Essential Thrombocytosis Medication

  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

Medication Summary

Treatment for essential thrombocytosis (primary thrombocythemia) commonly includes the use of hydroxyurea, which is an antimetabolite similar in structure to naturally occurring compounds required for normal cell function. This structural similarity allows many of the antimetabolites to serve as substrates for important cellular enzymes. These substrates inhibit cell replication by direct inhibition of the enzymes needed for DNA replication or DNA repair or by incorporating directly into DNA.

Tumors and healthy cells with high growth fractions (eg, bone marrow) are sensitive to inhibition by the antimetabolites. Anagrelide is an imidazoquinazoline drug that inhibits platelet aggregation. Anagrelide appears to decrease platelet counts by decreasing platelet production.

Interferon alfa is a biologic response modifier, and32 P is a radionuclide with direct myelosuppressive properties. Interferon alfa is not known to be teratogenic and does not cross the placenta, perhaps making it safe for use during pregnancy. Platelet counts rebound in most patients after stopping interferon. Platelet counts are reduced to less than 600,000/μ L in 90% of cases after 3 months. Adjust drug dosing to achieve a platelet count within the reference range (target range, < 450,000/μ L).

Low-dose aspirin may be used to control microvascular symptoms.

Consider the patient's age, status, and adverse effect profile, in addition to the drug's cost, when choosing the treatment agent.[24]

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Antimetabolites

Class Summary

Antimetabolites are similar in structure to the naturally occurring compounds required for the normal function of a cell. This structural similarity allows many of the antimetabolites to serve as substrates for important cellular enzymes, and they inhibit cell replication by direct inhibition of the enzymes needed for DNA replication or repair or by incorporating directly into DNA. Tumors and normal cells with high growth fractions (eg, bone marrow) are sensitive to inhibition by the antimetabolites.

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Hydroxyurea (Hydrea)

 

Inhibitor of deoxynucleotide synthesis and one of the drugs of choice for inducing hematologic remission in chronic myelogenous leukemia. Less leukemogenic than alkylating agents (eg, busulfan, melphalan, chlorambucil). Myelosuppressive effects last a few days to a week and are easier to control than those of alkylating agents; busulfan has prolonged bone marrow suppression and can cause pulmonary fibrosis. The dose can be administered as a single daily dose or divided into 2-3 doses at higher dose ranges. Changes in blood cell counts may take 3-4 d to be apparent after a change in the drug dose.

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Imidazoquinazolines

Class Summary

Imidazoquinazoline agents cause suppression of megakaryocytes and decrease in platelet counts without affecting other hematopoietic cell lines.

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Anagrelide (Agrylin)

 

Mechanism by which anagrelide reduces blood platelet count remains under investigation. Inhibits cyclic nucleotide phosphodiesterase and the release of arachidonic acid from phospholipase, possibly by inhibiting phospholipase A2. Effective in polycythemia vera with elevated platelet counts. Studies in patients support a hypothesis of dose-related reduction in platelet production, resulting from a decrease in megakaryocyte hypermaturation.

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Biologic response modifiers

Class Summary

The exact mechanism of action of biologic response modifiers is undetermined. These agents may be beneficial because of myelosuppressive and antiproliferative effects.

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Interferon alfa (Roferon-A, Intron A)

 

Myelosuppressive protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.

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Radionuclides

Class Summary

Radionuclides have myelosuppressive properties.

Phosphorous-32

 

A beta particle emitter, which is myelosuppressive. Affects all cell types.

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Contributor Information and Disclosures
Author

Asheesh Lal, MBBS, MD  Physician, Department of Internal Medicine, Lexington Medical Center

Asheesh Lal, MBBS, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Wadie F Bahou, MD  Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Epstein E, Goedel A. Hammorhagische thrombocythamie bei vascularer schrumpfmilz. Virch Arch (Pathol Anat). 1934;292:233.

  2. Barbui T, Finazzi G. Treatment indications and choice of a platelet-lowering agent in essential thrombocythemia. Curr Hematol Rep. May 2003;2(3):248-56. [Medline].

  3. Ruggeri M, Gisslinger H, Tosetto A, et al. Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia. Am J Hematol. Sep 2002;71(1):1-6. [Medline]. [Full Text].

  4. Harrison CN, Donohoe S, Carr P, et al. Patients with essential thrombocythaemia have an increased prevalence of antiphospholipid antibodies which may be associated with thrombosis. Thromb Haemost. May 2002;87(5):802-7. [Medline].

  5. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. Apr 27 1995;332(17):1132-6. [Medline]. [Full Text].

  6. Bucalossi A, Marotta G, Bigazzi C, Galieni P, Dispensa E. Reduction of antithrombin III, protein C, and protein S levels and activated protein C resistance in polycythemia vera and essential thrombocythemia patients with thrombosis. Am J Hematol. May 1996;52(1):14-20. [Medline].

  7. Colombi M, Radaelli F, Zocchi L, Maiolo AT. Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer. Jun 1 1991;67(11):2926-30. [Medline].

  8. Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer. Aug 1 1990;66(3):549-56. [Medline].

  9. Chistolini A, Mazzucconi MG, Ferrari A, et al. Essential thrombocythemia: a retrospective study on the clinical course of 100 patients. Haematologica. Nov-Dec 1990;75(6):537-40. [Medline].

  10. Hehlmann R, Jahn M, Baumann B, Köpcke W. Essential thrombocythemia. Clinical characteristics and course of 61 cases. Cancer. Jun 15 1988;61(12):2487-96. [Medline].

  11. Bellucci S, Janvier M, Tobelem G, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer. Dec 1 1986;58(11):2440-7. [Medline].

