Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Diagnosis and clinical manifestations of essential thrombocythemia

Ayalew Tefferi, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Alan G Rosmarin, MD


The chronic myeloproliferative disorders (CMPD) are classified into several subgroups, of which four are well characterized (figure 1): chronic myeloid leukemia (CML), polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET, also called essential thrombocytosis or primary thrombocytosis) [1]. (See "Overview of the myeloproliferative neoplasms".)

CML, PV, and PMF can be diagnosed via well accepted clinical and laboratory criteria; ET is alone among these CMPDs in that it is diagnosed by excluding causes of reactive thrombocytosis, and by excluding presence of the other CMPDs [2]. At present, ET is not a cytogenetically or morphologically defined disease entity; the diagnosis of ET refers to the presence of a chronic nonreactive thrombocythemic state that is not accounted for by one of the other chronic myeloproliferative disorders (CMPDs) [3].

The clinical manifestations and diagnosis of ET will be reviewed here. The general approach to the patient with an elevated platelet count, and the treatment of ET are discussed separately. (See "Approach to the patient with thrombocytosis" and "Prognosis and treatment of essential thrombocythemia".)


Neither thrombopoietin (TPO) nor its receptor (c-Mpl) has been implicated in the pathogenesis of ET. Mutations involving the c-Mpl gene are only rarely identified in ET [4], and endogenous megakaryocyte colony growth does not appear to be dependent on an autocrine stimulation involving TPO [5,6]. This is in contrast to autosomal dominant familial essential thrombocythemia where activating mutations in the genes for TPO or c-Mpl, or mutations in the genes for other proteins are responsible for TPO-mediated thrombocytosis. (See "Biology and physiology of thrombopoietin", section on 'Familial thrombocythemia'.)

Serum TPO levels in ET have been reported to be inappropriately normal or elevated [7,8]. This unexpected finding may be a result of increased bone marrow stromal production of TPO [9] or decreased ligand clearance associated with reduced platelet c-Mpl expression in patients with ET [10].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jan 9, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Tefferi A. The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview. Mayo Clin Proc 1998; 73:1177.
  2. Schafer AI. Thrombocytosis. N Engl J Med 2004; 350:1211.
  3. Harrison CN. Current trends in essential thrombocythaemia. Br J Haematol 2002; 117:796.
  4. Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108:3472.
  5. Kiladjian JJ, Elkassar N, Hetet G, et al. Study of the thrombopoitin receptor in essential thrombocythemia. Leukemia 1997; 11:1821.
  6. Taksin AL, Couedic JP, Dusanter-Fourt I, et al. Autonomous megakaryocyte growth in essential thrombocythemia and idiopathic myelofibrosis is not related to a c-mpl mutation or to an autocrine stimulation by Mpl-L. Blood 1999; 93:125.
  7. El-Kassar N, Hetet G, Brière J, Grandchamp B. Clonality analysis of hematopoiesis and thrombopoietin levels in patients with essential thrombocythemia. Leuk Lymphoma 1998; 30:181.
  8. Griesshammer M, Hornkohl A, Nichol JL, et al. High levels of thrombopoietin in sera of patients with essential thrombocythemia: cause or consequence of abnormal platelet production? Ann Hematol 1998; 77:211.
  9. Hirayama Y, Sakamaki S, Matsunaga T, et al. Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells. Blood 1998; 92:46.
  10. Horikawa Y, Matsumura I, Hashimoto K, et al. Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia. Blood 1997; 90:4031.
  11. Fialkow PJ, Faguet GB, Jacobson RJ, et al. Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. Blood 1981; 58:916.
  12. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med 2006; 355:2452.
  13. el-Kassar N, Hetet G, Brière J, Grandchamp B. Clonality analysis of hematopoiesis in essential thrombocythemia: advantages of studying T lymphocytes and platelets. Blood 1997; 89:128.
  14. Janssen JW, Anger BR, Drexler HG, et al. Essential thrombocythemia in two sisters originating from different stem cell levels. Blood 1990; 75:1633.
  15. Chen GL, Prchal JT. X-linked clonality testing: interpretation and limitations. Blood 2007; 110:1411.
  16. Champion KM, Gilbert JG, Asimakopoulos FA, et al. Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes. Br J Haematol 1997; 97:920.
  17. Harrison CN, Gale RE, Machin SJ, Linch DC. A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications. Blood 1999; 93:417.
  18. Shih LY, Lin TL, Lai CL, et al. Predictive values of X-chromosome inactivation patterns and clinicohematologic parameters for vascular complications in female patients with essential thrombocythemia. Blood 2002; 100:1596.
