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Essential Thrombocythemia (ET)

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Chronic Myeloid Neoplasias and Clonal Overlap Syndromes

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Abstract

Essential Thrombocythemia (ET) is a chronic myeloid disorder with megakaryocytic proliferation in the bone marrow resulting in a persistent increase in platelets in the peripheral blood, with ensuing thrombohemorrhagic symptoms. Furthermore, mild leukocytosis, lack of hepatosplenomegaly and excellent prognosis with only rare transformation to acute leukemia are typical characteristics of this disease.

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References

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. 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

    Article  PubMed  Google Scholar 

  4. Elliott MA, Tefferi A (2005) Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128: 275–290

    Article  CAS  PubMed  Google Scholar 

  5. Harrison CN (2005) Platelets and thrombosis in myeloproliferative diseases. Hematol Am Soc Hematol Educ Program 409–415

    Google Scholar 

  6. Gisslinger H (2007) Essential thrombocythemia: a prospective analysis of efficacy and safety of angrelide for long term treatment in patients below and above the age of 60 years. Blood 110(11): Abstract 3561

    Google Scholar 

  7. Harrison CN, Campbell PJ, Buck G et al. (2005) Hydroxyurea comparedwith anagrelide in high-risk essential thrombocythemia. N Engl J Med 353: 33–45

    Article  CAS  PubMed  Google Scholar 

  8. De SV, Za T, Rossi E et al. (2008) Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments. Haematologica 93: 372–380

    Article  CAS  Google Scholar 

  9. Gangat N, Wolanskyj AP, McClure RF et al. (2007) Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 21: 270–276

    Article  CAS  PubMed  Google Scholar 

  10. Harrison CN, Gale RE, Machin SJ, Linch DC (1999) 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 93: 417–424

    CAS  PubMed  Google Scholar 

  11. Shih LY, Lin TL, Dunn P et al. (2001) Clonality analysis using X-chromosome inactivation patterns by HUMARA-PCR assay in female controls and patients with idiopathic thrombocytosis in Taiwan. Exp Hematol 29: 202–208

    Article  CAS  PubMed  Google Scholar 

  12. Shih LY, Lin TL, Lai CL et al. (2002) Predictive values of X-chromosome inactivation patterns and clinicohematologic parameters for vascular complications in female patients with essential thrombocythemia. Blood 100: 1596–1601

    Article  CAS  PubMed  Google Scholar 

  13. el Kassar N, Hetet G, Li Y, Briere J, Grandchamp B (1995) Clonal analysis of haemopoietic cells in essential thrombocythaemia. Br J Haematol 90: 131–137

    Article  PubMed  Google Scholar 

  14. Chen GL, Prchal JT (2007) X-linked clonality testing: interpretation and limitations. Blood 110: 1411–1419

    Article  CAS  PubMed  Google Scholar 

  15. Chiusolo P, La Barbera EO, Laurenti L et al. (2001) Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia. Exp Hematol 29: 670–676

    Article  CAS  PubMed  Google Scholar 

  16. Vannucchi AM, Grossi A, Pancrazzi A et al. (2004) PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia. Br J Haematol 127: 214–219

    Article  CAS  PubMed  Google Scholar 

  17. Florensa L, Bellosillo B, Besses C et al. (2006) JAK2 V617F mutation analysis in different myeloid lineages (granulocytes, platelets, CFU-MK, BFU-E and CFU-GM) in essential thrombocythemia patients. Leukemia 20: 1903–1905

    Article  CAS  PubMed  Google Scholar 

  18. Tefferi A, Sirhan S, Lasho TL et al. (2005) Concomitant neutrophil JAK2 mutation screening and PRV-1 expression analysis in myeloproliferative disorders and secondary polycythaemia. Br J Haematol 131: 166–171

    Article  CAS  PubMed  Google Scholar 

  19. Vannucchi AM, Pancrazzi A, Bogani C, Antonioli E, Guglielmelli P (2006) A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by ARMS-PCR and capillary electrophoresis. Leukemia 20: 1055–1060

    Article  CAS  PubMed  Google Scholar 

  20. Dobo I, Boiret N, Lippert E et al. (2004) A standardized endogenous megakaryocytic erythroid colony assay for the diagnosis of essential thrombocythemia. Haematologica 89: 1207–1212

    PubMed  Google Scholar 

  21. Mossuz P (2006) Influence of the assays of endogenous colony formation and serum erythropoietin on the diagnosis of polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 32: 246–250

    Article  CAS  PubMed  Google Scholar 

  22. Shih LY, Lee CT (1994) Identification of masked polycythemia vera from patients with idiopathic marked thrombocytosis by endogenous erythroid colony assay. Blood 83: 744–748

    CAS  PubMed  Google Scholar 

  23. Dobo I, Mossuz P, Campos L et al. (2001) Comparison of four serum-free, cytokine-free media for analysis of endogenous erythroid colony growth in polycythemia vera and essential thrombocythemia. Hematol J 2: 396–403

    Article  CAS  PubMed  Google Scholar 

  24. Griesshammer M, Klippel S, Strunck E et al. (2004) PRV-1 mRNA expression discriminates two types of essential thrombocythemia. Ann Hematol 83: 364–370

    Article  CAS  PubMed  Google Scholar 

  25. Jelinek J, Li J, Mnjoyan Z, Issa JP, Prchal JT, Afshar-Kharghan V (2007) Epigenetic control of PRV-1 expression on neutrophils. Exp Hematol 35: 1677–1683

    Article  CAS  PubMed  Google Scholar 

  26. Vannucchi AM, Guglielmelli P, Antonioli E et al. (2006) Inconsistencies in the association between the JAK2(V617F) mutation and PRV-1 over-expression among the chronic myeloproliferative diseases. Br J Haematol 132: 652–654

    Article  PubMed  Google Scholar 

  27. Goerttler PS, Steimle C, Marz E et al. (2005) The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients. Blood 106: 2862–2864

    Article  CAS  PubMed  Google Scholar 

  28. Goerttler PL, Marz E, Johansson PL et al. (2005) Thrombotic and bleeding complications in four subpopulations of patients with essential thrombocythemia defined by c-Mpl protein expression and PRV-1 mRNA levels. Haematologica 90: 851–853

    CAS  PubMed  Google Scholar 

  29. Teofili L, Martini M, Guidi F, Venditti D, Leone G, Larocca ML (2004) The PRV-1 gene expression in essential thrombocythemia. Blood 104: 2995–2996

    Article  PubMed  Google Scholar 

  30. Passamonti F, Pietra D, Rumi E et al. (2005) PRV-1 and its correlation with treatments and disease status in 210 patients with polycythemia vera and essential thrombocythemia. Leukemia 19: 888–889

    Article  CAS  PubMed  Google Scholar 

  31. Puigdecanet E, Espinet B, Villa O et al. (2006) Detection of abnormalities of PRV-1, TPO, and c-MPL genes detected by fluorescence in situ hybridization in essential thrombocythemia. Cancer Genet Cytogenet 167: 39–42

    Article  CAS  PubMed  Google Scholar 

  32. Griesshammer M, Kubanek B, Beneke H et al. (2000) Serum erythropoietin and thrombopoietin levels in patients with essential thrombocythaemia. Leuk Lymphoma 36: 533–538

