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Excerpted from the GeneReview: Prothrombin-Related Thrombophilia
Prothrombin-related thrombophilia is characterized by venous thromboembolism (VTE) manifest most commonly in adults as deep-vein thrombosis (DVT) in the legs or pulmonary embolism. The clinical expression of prothrombin-related thrombophilia is variable; many individuals heterozygous or homozygous for the 20210G>A (G20210A or c.*97G>A) allele in F2 never develop thrombosis, and while most heterozygotes who develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years. The relative risk for DVT in adults heterozygous for the 20210G>A allele is two- to fivefold increased; in children, the relative risk for thrombosis is three- to fourfold increased. 20210G>A heterozygosity has at most a modest effect on recurrence risk after a first episode. Although prothrombin-related thrombophilia may increase the risk for pregnancy loss, its association with preeclampsia and other complications of pregnancy such as intrauterine growth restriction and placental abruption remains controversial. Factors that predispose to thrombosis in prothrombin-related thrombophilia include: the number of 20210G>A alleles; presence of coexisting genetic abnormalities including factor V Leiden; and acquired thrombophilic disorders (e.g., antiphospholipid antibodies). Circumstantial risk factors for thrombosis include pregnancy and oral contraceptive use. Some evidence suggests that the risk for VTE in 20210G>A heterozygotes increases after travel.

Genes See tests for all associated and related genes

  • Also known as: F13A, F13A1
    Summary: coagulation factor XIII A chain

  • Also known as: PT, RPRGL2, THPH1, F2
    Summary: coagulation factor II, thrombin

  • Also known as: FSAP, HABP, HGFAL, NMTC5, PHBP, HABP2
    Summary: hyaluronan binding protein 2

  • Also known as: , MTHFR
    Summary: methylenetetrahydrofolate reductase

Clinical features


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Practice guidelines

  • ACMG, 2015
    Don't order MTHFR genetic testing for the risk assessment of hereditary thrombophilia.
  • ACMG, 2013
    ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing.
  • ACOG, 2011
    Practice bulletin no. 124: inherited thrombophilias in pregnancy.
  • EGAPP, 2011
    Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members.
  • Brit Cmt Stand Hematol, 2010
    Clinical guidelines for testing for heritable thrombophilia.
  • ACOG, 2010
    The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists.

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