From the Guidelines
Polycythemia is primarily caused by either primary factors, such as genetic mutations in the JAK2 gene, or secondary factors, including low oxygen levels due to high altitude, chronic lung diseases, heart conditions, or sleep apnea, as well as other causes like smoking, kidney diseases, tumors, certain medications, and dehydration. The causes of polycythemia can be broadly categorized into primary and secondary factors. Primary polycythemia, also known as polycythemia vera, is a result of genetic mutations that lead to the overproduction of red blood cells by the bone marrow, independent of normal regulatory mechanisms 1. On the other hand, secondary polycythemia occurs when the body increases red blood cell production in response to low oxygen levels, which can be caused by various factors such as living at high altitudes, chronic lung diseases like COPD, heart conditions that reduce oxygen delivery, or sleep apnea 1.
Some of the key secondary causes of polycythemia include:
- Living at high altitudes
- Chronic lung diseases like COPD
- Heart conditions that reduce oxygen delivery
- Sleep apnea
- Smoking, as carbon monoxide reduces oxygen-carrying capacity
- Certain kidney diseases or tumors that lead to excessive erythropoietin production, stimulating red blood cell formation
- Medications, including testosterone and erythropoietin therapy, which may trigger polycythemia
- Dehydration, which can cause relative polycythemia by concentrating blood components without actually increasing red blood cell production
Understanding the specific cause of polycythemia is crucial for proper treatment, which may range from phlebotomy (blood removal) for primary polycythemia to addressing underlying conditions in secondary cases 2. It is essential to note that the management of polycythemia vera and other myeloproliferative neoplasms has evolved over time, with recent guidelines providing critical concepts and management recommendations, including the definition of resistance or intolerance to hydroxyurea 2.
In terms of management, phlebotomy remains the cornerstone treatment for primary polycythemia, while addressing the underlying cause is essential for secondary polycythemia. The European LeukemiaNet has provided definitions of resistance or intolerance to hydroxyurea in patients with polycythemia vera and essential thrombocythemia, which can guide treatment decisions 2. Overall, a comprehensive understanding of the causes and management of polycythemia is essential for improving patient outcomes and reducing morbidity and mortality.
From the Research
Causes of Polycythemia
The causes of polycythemia can be primary or secondary. Primary polycythemia, also known as polycythemia vera, is a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 3. It is caused by an acquired somatic mutation of a hematopoietic stem cell with exaggerated myeloid proliferation 4.
Primary Polycythemia
Primary polycythemia can be further divided into:
- Polycythemia vera (PV): a myeloproliferative neoplasm characterized by clonal erythrocytosis, leukocytosis, thrombocytosis, splenomegaly, and increased risk of thrombosis 5, 6
- Primary familial and congenital polycythemias: result from inborn mutations affecting hematopoietic and erythroid cells 4
Secondary Polycythemia
Secondary polycythemia is caused by hypoxic stimuli, such as:
- Obstructive sleep apnea (OSA) 7
- Chronic obstructive pulmonary disease (COPD) 7
- Tobacco smoking 3
- Other conditions that lead to chronic hypoxia
Key Factors
Some key factors that contribute to the development of polycythemia include:
- JAK2 gene variant: present in more than 95% of patients with polycythemia vera 3
- Erythrocytosis: an increase in red blood cell mass, which is a hallmark of polycythemia vera 3, 5
- Leukocytosis and thrombocytosis: often present in patients with polycythemia vera 3, 5
- Hypertension: frequently associated with both primary and secondary polycythemia 7