Essential Thrombocythemia (ET)

  • Lisa Pleyer
  • Victoria Faber
  • Daniel Neureiter
  • Daniel Neureiter
  • Richard Greil


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.


Polycythemia Vera Essential Thrombocythemia Myeloproliferative Disorder JAK2 V617F JAK2 V617F Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Johansson P (2006) Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 32: 171–173PubMedCrossRefGoogle Scholar
  2. [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: 159–166PubMedCrossRefGoogle Scholar
  3. [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: 755–761PubMedCrossRefGoogle Scholar
  4. [4]
    Elliott MA, Tefferi A (2005) Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128: 275–290PubMedCrossRefGoogle Scholar
  5. [5]
    Harrison CN (2005) Platelets and thrombosis in myeloproliferative diseases. Hematol Am Soc Hematol Educ Program 409–415Google Scholar
  6. [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 3561Google Scholar
  7. [7]
    Harrison CN, Campbell PJ, Buck G et al. (2005) Hydroxyurea comparedwith anagrelide in high-risk essential thrombocythemia. N Engl J Med 353: 33–45PubMedCrossRefGoogle Scholar
  8. [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: 372–380CrossRefGoogle Scholar
  9. [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: 270–276PubMedCrossRefGoogle Scholar
  10. [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: 417–424PubMedGoogle Scholar
  11. [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: 202–208PubMedCrossRefGoogle Scholar
  12. [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: 1596–1601PubMedCrossRefGoogle Scholar
  13. [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: 131–137PubMedCrossRefGoogle Scholar
  14. [14]
    Chen GL, Prchal JT (2007) X-linked clonality testing: interpretation and limitations. Blood 110: 1411–1419PubMedCrossRefGoogle Scholar
  15. [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: 670–676PubMedCrossRefGoogle Scholar
  16. [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: 214–219PubMedCrossRefGoogle Scholar
  17. [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: 1903–1905PubMedCrossRefGoogle Scholar
  18. [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: 166–171PubMedCrossRefGoogle Scholar
  19. [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: 1055–1060PubMedCrossRefGoogle Scholar
  20. [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: 1207–1212PubMedGoogle Scholar
  21. [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: 246–250PubMedCrossRefGoogle Scholar
  22. [22]
    Shih LY, Lee CT (1994) Identification of masked polycythemia vera from patients with idiopathic marked thrombocytosis by endogenous erythroid colony assay. Blood 83: 744–748PubMedGoogle Scholar
  23. [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: 396–403PubMedCrossRefGoogle Scholar
  24. [24]
    Griesshammer M, Klippel S, Strunck E et al. (2004) PRV-1 mRNA expression discriminates two types of essential thrombocythemia. Ann Hematol 83: 364–370PubMedCrossRefGoogle Scholar
  25. [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: 1677–1683PubMedCrossRefGoogle Scholar
  26. [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: 652–654PubMedCrossRefGoogle Scholar
  27. [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: 2862–2864PubMedCrossRefGoogle Scholar
  28. [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: 851–853PubMedGoogle Scholar
  29. [29]
    Teofili L, Martini M, Guidi F, Venditti D, Leone G, Larocca ML (2004) The PRV-1 gene expression in essential thrombocythemia. Blood 104: 2995–2996PubMedCrossRefGoogle Scholar
  30. [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: 888–889PubMedCrossRefGoogle Scholar
  31. [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: 39–42PubMedCrossRefGoogle Scholar
  32. [32]
    Griesshammer M, Kubanek B, Beneke H et al. (2000) Serum erythropoietin and thrombopoietin levels in patients with essential thrombocythaemia. Leuk Lymphoma 36: 533–538PubMedCrossRefGoogle Scholar
  33. [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: 131–135PubMedCrossRefGoogle Scholar
