Skip to main content

Advertisement

SpringerLink
Log in

Essential thrombocythemia: past and present

  • IM - Review
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained increase in platelet number and tendency for thromboembolism. A somatic point mutation that causes a constitutive activation of the JAK2 gene is found in one in two ET patients. ET is more common in women, its incidence being 0.6–2.5/100,000 patient/year and the median age at diagnosis is 65–70 years. ET can affect all age groups, including children (0.09 cases/year), and is often diagnosed in the third–fourth decade of life. Rare cases of familial ET have been reported. Miscarriages are 3–4 times more common among women with ET than in the general population, especially in patients carrying JAK2V617F. Microvascular disturbances are typical of ET, but a major thrombosis (2/3 arterial and 1/3 venous; 1, 2–3% patient/year) is the main cause of morbidity and mortality. Age over 60 years and/or previous thrombosis are validated risk factor for thrombosis. Hemorrhages occur in 0.33% patient/year, mainly in those with a platelet count over 1,500 × 109/L. Progression to myelofibrosis and leukemia is more common in patients carrying the JAK2V617F mutation, and is estimated to occur in 0.16% and 0.12% patient/year, respectively. The ET-related mortality ratio with respect to the general population is 1:1, while for polycythemia vera it is 1.6:1. Low-dose aspirin is useful for microvascular disturbances, and in the primary and secondary prevention of major thrombosis in high-risk patients, but it is not recommended in patients with a platelet count over 1,500 × 109/L. Hydroxyurea is used as first-line treatment in high-risk patients. Other drugs available are alpha-interferon, anagrelide, pipobroman and busulphan.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Epstein E, Goedel A (1934) Hemorrhagische Thrombozythamie bei vascularer Schrumpfmilz (Hemorrhagic thrombocythemia with a vascular, sclerotic spleen). Virchows Archiv Pathos Anat Histopathol 293:233–248

    Article  Google Scholar 

  2. Fanger H, Lj CellaJr, Litchman H (1954) Thrombocythemia: report of three cases and review of literature. N Engl J Med 250:456–461

    Article  PubMed  CAS  Google Scholar 

  3. Gunz FW (1960) Hemorrhagic thrombocythemia: a critical review. Blood 15:706–723

    PubMed  CAS  Google Scholar 

  4. Ozer FL, Traux WE, Miesch DC et al (1960) Primary hemorrhagic thrombocythemia. Am J Med 28:807–823

    Article  PubMed  CAS  Google Scholar 

  5. Dameshek W (1951) Some speculation on the myeloproliferative syndromes. Blood 6:372–375

    PubMed  CAS  Google Scholar 

  6. Fialkow PJ, Faguet GB, Jacobson RJ et al (1981) Evidence that essential thrombocythemia is a clonal disorder with origin in multipotent stem cell. Blood 58:916–919

    PubMed  CAS  Google Scholar 

  7. Murphy S, Iland J, Rosenthal D et al (1986) Essential thrombocythemia: clinical and laboratory characteristics at presentation. Semin Hematol 23:177–192

    PubMed  CAS  Google Scholar 

  8. Vardiman JW, Harris NL, Brunning RD (2002) The world health organization (WHO) classification of the myeloid neoplasms. Blood 14:2202–2292

    Google Scholar 

  9. Levine RL, Belisle C, Wadleigh M et al (2006) X-inactivation based clonality analysis and quantitative JAK2V617F assessment reveals a strong association between clonality and JAK2V617F in PV but not ET/MMM and identifies a subset of JAK2V617F negative ET and MMM patients with clonal hematopoiesis. Blood 107:4139–4141

    Article  PubMed  CAS  Google Scholar 

  10. 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 7:387–397

    Article  PubMed  CAS  Google Scholar 

  11. Baxter EJ, Scott LM, Campbell PJ et al (2005) Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061

    PubMed  CAS  Google Scholar 

  12. Kralovics R, Teo SS, Buser AS et al (2005) Altered gene expression in myeloproliferative disorders correlates with activation of signalling by the V617F mutation of Jak2. Blood 106:3374–3376

    Article  PubMed  CAS  Google Scholar 

  13. James C, Ugo V, Le Couedic JP et al (2005) A unique clonal Jak2 mutation leading to constitutive signaling causes polycythemia vera. Nature 434:1144–1148

