Warfarin (Coumadin) sensitivity- Medical Indications
Warfarin (Coumadin®) sensitivity 
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- Medical Indications: Warfarin is indicated for the prevention and/or treatment of venous thrombosis and pulmonary embolism. It is prescribed for the prevention of complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin is prescribed to reduce the risk of death, recurrent myocaridial infarction and associated thromboembolic events such as stroke.
- Mechanism of action: Warfarin inhibits vitamin K epoxide reductase (encoded by the VKORC1 gene), thus reducing vitamin K recycling. This inhibition leads to a reduction in blood clotting.
- Adverse reactions: The most serious side effect of warfarin is hemorrhage (bleeding), which may be fatal. It is very important to properly adjust warfarin dose, since people metabolize the drug differently. Individuals may be normal, intermediate or poor metabolizers of warfarin. Patients should have routine blood draws to measure prothrombin (PT) clotting time, which is reported in International Units (INR). Physicians use these periodic tests to adjust the individual's warfarin dosage.
- Pharmacogenetics: Warfarin is the active drug, and the elimination of warfarin is almost entirely by metabolism. It is metabolized by liver cytochrome P-450 enzymes and excreted in the urine and bile duct. The hepatic P-450 enzyme principally involved in warfarin metabolism is encoded by the CYP2C9 gene. As much as 50% of the general poplulation may have one or more genetic variants of CYP2C9 that reduce the efficiency of warfarin metabolism. Warfarin efficacy can be achieved in these individuals at lower doses, which will also reduce the risk of adverse reactions. There is also a genetic variant of the VKORC1 gene that reduces its function in the absence of warfarin. These individuals may also be maintained on lower doses of warfarin to achieve efficacy with reduced side effects.
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Additional information on warfarin sensitivity test:
Additional pharmacogenetics information: