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The treatment of choice is phlebotomy One unit of blood (approximately 500 mL) is removed weekly until the hematocrit is less than 45%; the hematocrit is maintained at less than 45% by repeated phlebotomy as necessary Because repeated phlebotomy intentionally produces iron deficiency, the requirement for phlebotomy should gradually decrease It is important to avoid medicinal iron supplementation, as this can thwart the goals of a phlebotomy program Maintaining the hematocrit at normal levels has been shown to decrease the incidence of thrombotic complications A diet low in iron may also increase the intervals between phlebotomies Occasionally, myelosuppressive therapy is indicated Indications include a high phlebotomy requirement, thrombocytosis, and intractable pruritus There is evidence that reduction of the platelet count to less than 600,000/mcL will reduce the risk of thrombotic complications Alkylating agents have been shown to increase the risk of conversion of this disease to acute leukemia and should be avoided Hydroxyurea is now being widely used when myelosuppressive therapy is indicated The usual dose is 500 1500 mg/d orally, adjusted to keep platelets < 500,000/mcL without reducing the neutrophil count to < 2000/mcL Anagrelide may be substituted or added when hydroxyurea is not well tolerated, but it is not the preferred initial agent Low-dose aspirin (75 81 mg daily) has been shown to reduce the risk of thrombosis without excessive bleeding, and should be part of therapy for all patients without contraindications to aspirin Allopurinol may be indicated for hyperuricemia Antihistamine therapy with diphenhydramine or other H1blockers may be helpful for control of pruritus, and some reports suggest the efficacy of selective serotonin reuptake inhibitors in refractory cases



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Elevated platelet count in absence of other causes Normal red blood cell mass Absence of Philadelphia chromosome

Figure 14-26

Essential thrombocytosis is an uncommon myeloproliferative disorder of unknown cause in which marked proliferation of the megakaryocytes in the bone marrow leads to elevation of the platelet count As with polycythemia vera, the recent finding of a high frequency of mutations of JAK2 in these patients promises to advance the understanding of this disorder





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The median age at presentation is 50 60 years, and there is a slightly increased incidence in women The disorder is often suspected when an elevated platelet count is found Less frequently, the first sign is thrombosis, which is the most common clinical problem The risk of thrombosis rises with age Venous thromboses may occur in unusual sites such as the mesenteric, hepatic, or portal vein Some patients experience erythromelalgia, painful burning of the hands accompanied by erythema; this symptom is reliably relieved by aspirin Bleeding, typically mucosal, is less common and is related to a concomitant qualitative platelet defect Splenomegaly is present in at least 25% of patients

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An elevated platelet count is the hallmark of this disorder, and may be over 2,000,000/mcL The white blood cell count is often mildly elevated, usually not above 30,000/ mcL, but with some immature myeloid forms The hematocrit is normal The peripheral blood smear reveals large platelets, but giant degranulated forms seen in myelofibrosis are not observed Red blood cell morphology is normal The bone marrow shows increased numbers of megakaryocytes but no other morphologic abnormalities The

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Polycythemia is an indolent disease with median survival of 11 15 years The major cause of morbidity and mortality is arterial thrombosis Over time, polycythemia vera may convert to myelofibrosis or to chronic myelogenous leukemia In approximately 5% of cases, the disorder progresses to acute myelogenous leukemia, which is usually refractory to therapy

Harrison CN et al; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia N Engl J Med 2005 Jul 7;353(1):33 45 [PMID: 16000354]

Philadelphia chromosome is absent but should be assayed by molecular testing of peripheral blood for the bcr/abl fusion gene in all suspected cases to differentiate the disorder from chronic myeloid leukemia

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Essential thrombocytosis must be distinguished from secondary causes of an elevated platelet count In reactive thrombocytosis, the platelet count seldom exceeds 1,000,000/ mcL Inflammatory disorders such as rheumatoid arthritis and ulcerative colitis cause significant elevations of the platelet count, as may chronic infection The thrombocytosis of iron deficiency is observed only when anemia is significant The platelet count is temporarily elevated after splenectomy JAK2 mutations are found in 50% of cases Regarding other myeloproliferative disorders, the lack of erythrocytosis distinguishes it from polycythemia vera Unlike myelofibrosis, red blood cell morphology is normal, nucleated red blood cells are absent, and giant degranulated platelets are not seen In chronic myeloid leukemia, the Philadelphia chromosome (or bcr/abl by molecular testing) establishes the diagnosis

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