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Diagnosis and clinical manifestations of essential thrombocythemia

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


Essential thrombocythemia (ET) is one of the chronic myeloproliferative neoplasms (MPNs), which are collectively characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. ET has also been called essential thrombocytosis and primary thrombocytosis. It is characterized by excessive, clonal platelet production with a tendency for thrombosis and hemorrhage. (See "Overview of the myeloproliferative neoplasms".)

The clinical manifestations and diagnosis of ET will be reviewed here. The prognosis and treatment of this disorder are presented separately as is the general approach to the patient with an elevated platelet count. (See "Approach to the patient with thrombocytosis" and "Prognosis and treatment of essential thrombocythemia" and "Overview of the myeloproliferative neoplasms".)


The pathogenesis of ET is not completely understood. ET is a clonal stem cell disorder and the increased platelet counts are a result of excessive platelet production and not prolonged platelet survival in the peripheral blood.  

Approximately 90 percent of cases have a somatically acquired driver mutation in JAK2, CALR, or MPL. These mutations result in the upregulation of JAK-STAT target genes, demonstrating the central importance of this pathway in the pathogenesis of ET. Ongoing investigations are aimed at determining the significance of these and other mutations in the genesis of ET and the other myeloproliferative neoplasms as well as their relative roles in determining disease phenotype, leukemic transformation, and the level of involvement of stem cells in these disorders. This is described in more detail separately. (See 'Genetic features' below and "Overview of the myeloproliferative neoplasms", section on 'Mutations in PV, ET, and PMF'.)

While most cases of ET appear to be sporadic, families with an increased incidence of ET have been described, with affected members having the same or different ET-defining mutations or even different MPN type [1,2]. Familial cases are thought to be due to a genetic predisposition to acquire somatic mutations rather than to direct inheritance of germline mutations.  

