To determine whether you have an inherited gene mutation that increases your risk of developing a blood clot, including a deep venous thrombosis (DVT) and/or venous thromboembolism (VTE)
Factor V Leiden Mutation and PT 20210 Mutation
When you have had an unexplained blood clot (thrombotic episode), especially when you are less than 50 years old, have recurrent DVT or VTE episodes, experienced DVT or VTE during pregnancy, had DVT at unusual sites, or have a strong family history of thrombosis
A blood sample drawn from a vein in your arm
Factor V Leiden and prothrombin 20210 (PT 20210 or Factor II mutation) are genetic mutations that are associated with an increased risk of developing inappropriate blood clots. These mutations are tested by two separate tests that evaluate a person's DNA to look for the mutations. The two tests are often performed together to help determine if an individual has an inherited risk for excessive clotting.
Factor V and prothrombin are coagulation factors (sometimes called clotting factors), two of a group of proteins essential for proper blood clot formation. When an injury occurs and bleeding starts, a process called hemostasis begins to form a plug at the injury site to help stop the bleeding. Blood cells called platelets adhere to and aggregate at the injury site, and a coagulation cascade begins to activate coagulation factors in sequence. Eventually, a blood clot forms. Once the area has healed, the blood clot dissolves.
There must be an adequate number of each of the coagulation factors, and each must function normally in order for a stable blood clot to form and then dissolve when no longer needed. A deficiency in clotting factors (quantitative defect) or clotting factors that do not work properly (qualitative defect) can lead to excessive bleeding or clotting (thrombosis).
Factor V Leiden and PT 20210 are two mutations that individuals may inherit from their parents that may cause an increased risk of excessive clotting. They are inherited in an autosomal dominant manner. A person may inherit one mutated gene copy and be heterozygous or may inherit two mutated gene copies and be homozygous. This may determine to what extent the person is affected. (For additional details, read the section on Autosomal Dominant Inheritance in the Genetic Disorders article.)
These two mutations are independent and are tested separately, but the tests are often performed at the same time as part of the investigation of a blood clot (thrombotic episode) in someone who is suspected of having an inherited risk factor for an excessive clotting (hypercoagulable) disorder. Each test is used to identify whether or not the specific mutation is present and to determine whether the person has one copy (heterozygous) or two copies (homozygous) of that mutation.
- During blood clotting, factor V is normally inactivated by a protein called activated protein C (APC) to prevent the blood clot from growing too large. But a factor V Leiden genetic mutation can lead to an altered factor V protein that resists inactivation by APC. The result is that clotting remains more active than usual, increasing risks of a blood clot forming in the deep veins of legs (DVT) or breaking off and blocking a vein (venous thromboembolism or VTE).
- During blood clotting, an enzyme converts prothrombin to form thrombin. A mutation in the gene that codes for prothrombin called prothrombin 20210 can lead to increased amount of prothrombin and therefore abnormal clotting and an increased risk of a DVT or VTE.
- How is the test used?
Factor V Leiden (FVL) mutation and prothrombin 20210 (PT 20210) mutation tests are two tests often used together to help diagnose the cause of inappropriate blood clot (thrombus) formation, including deep vein thrombosis (DVT) and/or venous thromboembolism (VTE).
Testing for factor V Leiden and PT 20120 mutations is used to help determine if an individual has inherited a disorder associated with blood clots and can determine whether the person has one copy or two copies of the mutation (heterozygous or homozygous.)
These tests may be ordered to help determine the reason for an initial harmful blood clot (thrombotic episode), especially when it occurs in a person under 50 years old, is unprovoked, or is in an unusual place such as the liver (hepatic), the kidneys (renal), the brain (cerebral), the gut and pelvis (mesenteric), or in the eye veins. These tests may also be ordered if VTE is recurrent or there is a strong family history of thrombosis.
Experts do not recommend screening the general population and are divided on testing family members of those with a factor V Leiden or PT 20210 mutation. If the mutation is present, then the person is at a higher risk for developing a blood clot, but there is variability in how the gene is actually expressed. With factor V Leiden, for example, only 10% of those with the factor V Leiden mutation will ever have a thrombotic episode.
- When is it ordered?
Factor V Leiden mutation and PT 20210 tests are ordered when it is suspected that a person has an inherited risk factor for blood clots, for example, when an individual:
- Has a first deep venous thrombosis (DVT) or venous thromboembolism (VTE) before age 50
- Has recurring DVT or PE
- Has a blood clot in an unusual part of the body such as the veins of the liver (hepatic), the kidneys (renal), the brain (cerebral), the gut and pelvis (mesenteric), or in the eye veins
- Has a personal or family history of recurrent DVT or VTE
- Has a first VTE related to oral contraceptive use, pregnancy or hormone replacement therapy
- Experiences unexplained miscarriages, especially those occurring in the second or third trimester of pregnancy
These tests may be ordered when a first-degree family member, such as parent or sibling, has a factor V Leiden or PT 20210 gene mutation. However, a panel assembled by the Centers for Disease Control and Prevention to evaluate practical genomics recommended in 2011 that if the goal is to decide on treatment with anticoagulant medication, adults without VTE symptoms do not need to be tested even if their family members have the PT 20210 or the factor V Leiden mutation.
