• Genes and health
• Conditions we cover
• Warfarin Metabolism
• Complete scan
• Cancer scan
• Cardio scan
• Advanced features

Many factors affect the warfarin dose requirements of individuals, including age, weight, diet, disease history, and other medications.

In addition, it is now known that certain genetic variants have a significant impact on how sensitive people are to warfarin.

These genetic variations explain about 50% of the required dose difference between individuals and therefore constitute important information for your physician if you are on, or ever to be started on warfarin therapy.

Warfarin is a ‘blood-thinning’ medication

Warfarin is a type of medication commonly known as a blood thinner or anticoagulant. It is widely used to decrease the risk of blood clot formation in arteries and veins and to prevent existing blood clots from growing and breaking off. The primary danger from blood clots is when they get lodged in narrow arteries, for example in the brain (causing stroke) or in the lungs (causing pulmonary embolism).

Physicians must monitor patients closely when starting warfarin therapy

Determining the appropriate dose for someone starting warfarin therapy is extremely challenging, since the dose required for recommended therapeutic levels differs between individuals. A physician prescribing warfarin must monitor its blood-thinning effect by frequent blood-testing, using the International Normalized Ratio (INR) test. On the basis of results from such tests, the physician must adjust the dose of warfarin to ensure the desired therapeutic level of blood thinning.

Bleeding can occur if the dose exceeds an individual’s requirements

The most common adverse side-effect of warfarin therapy is internal bleeding. The risk of major bleeding is low, but must always be taken into consideration when therapy with warfarin is initiated. The risk of bleeding due to warfarin can increase when the dose exceeds an individual’s requirements and due to interaction with other medications or certain foods.

Environmental and genetic factors affect warfarin dose requirements

Many factors affect the warfarin dose requirements of individuals, including age, weight, diet, disease history and other medications. In addition, it is now known that genetic variants in the genes encoding vitamin K epoxide reductase (VKORC1) and cytochrome p450 2C9 (CYP2C9) have a significant impact on people’s sensitivity to warfarin. Individuals with particular variations in these genes require a lower warfarin dose to maintain therapeutic levels of anticoagulation. Individuals with other variations require higher doses. Together these genetic variations explain about 50% of the required dose difference between individuals and therefore constitute important information for physicians when initiating warfarin therapy.

deCODEme interprets the genetics of your warfarin metabolism

The deCODEme Complete Scan identifies the rs9923231 sequence variant in the VKORC1 gene on chromosome 16 and the CYP2C9*1, CYP2C9*2 and CYP2C9*3 variants in the cytochrome p450 2C gene on chromosome 10 and provides an interpretation of the associated impact on warfarin sensitivity for individuals of European descent.

Please note that these variants only provide information about your genetic propensity in relation to warfarin sensitivity and that many other factors can affect your actual sensitivity to warfarin. It is essential that any decisions about warfarin therapy and dose size be taken in consultation with a physician.

Factors associated with warfarin sensitivity

Both genetic and environmental factors such as foods and medications can affect the anticoagulation effect of warfarin:

• Genetics. Variants in both vitamin K epoxide reductase (VKORC1) and cytochrome p450 2C9 (CYP2C9) have a significant impact on warfarin sensitivity. Carriers of specific variations may be more sensitive to warfarin and may therefore require significantly lower doses than those with other variations. Variations in VKORC1 have a much greater impact on warfarin sensitivity than variations in CYP2C9, particularly during the initiation of therapy.
• Ethnicity. There are significant differences in warfarin dose requirements among different ethnic groups. Specifically, it has been recognized that people of East Asian descent require on average a 30-40% lower warfarin dose than individuals of European descent. In recent years it has become apparent that the VKORC1 gene variants that are associated with lower warfarin doses are much more common in Asians than Europeans, explaining most, if not all, of the difference attributable to ancestry.
• Foods high in vitamin K. Vitamin K is a natural blood-clotting factor and can reverse the blood-thinning effects of warfarin. Broccoli, lettuce, spinach and liver are all high in vitamin K. It is not recommended to eliminate these foods from the diet when taking warfarin, but to eat them in consistent amounts so as to maintain a balance with respect to warfarin dosing.
• Alcohol. Excessive use of alcohol is also known to affect the metabolism of warfarin and can increase its blood-thinning effects.
• Interaction with other medications. Many medications interact with warfarin, affecting its anticoagulation activity, including aspirin, some antibiotics and birth control pills. Warfarin also interacts with many herbal remedies.

More information

You can learn more about warfarin and warfarin dosing by talking to your doctor and visiting these websites:

• Medline Plus article on Warfarin
• The Mayo Clinic on Warfarin
• The American Academy of Family Physicians on Warfarin
• A Guide for Warfarin Dosing from the Barnes-Jewish Hospital Anticoagulation Service
• Drug Information -Up-to-date information on prescription and over-the-counter medications
• Drug Side Effects -Gets the latest consumer alerts about medication side effects

This content was last reviewed on February 09, 2010.

The conditions we cover: ABO Blood Types, Abdominal Aortic Aneurysm, Age Related Macular Degeneration, Alcohol Flush Reaction, Alzheimer’s Disease, Asthma, Atrial Fibrillation, Basal Cell Carcinoma, Bitter Taste Perception, Bladder Cancer, Brain Aneurysm, Brain Cancer-Glioma, Breast Cancer, Celiac Disease, Chronic Kidney Disease, Chronic Lymphocytic Leukemia, Colorectal Cancer, Crohn’s Disease, Essential Tremor, Exfoliation Glaucoma, Eye Color, Gallstones, Gout, Heart Attack, Hemochromatosis, Hypertension, Kidney Stones, Lactose Intolerance, Lung Cancer, Male Pattern Baldness, Multiple Sclerosis, Nicotine Dependence, Obesity, Ovarian Cancer, Pancreatic Cancer, Peripheral Arterial Disease, Prostate Cancer, Psoriasis, Restless Legs Syndrome, Rheumatoid Arthritis, Statin Induced Myopathy, Systemic Lupus Erythematosus, Testicular Cancer, Thyroid Cancer, Type 1 Diabetes, Type 2 Diabetes, Ulcerative Colitis, Venous Thromboembolism, Warfarin Metabolism.