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The complete evaluation of erythrocytosis: congenital and acquired.

Leukemia 2009 May
The approach to a patient with erythrocytosis is greatly simplified by assessing the clonality of the process upfront. In this regard, there has been a dramatic shift toward genetic testing and away from traditional tests, such as measurement of red cell mass. Clonal erythrocytosis is the diagnostic feature of polycythemia vera (PV) and is almost always associated with a JAK2 mutation (JAK2V617F or exon 12). All other scenarios represent non-clonal erythrocytosis, often referred to as secondary erythrocytosis. Serum erythropoietin (Epo) level is usually normal or elevated in secondary erythrocytosis and subnormal in PV. Therefore, in a patient with acquired erythrocytosis, it is reasonable to begin the diagnostic work-up with peripheral blood JAK2 mutation analysis and serum Epo measurement to distinguish PV from secondary erythrocytosis. Conversely, the patient with life-long erythrocytosis is more likely to suffer from congenital polycythemia and should therefore be evaluated for germline mutations that result in enhanced Epo effect (for example, Epo receptor mutations), altered intracellular oxygen sensing (for example, mutations involving the von Hippel-Lindau tumor suppressor gene) or decreased P50 (for example, high-oxygen-affinity hemoglobinopathy). The order of tests in this instance depends on the clinical scenario and serum Epo level.

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