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JAK2V617F positive early stage myeloproliferative disease (essential thrombocythemia) as the cause of portal vein thrombosis in two middle-aged women: therapeutic implications in view of the literature

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Abstract

The present study describes portal vein thrombosis (PVT) in two women as the first and single presenting symptom of latent or masked myeloproliferative disease (MPD). Essential thrombocythemia (ET) was suspected by a sustained increase in platelet count (>400 × 109/l) and slight splenomegaly on echogram. ET could be diagnosed by the presence of large platelet in peripheral blood smear, an increase in clustered large megakaryocytes in bone marrow smear and the presence of the JAK2V617F mutation. A subsequent biopsy specimen was consistent with the diagnosis of true ET. In patients with a first episode of splanchnic vein thrombosis (SVT), analysis of any venous thrombophilic risk factors as well as a JAK2V617F mutation status indicative for MPD is warranted. Administration of heparin followed by oral anticoagulation with vitamin K antagonists is the treatment of choice in patients with SVT. Anticoagulation therapy combined with low-dose aspirin and proper treatment of the MPD is recommended in patients with SVT associated with the JAK2V617F mutation.

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References

  1. Michiels JJ (1997) Diagnostic criteria of the myeloproliferative disorders (MPD): essential thrombocythemia, polycythemia vera and chronic megakaryocytic, granulocytic metaplasia (myeloproliferation). Neth J Med 51:57–64

    Article  PubMed  CAS  Google Scholar 

  2. Michiels JJ, Kutti J, Stark P, Bazzan M, Gugliotta L, Marchioli R, Griesshammer M, Van Genderen PJJ, Brière J, Kiladjian JJ, Barbui T, Finazzi G, Berlin NI, Pearson TC, Green AC, Fruchtman SM, Silver RT, Hansmann E, Wehmeier A, Lengfelder E, Landolfi R, Kvasnicka HM, Hasselbalch H, Cervantes F, Relly JT, Demory JL, Gisslinger H, Guardiola Ph, Martyré MC, Le Bousse-Kerdiles MC, Thiele J (1999) Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thromboythemia, polycythemia vera and essential megakaryocytic granulocytic myeloproliferation and myelofibrosis. Neth J Med 54:46–62

    Article  PubMed  CAS  Google Scholar 

  3. Thiele J, Kvasnicka HM (2003) Chronic myeloproliferative disorders with thrombocythemia: a comparative study of two classifications systems (PVSG–WHO) on 839 patients. Ann Hematol 82:148–152

    PubMed  CAS  Google Scholar 

  4. Florena AM, Tripodo C, Iannitto E, Porcasi R, Ingrao S, Franco V (2004) Value of bone marrow biopsy in the diagnosis of essential thrombocythemia. Haematologica 89:911–919

    PubMed  Google Scholar 

  5. Gianelli U, Vener C, Ravielle PR, Moro A, Savi F, Annaloro C, Somalvico F, Radaella F, Franco V, Delliliers GL (2006) Essential thrombocythemia or chronic myelofibrosis? A single-center study based on hematopoietic bone marrow histology. Leuk Lymph 47:1774–1781

    Article  Google Scholar 

  6. Michiels JJ, Thiele J (2002) Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 76:133–145

    PubMed  Google Scholar 

  7. Michiels JJ, De Raeve H, Berneman Z, Van Bockstaele D, Hebeda K, Lam K, Schroyens W (2006) The 2001 World Health Organization (WHO) and updated European clinical and pathological (ECP) criteria for the diagnosis, classification and staging of the Ph1-chromosome negative chronic myeloproliferative disorders (MPD). Sem Thromb Hemostas 32:307–340

    Article  Google Scholar 

  8. Michiels JJ, Berneman Z, Schroyens, Hebeda K, Lam K De Raeve H, Schwarz J (2007) WHO bone marrow features and European clinical molecular and pathological criteria for the diagnosis of myeloproliferative disorders. Leukemia (in press)

  9. Tefferi A, Pardanani A (2006) Mutation screening for JAK2V617F: when to order the test and how to interpret the results. Leukemia Res 108:3472–3476

    Google Scholar 

  10. Murphy S, Iland H, Rosenthal D et al (1986) Essential thrombocythemia: An interim report from the Polycythemia Vera Study Group. Semin Hematol 23:177–182

