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Factor V Leiden Thrombophilia

Last updated March 21, 2018

Factor V Leiden (FVL) Thrombophilia is the most common inherited (passed on to children) disorder causing thrombophilia. Thrombophilia is a hereditary condition in which, there is an increased tendency to develop abnormal blood clots, especially in the veins of the leg.


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

  • Activated Protein C Resistance Leiden Type
  • Factor V:G1691A Mutation
  • Hereditary Resistance to Activated Protein C

What is Factor V Leiden Thrombophilia? (Definition/Background Information)

  • Factor V Leiden (FVL) Thrombophilia is the most common inherited (passed on to children) disorder causing thrombophilia. Thrombophilia is a hereditary condition in which, there is an increased tendency to develop abnormal blood clots, especially in the veins of the leg
  • In this condition, there is an alteration in Factor V due to a point mutation in the gene encoding Factor V
    • This mutation is called Factor V Leiden (named after a Dutch University, where it was discovered)
    • It is inherited in an autosomal dominant manner             
  • Normally Factor V (factor 5) is one of the factors in the coagulation system, which is responsible for clotting of blood. Due to the mutation and the resulting abnormal Factor V, the clot gets bigger than what it should be. This can even lead to life-threatening clinical situations
  • Fortunately, most individuals with Factor V Leiden mutation do not form abnormal clots (thrombosis) except in certain clinical situations
  • The disorders most commonly associated with Factor V Leiden mutation are deep vein thrombosis (DVT) of the leg, pulmonary embolism (clot blockage of respiratory circulation), miscarriages, etc.
  • The usual treatment options for abnormal clot formation are the use of anticoagulants such as heparin, warfarin, rivaroxaban, etc.
  • Future episodes of abnormal clot formation can be prevented after the first thrombotic episode is diagnosed (that it is due to FVL mutation). Preventative options may include avoidance of oral contraceptive pills, limiting immobilization, etc.
  • The overall prognosis of Factor V Leiden mutation associated abnormal clot formation is generally good with prompt diagnosis, treatment, and appropriate prevention strategies

Note: FVL mutation is different from Factor V deficiency, where the latter is associated with abnormal bleeding tendencies.

Who gets Factor V Leiden Thrombophilia? (Age and Sex Distribution)

  • Factor V Leiden Thrombophilia is more common in individuals of European descent. Up to 5% of these individuals have this mutation. It is very rare in individuals of African or Asian origin
  • Although individuals are born with this FVL mutation, they do not develop thrombophilia, until they reach late adolescence or adulthood. Only 10% of individuals with Factor V Leiden develop thrombophilia
  • Although the mutation is equally common in men and women, women more often manifest the condition due to abnormal clot formations, especially in situations such as pregnancy or while taking estrogen hormone

What are the Risk Factors for Factor V Leiden Thrombophilia? (Predisposing Factors)

A family history of Factor V Leiden mutation increases one’s risk to develop FVL Thrombophilia.

  • Factor V Leiden mutation is inherited in an autosomal dominant manner, indicating that those with a family history of the condition are at a high risk of developing this condition
  • Individuals with 1 gene (heterozygotes) mutations have 4 times the risk of developing thrombophilia
  • Individuals with 2 gene (homozygotes) mutations have 8 times the risk of developing thrombophilia

Other factors that increase the risk of thrombophilia in individuals with FVL mutation include:

  • Individuals of European descent (whites) are more at risk to develop FVL Thrombophilia
  • Pregnancy
  • Taking oral contraceptives (birth control pills)
  • Taking hormone replacement therapy
  • Taking medications, such as selective estrogen receptor modulators, which include tamoxifen and raloxifene to treat breast cancer
  • Older age, especially over the age of 60 years
  • Overweight or obesity
  • Immobilization due to:
    • Injury to the leg
    • Surgery or any long medical procedure
    • Travelling for long hours (such as in an airplane) without any movement to the leg 

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones 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 Factor V Leiden Thrombophilia? (Etiology)

The causes of Factor V Leiden Thrombophilia include:

  • It is caused due to Factor V Leiden mutation
  • This mutation is inherited in an autosomal dominant manner
    • The basic genetic material is made up of genes. Each gene is paired and one of each gene pair comes from each parent
    • If both genes are without any defects, then it is a healthy gene pair

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 functioning 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.

