Seminars in Hematology
Volume 42, Issue 4 , Pages 230-238 , October 2005

Essential Thrombocythemia

  • Guido Finazzi

      Affiliations

    • Department of Hematology, Ospedali Riuniti, Bergamo, Italy.
    • Corresponding Author InformationAddress correspondence to Guido Finazzi, Senior Consultant, Hematology, Ospedali Riuniti, Largo Barozzi 1, 24128 Bergamo, Italy.
    • ,
  • Claire Harrison

      Affiliations

    • Department of Hematology, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK.

References 

  1. Fialkow PJ , Faguet GB , Jacobson RJ , Vaidya K , Murphy S . Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell . Blood . 1981;58:916–919
  2. el-Kassar N , Hetet G , Briere J , Grandchamp B . Clonality analysis of hematopoiesis in essential thrombocythemia (Advantages of studying T lymphocytes and platelets) . Blood . 1997;89:128–134
  3. Harrison CN , Gale RE , Machin SJ , Linch DC . A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications . Blood . 1999;93:417–424
  4. Shih LY , Lin TL , Lai CL , Dunn P , Wu JH , Wang PN , et al.   Predictive values of X-chromosome inactivation patterns and clinicohematologic parameters for vascular complications in female patients with essential thrombocythemia . Blood . 2002;100:1596–1601
  5. Chiusolo P , La Barbera EO , Laurenti L , Piccirillo N , Sora F , Giordano G , et al.   Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia . Exp Hematol . 2001;29:670–676
  6. Temerinac S , Klippel S , Strunck E , Roder S , Lubbert M , Lange W , et al.   Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera . Blood . 2000;95:2569–2576
  7. Liu E , Jelinek J , Pastore YD , Guan Y , Prchal JF , Prchal JT . Discrimination of polycythemias and thrombocytoses by novel, simple, accurate clonality assays and comparison with PRV-1 expression and BFU-E response to erythropoietin . Blood . 2003;101:3294–3301
  8. Kralovics R , Buser AS , Teo SS , Coers J , Tichelli A , van der Maas AP , et al.   Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders . Blood . 2003;102:1869–1871
  9. Messinezy M , Westwood NB , El-Hemaidi I , Marsden JT , Sherwood RS , Pearson TC . Serum erythropoietin values in erythrocytoses and in primary thrombocythaemia . Br J Haematol . 2002;117:47–53
  10. Andreasson B , Harrison C , Lindstedt G , Linch D , Kutti J . Monoclonal myelopoiesis and subnormal erythropoietin concentration are independent risk factors for thromboembolic complications in essential thrombocythemia . Blood . 2003;101:783–784
  11. Cerutti A , Custodi P , Duranti M , Noris P , Balduini CL . Thrombopoietin levels in patients with primary and reactive thrombocytosis . Br J Haematol . 1997;99:281–284
  12. Harrison CN , Gale RE , Pezella F , Mire-Sluis A , Machin SJ , Linch DC . Platelet c-mpl expression is dysregulated in patients with essential thrombocythaemia but this is not of diagnostic value . Br J Haematol . 1999;10:139–147
  13. Wiestner A , Schlemper RJ , van der Maas AP , Skoda RC . An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia . Nat Genet . 1998;18:49–52
  14. Kondo T , Okabe M , Sanada M , Kurosawa M , Suzuki S , Kobayashi M , et al.   Familial essential thrombocythemia associated with one-base deletion in the 5′-untranslated region of the thrombopoietin gene . Blood . 1998;92:1091–1096
  15. Ghilardi N , Skoda RC . A single-base deletion in the thrombopoietin (TPO) gene causes familial essential thrombocythemia through a mechanism of more efficient translation of TPO mRNA . Blood . 1999;94:1480–1482
  16. Jorgensen MJ , Raskind WH , Wolff JF , Bachrach HR , Kaushansky K . Familial thrombocytosis associated with overproduction of thrombopoietin due to a novel splice donor site mutation . Blood . 1997;92:205a; (suppl 1, abstr)
