Factor V Leiden PCR blood coagulation

The DNA Factor V Leiden PCR test from blood measures the genetic predisposition to thrombosis (EDTA) + Declaration of Consent.

Factor five Leiden is an abnormal form of one of the proteins that regulate blood clotting. The term is also used for the disorder that results from it. In this disorder, a point mutation has occurred in the gene for clotting factor V. In someone who is heterozygous for factor V Leiden, there is a slightly increased tendency for blood to clot; in someone who is homozygous for the factor, the tendency is many times greater.

The mutation is named after the city of Leiden in the Netherlands. It was first identified at Leiden University by Prof. R.M. Bertina et al. in 1994.

There is an increased risk of blood clot formation in the blood vessels. This can result in spontaneous thrombosis. The heterozygous form of the mutation gives a five- to tenfold increased risk of thrombosis. The homozygous form of the mutation gives a fifty- to one hundred-fold increased risk of thrombosis. The risk of pulmonary embolism is increased by a factor of fifteen in heterozygous carriers of factor V Leiden.

Pregnancies in women with this disorder are more likely to end in miscarriage or stillbirth. This is because the mutated coagulation gene causes clot formation in the placenta. For women with factor-V-Leiden mutation who have previously experienced venous thrombosis, the use of contraceptive pill is not advised.

When can you do this test:

• if thrombosis runs in the family (recurrent venous thrombosis/long embolism)
• if the factor V-Leiden mutation is known to be present in one of the parents or close relatives
• in case of thrombosis in the veins at a young age
• in case of thrombosis without obvious cause or in an unusual place
• for repeat abortions in the second and third trimesters
• in women with a history of thrombotic pregnancy complications

The Factor-V-Leiden mutation can be demonstrated using the polymerase chain reaction (PCR).
There may be no mutation or wild-type.
There may be 1 mutated allele (heterozygous) or both alleles are mutated (homozygous).

Detection of the mutation on DNA provides very high certainty.
In patients who have undergone bone marrow transplantation or liver transplantation, testing for DNA isolated from the patient's peripheral blood cells is futile.

Factor V Leiden is the most common coagulation abnormality. The mild form of Factor V Leiden (heterozygotes for the fVL mutation) occurs in 3 to 8 in 100 people.
About 1 in 5000 people have the severe form (homozygotes).

The question arises as to why such an apparently harmful mutation nevertheless occurs in such a relatively large percentage of the population. It is possible that being heterozygous for the defect provides an evolutionary advantage. Some researchers speculate that in the evolutionary past a carrier of the gene was less likely to bleed to death after childbirth, a fairly significant cause of death in the absence of modern obstetric care. Similar hypotheses have been established for sickle cell anemia and cystic fibrosis, two other disorders for which a significant percentage of the population is heterozygous.

With timely detection of the condition, there is a very favorable prognosis. The health problems that thrombosis causes, and the risks of pregnancy, can then be reduced with medication. People who know they are carriers of the condition can take blood thinners for thrombosis prevention. However, this is currently generally not done before a thrombosis has occurred, as the use of blood thinners also carries significant risks. However, it is advised to avoid risky situations and, if this is not possible, to give anticoagulation preventively if necessary.

Homozygous women are usually advised not to use the contraceptive pill because of the increased risk of thrombosis. In heterozygotes, this is not considered irresponsible by most doctors. In this case, it is even more important than in people without the disorder not to smoke as well.

Thrombosis risk is determined by a combination of factors. Other risk factors may also play a role such as protein C deficiency, protein S deficiency, antithrombin deficiency, prothrombin mutation, antiphospholipid syndrome, hyperhomocysteinemia, elevated factor-VIII levels.
Surgery, trauma, malignancy or oral contraception may also promote the development of thrombosis. A consent form from the patient is required.