  19. Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood 2006; 107:4214.
  20. Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol 1999; 61:10.
  21. Rozman C, Giralt M, Feliu E, et al. Life expectancy of patients with chronic nonleukemic myeloproliferative disorders. Cancer 1991; 67:2658.
  22. Tefferi A, Fonseca R, Pereira DL, Hoagland HC. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc 2001; 76:22.
  23. Ma X, Vanasse G, Cartmel B, et al. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol 2008; 83:359.
  24. Cortelazzo S, Viero P, Finazzi G, et al. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 1990; 8:556.
  25. Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer 1990; 66:549.
  26. Bellucci S, Janvier M, Tobelem G, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer 1986; 58:2440.
  27. Gugliotta L, et al. Epidemiological, diagnostic, therapeutic, and prognostic aspects of essential thrombocythemia in a retrospective study of the GIMMC group in two thousand patients. Blood 1997; 90:348a.
  28. van Genderen PJ, Mulder PG, Waleboer M, et al. Prevention and treatment of thrombotic complications in essential thrombocythaemia: efficacy and safety of aspirin. Br J Haematol 1997; 97:179.
  29. Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia. Ann Intern Med 1995; 123:656.
  30. Yang RC, Qian LS. Essential thrombocythaemia in children: a report of nine cases. Br J Haematol 2000; 110:1009.
  31. Hasle H, Wadsworth LD, Massing BG, et al. A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada. Br J Haematol 1999; 106:1027.
  32. Fu R, Zhang L, Yang R. Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment. Br J Haematol 2013; 163:295.
  33. Kucine N, Chastain KM, Mahler MB, Bussel JB. Primary thrombocytosis in children. Haematologica 2014; 99:620.
  34. Hasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia 1995; 9:1569.
  35. Giona F, Teofili L, Moleti ML, et al. Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome. Blood 2012; 119:2219.
  36. Randi ML, Putti MC, Scapin M, et al. Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood 2006; 108:3600.
  37. Teofili L, Giona F, Martini M, et al. Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia. J Clin Oncol 2007; 25:1048.
  38. Langabeer SE, Haslam K, McMahon C. A prenatal origin of childhood essential thrombocythaemia. Br J Haematol 2013; 163:674.
  39. Etheridge SL, Cosgrove ME, Sangkhae V, et al. A novel activating, germline JAK2 mutation, JAK2R564Q, causes familial essential thrombocytosis. Blood 2014; 123:1059.
  40. Chistolini A, Mazzucconi MG, Ferrari A, et al. Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. Haematologica 1990; 75:537.
  41. Kurzrock R, Cohen PR. Erythromelalgia and myeloproliferative disorders. Arch Intern Med 1989; 149:105.
  42. Michiels JJ, van Genderen PJ, Jansen PH, Koudstaal PJ. Atypical transient ischemic attacks in thrombocythemia of various myeloproliferative disorders. Leuk Lymphoma 1996; 22 Suppl 1:65.
  43. van Genderen PJ, Prins FJ, Michiels JJ, Schrör K. Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent. Br J Haematol 1999; 104:438.
  44. Michiels JJ, Abels J, Steketee J, et al. Erythromelalgia caused by platelet-mediated arteriolar inflammation and thrombosis in thrombocythemia. Ann Intern Med 1985; 102:466.
  45. Michiels JJ, Koudstaal PJ, Mulder AH, van Vliet HH. Transient neurologic and ocular manifestations in primary thrombocythemia. Neurology 1993; 43:1107.
  46. Ruggeri M, Finazzi G, Tosetto A, et al. No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol 1998; 103:772.
  47. Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128:275.
  48. Hobbs CM, Manning H, Bennett C, et al. JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a knock-in mouse model of essential thrombocythemia. Blood 2013; 122:3787.
  49. Colombi M, Radaelli F, Zocchi L, Maiolo AT. Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer 1991; 67:2926.
  50. Carobbio A, Thiele J, Passamonti F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 2011; 117:5857.
  51. Gangat N, Wolanskyj AP, Schwager SM, et al. Estrogen-based hormone therapy and thrombosis risk in women with essential thrombocythemia. Cancer 2006; 106:2406.
  52. Griesshammer M, Bangerter M, van Vliet HH, Michiels JJ. Aspirin in essential thrombocythemia: status quo and quo vadis. Semin Thromb Hemost 1997; 23:371.
  53. Ruggeri M, Rodeghiero F, Tosetto A, et al. Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 2008; 111:666.
  54. Budde U, Schaefer G, Mueller N, et al. Acquired von Willebrand's disease in the myeloproliferative syndrome. Blood 1984; 64:981.