  • The probability of an individual with Factor V Leiden mutation developing abnormal clot formation (thrombosis) depends on the following factors:
    • Individuals with 1 gene (heterozygotes) mutation have 4 times the risk of developing thrombophilia. These individuals inherit only one copy of abnormal gene from one parent
    • Individuals with 2 gene (homozygotes) mutations have 8 times the risk of developing thrombophilia. These individuals inherit two copies of abnormal genes, one from each parent
    • Other factors which precipitate abnormal clotting in these susceptible individuals include pregnancy, oral contraceptive pills, hormone replacement therapy, anti-cancer drugs, smoking, and other factors
    • The risk of thrombophilia is increased when there is an associated mutation in another gene that is responsible for anti-clotting mechanisms           
  • Normally, a blood clot forms to stop bleeding that occurs as a result of any cut or injury to the vein or artery. A blood clot is the result of chemical reactions that takes place between specialized blood cells, called platelets, and proteins in blood called clotting factors. There are 13 major coagulation factors numbered I to XIII, which includes Factor V
  • Anti-clotting factors present in blood help in controlling the formation of excessive blood clots than what is really required. One of the anti-clotting proteins (called Protein C) breaks down Factor V and keeps it from being reused and forming further clots
  • In Factor V Leiden Thrombophilia, the mutated Factor V Leiden product does not allow Protein C to break it down, leading to excess clot formation (thrombosis)

What are the Signs and Symptoms of Factor V Leiden Thrombophilia?

The signs and symptoms of Factor V Leiden Thrombophilia include:

  • It is important to note that most individuals (about 90% of them) with Factor V Leiden mutation do not have abnormal clot formation (thrombosis)
  • Thrombosis is predominantly seen in the veins than in the arteries
  • Thrombosis involving the deep veins (deep vein thrombosis/DVT) most commonly involves the leg, but occasionally can occur in the eyes, brain, kidney, and at other body locations
  • DVT of the leg presents with swelling , pain, tenderness to touch, and increased warmness of the affected leg
  • The clot can break away, travel through the blood, and compromise blood circulation of the lungs (known as pulmonary embolism or PE). This is a life-threatening situation and can present with chest pain, difficulty in breathing, blood-tinged cough, etc.
  • Pregnant women may suffer a miscarriage due to thrombophilia. This may recur each time they are pregnant
    • Thrombophilia can also cause high blood pressure in pregnant women (preeclampsia)
    • However, it is important to note that most woman with Factor V Leiden mutation do not develop complications during pregnancy

How is Factor V Leiden Thrombophilia Diagnosed?

The following procedures may be used to diagnose Factor V Leiden Thrombophilia:

  • Complete evaluation of the individual’s medical (and family) history and a thorough physical examination
  • During history-taking the physician may want to know the following:
    • When the symptoms began and whether they are becoming worse
    • List of prescription and over-the-counter medications currently being taken such as oral contraceptive pill, herbal medications, medications for blood pressure control, etc.
    • Personal and family history of bleeding tendencies, thrombotic tendencies, miscarriages, complications of pregnancies, surgeries, and travel history (if required)            
  • Hematologist consultation is often necessary, as they are the experts in dealing with disorders of blood
  • The physician may suspect an episode of Factor V Leiden Thrombophilia, if the individual has had the following:
    • Thrombosis of veins
    • Pregnancy loss
    • Family history of the condition 
  • Confirmation of the presence of FVL Thrombophilia can be done through blood tests.
  • Screening tests are done first. They include:
    • Complete blood count
    • Peripheral blood film (smear)
    • Prothrombin time
    • Activated partial thromboplastin time
  • Confirmatory tests are undertaken next, if the suspicion for FVL Thrombophilia is still high. They include:
    • Activated protein C resistance test (or assay)
    • Factor V Leiden mutation genetic test: This is most specific test for this condition. It will also determine if one or two copies of the mutation has been inherited          
  • Other diagnostic tests are done to either confirm or rule-out thrombosis of the involved organs. The may include Doppler scan for DVT, VQ scan or CT angiography for pulmonary embolism, etc.