  34. [34]
    Vannucchi AM, Barbui T (2007) Thrombocytosis and thrombosis. Hematol Am Soc Hematol Educ Program 2007: 363–370Google Scholar
  35. [35]
    Guglielmelli P, Pancrazzi A, Bergamaschi G et al. (2007) Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. Br J Haematol 137: 244–247PubMedCrossRefGoogle Scholar
  36. [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: 714–717PubMedCrossRefGoogle Scholar
  37. [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: 6224–6229PubMedCrossRefGoogle Scholar
  38. [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: 71–77PubMedCrossRefGoogle Scholar
  39. [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: 346–352PubMedCrossRefGoogle Scholar
  40. [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: 3548–3555PubMedCrossRefGoogle Scholar
  41. [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: 375–379PubMedCrossRefGoogle Scholar
  42. [42]
    Pardanani A (2008) JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials. Leukemia 22: 23–30PubMedCrossRefGoogle Scholar
  43. [43]
    Kralovics R, Skoda RC (2005) Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood Rev 19: 1–13Google Scholar
  44. [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: 737–740PubMedCrossRefGoogle Scholar
  45. [45]
    Randi ML, Putti MC, Scapin M et al. (2006) Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood 108: 3600–3602PubMedCrossRefGoogle Scholar
  46. [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: 1048–1053PubMedCrossRefGoogle Scholar
  47. [47]
    Baxter EJ, Scott LM, Campbell PJ et al. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365: 1054–1061PubMedGoogle Scholar
  48. [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: 1144–1148PubMedCrossRefGoogle Scholar
  49. [49]
    Kralovics R, Passamonti F, Buser AS et al. (2005) A gain-offunction mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352: 1779–1790PubMedCrossRefGoogle Scholar
  50. [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: 387–397PubMedCrossRefGoogle Scholar
  51. [51]
    Jones AV, Kreil S, Zoi K et al. (2005) Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 106: 2162–2168PubMedCrossRefGoogle Scholar
  52. [52]
    Antonioli E, Guglielmelli P, Poli G et al. (2008) Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia. Haematologica 93: 41–48PubMedCrossRefGoogle Scholar
  53. [53]
    Kittur J, Knudson RA, Lasho TL et al. (2007) Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 109: 2279–2284PubMedCrossRefGoogle Scholar
  54. [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: 3913–3915PubMedCrossRefGoogle Scholar
  55. [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: 1331–1332PubMedCrossRefGoogle Scholar
  56. [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: 840–846PubMedCrossRefGoogle Scholar
  57. [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: 3676–3682PubMedCrossRefGoogle Scholar
  58. [58]
    Tefferi A, Lasho TL, Gilliland G (2005) JAK2 mutations in myeloproliferative disorders. N Engl J Med 353: 1416–1417PubMedCrossRefGoogle Scholar
  59. [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: 1241–1243PubMedCrossRefGoogle Scholar
  60. [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: 310–316PubMedCrossRefGoogle Scholar
  61. [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: 1480–1482PubMedGoogle Scholar
  62. [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: 1091–1096PubMedGoogle Scholar
  63. [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: e270PubMedCrossRefGoogle Scholar
  64. [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: 3472–3476PubMedCrossRefGoogle Scholar
  65. [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: 11444–11447PubMedCrossRefGoogle Scholar
  66. [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: 1641–1646PubMedCrossRefGoogle Scholar
  67. [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: 2358–2362PubMedCrossRefGoogle Scholar
  68. [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: 378–379PubMedCrossRefGoogle Scholar
  69. [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: 1739–1743PubMedCrossRefGoogle Scholar
