What causes elevated red blood cell (RBC) count, also known as erythrocytosis?

From the Guidelines

Elevated red blood cell counts can be caused by various conditions, including polycythemia vera, a bone marrow disorder, as well as secondary polycythemia due to factors such as dehydration, high altitude, smoking, lung diseases, heart conditions, kidney diseases, and certain medications or genetic conditions. The causes of elevated red blood cell counts can be broadly categorized into primary and secondary polycythemia. Primary polycythemia, also known as polycythemia vera, is a clonal myeloproliferative disorder characterized by the overproduction of red blood cells, white blood cells, and platelets 1. Secondary polycythemia, on the other hand, is often mediated by increased erythropoietin (EPO) levels, which can be caused by various factors such as hypoxia, kidney disease, or certain medications 1.

Some of the common causes of secondary polycythemia include:

• Dehydration, which concentrates blood components
• Living at high altitudes, where lower oxygen levels stimulate red blood cell production
• Smoking, which reduces oxygen availability
• Certain lung diseases like COPD that decrease oxygen levels
• Heart conditions that affect blood oxygenation
• Kidney diseases, particularly renal cell carcinoma which can produce excess erythropoietin
• Certain medications like testosterone or erythropoietin that can increase red blood cell production
• Genetic conditions like congenital erythrocytosis that may cause elevated levels from birth

The body increases red blood cell production when it senses low oxygen levels, as these cells carry oxygen throughout the body. Treatment depends on identifying and addressing the underlying cause, which may include lifestyle changes, medication adjustments, or specific treatments for conditions like polycythemia vera, which might require phlebotomy (blood removal) or medications to reduce blood cell production 1. It is essential to note that the management of secondary polycythemia should take into account the balance between the physiological benefit of an increased hematocrit level and the possible impairment of oxygen delivery to tissues as a result of increased whole blood viscosity.

From the Research

Causes of Elevated Red Blood Cells

Elevated red blood cells, also known as erythrocytosis, can be caused by various factors. The causes can be classified into primary and secondary, as well as congenital and acquired.

• Primary causes:
  • Polycythemia vera (PV), a chronic clonal progressive myeloproliferative neoplasm, is the most common primary acquired disorder 2, 3
  • PV is characterized by a JAK2 mutation, which is present in >95% of patients with PV 3
• Secondary causes:
  • Increased erythropoietin (EPO) production, which can be caused by various conditions such as hypoxia or tumors 2, 4
  • Other non-hematological pathologies, such as chronic obstructive pulmonary disease (COPD) or sleep apnea, can also lead to secondary erythrocytosis 2
• Congenital causes:
  • Rare genetic disorders, such as congenital polycythemia, can cause elevated red blood cells 2
  • Mutations in genes such as JAK2, CALR, and MPL can also contribute to congenital erythrocytosis 5
• Acquired causes:
  • Acquired polycythemia, which can be caused by factors such as high altitude, smoking, or testosterone replacement therapy 4
  • Other acquired conditions, such as renal cell carcinoma or hepatoma, can also lead to elevated red blood cells 4

Diagnosis and Investigation

The diagnosis of erythrocytosis involves measuring the erythropoietin level, which can help distinguish between primary and secondary causes 2. Further investigation, such as mutational testing, bone marrow biopsy, and imaging studies, may be necessary to determine the underlying cause of the elevated red blood cells 2, 5.

Treatment and Management

The treatment and management of erythrocytosis depend on the underlying cause. For primary causes such as PV, treatment may involve phlebotomy, aspirin, and cytoreductive therapy 3, 5. For secondary causes, treatment may involve addressing the underlying condition, such as hypoxia or tumors 4. In some cases, novel therapeutic modalities, such as gene therapy or interference with aberrant signaling pathways, may be considered 6.