Prothrombin G20210A mutation
- Kenneth A Bauer, MD
Kenneth A Bauer, MD
- Professor of Medicine
- Harvard Medical School
The prothrombin G20210A mutation is the second most common inherited thrombophilia after the factor V Leiden mutation. Challenging clinical issues include the decisions regarding when to test for the mutation and how to manage individuals with the mutation, either in the setting of venous thromboembolism (VTE) or as an incidental finding.
This topic reviews the diagnosis of prothrombin G20210A and the management of individuals who carry the mutation.
Separate topic reviews discuss other thrombophilias and the role of thrombophilia screening in various populations:
●Factor V Leiden (FVL) mutation – (See "Factor V Leiden and activated protein C resistance".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Meeks SL, Abshire TC. Abnormalities of prothrombin: a review of the pathophysiology, diagnosis, and treatment. Haemophilia 2008; 14:1159.
- 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; 88:3698.
- Girolami A, Scarano L, Tormene D, Cella G. Homozygous patients with the 20210 G to A prothrombin polymorphism remain often asymptomatic in spite of the presence of associated risk factors. Clin Appl Thromb Hemost 2001; 7:122.
- Gehring NH, Frede U, Neu-Yilik G, et al. Increased efficiency of mRNA 3' end formation: a new genetic mechanism contributing to hereditary thrombophilia. Nat Genet 2001; 28:389.
- Mannucci PM, Franchini M. Classic thrombophilic gene variants. Thromb Haemost 2015; 114:885.
- Carter AM, Sachchithananthan M, Stasinopoulos S, et al. Prothrombin G20210A is a bifunctional gene polymorphism. Thromb Haemost 2002; 87:846.
- Pollak ES, Lam HS, Russell JE. The G20210A mutation does not affect the stability of prothrombin mRNA in vivo. Blood 2002; 100:359.
- Soria JM, Almasy L, Souto JC, et al. Linkage analysis demonstrates that the prothrombin G20210A mutation jointly influences plasma prothrombin levels and risk of thrombosis. Blood 2000; 95:2780.
- Gelfi C, Viganò A, Ripamonti M, et al. A proteomic analysis of changes in prothrombin and plasma proteins associated with the G20210A mutation. Proteomics 2004; 4:2151.
- Ceelie H, Spaargaren-van Riel CC, Bertina RM, Vos HL. G20210A is a functional mutation in the prothrombin gene; effect on protein levels and 3'-end formation. J Thromb Haemost 2004; 2:119.
- Miyawaki Y, Suzuki A, Fujita J, et al. Thrombosis from a prothrombin mutation conveying antithrombin resistance. N Engl J Med 2012; 366:2390.
- Dunn ST, Allen RA, Bates F, et al. Abnormal melt curve profile during prothrombin 20210G --> A analysis due to the 20209C --> T variant. Blood Coagul Fibrinolysis 2006; 17:599.
- Itakura H, Telen MJ, Hoppe CC, et al. Characterization of a novel prothrombin variant, Prothrombin C20209T, as a modifier of thrombotic risk among African-Americans. J Thromb Haemost 2005; 3:2357.
- Hooper WC, Roberts S, Dowling N, et al. The prevalence of the prothrombin gene variant C20209T in African-Americans and Caucasians and lack of association with venous thromboembolism. Thromb Res 2006; 118:767.
- Pérez-Ceballos E, Corral J, Alberca I, et al. Prothrombin A19911G and G20210A polymorphisms' role in thrombosis. Br J Haematol 2002; 118:610.
- Martinelli I, Battaglioli T, Tosetto A, et al. Prothrombin A19911G polymorphism and the risk of venous thromboembolism. J Thromb Haemost 2006; 4:2582.
- Rosendaal FR, Doggen CJ, Zivelin A, et al. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost 1998; 79:706.
- Zivelin A, Rosenberg N, Faier S, et al. A single genetic origin for the common prothrombotic G20210A polymorphism in the prothrombin gene. Blood 1998; 92:1119.
- Leroyer C, Mercier B, Oger E, et al. Prevalence of 20210 A allele of the prothrombin gene in venous thromboembolism patients. Thromb Haemost 1998; 80:49.
- Souto JC, Coll I, Llobet D, et al. The prothrombin 20210A allele is the most prevalent genetic risk factor for venous thromboembolism in the Spanish population. Thromb Haemost 1998; 80:366.
- Margaglione M, Brancaccio V, Giuliani N, et al. Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. Ann Intern Med 1998; 129:89.
- Hillarp A, Zöller B, Svensson PJ, Dahlbäck B. The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. Thromb Haemost 1997; 78:990.
- Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism--pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001; 86:809.
- De Stefano V, Martinelli I, Mannucci PM, et al. 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; 341:801.
