Factor V Leiden mutation and prothrombin 20210 mutation tests are ordered, along with other tests related to thrombophilia, to help diagnose the cause for venous thromboembolism (VTE). They are 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 pelvis, or in the eye veins.

The initial screen for factor V Leiden is activated protein C (APC) resistance testing. Activated protein C helps to regulate coagulation by inactivating factor Va, which slows the clotting process in plasma. If a person is found to have a resistance to APC through testing, he may be at an increased risk for thrombosis. About 95% of the time, those who have APC resistance are found to have it due to a factor V Leiden mutation. If resistance is present, then a test for the factor V Leiden gene mutation is done, both to confirm the diagnosis and to determine whether the patient is heterozygous or homozygous for the mutation.

The PT 20210 mutation must be diagnosed with genetic testing, checking directly for the gene mutation and determining whether the patient is heterozygous or homozygous. Although prothrombin levels are usually moderately elevated with this mutation and could be measured, they are not clinically useful in finding this mutation.

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.

Factor V Leiden mutation and PT 20210 tests are ordered when a patient has a first venous thromboembolism (VTE) at less than 50 years old or in an unusual part of the body. They may be ordered when a patient has a personal or family history of recurrent VTE, a first VTE related to oral contraceptive use, pregnancy or hormone replacement therapy, or when they are experiencing unexplained miscarriages, especially those occurring in the second or third trimester of the pregnancy.

These assays are often ordered when a family member has a factor V Leiden or PT 20210 gene mutation. If asymptomatic patients know 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, even if the patients have the mutation, they may never experience a VTE.

Once APC resistance testing, factor V Leiden mutation testing, and PT 20210 gene mutation testing have been done, they are usually not repeated unless there is a need for verification.

While a positive APC resistance assay is confirmed by the factor V Leiden mutation test, the factor V Leiden mutation and the PT 20210 mutation tests require no further confirmation.

Resistance to activated protein C is due to factor V Leiden 95% of the time, but if resistance is present, the factor V Leiden mutation should be confirmed with genetic testing.

If genetic testing shows one factor V Leiden gene copy, then the patient is heterozygous; if there are two copies, then the patient is homozygous. If there is one PT 20210 gene copy, then the patient is heterozygous; if there are two copies, then the patient is homozygous.

The risk potential of the mutation(s) will be variable and individual. If the patient is asymptomatic, he or she may never have a VTE. If the patient has had one or more thrombotic events, then the mutation(s) is the most likely cause and the patient is at an increased risk for another one. If no mutations are found, then it is likely that the person’s 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 patient can have more than one of them, and their associated risks are cumulative. Added to these 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 patient is heterozygous for Factor V Leiden, she may be at about a 2 to 3 fold greater than normal risk of developing a VTE. If she also uses oral contraceptives, the combined risk can increase to 25 times the risk for factor V Leiden heterozygosity alone.

Some studies have found an association between factor V Leiden mutation and recurrent miscarriages.