Factor II, DNA Analysis
Prothrombin Gene Analysis
Prothrombin Gene Mutation
Detection of mutation in the factor II (prothrombin) gene (OMIM 176930) causing increased risk of thrombosis
Details of how the blood coagulation system is regulated have become well understood in recent years. Many of the abnormalities that cause some patients to have an increased risk for thrombosis have been defined at the molecular level. A point mutation in the factor II (prothrombin) gene is the second most common cause of inherited thrombosis (after factor V Leiden) and accounts for up to 20% of inherited thrombophilia. Six percent to 8% of people with a first-time venous clot have this mutation. The incidence of this mutation in the Caucasian population is 1% to 2% and in African-Americans it is 0.1%. Heterozygous carriers of this mutation have a threefold increase for venous thrombosis. The magnitude of the risk associated with homozygosity for this mutation may further increase the risk for venous thrombosis, but this has not been fully established. The mutation has been reported in patients with idiopathic portal vein thrombosis or cerebral vein thrombosis, in patients using oral contraceptives, and in pregnant patients with placental abruptions and fetal growth restrictions.
The mutation, substitution of a guanine with an adenine at nucleotide 20210, lies outside the coding region of the factor II gene. Instead, it is found in the 3′-untranslated region of the messenger RNA. This variant is associated with prothrombin levels that are 30% higher than normal, although the mechanism responsible for this elevation is not fully understood. Prothrombin is cleaved to thrombin, which acts as a serine protease in the coagulation cascade, and promotes clotting activity by producing fibrin. Elevated levels of prothrombin create a mild hypercoagulable state that is associated with deep vein thrombosis.
The risk of venous thrombosis increases exponentially in patients with more than one risk factor, including age, surgery, oral contraceptive use, pregnancy, elevated homocysteine levels, or malignancy. A 2005 study reports malignancy carries a sevenfold increased risk for thrombosis, and that this effect is most pronounced for hematological malignancies, for recently diagnosed cancers, and/or for patients with distant metastases. Malignancy and genetic predisposition together may compound risk, as carriers of factor V Leiden mutation who have cancer are more likely to develop thrombosis than mutation carriers without cancer. A similar relationship between malignancy and prothrombin mutations has been proposed, but is not as well substantiated.
Testing for other known causes of thrombophilia may also be pursued. Another common cause of thrombosis is the factor V Leiden mutation (R506Q), and up to 40% of the factor II/prothrombin mutation carriers also carry the factor V Leiden mutation. Beyond the R506Q (Leiden) mutation, evaluation of plasma homocysteine levels, as well as testing for deficiencies of antithrombin III, protein C, and protein S may be indicated.
Whole blood or buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)
7 mL whole blood or buccal swab kit
3 mL whole blood or two buccal swabs
Lavender-top (EDTA) tube, yellow-top (ACD) tube, or buccal swab kit
Maintain specimen at room temperature.
Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab
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