  12. Kwon M, Osorio S, Muñoz C, Sánchez JM, Buno I, Díez-Martín JL. Essential thrombocythemia in patients with platelet counts below 600x10(9)/L: applicability of the 2008 World Health Organization diagnostic criteria revision proposal. Am J Hematol. Jul 2009;84(7):452-4. [Medline].

  13. Cervantes F. Management of essential thrombocythemia. Hematology Am Soc Hematol Educ Program. 2011;2011:215-21. [Medline].

  14. Lee HS, Park LC, Lee EM, Lee SJ, Shin SH, Im H, et al. Incidence Rates and Risk Factors for Vascular Events in Patients With Essential Thrombocythemia: A Multicenter Study From Korea. Clin Lymphoma Myeloma Leuk. Nov 14 2011;[Medline].

  15. Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. May 1999;61(1):10-5. [Medline]. [Full Text].

  16. Tefferi A, Fonseca R, Pereira DL, Hoagland HC. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc. Jan 2001;76(1):22-8. [Medline].

  17. Girodon F, Bonicelli G, Schaeffer C, Mounier M, Carillo S, Lafon I, et al. Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: a population-based study. Haematologica. Jun 2009;94(6):865-9. [Medline].

  18. Spanoudakis E, Margaritis D, Kotsianidis I, et al. Long-term bone marrow cultures (LTBMC) from essential thrombocythemia (ET) patients with or without JAK2617V>F mutation. Leuk Res. Oct 2008;32(10):1593-6. [Medline].

  19. Teofili L, Martini M, Cenci T, et al. Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases. Int J Cancer. Oct 1 2008;123(7):1586-92. [Medline].

  20. Ohyashiki K, Kodama A, Ohyashiki JH. Recurrent der(9;18) in essential thrombocythemia with JAK2 V617F is highly linked to myelofibrosis development. Cancer Genet Cytogenet. Oct 2008;186(1):6-11. [Medline].

  21. Zhan H, Spivak JL. The diagnosis and management of polycythemia vera, essential thrombocythemia, and primary myelofibrosis in the JAK2 V617F era. Clin Adv Hematol Oncol. May 2009;7(5):334-42. [Medline].

  22. Campbell PJ, Bareford D, Erber WN, Wilkins BS, Wright P, Buck G, et al. Reticulin accumulation in essential thrombocythemia: prognostic significance and relationship to therapy. J Clin Oncol. Jun 20 2009;27(18):2991-9. [Medline].

  23. [Best Evidence] Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. Jul 7 2005;353(1):33-45. [Medline]. [Full Text].

  24. Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. May 14 2009;113(20):4829-33. [Medline].

  25. Gugliotta L, Marchioli R, Fiacchini M, et al. Epidemiological, diagnostic, therapeutic and prognostic aspects of essential thrombocythemia in a retrospective study of the GIMMC group in two thousand patients [abstract]. Blood. 1997;90(suppl 1):348a.

  26. Besses C, Cervantes F, Pereira A, et al. Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia. Feb 1999;13(2):150-4. [Medline].

  27. Budde U, Schaefer G, Mueller N, et al. Acquired von Willebrand's disease in the myeloproliferative syndrome. Blood. Nov 1984;64(5):981-5. [Medline]. [Full Text].

  28. 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(3):124-7. [Medline].

  29. Chistolini A, Filoni V, Dragoni F, et al. Hepatitis C virus antibody in coagulopathic patients: ELISA and RIBA methods. Haematologica. Jul-Aug 1993;78(4):252-4. [Medline].

  30. el-Kassar N, Hetet G, Brière J, Grandchamp B. Clonality analysis of hematopoiesis in essential thrombocythemia: advantages of studying T lymphocytes and platelets. Blood. Jan 1 1997;89(1):128-34. [Medline]. [Full Text].

  31. Elliott MA, Tefferi A. Interferon-alpha therapy in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 1997;23(5):463-72. [Medline].

  32. Emilia G, Sacchi S, Temperani P. Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis. Leuk Lymphoma. Mar 1993;9(4-5):423-6. [Medline].

  33. Fabris F, Casonato A, Grazia del Ben M, De Marco L, Girolami A. Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis. Br J Haematol. May 1986;63(1):75-83. [Medline].

  34. 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. Jan 15 1999;93(2):417-24. [Medline]. [Full Text].

  35. Jantunen R, Juvonen E, Ikkala E, et al. The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia. Ann Hematol. Feb 2001;80(2):74-8. [Medline].

  36. Kobayashi S, Teramura M, Hoshino S, et al. Circulating megakaryocyte progenitors in myeloproliferative disorders are hypersensitive to interleukin-3. Br J Haematol. Apr 1993;83(4):539-44. [Medline].

  37. Randi ML, Barbone E, Zerbinati P, et al. Essential thrombocythemia following polycythemia vera: an unusual sequence. J Med. 1996;27(5-6):363-8. [Medline].

  38. Shabbad E, Cassel A, Froom P, Aghai E. Effect of adherent cells on the regulation of BFU-E in patients with myeloproliferative disease. Am J Hematol. Apr 1990;33(4):225-9. [Medline].

  39. van Genderen PJ, Michiels JJ, van der Poel-van de Luytgaarde SC, van Vliet HH. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: relationship with platelet count. Ann Hematol. Aug 1994;69(2):81-4. [Medline].

  40. Zauli G, Visani G, Catani L, et al. Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet-derived transforming growth factor beta 1, produced in normal amount, in patients with essential thrombocythaemia. Br J Haematol. Jan 1993;83(1):14-20. [Medline].

 
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Peripheral blood smear in essential thrombocytosis showing increased platelet numbers. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.
Bone marrow biopsy in essential thrombocytosis showing increased megakaryocytes. Courtesy Wei Wang, MD, and John Lazarchick, MD; Department of Pathology, Medical University of South Carolina.
 
 
 
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