    Article  PubMed  CAS  Google Scholar 

  14. Zhao R, Xing S, Li Z et al (2005) Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem 280:22788–22792

    Article  PubMed  CAS  Google Scholar 

  15. Skoda R (2007) The genetic basis of myeloproliferative disorders. Hematology Am Soc Hematol 2007:1–10

  16. Wolanskyj AP, Lasho TL, Schawager SM et al (2005) JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 131:208–213

    Article  PubMed  CAS  Google Scholar 

  17. Campbell PJ, Scott LM, Buck G et al (2005) Definition of subtypes of essential thrombocythemia and relation to polycythemia vera based on Jak2 V617F mutation status: a prospective study. Lancet 366:1945–1953

    Article  PubMed  CAS  Google Scholar 

  18. Johansson P (2006) Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemostas 32:171–173

    Article  Google Scholar 

  19. Randi ML, Putti MC, Scapin M et al (2007) Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood 108:3600–3602

    Article  CAS  Google Scholar 

  20. Tefferi A, Thiele J, Orazi A et al (2007) Proposals and rationale of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 110:1092–1097

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Wilkins BS, Erber WN, Bareford D et al (2007) Bone marrow pathology in essential thrombocythemia: intra-observer reliability and utility for identifying disease subtypes. Blood 111:60–70

    Article  PubMed  CAS  Google Scholar 

  23. Elliott MA, Tefferi A (2005) Thrombosis and hemorrhage in polycythemia vera and essential thrombocythemia. Br J Haematol 128:275–290

    Article  PubMed  CAS  Google Scholar 

  24. Cervantes F, Passamonti F, Barosi G (2008) Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 22:905–914

    Article  PubMed  CAS  Google Scholar 

  25. Fabris F, Randi M, Casonato A et al (1980) Platelet aggregation and thrombopheresis in thrombocythemia. Thromb Haemostas 4:169

    Google Scholar 

  26. Carobbio A, Finazzi G, Guerini V et al (2007) Leucocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factor and JAK2 mutation status. Blood 109:2310–2313

    Article  PubMed  CAS  Google Scholar 

  27. Falanga A, Marchetti M, Evangelista V et al (2000) Polymorphonuclear leucocytes activation and hemostasis in patients with essential thrombocythemia and polycythemia vera. Blood 96:4261–4266

    PubMed  CAS  Google Scholar 

  28. Carobbio A, Finazzi G, Antonioli E et al (2008) Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia. Blood 112:3135–3137

    Article  PubMed  CAS  Google Scholar 

  29. Harrison CN, Campbell RJ, Buck G et al (2005) Hydroxyurea compared with anagrelide in high risk essential thrombocythemia. N Engl J Med 353:33–45

    Article  PubMed  CAS  Google Scholar 

  30. Vannucchi A, AM, Antonioli E, Guglielmelli P et al (2007) Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera and essential thrombocythemia. Blood 110:840–846

  31. Barbui T, Barosi G, Grossi A et al (2004) Practice guidelines for the therapy of essential thrombocythemia. Haematologica 89:15–232

    Google Scholar 

  32. Cortelazzo S, Viero P, Finazzi G et al (1990) Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 8:556–562

    PubMed  CAS  Google Scholar 

  33. Kiladijan JJ, Cervantes F, Leebeek FWG et al (2008) The impact of Jak2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis. A report on 241 cases. Blood 111:4922–4929

    Article  CAS  Google Scholar 

  34. Randi ML, Rossi C, Barbone E et al (1994) Superior sagittal sinus thrombosis in 5 patients with essential thrombocythemia: a possible disease variant. Rev Iberoam Tromb Hemostasia 7:76–78

    Google Scholar 

  35. Federici A, Rand JH, Mannucci PM (2001) Acquired von Willebrand syndrome: an important bleeding complication to be considered in patients with lymphoproliferative and myeloproliferative disorders. Hematol J 2:358–362

