Internal and Emergency Medicine

, Volume 5, Issue 5, pp 375–384 | Cite as

Polycythemia vera

  • Raffaele Landolfi
  • Maria Anna Nicolazzi
  • Angelo Porfidia
  • Leonardo Di Gennaro
IM - Review


The diagnostic approach to a patient with polycythemia has been greatly simplified by the introduction of new genetic testing in addition to traditional tests, such as measurement of red cell mass and serum erythropoietin (Epo) level. Clonal erythrocytosis, which is the diagnostic feature of polycythemia vera (PV), is almost always associated with a JAK2 mutation (JAK2V617F or exon 12). Therefore, in a patient with acquired erythrocytosis, it is reasonable to begin the diagnostic work-up with JAK2 mutation analysis to distinguish PV from secondary erythrocytosis. The clinical course of PV is marked by a high incidence of thrombotic complications that represent the main cause of morbidity and mortality in these patients. Blood hyperviscosity as well as platelet and leukocyte quantitative, and qualitative abnormalities play a major role in the pathogenesis of thrombophilia. Prevention of vascular events and minimizing the risk of disease transition into acute leukaemia are the main targets of the whole PV treatment strategy. This can rely on the use of low-dose aspirin in most patients, while the choice of the optimal cytoreductive strategy is based on the individual vascular risk. Phlebotomy is still the preferred treatment in subjects at low risk, while hydroxyurea or pipobroman is usually administered to most elderly subjects or subjects with a previous vascular history. The use of pegylated interferon, imatinib, and JAK2 inhibitors is currently being evaluated.


Polycythemia Polycythemia vera Myeloproliferative disease Thrombosis JAK2 mutation 


