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Thromb Haemost 1999; 81(01): 14-17
DOI: 10.1055/s-0037-1614409
Review Article
Schattauer GmbH

The Risk of Early Recurrent Venous Thromboembolism after Oral Anticoagulant Therapy in Patients with the G20210A Transition in the Prothrombin Gene

Sabine Eichinger
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Erich Minar
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Mirko Hirschl
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Christine Bialonczyk
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Milena Stain
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Christine Mannhalter
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Andreas Stümpflen
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Barbara Schneider
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Klaus Lechner
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
,
Paul Alexander Kyrle
1   From the Departments of Internal Medicine I, Division of Hematology and Hemostaseology, and Internal Medicine II, Division of Angiology, Department of Medical Statistics, University of Vienna, Hanuschkrankenhaus, Vienna, and Wilhelminenspital, Vienna, Austria
› Author Affiliations
Further Information

Correspondence to:

Dr. Sabine Eichinger
Department of Internal Medicine I
Division of Hematology/Hemostaseology
Waehringer Guertel 18-20, A-1090 Vienna
Austria
Phone: +43 1 40400 4410   
Fax: +43 1 4026930

Publication History

Publication Date:
08 December 2017 (online)

Also available at
 
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Summary

A G20210A transition in the prothrombin gene is a common risk factor of venous thrombosis. The risk of recurrent venous thrombo-embolism in carriers of the 20210A allele is unknown and guidelines for secondary thromboprophylaxis in these patients are not available.

In a prospective multicenter trial, 492 patients with a history of objectively documented venous thromboembolism were followed for a mean observation time of 24 ± 16 months after discontinuation of oral anticoagulants. Forty-two patients (8.5%) were carriers of the 20210A allele. Three of the 42 patients with the G20210A mutation (7%) and 54 of 450 patients without the mutation (12%) experienced recurrent venous thrombosis. At 24 months, the probability of recurrence was 8% (95% CI 0-16.7) in patients with the mutation and was 12.2% (95% CI 8.8-15.6) in patients without the mutation.

In conclusion, the risk of early recurrent venous thromboembolism is not higher in patients with the G20210A mutation than in those without the mutation. Therefore, long-term secondary thromboprophylaxis with oral anticoagulants in heterozygous carriers of the 20210A allele is not justified.


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  • References

  • 1 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: 3698-703.
    PubMedSearch in Google Scholar
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    Thieme ConnectPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
  • 6 Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993-7.
    CrossrefPubMedSearch in Google Scholar
  • 7 Eichinger S, Pabinger I, Stümpflen A, Hirschl M, Bialonczyk C, Schneider B, Mannhalter C, Minar E, Lechner K, Kyrle PA. The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. Thromb Haemost 1997; 77: 624-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Simioni P, Prandoni P, Lensing AWA, Scudeller A, Sardella C, Prins MH, Villalta S, Dazzi F, Girolami A. The risk of recurrent venous thrombo-embolism in patients with an Arg509→Gin mutation in the gene for factor V (factor V Leiden). N Engl J Med 1997; 336: 399-403.
    CrossrefPubMedSearch in Google Scholar
  • 9 Ridker PM, Miletich JP, Stampfer MJ, Goldhaber SZ, Lindpaintner K, Hennekens CH. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 1995; 92: 2800-2.
    CrossrefPubMedSearch in Google Scholar
  • 10 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
    CrossrefPubMedSearch in Google Scholar
  • 11 Pabinger I, Brücker S, Kyrle PA, Schneider B, Korninger HC, Niessner H, Lechner K. Hereditary deficiency of antithrombin III, protein C, and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening. Blood Coagul Fibrinolysis 1992; 3: 547-53.
    CrossrefPubMedSearch in Google Scholar
  • 12 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81.
    CrossrefPubMedSearch in Google Scholar
  • 13 Palaretti G, Leali N, Coccheri S, Poggi M, Manotti C, d’Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berettini M, Musolesi S. on behalf of the Italian Study on Complications of Oral Anticoagulant Therapy. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996; 348: 423-8.
    CrossrefPubMedSearch in Google Scholar
  • 14 Zöller B, Berntsdotter A, Garcia de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85: 3518-23.
    PubMedSearch in Google Scholar
  • 15 Koeleman BP, Reitsma PH, Allart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84: 1031-5.
    PubMedSearch in Google Scholar
  • 16 van Boven HH, Reitsma PH, Rosendaal FR, Baiston TA, Chowdhury V, Bauer KA, Scharrer I, Conard J, Lane DA. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency. Thromb Haemost 1996; 75: 417-21.
    Thieme ConnectPubMedSearch in Google Scholar

