Polycythemia vera

Last updated: June 25, 2022

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Polycythemia vera is a chronic myeloproliferative neoplasm most commonly caused by a gain of function mutation in the JAK2 gene, leading to polycythemia 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., relative polycythemia, hypoxia-induced polycythemia, autonomous production of EPO, other myeloproliferative neoplasms) and diagnostic criteria for polycythemia vera 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 high-risk polycythemia vera 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., post-PV myelofibrosis, myelodysplasia, or acute myelogenous leukemia (AML).

Epidemiological data refers to the US, unless otherwise specified.


Patients with polycythemia vera are at increased risk of thrombosis and bleeding.

Approach [3][9][10]

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. [12]

Diagnostic criteria

Diagnostic criteria for polycythemia vera [9][10]

Findings
Major criteria
Minor criterion

Diagnostic confirmation

  • All three major criteria are present

  • OR JAK2 mutation is not detected but two major criteria PLUS minor criterion are met

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 myelobfibrosis (the spent phase). [12][13]

Bone marrow biopsy may not be routinely required in patients with extremely elevated Hgb and Hct (i.e., : Hgb > 18.5 g/dL, Hct 55.5%; in : Hgb > 16.5 g/dL, Hct 49.5%). [3][9][10]

Findings on routine laboratory studies [3]

Confirmatory laboratory studies are detailed in “Diagnostic criteria for polycythemia vera.” Additional findings on routine laboratory studies for polycythemia include: [10][14]

Polycythemia vera may present with erythrocytosis alone or, in > 50% of patients, erythrocytosis, in combination with leukocytosis and/or thrombocytosis. [9]

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. [12][16]

Microcytic erythrocytosis is only associated with polycythemia vera, beta-thalassemia trait, and hypoxic erythrocytosis. [12][16]

Causes of polycythemia [16]
RBC mass EPO Oxygen saturation (SaO2) Expected plasma volume Underlying conditions

Primary polycythemia

  • Typically ↓
  • Normal
  • Normal
Secondary polycythemia Physiologically appropriate
  • Normal or ↓
  • Normal
Physiologically inappropriate
  • ↑↑
  • Normal
  • Normal
Medication-induced polycythemia
  • Normal
  • Normal or ↓ [19]
Relative polycythemia
  • Normal or minimally ↑
  • Normal
  • Normal

An elevated EPO suggests secondary polycythemia. [16]

The differential diagnoses listed here are not exhaustive.

Approach [3][14][22][23]

The management of polycythemia vera focuses on decreasing the risk of thromboembolic events, which are the most common cause of mortality in patients with polycythemia vera. [3]

Hemopoietic stem cell transplant is not used in the management of polycythemia vera but may be considered in post-PV myelofibrosis. [12][22]

Reduction of blood cell counts [9][14][23][27]

Regular therapeutic phlebotomy

  • Indications: all patients [3][9][23]
  • Procedure: removal of blood (e.g., 250–500 mL) via venipuncture at scheduled intervals
  • Frequency: based on the patient's response to treatment . [3]

Cytoreductive therapy [3][22][23][25]

JAK2 inhibitors are highly effective at treating symptomatic splenomegaly; splenectomy is now rarely required in patients with polycythemia vera. [16]
Do not treat iron deficiency in patients with polycythemia vera; maintaining iron deficiency prevents rapid reexpansion of RBC mass after phlebotomy. [16]

Further prevention of thromboembolic events [14][22][23]

Smoking cessation is associated with a decreased risk of thrombosis. [3]

Patients with extreme thrombocytosis may develop acquired von Willebrand disease. If platelet count is > 1 million/μL, perform a ristocetin cofactor assay and consider stopping aspirin if ristocetin cofactor activity is < 20%. [14]

Symptomatic management [16][23]

Polycythemia vera is a potentially life-threatening disease because of the numerous complications associated with it.

Thrombotic complications [5][29]

Hemorrhagic complications [5]

Gout [5]

Late stages [5]

We list the most important complications. The selection is not exhaustive.

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