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Disease Profile

Factor V Leiden thrombophilia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hereditary resistance to activated protein C; APC resistance, Leiden type

Categories

Blood Diseases

Summary

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.

Symptoms

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]

Cause

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.

Diagnosis

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]

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]

Treatment

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]

Organizations

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

    Organizations Providing General Support

      Learn more

      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.

          References

          1. Factor V Leiden thrombophilia. Genetics Home Reference. August 2010; https://ghr.nlm.nih.gov/condition=factorvleidenthrombophilia.
          2. Kujovich J.. Factor V Leiden thrombophilia. GeneReviews. March 2010; https://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; https://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; https://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; https://www.genome.gov/15015167.

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