Erythropoietin is a hypoxia-induced hormone that is a major regulator of normal erythropoiesis. Over the last decade, the production of recombinant human erythropoietin has revolutionized the treatment of anemia associated with chronic renal failure, and has led to a greater understanding of anemia pathophysiology and to the elucidation of the interactions of erythropoietin, iron, and erythropoiesis.

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Erythropoietin benefit
Potential survival benefits associated with correction of anemia have expanded considerably the indications of erythropoietin use in various patient populations and are leading to consideration of earlier, more aggressive treatment of moderate anemia. The results of such treatment are promising in a variety of new clinical settings, including anemia associated with congestive heart failure. Furthermore, the erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes and preclinical studies have established erythropoietin to be a pleiotropic cytokine with anti-apoptotic activity and tissue-protective actions in the cardiovascular system, beyond correction of hemoglobin levels. However, one should be cautious about being overly excited about these possibilities until more studies are done. See below for potential side effects and risks.

Erythropoietin side effects
Despite some potential adverse effects, such as hypertension, and the occurrence of erythropoietin resistance, early studies in mild heart failure patients with anemia suggest that erythropoietin therapy is effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Achieving higher target hemoglobin levels with erythropoietic agents in patients with renal insufficiency is associated with a significantly higher risk of serious and life-threatening cardiovascular complications.

Use of erythropoiesis-stimulating agents in cancer patients undergoing chemotherapy has increased 10-fold since their introduction, yet there's been no associated decline in the rate of blood transfusions. Dr. Dawn L. Hershman, of Columbia University Medical Center, New York City, noted in an email to Reuters Health.

"There was concern from the beginning that thromboembolism may be a complication associated with these drugs," she noted.

Using the Surveillance, Epidemiology and End-Results-Medicare database, Dr. Hershman and colleagues identified 56,210 patients aged 65 and older who received chemotherapy between 1991 and 2002. Of these, 15,346 (27%) received an erythropoiesis-stimulating agent.

According to a report in the November 10th online issue of the Journal of the National Cancer Institute, the proportion of patients treated with erythropoietin or darbepoetin increased from 4.8% in 1991 to 45.9% in 2002 (p < 0.001).

Despite this increase, the annual rate of blood transfusions was a constant 22% during the same time period, the report states. "Many of the patients in the study received both erythropoiesis-stimulating agents and blood transfusions over the course of their treatment," Dr. Hershman told Reuters Health.

In addition, the records showed that venous thromboembolism developed in 14.3% of patients who received an erythropoiesis-stimulating agent compared to 9.8% of those who did not (hazard ratio, 1.93). Overall survival was no different in those who did and did not receive these drugs.

Erythropoiesis-stimulating agents, the authors note in their report, are of particular interest from a public policy standpoint because they're so costly. "The total US sales of erythropoiesis-stimulating agents increased from $6.4 billion in 2002 to $10 billion in 2006, accounting for a greater Medicare Part B expenditure than any other drug," they said.

"We speculate that this use was fueled by aggressive marketing to patients and physicians that focused on a promise of increased energy during chemotherapy treatment," the researchers write.

This study, Dr. Hershman said, "stresses the need to continue to monitor new drugs for long-term safety. It is also important to make sure the benefits outweigh the risks."

J Natl Cancer Inst 2009.
 

Erythropoietin anemia drug side effects and risks
The risks of anemia drugs known as erythropoiesis-stimulating agents, or ESAs are many. Studies show that patients with breast or advanced cervical cancers who receive erythropoiesis-stimulating agents to treat anemia caused by chemotherapy died sooner or have more rapid tumor growth than similar patients who don't receive the anemia drugs.

Erythropoietin and cholesterol
Long-term treatment with erythropoietin increases serum HDL-cholesterol levels in patients with chronic kidney disease.

Erythropoietin and hepatitis
Treatment with erythropoietin worsens thrombocytopenia induced by pegylated-interferon-alpha therapy in patients with chronic hepatitis C infection.

This erythropoietin page was last updated in February 2008.