Best Practice & Research Clinical Haematology
Volume 19, Issue 3 , Pages 439-453 , September 2006

Essential thrombocythaemia

  • Anthony R. Green, PhD, FRCpath, F Med Sci

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +44 1223 336 835; Fax: +44 1223 762 670.

References 

  1. Epstein E, Goedel A. Haemorrhagische thrombocythamie bei vascularer schrumpfmilz. Virchows Archiv Abteilung. 1934;293:233–247
  2. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6:372–375
  3. Fialkow JP, Faguet GB, Jacobson RJ, et al. Evidence that essential thrombocythaemia is a clonal disorder with origin in a multipotent stem cell. Blood. 1981;58:916–919
  4. 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(10):3310–3321
  5. Kawasaki H, Nakano T, Kohdera U, Kobayashi Y. Hypersensitivity of megakaryocyte progenitors to thrombopoietin in essential thrombocythemia. Am J Hematol. 2001;68:194–197
  6. Li Y, Hetet G, Maurer A-M, et al. Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralisable by antibodies against IL3, IL6 and GM-CSF. Br J Haematol. 1994;87:471–476
  7. Kobayashi S, Teramura M, Hoshino S, et al. Circulating megakaryocyte progenitors in myeloproliferative disorders are hypersensitive to interleukin-3. Br J Haematol. 1993;83:539–544
  8. Cerutti A, Custodi P, Duranti M, et al. Thrombopoietin levels in patients with primary and reactive thrombocytosis. Br J Haematol. 1997;99(2):281–284
  9. Harrison CN, Gale RE, Pezella F, et al. Platelet c-mpl expression is dysregulated in patients with essential thrombocythaemia but this is not of diagnostic value. Br J Haematol. 1999;107(1):139–147
  10. 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
  11. Kondo T, Okabe M, Sanada 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
  12. 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
  13. Jorgensen MJ, Raskind WH, wolff JF, et al. Familial thrombocytosis associated ith overproduction of thrombopoietin due to a novel splice donor site mutation. Blood. 1998;92(suppliment 1):205a
  14. Allen AJ, Gale RE, Harrison CN, et al. 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(4):232–237
  15. Harrison CN, Gale RE, Wiestner AC, et al. 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(5):1341–1343
  16. Horikawa Y, Matsumura I, Hashimoto K, et al. Markedly reduced expression of platelet c-mpl receptor in essential thrombocythaemia. Blood. 1997;90:4031–4038
  17. 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
  18. Ding J, Komatsu H, Wakita 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
  19. Moliterno AR, Williams DM, Gutierrez-Alamillo LI, et al. Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci USA. 2004;101:11444–11447
  20. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1045–1061
  21. 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, in press.
  22. Kralovics R, Passamonti F, Teo SS, Buser AS, Tiedt R, Tichellie A, et al. A gain of function mutation in Jak2 is frequently found in patients with myeloproliferative disorders, in press.
  23. 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, in press.
  24. Murphy S. Therapeutic dilemmas: balancing the risks of bleeding, thrombosis, and leukemic transformation in myeloproliferative disorders (MPD). Thromb Haemost. 1997;78:622–626
  25. Westwood NB, Pearson TC. Diagnostic applications of haemopoietic progenitor culture techniques in polycythaemias and thrombocythaemias. Leuk Lymphoma. 1996;22(supplement 1):95–103
  26. 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(2):417–424
  27. Shih LY, Lin TL, Lai CL, 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
  28. El-Kassar N, Hetet G, Briere J, Grandchamp B. Clonality analysis of hematopoiesis in essential thrombocythaemia: advantages of studying T lymphocytes and platelets. Blood. 1997;89:128–134
  29. Chiusolo P, La Barbera EO, Laurenti L, et al. Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia. Exp Hematol. 2001;29(6):670–676
  30. Busque L, Mio R, Mattioli J, et al. Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. Blood. 1996;88:59–65
  31. Gale RE, Fielding AK, Harrison CN, Linch dC. Acquired skewing of x-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age. Br J Haematol. 1997;98:512–519
  32. Champion KM, Gilbert JGR, Asimakopoulos FA, et al. Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes. Br J Haematol. 1997;97:920–926
  33. Temerinac S, Klippel S, Strunck E, et al. Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera. Blood. 2000;95(8):2569–2576
  34. Griesshammer M, Klippel S, Strunck E, et al. PRV-1 mRNA expression discriminates two types of essential thrombocythemia. Ann Hematol. 2004;83(6):364–370
  35. Liu E, Jelinek J, Pastore YD, et al. 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
  36. Kralovics R, Buser AS, Teo SS, et al. Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders. Blood. 2003;102(5):1869–1871