    PubMed  CAS  Google Scholar 

  11. WHO (2001) WHO classification of the chronic myeloproliferative diseases (CMPD) polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia and CMPD unclassifiable. In: Jaffe S, Harris NL, Stein H et al (eds) WHO classification of tumours. Tumours of haematopoiesis and lymphoid tissues. IARC, Lyon, pp 31–42

    Google Scholar 

  12. Lengfelder E, Hochhaus A, Kronawitter U et al (1998) Should a platelet count of 600 × 109/l be used as a diagnostic criterion in essential thrombocythemia? An analysis of the natural course including early stages. Br J Haematol 100:15–23

    Article  PubMed  CAS  Google Scholar 

  13. Sacchi S, Vinci G, Gugliotta L, Rupoli S, Garganti L, Martinelli V, Baraveli S, Lazzarino M, Finazzi G (2000) Diagnosis of essential thrombocythemia at platelet counts between 400 and 600 × 109/l. Gruppo Italiano Malattie Mieloproliferative Chroniche (GIMMC). Haematologica 85:492–495

    PubMed  CAS  Google Scholar 

  14. Baxter EJ, Scott LM, Campbell PJ, East C, et al (2005) Acquired mutation of the tyrosine kinase in human myeloproliferative disorders. Lancet 365:1054–1061

    PubMed  CAS  Google Scholar 

  15. Gangat N, Wolanski AP, Tefferi A (2006) Abdominal vein thrombosis in essential thrombocythemia: prevalence, clinical correlates, and prognostic implications. Eur J Haematol 77:327–333

    Article  PubMed  Google Scholar 

  16. Elliott MA, Tefferi A (2005) Thrombosis and hemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128:275–290

    Article  PubMed  CAS  Google Scholar 

  17. Denninger MH, Chait Y, Casadeval N et al (2000) Cause of portal or hepatic vein thrombosis in adults: the role of multiple concurrent factors. Hepatology 21:587–591

    Article  Google Scholar 

  18. Mohanty D, Shetty S, Ghosh K, Pawar A, Abraham P (2001) Hereditary thrombophilia as a cause of Budd–Chiari syndrome: a study from Western India. Hepatology 34:666–670

    Article  PubMed  CAS  Google Scholar 

  19. Janssen HL, Meinardi JR, Vleggaar FP, van Uum SH, Haagsma EB, van der Meer FJ et al (2000) FactorV Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd–Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood 96:2364–2368

    PubMed  CAS  Google Scholar 

  20. Valla D, Casadeval N, Lacombe C et al (1985) Primary myeloproliferative disorder and hepatic vein thrombosis. A prospective study of erytroid colony formation in vitro in 20 patients with Budd–Chiari syndrome. Ann Intern Med 103:329–334

    PubMed  CAS  Google Scholar 

  21. Valla D, Casadevall N, Huisse MG et al (1988) Etiology of portal vein thrombosis in adults. A prospective evaluation of primary myeloproliferative disorders. Gastroenterology 94:1063–1069

    PubMed  CAS  Google Scholar 

  22. Teofili L, De stefano V, Leone G et al (1992) Hematological causes of venous thrombosis in young people; high incidence of myeloproliferative disorders as underlying disease in patients with splanchnic vein thrombosis. Thromb Haemostas 67:2970301

    Google Scholar 

  23. 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. Sem Thromb Hemostas 23:411–418

    Article  Google Scholar 

  24. Chait Y, Condat B, Cazals-Hatem D et al (2005) Relevance of the criteria commonly used to diagnose myeloproliferative disorders in patients with splanchnic vein thrombosis. Br J Haematol 129:553–560

    Article  PubMed  Google Scholar 

  25. Brière J (2006) Budd–Chiari syndrome and portal vein thrombosis associated with myeloprioliferative disorders: diagnosis and management. Sem Thromb Hemostas 32:208–218

    Article  Google Scholar 

  26. Patel RK, Lea NC, Heneghan A, Westwood N et al (2006) Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd–Chiari Syndrome. Gastroenterology 130:2031–2038

