Dictionary:

erythropoietin

  (ĭ-rĭth'rō-poi-ē'tĭn)

Also from Answers.com... Herpes What is Herpes? Learn the signs and symptoms.

1. A glycoprotein hormone that stimulates the production of red blood cells by stem cells in bone marrow. Produced mainly by the kidneys, it is released in response to decreased levels of oxygen in body tissue.
2. Epoetin alfa.

[ERYTHROPOIET(IC) + –IN.]

Key Terms: Anemia, Blood transfusion, Chemotherapy, Food and Drug Administration, Intravenous, Subcutaneous.

Definition

Erythropoietin, which is also referred to by the names Epogen, Procrit, epoetin alfa, and EPO, is a medicine used to treat a low red blood cell count.

Purpose

Erythropoietin is a drug approved by the Food and Drug Administration (FDA) to treat low red blood cell counts called anemia. This anemia can be caused by cancer chemotherapy treatment, kidney failure, or a drug used to treat AIDs. Erythropoietin has also been used to increase the red blood cell count in patients who are anemic and scheduled to have surgery. This can decrease the risk of needing blood transfusions.

Description

Erythropoietin is a natural substance made by the kidneys in the body. Sometimes the body cannot make enough erythropoietin to cause red blood cells to be produced. The synthetic drug erythropoietin can be given to act like the natural erythropoietin and increase red blood cells.

Chemotherapy drugs destroy cancer cells, but they also destroy normal cells in the bone marrow. Oxygen, which is needed by the body to make energy, is carried to cells by the red blood cells. The destruction of the red blood cells causes anemia, which can make patients feel tired or dizzy.

Erythropoietin acts to stimulate the bone marrow to make more red blood cells. Patients need an adequate supply of iron in the body for erythropoietin to work best. If a patient's iron is low, the doctor may recommend oral iron tablets to keep the level of iron up. The increase in red blood cell levels should be seen in two to six weeks after beginning therapy in cancer-related anemia patients. When the red blood cell count rises, patients generally feel better.

Recommended Dosage

Erythropoietin is a clear, colorless liquid that must be kept refrigerated. It is administered as an intravenous injection or an injection directly underneath the skin, referred to as a subcutaneous injection. There are several dosing schedules used to treat patients with anemia.

To Treat Cancer-Related Anemia

Erythropoietin is dosed in units per kilogram of body weight, starting at 150 units per kilograms of body weight administered three times per week. This dosage can be increased to 300 units per kilogram of body weight three times per week.

Manufacturers continue to improve the effectiveness of the drug and physicians select dosage amount and frequency based on the drug type, brand, method of administration, and the individual patient's situation. Erythropoietin may be administered at a physician office or at home subcutaneously. Typically, it has been administered once a week, though in 2004, a study revealed that a form of the drug could safely be dosed every two weeks for some cancer patients, making it more convenient.

To Treat Patients With Renal Failure

Erythropoietin starting dose is 50-100 units per kilogram of body weight three times a week. This would be adjusted based on blood work and patient response.

To Treat Aids Patients on the Drug Zidovudine

Erythropoietin starting dose is 100 units per kilogram of body weight three times per week for 8 weeks. This would be adjusted based on blood counts and patient response.

To Treat Patients Prior to Surgery

Erythropoietin starting dose is 300 units per kilogram of body weight per day for 10 days prior to surgery, the day of surgery, and four days after surgery.

An alternate schedule is erythropoietin 600 units per kilogram of body weight administered once weekly beginning three weeks before surgery, then a fourth dose on the day of surgery.

Surgery patients need to take iron replacement with the start of erythropoietin injections.

Precautions

Blood counts will be monitored before receiving erythropoietin and regularly while on the drug erythropoietin. This allows the doctor to determine if patients are candidates for this treatment and if the dose the patient is receiving needs to be increased or decreased.

Blood pressure should also be monitored regularly while on erythropoietin. Patients who have high blood pressure that is not under control should not use erythropoietin.

Patients may be instructed to take oral iron tablets while on erythropoietin to increase the drug's effectiveness.

It is not recommended to give erythropoietin to patients who have cancer, such as leukemias, arising from their bone marrow.

Patients with a known previous allergic reaction to erythropoietin or the drug albumin should tell their doctor.

Patients who may be pregnant or trying to become pregnant should tell their doctor before receiving erythropoietin.

Side Effects

A common side effect due to erythropoietin administration is pain or burning at the site of the injection. This can be decreased by making sure that the erythropoietin is at room temperature before giving the infection. Ice can be placed in the area of injection to numb it before receiving the shot, and the site of injection should be changed with each shot.

Common side effects of patients who receive erythropoietin include diarrhea and swelling.

Less common side effects in cancer patients include fever, nausea and vomiting, fatigue, shortness of breath, and weakness.