    Article  PubMed  CAS  Google Scholar 

  36. Passamonti F, Rumi E, Pungolino E et al (2004) Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med 117:755–761

    Google Scholar 

  37. Hasle H (2000) Incidence of essential thrombocythemia in children. Br J Haematol 110:751

    Article  PubMed  CAS  Google Scholar 

  38. Randi ML, Putti MC, Fabris F (2000) Features of essential thrombocythemia in childhood: study of five children. Br J Haematol 108:86–89

    Article  PubMed  CAS  Google Scholar 

  39. Dror Y, Zipursky A, Blanchette VS (1999) Essential thrombocythemia in children. J Ped Hematol Oncol 21:356–363

    Article  CAS  Google Scholar 

  40. Randi ML, Putti MC, Pacquola E (2004) Normal thrombopoietin and its receptor (c-mpl) genes in children with essential thrombocythemia. Pediatr Blood Cancer 43:1–4

    Article  Google Scholar 

  41. Randi ML, Putti MC (2004) Essential thrombocythemia in children: is a treatment needed? Exp Opin Pharmacother 5:1009–1014

    Article  Google Scholar 

  42. Passamonti F, Ml Randi, Rumi E et al (2007) Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the Jak2 (617V>F) mutation. Blood 110:485–489

    Article  PubMed  CAS  Google Scholar 

  43. Harrison C (2005) Essential thrombocythemia: challenges and evidence-based management. Br J Haematol 130:153–165

    Article  PubMed  Google Scholar 

  44. Griesshammer M, Bangerter M, van Vliet HH (1997) Aspirin in essential thrombocythemia: status quo and quo vadis. Semin Thromb Hemostas 23:371–377

    Article  CAS  Google Scholar 

  45. Landolfi R, Marchioli R, Kutti J et al (2004) Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 350:114–124

    Article  PubMed  CAS  Google Scholar 

  46. Cortellazo S, Finazzi G, Ruggeri M et al (1995) Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332:1132–1136

    Article  Google Scholar 

  47. Randi ML, Ruzzon E, Tezza F (2005) Toxicity and side effects of hydroxyurea used for primary thrombocythemia. Platelets 16:181–184

    Article  PubMed  CAS  Google Scholar 

  48. Finazzi G, Ruggeri M, Rodeghiero F et al (2000) Second malignancies in patients with essential thrombocythemia treated with busulphan and hydroxyurea: long-term follow-up of a randomised clinical trial. Br J Haematol 110:577–583

    Article  PubMed  CAS  Google Scholar 

  49. Passamonti F, Malabarba L, Orlandi E et al (2002) Pipobroman is safe and effective treatment for patients with essential thrombocythemia at high risk of thrombosis. Br J Haematol 116:855–861

    Article  PubMed  CAS  Google Scholar 

  50. Petitt RM, Silverstein MN, Petrone ME (1997) Anagrelide for control of thrombocythemia in polycythemia and other myeloproliferative disorders. Semin Hematol 34:51–54

    PubMed  CAS  Google Scholar 

  51. Storen EC, Tefferi A (2001) Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 97:863–866

    Article  PubMed  CAS  Google Scholar 

  52. Barosi G, Besses C, Birgegard G et al (2007) A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group. Leukemia 21:277–280

    Article  PubMed  CAS  Google Scholar 

  53. Barosi G, Birgegard G, Finazzi G et al (2009) Response criteria for essential thrombocythemia and polycythemia vera: results of a ELN consensus conference. Blood [e-pub ahead of print]

  54. Apperley JF, Gardembas M, Melo JV et al (2002) Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 347:472–480

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Italian Ministry for University and Research (MIUR), grant of Ministero Italiano della Università e Ricerca (COFIN, nos. 2002027001-002) Rome, Italy. We are indebted to Drs. Raffaella Scandellari and Fabiana Tezza for their scientific and clinical collaboration.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.

Author information

Authors and Affiliations

  1. Department of Medical and Surgical Sciences, University of Padua Medical School, Via Giustiniani 2, 35128, Padua, Italy

    Fabrizio Fabris & Maria Luigia Randi

Authors
  1. Fabrizio Fabris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Luigia Randi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabrizio Fabris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fabris, F., Randi, M.L. Essential thrombocythemia: past and present. Intern Emerg Med 4, 381–388 (2009). https://doi.org/10.1007/s11739-009-0284-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-009-0284-x

Keywords

Search

Navigation