Digestive Diseases and Sciences

, Volume 53, Issue 10, pp 2778–2783 | Cite as

JAK2V617F Mutation in Patients with Portal Vein Thrombosis

  • Yusuf Bayraktar
  • Ozgur Harmanci
  • Yahya Büyükasik
  • Ali Ibrahim Shorbagi
  • Aysegul Hasegeli Sungur
  • Cemaliye Akyerli Boylu
  • Aytemiz Gürgey
  • Ferhun Balkanci
Original Paper


In a retrospective cohort, we investigated the presence of the JAK2V617F mutation in chronic non-cirrhotic portal vein thrombosis (PVT) patients, irrespective of the presence or absence of myeloproliferative diseases (MPDs). We identified 25 patients in whom thrombophilia workup was completed. The diagnoses of MPDs were made according to the World Health Organization (WHO) criteria. JAK2V617F mutation analysis was performed by allele-specific polymerase chain reaction (PCR). There were 9 male and 16 female patients. Prior to JAK2V617F analysis, there were one or more thrombophilic risk factors in 19 patients (76%). The JAK2V617F mutation analysis revealed the presence of this mutation (all in the heterozygote state) in six patients (24%; two male, four female). Five of the six cases with prior clinical diagnosis of MPDs were found to have wild-type JAK2. We found that the addition of JAK2V617F analysis into the thrombophilia workup in patients with chronic PVT contributes to a 4% increase in the diagnosis of thrombophilic conditions.