Conflict of interest



  1. 1.
    Tefferi A, Thiele J, Orazi A et al (2007) 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 110:1092–1097CrossRefPubMedGoogle Scholar
  2. 2.
    Tefferi A, Vardiman JW (2008) Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22:14–22CrossRefPubMedGoogle Scholar
  3. 3.
    Spanoudakis E, Tsatalas C (2009) Hemopoiesis in Ph-negative chronic myeloproliferative disorders. Curr Stem Cell Res Ther 4:154–160CrossRefPubMedGoogle Scholar
  4. 4.
    Vannucchi AM, Guglielmelli P, Tefferi A (2009) Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin 59:171–191CrossRefPubMedGoogle Scholar
  5. 5.
    Spivak JL (2004) The chronic myeloproliferative disorders: clonality and clinical heterogeneity. Semin Hematol 41:1–5CrossRefPubMedGoogle Scholar
  6. 6.
    Fabris F, Randi ML (2009) Essential thrombocythemia: past and present. Intern Emerg Med 4:381–388CrossRefPubMedGoogle Scholar
  7. 7.
    Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S, Dupriez B, Levine RL, Passamonti F, Gotlib J, Reilly JT, Vannucchi AM, Hanson CA, Solberg LA, Orazi A, Tefferi A, International Working Group for Myelofibrosis Research, Treatment (IWG-MRT) (2008) Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 22:437–438CrossRefPubMedGoogle Scholar
  8. 8.
    Patnaik MM, Tefferi A (2009) The complete evaluation of erythrocytosis: congenital and acquired. Leukemia 23:834–844CrossRefPubMedGoogle Scholar
  9. 9.
    Vaquez H (1895) Sur une forme speciale de cyanose s’accompanant d’hyperglobulie excessive et peristente (On a special form of cyanosis accompanied by excessive and persistent erythrocytosis). Compt rend Soc de biol and suppl note. Bull et mem Soc med d’hop de Paris 12:60Google Scholar
  10. 10.
    Cabot RC (1900) A second case of chronic cyanosis without assignable cause. Boston Med Surg J 142:275Google Scholar
  11. 11.
    Osler W (1908) A clinical lecture on erythraemia (polycythaemia with cyanosis, maladie de Vaquez). Lancet 1:143–146Google Scholar
  12. 12.
    Wasserman LR (1986) Polycythemia Vera Study Group: a historical perspective. Semin Hematol 23:183–187PubMedGoogle Scholar
  13. 13.
    James C, Ugo V, Le Couédic JP et al (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148CrossRefPubMedGoogle Scholar
  14. 14.
    Kralovics R, Passamonti F, Buser AS et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790CrossRefPubMedGoogle Scholar
  15. 15.
    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, Project Cancer Genome (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061PubMedGoogle Scholar
  16. 16.
    Levine RL, Wadleigh M, Cools J et al (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397CrossRefPubMedGoogle Scholar
  17. 17.
    Vannucchi AM (2009) Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia. Intern Emerg Med [Epub ahead of print]Google Scholar
  18. 18.
    Zanjani ED, Lutton JD, Hoffman R, Wasserman LR (1977) Erythroid colony formation by polycythemia vera bone marrow in vitro. Dependence on erythropoietin. J Clin Invest 59:841CrossRefPubMedGoogle Scholar
  19. 19.
    Skoda R, Prchal JT (2005) Lessons from familial myeloproliferative disorders. Semin Hematol 42:266–273CrossRefPubMedGoogle Scholar
  20. 20.
    Scott LM, Tong W, Levine RL et al (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356:459–468CrossRefPubMedGoogle Scholar
  21. 21.
    Pardanani AD, Levine RL, Lasho T et al (2006) MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 108:3472–3476CrossRefPubMedGoogle Scholar
  22. 22.
    Delhommeau F, Dupont S, Della Valle V et al (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 360:2289–2301CrossRefPubMedGoogle Scholar
  23. 23.
    Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, Edwards BK, List AF (2008) Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004: utilizing data from the NAACCR and SEER programs. Blood 112:45–52CrossRefPubMedGoogle Scholar
  24. 24.
    Cervantes F, Passamonti F, Barosi G (2008) Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 22:905–914CrossRefPubMedGoogle Scholar
  25. 25.
    Marchioli R, Finazzi G, Landolfi R et al (2005) Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23:2224–2232CrossRefPubMedGoogle Scholar
  26. 26.
    Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T, European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators (2004) Efficacy and safety of low dose aspirin in polycythemia vera. N Engl J Med 350:114–124CrossRefPubMedGoogle Scholar
  27. 27.
    Prchal JT (2003) Classification and molecular biology of polycythemias (erythrocytoses) and thrombocytosis. Hematol Oncol Clin North Am 17:1151CrossRefPubMedGoogle Scholar
  28. 28.
    Pieri L, Bogani C, Guglielmelli P et al (2009) The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera. Haematologica 94:1537–1545CrossRefPubMedGoogle Scholar
  29. 29.
    Ishii T, Wang J, Zhang W et al (2009) Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders. Blood 113:5942–5950PubMedGoogle Scholar
  30. 30.
    Torgano G, Mandelli C, Massaro P, Abbiati C (2002) Gastroduodenal lesions in polycythaemia vera: frequency and role of Helicobacter pylori. Br J Haematol 117:198CrossRefPubMedGoogle Scholar
  31. 31.
    Michiels JJ, Berneman Z, Bockstaele DV et al (2006) Clinical and laboratory features, pathology of platelet-mediated thrombosis and bleeding complications and the molecular etiology of essential thrombocythemia and polycythemia vera: therapeutic implications. Semin Thromb Hemost 32:174–207CrossRefPubMedGoogle Scholar
  32. 32.
    Gruppo Italiano Studio Policitemia (1995) Polycythemia vera: the natural history of 1213 patients followed for 20 years. Ann Intern Med 123:656–664Google Scholar
  33. 33.
    Passamonti F, Brusamolino E, Lazzarino M et al (2000) Efficacy of pipobroman in the treatment of polycythemia vera: long-term results in 163 patients. Haematologica 85:1011–1018PubMedGoogle Scholar
