What are the other Names for this Condition? (Also known as/Synonyms)

• Coumadin Resistance
• Coumarin Resistance
• Poor Metabolism of Coumadin

What is Warfarin Resistance? (Definition/Background Information)

• Warfarin Resistance is a condition that is characterized by a high tolerance for a "blood-thinning" medication called warfarin. Warfarin is an anticoagulant that is often prescribed to people who are at an increased risk for blood clots
• Some people with a Warfarin Resistance do not respond to the drug at all, while others can achieve the benefits of warfarin treatment at a high dose. In either case, affected people will still be at an elevated risk for blood clots when given the standard dose of warfarin
• The metabolism of warfarin and the drug's effects in the body are complex traits that are determined by several genes as well as environmental and lifestyle factors such as gender, age, weight, diet, and other medications
• One specific genetic polymorphism in the VKORC1 gene accounts for approximately 20% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant manner

(Source: Warfarin Resistance; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

• Warfarin Resistance can either be hereditary or acquired. Acquired Warfarin Resistance can develop due to non-compliance, interaction with other drugs that inhibit the effect of warfarin, increased clearance of drug from the body, and low absorption of the drug

Who gets Warfarin Resistance? (Age and Sex Distribution)

• Warfarin Resistance is a rare disorder that may affect adults who are prescribed warfarin
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Warfarin Resistance? (Predisposing Factors)

• A positive family history may be an important risk factor, since Warfarin Resistance can be inherited
• The risk factors for acquired Warfarin Resistance may include:
• Being a “rapid-metabolizer” of drugs
• Using supplements of vitamin K at high doses
• Using drugs, such as barbiturates, cortisones, oral contraceptives, and multivitamins, among other prescription medications

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Warfarin Resistance? (Etiology)

• Warfarin Resistance of the hereditary type may be caused by one specific genetic polymorphism in the VKORC1 gene, which accounts for approximately 20% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant manner

(Source: Warfarin Resistance; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

In addition, acquired Warfarin Resistance can be caused by:

• Individuals not using the medicine as recommended (non-compliance)
• Low absorption of the drug
• Increased clearance (metabolizing) of the drug, such that the drug is not effective
• Interaction with other substances an individual may be taking, which may include barbiturates, cortisones, multivitamins, and oral contraceptives, among others
• High intake of vitamin K (such as through certain health foods), which promotes clotting

What are the Signs and Symptoms of Warfarin Resistance?

The signs and symptoms of Warfarin Resistance may vary among affected individuals in type and severity, and may include:

• Abnormality of blood and blood-forming tissues
• Abnormality of metabolism/homeostasis

(Source: Warfarin Resistance; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Warfarin Resistance Diagnosed?

Warfarin Resistance is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Warfarin Resistance?

The complications of Warfarin Resistance may include:

• Increased risk of clotting
• Bleeding complications
• Increased risk of thrombosis

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Warfarin Resistance Treated?

• Hereditary Warfarin Resistance may not be treatable, since it is a genetic condition. In such cases, treatment is usually given to manage the signs and symptoms and any complication that develops
• Acquired Warfarin Resistance may be treatable by:
• Ensuring compliance by affected individuals
• Increasing warfarin dosage
• Prescription of an alternate coagulant
• If possible, reducing vitamin K intake and other drugs that may be inhibiting warfarin action

How can Warfarin Resistance be Prevented?

Hereditary Warfarin Resistance may not be preventable, since it is a genetic disorder.

• Acquired Warfarin Resistance may be prevented by following the recommendations for proper dosage of warfarin, and disclosure of all medications and supplements being used to the healthcare provider. The latter may aid the healthcare provider in determining the proper dose of warfarin to be prescribed 
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired disorders such as Warfarin Resistance
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Warfarin Resistance? (Outcomes/Resolutions)

• The prognosis of Warfarin Resistance is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Warfarin Resistance:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/