JAK2V617F mutation Portal vein thrombosis Myeloproliferative diseases 


  1. 1.
    Condat B, Pessione F, Hillaire S, Denninger MH, Guillin MC, Poliquin M, Hadengue A, Erlinger S, Valla D (2001) Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology 120:490–497PubMedCrossRefGoogle Scholar
  2. 2.
    Sarin SK, Agarwal SR (2002) Extrahepatic portal vein obstruction. Semin Liver Dis 22:43–58PubMedCrossRefGoogle Scholar
  3. 3.
    Gürgey A, Haznedaroglu IC, Egesel T, Büyükasik Y, Ozcebe OI, Sayinalp N, Dundar SV, Bayraktar Y (2001) Two common genetic thrombotic risk factors: factor V Leiden and prothrombin G20210A in adult Turkish patients with thrombosis. Am J Hematol 67:107–111PubMedCrossRefGoogle Scholar
  4. 4.
    Egesel T, Büyükasik Y, Dundar SV, Gürgey A, Kirazli S, Bayraktar Y (2000) The role of natural anticoagulant deficiencies and factor V Leiden in the development of idiopathic portal vein thrombosis. J Clin Gastroenterol 30:66–71PubMedCrossRefGoogle Scholar
  5. 5.
    Bayraktar Y, Balkanci F, Bayraktar M, Calguneri M (1997) Budd-Chiari syndrome: a common complication of Behçet’s disease. Am J Gastroenterol 92:858–862PubMedGoogle Scholar
  6. 6.
    Bayraktar Y, Balkanci F, Kansu E, Dundar S, Uzunalimoglu B, Kayhan B, Telatar H, Gurakar A, Van Thiel DH (1995) Cavernous transformation of the portal vein: a common manifestation of Behçet’s disease. Am J Gastroenterol 90:1476–1479PubMedGoogle Scholar
  7. 7.
    Denninger MH, Chait Y, Casadevall N, Hillaire S, Guillin MC, Bezeaud A, Erlinger S, Brière J, Valla D (2000) Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology 31:587–591PubMedCrossRefGoogle Scholar
  8. 8.
    Janssen HL, Wijnhoud A, Haagsma EB, van Uum SH, van Nieuwkerk CM, Adang RP, Chamuleau RA, van Hattum J, Vleggaar FP, Hansen BE, Rosendaal FR, van Hoek B (2001) Extrahepatic portal vein thrombosis: aetiology and determinants of survival. Gut 49:720–724PubMedCrossRefGoogle Scholar
  9. 9.
    Valla D, Casadevall N, Huisse MG, Tulliez M, Grange JD, Muller O, Binda T, Varet B, Rueff B, Benhamou JP (1988) Etiology of portal vein thrombosis in adults. A prospective evaluation of primary myeloproliferative disorders. Gastroenterology 94:1063–1069PubMedGoogle Scholar
  10. 10.
    Valla D, Casadevall N, Lacombe C, Varet B, Goldwasser E, Franco D, Maillard JN, Pariente EA, Leporrier M, Rueff B, Muller O, Benhamou J-P (1985) Primary myeloproliferative disorder and hepatic vein thrombosis. A prospective study of erythroid colony formation in vitro in 20 patients with Budd-Chiari syndrome. Ann Intern Med 103:329–334PubMedGoogle Scholar
  11. 11.
    Valla DC, Condat B (2000) Portal vein thrombosis in adults: pathophysiology, pathogenesis and management. J Hepatol 32:865–871PubMedCrossRefGoogle Scholar
  12. 12.
    De Stefano V, Teofili L, Leone G, Michiels JJ (1997) Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis. Semin Thromb Hemost 23:411–418PubMedCrossRefGoogle Scholar
  13. 13.
    Chait Y, Condat B, Cazals-Hatem D, Rufat P, Atmani S, Chaoui D, Guilmin F, Kiladjian JJ, Plessier A, Denninger MH, Casadevall N, Valla D, Brière JB (2005) Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br J Haematol 129:553–560PubMedCrossRefGoogle Scholar
  14. 14.
    Vardiman JW, Harris NL, Brunning RD (2002) The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100:2292–2302PubMedCrossRefGoogle Scholar
  15. 15.
    Peterson P, Wasserman LR (1995) The natural history of polycythemia vera. In: Wasserman LR, Berk PD, Berlin NI (eds) Polycythemia vera and the myeloproliferative disorders. WB Saunders, Philadelphia, pp 14–21Google Scholar
  16. 16.
    Patel RK, Lea NC, Heneghan MA, Westwood NB, Milojkovic D, Thanigaikumar M, Yallop D, Arya R, Pagliuca A, Gäken J, Wendon J, Heaton ND, Mufti GJ (2006) Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology 130:2031–2038PubMedCrossRefGoogle Scholar
  17. 17.
    Lemoine F, Najman A, Baillou C, Stachowiak J, Boffa G, Aegerter P, Douay L, Laporte JP, Gorin NC, Duhamel G (1986) A prospective study of the value of bone marrow erythroid progenitor cultures in polycythemia. Blood 68:996–1002PubMedGoogle Scholar
  18. 18.
    Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR; Cancer Genome Project (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061PubMedGoogle Scholar
  19. 19.
    Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D’Andrea A, Fröhling S, Döhner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397PubMedCrossRefGoogle Scholar
  20. 20.
    James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148PubMedCrossRefGoogle Scholar
  21. 21.
    Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790PubMedCrossRefGoogle Scholar
  22. 22.
    Levine JS, Branch W, Rausch J (2002) The antiphospholipid syndrome. N Engl J Med 346:752–763PubMedCrossRefGoogle Scholar
  23. 23.
    Harmanci O, Ersoy O, Gürgey A, Büyükasik Y, Gedikoglu G, Balkanci F, Sivri B, Bayraktar Y (2007) The etiologic distribution of thrombophilic factors in chronic portal vein thrombosis. J Clin Gastroenterol 41:521–527PubMedCrossRefGoogle Scholar
  24. 24.
    Harmanci O, Büyükasik Y, Kirazli S, Balkanci F, Bayraktar Y (2006) Does endothelium agree with the concept of idiopathic hepatic vessel thrombosis? World J Gastroenterol 28:1273–1277Google Scholar
  25. 25.
    Egesel T, Unsal I, Bayraktar Y (2002) Antiphospholipid antibodies and lipoprotein (a) as etiologic or contributory factors in patients with idiopathic cavernous transformation of portal vein. Turk J Gastroenterol 13:89–93PubMedGoogle Scholar
  26. 26.
    Primignani M, Barosi G, Bergamaschi G, Gianelli U, Fabris F, Reati R, Dell’Era A, Bucciarelli P, Mannucci PM (2006) Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology 44:1528–1534PubMedCrossRefGoogle Scholar
  27. 27.
    Colaizzo D, Amitrano L, Tiscia GL, Scenna G, Grandone E, Guardascione MA, Brancaccio V, Margaglione M (2007) The JAK2 V617F mutation frequently occurs in patients with portal and mesenteric venous thrombosis. J Thromb Haemost 5:55–61PubMedCrossRefGoogle Scholar
  28. 28.
    De Stefano V, Fiorini A, Rossi E, Za T, Farina G, Chiusolo P, Sica S, Leone G (2007) Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 5:708–714PubMedCrossRefGoogle Scholar
  29. 29.
    Ko KH, Kim NK, Yim DJ, Hong SP, Park PW, Rim KS, Kim S, Hwang SG (2006) Polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) and thymidylate synthase enhancer region (TSER) as a risk factor of cholangiocarcinoma in a Korean population. Anticancer Res 26:4229–4233PubMedGoogle Scholar
  30. 30.
    Bolufer P, Barragan E, Collado M, Cervera J, López JA, Sanz MA (2006) Influence of genetic polymorphisms on the risk of developing leukemia and on disease progression. Leuk Res 30:1471–1491PubMedCrossRefGoogle Scholar
  31. 31.
    Hubner RA, Lubbe S, Chandler I, Houlston RS (2007) MTHFR C677T has differential influence on risk of MSI and MSS colorectal cancer. Hum Mol Genet 16:1072–1077PubMedCrossRefGoogle Scholar
  32. 32.
    Elliott MA, Tefferi A (2005) Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128:275–290PubMedCrossRefGoogle Scholar
  33. 33.
    Barbui T (2007) The targets of therapy in polycythemia vera and thrombocythemia. Turk J Hematol 24(Suppl 1):54Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Yusuf Bayraktar
    • 1
  • Ozgur Harmanci
    • 1
  • Yahya Büyükasik
    • 2
  • Ali Ibrahim Shorbagi
    • 1
  • Aysegul Hasegeli Sungur
    • 3
  • Cemaliye Akyerli Boylu
    • 4
  • Aytemiz Gürgey
    • 5
  • Ferhun Balkanci
    • 6
  1. 1.Department of GastroenterologyHacettepe University Faculty of MedicineSihhiyeTurkey
  2. 2.Department of HematologyHacettepe University Faculty of MedicineSihhiyeTurkey
  3. 3.Department of PathologyHacettepe University Faculty of MedicineSihhiyeTurkey
  4. 4.Department of OncologyHacettepe University Faculty of MedicineSihhiyeTurkey
  5. 5.Department of Pediatric HematologyHacettepe University Faculty of MedicineSihhiyeTurkey
  6. 6.Department of RadiologyHacettepe University Faculty of MedicineSihhiyeTurkey

Personalised recommendations