  55. van Genderen PJ, Budde U, Michiels JJ, et al. The reduction of large von Willebrand factor multimers in plasma in essential thrombocythaemia is related to the platelet count. Br J Haematol 1996; 93:962.
  56. Fabris F, Casonato A, Grazia del Ben M, et al. Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis. Br J Haematol 1986; 63:75.
  57. Rolf N, Suttorp M, Budde U, et al. Essential thrombocythaemia in a teenage girl resulting in acquired von Willebrand syndrome with joint haemorrhage and menorrhagia. Thromb Haemost 2010; 103:1272.
  58. Murphy S, Peterson P, Iland H, Laszlo J. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol 1997; 34:29.
  59. Emilia G, Sacchi S, Temperani P, et al. Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis. Leuk Lymphoma 1993; 9:423.
  60. Randi ML, Barbone E, Zerbinati P, et al. Essential thrombocythemia following polycythemia vera: an unusual sequence. J Med 1996; 27:363.
  61. Tefferi A, Silverstein MN, Hoagland HC. Primary thrombocythemia. Semin Oncol 1995; 22:334.
  62. Cervantes F, Alvarez-Larrán A, Talarn C, et al. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol 2002; 118:786.
  63. Cervantes F, Tassies D, Salgado C, et al. Acute transformation in nonleukemic chronic myeloproliferative disorders: actuarial probability and main characteristics in a series of 218 patients. Acta Haematol 1991; 85:124.
  64. Sterkers Y, Preudhomme C, Laï JL, et al. Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998; 91:616.
  65. Geller SA, Shapiro E. Acute leukemia as a natural sequel to primary thrombocythemia. Am J Clin Pathol 1982; 77:353.
  66. Shibata K, Shimamoto Y, Suga K, et al. Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation--a brief review of recent literature. Acta Haematol 1994; 91:84.
  67. Griesshammer M, Heimpel H, Pearson TC. Essential thrombocythemia and pregnancy. Leuk Lymphoma 1996; 22 Suppl 1:57.
  68. Passamonti F, Randi ML, Rumi E, et al. Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood 2007; 110:485.
  69. Pagliaro P, Arrigoni L, Muggiasca ML, et al. Primary thrombocythemia and pregnancy: treatment and outcome in fifteen cases. Am J Hematol 1996; 53:6.
  70. Beressi AH, Tefferi A, Silverstein MN, et al. Outcome analysis of 34 pregnancies in women with essential thrombocythemia. Arch Intern Med 1995; 155:1217.
  71. Picardi M, Martinelli V, Ciancia R, et al. Measurement of spleen volume by ultrasound scanning in patients with thrombocytosis: a prospective study. Blood 2002; 99:4228.
  72. Wolanskyj AP, Lasho TL, Schwager SM, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005; 131:208.
  73. Kadikoylu G, Onbasili A, Tekten T, et al. Functional and morphological cardiac changes in myeloproliferative disorders (clinical study). Int J Cardiol 2004; 97:213.
  74. Dingli D, Utz JP, Krowka MJ, et al. Unexplained pulmonary hypertension in chronic myeloproliferative disorders. Chest 2001; 120:801.
  75. Altintas A, Karahan Z, Pasa S, et al. Pulmonary hypertension in patients with essential thrombocythemia and reactive thrombocytosis. Leuk Lymphoma 2007; 48:1981.
  76. Murphy S, Iland H, Rosenthal D, Laszlo J. Essential thrombocythemia: an interim report from the Polycythemia Vera Study Group. Semin Hematol 1986; 23:177.
  77. Imbert M, Vardiman JW, Pierre R. Essential thrombocythaemia. In: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds), IARC Press, Lyon 2001.
  78. Harrison CN. Essential thrombocythaemia: challenges and evidence-based management. Br J Haematol 2005; 130:153.
  79. Tefferi A, Thiele J, Orazi A, et al. 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 2007; 110:1092.
  80. Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood 2008; 112:231.
  81. Iland H, Laszlo J, Murphy S. Essential thrombocythemia. In: Polycythemia Vera and the Myeloproliferative Disorders, Wasserman LR, Berk PD, Berlin NI (Eds), Saunders, Philadelphia 1995. p.292.
  82. Damaj G, Delabesse E, Le Bihan C, et al. Typical essential thrombocythaemia does not express bcr-abelson fusion transcript. Br J Haematol 2002; 116:812.
  83. Tefferi A, Ho TC, Ahmann GJ, et al. Plasma interleukin-6 and C-reactive protein levels in reactive versus clonal thrombocytosis. Am J Med 1994; 97:374.