  70. [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: 683–687PubMedCrossRefGoogle Scholar
  71. [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: 110–111PubMedGoogle Scholar
  72. [72]
    Panani AD (2006) Cytogenetic findings in untreated patients with essential thrombocythemia. In Vivo 20: 381–384PubMedGoogle Scholar
  73. [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: 1092–1097PubMedCrossRefGoogle Scholar
  74. [74]
    Steensma DP, Tefferi A (2002) Cytogenetic and molecular genetic aspects of essential thrombocythemia. Acta Haematol 108: 55–65PubMedCrossRefGoogle Scholar
  75. [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: 112–116PubMedCrossRefGoogle Scholar
  76. [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: 1247–1252PubMedCrossRefGoogle Scholar
  77. [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: 528–544PubMedCrossRefGoogle Scholar
  78. [78]
    Michiels JJ, ten Kate FW, Vuzevski VD, Abels J (1984) Histopathology of erythromelalgia in thrombocythaemia. Histopathology 8: 669–678PubMedCrossRefGoogle Scholar
  79. [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: 199–205PubMedCrossRefGoogle Scholar
  80. [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: 345–347PubMedCrossRefGoogle Scholar
  81. [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: 2031–2038PubMedCrossRefGoogle Scholar
  82. [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: 681–682PubMedGoogle Scholar
  83. [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: 1528–1534PubMedCrossRefGoogle Scholar
  84. [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): 57–60PubMedCrossRefGoogle Scholar
  85. [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: 4418PubMedCrossRefGoogle Scholar
  86. [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): 4922–4929PubMedCrossRefGoogle Scholar
  87. [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: 472–475CrossRefGoogle Scholar
  88. [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: 1828–1829PubMedCrossRefGoogle Scholar
  89. [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: 556–562PubMedGoogle Scholar
  90. [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: 213–223PubMedGoogle Scholar
  91. [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: 2926–2930PubMedCrossRefGoogle Scholar
  92. [92]
    Fenaux P, Simon M, Caulier MT, Lai JL, Goudemand J, Bauters F (1990) Clinical course of essential thrombocythemia in 147 cases. Cancer 66: 549–556PubMedCrossRefGoogle Scholar
  93. [93]
    Fey MF (1985) Spontaneous massive abdominal wall hematoma in polycythemia vera. Acta Haematol 73: 122–123PubMedCrossRefGoogle Scholar
  94. [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: 199–201PubMedCrossRefGoogle Scholar
  95. [95]
    Pedersen LM, Milman N (2003) Diagnostic significance of platelet count and other blood analyses in patients with lung cancer. Oncol Rep 10: 213–216PubMedGoogle Scholar
  96. [96]
    Uppenkamp M, Makarova E, Petrasch S, Brittinger G (1998) Thrombopoietin serum concentration in patients with reactive and myeloproliferative thrombocytosis. Ann Hematol 77: 217–223PubMedCrossRefGoogle Scholar
  97. [97]
    Straneva JE, van Besien KW, Derigs G, Hoffman R (1992) Is interleukin 6 the physiological regulator of thrombopoiesis? Exp Hematol 20: 47–50PubMedGoogle Scholar
  98. [98]
    Dame C, Sutor AH (2005) Primary and secondary thrombocytosis in childhood. Br J Haematol 129: 165–177PubMedCrossRefGoogle Scholar
  99. [99]
    Thiele J, Kvasnicka HM (2006) Clinicopathological criteria for differential diagnosis of thrombocythemias in various myeloproliferative disorders. Semin Thromb Hemost 32: 219–230PubMedCrossRefGoogle Scholar
  100. [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: 1031–1038PubMedCrossRefGoogle Scholar
  101. [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: 14–22PubMedCrossRefGoogle Scholar
  102. [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: 354–359PubMedCrossRefGoogle Scholar
  103. [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: 589–604PubMedCrossRefGoogle Scholar
  104. [104]
