From the Guidelines
Polycythemia is primarily caused by either an overproduction of red blood cells due to genetic mutations, as seen in polycythemia vera, or in response to increased erythropoietin levels, which can be due to various factors including chronic hypoxia, kidney diseases, or tumors. The causes of polycythemia can be broadly classified into several categories, including:
- Apparent polycythemia, which is not a true increase in red blood cells but appears as elevated hematocrit due to decreased plasma volume, often from dehydration 1
- Relative polycythemia, which can be caused by factors such as dehydration or diuretic use
- True polycythemia, which can be further divided into primary polycythemia (polycythemia vera) and secondary polycythemia
- Polycythemia vera, which is caused by genetic mutations, particularly the JAK2 gene mutation, leading to autonomous red cell production independent of normal regulatory mechanisms 1
- Secondary polycythemia, which occurs in response to increased erythropoietin levels, and can be caused by factors such as:
- Chronic hypoxia, which can be due to living at high altitude, chronic lung disease, sleep apnea, or smoking 1
- Certain kidney diseases, such as renal cell cancer or polycystic kidney disease 1
- Tumors that secrete erythropoietin, such as hepatocellular carcinoma or cerebellar hemangioblastoma 1
- Use of anabolic steroids or erythropoietin doping 1 It is essential to determine the underlying cause of polycythemia to provide appropriate treatment, which can include phlebotomy, medications like hydroxyurea, and addressing the underlying condition for secondary causes 1. Untreated polycythemia can lead to serious complications like blood clots, stroke, and heart problems due to increased blood viscosity from excess red cells.
From the Research
Causes of Polycythemia
- Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 2
- The JAK2 gene variant is found in more than 95% of patients with PV, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea 2
- Primary polycythemias result from an acquired or inborn mutation affecting hematopoietic and erythroid cells, with polycythemia vera being the best-known type 3
- Molecular biology of polycythemias suggests that primary polycythemias result from abnormalities expressed in hematopoietic progenitors, while secondary polycythemia is caused by circulating factors 4
Types of Polycythemia
- Primary polycythemia: caused by an acquired or inborn mutation affecting hematopoietic and erythroid cells 3
- Secondary polycythemia: caused by circulating factors, such as erythropoietin 4
- Primary familial and congenital polycythemias: result from inborn mutations affecting hematopoietic and erythroid cells, with different molecular mechanisms in different families 3
Pathogenesis of Polycythemia
- Exaggerated myeloid proliferation due to an acquired somatic mutation of a hematopoietic stem cell 3
- Increased proliferation or decreased apoptosis of erythroid progenitors, or delayed erythroid differentiation with an increased number of progenitor cell divisions 4
- Altered signal transduction leading to excessive erythrocyte production 3