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Prothrombin G20210A (Factor II)

A DNA test for a common inherited change in the F2 gene that lets blood clot a little more easily. Most people who carry it never have a problem clot.

AI-verified against cited sources. Awaiting expert reviewAlso called G20210A, PGMLOINC 24475-6

What it is

Prothrombin (also called factor II) is a protein your blood uses to form clots. The G20210A variant in the F2 gene makes your body produce more prothrombin than usual, so clots can form more easily. You get one copy of the gene from each parent, so the result is not detected (no copies), heterozygous (one copy, G/A) or homozygous (two copies, A/A). This is a DNA test on a blood sample. It is not the same as the prothrombin time (PT/INR) or factor II activity, which measure how well your blood clots right now.

Why it matters

The test is used to learn whether a clotting tendency runs in a family or to look into a clot that has already happened. Prothrombin thrombophilia is the second most common inherited clotting tendency after factor V Leiden. One copy raises the chance of a harmful vein clot (such as a deep vein thrombosis) about two to five times compared with average, but most people with it never have one. Guidelines such as the American Society of Hematology's 2023 guideline recommend testing in some situations and advise against it in others.

If it’s high

A heterozygous (G/A) result means you carry one copy of the variant. About 2 to 5 in 100 Americans of European ancestry do, and it is much less common in people of African, Asian and Native American ancestry. One copy raises the chance of a harmful vein clot, but most people with it never have a clot. Surgery, injury, long trips, pregnancy, estrogen-containing medicines, obesity and a family history of clots all add to the chance. A homozygous (A/A) result is rarer and is linked with a higher chance of clots, sometimes at a younger age. Research suggests pregnancy loss may be somewhat more likely, and links to other pregnancy complications are still debated. Your clinician reads the result together with your own and your family's clot history.

Common causes

  • You inherited the variant from one parent (one copy) or both parents (two copies). It is passed on in a dominant pattern, so one copy is enough to matter.
  • Ancestry: it is most common in people of European ancestry, found in about 2 to 5 in 100 Americans of European ancestry

What can help

  • Share your own and your family's history of blood clots with your clinician, since that history matters as much as this result
  • Mention the result before surgery, long stretches in bed, pregnancy, or starting hormone-containing medicines, so your clinician can weigh it with your other risk factors
  • Move your legs often during long plane or car trips, and don't smoke
  • Ask whether any other clotting tests make sense for you

What can affect your result

  • Ancestry: most common in people of European descent, and much less common in African, Asian and Native American groups
  • Other inherited clotting changes, such as factor V Leiden, can add to the chance of a clot
  • Surgery, injury, pregnancy, long stretches without moving, obesity, smoking and estrogen-containing medicines affect whether a clot forms
  • The result is fixed at birth, so blood thinners, a recent clot, pregnancy and illness do not change it
  • The test reads inherited DNA, so blood thinners, a recent clot, pregnancy, illness, food and fasting do not change the result. Clotting-activity tests do not work that way: ASH notes that protein C, protein S and antithrombin results can be thrown off by acquired causes.
  • A previous bone marrow transplant from a donor will interfere with the test, because the DNA may come from the donor's cells (Mayo Clinic Laboratories).
  • The test looks only at this one variant. It will not find clotting tendencies caused by other mechanisms (Mayo Clinic Laboratories).
  • This DNA test is different from the prothrombin time (PT/INR) and from factor II activity. Those measure how your blood clots now, and blood thinners such as warfarin change them.

The result is fixed at birth and does not change.

When to talk to a clinician

Having the variant is not an emergency. Contact a clinician promptly if one leg or arm is swollen, painful, red or warm. Call 911 or your local emergency number for chest pain, trouble breathing, coughing up blood or fainting.

Questions you could ask

  • Why was this test ordered for me, and will the result change my care?
  • Are any other clotting tests worth doing alongside it?
  • How does this result fit with my own and my family's history of blood clots?
  • Does it change how we think about surgery, long trips, pregnancy or hormone-containing medicines for me?
  • Should any of my relatives talk with their own clinicians about testing?

Questions people ask

I'm heterozygous. Does that mean I will get a blood clot?

No. One copy raises the chance of a vein clot about two to five times compared with average, but most people with one copy never have a clot. Your own chance also depends on other things, such as surgery, pregnancy, hormones, weight and family history.

Is this the same as my PT or INR?

No. The prothrombin time (PT/INR) measures how quickly your blood clots right now and changes with blood-thinning medicine or liver problems. The G20210A test reads your DNA and never changes. A normal PT/INR does not tell you whether you carry the variant.

Does this matter if I'm pregnant, or if I take estrogen?

Pregnancy and estrogen-containing medicines are clot risk factors that add to inherited ones. Whether your result changes any plan depends on your own and your family's history. Talk with your clinician, and do not change any medicine on your own.

Show the science and sources

For clinicians and researchers

F2 encodes prothrombin (factor II). G20210A (rs1799963) is c.*97G>A in current notation, a change in the 3' untranslated region of the gene (legacy numbering 20210, LOINC 'F2 gene c.20210G>A'). The variant leads to too much prothrombin, which leads to more thrombin and more clot formation (MedlinePlus Genetics). Inheritance is autosomal dominant. Heterozygous carriers have a risk of harmful clots two to five times above average, and homozygotes a higher risk, with clots that may be more frequent and earlier (MedlinePlus Genetics). The frequency is 2 to 5% in Americans of European ancestry. The ASH 2023 thrombophilia testing guideline covers factor V Leiden, the prothrombin 20210A mutation (PGM), antithrombin, protein C and protein S deficiency and antiphospholipid antibodies. For people who have had a first VTE and finished initial treatment, it makes conditional recommendations (very low certainty) about testing to guide how long to continue anticoagulant treatment: not to test after an unprovoked VTE, a VTE provoked by surgery or an unspecified VTE, and to test after a VTE provoked by a nonsurgical major transient risk factor, pregnancy or the postpartum period, or combined oral contraceptive use. It also suggests not testing relatives for a known family FVL or PGM when they have only a minor provoking risk factor, to guide thromboprophylaxis. It makes a strong recommendation against testing women from the general population before they start combined oral contraceptives (Middeldorp 2023). The guideline also warns that functional tests for antithrombin, protein C and protein S can be skewed by acquired deficiencies, which does not apply to a genotype. ACOG Practice Bulletin 197 (2018) reviews screening and management of inherited thrombophilias in pregnancy and notes limited evidence to guide screening. Mayo Clinic Laboratories runs direct variant analysis on EDTA blood (test PTNT) with a reference result of 'Negative', reports it under LOINC 24475-6, says the assay detects only the F2 c.*97G>A variant and that an allogeneic bone marrow transplant will interfere. Labs report the result as G/G, G/A or A/A, or as not detected, heterozygous or homozygous (LOINC answer list for 24475-6). Do not confuse the gene result with factor II activity or prothrombin time.

LOINC 24475-6 (primary), 24476-4. Specimen: whole-blood.

Sources

  1. Prothrombin thrombophilia, MedlinePlus Genetics, National Library of Medicine
  2. American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing, Blood Advances (2023)
  3. ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy, Obstetrics & Gynecology (2018)
  4. Prothrombin G20210A Mutation, Blood (test PTNT), Mayo Clinic Laboratories
  5. Deep vein thrombosis, MedlinePlus Medical Encyclopedia, National Library of Medicine
  6. rs1799963 (F2 c.*97G>A, prothrombin G20210A), NCBI dbSNP

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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