    Beck MR Jr, Eckstein EC (1980) Preliminary report on platelet concentration in capillary tube flows of whole blood. Biorheology 17: 455–464PubMedGoogle Scholar
  105. [105]
    Turitto VT, Weiss HJ (1983) Platelet and red cell involvement in mural thrombogenesis. Ann NY Acad Sci 416: 363–376PubMedCrossRefGoogle Scholar
  106. [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: 174–207PubMedCrossRefGoogle Scholar
  107. [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: 21–24PubMedCrossRefGoogle Scholar
  108. [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: 2666–2672PubMedCrossRefGoogle Scholar
  109. [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: 191–197PubMedGoogle Scholar
  110. [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: 114–124PubMedCrossRefGoogle Scholar
  111. [111]
    Landolfi R, Di Gennaro L (2008) Prevention of thrombosis in polycythemia vera and essential thrombocythemia. Haematologica 93: 331–335PubMedCrossRefGoogle Scholar
  112. [112]
    Tefferi A, Gangat N, Wolanskyj A (2007) The interaction between leukocytosis and other risk factors for thrombosis in essential thrombocythemia. Blood 109: 4105PubMedCrossRefGoogle Scholar
  113. [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: 523–530PubMedCrossRefGoogle Scholar
  114. [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: 4261–4266PubMedGoogle Scholar
  115. [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: 239–247PubMedCrossRefGoogle Scholar
  116. [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: 143–151PubMedCrossRefGoogle Scholar
  117. [117]
    Chlopicki S, Lomnicka M, Gryglewski RJ (2003) Obligatory role of lipid mediators in platelet-neutrophil adhesion. Thromb Res 110: 287–292PubMedCrossRefGoogle Scholar
  118. [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: 215–226PubMedCrossRefGoogle Scholar
  119. [119]
    Budde U, Schaefer G, Mueller N et al. (1984) Acquired von Willebrand’s disease in the myeloproliferative syndrome. Blood 64: 981–985PubMedGoogle Scholar
  120. [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: 2310–2313PubMedCrossRefGoogle Scholar
  121. [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: 2446–2452PubMedCrossRefGoogle Scholar
  122. [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: 702–711PubMedCrossRefGoogle Scholar
  123. [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: 169–175PubMedGoogle Scholar
  124. [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: 135–136PubMedCrossRefGoogle Scholar
  125. [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: 210–216PubMedCrossRefGoogle Scholar
  126. [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: 1945–1953PubMedCrossRefGoogle Scholar
  127. [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 HematolGoogle Scholar
  128. [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 JGoogle Scholar
  129. [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: 485–489PubMedCrossRefGoogle Scholar
  130. [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: 150–154PubMedCrossRefGoogle Scholar
  131. [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: 74–78PubMedCrossRefGoogle Scholar
  132. [132]
    Watson KV, Key N (1993) Vascular complications of essential thrombocythaemia: a link to cardiovascular risk factors. Br J Haematol 83: 198–203PubMedCrossRefGoogle Scholar
  133. [133]
    Cervantes F, Passamonti F, Barosi G (2008) Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 22(5): 905–914PubMedCrossRefGoogle Scholar
  134. [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: 215–232PubMedGoogle Scholar
  135. [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: 666–671PubMedCrossRefGoogle Scholar
  136. [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: 772–777PubMedCrossRefGoogle Scholar
  137. [137]
    Griesshammer M, Grunewald M, Michiels JJ (2003) Acquired thrombophilia in pregnancy: essential thrombocythemia. Semin Thromb Hemost 29: 205–212PubMedCrossRefGoogle Scholar
  138. [138]
    Candoni A, Fanin R, Michelutti T, Russo D, Michelutti A (2002) Pregnancy and abortion in women with essential thrombocythemia. Am J Hematol 69: 233–234PubMedCrossRefGoogle Scholar