    Article  CAS  PubMed  Google Scholar 

  33. Tomita N, Motomura S, Sakai R et al. (2000) Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia. Am J Hematol 63: 131–135

    Article  CAS  PubMed  Google Scholar 

  34. Vannucchi AM, Barbui T (2007) Thrombocytosis and thrombosis. Hematol Am Soc Hematol Educ Program 2007: 363–370

    Google Scholar 

  35. Guglielmelli P, Pancrazzi A, Bergamaschi G et al. (2007) Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. Br J Haematol 137: 244–247

    Article  CAS  PubMed  Google Scholar 

  36. Teofili L, Pierconti F, Di Febo A et al. (2002) The expression pattern of c-mpl in megakaryocytes correlates with thrombotic risk in essential thrombocythemia. Blood 100: 714–717

    Article  CAS  PubMed  Google Scholar 

  37. Jamieson CH, Gotlib J, Durocher JA et al. (2006) The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci USA 103: 6224–6229

    Article  CAS  PubMed  Google Scholar 

  38. Delhommeau F, Dupont S, Tonetti C et al. (2007) Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis. Blood 109: 71–77

    Article  CAS  PubMed  Google Scholar 

  39. Bellanne-Chantelot C, Chaumarel I, Labopin M et al. (2006) Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders. Blood 108: 346–352

    Article  CAS  PubMed  Google Scholar 

  40. Campbell PJ, Baxter EJ, Beer PA et al. (2006) Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood 108: 3548–3555

    Article  CAS  PubMed  Google Scholar 

  41. Theocharides A, Boissinot M, Girodon F et al. (2007) Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood 110: 375–379

    Article  CAS  PubMed  Google Scholar 

  42. Pardanani A (2008) JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials. Leukemia 22: 23–30

    Article  CAS  PubMed  Google Scholar 

  43. Kralovics R, Skoda RC (2005) Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood Rev 19: 1–13

    Google Scholar 

  44. Mesa RA, Verstovsek S, Cervantes F et al. (2007) Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT). Leuk Res 31: 737–740

    Article  PubMed  Google Scholar 

  45. Randi ML, Putti MC, Scapin M et al. (2006) Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood 108: 3600–3602

    Article  CAS  PubMed  Google Scholar 

  46. Teofili L, Giona F, Martini M et al. (2007) Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia. J Clin Oncol 25: 1048–1053

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  48. James C, Ugo V, Le Couedic JP et al. (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434: 1144–1148

    Article  CAS  PubMed  Google Scholar 

  49. Kralovics R, Passamonti F, Buser AS et al. (2005) A gain-offunction mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352: 1779–1790

    Article  CAS  PubMed  Google Scholar 

  50. 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  CAS  PubMed  Google Scholar 

  51. Jones AV, Kreil S, Zoi K et al. (2005) Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 106: 2162–2168

    Article  CAS  PubMed  Google Scholar 

  52. Antonioli E, Guglielmelli P, Poli G et al. (2008) Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia. Haematologica 93: 41–48

    Article  CAS  PubMed  Google Scholar 

  53. Kittur J, Knudson RA, Lasho TL et al. (2007) Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 109: 2279–2284

    Article  PubMed  Google Scholar 

  54. Moliterno AR, Williams DM, Rogers O, Spivak JL (2006) Molecular mimicry in the chronic myeloproliferative disorders: reciprocity between quantitative JAK2V617F and Mpl expression. Blood 108: 3913–3915

    Article  CAS  PubMed  Google Scholar 

  55. Bellosillo B, Martinez-Aviles L, Gimeno E et al. (2007) A higher JAK2 V617F-mutated clone is observed in platelets than in granulocytes from essential thrombocythemia patients, but not in patients with polycythemia vera and primary myelofibrosis. Leukemia 21: 1331–1332

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  57. Passamonti F, Rumi E, Pietra D et al. (2006) Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Blood 107: 3676–3682

    Article  CAS  PubMed  Google Scholar 

  58. Tefferi A, Lasho TL, Gilliland G (2005) JAK2 mutations in myeloproliferative disorders. N Engl J Med 353: 1416–1417

    Article  CAS  PubMed  Google Scholar 

  59. Gale RE, Allen AJ, Nash MJ, Linch DC (2007) Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years. Blood 109: 1241–1243

    Article  CAS  PubMed  Google Scholar 

  60. Ghilardi N, Wiestner A, Kikuchi M, Ohsaka A, Skoda RC (1999) Hereditary thrombocythaemia in a Japanese family is caused by a novel point mutation in the thrombopoietin gene. Br J Haematol 107: 310–316

    Article  CAS  PubMed  Google Scholar 

  61. Ghilardi N, Skoda RC (1999) A single-base deletion in the thrombopoietin (TPO) gene causes familial essential thrombocythemia through a mechanism of more efficient translation of TPO mRNA. Blood 94: 1480–1482

    CAS  PubMed  Google Scholar 

  62. Kondo T, Okabe M, Sanada M et al. (1998) Familial essential thrombocythemia associated with one-base deletion in the 5′-untranslated region of the thrombopoietin gene. Blood 92: 1091–1096

    CAS  PubMed  Google Scholar 

  63. Pikman Y, Lee BH, Mercher T et al. (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 3: e270

    Article  PubMed  CAS  Google Scholar 

  64. Pardanani AD, Levine RL, Lasho T et al. (2006) MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 108: 3472–3476

    Article  CAS  PubMed  Google Scholar 

  65. Moliterno AR, Williams DM, Gutierrez-Alamillo LI, Salvatori R, Ingersoll RG, Spivak JL (2004) Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci USA 101: 11444–11447

    Article  CAS  PubMed  Google Scholar 

  66. Williams DM, Kim AH, Rogers O, Spivak JL, Moliterno AR (2007) Phenotypic variations and new mutations in JAK2V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis. Exp Hematol 35: 1641–1646

    Article  CAS  PubMed  Google Scholar 

  67. Pardanani A, Lasho TL, Finke C et al. (2007) Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic colonies and B and T lymphocytes. Stem Cells 25: 2358–2362

    Article  CAS  PubMed  Google Scholar 

  68. Hu WY, Zhao Y, Ishii T et al. (2007) Haematopoietic cell lineage distribution of MPLW515L/K mutations in patients with idiopathic myelofibrosis. Br J Haematol 137: 378–379

    Article  CAS  PubMed  Google Scholar 

  69. Tefferi A, Strand JJ, Lasho TL et al. (2006) Respective clustering of unfavorable and favorable cytogenetic clones in myelofibrosis with myeloid metaplasia with homozygosity for JAK2(V617F) and response to erythropoietin therapy. Cancer 106: 1739–1743

    Article  CAS  PubMed  Google Scholar 

  70. Lasho TL, Pardanani A, McClure RF et al. (2006) Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time. Br J Haematol 135: 683–687

    Article  CAS  PubMed  Google Scholar 

  71. Zamora L, Espinet B, Florensa L, Besses C, Salido M, Sole F (2003) Incidence of trisomy 8 and 9, deletion of D13S319 and D20S108 loci and BCR/ABL translocation in non-treated essential thrombocythemia patients: an analysis of bone marrow cells using interphase fluorescence in situ hybridization. Haematologica 88: 110–111

