Feature Articles

ESA Drugs Treat Anemia By Stimulating Red Blood Cell Production

April 8, 2009

Bottles and needleMedications that increase the production of red blood cells, called erythropoiesis-stimulating agents (ESAs), are one of the most common drugs used to treat anemia. ESAs stimulate your body’s natural process for making more red blood cells. They can be given alone or in combination with some other treatments for the underlying cause of anemia. Before the mid-1980s there were no effective therapies to increase the production of red blood cells. People with severe anemia were treated with blood transfusions, which can cause infections, allergic reactions and other immunologic effects.1 In 1989, the first ESA drug was approved for use, revolutionizing the treatment of anemia. Today, blood transfusions are usually reserved for life threatening situations and ESAs have become a common treatment for anemia.

While ESAs are a common anemia therapy, they are not the only available treatment. Many different conditions can cause anemia, including poor nutrition, bleeding, pregnancy, kidney disease and other chronic diseases. Knowing how to treat anemia depends largely on what is causing you to have fewer red blood cells – measured as hemoglobin level. Some treatments can include iron, B12 or folic acid supplements; treating the underlying disease; or increasing the number of healthy red blood cells with ESAs or a blood transfusion.

The Roles of Natural Erythropoietin and ESAs

If you have anemia your blood isn’t able to carry and distribute enough oxygen to different tissues and organs. As a result, you may feel tired or have other symptoms depending on the severity of anemia. People with severe anemia may feel tired, fatigued or experience shortness of breath, which can cause problems carrying out routine activities. Erythropoietin is a natural substance made by certain kidney cells. These kidney cells are very sensitive to the amount of oxygen in your blood. When these cells determine that your oxygen level is low, they release more erythropoietin. The erythropoietin then signals your bone marrow to make more red blood cells in order to carry more oxygen throughout the body.2

Erythropoiesis-stimulating Agents Available in the United States
Trade Name Generic Name (Brand)
Procrit Erythropoietin alfa
Epogen Erythropoietin alfa
Aranesp Darbepoetin alfa
Product Package Inserts. August 2008.3-5

Sometimes the kidneys cannot make enough erythropoietin. If this is the case, your doctor may prescribe an ESA. Synthetic ESA drugs act like the natural erythropoietin, and are given to help the body produce more red blood cells and raise hemoglobin levels. Currently there are two ESA drugs available in the United States to treat anemia: erythropoietin alfa, which is also referred to by the brand names Epogen3 and Procrit,4 and darbepoetin alfa, which is also referred to by the brand name Aranesp.5

What Types of Patients Receive ESAs?

ESAs are approved by the Food and Drug Administration (FDA) to treat anemia which has been caused by cancer chemotherapy treatment, kidney failure, or a drug used to treat AIDS. Erythropoietin has also been approved for use to increase the red blood cell count in anemic patients who are scheduled to have surgery. This can decrease the need for blood transfusions following surgery. Though not yet approved by the FDA, ESAs have also been shown to be of benefit in managing anemia in elderly people,6 in people with inflammatory bowel disease,7 and in people with rheumatoid arthritis.8

How Are ESAs Administered?

How Synthetic ESA Drugs Work

Erythropoietin is a natural substance made n your body by the kidneys. Sometimes the kidneys cannot produce enough erythropoietin to make the red blood cells you need. If this is the case, your doctor may prescribe an erythropoiesis-stimulating agent (ESA). Synthetic ESA drugs act like the natural erythropoietin, and can be given to increase red blood cells.