  139. [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: 786–790PubMedCrossRefGoogle Scholar
  140. [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: 1218–1223PubMedCrossRefGoogle Scholar
  141. [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: 386–390PubMedCrossRefGoogle Scholar
  142. [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): 1402–1412PubMedCrossRefGoogle Scholar
  143. [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: 616–622PubMedGoogle Scholar
  144. [144]
    Hernandez JA, Florensa L, Sole F, Bosch MA, Espinet B (2001) Acute myeloid leukemia with 17p abnormality in untreated essential thrombocythemia. Leukemia 15: 1308PubMedCrossRefGoogle Scholar
  145. [145]
    Tefferi A (1998) Is hydroxyurea leukemogenic in essential thrombocythemia? Blood 92: 1459–1460PubMedGoogle Scholar
  146. [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: 1132–1136PubMedCrossRefGoogle Scholar
  147. [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: 695–698PubMedCrossRefGoogle Scholar
  148. [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: 238–244PubMedCrossRefGoogle Scholar
  149. [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: 1–6PubMedCrossRefGoogle Scholar
  150. [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: 172–176PubMedGoogle Scholar
  151. [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: 153–159PubMedGoogle Scholar
  152. [152]
    Barbui T, Finazzi G (2005) When and how to treat essential thrombocythemia. N Engl J Med 353: 85–86PubMedCrossRefGoogle Scholar
  153. [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 3547Google Scholar
  154. [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: 187–190PubMedGoogle Scholar
  155. [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: 372–374PubMedCrossRefGoogle Scholar
  156. [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: 261–262PubMedGoogle Scholar
  157. [157]
    Randi ML, Ruzzon E, Tezza F, Luzzatto G, Fabris F (2005) Toxicity and side effects of hydroxyurea used for primary thrombocythemia. Platelets 16: 181–184PubMedCrossRefGoogle Scholar
  158. [158]
    Braester A, Quitt M (2000) Hydroxyurea as a cause of drug fever. Acta Haematol 104: 50–51PubMedCrossRefGoogle Scholar
  159. [159]
    Lannemyr O, Kutti J (1999) Hydroxyurea as a cause of drug fever in essential thrombocythaemia. Eur J Haematol 62: 354–355PubMedGoogle Scholar
  160. [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: 277–280PubMedCrossRefGoogle Scholar
  161. [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 91–94Google Scholar
  162. [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: 215–218PubMedCrossRefGoogle Scholar
  163. [163]
    Storen EC, Tefferi A (2001) Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 97: 863–866PubMedCrossRefGoogle Scholar
  164. [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: 481–491PubMedCrossRefGoogle Scholar
  165. [165]
    Raghavan M, Mazer MA, Brink DJ (2003) Severe hypersensitivity pneumonitis associated with anagrelide. Ann Pharmacother 37: 1228–1231PubMedCrossRefGoogle Scholar
  166. [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: 2551–2557PubMedCrossRefGoogle Scholar
  167. [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: 245–248PubMedGoogle Scholar
  168. [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: 289–294PubMedCrossRefGoogle Scholar
  169. [169]
    Catani L, Gugliotta L, Cascione ML et al. (1991) Platelet function and interferon alpha-2a treatment in essential thrombocythaemia. Eur J Haematol 46: 158–162PubMedGoogle Scholar
  170. [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: 409–416PubMedCrossRefGoogle Scholar
  171. [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: 1281–1282PubMedGoogle Scholar
  172. [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 2600Google Scholar
  173. [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: 2397–2405PubMedCrossRefGoogle Scholar
  174. [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: 2037–2040PubMedCrossRefGoogle Scholar
  175. [175]