    CAS  PubMed  Google Scholar 

  72. Panani AD (2006) Cytogenetic findings in untreated patients with essential thrombocythemia. In Vivo 20: 381–384

    PubMed  Google Scholar 

  73. 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: 1092–1097

    Article  CAS  PubMed  Google Scholar 

  74. Steensma DP, Tefferi A (2002) Cytogenetic and molecular genetic aspects of essential thrombocythemia. Acta Haematol 108: 55–65

    Article  CAS  PubMed  Google Scholar 

  75. Hirose Y, Masaki Y, Sugai S (2002) Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of four cases. Eur J Haematol 68: 112–116

    Article  PubMed  Google Scholar 

  76. Hsiao HH, Ito Y, Sashida G, Ohyashiki JH, Ohyashiki K (2005) De novo appearance of der(1;7)(q10;p10) is associated with leukemic transformation and unfavorable prognosis in essential thrombocythemia. Leuk Res 29: 1247–1252

    Article  CAS  PubMed  Google Scholar 

  77. Michiels JJ, Berneman Z, Schroyens W et al. (2006) Plateletmediated erythromelalgic, cerebral, ocular and coronary microvascular ischemic and thrombotic manifestations in patients with essential thrombocythemia and polycythemia vera: a distinct aspirin-responsive and coumarin-resistant arterial thrombophilia. Platelets 17: 528–544

    Article  CAS  PubMed  Google Scholar 

  78. Michiels JJ, ten Kate FW, Vuzevski VD, Abels J (1984) Histopathology of erythromelalgia in thrombocythaemia. Histopathology 8: 669–678

    Article  CAS  PubMed  Google Scholar 

  79. Michiels JJ, Berneman Z, Schroyens W, Koudstaal PJ, Lindemans J, van Vliet HH (2006) Platelet-mediated thrombotic complications in patients with ET: reversal by aspirin, platelet reduction, and not by coumadin. Blood Cells Mol Dis 36: 199–205

    Article  CAS  PubMed  Google Scholar 

  80. Falconer J, Pineo G, Blahey W, Bowen T, Docksteader, B, Jadusingh I (1987) Essential thrombocythemia associated with recurrent abortions and fetal growth retardation. Am J Hematol 25: 345–347

    Article  CAS  PubMed  Google Scholar 

  81. Patel RK, Lea NC, Heneghan MA et al. (2006) Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology 130: 2031–2038

    Article  CAS  PubMed  Google Scholar 

  82. Plume G, Vaya A, Ferrando F, Mira Y, Orbis F (2007) JAK2V617F mutation as a marker of a latent myeloproliferative disorder in a patient with Budd-Chiari syndrome and factor V Leiden mutation. Thromb Haemost 98: 681–682

    CAS  PubMed  Google Scholar 

  83. Primignani M, Barosi G, Bergamaschi G et al. (2006) Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology 44: 1528–1534

    Article  CAS  PubMed  Google Scholar 

  84. Thurmes PJ, Steensma DP (2006) Elevated serum erythropoietin levels in patients with Budd-Chiari syndrome secondary to polycythemia vera: clinical implications for the role of JAK2 mutation analysis. Eur J Haematol 77(1): 57–60

    Article  CAS  PubMed  Google Scholar 

  85. Bergamaschi GM, Primignani M, Barosi G et al. (2008) MPL and JAK2exon 12 mutations in patients with the Budd-Chiari syndrome or extrahepatic portal vein obstruction. Blood 111: 4418

    Article  CAS  PubMed  Google Scholar 

  86. Kiladjian JJ, Cervantes F, Leebeek FW 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(10): 4922–4929

    Article  CAS  PubMed  Google Scholar 

  87. P’ng S, Carnley B, Baker R, Kontorinis N, Cheng W (2008) Undiagnosed myeloproliferative disease in cases of intraabdominal thrombosis: the utility of the JAK2617F mutation. Clin Gastroenterol Hepatol 6: 472–475

    Article  CAS  Google Scholar 

  88. Pardanani A, Lasho TL, Schwager S et al. (2007) JAK2V617F prevalence and allele burden in non-splanchnic venous thrombosis in the absence of overt myeloproliferative disorder. Leukemia 21: 1828–1829

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  90. Randi ML, Stocco F, Rossi C, Tison T, Girolami A (1991) Thrombosis and hemorrhage in thrombocytosis: evaluation of a large cohort of patients (357 cases). J Med 22: 213–223

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  93. Fey MF (1985) Spontaneous massive abdominal wall hematoma in polycythemia vera. Acta Haematol 73: 122–123

    Article  CAS  PubMed  Google Scholar 

  94. Ishihara S, Yasuhara H, Ogawa S, Muto T (2000) Successful surgical treatment for spontaneous retroperitoneal hematoma in polycythemia vera: report of a case. Surg Today 30: 199–201

    Article  CAS  PubMed  Google Scholar 

  95. Pedersen LM, Milman N (2003) Diagnostic significance of platelet count and other blood analyses in patients with lung cancer. Oncol Rep 10: 213–216

    PubMed  Google Scholar 

  96. Uppenkamp M, Makarova E, Petrasch S, Brittinger G (1998) Thrombopoietin serum concentration in patients with reactive and myeloproliferative thrombocytosis. Ann Hematol 77: 217–223

    Article  CAS  PubMed  Google Scholar 

  97. Straneva JE, van Besien KW, Derigs G, Hoffman R (1992) Is interleukin 6 the physiological regulator of thrombopoiesis? Exp Hematol 20: 47–50

    CAS  PubMed  Google Scholar 

  98. Dame C, Sutor AH (2005) Primary and secondary thrombocytosis in childhood. Br J Haematol 129: 165–177

    Article  CAS  PubMed  Google Scholar 

  99. Thiele J, Kvasnicka HM (2006) Clinicopathological criteria for differential diagnosis of thrombocythemias in various myeloproliferative disorders. Semin Thromb Hemost 32: 219–230

    Article  PubMed  Google Scholar 

  100. Michiels JJ, De Raeve H, Hebeda K et al. (2007) WHO bone marrow features and European clinical, molecular, and pathological (ECMP) criteria for the diagnosis of myeloproliferative disorders. Leuk Res 31: 1031–1038

    Article  CAS  PubMed  Google Scholar 

  101. 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: 14–22

    Article  CAS  PubMed  Google Scholar 

  102. Teofili L, Martini M, Cenci T et al. (2007) Different STAT-3 and STAT-5 phosphorylation discriminates among Ph-negative chronic myeloproliferative diseases and is independent of the V617F JAK-2 mutation. Blood 110: 354–359

    Article  CAS  PubMed  Google Scholar 

  103. Michiels JJ, Berneman Z, Schroyens W, Finazzi G, Budde U, van Vliet HH (2006) The paradox of platelet activation and impaired function: platelet-von Willebrand factor interactions, and the etiology of thrombotic and hemorrhagic manifestations in essential thrombocythemia and polycythemia vera. Semin Thromb Hemost 32: 589–604

    Article  CAS  PubMed  Google Scholar 

  104. Beck MR Jr, Eckstein EC (1980) Preliminary report on platelet concentration in capillary tube flows of whole blood. Biorheology 17: 455–464

