Prothrombin Gene Mutation, Factor II - F2

Factor-II gene

Klinische Symptomatik

Patients with thromboembolic events may have an acquired or genetically determined disease cause. Besides rare genetic defects in the antithrombin III gene, protein S gene or protein C gene one major cause for increased thrombosis risk is the genetically determined dysfunction of coagulation factor V to activated protein C (APC-resistance). Likewise, increased thrombosis risk is evident in individuals with increased prothrombin levels.

The precursor prothrombin is converted to thrombin which, in turn, is active in the process of conversion from fibrinogen to fibrin. Due to the genetic defect prothrombin levels increase, which disturbs the delicate equilibrium between coagulation cascade and fibrinolysis. The increased conversion from fibrinogen to fibrin thus leads to hypercoagulation.

Approx. 2% of our population carry a heterozygous genetic defect G20210A in the prothrombin gene increasing the risk for thrombosis 3- to 4-fold. Homozygous carriers of the G20210A mutation are very rare. Since thrombosis risk increases several fold in mutation carriers who simultaneously carry a factor V Leiden mutation, all carriers of the G20210A mutation should undergo analysis for the factor V Leiden mutation as well. Furthermore, additional risk factors such as smoking and hormonal contraception are to be avoided.

Medication for thrombosis prophylaxis should be given in the case of additional risk factors such as immobilization following surgery, pregnancy or other diseases of the coagulation system (e.g. factor V Leiden mutation, MTHFR gene defect).

Genetik

The prothrombin gene (F2) is located on chromosome 11 (11p11.2). The underlying mutation is a base transition G->A in position 20210 of the prothrombin gene.

Häufigkeit

Heterozygous carriers: 1 : 50
Homozygous carriers: rare

 

Diagnostik