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) are genetic mutations that are associated with an increased risk of developing inappropriate blood clots. Two separate tests for these mutations are often performed together to detect the mutations and help determine if an individual has an inherited risk for excessive clotting.
Factor V and prothrombin are coagulation 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. Too little of the factors, or ones that are dysfunctional, can lead to bleeding or inappropriate 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. 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.
- During hemostasis, 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).
Factor V Leiden mutation is the most common inherited predisposition to abnormal clotting in the United States and it is most common in the Caucasian population. Between 3 and 8 percent 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.
- During normal blood clotting, an enzyme splits prothrombin to form thrombin. A mutation in the gene that codes for prothrombin called prothrombin 20210 can lead to increased amount of prothrombin, abnormal clotting, and an increased risk of a DVT or VTE.
A person 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 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 1-2% of the general population), it is also more prevalent in Caucasians than in those of other ethnic backgrounds.
These 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.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
How is it 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).
Factor V and prothrombin are two coagulation factors essential for proper blood clot formation. People who have a mutation in one of the genes that code for these factors have an increased risk of blood clots. (See "What is being tested?" for more on this.)
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 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.
Several other tests may be used to help identify additional factors that may be contributing to excessive clotting (thrombophilia). Some of these include:
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 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.
People with two copies of the Factor V Leiden mutation (homozygous) may have up to 80 times the risk of developing a blood clot while those with one copy have 4 to 8 times the risk.
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.
The risk potential of the mutation(s) will be variable and individual. If someone is asymptomatic, he or she may never have a deep vein thrombosis (DVT) and/or VTE. If the person has had one or more thrombotic events, then the mutation(s) is the most likely cause and the person is at an increased risk for another one. 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 of them, and their associated risks are cumulative. Added to inherited risks and acquired risks are controllable risk factors, such as oral contraceptive use, that may exacerbate the combined underlying risk factors. For instance, if a woman is heterozygous for Factor V Leiden, 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 30 times the risk for Factor V Leiden heterozygosity alone.
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. About 90% of the time, APC resistance is due to a Factor V Leiden mutation. If resistance is present, then a test for the Factor V Leiden gene mutation is performed on the affected 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 an association between Factor V Leiden mutation and recurrent miscarriages.
Although prothrombin levels are usually moderately elevated with a PT20210 mutation and could be measured, they are not clinically useful in identifying the 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 with a combination of heparin, warfarin, and low-molecular weight heparins. At the end of this time period, the person's risk level is assessed to see if further treatment is necessary.
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.
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.
On This Site
Elsewhere On The Web
American Heart Association, Circulation: Factor V Leiden
American Heart Association, Circulation: PT 20210 mutation
National Heart, Lung and Blood Institute: What is deep vein thrombosis?
Genetic Home Reference: Factor V Leiden thrombophilia
National Human Genome Institute: Factor V Leiden thrombophilia
March of Dimes: The Thrombophilias and Pregnancy