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Warfarin (Coumaden)

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Overview

Warfarin is marketed under the name Coumadin. Other names include Jantoven and Marevan

What is Warfarin?

Warfarin is also called Coumaden. It is a drug used by doctors to treat or prevent blood clots, and is most often prescribed to those at risk of deep vein thrombosis, pulmonary embolism, and stroke. Warfarin works by thinning the blood to keep it from clotting so that it flows easier through the body. Warfarin is sometimes called a 'blood thinner'.

What is being tested?

A genetic test can look at gene differences (called variants) that affect how your body breaks down the drug warfarin. People react differently to medicine, and some of those different reactions can be related to their genes. Certain variants are linked to a slower drug effect, while other variants may lead to faster drug effects in the body. Variants in two genes in particular - CYP2C9 and VKORC1 - are involved in how people process warfarin. This test will look for some of the genetic differences in the CYP2C9 and VKORC1 genes that can make people respond more rapidly or more slowly to warfarin.

How will this affect my health care?

Reaching just the right dose of warfarin can be difficult. Deciding on the right dose is affected by many clinical factors including age, sex, weight, height, smoking status, and interacting medications.

Your doctor will use your genetic test information together with your clinical factors to better predict the best warfarin dose for you. This test can help to your doctor to decide on the best starting dose of warfarin for you. It is also possible that your doctor will not to do anything different.

You should follow your doctor's instructions on taking any medication. Do not change your medications on your own before speaking with your doctor. If you have any questions about your test results or the medications you are on, please talk with your doctor.

More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

Background

Why test for genetic interactions with Warfarin?
By performing a test on your DNA, we may be able to anticipate how you will respond to warfarin and to modify your treatment accordingly. In the video to the right, Dr. Iftikhar Kullo (Mayo Clinic)explains that not everyone responds in the same way to warfarin. The dose that patients receive depends on their age, gender, race, and weight. In addition, genetic factors dictate an individual's response to the drug. Calculators are available to doctors to help determine the correct dose for each patient.

How will this affect my treatment?
If genetic testing does indicate that you may not respond optimally to treatment with warfarin, your doctor should change your prescription.

Can taking Warfarin cause any problems?
For the majority of people taking warfarin will not cause any problems. The most common side effect, found in 1-3% of people taking warfarin, is bleeding, which can become serious.

Are any other complications associated with Warfarin?
Large doses of warfarin can cause necrosis, severe damage to the skin and tissue. Although rare, taking warfarin can also damage organs, including the pancreas, spleen, and liver.

Who is affected?
Genetic differences that affect how people respond to warfarin are relatively common. As outlined immediately below, there is a relationship between ancestry and risk of warfarin sensitivity.

Do different populations respond differently to Warfarin?
Variants in two genes in particular - CYP2C9 and VKORC1 - are involved in how people process warfarin.

For CYP2C9, the two most common versions of the gene are CYP2C9*2 and CYP2C9*3:

  • CYP2C9*2 is found in 8-19% of Caucasians, in 0-12% of African Americans, and in 0-4% Asians.
  • CYP2C9*3 is found in 5-16% of Caucasians, in 0-6% of African Americans, and in 1-8% of Asians.
  • Warfarin sensitivity related to the VKORC1 gene is associated with a generic mutation called 1639G>A. This is found in 89% of Asians, 37% of Caucasians, and 14% of African Americans.

    Do reactions to Warfarin and other drugs run in my family?
    We typically inherit two gene copies from each parent. If you have a genetic difference that affects how you respond to warfarin, it is likely to have been inherited from one or both of your parents, and it is possible you will pass this to your children. However, this is not always the case, and a large variety of inheritance scenarios are possible. If you are concerned about this, we strongly advise you to discuss with your doctor or healthcare provider.

    Is there a difference between being a carrier and being predisposed to a particular drug response?
    You may carry a genetic a difference that does not affect how you response to warfarin, but may affect how your children might respond. A full discussion of the relevant scenarios/implications are beyond the scope of this site, however, and we recommend you discuss with your doctor or healthcare provider if this is a concern.

    Why do genetic differences make people respond to warfarin differently?

    The CYP2C9 gene codes for a protein involved in the breakdown (metabolism) of warfarin. People with variations in this gene may metabolize warfarin more slowly, resulting in slower clearance of the drug and accumulation in the body over time. They may require a lower dose of the drug.

    The VKORC1 gene codes for the protein that warfarin targets. A variation in this gene may result in a protein change that may be more sensitive or less sensitive (or resistant) to the anticoagulant effect of warfarin. Depending on the variant present, the person tested may need a lower or higher initial dose of warfarin.

    More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

    Genetic Test

    Weblink to Learn.Genetic Module, Making SNPs Make Sense

    What is the test?

