Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • How to Manage…
  • Published:

How to Manage…

How to manage essential thrombocythemia

Leukemia volume 26, pages 875–882 (2012)Cite this article

Abstract

I use the hematological, morphological and molecular criteria recently established by the World Health Organization to diagnose essential thrombocytemia. In these patients, major causes of morbidity and mortality are represented by thrombosis and bleeding, whereas progression to myelofibrosis and transformation to acute leukemia are more rare. Myelosuppressive therapy can reduce the rate of vascular complications, but there is some concern about treatment-related toxicity. Therefore, I follow a risk-oriented therapeutic approach to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established predictors of cardiovascular events are represented by older age and previous thrombosis, whereas recent data suggest a prognostic role for novel risk factors, including leukocytosis and JAK2V617F mutational status. There is no indication for therapeutic intervention in asymptomatic, low-risk patients, while I treat high-risk patients with hydroxyurea (HU) first. Other therapeutic options, such as interferon alpha or anagrelide, may find place in selected patients including those who are resistant or intolerant to HU. I follow a risk-oriented approach also for management of pregnancy. Low-risk women are given low-dose aspirin throughout pregnancy and prophylactic low-molecular-weight heparin (LMWH) post partum, whereas LMWH throughout pregnancy and/or interferon-alpha can be required in high-risk cases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011; 29: 3179–3184.

    Article  Google Scholar 

  2. Cortelazzo S, Viero P, Finazzi G, D'Emilio A, Rodeghiero F, Barbui T . Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 1990; 8: 556–562.

    Article  CAS  Google Scholar 

  3. Tefferi A, Vainchenker W . Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 2011; 29: 573–582.

    Article  CAS  Google Scholar 

  4. Thiele J, Kvasnicka HM, Orazi A . Bone marrow histopathology in myeloproliferative disorders–current diagnostic approach. Semin Hematol 2005; 42: 184–195.

    Article  Google Scholar 

  5. Finazzi G, Barbui T . Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia 2008; 22: 1494–1502.

    Article  CAS  Google Scholar 

  6. Finazzi G, Hu M, Barbui T, Hoffman R . Essential thrombocythemia. In: Hoffman R, Benz Jr EJ, Shattil SJ, Furie B, Silberstein LE, McGlave P, Heslop H (eds). Hematology Basic Principles and Practice, 5th edn Churchill Livingstone: Philadelphia, 2009, pp 1149–1166.

    Google Scholar 

  7. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA 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.

    Article  CAS  Google Scholar 

  8. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ et al. JAK2 V617F mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005; 131: 208–213.

    Article  CAS  Google Scholar 

  9. Thiele J, Kvasnicka HM, Müllauer L, Buxhofer-Ausch V, Gisslinger B, Gisslinger H . Essential thrombocythemia versus early primary myelofibrosis: a multicenter study to validate the WHO classification. Blood 2011; 117: 5710–5718.

    Article  CAS  Google Scholar 

  10. Schmitt-Graeff AH, Teo SS, Olschewski M, Schaub F, Haxelmans S, Kirn A et al. JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica 2008; 93: 34–40.

    Article  CAS  Google Scholar 

  11. Wilkins BS, Erber WN, Bareford D, Buck G, Wheatley K, East CL et al. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood 2008; 111: 60–70.

    Article  CAS  Google Scholar 

  12. Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011; 29: 761–770.

    Article  Google Scholar 

  13. Barbui T, Barosi G, Grossi A, Gugliotta L, Liberato LN, Marchetti M et al. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. Haematologica 2004; 89: 215–222.

    CAS  PubMed  Google Scholar 

  14. Elliott MA, Tefferi A . Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2004; 128: 275–290.

    Article  Google Scholar 

  15. Michiels JJ, Abels J, Steketee J, van Vliet HH, Vuzevski VD . Erythromelalgia caused by platelet mediated arteriolar inflammation and thrombosis in thrombocythemia. Ann Intern Med 1985; 102: 466–471.

    Article  CAS  Google Scholar 

  16. Mitus AJ, Barbui T, Shulman LN, Rosenthal DS, Viero P, Cortelazzo S et al. Hemostatic complications in young patients with essential thrombocythemia. Am J Med 1990; 88: 371–375.

    Article  CAS  Google Scholar 

  17. Ruggeri M, Finazzi G, Tosetto A, Riva S, Rodeghiero F, Barbui T . No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol 1998; 103: 772–777.

    Article  CAS  Google Scholar 

  18. Tefferi A, Gangat N, Wolanskyj AP . Management of extreme thrombocytosis in otherwise low-risk essential thrombocythemia: does number matter? Blood 2006; 108: 2493–2494.

    Article  CAS  Google Scholar 

  19. van Genderen PJJ, Budde A, Michiels JJ, van Strik R, van Vliet HH . The reduction of large von Willebrand factor multimers in plasma in essential thrombocythemia is related to the platelet count. Br J Haematol 1996; 93: 962–965.

    Article  CAS  Google Scholar 

  20. Barbui T, Carobbio A, Rambaldi A, Finazzi G . Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood 2009; 114: 759–763.