    Quintas-Cardama A, Verstovsek S (2007) Experience with oral interferon-alpha in patients with essential thrombocythemia and polycythemia vera. Am J Hematol 82: 859PubMedCrossRefGoogle Scholar
  176. [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: 2016–2020PubMedCrossRefGoogle Scholar
  177. [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: 74–78PubMedCrossRefGoogle Scholar
  178. [178]
    Iwashita T, Fujitani M, Yamamoto Y, Katsurada T, Yoshida Y (2006) Interferon-alfa treatment of essential thrombocythemia during pregnancy. Intern Med 45: 1161–1164PubMedCrossRefGoogle Scholar
  179. [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: 1339–1342PubMedGoogle Scholar
  180. [180]
    Chistolini A, Mazzucconi MG, Ferrari A et al. (1990) Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. Haematologica 75: 537–540PubMedGoogle Scholar
  181. [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: 855–861PubMedCrossRefGoogle Scholar
  182. [182]
    Mazzucconi MG, Francesconi M, Chistolini A et al. (1986) Pipobroman therapy of essential thrombocythemia. Scand J Haematol 37: 306–309PubMedGoogle Scholar
  183. [183]
    Passamonti F, Lazzarino M (2003) Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma 44: 1483–1488PubMedCrossRefGoogle Scholar
  184. [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: 517–521CrossRefGoogle Scholar
  185. [185]
    Triffet A, Straetmans N, Ferrant A (2001) Bone marrow aplasia after pipobroman: an immune-mediated mechanism? Br J Haematol 115: 713–714PubMedCrossRefGoogle Scholar
  186. [186]
    Perreau-Boutet MC, Najman A, Stachowiak J, Parlier Y, Gorin NC, Duhamel G (1982) Management of polycythaemia with pipobroman. Nouv Presse Med 11: 2549–2553PubMedGoogle Scholar
  187. [187]
    Bouscary D, Jondeau K, Viguie F et al. (1999) Aplastic anemia responsive to cyclosporine complicating the evolution of polycythemia vera. Leuk Lymphoma 33: 607–611PubMedGoogle Scholar
  188. [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: 3115–3116Google Scholar
  189. [189]
    Brodsky I (1998) Busulfan versus hydroxyurea in the treatment of polycythemia vera (PV) and essential thrombocythemia (ET). Am J Clin Oncol 21: 105–106PubMedCrossRefGoogle Scholar
  190. [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: 229–237PubMedCrossRefGoogle Scholar
  191. [191]
    Shvidel L, Sigler E, Haran M et al. (2007) Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia. Leukemia 21: 2071–2072PubMedCrossRefGoogle Scholar
  192. [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: 249–250PubMedGoogle Scholar
  193. [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: 21–26PubMedGoogle Scholar
  194. [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): 111–119PubMedGoogle Scholar
  195. [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: 461–467PubMedGoogle Scholar
  196. [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: 1843–1848PubMedGoogle Scholar
  197. [197]
    Greist A (2002) The role of blood component removal in essential and reactive thrombocytosis. Ther Apher 6: 36–44PubMedCrossRefGoogle Scholar
  198. [198]
    Liumbruno G, Centoni PE, Ceretelli S, Sodini ML (2000) Rapid reduction of platelet numbers in thrombocytosis. Ther Apher 4: 374–376PubMedCrossRefGoogle Scholar
  199. [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: 851–855PubMedGoogle Scholar
  200. [200]
    Baron BW, Mick R, Baron JM (1993) Combined plateletpheresis and cytotoxic chemotherapy for symptomatic thrombocytosis in myeloproliferative disorders. Cancer 72: 1209–1218PubMedCrossRefGoogle Scholar
  201. [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: 197–200Google Scholar
  202. [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: 256–259PubMedCrossRefGoogle Scholar
  203. [203]
    Rocca B, Ciabattoni G, Tartaglione R et al. (1995) Increased thromboxane biosynthesis in essential thrombocythemia. Thromb Haemost 74: 1225–1230PubMedGoogle Scholar
  204. [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: 1965–1971PubMedGoogle Scholar
  205. [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: 942–946PubMedGoogle Scholar
  206. [206]
    Hovens MM, Snoep JD, Tamsma JT, Huisman MV (2006) Aspirin in the prevention and treatment of venous thromboembolism. J Thromb Haemost 4: 1470–1475PubMedCrossRefGoogle Scholar