  37. Messinezy M, Westwood NB, El-Hemaidi I, et al. Serum erythropoietin values in erythrocytoses and in primary thrombocythaemia. Br J Haematol. 2002;117:47–53
  38. Andreasson B, Harrison C, Lindstedt G, et al. Monoclonal myelopoiesis and subnormal erythropoietin concentration are independent risk factors for thromboembolic complications in essential thrombocythemia. Blood. 2003;101:783
  39. 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(11):1126–1134
  40. Thiele J, Kvasnicka HM, Zankovich R, Diehl V. Clinical and morphological criteria for the diagnosis of prefibrotic idiopathic (primary) myelofibrosis. Ann Hematol. 2001;80:160–165
  41. Annaloro C, Lambertenghi Deliliers G, Oriani A, et al. Prognostic significance of bone marrow biopsy in essential thrombocythemia. Haematologica. 1999;84(1):17–21
  42. Lengfelder E, Hochhaus A, Kronawitter U, et al. Should a platelet limit of 600×10(9)/l be used as a diagnostic criterion in essential thrombocythaemia? an analysis of the natural course including early stages. Br J Haematol. 1998;100(1):15–23
  43. Sacchi S, Vinci G, Gugliotta L, et al. Diagnosis of essential thrombocythemia at platelet counts between 400 and 600×10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC). Haematologica. 2000;85(5):492–495
  44. Cortelazzo S, Viero P, Finazzi G, et al. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythaemia. J Clin Oncol. 1990;8:556–562
  45. Jensen MK, de Nully BP, Lund BV, et al. Increased circulating platelet-leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count. Eur J Haematol. 2001;66:143–151
  46. Falanga A, Marchetti M, Evangelista V, et al. Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera. Blood. 2000;96:4261–4266
  47. Harrison CN, Donohoe S, Carr P, et al. Patients with essential thrombocythaemia have an increased prevalence of antiphospholipid antibodies which may be associated with thrombosis. Thomb Haemost. 2002;87:802–807
  48. Yoon SY, Li CY, Tefferi A. Megakaryocyte c-Mpl expression in chronic myeloproliferative disorders and the myelodysplastic syndrome: immunoperoxidase staining patterns and clinical correlates. Eur J Haematol. 2000;65:170–174
  49. Johansson P, Ricksten A, Wennstrom L, et al. Increased risk for vascular complications in PRV-1 positive patients with essential thrombocythemia. Br J Haematol. 2003;123:513–516
  50. Ruggeri M, Gisslinger H, Tosetto A, et al. Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol. 2002;71:1–6
  51. Besses C, Cervantes F, Pereira A, et al. Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia. 1999;13(2):150–154
  52. van Genderen PJ, Prins FJ, Lucas IS, et al. Decreased half-life time of plasma von Willebrand factor collagen binding activity in essential thrombocythemia: normalization after cytoreduction of the increased platelet count. Br J Haematol. 1997;99:832–836
  53. Tatarsky I, Sharon R. Management of polycythemia with hydroxyurea. Semin Hematol. 1997;34:24–28
  54. Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, et al. A randomized comparison of hydroxyurea and anagrelide in high-risk essential thrombocythemia: the Medical Research Council PT-1 trial. N Engl J Med, in press.
  55. Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114–124
  56. Cervantes F, Alvarez-Larran A, Talarn C, et al. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol. 2002;118(3):786–790
  57. Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polychythemia vera and essential thrombocythemia. Am J Med. 2004;117:755–761
  58. Rozman C, Giralt M, Feliu E, et al. Life expectancy of patients with chronic nonleukemic myeloproliferative disorders. Cancer. 1991;67(10):2658–2663
  59. Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. 1999;61(1):10–15
  60. Jensen MK, de Nully BP, Nielsen OJ, Hasselbalch HC. Incidence, clinical features and outcome of essential thrombocythemia in a well defined geographical area. Eur J Haematol. 2000;65:132–139
  61. 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(12):539–543
  62. Tartaglia AP, Goldberg JD, Berk PD, Wasserman LR. Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol. 1986;23(3):172–176
  63. van Genderen PJ, Michiels JJ, van Strik R, et al. Platelet consumption in thrombocythemia complicated by erythromelalgia: reversal by aspirin. Thromb Haemost. 1995;73(2):210–214
  64. van Genderen PJ, Mulder PG, Waleboer M, et al. Prevention and treatment of thrombotic complications in essential thrombocythaemia: efficacy and safety of aspirin. Br J Haematol. 1997;97(1):179–184
  65. Antithrombotic TC. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J. 2002;324(7329):71–86
  66. Lauer MS. Clinical practice. Aspirin for primary prevention of coronary events. N Engl J Med. 2002;346(19):1468–1474
  67. Michiels JJ, Koudstaal PJ, Mulder AH, van Vliet HH. Transient neurologic and ocular manifestations in primary thrombocythemia. Neurology. 1993;43(6):1107–1110
  68. Griesshammer M, Bangerter M, van Vliet HH, Michiels JJ. Aspirin in essential thrombocythemia: status quo and quo vadis. Semin Thromb Hemost. 1997;23(4):371–377