  34. 34.
    Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A (2007) Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol 138:354–358CrossRefPubMedGoogle Scholar
  35. 35.
    De Stefano V, Fiorini A, Rossi E et al (2007) Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 5:708–714CrossRefPubMedGoogle Scholar
  36. 36.
    Briere JB (2006) Budd–Chiari Syndrome and portal vein thrombosis associated with myeloproliferative disorders: diagnosis and management. Semin Haemost Thrombosis 32:208–218CrossRefGoogle Scholar
  37. 37.
    Ugo V, Le Gal G, Lecucq L, Mottier D, Oger E, Collaborative Study Group EDITH (2008) Prevalence of the JAK2 V617F mutation is low among unselected patients with a first episode of unprovoked venous thromboembolism. J Thromb Haemost 6:203–205CrossRefPubMedGoogle Scholar
  38. 38.
    Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, Tognoni G, Marchioli R, European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) (2007) Leukocytosis as a major thrombotic risk factor in patients with Polycythemia Vera. Blood 109:2446–2452CrossRefPubMedGoogle Scholar
  39. 39.
    Barbui T, Carobbio A, Rambaldi A, Finazzi G (2008) Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Leukemia 22:1494–1502CrossRefPubMedGoogle Scholar
  40. 40.
    De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E, Micò C, Tieghi A, Cacciola RR, Santoro C, Gerli G, Guglielmelli P, Pieri L, Scognamiglio F, Rodeghiero F, Pogliani EM, Finazzi G, Gugliotta L, Leone G, Barbui T, GIMEMA Chronic Myeloproliferative Neoplasms Working Party (2010) Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia. Am J Hematol 85:97–100PubMedGoogle Scholar
  41. 41.
    Landolfi R, Di Gennaro L, Falanga A (2008) Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation. Leukemia 22:2020–2028CrossRefPubMedGoogle Scholar
  42. 42.
    Landolfi R, Ciabattoni G, Patrignani P et al (1992) Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo. Blood 80:1965PubMedGoogle Scholar
  43. 43.
    Carobbio A, Finazzi G, Antonioli E et al (2009) JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera. Exp Hematol 37:1016–1021CrossRefPubMedGoogle Scholar
  44. 44.
    Tartaglia A, Goldberg J, Berk P, Wasserman L (1986) Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol 23:172–176PubMedGoogle Scholar
  45. 45.
    Landolfi R, Cipriani MC, Novarese L (2006) Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: pathogenetic mechanisms and prevention. Best Pract Res Clin Haematol 19:617–633CrossRefPubMedGoogle Scholar
  46. 46.
    Patrono C, Garcia Rodriguez L, Landolfi R, Baigent C (2005) Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 353:2373–2383CrossRefPubMedGoogle Scholar
  47. 47.
    Alvarez-Larrán A, Bellosillo B, Martínez-Avilés L et al (2009) Postpolycythaemic myelofibrosis: frequency and risk factors for this complication in 116 patients. Br J Haematol 146:504–509CrossRefPubMedGoogle Scholar
  48. 48.
    Finazzi G, Caruso V, Marchioli R, Capnist G, Chisesi T, Finelli C, Gugliotta L, Landolfi R, Kutti J, Gisslinger H, Marilus R, Patrono C, Pogliani EM, Randi ML, Villegas A, Tognoni G, Barbui T, ECLAP Investigators (2005) Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood 105:2664–2670CrossRefPubMedGoogle Scholar
  49. 49.
    Finazzi G, Barbui T (2007) The treatment of polycythaemia vera: an update in the JAK2 era. Intern Emerg Med 2:13–18CrossRefPubMedGoogle Scholar
  50. 50.
    Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD (1995) Treatment of polycythemia vera: a summary of clinical trials conducted by the Polycythemia Vera Study Group. In: Wasserman LR, Berk PD, Berlin NI (eds) Polycythemia vera and the myeloproliferative disorders. WB Saunders, Philadelphia, p 166Google Scholar
  51. 51.
    Najean Y, Rain J-D (1997) The very long term evolution of polycythemia vera: an analysis of 318 patients initially treated by phlebotomy or 32P between 1969 and 1981. Semin Hematol 34:6–16PubMedGoogle Scholar
  52. 52.
    Messinezy M, Pearson TC (1995) Incidence of myelofibrosis following treatment of primary polycythaemia by venesection. Br J Haematol 89:228–230PubMedGoogle Scholar
  53. 53.
    Silver RT (1988) Recombinant interferon-alpha for treatment of polycythaemia vera. Lancet 2:403CrossRefPubMedGoogle Scholar
  54. 54.
    Kiladjian JJ, Chomienne C, Fenaux P (2008) Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms. Leukemia 22:1990CrossRefPubMedGoogle Scholar
  55. 55.
    Anagrelide Study Group (1992) Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Am J Med 92:69–76CrossRefGoogle Scholar
  56. 56.
    Gruppo Italiano Studio Policitemia (1997) Low-dose aspirin in polycythaemia vera: a pilot study. Br J Haematol 97:453–456CrossRefGoogle Scholar
  57. 57.
    Barosi G, Rosti V (2009) Novel strategies for patients with chronic myeloproliferative disorders. Curr Opin Hematol 16:129–134CrossRefPubMedGoogle Scholar
  58. 58.
    Gaikwad A, Verstovsek S, Yoon D, Chang KT, Manshouri T, Nussenzveig R, Cortes J, Vainchenker W, Prchal JT (2007) Imatinib effect on growth and signal transduction in polycythemia vera. Exp Hematol 35:931–938CrossRefPubMedGoogle Scholar
  59. 59.
    Reiter A, Walz C, Cross NC (2007) Tyrosine kinases as therapeutic targets in BCR-ABL negative chronic myeloproliferative disorders. Curr Drug Targets 8:205–216CrossRefPubMedGoogle Scholar
  60. 60.
    Levine RL, Pardanani A, Tefferi A, Gilliland DG (2007) Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer 7:673–683CrossRefPubMedGoogle Scholar

Copyright information

© SIMI 2010

Authors and Affiliations

  • Raffaele Landolfi
    • 1
  • Maria Anna Nicolazzi
    • 1
  • Angelo Porfidia
    • 1
  • Leonardo Di Gennaro
    • 1
  1. 1.Institute of Internal Medicine and Geriatrics, Haemostasis Research CenterCatholic University School of MedicineRomeItaly

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