    This test may help your doctor decide on the dose of warfarin you should receive. As mentioned in the Overview, the test specifically focuses on two genes - CYP2C9 and VKORC1. The amount of warfarin you need will depend on the type of CYP2C9 and VKORC1 you have inherited. However, the dose you receive will also greatly depend upon your health, age, gender, diet, and other medications.

    NOTE: The test only looks for the more common types of CYP2C9 and VKORC1, and may not test for rare types that could be involved in your personal response to warfarin.

    What will the test result mean?

    Genetic testing for warfarin sensitivity may be used to help determine your response to warfarin and to help select appropriate doses. It does this by identifying variations in certain genes. Certain variations in the VCORC1 or CYP2C9 genes may result in a protein change that affect how individuals are more sensitive or less sensitive (or resistant) to the blood-thinning effect of warfarin. Depending on the variant present, the person tested may need a lower or higher initial dose of warfarin.

    For some, this testing may be used to help determine an appropriate dose because you previously took warfarin and either experienced inappropriate clotting or bleeding episodes while on warfarin, or had to go through many dose adjustments to reach a stable anticoagulant ("blood-thinning") effect.

    How is the test being performed?
    Testing is performed on your DNA, usually extracted from a blood sample. For many patients, your hospital or treatment center may already have some of your DNA stored in a biobank. You may be asked for an additional sample or be asked to give us permission to do testing on the existing samples.

    Will it hurt?
    For some patients, we may need an additional blood sample. Taking blood may cause some pain, bleeding or bruising at the spot where the needle enters your body. Rarely, taking blood may cause fainting or infection.

    Is it safe?
    There is a risk that you may experience pain or bleeding if you need to give an additional blood sample. Risks concerning privacy are discussed under Privacy & Sharing.

    How long will I have to wait for results?
    Unfortunately, we cannot give an accurate estimate for the time you will have to wait for results - this will depend on the resources available at the center where you receive treatment.

    Is this a standard test?
    Although increasingly more common, this test is not yet standard, and is typically offered as part of a research study.

    What type of test is this?
    Is this test intended to confirm a diagnosis? No
    Is this test intended to predict a family history of disease? No
    Is this test intended to check if I am a carrier for a particular disease? No
    Is this test intended to screen for genetic disorders? No
    Is this test intended to screen for disorders related to pregnancy? No
    Is this test intended to screen for disorders related to newborns? No

    Will I need to have this test done more than once?
    No, you should not need to have this test done more than once. You will need to keep track of your testing result in order to share with all of your doctors, including those you see at other medical care centers.

    More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

    Treatment

    How will this test affect my treatment?

    For most people tested, it is likely that your treatment options will stay the same and that you will begin treatment with warfarin as scheduled, or you will maintain you treatment with warfarin . If this is not the case, your doctor will either change your recommended dose of warfarin or recommend a new treatment.

    In the embedded video, Dr. Murray Brilliant (Marshfield Clinic) explains that we all respond to drugs differently, and that genetic testing is helpful in guiding treatment.

    How will this result be used?

    Genetic testing for warfarin sensitivity may be used to help determine your response to warfarin and to help select appropriate doses. It does this by identifying variations in certain genes. Certain variations in the VCORC1 or CYP2C9 genes may result in a protein change that affect how individuals are more sensitive or less sensitive (or resistant) to the blood-thinning effect of warfarin. Depending on the variant present, the person tested may need a lower or higher initial dose of warfarin.

    For some, this testing may be used to help determine an appropriate dose because you previously took warfarin and either experienced inappropriate clotting or bleeding episodes while on warfarin, or had to go through many dose adjustments to reach a stable anticoagulant ('blood-thinning') effect.

    The result will be put into your medical record for your doctor to have access to use when deciding about prescribing warfarin. Your doctor may:

  • Do other tests to see how you might respond to warfarin
  • Do nothing and continue with your planned course of treatment
  • Switch your dose if you are on warfarin and having difficulty with control
  • Regardless of your genetic makeup, your response to warfarin therapy will still need to be monitored with regular PT/INR tests.

    Will I be referred to a specialist?
    It is unlikely that you will be referred to a specialist, but you may request an appointment with a genetic counselor.

    Is there anything else I should know?
    You should follow your doctor's instructions when taking any medication. Do not change your medications on your own before speaking with your doctor.

    More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

    Privacy & Sharing

    Should I tell other healthcare providers about my test result?
    If your doctor who prescribes medication for you doesn't already know about your test result, we do recommend that you share this information with him/her. However, as explained by Maureen Smith (Nortwestern University) in the embedded video, what you decide to do with your results is up to you.