Correspondence to:

Dr. Sabine Eichinger
Department of Internal Medicine I
Division of Hematology/Hemostaseology
Waehringer Guertel 18-20, A-1090 Vienna
Austria
Phone: +43 1 40400 4410   
Fax: +43 1 4026930

  • References

  • 1 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: 3698-703.
    PubMedSearch in Google Scholar
  • 2 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: 990-2.
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Cumming AM, Keeny S, Salden A, Bhavnani M, Shwe M, Shwe KH, Hay CRM. The prothrombin gene G20210A variant: prevalence in a U.K. anti-Eichinger et al.: Recurrent Venous Thrombosis and G20210A Transition in Prothrombin Gene coagulant clinic population. Brit J Haematol 1997; 98: 353-5.
    CrossrefPubMedSearch in Google Scholar
  • 4 Schulman S, Rhedin A-S, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H, Viering S, Nordlander S, Leijd B, Jönsson K-Å, Hjorth M, Linder O, Boberg J. and the Duration of Anticoagulation Trial Study Group. Comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332: 1661-5.
    CrossrefPubMedSearch in Google Scholar
  • 5 Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan A, Polistena P, Bernardi E, Prins MH. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1-7.
    CrossrefPubMedSearch in Google Scholar
  • 6 Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 993-7.
    CrossrefPubMedSearch in Google Scholar
  • 7 Eichinger S, Pabinger I, Stümpflen A, Hirschl M, Bialonczyk C, Schneider B, Mannhalter C, Minar E, Lechner K, Kyrle PA. The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. Thromb Haemost 1997; 77: 624-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Simioni P, Prandoni P, Lensing AWA, Scudeller A, Sardella C, Prins MH, Villalta S, Dazzi F, Girolami A. The risk of recurrent venous thrombo-embolism in patients with an Arg509→Gin mutation in the gene for factor V (factor V Leiden). N Engl J Med 1997; 336: 399-403.
    CrossrefPubMedSearch in Google Scholar
  • 9 Ridker PM, Miletich JP, Stampfer MJ, Goldhaber SZ, Lindpaintner K, Hennekens CH. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 1995; 92: 2800-2.
    CrossrefPubMedSearch in Google Scholar
  • 10 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
    CrossrefPubMedSearch in Google Scholar
  • 11 Pabinger I, Brücker S, Kyrle PA, Schneider B, Korninger HC, Niessner H, Lechner K. Hereditary deficiency of antithrombin III, protein C, and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening. Blood Coagul Fibrinolysis 1992; 3: 547-53.
    CrossrefPubMedSearch in Google Scholar
  • 12 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81.
    CrossrefPubMedSearch in Google Scholar
  • 13 Palaretti G, Leali N, Coccheri S, Poggi M, Manotti C, d’Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berettini M, Musolesi S. on behalf of the Italian Study on Complications of Oral Anticoagulant Therapy. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996; 348: 423-8.
    CrossrefPubMedSearch in Google Scholar
  • 14 Zöller B, Berntsdotter A, Garcia de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85: 3518-23.
    PubMedSearch in Google Scholar
  • 15 Koeleman BP, Reitsma PH, Allart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84: 1031-5.
    PubMedSearch in Google Scholar
  • 16 van Boven HH, Reitsma PH, Rosendaal FR, Baiston TA, Chowdhury V, Bauer KA, Scharrer I, Conard J, Lane DA. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency. Thromb Haemost 1996; 75: 417-21.
    Thieme ConnectPubMedSearch in Google Scholar

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