  17. Allen AJ , Gale RE , Harrison CN , Machin SJ , Linch DC . Lack of pathogenic mutations in the 5′-untranslated region of the thrombopoietin gene in patients with non-familial essential thrombocythaemia . Eur J Haematol . 2001;67:232–237
  18. Harrison CN , Gale RE , Wiestner AC , Skoda RC , Linch DC . The activating splice mutation in intron 3 of the thrombopoietin gene is not found in patients with non-familial essential thrombocythaemia . Br J Haematol . 1998;102:1341–1343
  19. Horikawa Y , Matsumura I , Hashimoto K , Shiraga M , Kosugi S , Tadokoro S , et al.   Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia . Blood . 1997;90:4031–4038
  20. Moliterno AR , Hankins WD , Spivak JL . Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera . N Engl J Med . 1998;338:572–580
  21. Ding J , Komatsu H , Wakita A , Kato-Uranishi M , Ito M , Satoh A , et al.   Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin . Blood . 2004;103:4198–4200
  22. Axelrad AA , Eskinazi D , Correa PN , Amato D . Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia . Blood . 2000;96:3310–3321
  23. Kawasaki H , Nakano T , Kohdera U , Kobayashi Y . Hypersensitivity of megakaryocyte progenitors to thrombopoietin in essential thrombocythemia . Am J Hematol . 2001;68:194–197
  24. Li Y , Hetet G , Maurer AM , Chait Y , Dhermy D , Briere J . Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM-CSF . Br J Haematol . 1994;87:471–476
  25. James C , Ugo V , Le Couedic JP , Staerk J , Delhommeau F , Lacout C , et al.   A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera . Nature . 2005;434:1144–1148
  26. Baxter EJ , Scott LM , Campbell PJ , East C , Fourouclas N , Swanton S , et al.   Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders . Lancet . 2005;365:1054–1061
  27. Levine RL , Wadleigh M , Cools J , Ebert BL , Wernig G , Huntly BJ , et al.   Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis . Cancer Cell . 2005;4:387–397
  28. Kralovics R , Passamonti F , Buser AS , Teo S-S , Tiedt R , Passweg JR , et al.   A gain-of-function mutation of JAK2 in myeloproliferative disorders . N Engl J Med . 2005;352:1779–1790
  29. Murphy S , Peterson P , Iland H , Laszlo J . Experience of the Polycythemia Vera Study Group with essential thrombocythemia (A final report on diagnostic criteria, survival and leukemic transition by treatment) . Semin Hematol . 1997;34:29–39
  30. Imbert M , Pierre R , Thiele J , Vardiman JW , Brunning RD , Flandrin G . Essential thrombocythemia . In:  Jaffe ES ,  Harris NL ,  Stein H ,  Vardiman JW editor. Pathology an Genetics of Tumours of Hematopoietic and Lymphoid Tissues . Lyon, France: IARC Press; 2001;p. 39–41
  31. Lengfelder E , Hochhaus A , Kronawitter U , Hoche D , Queisser W , Jahn-Eder M , et al.   Should a platelet limit 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 . 1998;100:15–23
  32. Sacchi S , Vinci G , Gugliotta L , Rupoli S , Gargantini L , Martinelli V , et al.   Diagnosis of essential thrombocythemia at platelet counts between 400 and 600 × 109/l . Haematologica . 2000;85:492–495
  33. Thiele J , Kvasnicka HM , Zankovich R , Diehl V . Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis . Haematologica . 2000;85:1126–1134
  34. Westwood NB , Pearson TC . Diagnostic applications of hemopoietic progenitor culture techniques in polycythaemias and thrombocythaemias . Leuk Lymphoma . 1996;22:95–103 (suppl 1)
  35. Bench AJ , Nacheva EP , Champion KM , Green AR . Molecular genetics and cytogenetics of myeloproliferative disorders . Baillieres Clin Haematol . 1998;11:819–848
  36. Mesa RA , Silverstein MN , Jacobsen SJ , Wollan PC , Tefferi A . Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia (An Olmsted County study, 1976-1995) . Am J Hematol . 1999;61:10–15
  37. Johansson P , Kutti J , Andreasson B , Safai-Kutti S , Vilen L , Wedel H , et al.   Trends in the incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders in the city of Goteborg, Sweden, during 1983-99 . J Int Med . 2004;256:161–165