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 Factor V Leiden Thrombophilia?

The complications of Factor V Leiden Thrombophilia include:

  • Complications that may occur during pregnancy:
    • Miscarriages
    • Preeclampsia: High blood pressure during pregnancy
    • Decreased fetal growth
    • Early separation of the placental membranes from the uterine wall prior to the due date (placental abruption)
    • Deep vein thrombosis
  • Pulmonary embolism: A blood clot can break free from DVT and travel to the lungs, compromising its blood circulation. This can become a life-threatening medical situation or even cause death

How is Factor V Leiden Thrombophilia Treated?

The treatment options of Factor V Leiden Thrombophilia include:

  • Withholding or avoiding precipitants (triggers) that would have caused abnormal blood clot formations
  • Blood thinning medicines are generally administered to treat individuals with active abnormal blood clot formation. The treatment options include:
    • Heparin (or low molecular weight heparin), administered through the vein, or under the skin
    • Warfarin (oral medication) may also be given, except during pregnancy, as it may cause birth defects
    • Generally, the initial treatment given is a combination of warfarin and heparin, followed by warfarin alone
    • Other medications that may be given include enoxaparin, dalteparin, dabigatran, and rivaroxaban
    • When an individual is taking anticoagulant medication, he/she should be monitored for side effects (bleeding) by the healthcare provider including by using periodic blood tests
    • Blood thinners are usually not prescribed to individuals with Factor V Leiden mutation, if they are not forming abnormal blood clots (i.e., having no symptoms). However, they may be prescribed blood thinners prophylactically, in situations such as elective major surgery, prolonged immobilization, and during other conditions  
  • During pregnancy, most women with Factor V Leiden have uneventful normal pregnancies. However, these individuals are at increased risk of developing blood clots. Hence, such individuals should be closely monitored by their healthcare provider during the pregnancy term

How can Factor V Leiden Thrombophilia be Prevented?

The preventative measures of Factor V Leiden Thrombophilia include:

  • Individuals who have developed abnormal clot formation in the past should undergo confirmatory testing, if they have risk factors and are suspects for Factor V Leiden mutation
  • Individuals who have been diagnosed with Factor V Leiden mutation can prevent thrombophilia to a certain extent by following simple measures such as:
    • By avoiding standing or sitting in the same position for a very long time
    • While travelling long distances either by plane or car, moving one’s legs or walking (in the aisle space) helps the blood to keep moving from the lower part of the body to the heart, avoiding blood stasis
    • Reducing body weight helps decrease pressure in the veins of the leg, thereby minimizing clot formation risks
    • Reducing body weight helps decrease pressure in the veins of the leg, thereby minimizing clot formation risks
    • Smoking should be stopped 
    • Women with FVL mutation may avoid oral contraceptive pills or estrogen-containing medications. They should also consult with their healthcare provider before conception, in order to educate themselves on how to reduce complications associated with pregnancy

What is the Prognosis of Factor V Leiden Thrombophilia? (Outcomes/Resolutions)

  • With prompt diagnosis and suitable treatment, the overall prognosis of Factor V Leiden (FVL) Thrombophilia is typically good. The risk of the condition may also be reduced through proper preventive strategies
  • Individuals with one gene mutation have better prognosis and less thrombotic episodes than individuals with two gene mutation
  • Individuals with one gene mutation do not have a reduction in life expectancy

Additional and Relevant Useful Information for Factor V Leiden Thrombophilia:

  • Deep vein thrombosis (DVT) is a blood clot that occurs in a deep vein of the leg. Most of these blood clots occur in the leg or thigh; though, they may also occur in other parts of the body

The following article link will help you understand deep vein thrombosis (DVT):

http://www.dovemed.com/diseases-conditions/deep-vein-thrombosis/

  • Factor V Leiden mutation and PT 20210 mutation tests are used to identify the presence of mutations and also if, the individual is homozygous or heterozygous for the same

The following article link will help you understand Factor V Leiden mutation and PT 20210 mutation tests:

http://www.dovemed.com/common-procedures/procedures-laboratory/factor-v-leiden-mutation-and-pt-20210-mutation-tests/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 28, 2015
Last updated: March 21, 2018