What is the standard treatment in essential thrombocythemia
Current Concepts of the Myeloproliferative Diseases
The treatment of patients with essential thrombocythemia (ET) should be based primarily on the expected risk of major thrombotic complications. Although the specific values chosen for separating different risk categories are in part arbitrary, the following recomendations can be made. Young asymptomatic subjects with platelet counts below 1,500×109/L are at lower risk and can be followed untreated. However, it should be emphasized that thrombotic events can also occur in a small percentage of these lower-risk cases. Low-dose aspirin (100–300 mg/day) should be given to patients with symptoms of microvascular occlusion, such as erythromelalgia or transient neurological attacks, and avoided in those with bleeding manifestations. The risk/benefit of low-dose aspirin in the primary prevention of thrombosis in asymptomatic patients remains uncertain. For high-risk patients (age >60 years, or platelet count >1,500×109/L, or previous thrombosis), hydroxyurea, plus aspirin in the case of thrombosis, is the treatment of choice because its efficacy in preventing thrombotic complications has been proven in a randomized clinical trial. However, the possible long-term leukemogenicity of this drug, as well as that of other effective cytoreductive agents such as busulphan and pipobroman, remains a major concern. Anagrelide and interferon could overcome this worry but their efficacy has been hitherto demonstrated only in lowering the platelet count. Controlled clinical studies showing a benefit in preventing thrombotic and hemorrhagic complications are urgently needed.
KeywordsPlatelet Count Hydroxyurea Polycythemia Vera Essential Thrombocythemia Thrombocytosis
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Fialkow PJ, Faguet GB, Jacobson RJ, et al. Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent cell.Blood.
Harrison CN, Gale RE, Machin SJ, Linch DC. A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorders and may be at lower risk of thrombotic complications.Blood.
Murphy S. Therapeutic dilemmas: balancing the risk of bleeding, thrombosis, and leukemic transformation in myeloproliferative disorders (MPD).Thromb Haemostas.
Murphy S, Iland HJ. Thrombocytosis. In: Thrombosis and Hemorrhage (1st ed.) Loscalzo J and Schafer AL eds. Williams and Wilkins, Baltimore, 1994. pp. 597–612.Google Scholar
Pearson TC. Primary Thrombocythaemia: diagnosis and management.Br J Haematol.
Rozman C, Giralt M, Feliu E, et al. Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.Cancer.
Murphy S, Iland HJ, Rosenthal D, et al. Essential thrombocythemia: an interim report from the Polycythemia Vera Study Group.Semin Hematol.
Murphy S, Peterson P, Iland H, et al. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment.Semin Hematol.
Dudley JM, Messinezy M, Eridani S, et al. Primary thrombocythemia: diagnostic criteria and a simple scoring system for positive diagnosis.Br J Haematol.
Kutti J, Wadenvik H. Diagnostic and differential criteria of essential thrombocyhemia and reactive thrombocytosis.Leuk Lymphoma.
Sawyer BM, Westwood NB, Pearson TC. Circulating megakaryocyte progenitor cells in patients with primary thrombocythemia and reactive thrombocytosis: results using a serum-deprived culture assay and positive detection technique.Eur J Hematol.
Lengfelder E, Hochhaus A, Kronawitter U, et al. Should a platelet limit of 600×109/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages.Br J Haematol.
Landolfi R, Rocca B, Patrono C. Bleeding and thrombosis in myeloproliferative disorders: mechanisms and treatment.Crit Review Oncol Hematol.
Koudstaal PJ, Koudstaal A. Neurologic and visual symptoms in essential thrombocythemia: efficacy of low-dose aspirin.Semin Thromb Haemostas.
Van Genderen PJJ, Michiels JJ. Erythromelalgia: a patognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera.Semin Thromb Haemostas.
De Stefano V, Teofili L, Leone G, et al. Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis.Semin Thromb Haemostas.
1997; 23:411–418.CrossRefGoogle Scholar
Barbui T, Cortelazzo S, Viero P, et al. Thrombohaemorrhagic complications in 101 cases of myeloproliferative disorders: Relationship to platelet number and function.Eur J Cancer Clin Oncol.
Bellucci S, Janvier M, Tobelem G, et al. Essential thrombocythemia: Clinical evolutionary and biological data.Cancer
. 1986;58:2440–2447.PubMedCrossRefGoogle Scholar
Hehlmann R, Jahn M, Baumann B, et al. Essential thrombocythemia: Clinical characteristics and course of 61 cases.Cancer.
Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases.Cancer.
Colombi M, Radaelli F, Zocchi L, et al. Thrombotic and hemorrhagic complications in essential thrombocytemia.Cancer.
Finazzi G, Budde U, Michiels JJ. Bleeding time and platelet function in essential thrombocythemia and other myeloproliferative syndromes.Leuk Lymphoma.
1996;22(suppl 1):71–78.PubMedGoogle Scholar
Rinder HM, Schuster JE, Rinder CS, et al. Correlation of thrombosis with increased platelet turnover in thrombocytosis.Blood.
Budde U, Scharf RE, Franke P, et al. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma.Blood.