    Article  PubMed  CAS  Google Scholar 

  27. Smalberg JH, Murad SD, Braakman E, Valk PJ, Janssen HLA, Leebeek FWG (2006) Myeloproliferative disease in the pathogenesis and survival of Budd–Chiari syndrome. Haematologica 91:1712–1713

    PubMed  Google Scholar 

  28. Collaizzo D, Amitrano L, Tiscia L, Scenna G, Grandone E, Guardascione MA, Brancaccio V, Margaglione M (2007) The JAK2 V617F mutation frequently occurs in patients with portal vein and mesenteric vein thrombosis J Thromb Haemostas 5:55–61

    Article  Google Scholar 

  29. De Stefano V, Fiorini A, Rossi E, Za T, Farina G, Reddiconto G, Chiusolo P, Leone G (2007) Incidence of the JAK2V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemostas (in press)

  30. Primignani M, Barosi G, Bergamaschi G, Gianelli U, Fabris F, Reati et al (2006) Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology 44:1528–1534

    Article  PubMed  CAS  Google Scholar 

  31. Boissinot M, Lippert E, Girodon F, Dobo I, Fouassier M, Masliah C, Praloran V, Hermouet S (2006) Latent myeloproliferative disorder revealed by the JAK2V617F mutation and endogenous megakaryocytic colonies in patients with splanchnic vein thrombosis. Blood 108:3323–3324

    Google Scholar 

  32. Murad SD, Valla, D, de Groen PC, Zeitoun G, Haagsma EB, Kuipers EJ, Janssen HLA (2006) Pathogenesis and treatment of Budd–Chiari syndrome combined with portal vein thrombosis. Am J Gastroenterology 101:83–90

    Article  Google Scholar 

  33. Tanaka M, Wanless IR (1998) Pathology of the liver in Budd–Chiari syndromr: portal vein thrombosis and the histogenesis of veno-centric cirrhosis, veno-portal cirrhosis, and large regenerative nodules. Hepatology 27:488–496

    Article  PubMed  CAS  Google Scholar 

  34. Cazals-Hatem D, Vilgrain V, Genin P, Denninger MH, Durand F, Belghiti J, Valla D, Degotti C (2003) Arterial and portal circulation and parenchymal changes in Budd–Chiari syndrome: a study in 17 exlanted livers. Hepatology 37:510–519

    Article  PubMed  Google Scholar 

  35. Janssen HLA, Wijnhoud A, Haagsma EB, van Uum SHM, van Nieuwkerk CMJ, Adang RPA, Chamuleau RAFM, van Hattum J, Vleggaar FP, Hansen BE, Rosendaal FR, van Hoek B (2001) Extrahepatic portal vein thrombosis: aetilogy and determinants of survival. Gut 49:720–724

    Article  PubMed  CAS  Google Scholar 

  36. 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 120:490–497

    Article  PubMed  CAS  Google Scholar 

  37. Van Genderen PJJ, Prins F, Michiels JJ, Schrör K (1999) Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent. Br J Haematol 104:438–441

    Article  PubMed  Google Scholar 

  38. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, BarbuiT (2004) Efficacy and safety of low-dose aspirin in polycythemia vera: results of the ECLAP trial. N Eng J Med 350:114–124

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium

    J. J. Michiels

  2. Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

    S. Commandeur

  3. Department of Internal Medicine, CZ Deventer Hospital, Deventer, The Netherlands

    G. J. Hoogenboom & J. J. Wegman

  4. Clinical Chemistry, CZ Deventer Hospital, Deventer, The Netherlands

    L. Scholten

  5. Department of Pathology, Deventer Hospital, Deventer, The Netherlands

    R. H. van Rijssel

  6. Department of Pathology, University Hospital Antwerp, Antwerp, Belgium

    H. De Raeve

  7. European Working Group on Myeloproliferative Disorders (EWG.MPD), Goodheart Institute, Rotterdam, The Netherlands

    J. J. Michiels

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  1. J. J. Michiels
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Correspondence to J. J. Michiels.

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Michiels, J.J., Commandeur, S., Hoogenboom, G.J. et al. JAK2V617F positive early stage myeloproliferative disease (essential thrombocythemia) as the cause of portal vein thrombosis in two middle-aged women: therapeutic implications in view of the literature. Ann Hematol 86, 793–800 (2007). https://doi.org/10.1007/s00277-007-0351-1

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