Abstract
The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5–40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan–Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4–25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5–115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9–10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Elliott MA, Tefferi A . Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2005; 128: 275–290.
Besses C, Cervantes F, Pereira A, Florensa L, Sole F, Hernandez-Boluda JC et al. Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia 1999; 13: 150–154.
Pasamonti F, Rumi E, Pungolino E, Malabarba L, Bertazzoni P, Valentino M et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med 2005; 118: 565–566.
Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A . Essential thrombocythemia beyond the first decade life expectancy, long-term complication rates and prognostic factors. Mayo Clin Proc 2006; 81: 159–166.
Cervantes F, Alvarez-Larrán A, Talarn C, Gómez M, Montserrat E . Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol 2002; 118: 786–790.
Kiladjian JJ, Rain JD, Bernard JF, Briere J, Chomienne C, Fenaux P . Long-term incidence of hematological evolution in three French prospective studies of hydroxyurea and pipobroman in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 2006; 32: 417–421.
Jensen MK, de Nully Brown P, Nielsen OJ, Hasselbalch HC . Incidence, clinical features and outcome of essential thrombocythemia in a well defined geographical area. Eur J Haematol 2000; 65: 132–139.
Tefferi A, Fonseca R, Pereira DL, Hoagland HC . A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc 2001; 76: 22–28.
Mitus AJ, Barbui T, Shulman LN, Rosenthal DS, Viero P, Cortelazzo S et al. Hemostatic complications in young patients with essential thrombocythemia. Am J Med 1990; 88: 371–375.
McIntyre KJ, Hoagland HC, Silverstein MN, Petitt RM . Essential thrombocythemia in young adults. Mayo Clin Proc 1991; 66: 149–154.
Frezzato M, Ruggeri M, Castaman G, Rodeghiero F . Polycythemia vera and essential thrombocythemia in young patients. Haematologica 1993; 78: 11–17.
Randi ML, Rossi C, Fabris F, Girolami A . Essential thrombocythemia in young adults: major thrombotic complications and complications during pregnancy – a follow-up study in 68 patients. Clin Appl Thromb Hemost 2000; 6: 31–35.
Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054–1061.
Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJP et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia and myeloid metaplasia with myelofibrosis. Cancer Cell 2005; 7: 387–397.
James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signaling causes polycythemia vera. Nature 2005; 434: 1144–1148.
Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779–1790.
Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT et al. Definition of subtypes of essential thrombocythemia and relation to polycythemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2006; 366: 1945–1953.
Randi ML, Putti MC, Scapin M, Pacquola E, Tucci F, Micalizzi C et al. Pediatric patients with essential thrombocythemia are mostly polyclonal and V617F JAK2 negative. Blood 2006; 108: 3600–3602.
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: 29–39.
Thiele J, Pierre R, Imbert M, Vardiman JW, Brunning RD, Flandrin G . Classification of tumours. In: Jaffe ES, Harris NL, Stein H and Vardiman JW (eds). Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. IARC Press: Lyon, 2001.
Levine RL, Belisle C, Wadleigh M, Zarieh D, Lee S, Chagnon P 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: 4139–4141.
Fowkes FGR, Housley E, Cawood EHH, Macintyre CCA, Ruckley CV, Prescott RJ . Edinburgh artery study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Intern J Epidemiol 1991; 20: 384–392.
Stewart JA, Dundas R, Howard RS, Rudd AG, Wolfe CDA . Ethnic differences in incidence of stroke: prospective study with stroke register. Br Med J 1999; 318: 967–971.
Heit JA, Silverstein MD, Mohr DN, Petterson TM, Lohse CM, ÓFallon M et al. The epidemiology of venous thromboembolism in the community. Thromb Haemost 2001; 86: 452–463.
Lampe FC, Morris RW, Walker M, Shaper GA, Whincup PH . Trends in rates of different forms of diagnosed coronary heart disease, 1978 to 2000: prospective, population based study of British men. Br Med J 2005; 330: 1046–1049.
Randi ML, Fabris F, Cella G, Rossi C, Girolami A . Cerebral vascular accidents in young patients with essential thrombocythemia; relation with other known cardiovascular risk factors. Angiology 1998; 49: 477–481.
Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of trombosis. N Eng J Med 1995; 332: 1132–1136.
Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Eng J Med 2005; 353: 33–45.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Alvarez-Larrán, A., Cervantes, F., Bellosillo, B. et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia 21, 1218–1223 (2007). https://doi.org/10.1038/sj.leu.2404693
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2404693
Keywords
This article is cited by
-
Essential Thrombocythemia in Adolescents and Young Adults: Clinical Aspects, Treatment Options and Unmet Medical Needs
Current Treatment Options in Oncology (2023)
-
Essential thrombocytosis: diagnosis, differential diagnosis, complications and treatment considerations of relevance for a cardiologist
Netherlands Heart Journal (2023)
-
Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis
Nature Communications (2023)
-
Natural history of polycythemia vera and essential thrombocythemia presenting with splanchnic vein thrombosis
Annals of Hematology (2020)
-
Zweitlinientherapie bei BCR-ABL-negativen myeloproliferativen Neoplasien
Wiener klinisches Magazin (2019)