Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by clonal proliferation of bone marrow stem cells with constitutive activation of JAK-STAT signaling, leading to hypersensitivity to erythropoietin and absolute erythrocytosis (elevated red cell mass) often accompanied by leukocytosis and thrombocytosis. Annual incidence is 0.5-2 per 100,000 with median age 65 years and slight male predominance. JAK2 V617F mutation in exon 14 is present in 95% of patients; remaining cases harbor JAK2 exon 12 mutations.
WHO 2022 diagnostic criteria require all 3 major criteria OR first 2 major + minor: Major: (1) Hemoglobin >16.5 g/dL men, >16 g/dL women OR hematocrit >49% men, >48% women OR red cell mass >25% above mean predicted; (2) Bone marrow biopsy showing hypercellularity for age with trilineage proliferation including pleomorphic mature megakaryocytes; (3) Presence of JAK2 V617F or JAK2 exon 12 mutation. Minor: subnormal serum erythropoietin level. Differential diagnosis includes secondary erythrocytosis from hypoxia (chronic lung disease, sleep apnea, high altitude, smoking), erythropoietin-secreting tumors (renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma), congenital polycythemias (Chuvash polycythemia, EPOR mutations).
Treatment is risk-adapted based on age and prior thrombosis: low-risk (age <60, no prior thrombosis) receives phlebotomy targeting hematocrit <45% (CYTO-PV trial showed reduced cardiovascular events vs <50% target) plus low-dose aspirin 81-100 mg daily. High-risk (age >=60 OR prior thrombosis) requires cytoreductive therapy: first-line hydroxyurea 500-1500 mg daily titrated to maintain hematocrit <45% and platelets <400,000/microL; pegylated interferon alfa-2a or ropeginterferon alfa-2b for younger patients (preferred during pregnancy and may achieve molecular response with reduced JAK2 V617F allele burden). Ruxolitinib (JAK1/2 inhibitor) is approved for hydroxyurea-resistant or intolerant PV, providing hematocrit control, spleen size reduction, and symptom relief. Major complications include arterial and venous thrombosis (cardiovascular events, stroke, deep vein thrombosis, splanchnic vein thrombosis especially Budd-Chiari syndrome), bleeding, transformation to post-PV myelofibrosis (10-20% at 20 years), and acute leukemia (3-10% at 20 years). Patients should manage cardiovascular risk factors (smoking cessation, BP, lipids, diabetes), avoid dehydration, and report new neurologic or thrombotic symptoms immediately.