Factor V Leiden
At a glance
When is examined for Factor V Leiden?
Why is examined for Factor V Leiden / Prothrombinmutation?
To determine an inherited gene mutation that increases the risk of venous thromboembolism (VTE – an inappropriate clot formation that breaks blood flow in the veins).
In which diseases should be examined for factor V Leiden / prothrombin mutation?
At or after an unexplained thrombotic episode, especially in relatively young patients (younger than 50 years) and in the absence of other thrombophilic risk factors.
With which sample material Factor V Leiden / Prothrombinmutation is performed?
With blood from a vein.
The sample material
What is being investigated?
Factor V and prothrombin are coagulation factors. These proteins (proteins) are z. B. activated in a vascular injury step by step in the so-called coagulation cascade. The end point of the coagulation cascade is the formation of a blood clot that closes the injured area of the vessel.
Factor V Leiden is a variant of factor V, which differs from factor V by an amino acid exchange. The basis of this difference is a genetic point mutation – the alteration of one of the nucleotides on the gene coding for the production of the factor V protein.
This altered protein has a normal function in blood clotting; however, it is degraded significantly slower than the normal factor V by the activated protein C (APC) during the coagulation cascade.
The prothrombin mutation G20210A does not lead to an altered form of the prothrombin protein, but the genetic point mutation lies in the promoter of the gene and thus leads to an increased synthesis of prothrombin and thus to higher plasma levels of prothrombin. This mutation and the resulting increased prothrombin mutation is associated with an increased risk of VTE.
Factor V Leiden and prothrombin mutation are mutations independent of each other; The purpose of the respective investigation is to find out whether one of the two mutations is present, the person affected is heterozygous or homozygous for this mutation or has the normal variant, the so-called wild type.
How is the sample material obtained for the study??
From blood from a vein of the arm.
Factor V Leiden test
How is the test used??
Studies of the Fakor-V Leiden and of the prothrombin G20210a are usually requested along with other tests for hypercoagulability to help diagnose the cause of venous thromboembolism (VTE) (known as thrombophilia diagnostics)..
They seek to find the reason for the first thrombotic episode, especially in relatively young patients (under 50 years of age), when no obvious triggering factors are known (eg prolonged bed rest) or when the thrombosis has occurred in an unusual location – such as at veins of the intestines (mesenterial) or the brain (cerebral).
Also, when investigating the cause of repeated miscarriages, the investigation may be helpful. The cause is thought to be small blood clots in the placenta vessels.
In place of the direct detection of Factor V Leiden, a functional study of activated protein C (APC) resistance is sometimes used. In about 95% of cases of APC resistance, there is also a mutation of Factor V Leiden; other genetic causes of APC resistance are responsible for up to 5%.
In the case of conspicuous APC resistance, a determination of the factor V Leiden gene mutation should be used to determine whether the individual is homozygous or heterozygous for the mutation. Dependent on this is the duration of anticoagulation (therapy with blood-thinning medications). In patients on anticoagulation, APC resistance can no longer be reliably determined.
The FII G20210A mutation always needs to be diagnosed by a genetic test that seeks directly after this mu- tation. It is examined whether the patient is homozygous or heterozygous for this change. Direct measurement of prothrombin levels is not recommended because it can not reliably differentiate between individuals with the wild-type mutation.
risks & prevention
When should precaution also factor V Leiden be investigated?
If this mutation is present, the risk of developing thrombosis is increased. However, when evaluating the results, it should be noted that the risk of thrombosis is regulated by a variety of factors. These factors can promote thrombosis (risk factors) and protect against it (protective factors). Therefore, many individuals, although they have the mutation (s), do not develop a VTE.
Test – When appropriate?
When can the test be useful??
Prothrombin mutation and Factor V Leiden are required when a patient experiences his first venous thromboembolism (VTE) at a relatively young age (less than 50 years) or in an unusual location.
Even if a patient has a personal or family history of recurrent VTE who suffers the first VTE in oral contraception, pregnancy, or hormone replacement therapy, or if there are unexplained recurrent miscarriages, a provision should be considered.
If a family member has a Factor V Leiden or FII G20210A mutation, the study may be useful. An asymptomatic person known to have one or more mutations may influence other controllable coagulation risk factors such as oral contraception, smoking, and hypercysteinemia, e.g. reduce risk during surgery or prolonged mobilization by anticoagulation.
The genetic tests Factor V Leiden mutation and FII G20210A mutation should only be performed once in a lifetime because they do not change.
The test result
What does the test result mean?
In 95% of cases, APC resistance is due to Factor V Leiden. If resistance is present, the factor V Leiden mutation should be confirmed by a genetic test.
Factor V Leiden is the most common thrombophilic coagulation disorder. The prevalence in people of European descent is about 5%. A patient with Factor V Leiden may be heterozygous (ie has one copy of the altered gene and one of the normal gene, called wild-type) or homozygous (more rarely, two copies of the altered gene).
The heterozygotes are about 5-10% more likely to develop a VTE than the normal population; the risk of homozygotes developing a VTE at some point in their lives.
The presence of a pt 20210 mutation with an altered gene copy is referred to as heterozygous, that of two altered copies as homozygous. The FII-G20210A mutation is less common than Factor V Leiden; They are found in about 1-2% of the population.
What else should you know? ?
Factor V Leiden, prothrombin mutation and the other acquired or inherited deficiencies of thrombophilic factors (risk of developing blood clots, protein C and S deficiency) are independent. You can thus carry more than one of the changes.
The respective risks of the thrombophilic factors can add up; in some forms, the combination of two factors is significantly less favorable than the two factors alone (“increased risk”).
The pseudohomozygous factor V Leiden is very rare. It is caused by an inherited heterozygous Factor V Leiden mutation and a heterozygous Factor V deficiency. Patients with these mutations have reduced levels of normal factor V and altered factor V Leiden protein (protein). Your risk of thrombosis is similar to that of a person who is homozygous for a Factor V Leiden mutation.
Hints & disorders
Stability and sample transport
Factor V Leiden and FII-G20210A mutations are typically performed with EDTA blood. Citrate blood as a study material is also possible; heparin blood is not suitable. Samples can be shipped at room temperature (mail order).
Molecular diagnosis is also possible with orally anticoagulated patients. Functional examination (APC resistance) may be disturbed by anticoagulants.
Quality Control Guidelines
According to the guidelines of the German Medical Association (RILIBÄK), there is no obligation to participate in external proficiency tests for the detection of the factor Veid gene mutation and the prothrombin G20210A gene mutation. Of course, internal controls and the determination of accuracy and precision must be carried out regularly. Voluntary participation in proficiency testing is possible.
Frequently Asked Questions (FAQ)
Should someone with a Factor V mutation be placed on long-term anticoagulation?
Carriers of a Factor V Leiden mutation have a very high risk of another thrombosis after an initial thrombosis. As a rule, therefore, a longer, possibly multi-year anticoagulation makes sense for them. Anticoagulation of patients who have not yet experienced thrombosis will generally be indicated only for other thrombophilic risk factors.
How is a deep vein thrombosis (VTE) treated??
Regardless of the underlying cause, a VTE is always treated with short-term anticoagulation (usually three to six months with a combination of heparin and oral anticoagulants such as Markumar). At the end of this period, it will be checked on the basis of the existing risk factors, if further therapy is necessary.
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