  38. Ruggeri M , Tosetto A , Frezzato M , Rodeghiero F . The rate of progression to polycythemia vera or essential thrombocythemia in patients with erythrocytosis or thrombocytosis . Ann Intern Med . 2003;139:470–475
  39. Elliott MA , Tefferi A . Thrombosis and haemorrhage in polycythemia vera and essential thrombocythaemia . Br J Haematol . 2005;128:275–290
  40. Barbui T , Barosi G , Grossi A , Gugliotta L , Liberato LN , Marchetti M , et al.   Evidence- and consensus-based practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology . Haematologica . 2004;89:215–232
  41. 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
  42. van Genderen PJ , Michiels JJ . Erythromelalgic, thrombotic and hemorrhagic manifestations of thrombocythaemia . Presse Med . 1994;23:73–77
  43. 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
  44. Besses C , Cervantes F , Pereira A , Florensa L , Sole F , Hernandez-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
  45. van Genderen PJ , Budde U , Michiels JJ , van Strik R , van Vliet HH . The reduction of large vonWillebrand multimers in plasma in essential thrombocythemia is related to the platelet count . Br J Haematol . 1996;93:962–965
  46. Cervantes F , Alvarez-Larran A , Talarn C , Gomez M , Montserrat E . Myelofibrosis with myeloid metaplasia following essential thrombocythemia (Actuarial probability, presenting characteristics and evolution in a series of 195 patients) . Br J Haematol . 2002;118:786–790
  47. Andersson PO , Ridell B , Wadenvik H , Kutti J . Leukemic transformation of essential thrombocythemia without previous cytoreductive treatment . Ann Hematol . 2000;79:40–42
  48. Tefferi A . Risk-based management in essential thrombocythemia. American Society of Hematology Education Program Book . In:  Schechter GP ,  Hoffman R ,  Schrier SL ,  Bajus JL editor. Hematology 1999 . Washington, DC: American Society of Hematology; 1999;p. 172–177
  49. Ruggeri M , Finazzi G , Tosetto A , Riva S , Rodeghiero F , Barbui T . No treatment for low-risk essential thrombocythemia (Results from a prospective study) . Br J Haematol . 1998;103:772–777
  50. 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
  51. Harrison CN , Green AR . Essential thrombocythemia . Hematol Oncol Clin North Am . 2003;17:1175–1190
  52. Sterkers Y , Preudhomme C , Lai J-L , Demory J-L , Caulier MT , Wattel E , et al.   Acute myeloid leukemia and myelodyslastic syndromes following essential thrombocythemia treated with hydroxyurea (High proportion of cases with 17p deletion) . Blood . 1998;91:616–622
  53. 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; (letter)
  54. Finazzi G , Caruso V , Marchioli R , Capnist G , Chisesi T , Finelli C , et al.   Acute leukemia in polycythemia vera. An analysis of 1638 patients enrolled in a prospective observational study . Blood . 2005;105:2664–2670
  55. Lofvenberg E , Nordenson I , Walhlin A . Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease . Cancer Genet Cytogenet . 1990;49:57–67
  56. Finazzi G , Ruggeri M , Rodeghiero F , Barbui T . Second malignancies in patients with essential thrombocythemia treated with busulphan and hydroxyurea (Long-term follow-up of a randomized clinical trial) . Br J Haematol . 2000;110:577–583
  57. Murphy S , Iland H , Rosenthal D , Laszlo J . Essential thrombocythemia (An interim report from the Polycythemia Vera Study Group) . Semin Hematol . 1986;23:177–182
  58. Hanft VN , Fruchtman SR , Pickens CV , Rosse WF , Howard TA , Ware RE . Acquired DNA mutations associated with in vivo hydroxyurea exposure . Blood . 2000;95:3589–3593
  59. Anagrelide Study Group . Anagrelide, a therapy for thrombocythemic states (experience in 577 patients) . Anagrelide Study Group. Am J Med . 1992;92:69–76