- Ehrenforth S, Ludwig G, Klinke S, et al. The prothrombin 20210 A allele is frequently coinherited in young carriers of the factor V Arg 506 to Gln mutation with venous thrombophilia. Blood 1998; 91:2209.
- Grandone E, Margaglione M, Colaizzo D, et al. Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations. Am J Obstet Gynecol 1998; 179:1324.
- Dentali F, Pomero F, Borretta V, et al. Location of venous thrombosis in patients with FVL or prothrombin G20210A mutations: systematic review and meta-analysis. Thromb Haemost 2013; 110:191.
- Dentali F, Ageno W, Bozzato S, et al. Role of factor V Leiden or G20210A prothrombin mutation in patients with symptomatic pulmonary embolism and deep vein thrombosis: a meta-analysis of the literature. J Thromb Haemost 2012; 10:732.
- Zhang P, Zhang J, Sun G, et al. Risk of Budd-Chiari syndrome associated with factor V Leiden and G20210A prothrombin mutation: a meta-analysis. PLoS One 2014; 9:e95719.
- Gonzalez JV, Barboza AG, Vazquez FJ, Gándara E. Prevalence and Geographical Variation of Prothrombin G20210A Mutation in Patients with Cerebral Vein Thrombosis: A Systematic Review and Meta-Analysis. PLoS One 2016; 11:e0151607.
- Martinelli I, Sacchi E, Landi G, et al. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med 1998; 338:1793.
- Simioni P, Prandoni P, Lensing AW, et al. Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis. Blood 2000; 96:3329.
- Lindmarker P, Schulman S, Sten-Linder M, et al. The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. DURAC Trial Study Group. Duration of Anticoagulation. Thromb Haemost 1999; 81:684.
- Eichinger S, Minar E, Hirschl M, et al. The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene. Thromb Haemost 1999; 81:14.
- De Stefano V, Martinelli I, Mannucci PM, et al. The risk of recurrent venous thromboembolism among heterozygous carriers of the G20210A prothrombin gene mutation. Br J Haematol 2001; 113:630.
- Segal JB, Brotman DJ, Necochea AJ, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 2009; 301:2472.
- Ho WK, Hankey GJ, Quinlan DJ, Eikelboom JW. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med 2006; 166:729.
- Marchiori A, Mosena L, Prins MH, Prandoni P. The risk of recurrent venous thromboembolism among heterozygous carriers of factor V Leiden or prothrombin G20210A mutation. A systematic review of prospective studies. Haematologica 2007; 92:1107.
- Sarecka-Hujar B, Kopyta I, Skrzypek M, Sordyl J. Association Between the 20210G>A Prothrombin Gene Polymorphism and Arterial Ischemic Stroke in Children and Young Adults-Two Meta-analyses of 3586 Cases and 6440 Control Subjects in Total. Pediatr Neurol 2017; 69:93.
- Ye Z, Liu EH, Higgins JP, et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367:651.
- Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 2003; 146:948.
- De Stefano V, Chiusolo P, Paciaroni K, et al. Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic disease in young patients. Blood 1998; 91:3562.
- Lalouschek W, Schillinger M, Hsieh K, et al. Matched case-control study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years. Stroke 2005; 36:1405.
- Lichy C, Reuner KH, Buggle F, et al. Prothrombin G20210A mutation, but not factor V Leiden, is a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischemia. Cerebrovasc Dis 2003; 16:83.
- Eikelboom JW, Baker RI, Parsons R, et al. No association between the 20210 G/A prothrombin gene mutation and premature coronary artery disease. Thromb Haemost 1998; 80:878.
- Bradley LA, Palomaki GE, Bienstock J, et al. Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review. Genet Med 2012; 14:39.
- Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. 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. Genet Med 2011; 13:67.
- Cooper PC, Rezende SM. An overview of methods for detection of factor V Leiden and the prothrombin G20210A mutations. Int J Lab Hematol 2007; 29:153.
- Gomez E, van der Poel SC, Jansen JH, et al. Rapid simultaneous screening of factor V Leiden and G20210A prothrombin variant by multiplex polymerase chain reaction on whole blood. Blood 1998; 91:2208.
- Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149:315.
- Varga EA, Moll S. Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation). Circulation 2004; 110:e15.
- Role of prothrombin in coagulation
- Prothrombin G20210A mutation
- Other prothrombin gene variants
- CLINICAL FEATURES
- Venous thromboembolism
- - Risk of VTE
- - Sites of thrombosis
- - Recurrence risk
- Arterial thrombosis
- Obstetric issues
- Mutation testing
- Differential diagnosis
- Patients with VTE
- Asymptomatic individuals
- Testing of first degree relatives
- SUMMARY AND RECOMMENDATIONS