PT 20210

What is being analysed?
Factor V and prothrombin are clotting factors, i.e. part of a series of proteins that are activated in sequence (in the so-called coagulation cascade) after a blood vessel is damaged. The end result of the coagulation cascade is the formation of a stable clot, which stops blood loss until the injury has healed.

Factor V Leiden is a variant of factor V caused by a point mutation (substitution of a single nucleotide) that replaces arginine at position 506 with glutamine. This mutation makes activated factor V resistant to breakdown by activated protein C (APC) during activation of the coagulation cascade. The result of this resistance is an increased level of thrombin in the blood and an increased risk of venous thromboembolism (VTE). It is also associated with pulmonary embolism (sudden blockage of the pulmonary arteries) and recurrent miscarriage, especially in the 2nd and 3rd trimesters.

The G20210A polymorphism of the prothrombin gene is caused by a point substitution that may be associated with an increased risk of VTE.

Factor V Leiden and PT 20210 are independent mutations, which means that the presence or absence of the mutation must be determined for each factor, and it must be established whether the person is heterozygous (only one gene affected) or homozygous (both genes affected) for that mutation.

How is the sample collected for testing?
The sample is usually obtained by drawing blood from a vein in the arm.

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
Factor V Leiden and PT 20210 tests are requested, alone or together with other investigations for a possible hypercoagulable state, to help identify the cause of venous thromboembolism (VTE). They are used to find the causes of a first thrombotic episode, especially when it occurs in a relatively young person (under 50), is not associated with acquired risk factors, or occurs in an unusual site, such as the circulation of the liver, kidneys, brain, abdomen or retina. These tests are also indicated after recurrent miscarriages, especially in the 2nd and 3rd trimesters, since thrombotic events are thought to be able to affect the blood vessels of the placenta too.

The activated protein C (APC) resistance test is used to screen for factor V Leiden. Approximately 95% of people with activated protein C resistance have the factor V Leiden mutation. If resistance is present, a test for the factor V Leiden mutation will be carried out, 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 a genetic test that looks directly for the mutation and determines whether the patient is heterozygous or homozygous for it. Although prothrombin levels are usually moderately raised in people with this mutation, and measuring plasma prothrombin activity could be considered for diagnosis, it is not clinically useful for detecting this mutation.

At present, experts do not recommend screening the general population, and there is not yet full agreement on whether the relatives of people with factor V Leiden or PT 20210 should be tested. If the mutation is present, the person has a higher risk of developing a clot, but it should be borne in mind that gene expression varies. In fact, some people with the mutation(s) will never develop VTE.

When is it requested?
Factor V Leiden and PT 20210 tests are indicated when a patient has a first episode of venous thromboembolism (VTE) at a relatively young age (under 50), or when the thrombotic event occurs in an unusual site. They are indicated when a patient has a personal or family history of recurrent VTE, a first VTE after using oral contraceptives, during pregnancy or during hormone replacement therapy, or after recurrent miscarriages, especially in the 2nd and 3rd trimesters.
Although there is no unanimous agreement, these tests may also be indicated when there is a family history of the factor V Leiden or PT 20210 mutation. If a person without symptoms carries one or more mutations, it is useful to look for other modifiable risk factors for VTE, such as oral contraceptive use, smoking or hyperhomocysteinaemia. The patient should be aware of the risk they face when exposed to triggering events such as immobilisation and surgery. On the other hand, it should be remembered that the mutation can be present without being associated with VTE.

Once activated protein C resistance or a factor V Leiden or PT 20210 mutation has been diagnosed, the test does not need to be repeated unless further confirmation becomes necessary.

What does the test result mean?
In 95% of cases APC resistance is caused by factor V Leiden, but if resistance is present, the factor V Leiden mutation should be confirmed with a genetic test.
Factor V Leiden is the most common inherited clotting disorder in white people. Its prevalence is highest in people of European origin, being present in about 5% of the white population. A patient with factor V Leiden can be heterozygous (one copy of the mutated gene and one normal copy) or homozygous (two copies of the mutated gene, which is rarer). Heterozygotes for factor V Leiden have a 3 to 8 times higher relative risk of developing venous thromboembolism (VTE), while in homozygotes the risk is much higher (30-140 times).

If only one copy of the gene carries the PT 20210 mutation, the person is heterozygous; if both genes are mutated, they are homozygous. Affected people, whether homozygous or heterozygous, may have increased thrombin production, with a resulting modest but significant increase in thrombotic risk. Although the PT 20210 mutation is less common than factor V Leiden (about 1-2% of the general population), here too its prevalence appears to be higher in the Caucasian population.

Is there anything else I should know?
The risk from factor V Leiden, PT 20210 and other inherited or acquired risk factors for thrombosis (for example protein C or S deficiency) is independent. When risk factors are combined, the risk of VTE is cumulative and multiplied. The risk can be made worse by modifiable factors such as taking oral contraceptives. For example, a person who is heterozygous for factor V Leiden already has a 3 to 8 times higher risk of VTE than a normal person. If oral contraceptives are added, the risk can reach 20-25 times.

“Pseudo-homozygous” factor V Leiden is rare. It can be caused by heterozygosity for the factor V Leiden mutation combined with a heterozygous factor V deficiency. Patients with these features have both reduced factor V levels and mutated factor V Leiden. Their degree of risk is comparable to that of people homozygous for factor V Leiden.

1. Can a person with the factor V Leiden mutation be kept on anticoagulant therapy long term?
2. How is venous thromboembolism treated?

1. Can a person with the factor V Leiden mutation be kept on anticoagulant therapy long term?
There are currently no definitive guidelines on how long patients with the factor V Leiden mutation should receive anticoagulant treatment. In general, because of the relatively low risk, heterozygotes without symptoms are not thought to need long-term treatment. For these people medium- to long-term prophylaxis is advisable when other acquired risk conditions are present (for example surgery or pregnancy). For factor V Leiden carriers with symptoms (previous episodes of VTE), a long-term anticoagulant treatment plan can be established individually, especially if there has been a pulmonary embolism.

2. How is venous thromboembolism treated?
Whatever the cause, VTE is usually treated with anticoagulant therapy started early (a combination of heparin or low-molecular-weight heparins with oral anticoagulants) for a period of 3-6 months. At the end of this period, based on an assessment of individual risk, a decision is made on whether therapy needs to continue.