Factor II (Prothrombin), DNA Analysis

CPT: 81240
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Test Details

Synonyms

  • Prothrombin DNA
  • Prothrombin Gene Analysis
  • Prothrombin Gene Mutation

Use

Detection of mutation in the factor II (prothrombin) gene (OMIM 176930) causing increased risk of thrombosis

Limitations

This test detects the factor II G20210A mutation and will help identify those individuals who carry this mutation and who are at increased risk of thrombosis; however, increased risk of thrombosis can be caused by a variety of genetic and nongenetic factors not screened for by this assay.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

Methodology

Polymerase chain reaction (PCR); restriction enzyme digestion

Additional Information

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. Genetic counselors are available for health care providers to discuss results, and for information on how to order additional testing, if desired, at 800-345-4363.

Specimen Requirements

Specimen

Whole blood or LabCorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)

Volume

7 mL whole blood or LabCorp buccal swab kit

Minimum Volume

3 mL whole blood or two buccal swabs

Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, or LabCorp buccal swab kit

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab

Clinical Information

References

Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005 Feb 9; 293(6):715-722. 15701913
College of American Pathologists Consensus Conference XXXVI: Diagnostic Issues in Thrombophilia. Arch Pathol Lab Med. 2002; 126(11):1277-1433. 12421135
Danneberg J, Abbes AP, Bruggeman BJ, Engel H, Gerrits J, Martens A. Reliable genotyping of the G-20210-A mutation of coagulation factor II (prothrombin). Clin Chem. 1998 Feb; 44(2):349-351. 9474038
De Stefano V, Martinelli I, Mannucci PM, et at. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med. 1999 Sep 9; 341(11):801-806. 10477778
Grody WW, Griffin JH, Taylor AK, et al. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med. 2001 Mar-Apr; 3(2):139-148. 11280951
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996; 88(10):3698-3703.8916933

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
511162 Factor II, DNA Analysis 24476-4 511194 Factor II, DNA Analysis 24476-4
511162 Factor II, DNA Analysis 24476-4 511989 Additional Information: N/A

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