Inherited thrombophilia is a genetically determined tendency to develop a recidivating deep venous and/or arterial thromboembolic disease without apparent causes in young individuals (< 50 years).
The causes of inherited thrombophilia are related to genetic changes such as those occurring in Factor V gene, in Factor II (or Prothrombin) gene , in the MTHFR gene and in PAI-1 (Plasminogen activator inhibitor 1).
The activated protein C (APC) is unable to inactivate Factor V if a particular mutation (G1691A), which is known as Factor V Leiden, has occurred in the Factor V gene. This mutation causes an increased thrombin production with a resulting procoagulant effect. Heterozygosity for Factor V Leiden confers a 5 to 10-fold increased risk of developing a venous thrombosis, whereas homozygosity confers a 50 to 100-fold increased risk. The risk of myocardial infarction in heterozygous individuals seems to be increased by 2 to 3-fold.
In the gene which codes for prothrombin (Factor II) a point mutation has been described which consists in a guanine replaced by an adenine (G20210A variant). This mutation is associated with an elevation of plasma levels of prothrombin to about 30%.
The frequency of homozygous individuals is extremely low. Heterozygous carriers have about a 2 to 3-fold higher risk to develop a venous thrombosis than the general population while homozygous carriers have a 80-fold increased risk. The risk of myocardial infarction in heterozygous individuals seems to be increased by about 5-fold in women and 1.5-fold in men.
Study of the mutations in the MTHFR gene that in our DNA is the sequence which codes for MTHFR (methylenetetrahydrofolate-reduttase) protein: the replacement of cytosine (C) with thymine (T) at position 677 in the MTHFR gene (C677T) reduces the enzymatic activity of the methylenetetrahydrofolate-reductase protein by 50%. This variant may cause increased plasma levels of homocysteine especially after oral loading with methionine.
Another variant, consisting in the replacement of an adenine with a cytosine at position 1298 in the MTHFR gene (A1298C), has been associated with a reduction of the MTHFR levels.
Relative risk for venous thromboembolism caused by a reduced MTHFR activity may increase in double-heterozygous carriers, that is if Factor V Leiden variant or prothrombin G20210A variant are also present.
Plasminogen activator inhibitor or PAI-1 (-675 4G/5G) is the major plasminogen (t-PA and u-PA) inhibitor, and prevents plasminogen conversion to plasmin and the consequent dissolution of the fibrin clot. The increase, or reduction of this inhibitor may induce thrombotic, or hemorrhagic disorders respectively.
The test is performed by Mass Array Analyzer within 7 working days from sample receipt.