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Factor V Leiden
Factor V Leiden is a genetic predisposition that makes blood more prone to clotting. It primarily affects the venous system, increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). This condition commonly affects individuals of European ancestry.
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Overview
Factor V Leiden is an inherited condition that causes a person's blood to clot more easily than usual. This increased tendency to clot is due to a specific change in the F5 gene, which codes for a protein called Factor V. While Factor V is essential for normal blood clotting to stop bleeding, the Factor V Leiden variation makes this protein more resistant to inactivation, leading to prolonged clotting activity [PMID:10629033]. It is one of the most common genetic risk factors for venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism.
Deep vein thrombosis (DVT) involves the formation of a blood clot within a deep vein, most commonly in the legs. A pulmonary embolism (PE) occurs when a part of this clot breaks off and travels to the lungs, blocking a blood vessel there. Factor V Leiden does not guarantee that a person will develop clots, but it increases their susceptibility, especially when other risk factors are present.
Symptoms & clinical features
Many individuals with Factor V Leiden never experience any symptoms and may be unaware they have the condition. Symptoms only arise if a blood clot forms. The most common presentation is deep vein thrombosis (DVT), mainly in the leg. Symptoms of DVT in the leg can include pain or tenderness, swelling, warmth, and redness in the affected area.
If a DVT travels to the lungs, it can cause a pulmonary embolism (PE). Symptoms of a PE can be more severe and include sudden shortness of breath, chest pain (often worse with deep breathing), rapid heart rate, lightheadedness, or coughing (sometimes with blood). It is important to seek immediate medical attention if these symptoms develop, as a PE can be life-threatening [PMID:24075240].
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Affected organs
Factor V Leiden primarily affects the cardiovascular system, specifically the veins. The main impact is on the deep veins of the lower limbs (legs and pelvis), where deep vein thrombosis (DVT) often forms. These clots can then potentially travel through the bloodstream to the lungs, leading to a pulmonary embolism (PE). While less common, clots might also form in other venous sites, such as the abdominal veins or cerebral veins.
Risks & severity
The severity of Factor V Leiden varies considerably. Many individuals with this genetic variation never experience a blood clot. However, it significantly increases the lifetime risk of developing venous thromboembolism (VTE). For those with one copy of the F5 Leiden mutation (heterozygous), the risk of VTE is generally 3 to 8 times higher than in the general population. Individuals with two copies (homozygous) face an even greater risk, estimated to be up to 80 times higher [PMID:24075240].
Clots can occur at any age, but the risk often increases with age. Other factors can further elevate the risk, such as surgery, prolonged immobility (e.g., long flights or bed rest), pregnancy, oestrogen-containing medications (like oral contraceptives or hormone replacement therapy), and certain medical conditions like cancer. While Factor V Leiden is primarily linked to venous clots, some research suggests a potential, though less clear, association with arterial clots (like heart attacks or strokes), especially in the presence of other risk factors.
Genetic causes
Factor V Leiden is caused by a specific alteration, or mutation, in the F5 gene. The F5 gene provides instructions for making a protein called coagulation factor V. This protein is a crucial component of the coagulation cascade, a series of steps that leads to blood clot formation when a blood vessel is injured. Normally, after Factor V has done its job in promoting clotting, another protein called activated protein C (APC) inactivates it, ensuring that clotting does not become excessive.
In individuals with Factor V Leiden, the F5 gene has a point mutation, meaning a single change in the DNA sequence. This change creates a modified Factor V protein that is resistant to inactivation by APC. Because the mutated Factor V remains active for longer than it should, the blood has an increased tendency to clot, predisposing individuals to thrombosis [PMID:10629033]. This genetic change is inherited in an autosomal dominant pattern.
- F5 coagulation factor VThe F5 gene provides instructions for coagulation factor V, a protein crucial for blood clotting and regulating the coagulation system.
Inheritance pattern
Factor V Leiden is inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of the altered F5 gene from either parent to have the condition. If a parent has Factor V Leiden, there is a 50% chance with each pregnancy that their child will also inherit the altered gene.
It is possible to inherit two copies of the altered gene, one from each parent. Individuals with two copies (known as homozygous) typically have a higher risk of developing blood clots compared to those with one copy (heterozygous). Relatives of individuals with Factor V Leiden may be offered genetic counselling and testing to understand their own risk.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of Factor V Leiden is typically initiated after an individual experiences an unexplained blood clot, or if there is a strong family history of blood clots. The initial screening test often involves a functional activated protein C (APC) resistance assay. If this test indicates APC resistance, a more specific genetic test is performed to confirm the presence of the F5 Leiden mutation.
