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Medical Author:

Siamak T. Nabili, MD, MPH

Siamak T. Nabili, MD, MPH

Dr. Nabili received his undergraduate degree from the University of California, San Diego (UCSD), majoring in chemistry and biochemistry. He then completed his graduate degree at the University of California, Los Angeles (UCLA). His graduate training included a specialized fellowship in public health where his research focused on environmental health and health-care delivery and management.

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Medical Editor:

Melissa Conrad Stöppler, MD, Chief Medical Editor

Melissa Conrad Stöppler, MD, Chief Medical Editor

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

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Contrary to primary polycythemia in which overproduction of red blood cell results from increased sensitivity or responsiveness to Epo (often with lower than normal levels of Epo), in secondary polycythemia, more red cells are produced because of high levels of circulating Epo.

The main reasons for higher than normal Epo are chronic hypoxia (poor blood oxygen levels over the long-term), poor oxygen delivery due to abnormal red blood cell structure, and tumors releasing inappropriately high amounts of Epo.

Some of the common conditions that can result in elevated erythropoietin due to chronic hypoxia or poor oxygen supply include:

• chronic obstructive pulmonary disease (COPD, emphysema, chronic bronchitis),
  
  
• pulmonary hypertension,
  
  
• hypoventilation syndrome,
  
  
• congestive heart failure,
  
  
• obstructive sleep apnea,
  
  
• poor blood flow to the kidneys, and
  
  
• living in high altitudes.

2,3-BPG deficiency is a condition in which the hemoglobin molecule in the red blood cells has an abnormal structure. In this condition, hemoglobin has a higher affinity to hold on to oxygen and is less likely to release it to the tissues. This results in more red blood cells being produced in response to what the tissues in the body perceive as an inadequate oxygen level. The outcome is more circulating red blood cells.

Certain tumors have a tendency to secrete inappropriately high amounts of Epo, leading to polycythemia. The common Epo-releasing tumors are:

• liver cancer (hepatocellular carcinoma),
  
  
• kidney cancer (renal cell carcinoma),
  
  
• adrenal adenoma or adenocarcinoma, and
  
  
• uterine cancer.

There also are more benign conditions that may cause increase Epo secretion, such as kidney cysts and kidney obstruction.

Chronic carbon monoxide exposure can also lead to polycythemia. Hemoglobin naturally has a higher affinity for carbon monoxide than for oxygen. Therefore, when carbon monoxide molecules attach to hemoglobin, polycythemia (increased red cell and hemoglobin production) may occur in order to compensate for the poor oxygen delivery by the existing hemoglobin molecules. A similar scenario can also occur with carbon dioxide in long-term cigarette smoking.

Polycythemia in newborns (neonatal polycythemia) is often caused by transfer of maternal blood from the placenta or blood transfusions. Prolonged poor oxygen delivery to the fetus (intrauterine hypoxia) due to insufficiency of the placenta can also lead to neonatal polycythemia.

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