    CAS  PubMed  Google Scholar 

  21. Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A . Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc 2006; 81: 159–166.

    Article  Google Scholar 

  22. Carobbio A, Finazzi G, Guerini V, Spinelli O, Delaini F, Marchioli R et al. Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors and JAK2 mutation status. Blood 2007; 109: 2310–2313.

    Article  CAS  Google Scholar 

  23. Palandri F, Polverelli N, Catani L, Ottaviani E, Baccarani M, Vianelli N . Impact of leukocytosis on thrombotic risk and survival in 532 patients with essential thrombocythemia: a retrospective study. Ann Hematol 2011; 90: 933–938.

    Article  Google Scholar 

  24. Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. J Clin Oncol 2008; 26: 2732–2736.

    Article  CAS  Google Scholar 

  25. Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood 2007; 109: 2446–2452.

    Article  CAS  Google Scholar 

  26. Gangat N, Wolanskyj AP, Schwager SM, Hanson CA, Tefferi A . Leukocytosis at diagnosis and the risk of subsequent thrombosis in patients with low-risk essential thrombocythemia and polycythemia vera. Cancer 2009; 115: 5740–5745.

    Article  Google Scholar 

  27. Passamonti F, Rumi E, Pascutto C, Cazzola M, Lazzarino M . Increase in leukocyte count over time predicts thrombosis in patients with low-risk essential thrombocythemia. J Thromb Haemost 2009; 7: 1587–1589.

    Article  CAS  Google Scholar 

  28. Arellano-Rodrigo E, Alvarez-Larran A, Reverter JC, Villamor N, Colomer D, Cervantes F . Increased platelet and leukocyte activation as contributing mechanisms for thrombosis in essential thrombocythemia and correlation with the JAK2 mutational status. Haematologica 2006; 91: 169–175.

    CAS  PubMed  Google Scholar 

  29. Marchetti M, Castoldi E, Spronk HM, van Oerle R, Balducci D, Barbui T et al. Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera. Blood 2008; 112: 4061–4068.

    Article  CAS  Google Scholar 

  30. Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005; 366: 1945–1953.

    Article  CAS  Google Scholar 

  31. Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C . The presence of the JAK2 V617F mutation is associated with higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol 2005; 132: 244–250.

    Article  Google Scholar 

  32. Finazzi G, Rambaldi A, Guerini V, Carobbio A, Barbui T . Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F status. Haematologica 2007; 92: 135–136.

    Article  Google Scholar 

  33. Antonioli E, Guglielmelli P, Pancrazzi A, Bogani C, Verrucci M, Ponziani V et al. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005; 19: 1847–1849.

    Article  CAS  Google Scholar 

  34. Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Büller HR, Cattaneo M . Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythemia or idiopathic myelofibrosis: a systematic review. Thromb Res 2009; 124: 409–417.

    Article  CAS  Google Scholar 

  35. De Stefano V, Za T, Rossi E, Vannucchi AM, Ruggeri M, Elli E et al. Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation. Ann Hematol 2010; 85: 97–100.

    Google Scholar 

  36. Campbell PJ, Bareford D, Erber WN, Wilkins BS, Wright P, Buck G et al. Reticulin accumulation in essential thrombocythemia: prognostic significance and relation to therapy. J Clin Oncol 2009; 27: 2991–2999.

    Article  CAS  Google Scholar 

  37. Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M et al. Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008-WHO-criteria. Leukemia; e-pub ahead of print 16 September 2011.

  38. Barbui T, Carobbio A, Finazzi G, Vannucchi AM, Barosi G, Antonioli E et al. Inflammation and thrombosis in essential thrombocythemia and polycythemia vera: different role of C-reactive protein and pentraxin 3. Haematologica 2011; 96: 315–318.

    Article  CAS  Google Scholar 

  39. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A . Circulating interleukin (IL)-8, IL-2R, IL-12 and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 2011; 29: 1356–1363.

    Article  CAS  Google Scholar 

  40. Tefferi A, Fonseca R, Pereira D, Hoagland HC . A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc 2001; 76: 22–28.

    Article  CAS  Google Scholar 

  41. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004; 350: 114–124.

    Article  CAS  Google Scholar 

  42. Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005; 353: 33–45.

    Article  CAS  Google Scholar 

  43. Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, Pérez-Andreu V, Hernández-Boluda JC et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 2010; 116: 1205–1210.

    Article  CAS  Google Scholar 

  44. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F et al. Hydroxyurea in the treatment of patients with essential thrombocythemia at high risk of thrombosis: a prospective randomized trial. N Engl J Med 1995; 332: 1132–1136.

    Article  CAS  Google Scholar 

  45. Maugeri N, Giordano G, Petrilli MP, Fraticelli V, de Gaetano G, Cerletti C et al. Inhibition of tissue factor expression by hydroxyurea in polimorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug? J Thromb Haemost 2006; 4: 2593–2598.

    Article  CAS  Google Scholar 

  46. Sterkers Y, Preudhomme C, Laï JL, Demory JL, Caulier MT, Wattel E et al. Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998; 91: 616–622.