  84. Campbell PJ, Scott LM, Buck G, et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005; 366:1945.
  85. Gangat N, Wolanskyj AP, McClure RF, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 2007; 21:270.
  86. Rumi E, Pietra D, Ferretti V, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2013.
  87. Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 2013.
  88. Levine RL, Belisle C, Wadleigh M, et al. X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood 2006; 107:4139.
  89. Gale RE, Allen AJ, Nash MJ, Linch DC. 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 2007; 109:1241.
  90. Kittur J, Knudson RA, Lasho TL, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 2007; 109:2279.
  91. Cheung B, Radia D, Pantelidis P, et al. The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol 2006; 132:244.
  92. Zhang S, Qiu H, Fischer BS, et al. JAK2 V617F patients with essential thrombocythemia present with clinical features of polycythemia vera. Leuk Lymphoma 2008; 49:696.
  93. Toyama K, Karasawa M, Yamane A, et al. JAK2-V617F mutation analysis of granulocytes and platelets from patients with chronic myeloproliferative disorders: advantage of studying platelets. Br J Haematol 2007; 139:64.
  94. Wong RS, Cheng CK, Chan NP, et al. JAK2 V617F mutation is associated with increased risk of thrombosis in Chinese patients with essential thrombocythaemia. Br J Haematol 2008; 141:902.
  95. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013; 369:2391.
  96. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013; 369:2379.
  97. Giona F, Teofili L, Capodimonti S, et al. CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence. Blood 2014; 123:3677.
  98. Chao MP, Gotlib J. Two faces of ET: CALR and JAK2. Blood 2014; 123:1438.
  99. Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 2008; 112:141.
  100. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood 2008; 112:844.
  101. Cerutti A, Custodi P, Duranti M, et al. Thrombopoietin levels in patients with primary and reactive thrombocytosis. Br J Haematol 1997; 99:281.
  102. Juvonen E, Ikkala E, Oksanen K, Ruutu T. Megakaryocyte and erythroid colony formation in essential thrombocythaemia and reactive thrombocytosis: diagnostic value and correlation to complications. Br J Haematol 1993; 83:192.
  103. Jenkins RB, Tefferi A, Solberg LA Jr, Dewald GW. Acute leukemia with abnormal thrombopoiesis and inversions of chromosome 3. Cancer Genet Cytogenet 1989; 39:167.
  104. Patel K, Kelsey P. Primary acquired sideroblastic anemia, thrombocytosis, and trisomy 8. Ann Hematol 1997; 74:199.
  105. Thiele J, Zankovich R, Steinberg T, et al. Primary (essential) thrombocythemia versus initial (hyperplastic) stages of agnogenic myeloid metaplasia with thrombocytosis--a critical evaluation of clinical and histomorphological data. Acta Haematol 1989; 81:192.
  106. Stoll DB, Peterson P, Exten R, et al. Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome. Am J Hematol 1988; 27:77.
  107. Mittelman F. The Third International Workshop on Chromosomes in Leukemia. Lund, Sweden, July 21-25, 1980. Introduction. Cancer Genet Cytogenet 1981; 4:96.
  108. Teofili L, Martini M, Luongo M, et al. Overexpression of the polycythemia rubra vera-1 gene in essential thrombocythemia. J Clin Oncol 2002; 20:4249.
  109. Tefferi A, Lasho TL, Wolanskyj AP, Mesa RA. Neutrophil PRV-1 expression across the chronic myeloproliferative disorders and in secondary or spurious polycythemia. Blood 2004; 103:3547.
  110. Axelrad AA, Eskinazi D, Correa PN, Amato D. Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia. Blood 2000; 96:3310.
  111. Mi JQ, Blanc-Jouvan F, Wang J, et al. Endogenous megakaryocytic colony formation and thrombopoietin sensitivity of megakaryocytic progenitor cells are useful to distinguish between essential thrombocythemia and reactive thrombocytosis. J Hematother Stem Cell Res 2001; 10:405.
  112. Escoffre-Barbe M, Amiot L, Beaucournu P, et al. Spontaneous megakaryocytic colony formation does not discriminate between essential thrombocythemia and polycythemia vera. Am J Hematol 2006; 81:554.
  113. Thiele J, Kvasnicka HM, Orazi A, et al. Essential thrombocythaemia. In: WHO classification of tumours of haematopoietic and lymphoid tissues, 4th ed, Swerdlow SH, Campo E, Harris NL (Eds), WHO Press, Lyon 2008. p.48.
  114. Tefferi A, Skoda R, Vardiman JW. Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics. Nat Rev Clin Oncol 2009; 6:627.