    PubMed  Google Scholar 

  105. Turitto VT, Weiss HJ (1983) Platelet and red cell involvement in mural thrombogenesis. Ann NY Acad Sci 416: 363–376

    Article  CAS  PubMed  Google Scholar 

  106. Michiels JJ, Berneman Z, Van Bockstaele D, van der Planken M, De Raeve H, Schroyens W (2006) Clinical and laboratory features, pathobiology of platelet-mediated thrombosis and bleeding complications, and the molecular etiology of essential thrombocythemia and polycythemia vera: therapeutic implications. Semin Thromb Hemost 32: 174–207

    Article  CAS  PubMed  Google Scholar 

  107. Afshar-Kharghan V, Lopez JA, Gray LA et al. (2004) Hemostatic gene polymorphisms and the prevalence of thrombotic complications in polycythemia vera and essential thrombocythemia. Blood Coagul Fibrinolysis 15: 21–24

    Article  CAS  PubMed  Google Scholar 

  108. Undas A, Brummel K, Musial J, Mann KG, Szczeklik A (2001) Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation 104: 2666–2672

    Article  CAS  PubMed  Google Scholar 

  109. Wehmeier A, Fricke S, Scharf RE, Schneider W (1990) A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders. Eur J Haematol 45: 191–197

    CAS  PubMed  Google Scholar 

  110. 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  CAS  PubMed  Google Scholar 

  111. Landolfi R, Di Gennaro L (2008) Prevention of thrombosis in polycythemia vera and essential thrombocythemia. Haematologica 93: 331–335

    Article  CAS  PubMed  Google Scholar 

  112. Tefferi A, Gangat N, Wolanskyj A (2007) The interaction between leukocytosis and other risk factors for thrombosis in essential thrombocythemia. Blood 109: 4105

    Article  CAS  PubMed  Google Scholar 

  113. Falanga A, Marchetti M, Vignoli A, Balducci D, Barbui T (2005) Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera. Exp Hematol 33: 523–530

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  115. Falanga A, Marchetti M, Barbui T, Smith CW (2005) Pathogenesis of thrombosis in essential thrombocythemia and polycythemia vera: the role of neutrophils. Semin Hematol 42: 239–247

    Article  CAS  PubMed  Google Scholar 

  116. Jensen MK, de Nully BP, Lund BV, Nielsen OJ, Hasselbalch HC (2001) Increased circulating platelet-leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count. Eur J Haematol 66: 143–151

    Article  CAS  PubMed  Google Scholar 

  117. Chlopicki S, Lomnicka M, Gryglewski RJ (2003) Obligatory role of lipid mediators in platelet-neutrophil adhesion. Thromb Res 110: 287–292

    Article  CAS  PubMed  Google Scholar 

  118. Brun M, Bourdoulous S, Couraud PO, Elion J, Krishnamoorthy R, Lapoumeroulie C (2003) Hydroxyurea downregulates endothelin-1 gene expression and upregulates ICAM-1 gene expression in cultured human endothelial cells. Pharmacogenomics J 3: 215–226

    Article  CAS  PubMed  Google Scholar 

  119. Budde U, Schaefer G, Mueller N et al. (1984) Acquired von Willebrand’s disease in the myeloproliferative syndrome. Blood 64: 981–985

    CAS  PubMed  Google Scholar 

  120. Carobbio A, Finazzi G, Guerini V et al. (2007) Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status. Blood 109: 2310–2313

    Article  CAS  PubMed  Google Scholar 

  121. Landolfi R, Di Gennaro L, Barbui T et al. (2007) Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood 109: 2446–2452

    Article  CAS  PubMed  Google Scholar 

  122. Falanga A, Marchetti M, Vignoli A et al. (2007) V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Hematol 35: 702–711

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  124. Finazzi G, Rambaldi A, Guerini V, Carobbo A, Barbui T (2007) Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2V617F mutation status. Haematologica 92: 135–136

    Article  PubMed  Google Scholar 

  125. Heller PG, Lev PR, Salim JP et al. (2006) JAK2V617F mutation in platelets from essential thrombocythemia patients: correlation with clinical features and analysis of STAT5 phosphorylation status. Eur J Haematol 77: 210–216

    Article  CAS  PubMed  Google Scholar 

  126. Campbell PJ, Scott LM, Buck G et al. (2005) Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 366: 1945–1953

    Article  CAS  PubMed  Google Scholar 

  127. Moreno MJ, Lozano ML, Roldan V et al. (2008) JAK2V617F, hemostatic polymorphisms, and clinical features as risk factors for arterial thrombotic events in essential thrombocythemia. Ann Hematol

    Google Scholar 

  128. Lieu CH, Wu HS, Hon YC et al. (2008) Prevalence of the JAK2-V617F mutation in Taiwanese patients with chronic myeloproliferative disorders. Intern Med J

    Google Scholar 

  129. Passamonti F, Randi ML, 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  CAS  PubMed  Google Scholar 

  130. Besses C, Cervantes F, Pereira A et al. (1999) Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia 13: 150–154

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  132. Watson KV, Key N (1993) Vascular complications of essential thrombocythaemia: a link to cardiovascular risk factors. Br J Haematol 83: 198–203

    Article  CAS  PubMed  Google Scholar 

  133. Cervantes F, Passamonti F, Barosi G (2008) Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 22(5): 905–914

    Article  CAS  PubMed  Google Scholar 

  134. Barbui T, Barosi G, Grossi A et al. (2004) 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 89: 215–232

    CAS  PubMed  Google Scholar 

  135. Ruggeri M, Rodeghiero F, Tosetto A et al. (2008) Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 111: 666–671

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  137. Griesshammer M, Grunewald M, Michiels JJ (2003) Acquired thrombophilia in pregnancy: essential thrombocythemia. Semin Thromb Hemost 29: 205–212

    Article  PubMed  Google Scholar 

  138. Candoni A, Fanin R, Michelutti T, Russo D, Michelutti A (2002) Pregnancy and abortion in women with essential thrombocythemia. Am J Hematol 69: 233–234

    Article  PubMed  Google Scholar 

  139. Cervantes F, Alvarez-Larran A, Talarn C, Gomez M, Montserrat E (2002) Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol 118: 786–790

    Article  PubMed  Google Scholar 

  140. Alvarez-Larran A, Cervantes F, Bellosillo B et al. (2007) Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia 21: 1218–1223

    Article  CAS  PubMed  Google Scholar 

  141. Tefferi A, Gangat N, Wolanskyj AP et al. (2008) 20+ yr without leukemic or fibrotic transformation in essential thrombocythemia or polycythemia vera: predictors at diagnosis. Eur J Haematol 80: 386–390

    Article  PubMed  Google Scholar 

  142. Plo I, Nakatake M, Malivert L et al. (2008) JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders. Blood 112(4): 1402–1412

    Article  CAS  PubMed  Google Scholar 

  143. Sterkers Y, Preudhomme C, Lai JL et al. (1998) Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 91: 616–622

    CAS  PubMed  Google Scholar 

  144. Hernandez JA, Florensa L, Sole F, Bosch MA, Espinet B (2001) Acute myeloid leukemia with 17p abnormality in untreated essential thrombocythemia. Leukemia 15: 1308

