What is factor V Leiden thrombophilia?
Factor V Leiden thrombophilia
is an inherited disorder that results in an increased risk of developing abnormal blood clots. Factor V Leiden is the name of a specific gene mutation
in the F5
gene. This gene plays a critical role in the normal formation of blood clots in response to an injury. People can inherit one or two copies of the factor V Leiden gene mutation. Those who inherit one copy are called heterozygotes.
People who inherit two copies of the mutation, one from each parent, are called homozygotes
. Having the factor V Leiden mutation increases your risk for developing a clot in your legs called a deep venous thrombosis (DVT)
. It also increases your risk of developing a clot that travels through the bloodstream and lodges in the lungs, called a pulmonary embolism (PE)
Last updated: 6/29/2012
What are the signs and symptoms of factor V Leiden thrombophilia?
Individuals affected by factor V Leiden thrombophilia have an increased risk of developing blood clots. The severity of factor V Leiden thrombophilia is extremely variable. Many individuals with the factor V Leiden allele
never develop a blood clot. Although most individuals with factor V thrombophilia do not experience their first thrombotic event until adulthood, some have recurrent thromboembolism before age 30 years. The chance a person will develop a blood clot is affected by the number of factor V Leiden mutations, the presence of coexisting genetic abnormalities, and non-genetic risk factors. Non-genetic risk factors include surgery, long periods of not moving (like sitting on a long airplane ride), birth control pills and other female hormones, childbirth within the last 6 months, and traumas or fractures.
Individuals who inherit one copy of the factor V Leiden mutation have a fourfold to eightfold increase in the chance of developing a clot. Homozygotes (people who inherit two factor V Leiden mutations) may have up to 80 times the usual risk of developing a blood clot. Considering that the risk of developing an abnormal blood clot averages about 1 in 1,000 per year in the general population, the presence of one copy of the factor V Leiden mutation increases that risk to 4 to 8 in 1,000, and having two copies of the mutation may raise the risk as high as 80 in 1,000.
People with factor V Leiden have an increased chance of having a blood clot that forms in large veins in the legs (deep venous thrombosis, or DVT
) or a clot that travels through the bloodstream and lodges in the lungs (pulmonary embolism, or PE
Symptoms of deep vein thrombosis usually include leg pain, tenderness, swelling, increased warmth or redness in one leg. The symptoms of pulmonary embolism usually include cough, chest pain, shortness of breath or rapid heartbeat or breathing.
To learn more about the symptoms of DVT and PE, click here
Last updated: 6/29/2012
What causes factor V Leiden thrombophilia?
Factor V Leiden thrombophilia is caused by a specific mutation in the Factor V gene
. Factor V
plays a critical role in the formation of blood clots in response to injury. Genes are our body’s instructions for making proteins. The factor V gene instructs the body how to make a protein called coagulation factor V. Coagulation factor V is involved in a series of chemical reactions that hold blood clots together. A molecule called activated protein C (APC) prevents blood clots from growing too large by inactivating factor V.
Last updated: 6/29/2012
How is factor V Leiden inherited?
Factor V Leiden is a genetic condition and can be inherited from a parent. It is important to understand that each person inherits two copies of every gene, one from their mother and the other copy from their father. Individuals who inherit one copy of the factor V Leiden mutation from a parent are called heterozygotes.
Heterozygotes have a 50% chance with each pregnancy of passing the mutated gene to their offspring (and therefore they also have a 50% chance of having a child who does not inherit the gene mutation). People who inherit two copies of the mutation, one from each parent, are called homozygotes
. Homozygotes will always pass one copy of the mutated gene to their offspring.
If both parents are heterozygotes (carry one factor V Leiden mutation) than they would have a 25% chance of having a child with two factor V Leiden mutations, a 25% chance of having a child with no mutations, and a 50% chance of having a child with one mutation.
Last updated: 4/20/2011
How is factor V Leiden thrombophilia diagnosed?
No clinical features (signs and/or symptoms) are specific for factor V Leiden thrombophilia. The diagnosis of factor V Leiden thrombophilia requires a coagulation screening test or DNA analysis of F5, the gene for factor V, to identify the specific mutation that causes this condition.
The APC (activated protein C) resistance assay, a coagulation screening test, measures the anticoagulant response to APC. This screening test has a sensitivity and specificity for factor V Leiden approaching 100%. The sensitivity of a test is a measure of the test's ability to detect a positive result when someone has the condition, while the specificity is a measure of the test's ability to identify negative results.Targeted mutation analysis (a type of DNA test) of the F5 gene for the Leiden mutation is considered definitive and has a mutation detection frequency of approximately 100%. This means that approximately all individuals who have the factor V Leiden mutation will be detected by this genetic test. It is generally recommended that individuals who test positive by another means should then have the DNA test both for confirmation and to distinguish heterozygotes (individuals with a mutation in one copy of the gene) from homozygotes (individuals with mutations in both copies of the gene).
Last updated: 7/13/2011
How might factor V Leiden be treated?
The management of individuals with factor V Leiden depends on the clinical circumstances. People with factor V Leiden who have had a deep venous thrombosis (DVT)
or pulmonary embolism (PE)
are usually treated with blood thinners, or anticoagulants. Anticoagulants such as heparin and warfarin are given for varying amounts of time depending on the person's situation. It is not usually recommended that people with factor V Leiden be treated lifelong with anticoagulants if they have had only one DVT or PE, unless there are additional risk factors present. Having had a DVT or PE in the past increases a person's risk for developing another one in the future, but having factor V Leiden does not seem to add to the risk of having a second clot. In general, individuals who have factor V Leiden but have never had a blood clot are not routinely treated with an anticoagulant. Rather, these individuals are counseled about reducing or eliminating other factors that may add to one's risk of developing a clot in the future. In addition, these individuals may require temporary treatment with an anticoagulant during periods of particularly high risk, such as major surgery.
Factor V Leiden increases the risk of developing a DVT during pregnancy by about seven-fold. Women with factor V Leiden who are planning pregnancy should discuss this with their obstetrician and/or hematologist. Most women with factor V Leiden have normal pregnancies and only require close follow-up during pregnancy. For those with a history of DVT or PE, treatment with an anticoagulant during a subsequent pregnancy can prevent recurrent problems. 
Last updated: 4/20/2011