Polycythemia vera

Polycythemia vera is a chronic myeloproliferative neoplasm of the hematopoietic stem cell. An acquired mutation — JAK2 V617F in the great majority of cases — makes erythroid progenitors behave as though the erythropoietin receptor were permanently switched on, so red cell production continues independently of the normal signal. The result is an elevated hematocrit and red cell mass, frequently accompanied by thrombocytosis and leukocytosis, since the mutated clone gives rise to all three lineages.

The laboratory pattern distinguishes it from other causes of a high hematocrit. In polycythemia vera the red cell mass is genuinely increased and serum erythropoietin is low, because the marrow is not responding to a hormonal signal. In secondary polycythemia — chronic hypoxia from lung disease, high altitude, sleep apnea, or an EPO-secreting tumor — erythropoietin is elevated. In relative polycythemia from dehydration, the hematocrit rises only because plasma volume has fallen; red cell mass is normal.

Clinically, patients present with headache, dizziness, blurred vision, plethora, and hypertension from hyperviscosity, and characteristically with aquagenic pruritus — itching after a warm shower, attributed to histamine release from increased basophils. Erythromelalgia, or burning pain and redness in the hands and feet, reflects platelet-mediated microvascular occlusion. Thrombosis is the leading cause of morbidity, including unusual sites such as hepatic vein thrombosis (Budd-Chiari syndrome). Management centers on phlebotomy to lower hematocrit plus low-dose aspirin, with cytoreductive therapy such as hydroxyurea for higher-risk patients. A minority of cases progress to myelofibrosis or acute myeloid leukemia.

USMLE Step 1 tests the JAK2 association, the erythropoietin-based differential among primary, secondary, and relative polycythemia, and the classic pruritus and thrombosis findings, usually alongside the other myeloproliferative neoplasms and the leukemias.