    Article  CAS  PubMed  Google Scholar 

  145. Tefferi A (1998) Is hydroxyurea leukemogenic in essential thrombocythemia? Blood 92: 1459–1460

    CAS  PubMed  Google Scholar 

  146. Cortelazzo 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  CAS  PubMed  Google Scholar 

  147. Myers TJ, Steinberg WM, Rickles FR (1979) Polycythemia vera and mesenteric arterial thrombosis. A disease association resulting from decreased platelet sensitivity to aspirin. Arch Intern Med 139: 695–698

    Article  CAS  PubMed  Google Scholar 

  148. Chan FK, Ching JY, Hung LC et al. (2005) Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 352: 238–244

    Article  CAS  PubMed  Google Scholar 

  149. Liberopoulos EN, Elisaf MS, Tselepis AD et al. (2006) Upper gastrointestinal haemorrhage complicating antiplatelet treatment with aspirin and/or clopidogrel: where we are now? Platelets 17: 1–6

    Article  CAS  PubMed  Google Scholar 

  150. Tartaglia AP, Goldberg JD, Berk PD, Wasserman LR (1986) Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol 23: 172–176

    CAS  PubMed  Google Scholar 

  151. Michiels JJ, Berneman Z, Schroyens W, van Urk H (2003) Aspirin-responsive painful red, blue, black toe, or finger syndrome in polycythemia vera associated with thrombocythemia. Ann Hematol 82: 153–159

    CAS  PubMed  Google Scholar 

  152. Barbui T, Finazzi G (2005) When and how to treat essential thrombocythemia. N Engl J Med 353: 85–86

    Article  CAS  PubMed  Google Scholar 

  153. Gisslinger H, Kralovics R, Gotic M, Holowiecki J, Penka M, Widmann R, Petrides P (2007) Non-inferiority of anagrelide compared to hydroxyurea in newly diagnosed patients with essential thrombocythemia: the ANAHYDRET-study. Blood 110: Abstract 3547

    Google Scholar 

  154. Ruzzon E, Randi ML, Tezza F, Luzzatto G, Scandellari R, Fabris F (2006) Leg ulcers in elderly on hydroxyurea: a single center experience in Ph-myeloproliferative disorders and review of literature. Aging Clin Exp Res 18: 187–190

    PubMed  Google Scholar 

  155. Weinlich G, Schuler G, Greil R, Kofler H, Fritsch P (1998) Leg ulcers associated with long-term hydroxyurea therapy. J Am Acad Dermatol 39: 372–374

    Article  CAS  PubMed  Google Scholar 

  156. Randi ML, Ruzzon E, Luzzatto G, Tezza F, Girolami A, Fabris F (2005) Safety profile of hydroxyurea in the treatment of patients with Philadelphia-negative chronic myeloproliferative disorders. Haematologica 90: 261–262

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  158. Braester A, Quitt M (2000) Hydroxyurea as a cause of drug fever. Acta Haematol 104: 50–51

    Article  CAS  PubMed  Google Scholar 

  159. Lannemyr O, Kutti J (1999) Hydroxyurea as a cause of drug fever in essential thrombocythaemia. Eur J Haematol 62: 354–355

    CAS  PubMed  Google Scholar 

  160. 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  CAS  PubMed  Google Scholar 

  161. Mtvarelidze Z, Kvezereli-Kopadze A, Kvezereli-Kopadze M, Mestiashvili I (2008) Hematologic response to hydroxyurea therapy in children with beta-thalassemia major. Georgian Med News 91–94

    Google Scholar 

  162. Cacciola RR, Di Francesco E, Pezzella F, Tibullo D, Giustolisi R, Cacciola E (2007) Effect of anagrelide on platelet coagulant function in patients with essential thrombocythemia. Acta Haematol 118: 215–218

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  164. Fruchtman SM, Petitt RM, Gilbert HS, Fiddler G, Lyne A (2005) Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders. Leuk Res 29: 481–491

    Article  CAS  PubMed  Google Scholar 

  165. Raghavan M, Mazer MA, Brink DJ (2003) Severe hypersensitivity pneumonitis associated with anagrelide. Ann Pharmacother 37: 1228–1231

    Article  PubMed  Google Scholar 

  166. Saba R, Jabbour E, Giles F et al. (2005) Interferon alpha therapy for patients with essential thrombocythemia: final results of a phase II study initiated in 1986. Cancer 103: 2551–2557

    Article  CAS  PubMed  Google Scholar 

  167. Pogliani EM, Rossini F, Miccolis I et al. (1995) Alpha interferon as initial treatment of essential thrombocythemia. Analysis after two years of follow-up. Tumori 81: 245–248

    CAS  PubMed  Google Scholar 

  168. Sacchi S, Gugliotta L, Papineschi F et al. (1998) Alfainterferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET. Leukemia 12: 289–294

    Article  CAS  PubMed  Google Scholar 

  169. Catani L, Gugliotta L, Cascione ML et al. (1991) Platelet function and interferon alpha-2a treatment in essential thrombocythaemia. Eur J Haematol 46: 158–162

    CAS  PubMed  Google Scholar 

  170. Quintas-Cardama A, Kantarjian HM, Giles F, Verstovsek S (2006) Pegylated interferon therapy for patients with Philadelphia chromosome-negative myeloproliferative disorders. Semin Thromb Hemost 32: 409–416

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  172. Gugliotta L, Bulgarelli S, Vianelli N, Russo D, Baccarani M (2005) PEG intron treatment in 90 patients with essential thrombocythemia (ET) final report of a phase II study. Blood 106: Abstract 2600

    Google Scholar 

  173. Samuelsson J, Hasselbalch H, Bruserud O et al. (2006) A phase II trial of pegylated interferon alpha-2b therapy for polycythemia vera and essential thrombocythemia: feasibility, clinical and biologic effects, and impact on quality of life. Cancer 106: 2397–2405

    Article  CAS  PubMed  Google Scholar 

  174. Kiladjian JJ, Cassinat B, Turlure P et al. (2006) High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a. Blood 108: 2037–2040

    Article  CAS  PubMed  Google Scholar 

  175. Quintas-Cardama A, Verstovsek S (2007) Experience with oral interferon-alpha in patients with essential thrombocythemia and polycythemia vera. Am J Hematol 82: 859

    Article  PubMed  Google Scholar 

  176. Martinelli P, Martinelli V, Agangi A et al. (2004) Interferon alfa treatment for pregnant women affected by essential thrombocythemia: case reports and a review. Am J Obstet Gynecol 191: 2016–2020

    Article  CAS  PubMed  Google Scholar 

  177. Milano V, Gabrielli S, Rizzo N et al. (1996) Successful treatment of essential thrombocythemia in a pregnancy with recombinant interferon-alpha 2a. J Matern Fetal Med 5: 74–78

    Article  CAS  PubMed  Google Scholar 

  178. Iwashita T, Fujitani M, Yamamoto Y, Katsurada T, Yoshida Y (2006) Interferon-alfa treatment of essential thrombocythemia during pregnancy. Intern Med 45: 1161–1164

