Splanchnic vein thrombosis can be the presenting manifestation of myeloproliferative neoplasms. However, the diagnosis of a myeloproliferative neoplasm in these patients is often problematic, and more objective criteria are needed.
To determine the frequency of the mutation JAK2V617F in patients with splanchnic vein thromboses.
A consecutive series of 108 adult patients with portal vein thrombosis (n = 77) and Budd-Chiari syndrome (n = 31) referred for hemostasis evaluation was retrospectively studied, with a median follow-up of 51 months (1–104).
One or more prothrombotic risk factors were present in 63% of the patients. Twenty-four (22%) out of the 108 patients presented the JAK2V617F, including 2 cirrhotic patients. Most had a low mutated allele burden (median 16.5%). JAK2V617F was present in all four patients with a previous diagnosis of a myeloproliferative neoplasm. In nine JAK2V617F-positive patients, the diagnosis of a myeloproliferative neoplasm was made at the thrombosis work-up, during follow-up or after JAK2V617F detection. Among the other 11 patients carrying the mutation, 2 patients have died, 4 had no evidence suggesting a myeloproliferative neoplasm, 1 had a normal bone marrow biopsy, and the other 4 could not be persuaded to undergo a biopsy. Among the patients without an overt myeloproliferative neoplasm, 15 out of 99 (15%) presented the JAK2V617F mutation. None of the JAK2V617F-negative patients have developed signs of a myeloproliferative neoplasm during follow-up.
Our findings suggest that JAK2V617F occurs in a high proportion of patients with splanchnic vein thrombosis, and reinforces the diagnostic utility of JAK2V617F testing in this setting.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23:2224–2232.
Anger BR, Seifried E, Scheppach J, Heimpel H. Budd-Chiari syndrome and thrombosis of other abdominal vessels in the chronic myeloproliferative diseases. Klin Wochenschr. 1989;67:818–825.
Bazzan M, Tamponi G, Schinco P, et al. Thrombosis-free survival and life expectancy in 187 consecutive patients with essential thrombocythemia. Ann Hematol. 1999;78:539–543.
Denninger MH, Chaït Y, Casadevall N, et al. Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology. 2000;31:587–591.
Janssen HLA, Meinardi JR, Vleggaar FP, et al. Factor V 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. 2000;96:2364–2368.
Valla D. Hepatic vein thrombosis (Budd-Chiari Syndrome). Semin Liver Dis. 2002;22:5–14.
Primignani M, Martinelli I, Bucciarelli P, et al. Risk factors for thrombophilia in extrahepatic portal vein obstruction. Hepatology. 2005;41:603–608.
Chait Y, Condat B, Cazals-Hatem D, et al. Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br J Haematol. 2005;129:553–560.
Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. 2002;100:4272–4290.
Thurmes PJ, Steensma DP. Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis. Eur J Haematol. 2006;77:57–60.
Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054–1061.
James C, Ugo V, Le-Couédic J-P, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144–1148.
Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and agnogenic myeloid metaplasia. Cancer Cell. 2005;7:387–397.
Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–1790.
Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006;107:4214–4222.
Smith CA, Fan G. The saga of JAK2 mutations and translocations in hematologic disorders: pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms. Hum Pathol. 2008;39:795–810.
De Stefano V, Fiorini A, Rossi E, et al. Incidence of the JAK2V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost. 2007;5:708–714.
Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. 2006;130:2031–2038.
Primignani M, Barosi G, Bergamaschi G, et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006;44:1528–1534.
Goulding C, Uttenthal B, Foroni L, et al. The JAK2 V617F tyrosine kinase mutation identifies clinically latent myeloproliferative disorders in patients presenting with hepatic or portal vein thrombosis. Int J Lab Haematol. 2008;30:415–419.
Regina S, Herault O, D’Alteroche L, Binet C, Gruel Y. JAK2 V617F is specifically associated with idiopathic splanchnic vein thrombosis. J Thromb Haemost. 2007;5:859–861.
Remacha AF, Estivill C, Sarda MP, et al. The V617F mutation of JAK2 is very uncommon in patients with thrombosis. Haematologica. 2007;92:285–286.
