Coagulation
Hereditary thrombophilia / hypercoagulopathies
Prothrombin gene mutation (G20210A) / hyperprothrombinemia

Author: Jeremy Parsons, M.D. (see Authors page)

Revised: 2 May 2016, last major update June 2012

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Prothrombin gene mutation (G20210A) / hyperprothrombinemia

Definition / General
  • Mutation in G to A transition at nucleotide 20210 in 3 untranslated portion of prothrombin gene, which introduces a new Hind III site
  • Associated with (may not directly cause) increased prothrombin levels, 2 - 5x increased risk of venous thrombosis
  • Patients with G20210A mutation have increased levels of TAFI (Thrombin Activated Fibrinolysis I, a protein that inhibits clot lysis), which makes clots exist longer, leading to increased thrombotic episodes
  • Risk is multiplicative if taking oral contraceptives and have factor V Leiden gene
  • Heterozygous form occurs in 1 - 2% of normal individuals, 6 - 20% of patients with venous thrombosis
  • Testing via nucleic acid based assay is preferred, as the lack of linearity of the clot - based Factor II assay at the high end makes this unsuitable for diagnostic use
Laboratory
  • Recommended patients to test:
    • Patients with recurrent venous thromboembolic events
    • First episode before age 50
    • First unprovoked venous thromboemboli at any age
    • Thromboses at unusual anatomic sites (cerebral, mesenteric, portal or hepatic veins)
    • Venous thromboemboli in patient with first degree relative with venous thromboemboli before age 50 years
    • Venous thromboemboli related to pregnancy or estrogen use, or unexplained pregnancy loss in second or third trimesters
    • Young individuals with myocardial infarction and no other risk factors
    • Also test factor V Leiden and other mutations (combination most clearly impacts clinical decision making)

  • Testing not recommended:
    • As general population screen
    • Routine test during pregnancy
    • Routine test before or during oral contraceptive use or hormone replacement therapy
    • As newborn initial test
    • As initial test in patients with arterial thrombotic events
Treatment
  • Patients with thromboemboli and this mutation should receive similar treatment as other patients with venous thromboemboli