ESAs are given by injection, either subcutaneously (under the skin) or intravenously (through an IV). They can be given in many dosing schedules, ranging from several times a week to once a month, depending on the drug chosen, the dose needed, and the reason you are receiving it.3-5 It may take several weeks to raise your hemoglobin level and relieve some of your symptoms. This is because your body must make new red blood cells to replace those that were lost. It normally takes about five to seven days to make a healthy red blood cell.9

Monitoring Your Body’s Response to ESAs

It is important to note that not everyone responds to ESAs and your hemoglobin levels may not go up. It is estimated that as many as 5-10% of patients have a decreased response, or no response, to ESA treatment. Some of the reasons for this lack of response include iron deficiency, blood loss, infection or inflammation. Sometimes correcting these problems will help your body to better respond to ESA drugs.10

Smiling patientESAs stimulate your bone marrow to make more red blood cells. Having more red blood cells raises your hemoglobin level. If your hemoglobin level stays too high or if your hemoglobin goes up too quickly, this may lead to health problems.11 Recently, the FDA has changed the instructions for ESA drugs, in order to make sure that hemoglobin levels stay below 12 g/dL.12 A recent study has shown that patients who need high doses of ESAs to maintain their hemoglobin levels may have a greater risk of cardiovascular problems and death.13

Your doctor will monitor your red blood cell counts on a regular basis if you are taking ESAs. All medicines may cause side effects, but many people have no, or minor, side effects. Occasionally, these medications may affect your heart function or may increase your chance of developing a blood clot, or after prolonged use, cause your red blood cell count to decrease. Let your doctor know immediately if you have chest pain, shortness of breath, or leg swelling and pain.11

Treating Anemia

The first step to treating anemia is to determine its cause. Once the cause is determined, your doctor can decide on the best treatment to correct the anemia. Many kinds of anemia can be alleviated by treating the underlying disease or problem. Several medications, including ESAs, are available to help correct anemia. ESAs have been administered successfully to millions of patients worldwide and are the standard of care for anemia treatment. ESAs may be the best treatment for you, but always discuss all treatment options thoroughly with your doctor. Communicate symptoms before, during and following any type of treatment, especially ESA treatment.


  1. Henry DH. Supplemental Iron: A Key to Optimizing the Response of Cancer-Related Anemia to rHuEPO? Oncologist. 1998;3(4):275-78. Link.
  2. Beaulieu NJ. Erythropoietin. In: Gale Encyclopedia of Cancer available at Healthline. Detroit, MI: The Gale Group Inc; 2002. Link. Accessed: March 3, 2009.
  3. Epogen Product Package Insert. August 2008. Link. Accessed: March 3, 2009.
  4. Procrit Product Package Insert. August 2008. Link. Accessed: March 3, 2009.
  5. Aranesp Product Package Insert. August 2008. Link. Accessed: March 3, 2009.
  6. Trovarelli T, Kahn B, Vernon S. Transfusion-free surgery is a treatment plan for all patients. AORN J. 1998 Nov;68(5):773-88. Link.
  7. Gasché C, Dejaco C, Waldhoer T, Tillinger W, Reinisch W, Fueger GF, Gangl A, Lochs H. Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial. Ann Intern Med. 1997 May 15;126(10):782-87. Link.
  8. Murphy EA, Bell AL, Wojtulewski J, Brzeski M, Madhok R, Capell HA. Study of erythropoietin in treatment of anaemia in patients with rheumatoid arthritis. BMJ. 1994 Nov 19;309(6965):1337-78. Link.
  9. van Iperen CE, Kraaijenhagen RJ, Biesma DH, Beguin Y, Marx JJ, van de Wiel A. Iron metabolism and erythropoiesis after surgery. Br J Surg. 1998 Jan;85(1):41-45. Link.
  10. Wei M, Bargman JM, Oreopoulos DG. Factors related to erythropoietin hypo-responsiveness in patients on chronic peritoneal dialysis. Int Urol Nephrol. 2007;39(3):935-40. Link.
  11. Procrit Medication Guide. August 2008. Link. Accessed: March 3, 2009.
  12. U.S. Food and Drug Administration. Information for Healthcare Professionals. Erythropoiesis Stimulating Agents (ESAs). Link. Accessed: March 3, 2009.
  13. Bohlius J, Brillant C, Clarke M et al. Recombinant Human Erythropoiesis Stimulating Agents in Cancer Patients: Individual Patient Data Meta-Analysis on Behalf of the EPO IPD Meta-Analysis Collaborative Group. ASH Annual Meeting Abstracts 2008;112:LBA-6. Link.