Prothrombin Mutation

Mutation of the prothrombin gene can be also called a mutation of factor II (FII), prothrombin mutation 20210 or is referred to as prothrombin G20210A. This is the second most common inherited thrombophilia.

Prothrombin 20210 mutation testing can be offered to you by the  doctor  if you or someone in your family had:

(1) a blood clot in one of the deep veins of the body (deep vein thrombosis);

(2) a blood clot that traveled through the bloodstream to the lungs (this is called pulmonary embolism or PE);

(3) a blood clot in an unusual location (eg. in the mesenteric veins or veins of the cerebral sinuses);

(4) a heart attack or stroke at a young age;

(5) recurrent pregnancy loss or stillbirth

If any of the above apply to you or your family member, it may indicate the presence of thrombophilia. Normally, there is a fine balance in the body which ensures that there is not too much bleeding or blood clotting. If this balance is disrupted, a blood clot may occur.

Throughout the course of a normal day, the blood vessels sustain many minor injuries of which you are not aware. In response, the body naturally triggers the “clotting cascade”—a sequence of events that allows the blood cells (platelets) and clotting proteins to respond to the site of the injury to clog up the vessel disruption and stop you from bleeding, and then to repair it. Although the activation of this clotting process occurs normally, a problem may arise in a person with thrombophilia. This is because he or she may possess blood clotting proteins in abnormal amounts, so that the clotting overshoots and a big blood clot may form.

Prothrombin is a protein in the blood that is required for the blood to clot. It is also called factor II. Blood clots are composed of a combination of blood platelets and a meshwork of the blood clotting protein fibrin. Prothrombin is a blood clotting protein that is needed to form fibrin. If somebody has too little prothrombin, he or she has a bleeding tendency. If an individual has too much prothrombin, blood clots may form when they shouldn’t.

Research of prothrombin mutation

In 1996 Poort with co-workers identified a substitution of glutamine for arginine at position 20210 in the noncoding region of the prothrombin gene. The presence of the mutated gene is associated with increased levels of prothrombin in the blood plasma by 30% in heterozygotes.

Prothrombin is a protein present in blood, which is essential for blood clotting. Also called factor II. The clot is formed by the combination of platelets and clotting protein mesh of fibrin. Prothrombin is a clotting protein that is necessary for fibrin formation. If someone has too low prothrombin, then he/she has a tendency to bleed. If someone has too much prothrombin, then he/she tends to have  blood clotting.

Prothrombin is dependent on vitamin K, which is converted to thrombin through prothrombinase complex. Thrombin plays a key role in the initiation of blood coagulation. If therefore G20210A mutation increases the level of thrombin in blood plasma it increases the risk of excessive blood coagulation and thrombosis.

Relative risks of  prothrombin G20210A mutation

This mutation is commonly connected with diseases of venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism. However, most people with this mutation, do not experience thromboembolism for their entire lives. People with this mutation who suffered from thrombosis or pulmonary embolism usually had other additional risk factors.

Mutation of the prothrombin gene represents 2-4 times higher risk for development of deep vein thrombosis and in patients with thrombosis occurs in 5-7,3%. Heterozygous constitution of mutation 20210 increases the risk of thrombotic events 2.8 times. Results of a 2005 study showed an increased risk of ischemic stroke in men younger than 60 years in connection with the presence of the prothrombin gene mutation. However, most studies indicated that the prothrombin mutation is not a risk factor for heart attack and stroke in middle and older age. Several studies have demonstrated that prothrombin mutation may increase the risk of heart attack in young women, especially  among the smokers.

No association was found between mutation of prothrombin gene and arterial thrombosis. A study from 2006 shows only a 1.3-fold increased risk of coronary heart events.

Prothrombin mutation risk is independent of the presence of factor V Leiden mutation, but the simultaneous occurrence of both significantly increases the risk of thromboembolic events.

Occurrence of prothrombin mutation

Heterozygous prothrombin mutations are found in about 2% of the US white population. The mutation is uncommon in African Americans (approximately 0.5%) and is rare in Asians, Africans, and Native Americans. The prothrombin 20210 mutation is equally as common in men and in women. The overall incidence of heterozygotes with this polymorphism is 2% in Europeans as well as for coagulation factor V (Leiden mutation) this mutation is extremely rare in colored races. Prothrombin 20210A has an estimated prevalence of 2% in the Caucasian population, while the mutation is more common in people with southern European origin than in people with North European origin. A study of patients in Turkey revealed the presence of the prothrombin 20210A mutation in 0.7% of patients.

The homozygous form is not common and its incidence is estimated at 1 in 10,000 individuals.

This mutation occurs frequently in families along with FV Leiden mutation, while its incidence is on the FV Leiden mutation-independent. Mutations occur in men and women and have nothing to do with the type of blood group.

Diagnostics of prothrombin mutation

Diagnosis of prothrombin gene mutation is carried out by a blood test. The blood is sent to a laboratory for analysis of DNA (genetic code), and it detects, if the patient is homozygote or heterozygote for this mutation. Although prothrombin mutation slightly increases the factor II in the blood, it is not appropriate to try by determining prothrombin levels in the blood of a person to diagnose whether he has a mutation or not.

How to minimize the risks of prothrombin mutation?

Risks are virtually the same as for other thrombophilias.

  • It is important to be able to recognize and respond to possible complications of thrombophilias
  • A healthy lifestyle and avoiding risk factors such as obesity, smoking
  • Avoid long immobility (e.g. when traveling) and dehydration
  • Avoid hormonal contraceptives (progestin contraception represents less risk than estrogen, but the risk exists).
  • Always tell to doctor that you have a thrombophilia
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