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.
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,
danger, risks, caution
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. Dr. Dawn L. Hershman, of Columbia University Medical Center, New York City, 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 5% in 1991 to 45% in 2002. 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," according to Dr. Dawn L. Hershman. J Natl Cancer Inst 2009.
Increased mortality with high doses in
Use of controversial anemia drugs at high levels likely worsens heart problems and possibly chances for survival in kidney patients, according to a U.S. Medicare advisory panel in March 2010. Outside experts on the panel told the Centers for Medicare & Medicaid Services (CMS) that they were confident that use of the blockbuster drugs, called erythropoiesis-stimulating agents (ESAs), in chronic kidney disease patients could cause harm. In a series of votes, most panelists said there was enough data to draw those conclusions about increased heart risks. At the same time, evidence also showed ESAs could improve patients' quality of life and help them be active. At issue is whether changes are needed to address use of the drugs - Johnson & Johnson's Procrit and Amgen's Aranesp and Epogen. Concerns over possible heart risks and strong warnings for their use in cancer patients have already caused sales to slump as doctors scale back. Like cancer patients undergoing chemotherapy, those with kidney disease can also feel the fatigue and weakness of anemia. ESA drugs aim to boost red blood cells and improve energy. Doctors use them to prevent unnecessary blood transfusions that carry their own risks as patients await possible kidney transplantation. Current guidelines call for ESAs - synthetic forms of the erythropoietin hormone - to raise red blood cell levels to between 10 grams and 12 grams per deciliter, but recent studies linked higher doses to strokes, heart attacks or even death.
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.
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.