  60. Jurgens DJ , Moreno-Aspitia A , Tefferi A . Anagrelide-associated cardiomyopathy in polycythemia vera and essential thrombocythemia . Haematologica . 2004;89:1394–1395
  61. Fruchtman SM , Petitt RM , Gilbert HS , Fiddler G , Lynne A  Anagrelide Study Group . Anagrelide (analysis of long term safety and leukemogenic potential in myeloproliferative diseases (MPDs)) . Blood . 2002;100:70a; (abstr)
  62. Fruchtman SM . Treatment paradigms in the management of myeloproliferative disorders . Semin Hematol . 2004;41:18–22
  63. Storen EC , Tefferi A . Long-term use of anagrelide in young patients with essential thrombocythemia . Blood . 2001;97:863–866
  64. Lengfelder E , Griesshammer M , Hehlmann R . Interferon-alpha in the treatment of essential thrombocythemia . Leuk Lymphoma . 1996;22(suppl 1):135–142
  65. 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
  66. Harrison CN , Campbell P , Buck G , Wheatley K , East C , Bareford D , et al.   The Medical Research Council PT1 Trial in Essential Thrombocythemia . N Engl J Med . 2005;353:33–45
  67. Balduini CL , Bertolino G , Noris P , Ascari E . Effect of anagrelide on platelet count and function in patients with thrombocytosis and myeloproliferative disorders . Haematologica . 1992;77:40–43
  68. Bellucci S , Legrand C , Boval B , Drouet L , Caen J . Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with anagrelide . Br J Haematol . 1999;104:886–892
  69. Petrides PE . Anagrelide (A decade of clinical experience with its use for the treatment of primary thrombocythaemia) . Exp Opin Pharmacother . 2004;5:1781–1798
  70. Silverstein MN , Tefferi A . Treatment of essential thrombocythemia with anagrelide . Semin Hematol . 1999;36:23–25
  71. Thiele J , Kvasnicka HM , Fuchs N , Brunnbauer K , Volkwein N , Schmitt-Graeff A . Anagrelide-induced bone marrow changes during therapy of chronic myeloproliferative disorders with thrombocytosis. An immunohistochemical and morphometric study of sequential trephine biopsies . Haematologica . 2003;88:1130–1138
  72. Lev PR , Marta RF , Vassallu P , Molinas FC . Variation of PDGF, TGFbeta, and bFGF levels in essential thrombocythemia patients treated with anagrelide . Am J Hematol . 2002;70:85–91
  73. Lev PR , Salim JP , Kornblihtt LI , Pirola CJ , Marta RF , Heller PG , et al.   PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide . Am J Hematol . 2005;78:155–157
  74. McNally RJ , Roman E , Cartwright RA . Leukemias and lymphomas (time trends in the UK, 1984-93) . Cancer Causes Control . 1999;10:35–42
  75. Griesshammer M , Bergmann L , Pearson T . Fertility, pregnancy and the management of myeloproliferative disorders . Baillieres Clin Haematol . 1998;11:859–874
  76. Griesshammer M , Grunewald M , Michiels JJ . Acquired thrombophilia in pregnancy (Essential thrombocythemia) . Semin Thromb Hemost . 2003;29:205–212
  77. Vantroyen B , Vanstraelen D . Management of essential thrombocythemia during pregnancy with aspirin, interferon alpha-2a and no treatment. A comparative analysis of the literature . Acta Haematol . 2002;107:158–169
  78. Bangerter M , Guthner C , Beneke H , Hildebrand A , Grunewald M , Griesshammer M . Pregnancy in essential thrombocythaemia (Treatment and outcome of 17 pregnancies) . Eur J Haematol . 2000;65:165–169
  79. Schmidt HH , Neumeister P , Kainer F , Karpf EF , Linkesch W , Sill H . Treatment of essential thrombocythemia during pregnancy (Antiabortive effect of interferon-alpha?) . Ann Hematol . 1998;77:291–292
  80. Williams JM , Schlesinger PE , Gray AG . Successful treatment of essential thrombocythaemia and recurrent abortion with alpha interferon . Br J Haematol . 1994;88:647–648

PII: S0037-1963(05)00082-X

doi: 10.1053/j.seminhematol.2005.05.022

Seminars in Hematology
Volume 42, Issue 4 , Pages 230-238 , October 2005

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