    CAS  PubMed  Google Scholar 

  47. Finazzi G, Ruggeri M, Rodeghiero F, Barbui T . Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis. Blood 2003; 101: 3749.

    Article  CAS  Google Scholar 

  48. Bjorkholm J, Derolf AR, Ekstrand C, Kristinsson SY, Ekstrand C, Goldin LR et al. Clinical risk for AML/MDS transformation in Philadelphia negative chronic myeloproliferative neoplasms. A population-based nested case-control study in Sweden. J Clin Oncol 2011; 29: 2410–2415.

    Article  Google Scholar 

  49. Lanzkron S, Strouse JJ, Wilson R, Beach MC, Haywood C, Park H et al. Systematic review: hydroxyurea for the treatment of adults with sickle cell disease. Ann Intern Med 2008; 148: 939–955.

    Article  Google Scholar 

  50. Barosi G, Besses C, Birgegard G, Briere J, Cervantes F, Finazzi G et al. A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group. Leukemia 2007; 21: 277–280.

    Article  CAS  Google Scholar 

  51. Silver RT . Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer 2006; 107: 451–458.

    Article  CAS  Google Scholar 

  52. Lengfelder E, Griesshammer M, Hehlmann R . Interferon-alpha in the treatment of essential thrombocythemia. Leuk Lymphoma 1996; 22 (Suppl.1): 135–142.

    Article  Google Scholar 

  53. Harrison C . Pregnancy and its management in the Philadelphia negative myeloproliferative diseases. Br J Haematol 2005; 129: 293–306.

    Article  CAS  Google Scholar 

  54. Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M et al. Pegylated interferon alpha-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008; 112: 3065–3072.

    Article  CAS  Google Scholar 

  55. Samuelsson J, Mutschler M, Birgegard G, Gram-Hansen P, Björkholm M, Pahl HL . Limited effects on JAK2 mutational status after pegylated interferon alpha-2b therapy in polycythemia vera and essential thrombocythemia. Haematologica 2006; 91: 1281–1282.

    PubMed  Google Scholar 

  56. Quintas-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S et al. Pegylated interferon alpha-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009; 27: 5418–5424.

    Article  CAS  Google Scholar 

  57. Fruchtman SM, Petitt RM, Gilbert HS, Fiddler G, Lyne A . Anagrelide: analysis of long term efficacy, safety and leukemogenic potential in myeloproliferative diseases. Leuk Res 2005; 5: 481–491.

    Article  Google Scholar 

  58. Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM et al. Final results of the ANAHYDRET study: non-inferiority of anagrelide compared to hydroxyurea in newly diagnosed WHO essential thrombocythemia patients. Blood 2008; 112, (abstract 661).

  59. Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Levy R et al. Durable Responses with the JAK1/ JAK2 Inhibitor, INCB018424, in patients with polycythemia vera (PV) and essential thrombocythemia (ET) refractory or intolerant to hydroxyurea (HU). Blood 2010; 116, (abstract 313).

  60. Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 2009; 113: 4829–4833.

    Article  CAS  Google Scholar 

  61. Tefferi A, Passamonti F . Essential thrombocyythemia and pregnancy: observations from recent studies and management recommenadtions. Am J Hematol 2009; 84: 629–630.

    Article  Google Scholar 

  62. Besses C, Cervantes F, Pereira A, Florensa L, Solé F, Hernández-Boluda JC et al. Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia 1999; 13: 150–154.

    Article  CAS  Google Scholar 

  63. Colombi M, Radaelli F, Zocchi L, Maiolo AT . Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer 1991; 67: 2926–2930.

    Article  CAS  Google Scholar 

  64. Jantunen R, Juvonen E, Ikkala E, Oksanen K, Anttila P, Ruutu T . The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia. Ann Hematol 2001; 80: 74–78.

    Article  CAS  Google Scholar 

  65. Bazzan M, Tamponi G, Schinco P, Vaccarino A, Foli C, Gallone G et al. Thrombosis-free survival and life expectancy in 187 consecutive patients with essential thrombocythemia. Ann Hematol 1999; 78: 539–543.

    Article  CAS  Google Scholar 

  66. Passamonti F, Rumi E, Arcaini L, Boveri E, Elena C, Pietra D et al. Prognostic factors for thrombosis, myelofibrosis and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica 2008; 93: 1645–1651.

    Article  Google Scholar 

  67. van Genderen PJJ, Michiels JJ . Erythromelalgic, thrombotic and hemorrhagic manifestations of thrombocythaemia. Presse Med 1994; 23: 73–77.

    CAS  PubMed  Google Scholar 

  68. Fenaux P, Simon M, Caulier MT, Lai JL, Goudemand J, Bauters F . Clinical course of essential thrombocythemia in 147 cases. Cancer 1990; 66: 549–556.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy

    G Finazzi

Authors
  1. G Finazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G Finazzi.

Ethics declarations

Competing interests

The author declares no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Finazzi, G. How to manage essential thrombocythemia. Leukemia 26, 875–882 (2012). https://doi.org/10.1038/leu.2011.306

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.306

Keywords

This article is cited by

Search

Advanced search

Quick links