  115. Santhosh-Kumar CR, Yohannan MD, Higgy KE, al-Mashhadani SA. Thrombocytosis in adults: analysis of 777 patients. J Intern Med 1991; 229:493.
  116. Robbins G, Barnard DL. Thrombocytosis and microthrombocytosis: a clinical evaluation of 372 cases. Acta Haematol 1983; 70:175.
  117. Custodi P, Cerutti A, Balduini CL. Which tests are most useful to distinguish between clonal and reactive thrombocytosis. Am J Med 1996; 101:233.
  118. Messinezy M, Westwood N, Sawyer B, et al. Primary thrombocythaemia: a composite approach to diagnosis. Clin Lab Haematol 1994; 16:139.
  119. Alexandrakis MG, Passam FH, Moschandrea IA, et al. Levels of serum cytokines and acute phase proteins in patients with essential and cancer-related thrombocytosis. Am J Clin Oncol 2003; 26:135.
  120. Emilia G, Marasca R, Zucchini P, et al. BCR-ABL rearrangement is not detectable in essential thrombocythemia. Blood 2001; 97:2187.
  121. Rice L, Popat U. Every case of essential thrombocythemia should be tested for the Philadelphia chromosome. Am J Hematol 2005; 78:71.
  122. Dekmezian R, Kantarjian HM, Keating MJ, et al. The relevance of reticulin stain-measured fibrosis at diagnosis in chronic myelogenous leukemia. Cancer 1987; 59:1739.
  123. Wilkins BS, Erber WN, Bareford D, et al. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood 2008; 111:60.
  124. Barbui T, Thiele J, Passamonti F, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011; 29:3179.
  125. Barbui T, Thiele J, Carobbio A, et al. Disease characteristics and clinical outcome in young adults with essential thrombocythemia versus early/prefibrotic primary myelofibrosis. Blood 2012; 120:569.
  126. Barbui T, Thiele J, Vannucchi AM, Tefferi A. Problems and pitfalls regarding WHO-defined diagnosis of early/prefibrotic primary myelofibrosis versus essential thrombocythemia. Leukemia 2013; 27:1953.
  127. Cervantes F, Colomer D, Vives-Corrons JL, et al. Chronic myeloid leukemia of thrombocythemic onset: a CML subtype with distinct hematological and molecular features? Leukemia 1996; 10:1241.
  128. Koike T, Uesugi Y, Toba K, et al. 5q-syndrome presenting as essential thrombocythemia: myelodysplastic syndrome or chronic myeloproliferative disorders? Leukemia 1995; 9:517.
  129. Issa S, Ingley K. A case of refractory anemia with ring sideroblasts and associated thrombocytosis. Blood 2013; 121:4256.
  130. Eyster ME, Saletan SL, Rabellino EM, et al. Familial essential thrombocythemia. Am J Med 1986; 80:497.
  131. Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC. An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet 1998; 18:49.
  132. Kondo T, Okabe M, Sanada M, et al. Familial essential thrombocythemia associated with one-base deletion in the 5'-untranslated region of the thrombopoietin gene. Blood 1998; 92:1091.
  133. Ding J, Komatsu H, Wakita A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 2004; 103:4198.
  134. Wiestner A, Padosch SA, Ghilardi N, et al. Hereditary thrombocythaemia is a genetically heterogeneous disorder: exclusion of TPO and MPL in two families with hereditary thrombocythaemia. Br J Haematol 2000; 110:104.
  135. Li J, Xia Y, Kuter DJ. The platelet thrombopoietin receptor number and function are markedly decreased in patients with essential thrombocythaemia. Br J Haematol 2000; 111:943.
  136. Teofili L, Larocca LM. Advances in understanding the pathogenesis of familial thrombocythaemia. Br J Haematol 2011; 152:701.
  137. El-Harith el-HA, Roesl C, Ballmaier M, et al. Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene. Br J Haematol 2009; 144:185.
  138. Teofili L, Giona F, Torti L, et al. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica 2010; 95:65.
  139. Mead AJ, Rugless MJ, Jacobsen SE, Schuh A. Germline JAK2 mutation in a family with hereditary thrombocytosis. N Engl J Med 2012; 366:867.
  140. Marty C, Saint-Martin C, Pecquet C, et al. Germ-line JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitors. Blood 2014; 123:1372.
  141. Rumi E, Harutyunyan AS, Pietra D, et al. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis. Blood 2014.
  142. Tecuceanu N, Dardik R, Rabizadeh E, et al. A family with hereditary thrombocythaemia and normal genes for thrombopoietin and c-Mpl. Br J Haematol 2006; 135:348.