Warfarin sensitivity

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What is warfarin sensitivity?

Warfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming. Warfarin is often prescribed to prevent blood clots in people with heart valve disease who have replacement heart valves, people with an irregular heart beat (atrial fibrillation), or those with a history of heart attack, stroke, or a prior blood clot in the deep veins of the arms or legs (deep vein thrombosis).

Many people with warfarin sensitivity take longer than normal to break down (metabolize) warfarin, so the medication is in their body longer than usual and they require lower doses. These individuals are classified as "slow metabolizers" of warfarin. Other people with warfarin sensitivity do not need as much drug to prevent clots because their clot forming process is already slower than average and can be inhibited by low warfarin doses. If people with warfarin sensitivity take the average dose (or more) of warfarin, they are at risk of an overdose, which can cause abnormal bleeding in the brain, gastrointestinal tract, or other tissues, and may lead to serious health problems or death.

Warfarin sensitivity does not appear to cause any health problems other than those associated with warfarin drug treatment.

How common is warfarin sensitivity?

The prevalence of warfarin sensitivity is unknown. However, it appears to be more common in people who are older, those with lower body weights , and individuals of Asian ancestry.

Of the approximately 2 million people in the U.S. who are prescribed warfarin annually, 35,000 to 45,000 individuals go to hospital emergency rooms with warfarin-related adverse drug events. While it is unclear how many of these events are due to warfarin sensitivity, the most common sign is excessive internal bleeding, which is often seen when individuals with warfarin sensitivity are given too much of the medication.

What genes are related to warfarin sensitivity?

Many genes are involved in the metabolism of warfarin and in determining the drug's effects in the body. Certain common changes (polymorphisms) in the CYP2C9 and VKORC1 genes account for 30 percent of the variation in warfarin metabolism due to genetic factors. Polymorphisms in other genes, some of which have not been identified, have a smaller effect on warfarin metabolism.

The CYP2C9 gene provides instructions for making an enzyme that breaks down compounds including steroids and fatty acids. The CYP2C9 enzyme also breaks down certain drugs, including warfarin. Several CYP2C9 gene polymorphisms can decrease the activity of the CYP2C9 enzyme and slow the body's metabolism of warfarin. As a result, the drug remains active in the body for a longer period of time, leading to warfarin sensitivity.

The VKORC1 gene provides instructions for making one piece (subunit) of the vitamin K epoxide reductase (VKOR) complex. The VKOR complex helps turn on (activate) clotting proteins in the pathway that forms blood clots. Warfarin prevents (inhibits) the action of VKOR and slows the activation of clotting proteins and clot formation. Certain VKORC1 gene polymorphisms decrease the amount of functional VKOR enzyme available to help activate clotting proteins. Individuals develop warfarin sensitivity because less warfarin is needed to inhibit the VKOR enzyme, as there is less functional enzyme that needs to be suppressed.

While changes in specific genes, particularly CYP2C9 and VKORC1, affect how the body reacts to warfarin, many other factors, including gender, age, weight, diet, and other medications, also play a role in the body's interaction with this drug.

Read more about the CYP2C9 and VKORC1 genes.

See a list of genes associated with warfarin sensitivity.

How do people inherit warfarin sensitivity?

The polymorphisms associated with this condition are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to result in warfarin sensitivity. However, different polymorphisms affect the activity of warfarin to varying degrees. Additionally, people who have more than one polymorphism in a gene or polymorphisms in multiple genes associated with warfarin sensitivity have a lower tolerance for the drug's effect or take even longer to clear the drug from their body.

Where can I find information about diagnosis or management of warfarin sensitivity?

These resources address the diagnosis or management of warfarin sensitivity and may include treatment providers.

You might also find information on the diagnosis or management of warfarin sensitivity inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about warfarin sensitivity?

You may find the following resources about warfarin sensitivity helpful. These materials are written for the general public.

MedlinePlus - Health information (4 links)
Additional NIH Resources - National Institutes of Health
National Heart, Lung, and Blood Institute: How is Excessive Blood Clotting Treated?
Educational resources - Information pages (6 links)
Patient support - For patients and families (2 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for warfarin sensitivity?

coumadin sensitivity
warfarin response

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about warfarin sensitivity?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding warfarin sensitivity?

acids ; atrial ; atrial fibrillation ; autosomal ; autosomal dominant ; cell ; clotting ; enzyme ;fatty acids ; fibrillation ; gastrointestinal ; gene ; heart attack ; heart valve ; inherited ; metabolism ;pharmacogenetics ; pharmacogenomics ; polymorphism ; prevalence ; sensitivity ; sign ; steroids ;subunit ; thrombosis ; veins ; warfarin

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (10 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook