Factor V Leiden
What is factor V Leiden (FVL)?
Factor V Leiden (FVL), or factor “5” Leiden, is a genetic mutation (change) that makes the blood more prone to abnormal clotting. Factor V Leiden is the most common genetic predisposition to blood clots. Individuals born with FVL are more likely to develop vein clots (deep vein thrombosis or DVT) and pulmonary embolism (PE), but not heart attacks, strokes or blood clots in the arteries of the legs.
FVL results from a mutation (change) of the gene that makes one of the proteins of our coagulation system, called factor V (or “factor 5”). Because each protein in our body is made by two different genes (one inherited from Mom, one inherited from Dad), there are two types of FVL: “heterozygous” (in which only one mutated copy of the F5 gene was inherited, either from the mother or the father), and “homozygous” (in which two mutated copies were inherited, one from each parent). The “heterozygous” FVL is by far the most common mutation. If you have FVL, the risk of developing abnormal blood clots may depend on whether you have the heterozygous or the homozygous mutation.
People who are born with FVL are at higher risk of developing DVT and PE. While DVT usually involves the veins of the legs or arms, it can more rarely occur in other veins of the body, such as veins of the liver, kidneys, intestines or brain. Pulmonary embolism occurs when pieces or fragments of a blood clot – usually from a DVT of the leg - break off and travel to the vessels in the lungs.
The mutation is named factor V “Leiden” because it was originally discovered at the University of Leiden in the Netherlands, in 1994.
Who is likely to have factor V Leiden (FVL)?
FVL can only be inherited from a parent who has the mutation, which is more common among individuals of Northern European ancestry. Children from a parent with heterozygous FVL mutation have a 25% chance of having inherited it from the parent who has the mutation.
How common is factor V Leiden (FVL)?
In the U.S., FVL is present in approximately 5% of the general population. It is less common in Native Americans and African-Americans than in those of Northern European ancestry.
In some countries of Northern Europe, FVL is found in up to 10-15% of the population. It is less common in South America, Africa and Asia, where it can be found in less than 1-3% of the population.
Symptoms and Causes
What causes factor V Leiden (FVL)?
FVL is caused by a genetic mutation to the Factor V (or “factor 5”) gene. This gene helps our body make the coagulation factor V protein, which is one of the many proteins in our coagulation system that help our blood clot after an injury. The FVL mutation makes coagulation factor V work in “overdrive,” which increases the tendency of the blood to clot. As a result, people with FVL are at higher risk of developing abnormal blood clots.
What are the symptoms of factor V Leiden (FVL)?
The FVL mutation in itself does not cause any symptoms. Most people who inherited FVL from their mother and/or father will never develop abnormal blood clots, so they may not even know that they have it. Some will have a family history of deep vein thrombosis/pulmonary embolism (DVT/PE) but will never have an abnormal blood clot in their lifetime.
People born with the FVL may have a personal or a family history of:
- DVT or PE before age 60
- Recurring DVT or PE
- DVT or PE during or immediately following pregnancy
- DVT or PE soon after beginning to take birth control pills or other hormonal treatments
When people who have FVL develop any symptoms, these will be related to DVT and PE, so it is important to recognize the symptoms of DVT or PE. Both of these conditions are medical emergencies.
If you have a DVT in a vein of the leg or arm, your symptoms in the affected area may include:
- Pain, tenderness
- Purple or “bluish” discoloration of the skin
- Skin that is warm to the touch, sometimes with a vivid red discoloration
Symptoms of PE may include:
- Sudden shortness of breath
- Sharp chest pain that gets worse by taking deep breaths, coughing or sneezing
- Rapid heartbeat and palpitations (tachycardia)
- Fainting or near-fainting
- Coughing up blood
Diagnosis and Tests
How is factor V Leiden (FVL) diagnosed?
Your doctor can diagnose FVL by ordering special screening and confirmatory blood tests that are specific to detect the presence of the mutation.
Despite the fact that FVL can be diagnosed by simple blood tests, such testing is not necessary in every person with a personal or family history of DVT or PE. If you think that testing may be indicated for you, it is very important that you discuss your concerns with your doctor(s) prior to being tested.
Management and Treatment
How is factor V Leiden (FVL) treated?
The factor V Leiden mutation itself does not have any specific treatment. But when a person is diagnosed with an acute deep vein thrombosis (DVT) or pulmonary emblolism (PE), treatment with anticoagulants (blood thinners) will be necessary and should be started as soon as possible. Depending on the severity of symptoms, other treatments may be necessary as well. Oftentimes those treatments will require hospitalization.
Individuals who happen to know that they have FVL – but have never had blood clots – do not have to be prescribed any blood thinners. But it is important that these individuals discuss with their doctors what they should be aware about – and what they can do to minimize – the risk of DVT or PE. Some issues that can be discussed with your doctor include:
- Effective measures to eliminate or reduce other risk factors for DVT or PE, such as smoking cessation, weight loss, and having a more active lifestyle
- Need (or not) to wear graded elastic compression stockings during long-haul flights and long road trips
- Avoidance of alcoholic beverages during long flights
- Counseling prior to taking birth control pills or before becoming pregnant
What other complications are associated with factor V Leiden (FVL)?
Other than the increased risk of developing DVT or PE, FVL may increase the risk of miscarriage or other pregnancy complications, such as preeclampsia and eclampsia, placental abruption (when the placenta separates too early from the wall of the uterus), and having a fetus that grows slower than is usual. Miscarriages associated with FVL are more likely to occur later in pregnancy (after the first trimester).
But because there are many risk factors associated with the development of those pregnancy complications, there is still debate and uncertainty as to how much the FVL mutation is a cause or just another contributing factor of those pregnancy complications.
Can factor V Leiden (FVL) be prevented?
No. There are currently no genetic treatments that can prevent inheritance of FVL from a parent.
Outlook / Prognosis
What is the prognosis (outlook) for people with factor V Leiden (FVL)?
Most people who have with FVL will never develop blood clots. Most women with the condition will have healthy, normal pregnancies. But the risks may be higher if a person has inherited two mutated copies of the gene (one from each parent).
If a person who has FVL develops a DVT or PE, treatment with an anticoagulant (blood thinner) will be prescribed for at least a few months. In most cases, the FVL mutation itself does not warrant lifelong anticoagulants. However, if a person has more than one episode of DVT or PE, or has additional clotting risks, long-term treatment with anticoagulants may be necessary.
When should I call my doctor if I have factor V Leiden (FVL)?
If you develop any symptoms of deep vein thrombosis or pulmonary embolism, you should either contact your doctor immediately or go to the nearest Emergency Department. These conditions can be life-threatening and require immediate medical treatment.
What questions should I ask my doctor about factor V Leiden (FVL)?
If you have FVL, you may have several questions for your doctor, including:
- What can I do to help prevent blood clots from forming?
- How can I make sure my pregnancy is healthy?
- What are the chances of passing down the Factor V genetic mutation to my children?
What type of doctor specializes in Factor V Leiden (FVL)?
After an initial discussion with your primary care physician, family doctor, or obstetrician/gynecologist, your provider may refer you to a vascular medicine specialist or a hematologist who specializes in thrombophilia. Thrombophilia is a term used to define clotting disorders in general, whether they are inherited (familial) or not.