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Literature review current through: Nov 2017. | This topic last updated: May 12, 2017.
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  1. Rumi E, Passamonti F, Della Porta MG, et al. Familial chronic myeloproliferative disorders: clinical phenotype and evidence of disease anticipation. J Clin Oncol 2007; 25:5630.
  2. 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; 123:2416.
  3. Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood 2017; 129:680.
  4. Kiladjian JJ, Elkassar N, Hetet G, et al. Study of the thrombopoitin receptor in essential thrombocythemia. Leukemia 1997; 11:1821.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Horikawa Y, Matsumura I, Hashimoto K, et al. Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia. Blood 1997; 90:4031.
  10. 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.
  11. 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.
  12. 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.
  13. Hultcrantz M, Wilkes SR, Kristinsson SY, et al. Risk and Cause of Death in Patients Diagnosed With Myeloproliferative Neoplasms in Sweden Between 1973 and 2005: A Population-Based Study. J Clin Oncol 2015; 33:2288.
  14. Srour SA, Devesa SS, Morton LM, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-12. Br J Haematol 2016; 174:382.
  15. Roaldsnes C, Holst R, Frederiksen H, Ghanima W. Myeloproliferative neoplasms: trends in incidence, prevalence and survival in Norway. Eur J Haematol 2017; 98:85.
  16. 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.
  17. Moulard O, Mehta J, Fryzek J, et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. Eur J Haematol 2014; 92:289.
  18. Girodon F, Bonicelli G, Schaeffer C, et al. Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: a population-based study. Haematologica 2009; 94:865.
  19. Rozman C, Giralt M, Feliu E, et al. Life expectancy of patients with chronic nonleukemic myeloproliferative disorders. Cancer 1991; 67:2658.
  20. 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.
  21. Ma X, Vanasse G, Cartmel B, et al. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol 2008; 83:359.
  22. 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.
  23. Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer 1990; 66:549.
  24. Bellucci S, Janvier M, Tobelem G, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer 1986; 58:2440.
  25. 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.
  26. Yang RC, Qian LS. Essential thrombocythaemia in children: a report of nine cases. Br J Haematol 2000; 110:1009.
  27. 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.
  28. Fu R, Zhang L, Yang R. Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment. Br J Haematol 2013; 163:295.
  29. Kucine N, Chastain KM, Mahler MB, Bussel JB. Primary thrombocytosis in children. Haematologica 2014; 99:620.
  30. Hasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia 1995; 9:1569.
  31. 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.
  32. Randi ML, Putti MC, Scapin M, et al. Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative. Blood 2006; 108:3600.
  33. 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.
  34. Langabeer SE, Haslam K, McMahon C. A prenatal origin of childhood essential thrombocythaemia. Br J Haematol 2013; 163:674.
  35. Etheridge SL, Cosgrove ME, Sangkhae V, et al. A novel activating, germline JAK2 mutation, JAK2R564Q, causes familial essential thrombocytosis. Blood 2014; 123:1059.
  36. 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.
  37. 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.
  38. Emanuel RM, Dueck AC, Geyer HL, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 2012; 30:4098.
  39. Scherber R, Dueck AC, Johansson P, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 2011; 118:401.
  40. Kadikoylu G, Onbasili A, Tekten T, et al. Functional and morphological cardiac changes in myeloproliferative disorders (clinical study). Int J Cardiol 2004; 97:213.
  41. Dingli D, Utz JP, Krowka MJ, et al. Unexplained pulmonary hypertension in chronic myeloproliferative disorders. Chest 2001; 120:801.
  42. Altintas A, Karahan Z, Pasa S, et al. Pulmonary hypertension in patients with essential thrombocythemia and reactive thrombocytosis. Leuk Lymphoma 2007; 48:1981.
  43. Chistolini A, Mazzucconi MG, Ferrari A, et al. Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. Haematologica 1990; 75:537.
  44. Kurzrock R, Cohen PR. Erythromelalgia and myeloproliferative disorders. Arch Intern Med 1989; 149:105.
  45. 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.
  46. 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.
  47. 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.
  48. Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood 2006; 107:4214.
  49. Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128:275.
  50. 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.
  51. 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.
  52. 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.
  53. Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia. Ann Intern Med 1995; 123:656.
  54. Gangat N, Wolanskyj AP, Schwager SM, et al. Estrogen-based hormone therapy and thrombosis risk in women with essential thrombocythemia. Cancer 2006; 106:2406.
  55. Griesshammer M, Bangerter M, van Vliet HH, Michiels JJ. Aspirin in essential thrombocythemia: status quo and quo vadis. Semin Thromb Hemost 1997; 23:371.
  56. 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.
  57. Griesshammer M, Heimpel H, Pearson TC. Essential thrombocythemia and pregnancy. Leuk Lymphoma 1996; 22 Suppl 1:57.
  58. 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.
  59. Pagliaro P, Arrigoni L, Muggiasca ML, et al. Primary thrombocythemia and pregnancy: treatment and outcome in fifteen cases. Am J Hematol 1996; 53:6.
  60. Beressi AH, Tefferi A, Silverstein MN, et al. Outcome analysis of 34 pregnancies in women with essential thrombocythemia. Arch Intern Med 1995; 155:1217.
  61. Swerdlow A, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissue, International Agency for Research on Cancer Press, Lyon 2008.
  62. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127:2391.
  63. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013; 369:2379.
  64. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013; 369:2391.
  65. 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.
  66. Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 2013.
  67. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 2014; 28:1472.
  68. Cazzola M, Kralovics R. From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms. Blood 2014; 123:3714.
  69. Milosevic Feenstra JD, Nivarthi H, Gisslinger H, et al. Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood 2016; 127:325.
  70. Cabagnols X, Favale F, Pasquier F, et al. Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients. Blood 2016; 127:333.
  71. 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.
  72. 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.
  73. Kittur J, Knudson RA, Lasho TL, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 2007; 109:2279.
  74. 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.
  75. 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.
  76. 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.
  77. 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.
  78. Giona F, Teofili L, Capodimonti S, et al. CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence. Blood 2014; 123:3677.
  79. Chao MP, Gotlib J. Two faces of ET: CALR and JAK2. Blood 2014; 123:1438.
  80. 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.
  81. Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 2008; 112:141.
  82. 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.
  83. 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.
  84. Murphy S, Iland H, Rosenthal D, Laszlo J. Essential thrombocythemia: an interim report from the Polycythemia Vera Study Group. Semin Hematol 1986; 23:177.
  85. 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.
  86. Harrison CN. Essential thrombocythaemia: challenges and evidence-based management. Br J Haematol 2005; 130:153.
  87. 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.
  88. 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.
  89. Schafer AI. Thrombocytosis. N Engl J Med 2004; 350:1211.
  90. Santhosh-Kumar CR, Yohannan MD, Higgy KE, al-Mashhadani SA. Thrombocytosis in adults: analysis of 777 patients. J Intern Med 1991; 229:493.
  91. Robbins G, Barnard DL. Thrombocytosis and microthrombocytosis: a clinical evaluation of 372 cases. Acta Haematol 1983; 70:175.
  92. 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.
  93. Custodi P, Cerutti A, Balduini CL. Which tests are most useful to distinguish between clonal and reactive thrombocytosis. Am J Med 1996; 101:233.
  94. Messinezy M, Westwood N, Sawyer B, et al. Primary thrombocythaemia: a composite approach to diagnosis. Clin Lab Haematol 1994; 16:139.
  95. 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.
  96. 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.
  97. Emilia G, Marasca R, Zucchini P, et al. BCR-ABL rearrangement is not detectable in essential thrombocythemia. Blood 2001; 97:2187.
  98. Rice L, Popat U. Every case of essential thrombocythemia should be tested for the Philadelphia chromosome. Am J Hematol 2005; 78:71.
  99. 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.
  100. 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.
  101. 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.
  102. 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.
  103. 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.
  104. 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.
  105. 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.
  106. Koike T, Uesugi Y, Toba K, et al. 5q-syndrome presenting as essential thrombocythemia: myelodysplastic syndrome or chronic myeloproliferative disorders? Leukemia 1995; 9:517.
  107. Issa S, Ingley K. A case of refractory anemia with ring sideroblasts and associated thrombocytosis. Blood 2013; 121:4256.
  108. Eyster ME, Saletan SL, Rabellino EM, et al. Familial essential thrombocythemia. Am J Med 1986; 80:497.
  109. 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.
  110. 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.
  111. 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.
  112. 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.
  113. 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.
  114. Teofili L, Larocca LM. Advances in understanding the pathogenesis of familial thrombocythaemia. Br J Haematol 2011; 152:701.
  115. 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.
  116. 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.
  117. Mead AJ, Rugless MJ, Jacobsen SE, Schuh A. Germline JAK2 mutation in a family with hereditary thrombocytosis. N Engl J Med 2012; 366:867.
  118. 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.
  119. 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.
  120. 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.