on INRs.

I'm not very likely to have too much spinach, either.

The thing to remember with warfarin management is to keep consistent -- I don't eat spinach now (or Kale or brocolli or other green stuff that some people have developed a taste for), so to be consistent, I still won't eat them.
 
I think the thing with drinking is probably a bit overblown -- unless you're talking about wine. There's a substance in wine that CAN have an impact on INRs.

I'm not very likely to have too much spinach, either.

The thing to remember with warfarin management is to keep consistent -- I don't eat spinach now (or Kale or brocolli or other green stuff that some people have developed a taste for), so to be consistent, I still won't eat them.

The reason I started this research is that there are some occasions, maybe once a year or so, when we cannot stay consistent for just one day. This is all from personal experience before OHS. I, for example, am very consistent when it comes to daily nutrient intake, but I can see occasions where this would not be the case.

Wedding of your child, sibling or best friend would constitute alcohol consumption where as you might drink nothing all year long. That one night you might drink 5+ drinks of hard liquor, but your usual drinking habit might be 1 drink (scotch or something other strong) per week.

Also, say you travel to Europe and go to an amazing restaurant with world renowned chef making your meal personally. Say the thing that he serves comes on a bad of spinach or asparagus. These 2 are super high in Vit. K and this being the once in a life time opportunity should be treated as just that and we should indulge.

In summary, I started this thread to share research or get feedback from those with know-how, for situations like above. I think Alcohol is easier to deal with as it's in and out of your system pretty fast (7 hours) http://alcoholism.about.com/cs/alerts/l/blnaa35.htm, however, Vit. K is a slightly different story, I almost believe we should be at a higher INR range for a day or so before we know we would really pig out on Vit. K and then reduce the Warfarin accordingly.

I will post things as I read more.
 
I don't think that your concern about drinking a lot once in a while, or eating a healthy dose of greens is that big a deal. It may be a bigger problem if you increased your dose a day or two before a planned green binge than it would just to enjoy yourself once in a while.

The problem - according to some studies - occurs when you are BELOW range for a week or so -- if, as it appears, you're over 3 months post-op. If you're really concerned, and have a meter, you an always test your INR 24 hours or so after a green binge -- but it probably wouldn't justify adding 1/2 dose extra to bring your INR up. If your normal dose keeps you in range, you'll probably get back in range pretty quickly without compensating with more warfarin.

As far as alcohol is concerned -- I've seen some people claiming concern about too much alcohol effecting INR -- but I haven't seen any real research on the matter. (If you drink enough alcohol to hurt your liver, perhaps the response to warfarin will be altered - but if you drink THAT much, you may have other problems of greater concern).

So -- my advice for occasional binges - whether alcohol or greens - is to enjoy yourself and, if you're really concerned about your INR, bring your meter with you and test the day after the binge.
 
Protimenow, I love your response. So far I have not found much on occasional (1 / year) binges if any while on warfarin. Might have to start extrapolating information out of NIH articles.
 

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