Van Genderen PJJ, Michiels JJ, van der Poel-van de Luytgaarde SCPAM, et al. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: relationship with platelet count.Ann Hematol.
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.
Randi ML, Fabris F, Rossi C, et al. Sex and age as prognostic factors in essential thrombocythemia.Haematologica
. 1992;77:402–404.PubMedGoogle Scholar
McIntyre K, Hoagland H, Silverstein M, et al. Essential thrombocythemia in young adults.Mayo Clin Proc.
1991;66: 149–154.PubMedGoogle Scholar
Mitus AJ, Barbui T, Shulman LN, et al. Hemostatic complications in young patients with essential thrombocythemia.Am J Med.
Kutti J. The management of thrombocytosis.Eur J Haematol.
Schafer AI. Essential thrombocythemia.Progr Hemostas Thromb.
Tefferi A, Silverstein MN, Hoagland HC. Primary thrombocythemia.Semin Oncol.
Barbui T, Finazzi G, Dupuy E, et al. Treatment strategies in essential thrombocythemia.Leuk Lymphoma.
1996;22(suppl 1): 149–160.PubMedCrossRefGoogle Scholar
Griesshammer M, Bangerter M, vanVliet HHDM, et al. Aspirin in essential thrombocythemia: status quo and quo vadis.Semin Thromb Haemostas.
Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy-I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.Br Med J.
1994;308: 81–106.Google Scholar
Kelly JP, Kaufman DW, Jurgelon JM, et al. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product.Lancet.
Pagliaro P, Arrigoni L, Muggiasca ML, et al. Primary thrombocyhthemia and pregnancy. Treatment and outcome in fifteen cases.Am J Hematol.
Griesshammer M, Heimpel H, Pearson TC. Essential thrombocythaemia and pregnancy.Leuk Lymphoma.
1996;22(suppl 1): 57–63.PubMedCrossRefGoogle Scholar
Beressi AH, Tefferi A, Silverstein MN, et al. Outcome analysis of 34 pregnancies in women with essential thrombocythemia.Arch Intern Med.
Shpilberg O, Shimon I, Sofer O, et al. Transient normal platelet count and decreased requirement for interferon during pregnancy in essential thrombocythemia.Br J Haematol.
Lofvenberg E, Walhlin A. Management of polycythaemia vera, essential thrombocythaemia and myelofibrosis with hydroxyurea.Eur J Haematol.
Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea in the treatment of patients with essential thrombocythemia at high risk of thrombosis: a prospective randomized trial.N Engl J Med.
Daoud MS, Gibson LE, Pittelkow MR. Hydroxyurea dermopathy: a unique lichenoid eruption complicating long-term therapy with hydroxyurea.J Am Acad Dermatol.
Best P, Daoud MS, Pittelkow MR et al. Hydroxyurea-induced leg ulceration in 14 patients.Ann Intern Med.
Nand S, Stock W, Godwin J, et al. Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia and myeloid metaplasia with myelofibrosis.Am J Hematol.
Lfvenberg E, Nordenson I, Walhlin A. Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease.Cancer Genet Cytogenet.
Weinfield A, Swolin B, Westin J. Acute leukaemia after hydroxyurea therapy in polycythemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications.Eur J Haematol.
Sterkers Y, Preudhomme C, Lai J-L, et al. Acute myeloid leukemia and myelodyslastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.Blood.
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.
Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Second malignancies in patients with essential thrombocythaemia treated with busulfan and hydroxyurea: long-term follow-up of a randomized clinical trial.Br J Haematol.
Van de Pette JEW, Prochazka AV, Pearson TC, et al. Primary thrombocythemia treated with busulfan.Br J Haematol.
1986; 62:229–237.PubMedCrossRefGoogle Scholar
Berk P, Goldberg J, Donovan P, et al. Therapeutic recommendations in polycythemia vera based on polycythemia vera study group protocols.Semin Hematol.
Haanen C, Mathe G for the EORTC. Treatment of polycythaemia vera by radioactive phosphorus or busulphan.Br J Cancer.
Lengfelder E, Griesshammer M, Hehlmann R. Interferon-alpha in the treatment of essential thrombocythemia.Leuk Lymphoma
. 1996;22(suppl 1):135–142.PubMedCrossRefGoogle Scholar
Tefferi A, Elliot MA, Solberg LA Jr, et al. New drugs in essential thrombocythemia and polycythemia vera.Blood Reviews
. 1997;11:1–7.PubMedCrossRefGoogle Scholar
Tefferi A, Silverstein MN, Petitt RM, et al. Anagrelide as a new platelet-lowering agent in essential thrombocythemia: mechanism of action, efficacy, toxicity, current indication.Semin Thromb Hemostas.
Petitt RM, Silverstein MN, Petrone ME. Anagrelide for control of thrombocythemia in polycythemia and other myeloproliferative disorders.Semi Hematol.
Anagrelide Study Group. Anagrelide, a therapy for thrombocythemic states: experience in 577 patients.Am J Med.
1992; 92:69–76.CrossRefGoogle Scholar
Storen EC, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia.Blood.
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