National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Factor V Leiden thrombophilia

Not a rare disease Not a rare disease
Other Names:
Hereditary resistance to activated protein C; APC resistance, Leiden type
Categories:
Factor V Leiden thrombophilia is a genetic disorder that makes it more likely for you to develop a blood clot sometime during your life. Still, it is estimated that 95% of people with factor V Leiden never develop a clot. When a clot does form, the clot most often occurs in your leg (deep venous thrombosis or DVT) or lungs (pulmonary embolism or PE).[1][2] Factor V Leiden is the name of a specific gene mutation in the F5 gene. This gene plays a role in how your body forms blood clots after an injury. People can inherit one or two copies of the factor V Leiden gene mutation. 

This condition should not be confused with Factor V deficiency, an inherited bleeding disorder that can cause excessive bleeding following surgery or trauma.
Last updated: 7/5/2019
People with factor V Leiden thrombophilia have a higher risk for blood clots. However, the severity of factor V Leiden thrombophilia varies greatly from person to person. Only 5% of people with one factor V Leiden mutation develop a clot by age 65.[3]

The chance a person with a factor V Leiden gene mutation develops a blood clot is affected by a number of factors, such as having a family history of clots, a second factor V Leiden gene mutation, a second genetic or acquired blood clotting disorder, and other 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, non-O blood group, cancer, and injuries (such as bone fractures).[1][2][3][4] 

The most common type of blood clots associated with factor V Leiden thrombophilia, are deep venous thrombosis or DVT and pulmonary embolism or PE.[1] Signs and symptoms of DVT include leg pain, tenderness, swelling, increased warmth or redness in one leg. Signs and symptoms of pulmonary embolism usually include cough, chest pain, shortness of breath or rapid heartbeat or breathing.[5] To learn more about the symptoms of DVT and PE, click here.

While less common, other possible sites of blood clots, include superficial veins of the leg, veins carrying blood from the digestive organs and spleen to the liver, veins carrying blood away from the liver, and veins supplying the brain. Factor V Leiden thrombophilia may contribute a small amount of risk toward a heart attack, stroke, or pregnancy complication.[4]
Last updated: 8/23/2017
Factor V Leiden thrombophilia is caused by a specific mutation in the F5 or Factor V gene. F5 plays a critical role in the formation of blood clots in response to injury.  Genes are our body’s instructions for making proteins. F5 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.[1][2] Factor V Leiden gene mutations cause factor V to be inactivated more slowly than normal.[3] This leaves more time for blood clots to form.
Last updated: 8/23/2017
We all inherit two copies of the F5 (factor V) gene. We inherit one copy from our mother and the other from our father. As a result, our risk for having factor V Leiden thrombophilia depends on the genetic status of each of our parents.

Most people with factor V Leiden thrombophilia have one "normal" F5 gene and one with the factor V Leiden gene mutation. People with one copy of the mutation are called heterozygotes. Assuming this person and a person without the mutation have a child, this couple would have a 50%, or 1 in 2 chance of having a child with a single F5 mutation.

Factor V Leiden thrombophilia is a relatively common condition. In some families, both parents have the F5 mutation. In this scenario, each child of the couple would have a 25% or 1 in 4 chance of having two mutations, a 25% chance of having no mutation, and a 50% chance of having a one mutation.[1]

People with two copies of the F5 mutation are said to be "homozygotes." They will always pass one copy of the mutated gene to their children.[1] A child's risk for a second  mutation will depend on whether or not his or her other parent has the F5 mutation.
Last updated: 1/24/2017
A diagnosis of factor V Leiden thrombophilia may be considered in people with a notable personal or family history of venous thromboembolism (VTE), such as having a VTE at an atypically young age, in an unusual location, or having multiple VTEs. A doctor may confirm the diagnosis by ordering a genetic or APC resistance test. Alternatively, it is becoming more common for people to learn they have a factor V Leiden gene mutation from an advertised genetic test they purchased directly.[4]
Last updated: 1/24/2017

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).[6]
Last updated: 1/24/2017
Treatment of factor V Leiden thrombophilia varies depending on the patient's medical history and current circumstances.

People with factor V Leiden thrombophilia who've had a deep venous thrombosis (DVT) or pulmonary embolism (PE) are usually treated with blood thinners, or anticoagulants (such as heparin and warfarin). Anticoagulants 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 they have additional blood clot risk factors.

People who have factor V Leiden but have never had a blood clot are not routinely treated with an anticoagulant. Instead, they are counseled about reducing or eliminating other factors that add to their risk for clots. They may require temporary treatment with an anticoagulant during periods of particularly high risk, such as major surgery.[7]

Women with factor V Leiden thrombophilia most often have normal pregnancies. Treatment with an anticoagulant during pregnancy and/or following delivery is often not needed, but may be recommended depending on the woman's personal and family health history, method of delivery, and other risk factors.[4][7]
Last updated: 1/24/2017
The factor V Leiden mutation is the most common inherited risk factor for abnormal blood clotting in the United States. Factor V Leiden mutations are estimated to be carried by:

5% of Caucasians
2% of Hispanic Americans
1% Native Americans
1% African Americans
0.5% Asian Americans

In addition, up to 14% of people in populations from Greece, Sweden, and Lebanon are thought to carry factor V Leiden.[4]

Having two factor V Leiden mutations is much rarer, affecting around 1 in 1,600 people.[3]
Last updated: 8/23/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Factor V Leiden thrombophilia. Click on the link to view a sample search on this topic.

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  1. Factor V Leiden thrombophilia. Genetics Home Reference. August 2010; http://ghr.nlm.nih.gov/condition=factorvleidenthrombophilia.
  2. Kujovich J.. Factor V Leiden thrombophilia. GeneReviews. March 2010; http://www.ncbi.nlm.nih.gov/books/NBK1368/.
  3. MacCallum P, Bowles L, Keeling D. Diagnosis and management of heritable thrombophilias. BMJ. 2014; 349:g4387. Accessed 8/23/2017.
  4. Bauer KA. Factor V Leiden and activated protein C resistance: Clinical manifestations and diagnosis. In: Leung LLK ed.,. UpToDate. Waltham, MA: UpToDate; 2015;
  5. Deep venous thrombosis. MedlinePlus. 2007; http://www.nlm.nih.gov/medlineplus/ency/article/000156.htm. Accessed 2/13/2008.
  6. Jody L Kujovich. Factor V Leiden Thrombophilia. GeneReviews. March 9, 2010; http://www.ncbi.nlm.nih.gov/books/NBK1368/#factor-v-leiden.Diagnosis. Accessed 7/13/2011.
  7. Learning About Factor V Leiden Thrombophilia. National Human Genome Research Institute (NHGRI). December 2010; http://www.genome.gov/15015167.