    Article  PubMed  Google Scholar 

  179. Brusamolino E, Canevari A, Salvaneschi L, Merante S, Bernasconi C (1984) Efficacy trial of pipobroman in essential thrombocythemia: a study of 24 patients. Cancer Treat Rep 68: 1339–1342

    CAS  PubMed  Google Scholar 

  180. Chistolini A, Mazzucconi MG, Ferrari A et al. (1990) Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. Haematologica 75: 537–540

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  182. Mazzucconi MG, Francesconi M, Chistolini A et al. (1986) Pipobroman therapy of essential thrombocythemia. Scand J Haematol 37: 306–309

    CAS  PubMed  Google Scholar 

  183. Passamonti F, Lazzarino M (2003) Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma 44: 1483–1488

    Article  CAS  PubMed  Google Scholar 

  184. De SV, Mazzucconi MG, Spadea A et al. (2003) Long-term evaluation of 164 patients with essential thrombocythaemia treated with pipobroman: occurrence of leukaemic evolution. Br J Haematol 123: 517–521

    Article  Google Scholar 

  185. Triffet A, Straetmans N, Ferrant A (2001) Bone marrow aplasia after pipobroman: an immune-mediated mechanism? Br J Haematol 115: 713–714

    Article  CAS  PubMed  Google Scholar 

  186. Perreau-Boutet MC, Najman A, Stachowiak J, Parlier Y, Gorin NC, Duhamel G (1982) Management of polycythaemia with pipobroman. Nouv Presse Med 11: 2549–2553

    CAS  PubMed  Google Scholar 

  187. Bouscary D, Jondeau K, Viguie F et al. (1999) Aplastic anemia responsive to cyclosporine complicating the evolution of polycythemia vera. Leuk Lymphoma 33: 607–611

    CAS  PubMed  Google Scholar 

  188. Neveu JP, Rain JD, Lejeune F, Ecard M, Fernand JP, Gruyer P, Brahimi S (2008) Aplasie medullaire au cours d’une polyglobulie traitee par Pipobroman. Seminaires Des Hopitaux de Paris 62: 3115–3116

    Google Scholar 

  189. Brodsky I (1998) Busulfan versus hydroxyurea in the treatment of polycythemia vera (PV) and essential thrombocythemia (ET). Am J Clin Oncol 21: 105–106

    Article  CAS  PubMed  Google Scholar 

  190. Van de Pette JE, Prochazka AV, Pearson TC, Singh AK, Dickson ER, Wetherley-Mein G (1986) Primary thrombocythaemia treated with busulphan. Br J Haematol 62: 229–237

    Article  PubMed  Google Scholar 

  191. Shvidel L, Sigler E, Haran M et al. (2007) Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia. Leukemia 21: 2071–2072

    Article  CAS  PubMed  Google Scholar 

  192. Berrebi A, Shvidel L, Shtalrid M, Klepfish A (2000) Short course of busulphan in essential thrombocythaemia: remodelling of an old strategy. Br J Haematol 109: 249–250

    CAS  PubMed  Google Scholar 

  193. Brandt L, Anderson H (1995) Survival and risk of leukaemia in polycythaemia vera and essential thrombocythaemia treated with oral radiophosphorus: are safer drugs available? Eur J Haematol 54: 21–26

    CAS  PubMed  Google Scholar 

  194. Najean Y, Rain JD, Dresch C et al. (1996) Risk of leukaemia, carcinoma, and myelofibrosis in 32P-or chemotherapy-treated patients with polycythaemia vera: a prospective analysis of 682 cases. The “French Cooperative Group for the Study of Polycythaemias”. Leuk Lymphoma 22(Suppl 1): 111–119

    PubMed  Google Scholar 

  195. Randi ML, Fabris F, Varotto L, Rossi C, Macri C, Girolami A (1990) Haematological complications in polycythaemia vera and thrombocythaemia patients treated with radiophosphorus (32P). Folia Haematol Int Mag Klin Morphol Blutforsch 117: 461–467

    CAS  PubMed  Google Scholar 

  196. Belak M, Jako J (2006) Indications of urgent plasma exchange and cytapheresis therapies — a review based on literature data and personal experience. Orv Hetil 147: 1843–1848

    PubMed  Google Scholar 

  197. Greist A (2002) The role of blood component removal in essential and reactive thrombocytosis. Ther Apher 6: 36–44

    Article  PubMed  Google Scholar 

  198. Liumbruno G, Centoni PE, Ceretelli S, Sodini ML (2000) Rapid reduction of platelet numbers in thrombocytosis. Ther Apher 4: 374–376

    Article  CAS  PubMed  Google Scholar 

  199. Sugawara A, Ebina K, Ohi H, Sawataishi J, Fukuda M (1991) Chronic subdural hematoma associated with primary thrombocythemia; report of an operated case, using plateletpheresis. No Shinkei Geka 19: 851–855

    CAS  PubMed  Google Scholar 

  200. Baron BW, Mick R, Baron JM (1993) Combined plateletpheresis and cytotoxic chemotherapy for symptomatic thrombocytosis in myeloproliferative disorders. Cancer 72: 1209–1218

    Article  CAS  PubMed  Google Scholar 

  201. Relakis C, Kyriakou D, Makrigiannakis AS et al. (1996) Successful pregnancy in a young woman with essential thrombocythemia treated with platelet apheresis. Haematologia (Budap.) 27: 197–200

    CAS  Google Scholar 

  202. Yamaguchi K, Hisano M, Sakata M et al. (2006) Periodic plateletpheresis during pregnancy in a high-risk patient with essential thrombocythemia. J Clin Apher 21: 256–259

    Article  PubMed  Google Scholar 

  203. Rocca B, Ciabattoni G, Tartaglione R et al. (1995) Increased thromboxane biosynthesis in essential thrombocythemia. Thromb Haemost 74: 1225–1230

    CAS  PubMed  Google Scholar 

  204. 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: 1965–1971

    CAS  PubMed  Google Scholar 

  205. Landolfi R, De Candia E, Rocca B et al. (1994) Effects of unfractionated and lowmolecular weight heparins on platelet thromboxane biosynthesis “in vivo”. Thromb Haemost 72: 942–946

    CAS  PubMed  Google Scholar 

  206. Hovens MM, Snoep JD, Tamsma JT, Huisman MV (2006) Aspirin in the prevention and treatment of venous thromboembolism. J Thromb Haemost 4: 1470–1475

    Article  CAS  PubMed  Google Scholar 

  207. Evangelista V, Manarini S, Dell’Elba G et al. (2005) Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost 94: 568–577

    CAS  PubMed  Google Scholar 

  208. Panagiotou I, Kelekis DA, Karatza C, Nikolaou V, Mouyia V, Brountzos EN (2007) Treatment of Budd-Chiari syndrome by transjugular intrahepatic portosystemic shunt. Hepatogastroenterology 54: 1813–1816

    CAS  PubMed  Google Scholar 

  209. Hermeziu B, Franchi-Abella S, Plessier A et al. (2008) Budd-Chiari syndrome and essential thrombocythemia in a child: favorable outcome after transjugular intrahepatic portosystemic shunt. J Pediatr Gastroenterol Nutr 46: 334–337

