Coagulation factors

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.


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The test is performed by Mass Array Analyzer within 7 working days from sample receipt.