Snapshot A 63-year-old man presents to urgent care with painful fingers and toes. He complains of a burning sensation, especially in the afternoon when the temperature is highest. He has had similar episodes in the past which resolve on its own. However, today his fingers are particularly painful. On review of systems, he reveals that he is fatigued and experiences night sweats and regular headaches. His weight today is 20 lbs lighter than his previous documented weight. Concerned, his physician orders a complete blood count and serum EPO level, both of which come back abnormal. His hemoglobin is 17 g/dL and his EPO level is well below normal. However, his peripheral blood smear shows RBC precursor cells. Introduction Myeloproliferative neoplasm with primarily increased production of RBCs Epidemiology presentation in the 60s-70s male and females equally affected potentially more prevalent in those of Ashkenazi Jewish descent Pathogenesis mutations in JAK2 (Janus kinase) V617F mutation constitutively active Janus Kinase → unregulated myeloproliferation erythrocytosis → ↑ blood viscosity leukocytosis thrombocytosis Associated conditions risk of progression to myelofibrosis or leukemia Presentation Symptoms highly viscous blood headaches visual disturbance thrombosis → erythromelalgia (rare but classic) painful burning sensation with increased temperatures in digits episodic blood clots in extremities hypertension bleeding from engorged vessels constitutional symptoms fatigue night sweats weight loss fever malaise pruritus exacerbated by hot water histamine release from increased basophils gouty attacks Physical exam hepatosplenomegaly bruising ischemic digits large retinal veins on funduscopy Evaluation Complete blood count with smear ↑ hemoglobin > 16 g/dL (female) or > 16.5 g/dL (male) ↑ hct > 48% (female) or > 49% (male) Bone marrow biopsy with hypercellularity prominent proliferation of all cell lines commonly seen with precursor cells confirms diagnosis baseline for assessing disease progression JAK2 mutation in peripheral blood – most accurate ↓ serum EPO ↑ RBC despite low EPO ↓ MCV SaO2 normal SaO2 EPO RBC mass Plasma Volume Hypoxemia ↓ ↑ ↑ Normal Polycythemia rubra vera Normal ↓ ↑ ↑ Ectopic erythopoeitin Normal ↑ ↑ Normal Smokers polycythemia Variable ↑ ↑ ↓ Stress polycythemia Normal Normal Normal ↓ Dehydration Normal Normal Normal ↓ Differential Diagnosis Secondary polycythemia Tumor-driven polycythemia Other myeloproliferative neoplasm Treatment For low risk patients (< 60 years old and no prior thrombosis) low-dose aspirin to prevent thrombosis perform phlebotomy until hematocrit is < 45% For high risk patients ( ≥ 60 years old and/or prior thrombosis) all the above plus hydroxyurea (decrease cell count) INF-α second-line ruxolitinib (JAK inhibitor) Gout prophylaxis allopurinol Pruritus antihistamines Prognosis, Prevention, and Complications Prognosis > 10 years with treatment 1.6x higher mortality than general population Complications thrombosis leading cause of morbidity and mortality 45% of all deaths in polycythemia vera Budd-Chiari syndrome occlusion of IVC or hepatic veins leading to congestive liver disease hemorrhage peptic ulcers increased histamine release from basophils gout progression to myelofibrosis CML AML