  207. [207]
    Evangelista V, Manarini S, Dell’Elba G et al. (2005) Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost 94: 568–577PubMedGoogle Scholar
  208. [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: 1813–1816PubMedGoogle Scholar
  209. [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: 334–337PubMedCrossRefGoogle Scholar
  210. [210]
    Wright CA, Tefferi A (2001) A single institutional experience with 43 pregnancies in essential thrombocythemia. Eur J Haematol 66: 152–159PubMedCrossRefGoogle Scholar
  211. [211]
    Eliyahu S, Shalev E (1997) Essential thrombocythemia during pregnancy. Obstet Gynecol Surv 52: 243–247PubMedCrossRefGoogle Scholar
  212. [212]
    Chow EY, Haley LP, Vickars LM (1992) Essential thrombocythemia in pregnancy: platelet count and pregnancy outcome. Am J Hematol 41: 249–251PubMedCrossRefGoogle Scholar
  213. [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: 165–169PubMedCrossRefGoogle Scholar
  214. [214]
    Jones EC, Mosesson MW, Thomason JL, Jackson TC (1988) Essential thrombocythemia in pregnancy. Obstet Gynecol 71: 501–503PubMedGoogle Scholar
  215. [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: 1217–1222PubMedCrossRefGoogle Scholar
  216. [216]
    Griesshammer M, Bergmann L, Pearson T (1998) Fertility, pregnancy and the management of myeloproliferative disorders. Baillieres Clin Haematol 11: 859–874PubMedCrossRefGoogle Scholar
  217. [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: 422–429PubMedCrossRefGoogle Scholar
  218. [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: 31–35PubMedCrossRefGoogle Scholar
  219. [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: 893–895PubMedCrossRefGoogle Scholar
  220. [220]
    Thornley S, Manoharan A (1994) Successful treatment of essential thrombocythemia with alpha interferon during pregnancy. Eur J Haematol 52: 63–64PubMedGoogle Scholar
  221. [221]
    Delage R, Demers C, Cantin G, Roy J (1996) Treatment of essential thrombocythemia during pregnancy with interferon-alpha. Obstet Gynecol 87: 814–817PubMedGoogle Scholar
  222. [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: 874–875PubMedGoogle Scholar
  223. [223]
    Fritz M, Vats K, Goyal RK (2005) Neonatal lupus and IUGR following alpha-interferon therapy during pregnancy. J Perinatol 25: 552–554PubMedCrossRefGoogle Scholar
  224. [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: 726–727PubMedCrossRefGoogle Scholar
  225. [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: 6–10PubMedCrossRefGoogle Scholar
  226. [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: 169–172PubMedCrossRefGoogle Scholar
  227. [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: 369–377PubMedCrossRefGoogle Scholar
  228. [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: 47–50PubMedCrossRefGoogle Scholar
  229. [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: 49–52PubMedCrossRefGoogle Scholar
  230. [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: 3384–3386PubMedCrossRefGoogle Scholar
  231. [231]
    Michiels JJ, Van Genderen PJ (1997) Essential thrombocythemia in childhood. Semin Thromb Hemost 23: 295–301PubMedCrossRefGoogle Scholar
  232. [232]
    Scherer S, Ferrari R, Rister M (2003) Treatment of essential thrombocythemia in childhood. Pediatr Hematol Oncol 20: 361–365PubMedGoogle Scholar
  233. [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: 4198–4200PubMedCrossRefGoogle Scholar
  234. [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: 706–714PubMedCrossRefGoogle Scholar
  235. [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: 383–386PubMedCrossRefGoogle Scholar
  236. [236]
    Kikuchi M, Tayama T, Hayakawa H, Takahashi I, Hoshino H, Ohsaka A (1995) Familial thrombocytosis. Br J Haematol 89: 900–902PubMedGoogle Scholar
  237. [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: 321–327PubMedGoogle Scholar
  238. [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: 616–620PubMedCrossRefGoogle Scholar
  239. [239]
