64-year-old man with fatigue, splenomegaly, and high hemoglobin
A 64-year-old man is evaluated for fatigue, early satiety, and intermittent headaches for 4 months. He has no bleeding or weight loss. Examination shows a palpable spleen tip 4 cm below the left costal margin. Hemoglobin is 17.8 g/dL, leukocyte count is 18,400/mm3, platelet count is 620,000/mm3, and erythropoietin level is low. Oxygen saturation is 98% on room air. Peripheral smear shows thrombocytosis without blasts. Which of the following is the most likely underlying driver of this patient's disorder?
See the answer and explanation below:
Post-Call Recovery Reads
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A
Explanation
Clinical Pearl:
Myeloproliferative neoplasms often present with overproduction of one or more mature myeloid cell lines, splenomegaly, and low erythropoietin when erythrocytosis is primary. A JAK2 mutation is the classic driver in polycythemia vera and is also common in essential thrombocythemia and primary myelofibrosis.
Explanation:
This patient has a myeloproliferative neoplasm, most consistent with polycythemia vera, given elevated hemoglobin, low erythropoietin, leukocytosis, thrombocytosis, and splenomegaly. The usual molecular basis is an acquired activating mutation in JAK2, which drives cytokine-independent myeloid proliferation and is central to current diagnostic criteria. BCR-ABL is the hallmark of chronic myeloid leukemia, which more often features marked granulocytosis and is defined by the Philadelphia chromosome rather than isolated primary erythrocytosis with low erythropoietin. Clonal plasma-cell proliferation describes multiple myeloma, which causes anemia, renal dysfunction, lytic bone disease, or hypercalcemia rather than panmyelosis. ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura, which presents with thrombocytopenia and hemolytic anemia, not elevated blood counts. Autoimmune marrow failure causes aplastic anemia, which leads to pancytopenia rather than overproduction of myeloid elements.
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