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Thread: Mature megakaryocyte, Essential Thrombocytosis picture - blood histology atlas

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    Red face Mature megakaryocyte, Essential Thrombocytosis picture - blood histology atlas

    Pathophysiology
    Platelet survival is normal in essential thrombocytosis. Megakaryocytes increase the production of platelets, causing thrombocytosis. The cause of this increase in platelet production remains unclear, though it may be a result of autonomous production, increased sensitivities to cytokines (eg, interleukin-3 [IL-3]), decreased inhibition to platelet-inhibiting factors (eg, transforming growth factor [TGF] beta), or defects in accessory cell microenvironment.

    Bone marrow megakaryocytic precursors (colony-forming unit–megakaryocyte [CFU-Meg]) from patients with essential thrombocytosis form colonies in the absence of exogenous thrombopoietin (Tpo). There is no evidence for mutations in the genes for Tpo, and patients with essential thrombocytosis have normal or even decreased plasma Tpo levels, possibly reflecting increased Tpo clearance due to the elevated circulating platelet mass.

    JAK2 mutations possibly turn the thrombopoietin receptor on permanently. JAK-2 mutation is only seen in 50% of patients. MPL (myeloproliferative leukemia virus oncogene) has been associated with a small number (approximately 4%) of essential thrombocytosis cases. Amino acid changes at position 505 or 515 result in a thrombopoietin receptor protein that is constantly turned on (constitutively activated), which in essential thrombocythemia leads to the overproduction of abnormal megakaryocytes and anincreased number of platelets.


    Somatic mutations in the calreticulin gene (CALR) are detected in peripheral blood in the approximately 65-85% of essential thrombocythemia cases that are negative for mutations in JAK2 and MPL. CALR mutations are mutually exclusive with JAK2 or MPL mutations. Patients with mutated CALR had a lower risk of thrombosis and longer overall survival than patients with mutated JAK2.

    The mechanism by which thrombocythemia produces hemorrhage or thrombosis is not well defined. Several defects have been described, including a decrease in aggregation, hyperaggregation, and intracellular concentration of various chemicals. In addition, reports show a decrease in von Willebrand ristocetin cofactor activity and high molecular weight von Willebrand factor multimers. Some reports show patients with an acquired deficiency of antithrombin III, protein C, and protein S.

    Physical
    In most patients with essential thrombocytosis, physical examination findings are unremarkable. Approximately 40-50% of patients present with splenomegaly; 20% present with hepatomegaly.

    Causes
    The etiology and predisposing factors for the development of essential thrombocytosis (primary thrombocythemia) remain unclear. Genetic transmission of this disorder is rare, although reports show several families with multiple members affected by essential thrombocytosis (primary thrombocythemia). Research suggests that a thrombopoietin production or receptor abnormality can cause familial essential thrombocytosis (primary thrombocythemia).
    Mature megakaryocyte, Essential Thrombocytosis picture attachment.php?s=e2b9e0aae146a5b9de8f3604971ceb33&attachmentid=1431&d=1439593648

    Histologic Findings
    Approximately 90% of patients with essential thrombocytosis show an increase in bone marrow cellularity. Megakaryocytic hyperplasia is present. Giant megakaryocytes are frequently observed, and clusters of megakaryocytes may be present. Significant dysplasia of the megakaryocytes is unusual. Hyperplasia of granulocyte and reticulocyte precursors is common. Bone marrow reticulin is usually increased, but collagen fibrosis is uncommon.

    In essential thrombocytosis, as in other myeloproliferative disorders, bone marrow iron stain results may be negative when other studies do not support the presence of iron deficiency. For practical purposes, a ferritin level that is within the reference range or increased, along with an RBC mean corpuscular volume (MCV) that is within the reference range, is sufficient to exclude reactive thrombocytosis secondary to iron deficiency and the possibility of polycythemia vera masked by iron deficiency.

    Consultations
    A hematologist can help manage patients with essential thrombocytosis as well as monitor the cytoreductive therapy.

    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.

    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.

    References:
    http://emedicine.medscape.com/articl...7-medication#2











    Last edited by Medical Photos; 08-14-2015 at 11:07 PM.

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