    Article  PubMed  Google Scholar 

  210. Wright CA, Tefferi A (2001) A single institutional experience with 43 pregnancies in essential thrombocythemia. Eur J Haematol 66: 152–159

    Article  CAS  PubMed  Google Scholar 

  211. Eliyahu S, Shalev E (1997) Essential thrombocythemia during pregnancy. Obstet Gynecol Surv 52: 243–247

    Article  CAS  PubMed  Google Scholar 

  212. Chow EY, Haley LP, Vickars LM (1992) Essential thrombocythemia in pregnancy: platelet count and pregnancy outcome. Am J Hematol 41: 249–251

    Article  CAS  PubMed  Google Scholar 

  213. Bangerter M, Guthner C, Beneke H, Hildebrand A, Grunewald M, Griesshammer M (2000) Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies. Eur J Haematol 65: 165–169

    Article  CAS  PubMed  Google Scholar 

  214. Jones EC, Mosesson MW, Thomason JL, Jackson TC (1988) Essential thrombocythemia in pregnancy. Obstet Gynecol 71: 501–503

    CAS  PubMed  Google Scholar 

  215. Beressi AH, Tefferi A, Silverstein MN, Petitt RM, Hoagland HC (1995) Outcome analysis of 34 pregnancies in women with essential thrombocythemia. Arch Intern Med 155: 1217–1222

    Article  CAS  PubMed  Google Scholar 

  216. Griesshammer M, Bergmann L, Pearson T (1998) Fertility, pregnancy and the management of myeloproliferative disorders. Baillieres Clin Haematol 11: 859–874

    Article  CAS  PubMed  Google Scholar 

  217. Griesshammer M, Struve S, Harrison CM (2006) Essential thrombocythemia/polycythemia vera and pregnancy: the need for an observational study in Europe. Semin Thromb Hemost 32: 422–429

    Article  PubMed  Google Scholar 

  218. Randi ML, Rossi C, Fabris F, Girolami A (2000) Essential thrombocythemia in young adults: major thrombotic complications and complications during pregnancy — a follow-up study in 68 patients. Clin Appl Thromb Hemost 6: 31–35

    Article  CAS  PubMed  Google Scholar 

  219. Nevruz O, Goktolga U, Avcu F, Ozsari L, Ural AU (2007) Multiple gestation in an essential thrombocythemia patient treated with interferon-alpha. Acta Obstet Gynecol Scand 86: 893–895

    Article  CAS  PubMed  Google Scholar 

  220. Thornley S, Manoharan A (1994) Successful treatment of essential thrombocythemia with alpha interferon during pregnancy. Eur J Haematol 52: 63–64

    CAS  PubMed  Google Scholar 

  221. Delage R, Demers C, Cantin G, Roy J (1996) Treatment of essential thrombocythemia during pregnancy with interferon-alpha. Obstet Gynecol 87: 814–817

    CAS  PubMed  Google Scholar 

  222. Vianelli N, Gugliotta L, Tura S, Bovicelli L, Rizzo N, Gabrielli A (1994) Interferon-alpha 2a treatment in a pregnant woman with essential thrombocythemia. Blood 83: 874–875

    CAS  PubMed  Google Scholar 

  223. Fritz M, Vats K, Goyal RK (2005) Neonatal lupus and IUGR following alpha-interferon therapy during pregnancy. J Perinatol 25: 552–554

    Article  PubMed  Google Scholar 

  224. Doubek M, Brychtova Y, Doubek R, Janku P, Mayer J (2004) Anagrelide therapy in pregnancy: report of a case of essential thrombocythemia. Ann Hematol 83: 726–727

    Article  PubMed  Google Scholar 

  225. Pagliaro P, Arrigoni L, Muggiasca ML, Poggio M, Russo U, Rossi E (1996) Primary thrombocythemia and pregnancy: treatment and outcome in fifteen cases. Am J Hematol 53: 6–10

    Article  CAS  PubMed  Google Scholar 

  226. Teofili L, Foa R, Giona F, Larocca LM (2008) Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients? Haematologica 93: 169–172

    Article  PubMed  Google Scholar 

  227. Veselovska J, Pospisilova D, Pekova S et al. (2008) Most pediatric patients with essential thrombocythemia show hypersensitivity to erythropoietin in vitro, with rare JAK2 V617F-positive erythroid colonies. Leuk Res 32: 369–377

    Article  CAS  PubMed  Google Scholar 

  228. Randi ML, Putti MC, Pacquola E, Luzzatto G, Zanesco L, Fabris F (2005) Normal thrombopoietin and its receptor (c-mpl) genes in children with essential thrombocythemia. Pediatr Blood Cancer 44: 47–50

    Article  CAS  PubMed  Google Scholar 

  229. Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC (1998) An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet 18: 49–52

    Article  CAS  PubMed  Google Scholar 

  230. Teofili L, Giona F, Martini M et al. (2007) The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia. Blood 110: 3384–3386

    Article  CAS  PubMed  Google Scholar 

  231. Michiels JJ, Van Genderen PJ (1997) Essential thrombocythemia in childhood. Semin Thromb Hemost 23: 295–301

    Article  CAS  PubMed  Google Scholar 

  232. Scherer S, Ferrari R, Rister M (2003) Treatment of essential thrombocythemia in childhood. Pediatr Hematol Oncol 20: 361–365

    PubMed  Google Scholar 

  233. Ding J, Komatsu H, Wakita A et al. (2004) Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 103: 4198–4200

    Article  CAS  PubMed  Google Scholar 

  234. Liu K, Kralovics R, Rudzki Z et al. (2008) A de novo splice donor mutation in the thrombopoietin gene causes hereditary thrombocythemia in a Polish family. Haematologica 93: 706–714

    Article  CAS  PubMed  Google Scholar 

  235. Kunishima S, Mizuno S, Naoe T, Saito H, Kamiya T (1998) Genes for thrombopoietin and c-mpl are not responsible for familial thrombocythaemia: a case study. Br J Haematol 100: 383–386

    Article  CAS  PubMed  Google Scholar 

  236. Kikuchi M, Tayama T, Hayakawa H, Takahashi I, Hoshino H, Ohsaka A (1995) Familial thrombocytosis. Br J Haematol 89: 900–902

    CAS  PubMed  Google Scholar 

  237. Slee PH, van Everdingen JJ, Geraedts JP, te VJ, den Ottolander GJ (1981) Familial myeloproliferative disease. Hematological and cytogenetic studies. Acta Med Scand 210: 321–327

    CAS  PubMed  Google Scholar 

  238. Stuhrmann M, Bashawri L, Ahmed MA et al. (2001) Familial thrombocytosis as a recessive, possibly X-linked trait in an Arab family. Br J Haematol 112: 616–620

    Article  CAS  PubMed  Google Scholar 

  239. Eyster ME, Saletan SL, Rabellino EM et al. (1986) Familial essential thrombocythemia. Am J Med 80: 497–502

    Article  CAS  PubMed  Google Scholar 

  240. Schlemper RJ, van der Maas AP, Eikenboom JC (1994) Familial essential thrombocythemia: clinical characteristics of 11 cases in one family. Ann Hematol 68: 153–158

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  242. van Dijken PJ, Woldendorp KH, van Wouwe JP (1996) Familial thrombocytosis in infancy presenting with a leukaemoid reaction. Acta Paediatr 85: 1132–1134

