From the Guidelines
Polycythemia is primarily caused by either primary bone marrow disorders, such as polycythemia vera, or secondary conditions that increase erythropoietin production, including chronic hypoxia, kidney diseases, and certain medications. The causes of polycythemia can be broadly categorized into primary and secondary polycythemia. Primary polycythemia, also known as polycythemia vera, results from genetic mutations, particularly in the JAK2 gene, leading to autonomous red blood cell production in the bone marrow 1. Secondary polycythemia develops in response to increased erythropoietin levels, which can occur due to various factors such as:
- Chronic hypoxia from conditions like COPD, sleep apnea, or high altitude living
- Certain kidney diseases, liver disorders, and erythropoietin-secreting tumors
- Medications like testosterone or erythropoietin therapy
- Relative polycythemia, which occurs when plasma volume decreases (dehydration, diuretics) without an actual increase in red blood cells
- Smoking, as carbon monoxide reduces oxygen-carrying capacity, triggering compensatory red blood cell production
According to the most recent and highest quality study, the management of polycythemia vera should address both short- and long-term objectives, including reducing the risk of thrombosis and evolution to myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia 1. Risk stratification is crucial in selecting patients with a low risk of vascular events, and phlebotomy and low-dose aspirin may be used to control hematocrit levels and delay the need for cytoreductive therapy.
Key points to consider in the management of polycythemia include:
- Risk stratification to identify patients with high-risk disease
- Phlebotomy to control hematocrit levels
- Low-dose aspirin to reduce the risk of thrombosis
- Cytoreductive therapy, such as hydroxyurea or interferon, to reduce the risk of evolution to myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia
- Monitoring for signs of disease progression and adjusting treatment accordingly.
From the Research
Causes of Polycythemia
The causes of polycythemia, a condition characterized by an excessive red blood cell count, can be understood by examining the underlying mechanisms of the disease.
- Primary polycythemias result from an acquired or inborn mutation affecting hematopoietic and erythroid cells 2.
- Polycythemia vera (PV), a type of primary polycythemia, is caused by an acquired somatic mutation of a hematopoietic stem cell with exaggerated myeloid proliferation 2.
- A single recurrent point mutation in the pseudokinase domain of JAK2 molecule (JAK2(V617F)) is present in >95% of patients with PV, leading to constitutive overproduction of red cells accompanied by low erythropoietin (EPO) levels 3.
- Secondary polycythemias are caused by conditions resulting in increased EPO production, such as tobacco smoking or sleep apnea 4.
Molecular Mechanisms
The molecular mechanisms causing primary polycythemias, including PV, are complex and involve altered signal transduction leading to excessive erythrocyte production 2, 3.
- The JAK2 gene variant is a key factor in the development of PV, and its presence helps distinguish PV from secondary causes of erythrocytosis 4, 3.
- Other molecular defects, such as mutations affecting hematopoietic and erythroid cells, may also contribute to the development of primary polycythemias 2.
Risk Factors
Several risk factors are associated with the development of polycythemia, including:
- Age: patients aged 60 years or older are at higher risk of thrombosis 4.
- Prior thrombosis: patients with a history of thrombosis are at higher risk of subsequent thrombotic events 4.
- Increased white blood cell count and platelet count: these factors can alter the prognosis of the disease 5.
- Cytokine levels: elevated cytokine levels can also impact the prognosis of polycythemia vera 5.