What can cause an increased Red Blood Cell (RBC) count?

From the Guidelines

An increased red blood cell (RBC) count can be caused by several conditions, with polycythemia vera being a primary cause, as well as other factors such as dehydration, high altitude, lung diseases, kidney diseases, smoking, and genetic disorders. According to the most recent and highest quality study, polycythemia vera is characterized by the presence of JAK2V617F or JAK2 exon 12 mutation, and a haemoglobin level >18.5 g/dl in men and >16.5 g/dl in women, or any other evidence of increased red cell volume 1. Other common causes of increased RBC count include:

• Dehydration, which concentrates blood components
• Living at high altitudes, where lower oxygen levels stimulate RBC production
• Lung diseases like COPD that reduce oxygen levels
• Certain kidney diseases, particularly those producing excess erythropoietin
• Smoking, which decreases oxygen-carrying capacity
• Certain medications including anabolic steroids and erythropoietin injections
• Genetic disorders like hemoglobin variants
• Some heart conditions that reduce oxygen delivery can also trigger increased RBC production, such as cyanotic congenital heart disease, which can lead to erythrocytosis as a compensatory response to improve oxygen transport 1.

Proper diagnosis typically requires additional blood tests, oxygen saturation measurements, and sometimes bone marrow examination. Treatment depends on identifying and addressing the underlying cause, which might include phlebotomy (blood removal) for polycythemia, smoking cessation, medication adjustments, or management of underlying conditions. For example, therapeutic phlebotomy may be indicated for patients with hemoglobin greater than 20 g per dL and hematocrit greater than 65%, associated with headache, increasing fatigue, or other symptoms of hyperviscosity in the absence of dehydration or anemia 1. However, repeated routine phlebotomies are not recommended due to the risk of iron depletion, decreased oxygen-carrying capacity, and stroke 1.

From the FDA Drug Label

1. 3 Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.

Testosterone can cause an increase in red blood cell mass, which may lead to an increased risk of thromboembolic events. Therefore, testosterone can cause an increased RBC 2.

From the Research

Causes of Increased RBC

• Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal erythrocytosis, which can lead to an increased red blood cell (RBC) count 3
• The JAK2 V617F mutation is present in almost all cases of PV and can make hematopoietic progenitor cells hypersensitive to erythropoietin, leading to increased erythropoiesis and RBC production 4
• Spontaneous erythropoiesis can also contribute to an increased RBC count in PV and essential thrombocythemia (ET) 4
• Other factors that may contribute to an increased RBC count include:
  • Leukocytosis (an increase in white blood cell count) 3
  • Thrombocytosis (an increase in platelet count) 3
  • Abnormal karyotype (chromosomal abnormalities) 3
  • Presence of adverse mutations, such as SRSF2, IDH2, RUNX1, and U2AF1 3