What can cause elevated red blood cell (RBC) counts, also known as erythrocytosis?

From the Guidelines

Elevated red blood cell counts can be caused by primary factors such as polycythemia vera, a bone marrow disorder, or secondary factors including living at high altitudes, chronic lung diseases, heart conditions, kidney diseases, smoking, and certain medications. The most recent and highest quality study on this topic is from 1, which provides a comprehensive review of polycythemia vera and its clinical recommendations. According to this study, primary causes of elevated red blood cell counts include polycythemia vera, which is a bone marrow disorder characterized by the production of too many red blood cells due to genetic mutations in the JAK2 gene. Secondary causes are more common and include:

• Living at high altitudes, where lower oxygen levels stimulate red blood cell production
• Chronic lung diseases like COPD that reduce oxygen levels
• Heart conditions that affect blood oxygenation
• Kidney diseases, particularly those involving increased erythropoietin production
• Smoking, which reduces oxygen-carrying capacity
• Certain medications like testosterone or erythropoietin Dehydration can also cause a relative increase in red blood cell concentration without actually increasing production. Some rare genetic disorders affecting hemoglobin can lead to elevated counts as well. Treatment depends on identifying and addressing the underlying cause, which might include phlebotomy (blood removal) for immediate management of symptoms like headaches, dizziness, or blood clotting risks. If you have elevated red blood cell counts, medical evaluation is essential to determine the specific cause and appropriate treatment, as suggested by 1 and supported by 1, which discusses the management of adults with congenital heart disease and the potential for elevated red blood cell counts due to chronic hypoxemia. It is also important to consider the potential risks and benefits of treatment, as noted in 1, which discusses the diagnosis and treatment of secondary polycythemia. Overall, a thorough medical evaluation is necessary to determine the underlying cause of elevated red blood cell counts and to develop an appropriate treatment plan, as emphasized by 1, which provides definitions and classifications of polycythemia.

From the Research

Causes of Elevated Red Blood Cell Counts

• Neoplastic diseases like polycythemia vera with proliferation of a cell clone 2
• Reactive forms resulting from chronic hypoxemia 2
• Physiologic form of polycythemia in highlanders and athletes training at high altitude 2
• Use of erythropoietin and its analogs as doping substances to induce polycythemia 2
• Chronic hypoxemia caused by lung disease or hypoventilation 2
• Myeloproliferative neoplasms like essential thrombocythemia 3, 4, 5
• Mutations in JAK2, CALR, or MPL genes 3, 4, 5
• Iron deficiency with microcytic polycythemia due to chronic hypoxia 6

Disease Features Associated with Elevated Red Blood Cell Counts

• Erythrocytosis and thrombocytosis 3, 4, 5
• Leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus 3, 4, 5
• Risk of leukemic or fibrotic transformation 3, 4, 5

Treatment and Management of Elevated Red Blood Cell Counts

• Phlebotomy to keep hematocrit below 45% 4, 5
• Aspirin therapy to prevent thrombohemorrhagic complications 4, 5
• Cytoreductive therapy with hydroxyurea, interferon-α, or busulfan for high-risk patients 4, 5
• Iron therapy to correct microcytic polycythemia due to chronic hypoxia 6