The variant causes elevated plasma prothrombin levels, possibly due to increased pre-mRNA stability. Prothrombin is the precursor to thrombin, which plays a key role in causing blood to clot. G20210A can thus contribute to a state of hypercoagulability, but not particularly with arterial thrombosis. A 2006 meta-analysis showed only a 1.3-fold increased risk for coronary disease.Deficiencies in the anticoagulants Protein C and Protein S further increase the risk five- to tenfold. Behind non-O blood type and factor V Leiden, prothrombin G20210A is one of the most common genetic risk factors for VTE.Increased production of prothrombin heightens the risk of blood clotting. Moreover, individuals who carry the mutation can pass it on to their offspring. The mutation increases the risk of developing deep vein thrombosis, which can damage veins throughout the body, causing pain and swelling and sometimes leading to disability. Most individuals do not require treatment but do need to be cautious during periods when the possibility of blood clotting are increased; for example, during pregnancy, after surgery, or during long flights. Occasionally, blood-thinning medication may be indicated to reduce the risk of clotting. Heterozygous carriers who take combined birth control pills are at a 15-fold increased risk of VTE, while carriers also heterozygous with factor V Leiden have an approximate 20-fold higher risk. In a recommendation statement on VTE, genetic testing for G20210A in adults that developed unprovoked VTE was disadvised, as was testing in asymptomatic family members related to G20210A carriers who developed VTE. In those who develop VTE, the results of thrombophilia tests rarely play a role in the length of treatment.
Cause
The polymorphism is located in a noncoding region of the prothrombin gene, replacing guanine with adenine. The position is at or near where the pre-mRNA will have the poly-A tail attached.
Diagnosis
Diagnosis of the prothrombin G20210A mutation is straightforward because the mutation involves a single base change that can be detected by genetic testing, which is unaffected by intercurrent illness or anticoagulant use. Measurement of an elevated plasma prothrombin level cannot be used to screen for the prothrombin G20210A mutation, because there is too great of an overlap between the upper limit of normal and levels in affected patients.
Treatment
Patients with the prothrombin mutation are treated similarly to those with other types of thrombophilia, with anticoagulation for at least three to six months. Continuing anticoagulation beyond three to six months depends on the circumstances surrounding thrombosis, for example, if the patient experiences a thromboembolic event that was unprovoked, continuing anticoagulation would be recommended. The choice of anticoagulant is based on a number of different factors. Patients with the prothrombin G20210A mutation who have not had a thromboembolic event are generally not treated with routine anticoagulation. However, counseling the patient is recommended in situations with increased thrombotic risk is recommended. Oral contraceptives should generally be avoided in women with the mutation as they increase the thrombotic risk.
Terminology
Because prothrombin is also known as factor II, the mutation is also sometimes referred to as the factor II mutation or simply the prothrombin mutation; in either case, the names may appear with or without the accompanying G20210A location specifier.