    Eyster ME, Saletan SL, Rabellino EM et al. (1986) Familial essential thrombocythemia. Am J Med 80: 497–502PubMedCrossRefGoogle Scholar
  240. [240]
    Schlemper RJ, van der Maas AP, Eikenboom JC (1994) Familial essential thrombocythemia: clinical characteristics of 11 cases in one family. Ann Hematol 68: 153–158PubMedCrossRefGoogle Scholar
  241. [241]
    Dror Y, Zipursky A, Blanchette VS (1999) Essential thrombocythemia in children. J Pediatr Hematol Oncol 21: 356–363PubMedCrossRefGoogle Scholar
  242. [242]
    van Dijken PJ, Woldendorp KH, van Wouwe JP (1996) Familial thrombocytosis in infancy presenting with a leukaemoid reaction. Acta Paediatr 85: 1132–1134PubMedCrossRefGoogle Scholar
  243. [243]
    Perez-Encinas M, Bello JL, Perez-Crespo S, De Miguel R, Tome S (1994) Familial myeloproliferative syndrome. Am J Hematol 46: 225–229PubMedCrossRefGoogle Scholar
  244. [244]
    Fernandez-Robles E, Vermylen C, Martiat P, Ninane J, Cornu G (1990) Familial essential thrombocythemia. Pediatr Hematol Oncol 7: 373–376PubMedCrossRefGoogle Scholar
  245. [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: 504–512PubMedCrossRefGoogle Scholar
  246. [246]
    Martiat P, Ifrah N, Rassool F et al. (1989) Molecular analysis of Philadelphia positive essential thrombocythemia. Leukemia 3: 563–565PubMedGoogle Scholar
  247. [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: 409–410PubMedCrossRefGoogle Scholar
  248. [248]
    Michiels JJ, Prins ME, Hagermeijer A et al. (1987) Philadelphia chromosome-positive thrombocythemia and megakaryoblast leukemia. Am J Clin Pathol 88: 645–652PubMedGoogle Scholar
  249. [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: 595–598PubMedGoogle Scholar
  250. [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: 227–231PubMedCrossRefGoogle Scholar
  251. [251]
    Rice L, Popat U (2005) Every case of essential thrombocythemia should be tested for the Philadelphia chromosome. Am J Hematol 78: 71–73PubMedCrossRefGoogle Scholar
  252. [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: 1801–1806PubMedCrossRefGoogle Scholar
  253. [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: 53–60PubMedCrossRefGoogle Scholar
  254. [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: 2768–2771PubMedGoogle Scholar
  255. [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: 77–82PubMedGoogle Scholar
  256. [256]
    Singer IO, Sproul A, Tait RC, Soutar R, Gibson B (1998) BCR-ABL transcripts detectable in all myeloproliferative states. Blood 92: Abstract 427aGoogle Scholar
  257. [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: 1990PubMedCrossRefGoogle Scholar
  258. [258]
    Emilia G, Marasca R, Zucchini P et al. (2001) BCR-ABL rearrangement is not detectable in essential thrombocythemia. Blood 97: 2187–2189PubMedCrossRefGoogle Scholar
  259. [259]
    Hackwell S, Ross F, Cullis JO (1999) Patients with essential thrombocythemia do not express BCR-ABL transcripts. Blood 93: 2420–2421PubMedGoogle Scholar
  260. [260]
    Kwong YL, Chiu EK, Liang RH, Chan V, Chan TK (1996) Essential thrombocythemia with BCR/ABL rearrangement. Cancer Genet Cytogenet 89: 74–76PubMedCrossRefGoogle Scholar
  261. [261]
    Morris CM, Fitzgerald PH, Hollings PE et al. (1988) Essential thrombocythaemia and the Philadelphia chromosome. Br J Haematol 70: 13–19PubMedCrossRefGoogle Scholar
  262. [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: 327–330PubMedGoogle Scholar
  263. [263]
    Marasca R, Luppi M, Zucchini P, Longo G, Torelli G, Emilia G (1998) Might essential thrombocythemia carry Ph anomaly? Blood 91: 3084–3085PubMedGoogle Scholar
  264. [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: 812–816PubMedCrossRefGoogle Scholar
  265. [265]
    Mesa RA (2007) Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders. Hematol Am Soc Hematol Educ Program 2007: 355–362Google Scholar

Copyright information

© Springer-Verlag/Wien 2010

Authors and Affiliations

  • Lisa Pleyer
    • 1
  • Victoria Faber
    • 1
  • Daniel Neureiter
    • 1
  • Daniel Neureiter
    • 1
  • Richard Greil
    • 1
  1. 1.Universitätsklinik für Innere Medizin IIIParacelsus Medizinische PrivatuniversitätSalzburgAustria

Personalised recommendations