Essential Thrombocytosis Medication

Updated: Aug 22, 2019
  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Medication

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 a phosphodiesterase-3 enzyme (PDE-3) inhibitor that inhibits platelet aggregation. Anagrelide appears to decrease platelet counts by decreasing platelet production.

Ruxolitinib is a Janus associated kinase (JAK1/JAK2) inhibitor. Busulfan is an alkylating agent that affects myeloid cells more than lymphoid cells. Each of these drugs decrease serum platelets.

Interferon alfa is a biologic response modifier. 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. [42]

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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.It is used off-label in the U.S. for essential thrombocytosis to decrease serum platelets. Hydroxyurea is 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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PDE-3 Inhibitors

Class Summary

Phosphodiesterase-3 enzyme (PDE-3) inhibitors suppress megakaryocyte maturation, and thereby decrease platelet counts without affecting other hematopoietic cell lines.

Anagrelide (Agrylin)

Mechanism by which anagrelide reduces blood platelet count remains under investigation. It 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 as it elicits a dose-related decrease in platelet production. It is approved in the U.S. for thrombocythemia. Studies in patients support a hypothesis of dose-related reduction in platelet production, resulting from a decrease in megakaryocyte hypermaturation.

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Kinase Inhibitors

Class Summary

Janus associated kinase (JAK) inhibitors (eg, ruxolitinib) mobilize signals to cytokine receptors that are disrupted by myelofibrosis.

Ruxolitinib (Jakafi)

Selectively inhibitors Janus associated kinase (JAK) inhibitors JAK1 and JAK2. These kinase inhibitors mediate signals if cytokines and growth factors responsible for hematopoiesis and immune function. It is indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.

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Biological 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 2b (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. Helps control thrombocytosis associated with myeloproliferative disorders.

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Antineoplastics, Alkylating

Busulfan (Busulfex, Myleran)

Has prolonged bone marrow suppression and can cause pulmonary fibrosis. Consider use if other agent ineffective.

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