  69. Ruggeri M, Castaman G, Rodeghiero F. Is ticlopidine a safe alternative to aspirin for management of myeloproliferative disorders?. Haematologica. 1993;78:18–21
  70. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005;352:238–244
  71. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332:1132–1136
  72. Barbui T, Barosi G, Grossi A, 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;89:215–232
  73. Finazzi G, Barbui T. Efficacy an safety of hydroxyurea in patients with essential thrombocythemia. Pathol Biol (Paris). 2001;49:167–169
  74. Hanft VN, Fruchtman SR, Pickens CV, et al. Acquired DNA mutations associated with in vivo hydroxyurea exposure. Blood. 2000;95(11):3589–3593
  75. Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long-term follow-up of a randomized clinical trial. Br J Haematol. 2000;110(3):577–583
  76. Sterkers Y, Preudhomme C, Lai JL, 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
  77. Bernasconi P, Boni M, Cavigliano PM, et al. Acute myeloid leukaemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea. Leukemia. 2002;16:2078–2083
  78. Anagrelide SG. Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Am J Med. 1992;92(1):69–76
  79. Jurgens DJ, Moreno-Aspitia A, Tefferi A. Anagrelide-associated cardiomyopathy in polycythemia vera and essential thrombocythemia. Haematologica. 2004;89:1394–1395
  80. Petitt RM, S MN, Petrone ME. Anagrelide for control of thrombocythemia in polycythemia and other myeloproliferative disorders. Semin Hematol. 1997;34(1):51–54
  81. Fruchtman SM, Petitt RM, Gilbert HS, et al. Anagrelide: analysis of long term safety and leukemogenic potential in myeloproliferative diseases (MPDs). Blood. 2002;100(11):[Ash Mtg Abstracts]
  82. Storen EC, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia. Blood. 2001;97(4):863–866
  83. Elliott MA, Tefferi A. Interferon-alpha therapy in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 1997;23(5):463–472
  84. Delage R, Demers C, Cantin G, Roy J. Treatment of essential thrombocythemia during pregnancy with interferon-alpha. Obstet Gynecol. 1996;87:814–817
  85. 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
  86. Passamonti F, Malabarba L, Orlandi E, et al. Pipobroman is safe and effective treatment for patients with essential thrombocythaemia at high risk of thrombosis. Br J Haematol. 2002;116:855–861
  87. Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997;90:3370–3377
  88. Van de Pette JE, Prochazka AV, Pearson TC, et al. Primary thrombocythaemia treated with busulphan. Br J Haematol. 1986;62(2):229–237
  89. Tsimberidou AM, Colburn DE, Welch MA. Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders. Cancer Chemother Pharmacol. 2003;52:229–234
  90. Bouchard BA, Tracy PB. Platelets, leukocytes, and coagulation. Curr Opin Hematol. 2001;8(5):263–269
  91. Brun M, Bourdoulous S, Couraud PO, et al. Hydroxyurea downregulates endothelin-1 gene expression and upregulates ICAM-1 gene expression in cultured human endothelial cells. Pharmacogenomics. 2003;3(4):215–226
  92. Nahavandi M, Tavakkoli F, Wyche MQ. Nitric oxide and cyclic GMP levels in sickle cell patients receiving hydroxyurea. Br J Haematol. 2002;119(3):855–857
  93. Tang SS, Frojmovic MM. Inhibition of platelet function by antithrombotic agents which selectively inhibit low-Km cyclic 3′,5′-adenosine monophosphate phosphodiesterase. J Lab Clin Med. 1980;95(2):241–257
  94. Fleming JS, Buyniski JP. A potent new inhibitor of platelet aggregation and experimental thrombosis, anagrelide (BL-4162A). Thromb Res. 1979;15(3-4):373–388
  95. Bellucci S, Legrand C, Boval B, et al. Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with Anagrelide. Br J Haematol. 1999;104(4):886–892
  96. Cacciola RR, Francesco ED, Giustolisi R, Cacciola E. Effects of anagrelide on platelet factor 4 and vascular endothelial growth factor levels in patients with essential thrombocythemia. Br J Haematol. 2004;126(6):885–886
  97. Lofvenberg E, Wahlin A, Roos G, Ost A. Reversal of myelofibrosis by hydroxyurea. Eur J Haematol. 1990;44:33–38
  98. Thiele J, Kvasnicka HM, Schmitt-Graeff A. Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study. Br J Haematol. 2000;108(1):64–71
  99. 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
  100. Lev PR, Salim JP, Kornblihtt LI, et al. PDFG-A, PDGF-B, TGFbeta, and bFGF and mRNA levels in patients with essential thrombocythemia treated with anagrelide. Am J Hematol. 2005;78:155–157
  101. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–2302
  102. 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 1. Blood. 2000;96:3310–3321
  103. Harrison CN, Campbell P, Buck G, et al. The Medical Research Council PT1 Trial in Essential Thrombocythemia. N Engl J Med. 2005;353:33–45

PII: S1521-6926(05)00092-7

doi: 10.1016/j.beha.2005.07.004

Best Practice & Research Clinical Haematology
Volume 19, Issue 3 , Pages 439-453 , September 2006

Article Tools