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

• Coumadin Sensitivity

What is Warfarin Sensitivity? (Definition/Background Information)

• Warfarin Sensitivity is a condition that is characterized by a reduced 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
• People with Warfarin Sensitivity respond more strongly to lower doses of warfarin and are, therefore, more likely to experience an overdose or other serious side effects from the medication. They may experience abnormal bleeding in the brain, gastrointestinal tract, or other tissues even at average doses
• 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
• Two specific genetic polymorphisms in the CYP2C9 and VKORC1 genes account for approximately 30-40% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant manner

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

Who gets Warfarin Sensitivity? (Age and Sex Distribution)

• Warfarin Sensitivity is a rare disorder affecting some adults who have been prescribed warfarin, an anticoagulant
• Both males and females may be affected
• Although individuals of all racial and ethnic groups may be affected, the condition is more prevalent in individuals of Asian descent

It is reported that in the United States, approximately 1.5-2% of those prescribed warfarin visit the emergency room for warfarin-related bleeding episodes.

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

• A positive family history may be an important risk factor, since Warfarin Sensitivity can be inherited
• In addition, the following are additional risk factors for Warfarin Sensitivity:
  • Advanced age
  • Low body weight
  • Being of Asian descent
  • Individuals who are “slow metabolizers” of drugs
  • Concurrent use of other medications, such as certain antibiotics
  • Presence of certain pre-existing conditions, other than the one for which warfarin is prescribed (such as liver disease, alcoholism, kidney malfunction, and cancer, among others)

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 Sensitivity? (Etiology)

• Warfarin Sensitivity is caused by two specific genetic polymorphisms in the CYP2C9 and VKORC1 genes, which account for approximately 30-40% of variation in the response to warfarin and can be passed on to future generations in an autosomal dominant manner
• 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

(Source: Warfarin Sensitivity; 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.

What are the Signs and Symptoms of Warfarin Sensitivity?

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

• Bleeding in the gastrointestinal tract leading to:
  • Fatigue
  • Chest pain 
  • Labored breathing
  • Blood in stools 
  • Tarry stools
• Brain hemorrhage, which may cause:
  • Headaches
  • Confusion
  • Weakness
• Bleeding in other body tissues

How is Warfarin Sensitivity Diagnosed?

Warfarin Sensitivity 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 Sensitivity?

The complications of Warfarin Sensitivity may include:

• Permanent brain damage
• Paralysis
• Severe bleeding in the gastrointestinal tract, which can be life-threatening

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

How is Warfarin Sensitivity Treated?

The treatment for Warfarin Sensitivity may include one or more of the following; it is dictated by the need for controlling bleeding:

• Vitamin K supplementation
• Fresh frozen plasma, if the bleeding is severe and an immediate reversal of warfarin is necessary
• Prothrombin complex concentrates are also used, if the bleeding is severe and an immediate reversal of warfarin is necessary

How can Warfarin Sensitivity be Prevented?

Warfarin Sensitivity may not be preventable, if it is a genetic disorder.

• Seeking medical attention for conditions that can cause Warfarin Sensitivity may help avoid bleeding episodes
• Disclosure of all prescription medications, supplements, and over-the-counter drugs being used to the healthcare provider may enable him/her to arrive at an effective dose of warfarin with minimal side effects
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired disorders such as Warfarin Sensitivity
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

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

• The prognosis of Warfarin Sensitivity 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 Sensitivity:

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

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