If asymptomatic family members know that they have one or more of the mutations, they may be motivated to address controllable clotting risk factors such as oral contraceptive use, smoking, and elevated levels of homocysteine and be more aware of the potential risks of factor(s) triggering events, such as immobilization and surgery. However, many of those with the mutation will never experience a DVT or VTE.
- What does the test result mean?
If genetic testing indicates that an individual has one factor V Leiden or PT 20210 gene copy, then the person is heterozygous; if there are two copies, then the person is homozygous for the mutation.
- Factor V Leiden mutation is the most common inherited predisposition to excessive clotting in the United States and it is most common in the Caucasian population. Between 3 and 8% of U.S. Caucasians carry one copy of the factor V Leiden mutation and about 1 in 5,000 people have two copies of the mutation. While homozygous cases of factor V Leiden are more rare, they also carry a higher risk of thrombosis. People with two copies of the mutation may have up to 80 times the risk of thrombophilia while those with one copy have 4 to 8 times the risk, compared to those who do not carry the mutation.
- Someone with a PT 20210 mutation may be heterozygous or homozygous, although it is very rare to find individuals who are homozygous. The affected heterozygous person will have a mild to moderate increase in their thrombin production, which is associated with 2.5 to 3 fold greater risk of developing a venous thromboembolism (VTE) in Caucasians; there is not enough information about risk in those who are homozygous. Although PT 20210 is less common in the U.S. than factor V Leiden, about 2 to 4% of Caucasians, usually of European ancestry, have a variation in the prothrombin gene. In the U.S., approximately 1 in 250 African Americans have the mutation.
The risk of excessive clotting from these mutation(s) varies from person to person. If you are asymptomatic, you may never have a DVT and/or VTE. If you have had one or more blood clots, then the mutation(s) is the most likely cause and you have an increased risk for another clot. If no mutations are found, then it is likely that the condition is due to another cause.
The risks that are associated with factor V Leiden, PT 20210, and other inherited and acquired factor deficiencies are independent. A person can have more than one risk factors for harmful blood clots, and their associated risks are cumulative. Added to inherited risks and acquired risks are controllable risk factors, such as use of oral contraceptives and hormone replacement therapy (HRT), that may worsen the combined underlying risk factors. For instance, if a woman has one gene copy with the factor V Leiden variant, she may be at about a 2 to 4 fold greater risk of developing a VTE. If she also uses oral contraceptives, the combined risk can increase to 35 times the risk for factor V Leiden heterozygosity alone, and women with factor V Leiden who take HRT have a 15-fold higher risk.
- Is there anything else I should know?
Sometimes, evaluation for the presence of a factor V Leiden mutation can begin with a test for activated protein C (APC) resistance, though it is not commonly performed nowadays. About 90% of the time, APC resistance is due to a factor V Leiden mutation, and the APC resistance ratio assay has a greater than 99% sensitivity for detecting a factor V Leiden mutation. If resistance is present, then a test for the factor V Leiden gene mutation is performed on the person's DNA, both to confirm the diagnosis and to determine whether the person has one or two copies of the mutation (is heterozygous or homozygous for the mutation).
Some studies have found a significant association between factor V Leiden mutation and recurrent miscarriages.
- In addition to factor V Leiden and PT 2010, what other tests might be done to evaluate excessive clotting?
Several other tests may be used to help identify additional factors that may be contributing to excessive clotting (thrombophilia). Some of these include:
- Lupus anticoagulant (LAC)
- Protein C and protein S
- Methylene tetrahydrofolate reductase (MTHFR) gene mutation
- Factor V gene R2 mutation
- How are deep vein thrombosis (DVT) and/or venous thromboembolism (VTE) treated?
Regardless of the underlying cause, a VTE is usually treated with a short course of anticoagulants, often 3 to 12 months. A combination of heparin, warfarin, and low-molecular weight heparins or one of the newer oral anticoagulants may be prescribed. At the end of this time period, the person's risk level is reassessed to see if further treatment is necessary. Lifetime prophylactic treatment may be needed for some patients.
- Should someone with a factor V Leiden mutation be on long-term anticoagulant therapy?
In general, no. Anticoagulant therapy is used when there is DVT and/or VTE. Long-term therapy may be considered for specific individuals, dependent upon the clinical situation. It should be noted that knowing whether a person with DVT/VTE has a factor V Leiden or prothrombin 20210 mutation does not change the intensity or duration of anticoagulant therapy.
- Will factor V Leiden or PT 20210 ever go away?
No. If you have one of these mutations, they are part of your genetic make-up and they will not go away. However, there are things you can do to lower your risk of developing a blood clot, such as not smoking.
- What is the clinical relevance of factor V R2 mutation?
R2 (A4070G) is a mild factor V mutation believed to confer additional APC resistance when it is present in individuals who are heterozygous for FVL (R506Q). By itself, the R2 mutation is not known to significantly contribute to venous thrombosis risk.