    Who will see my test results?
    People who have access to your medical record will be able to see your genetic test result. This may include health professionals such as doctors, nurses, pharmacists, and genetic counselors. However, health professionals from other centers or hospitals will likely not have access to your results.

    Should I tell other healthcare providers about my test result?
    If your doctor who prescribes medication for you doesn't already know about your test result, you should share this information with him/her.

    Should my other family members be tested to see how they might respond to warfarin?
    You may want to share your test results with your family, since they might have the same genetic variant as you.

    Will this affect my health insurance?
    No, your health insurance will not be affected by this warfarin test result.

    Who can I contact if they have any more questions?
    You can contact your local center, where you received the test. We have also included a recommend list of resources in the Videos & More tab to the right.

    Is it there a risk to my privacy?
    Research that uses information from medical records and that involves genetic testing can affect your privacy. Your participation in this research will be held strictly confidential, and only coded numbers will be used to identify specimens and research records. While it is impossible to absolutely guarantee that information in our secure system will never be known by others, we are taking every possible precaution to see that this does not happen.

    More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

    Risks

    What Should I Do If I Have Concerns About Genetic Test Results?
    If you are concerned about genetic test results you have received, you should discuss your concerns with your doctor. Your doctor should be able to explain results to you, and may recommend you to a genetic counselor or another doctor that can further help you understand your results. Maureen Smith (Northwestern University) discusses these concerns in the embedded video/

    Is there a reason why I may be a specific risk?
    Testing is recommended for all individuals undergoing or considering undergoing treatment with warfarin.

    Are there any implications for having children?
    No.

    If I am found to have a specific gene variant, am I at increased risk?
    For some individuals, there gene test result may indicate that they are at an increased risk of responding poorly to warfarin. Testing is done to help guide your doctor chose the best treatment for you.

    Can I expect to experience emotional consequences related to my test result?
    A range of reactions are possible and normal. Some patients may experience anxiety or other negative reactions related to their use/potential use of warfarin. If this is the case, please discuss with your doctor, who can address your concerns and refer you another health professional if required.

    Can I expect to experience social consequences related to my test result?
    We do not anticipate any social consequences related to use/potential use of warfarin. As always, however, if you do experience any negative social reactions, please discuss with your doctor who can address your concerns.

    Can I expect to experience an increase in anxiety?
    Many individual experience increased anxiety related to genetic testing. Again, please discuss with your doctor if this is the case.

    Are there any implications in terms of discrimination arising from the test result?
    Health insurance companies are prevented by law from discriminating against you based on your genetic test results. However, the same law does not apply to long-term disability insurance or to life insurance.

    If I am found to be at increased risk for responding poorly to warfarin, are there similar health implications for my family?
    If results indicate that you may respond poorly to warfarin, your family may be more likely to have a similar response should warfarin ever be considered an option for them. As such, you may want to discuss your results with your family.

    Are there likely to be emotional consequences for my family?
    Similar to patients, family members may experience a range of reactions, which is normal. We recommend that if you discuss any questions or problems with your healthcare provider.

    More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.

    Videos & More

    People Differ Greatly in how they Respond to Medicatons

    Dr. Dan Roden, a researcher at Vanderbilt University, explains that if you give the same dose of a drug to a large number of people, responses will vary. Some people will have a great response, some will have no response, while others will experience adverse side effects. Some of this variability resides in our genes. The science of pharmacogenetics is the science of trying to understand the genes that contribute to the variability of drug action.


    Genetic Testing to Predict Responses to Medication

    Dr. Hakon Hakonarson, a researcher at The Children's Hospital of Philadelphia, explains that genetic testing can now be used to predict responses to certain medications. This will help to prevent negative reactions and improve healthcare.

    RECOMMENDED WEBSITES

    Find a Genetic Counselor directory developed by the National Society of Genetic Counselors.

    Genetics Home Reference has basic information about genetics and links to other resources about genetics.

    Medline Plus has more information about warfarin, other drugs, and other health conditions.

    Lab Tests Online provides patient-centered reviews about lab testing and drug products.

    Daily Med provides high quality information about marketed drugs.

    The Pharmacogenomics Knowledge Base is a resource for medical professionals about how variation in human genetics leads to variation in response to drugs.

    About

    Are there geographical differences in service or treatment related to warfarin?
    Different centers have different policies in terms of how tests are administered and results shared. However, the results discussed in this document should be relevant to most individuals tested for warfarin-gene interactions.

    How is this paid for?
    If you received this test as part of the eMERGE research study, neither you nor your insurance company will have to pay anything toward this test

    When was this content last updated?
    January 15, 2014.

    More Questions? The National Society of Genetic Counselors has developed a directory to help locate genetic counseling services near you.
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