By DFK | October 23, 2013 at 10:39 AM EDT | 6 comments
Here is the description of atrial fibrillation from the National Heart Lung and Blood Institute (NHLBI):
Atrial fibrillation (A-tre-al fi-bri-LA-shun), or AF, is the most common type of arrhythmia (ah-RITH-me-ah). An arrhythmia is a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm.
AF occurs if rapid, disorganized electrical signals cause the heart's two upper chambers—called the atria (AY-tree-uh)—to fibrillate. The term "fibrillate" means to contract very fast and irregularly.
In AF, blood pools in the atria. It isn't pumped completely into the heart's two lower chambers, called the ventricles (VEN-trih-kuls). As a result, the heart's upper and lower chambers don't work together as they should.
People who have AF may not feel symptoms. However, even when AF isn't noticed, it can increase the risk of stroke. In some people, AF can cause chest pain or heart failure, especially if the heart rhythm is very rapid.
AF may happen rarely or every now and then, or it may become an ongoing or long-term heart problem that lasts for years.
One of the goals of treating AF is to:
- Prevent blood clots from forming, thus lowering the risk of stroke.
People who have AF are at increased risk for stroke. This is because blood can pool in the heart's upper chambers (the atria), causing a blood clot to form. If the clot breaks off and travels to the brain, it can cause a stroke.
Preventing blood clots from forming is probably the most important part of treating AF. The benefits of this type of treatment have been proven in multiple studies.
Doctors prescribe blood-thinning medicines to prevent blood clots. These medicines include warfarin (Coumadin®), dabigatran, heparin, and aspirin.
People taking warfarin (and some other) medicines need regular blood tests to check how well the medicines are working.
OK that is the information, adopted from the NHLBI. Now for some pharmacogenomic information. By the way, the strict definition of pharmacogenetics is the relationship between a single gene and drug response, whereas, pharmacogenomics is the relationship between all genes (the genome) and drug response...a slight difference. I use pharmacogenomics here, because there are, at least, two genes involved in an individual's response to warfarin. Here is my information:
So, how does this information impact the dosing of warfarin for me? Here is a dosing table for initial dosing of warfarin based on genetics. Please consider the following:
I know this is a "big chart" from the supplementary material provided by the Clinical Pharmacogenetic Implementation Consortium (CPIC), published in Clinical Pharmacology and Therapeutics in October of 2011 (free access article), however, you should be able to put together my genotype (*/*) and comment on my metabolizing of warfarin by the CYP2C9 metabolizing enzyme, based on my CYP2C9 genotype.
Then there is the issue of the drug (warfarin) target, here, an enzyme called VKORC1. Here is some information from the same CPIC source:
Individuals which have an A instead of a G at rs9923231 have increased sensitivity to warfarin. Here, there is less target protein made for warfarin to affect, so you need less warfarin...or in other words, there is warfarin sensitivity. So, look again at the above information and tell me what dose of warfarin you think I should start on, based solely on my genetics. I challenge you to look up warfarin and see what some of the adverse, or side effects there are and discuss what may happen to me if I get the wrong dose of warfarin. I look forward to some thoughts on this!