From the Guidelines
Polycythemia is primarily caused by either primary polycythemia vera, which is often driven by genetic mutations, or secondary polycythemia, which is a response to increased erythropoietin levels due to conditions such as chronic hypoxia or certain tumors. The causes of polycythemia can be broadly categorized into several types, including:
- Primary polycythemia (polycythemia vera), which is a result of genetic mutations in bone marrow stem cells, as discussed in the context of erythropoietin production and its regulation 1.
- Secondary polycythemia, which occurs in response to increased erythropoietin levels, often due to chronic hypoxia from conditions like high-altitude living, chronic lung disease, or sleep apnea, as well as certain kidney diseases or tumors that secrete erythropoietin 1.
- Relative polycythemia, which results from a reduction in plasma volume rather than an increase in red cell production, commonly seen in dehydration, diuretic use, or stress. The diagnosis and management of polycythemia depend on identifying the underlying cause, with treatments ranging from phlebotomy and medications like hydroxyurea for polycythemia vera to addressing the underlying condition for secondary forms, as the absence of a disease-specific positive marker necessitates the use of disease-characteristic biological and histological features to formulate a working diagnosis 1. Understanding the specific cause is crucial for proper management, as untreated polycythemia increases the risks of blood clots, stroke, and heart problems, highlighting the importance of diagnostic algorithms that may include the determination of serum erythropoietin levels and the examination of bone marrow histology 1.
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