Epidemiology
Etiology
- 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.
Pathophysiology
Clinical features
- Pruritus: Itching typically worsens when the skin comes into contact with warm water (aquagenic pruritus).
- Complications
- Venous thrombosis
- Arterial thrombosis
- Hemorrhagic complications
Diagnostics
Tip
Erythrocytosis associated with normal oxygen saturation and decreased serum EPO levels is strongly suggestive of polycythemia vera.
Differential diagnostics
- Absolute versus relative erythrocytosis: Hemoglobin and hematocrit levels cannot accurately differentiate these conditions. Direct measurement of the RBC mass is necessary. An increased total RBC mass indicates an absolute erythrocytosis; a normal RBC mass indicates a relative erythrocytosis.
- Estimated using ⁵¹Cr-tagged red blood cell, similar to Mark and recapture method
- Primary versus secondary erythrocytosis: Serum erythropoietin levels can be used to differentiate primary from secondary erythrocytosis. Primary erythrocytosis is associated with low erythropoietin levels and is caused by myeloproliferative disorders such as polycythemia vera. Secondary erythrocytosis is characterized by increased erythropoietin levels due to chronic hypoxia from high altitudes, smoking, or chronic obstructive pulmonary disease; or abnormal secretion by neoplastic or otherwise diseased tissues.
- Hypoxic versus other causes of secondary erythrocytosis: Measurement of the arterial oxygen saturation (SaO2) is important to exclude hypoxemia as a cause of the erythrocytosis. SaO2 < 92% (PaO2 < 65 mm Hg) can cause secondary polycythemia. SaO2 (measured as a percentage) should not be confused with PaO2 (measured as a partial pressure in mm Hg).