Genetic testing involves a blood sample, which is then analysed in a laboratory to look for the specific change in the F5 gene. In the UK, genetic testing for thrombophilia (a tendency to clot) may be offered through the NHS Genomic Medicine Service following a referral from a specialist (e.g., a haematologist) [R-code: R355]. Genetic counsellors can help explain the implications of testing for individuals and their families.
Management & lifestyle
Management for individuals with Factor V Leiden is highly individualised and depends on whether they have experienced a blood clot. Many individuals with Factor V Leiden who have never had a clot may not require specific preventative treatment. However, they are typically advised on lifestyle modifications, such as maintaining a healthy weight, staying hydrated, and avoiding prolonged immobility, particularly during long journeys or after surgery.
For individuals who have experienced a blood clot, treatment usually involves taking anticoagulant medications (blood thinners) for a specified period to prevent further clots. The duration of this treatment is decided by a specialist, often a haematologist, considering the circumstances of the clot and the individual's overall health and risk factors. In situations of high risk, such as major surgery or pregnancy, preventative measures like short-term anticoagulants might be considered even if the person has not had a prior clot. Regular discussions with healthcare professionals are key to determining the most appropriate management plan.
UK care pathway
In the UK, individuals suspected of having Factor V Leiden typically enter the NHS Genomic Medicine Service pathway following a referral from a general practitioner or specialist. This often occurs after an initial blood clot or if there is a significant family history of clotting disorders. Genetic testing for Factor V Leiden falls under the R355 'Thrombophilia (inherited)' record in the NHS National Genomic Test Directory. Patients are usually referred to a specialist (e.g., a haematologist or clinical geneticist) who can then arrange appropriate genetic testing and provide counselling. Genetic counsellors play a vital role in explaining inheritance patterns, risks to family members, and the implications of test results.
Frequently asked questions
If I have Factor V Leiden, will I definitely get blood clots?
No, having Factor V Leiden does not mean you will definitely develop blood clots. Many people with this genetic variation never experience a clot. It increases your risk, especially when other risk factors are present, but it is not a guarantee.
Can I pass Factor V Leiden on to my children?
Yes, Factor V Leiden is inherited in an autosomal dominant pattern. If you have one copy of the altered gene, each of your children has a 50% chance of inheriting it. If you have two copies, all of your children will inherit at least one copy.
Are there any lifestyle changes I can make to reduce my risk of clots?
Yes, maintaining a healthy weight, staying active, avoiding prolonged periods of immobility, and staying hydrated can help reduce your risk. If you are taking oestrogen-containing medications, discuss your Factor V Leiden status with your doctor.
What should I do if I think I am experiencing a blood clot?
If you experience symptoms such as sudden swelling, pain, warmth, or redness in a limb, or sudden shortness of breath and chest pain, you should seek urgent medical attention. These could be signs of a deep vein thrombosis or a pulmonary embolism.
Is Factor V Leiden more common in certain ethnic groups?
Yes, Factor V Leiden is notably more common in people of European descent. It is estimated to affect around 5% of this population, but it is rare in people of African or Asian ancestry.
References
- Applegate JS, Gronefeld D. Factor V Leiden. Radiologic technology. 2019. PMID: 30635457
- Martin KA, Cushman M. Factor V Leiden. JAMA. 2025. PMID: 40305030
- Albagoush SA, Koya S, Chakraborty RK. Factor V Leiden Mutation. 2023. PMID: 30521223
- Brooks JK, Elrafei A, Ord RA. Factor V Leiden thrombophilia dental considerations. General dentistry. 2019. PMID: 31199740
- Florell SR, Rodgers GM. Factor V Leiden: death and DNA. American journal of clinical pathology. 1999. PMID: 10078103
- Hajjar KA. Factor V Leiden--an unselfish gene? The New England journal of medicine. 1994. PMID: 7969330
- Shaw DM. Factor V Leiden: an overview. Clinical laboratory science : journal of the American Society for Medical Technology. 2006. PMID: 17181126
- Ament L. Factor V Leiden and contraception. Journal of midwifery & women's health. 2004. PMID: 14710141