Pardanani A, Lasho TL, Morice WG, Pruthi RK, Tefferi A. JAK2V617F is infrequently associated with arterial stroke in the absence of overt myeloproliferative disorder. J Thromb Haemost. 2007;5:1784–1785.
Colaizzo D, Amitrano L, Iannaccone L, et al. Gain-of-function gene mutations and venous thromboembolism: distinct roles in different clinical settings. J Med Genet. 2007;44:412–416.
Pardanani A, Lasho TL, Hussein K, et al. JAK2V617F mutation screening as part of the hypercoagulable work-up in the absence of splanchnic venous thrombosis or overt myeloproliferative neoplasm: assessment of value in a series of 664 consecutive patients. Mayo Clin Proc. 2008;83:457–459.
Xavier SG, Gadelha T, Schaffel R, et al. Low prevalence of the JAK2V617F in patients with ischemic stroke or cerebral venous thrombosis. Blood Coagul Fibrinolysis. 2008;19:468–469.
Pierre R, Imbert M, Thiele J, et al. WHO classification of the chronic myeloproliferative diseases (CMPD) polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia and CMPD unclassifiable. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours, vol. 3. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:32–44.
Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110:1092–1097.
Newton CR, Graham A, Heptinstall LE, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res. 1989;17:2503–2516.
Bonamino M, Gomes F, Guimarães-Sternberg C, et al. Qualitative and Quantitative Analysis of JAK2V617F Mutations Unravels Higher Responsiveness of JAK2 + ET Patients Treated with Hydroxyurea. 14th Congress of the EHA, 2009, abstract 1790 (ahead of print).
Jones AV, Kreil S, Zoi K, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood. 2005;106:2162–2168.
Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999;353:1167–1173.
Primignani M, Mannucci PM. The role of thrombophilia in splanchnic vein thrombosis. Semin Liver Dis. 2008;28:293–301.
De Stefano V, Teofili L, Leone G, Michiels JJ. 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. 1997;23:411–418.
Fimognari FL, Violi F. Portal vein thrombosis in liver cirrhosis. Intern Emerg Med. 2008;3:213–218.
Colaizzo D, Amitrano L, Tiscia GL, et al. The JAK2V617F mutation frequently occurs in patients with portal and mesenteric venous thrombosis. J Thromb Haemost. 2007;5:55–61.
Kiladjian JJ, Cervantes F, Leebeek FWG, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008;11:4922–4929.
Bayraktar Y, Harmanci O, Büyükasik Y, et al. JAK2V617F mutation in patients with portal vein thrombosis. Dig Dis Sci. 2008;53:2778–2783.
Landolfi R, Di Gennaro L, Falanga A. Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation. Leukemia. 2008;22:2020–2028.
Sozer S, Fiel MI, Schiano T, Xu M, Mascarenhas J, Hoffman R. The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome. Blood. 2009;113:5246–5249.
Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med. 2006;355:2452–2466.
Barosi G, Bergamaschi G, Marchetti M, et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood. 2007;110:4030–4036.
Vannucchi AM, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia. 2008;22:1299–1307.
McMahon C, Abu-Elmagd K, Bontempo FA, Kant JA, Swerdlow SH. JAK2 V617F mutation in patients with catastrophic intra-abdominal thromboses. Am J Clin Pathol. 2007;127:736–743.
De Stefano V, Fiorini A, Rossi E, et al. High prevalence of the JAK2 V617F mutation in patients with extrahepatic portal vein thrombosis. Hepatology. 2007;45:831–832.
Boissinot M, Lippert E, Girodon F, et al. Latent myeloproliferative disorder revealed by the JAK2–V617F mutation and endogenous megakaryocytic colonies in patients with splanchnic vein thrombosis. Blood. 2006;108:3223–3224.
Nelson Spector is supported by grants from Faperj and CNPq. Ilana Renault Zalcberg is supported by grants from the Swiss Bridge Foundation.
About this article
Cite this article
Xavier, S.G., Gadelha, T., Pimenta, G. et al. JAK2V617F Mutation in Patients with Splanchnic Vein Thrombosis. Dig Dis Sci 55, 1770–1777 (2010). https://doi.org/10.1007/s10620-009-0933-y