    Article  PubMed  Google Scholar 

  243. Perez-Encinas M, Bello JL, Perez-Crespo S, De Miguel R, Tome S (1994) Familial myeloproliferative syndrome. Am J Hematol 46: 225–229

    Article  CAS  PubMed  Google Scholar 

  244. Fernandez-Robles E, Vermylen C, Martiat P, Ninane J, Cornu G (1990) Familial essential thrombocythemia. Pediatr Hematol Oncol 7: 373–376

    Article  CAS  PubMed  Google Scholar 

  245. Michiels JJ, Berneman Z, Schroyens W et al. (2004) Philadelphia (Ph) chromosome-positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood: natural history and diagnostic differentiation from Ph-negative essential thrombocythemia. Ann Hematol 83: 504–512

    Article  PubMed  Google Scholar 

  246. Martiat P, Ifrah N, Rassool F et al. (1989) Molecular analysis of Philadelphia positive essential thrombocythemia. Leukemia 3: 563–565

    CAS  PubMed  Google Scholar 

  247. Girodon F, Bailly F, Barry M et al. (2005) Philadelphia chromosome-positive thrombocythemia without features of chronic myeloid leukemia (CML) in peripheral blood. Ann Hematol 84: 409–410

    Article  PubMed  Google Scholar 

  248. Michiels JJ, Prins ME, Hagermeijer A et al. (1987) Philadelphia chromosome-positive thrombocythemia and megakaryoblast leukemia. Am J Clin Pathol 88: 645–652

    CAS  PubMed  Google Scholar 

  249. Fadilah SA, Cheong SK (2000) BCR-ABL positive essential thrombocythaemia: a variant of chronic myelogerous leukaemia or a distinct clinical entity: a special case report. Singapore Med J 41: 595–598

    CAS  PubMed  Google Scholar 

  250. Paietta E, Rosen N, Roberts M, Papenhausen P, Wiernik PH (1987) Philadelphia chromosome positive essential thrombocythemia evolving into lymphoid blast crisis. Cancer Genet Cytogenet 25: 227–231

    Article  CAS  PubMed  Google Scholar 

  251. Rice L, Popat U (2005) Every case of essential thrombocythemia should be tested for the Philadelphia chromosome. Am J Hematol 78: 71–73

    Article  PubMed  Google Scholar 

  252. Daly K, Nandula SV, Murty VV, Nichols G (2005) Variant translocation with a deletion of derivative (9q) in a case of Philadelphia chromosome positive (Ph+) essential thrombocythemia (ET), a variant of chronic myelogenous leukemia (CML) with a poor prognosis. Leuk Lymphoma 46: 1801–1806

    Article  CAS  PubMed  Google Scholar 

  253. Pajor L, Kereskai L, Zsdral K et al. (2003) Philadelphia chromosome and/or bcr-abl mRNA-positive primary thrombocytosis: morphometric evidence for the transition from essential thrombocythaemia to chronic myeloid leukaemia type of myeloproliferation. Histopathology 42: 53–60

    Article  CAS  PubMed  Google Scholar 

  254. Blickstein D, Aviram A, Luboshitz J et al. (1997) BCR-ABL transcripts in bone marrowaspirates of Philadelphia-negative essential thrombocytopenia patients: clinical presentation. Blood 90: 2768–2771

    CAS  PubMed  Google Scholar 

  255. Aviram A, Blickstein D, Stark P et al. (1999) Significance of BCR-ABL transcripts in bone marrow aspirates of Philadelphia-negative essential thrombocythemia patients. Leuk Lymphoma 33: 77–82

    CAS  PubMed  Google Scholar 

  256. Singer IO, Sproul A, Tait RC, Soutar R, Gibson B (1998) BCR-ABL transcripts detectable in all myeloproliferative states. Blood 92: Abstract 427a

    Google Scholar 

  257. Heller P, Kornblihtt LI, Cuello MT, Larripa I, Najfeld V, Molinas FC (2001) BCR-ABL transcripts may be detected in essential thrombocythemia but lack clinical significance. Blood 98: 1990

    Article  CAS  PubMed  Google Scholar 

  258. Emilia G, Marasca R, Zucchini P et al. (2001) BCR-ABL rearrangement is not detectable in essential thrombocythemia. Blood 97: 2187–2189

    Article  CAS  PubMed  Google Scholar 

  259. Hackwell S, Ross F, Cullis JO (1999) Patients with essential thrombocythemia do not express BCR-ABL transcripts. Blood 93: 2420–2421

    CAS  PubMed  Google Scholar 

  260. Kwong YL, Chiu EK, Liang RH, Chan V, Chan TK (1996) Essential thrombocythemia with BCR/ABL rearrangement. Cancer Genet Cytogenet 89: 74–76

    Article  CAS  PubMed  Google Scholar 

  261. Morris CM, Fitzgerald PH, Hollings PE et al. (1988) Essential thrombocythaemia and the Philadelphia chromosome. Br J Haematol 70: 13–19

    Article  CAS  PubMed  Google Scholar 

  262. Cervantes F, Urbano-Ispizua A, Villamor N et al. (1993) Ph-positive chronic myeloid leukemia mimicking essential thrombocythemia and terminating into megakaryoblastic blast crisis: report of two cases with molecular studies. Leukemia 7: 327–330

    CAS  PubMed  Google Scholar 

  263. Marasca R, Luppi M, Zucchini P, Longo G, Torelli G, Emilia G (1998) Might essential thrombocythemia carry Ph anomaly? Blood 91: 3084–3085

    CAS  PubMed  Google Scholar 

  264. Damaj G, Delabesse E, Le Bihan C et al. (2002) Typical essential thrombocythaemia does not express bcr-abelson fusion transcript. Br J Haematol 116: 812–816

    Article  CAS  PubMed  Google Scholar 

  265. Mesa RA (2007) Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders. Hematol Am Soc Hematol Educ Program 2007: 355–362

    Google Scholar 

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  1. Universitätsklinik für Innere Medizin III, Paracelsus Medizinische Privatuniversität, Salzburg, Austria

    Dr. med. Dipl. Ing. biomed. inf. Lisa Pleyer (Editor), Dr. med. Victoria Faber, PD Dr. med. Daniel Neureiter M.A. (Editor), PD Dr. med. Daniel Neureiter M.A. (Editor) & Univ.-Prof. Dr. med. Richard Greil (Editor)

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  1. Dr. med. Dipl. Ing. biomed. inf. Lisa Pleyer
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  2. Dr. med. Victoria Faber
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    Richard Greil , Lisa Pleyer  & Viktoria Faber ,  & 

  2. Universitätsinstitut für Pathologie, Paracelsus Medizinische Privatuniversität, Salzburg, Austria

    Daniel Neureiter

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Pleyer, L., Faber, V., Neureiter, D., Neureiter, D., Greil, R. (2010). Essential Thrombocythemia (ET). In: Greil, R., Pleyer, L., Faber, V., Neureiter, D. (eds) Chronic Myeloid Neoplasias and Clonal Overlap Syndromes. Springer, Vienna. https://doi.org/10.1007/978-3-211-79892-8_2

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