Polycythemia vera is a chronic most commonly caused by a gain of function mutation in the JAK2 gene, leading to erythrocytosis with or without increases in granulocytes and platelets. The elevated blood cell mass results in hyperviscosity, which may manifest with fatigue, facial flushing, pruritus, erythromelalgia, headaches, dizziness, and, in severe cases, thromboembolic events (e.g., stroke, Budd-Chiari syndrome). Diagnosis is confirmed if other causes of polycythemia are ruled out (e.g., , hypoxia-induced polycythemia, autonomous EPO production) and are met. Management of polycythemia vera focuses on preventing thrombotic and bleeding events and treating associated symptoms (e.g., pruritus, gout). Therapeutic phlebotomy and aspirin are indicated in all patients. Additionally, patients with require cytoreductive therapies and, possibly, anticoagulation. Patients should be monitored carefully for the development of complications and transformation of polycythemia vera to another hematologic malignancy, e.g., , myelodysplasia, or (AML).
- Prevalence: approximately 44 per 100,000 population 
- Age at diagnosis: variable; more common in individuals aged > 60 years 
- Risk factors for polycythemia vera 
Epidemiological data refers to the US, unless otherwise specified.
- The JAK2 (Janus kinase 2) oncogene codes for a non-receptor tyrosine kinase in hematopoietic progenitor cells. JAK2 is essential for the regulation of erythropoiesis, thrombopoiesis (megakaryopoiesis), and granulopoiesis.
- 98% of patients with polcythemia vera have a mutation in the JAK2 gene (gain of function) → ↑ tyrosine kinase activity → erythropoietin-independent proliferation of the myeloid cell lines → ↑ blood cell mass (erythrocytosis, thrombocytosis, and granulocytosis) → hyperviscosity and slow blood flow → ↑ risk of thrombosis and poor oxygenation.
- Often asymptomatic (incidental finding on routine blood tests)
- Nonspecific symptoms: fatigue, difficulty concentrating, insomnia, abdominal pain
- Constitutional symptoms: weight loss, sweating
- Hyperviscosity syndrome: triad of mucosal bleeding, neurological symptoms, and visual changes
- Plethora; : flushed face with a purple hue; cyanotic lips
- Pruritus; : Itching typically worsens when the skin comes into contact with warm water (aquagenic pruritus).
- Nonspecific neurological symptoms : dizziness, headache, visual disturbances, tinnitus
- Splenomegaly : associated with early satiety and abdominal discomfort; less commonly hepatomegaly
- Peptic ulcer disease
- Symptoms of thrombotic and hemorrhagic complications (see “Complications” below)
- Suspect polycythemia vera in:
- Rule out other based on a thorough medical history, physical examination, and diagnostics as needed.
- Order confirmatory laboratory studies for polycythemia vera.
- Consider bone marrow studies in consultation with hematology. 
- Consider abdominal imaging to evaluate for splenomegaly.
- Confirm diagnosis based on the .
- Reevaluate for other if diagnostic criteria are not met.
Erythrocytosis associated with normal oxygen saturation and decreased serum EPO levels is strongly suggestive of polycythemia vera. Erythrocytosis associated with elevated serum EPO or decreased oxygen saturation suggests secondary polycythemia caused by chronic hypoxia.
The first presentation in patients with polycythemia vera may be a thrombotic event, in particular, hepatic vein thrombosis. Maintain a low threshold for working up older patients with new thrombosis. 
Diagnostic criteria for polycythemia vera 
|Major criteria|| |
|Minor criterion|| |
Hemoglobin levels may be normal in the prepolycythemic (masked) phase of polycythemia vera, elevated during the overt polycythemic phase, and then decreased in post-PV myelofibrosis (the spent phase). 
Findings on routine laboratory studies 
- ESR: ↓ or normal : 
- Peripheral smear 
- Serum : ↓ iron, ↓ ferritin 
- Markers of cell turnover: ↑ leukocyte alkaline phosphatase, uric acid, and/or LDH 
In patients with polycythemia vera and iron deficiency, microscopic findings of iron deficiency anemia (i.e., microcytic hypochromic anemia) are seen on peripheral blood smear, but with elevated rather than decreased hemoglobin levels. 
- Other : See below.
- Other myeloproliferative disorders: See “ .”
|Causes of polycythemia |
|Definition||Characteristic features||Underlying conditions|
|Secondary polycythemia||Physiologically appropriate secondary polycythemia|| |
|Physiologically inappropriate secondary polycythemia|
|Relative polycythemia|| |
The differential diagnoses listed here are not exhaustive.
- Consult hematology.
- Assess for acute severe complications, e.g., stroke or pulmonary embolus; if present:
- Assess risk category. 
- All patients
- High-risk patients or low-risk patients with persistent symptoms
The management of polycythemia vera focuses on decreasing the risk of , which are the most common cause of mortality in patients with polycythemia vera. 
Reduction of blood cell counts 
- Reduction in cell counts decreases hyperviscosity and thromboembolic events.
- Target hematocrit: ≤ 45% 
Regular therapeutic phlebotomy
- Indications: all patients 
- Procedure: removal of blood (e.g., 250–500 mL) via venipuncture at scheduled intervals
- Frequency: based on the patient's response to treatment . 
Cytoreductive therapy 
- Indications 
- First-line: hydroxyurea 
- Alternatives (e.g., refractory to or unable to tolerate hydroxyurea) 
symptomatic splenomegaly; splenectomy is now rarely required in patients with polycythemia vera.  are highly effective at treating
Do not treat iron deficiency in patients with polycythemia vera; maintaining iron deficiency prevents rapid reexpansion of RBC mass after phlebotomy. 
Further prevention of thromboembolic events 
- All patients: Start antiplatelet drugs (e.g., aspirin ) unless contraindicated. 
- High-risk polycythemia vera in patients with previous VTE: Start anticoagulants (e.g., , ).
Symptomatic management 
- Symptomatic hyperuricemia (e.g., gouty arthritis): Initiate allopurinol. 
- Pruritus: Treatments include antihistamines, SSRIs, and interferon-alpha. 
- Erythromelalgia 
- : PPIs or H2 receptor blockers
Polycythemia vera is a potentially life-threatening disease because of the numerous complications associated with it.
Thrombotic complications 
- Venous thrombosis
- Arterial thrombosis
Hemorrhagic complications 
- High cell turnover → increased uric acid
Late stages 
- , ( ): Additional genetic mutations may cause polycythemia vera to transition to other hematologic diseases.
- Post-polycythemia vera myelofibrosis: fibrotic transformation of the bone marrow
We list the most important complications. The selection is not exhaustive.
- Without treatment: mortality within 2 years of diagnosis (typically due to thrombotic complications)
- With treatment: median survival of 13.5 years; 24 years in those diagnosed before 60 years of age
- Progression to post-PV myelofibrosis: 6–15% of patients over 15 years
- Progression to AML or myelodysplastic syndrome: 5–18% of patients over 15 years