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Essential Thrombocytosis Medication

  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Nov 06, 2015
 

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.[33]

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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.

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.

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.

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, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, 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 Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

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.

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

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

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

  4. 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. 2002 Sep. 71(1):1-6. [Medline]. [Full Text].

  5. 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. 2002 May. 87(5):802-7. [Medline].

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

  7. 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. 1996 May. 52(1):14-20. [Medline].

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

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

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

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

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

  13. 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. 2009 Jul. 84(7):452-4. [Medline].

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

  15. 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. 2011 Nov 14. [Medline].

  16. Genetics Home Reference. Essential Thrombocythemia. U.S. National Library of Medicine. Available at http://ghr.nlm.nih.gov/condition/essential-thrombocythemia. November 2, 2015; Accessed: November 5, 2015.

  17. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014 Mar 6. 123 (10):1544-51. [Medline].

  18. 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. 1999 May. 61(1):10-5. [Medline]. [Full Text].

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

  20. 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. 2009 Jun. 94(6):865-9. [Medline]. [Full Text].

  21. [Guideline] Harrison CN, Butt N, Campbell P, Conneally E, Drummond M, Green AR, et al. Modification of British Committee for Standards in Haematology diagnostic criteria for essential thrombocythaemia. Br J Haematol. 2014 Nov. 167 (3):421-3. [Medline]. [Full Text].

  22. 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. 2008 Oct. 32(10):1593-6. [Medline].

  23. 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. 2008 Oct 1. 123(7):1586-92. [Medline].

  24. 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. 2008 Oct. 186(1):6-11. [Medline].

  25. 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. 2009 May. 7(5):334-42. [Medline].

  26. 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. 2009 Jun 20. 27(18):2991-9. [Medline].

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

  28. Riley CH, Brimnes MK, Hansen M, Jensen MK, Hasselbalch HC, Kjaer L, et al. Interferon-α induces marked alterations in circulating regulatory T cells, NK cell subsets and dendritic cells in patients with JAK2V617F -positive essential thrombocythemia and polycythemia vera. Eur J Haematol. 2015 Sep 19. [Medline].

  29. Verger E, Cassinat B, Chauveau A, Dosquet C, Giraudier S, Schlageter MH, et al. Clinical and molecular response to interferon alpha therapy in essential thrombocythemia patients with CALR mutations. Blood. 2015 Oct 20. [Medline].

  30. [Guideline] Barbui T, Barosi G, Grossi A, Gugliotta L, Liberato LN, Marchetti M, et al. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. Haematologica. 2004 Feb. 89 (2):215-32. [Medline]. [Full Text].

  31. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management. Am J Hematol. 2015 Feb. 90 (2):162-73. [Medline].

  32. Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, et al. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3. 373 (10):908-19. [Medline].

  33. 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. 2009 May 14. 113(20):4829-33. [Medline].

  34. 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.

  35. 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. 1999 Feb. 13(2):150-4. [Medline].

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

  37. 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].

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

  39. 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 Jan 1. 89(1):128-34. [Medline]. [Full Text].

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

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

  42. 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. 1986 May. 63(1):75-83. [Medline].

  43. 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. 2001 Feb. 80(2):74-8. [Medline].

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

  45. 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].

  46. 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. 1990 Apr. 33(4):225-9. [Medline].

  47. 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. 1994 Aug. 69(2):81-4. [Medline].

  48. 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. 1993 Jan. 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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