Seizures have been reported in patients with kidney failure who are taking erythropoietin.

Erythropoietin can cause an increase in blood pressure, but this is uncommon in cancer patients. Blood pressure should be monitored while on this medicine.

Interactions

In clinical studies erythropoietin did not have any drug interactions.

In addition to taking oral iron replacement, patients should increase their intake of iron in their diet. This would include eating foods such as red meats, green vegetables, and eggs.

Patients should tell their doctors if they have a known allergic reaction to erythropoietin or any other medications or substances, such as foods and preservatives. Before taking any new medications, including non-prescription medications, vitamins, and herbal medications, the patients should notify their doctors.

Resources

Periodicals

"Studies: Aranesp Dosed Semiweekly Is Comparable to Epoetin Alfa Once a Week." Obesity, Fitness & Wellness Week July 10, 2004: 59.

—Nancy J. Beaulieu, RPh., BCOP; Teresa G. Odle

A hormone produced by the kidneys. It stimulates the production of red blood cells. Recently a genetically engineered form of the hormone, called recombinant erythropoietin (rEPO), has been made. It has been used successfully to treat anaemia.

Some athletes take rEPO to boost their red cell content in order to improve their endurance capacity. The beneficial effects of rEPO on athletic performance are unproven, but the possibility of gaining an advantage over competitors is too strong a temptation for some athletes to resist. There is great concern about the possible harmful effects of rEPO. High doses are associated with potentially dangerous increases in blood pressure which may lead to strokes and heart attacks. Some doctors suspect that the increase in the number of deaths among competitive cyclists in Europe may be attributed to rEPO abuse. Erythropoietin and related products are banned by most sports federations. However, detection is not easy because EPO is a naturally occurring substance.

A hormone that stimulates the production of red blood cells in bone marrow. Erythropoietin is a blood protein produced primarily in the kidneys by the action of an enzyme released in response to hypoxia. A reduction in tissue oxygen pressure can increase red cell production by as much as 6-9 times. Altitude training, because of exposure to low oxygen partial pressures, increases EPO secretion and boosts the red blood cell count. Erythropoietin has been used by athletes to artificially raise the blood cell count and increase the oxygen-carrying capacity of blood. In addition to giving athletes an unfair advantage, blood boosting with EPO is potentially dangerous. The red blood cell count may be raised to dangerously high levels, increasing the viscosity of the blood and elevating blood pressure: this can lead to heart failure and increase the risk of stroke and thrombosis. Artificially enhancing the uptake, transfer or delivery of oxygen is in the World Anti-Doping Agency's 2005 list of prohibited methods. See also erythrogenin.

A glycoprotein hormone secreted mainly by the kidney. A profactor, erythropoietinogen, is first produced in the liver, transferred to the kidney and converted to active erythropoietin in the kidney. The erythropoietin acts on stem cells of the bone marrow to stimulate red blood cell production (erythropoiesis). Called also erythropoietin stimulating factor, erythrogenin.

• recombinant e. — used to treat dogs and cats with nonregenerative anemia of renal disease; animals develop antibodies to the human product.
• e. stimulating factor — see erythropoietin (above).

erythropoietin
Identifiers
Symbol	EPO
Entrez	2056
HUGO	3415
OMIM	133170
RefSeq	NM_000799
UniProt	P01588
Other data
Locus	Chr. 7 q21

Erythropoietin (IPA pronunciation: [ɪˌɹɪθ.ɹoˈpo.ɪ.tɪn], alternative pronunciations: [ɪˌrɪθroʊˈpɔɪtn, əˌrɪθroʊ-, əˌriθroʊ-]) or EPO is a glycoprotein hormone that is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. Also called hematopoietin or hemopoietin, it is produced by the kidney, and is the hormone regulating red blood cell production.

History

Hematologist Dr. John Adamson and nephrologist Dr. Joseph W. Eschbach looked at various forms of renal failure and the role of the natural hormone EPO in the formation of red blood cells. Studying sheep and other animals in the 1970s, the two scientists helped establish that EPO stimulates the production of red cells in bone marrow and could lead to a treatment for anemia in humans.

In the 1980s, Adamson, Eschbach and others helped lead a clinical trial at the Northwest Kidney Centers for a synthetic form of the hormone, Epogen produced by Amgen. The trial was successful; its results were published in The New England Journal of Medicine in January 1987. The study authors were Dr. Adamson, Dr. Joseph W. Eschbach, Dr. Joan C. Egrie, Dr. Michael R. Downing and Dr. Jeffrey K. Browne.

In 1989, the Food and Drug Administration approved the hormone, called Epogen, which remains in use.

Regulation

EPO is produced mainly by peritubular fibroblasts of the renal cortex. Regulation is believed to rely on a feed-back mechanism measuring blood oxygenation. Constitutively synthesized transcription factors for EPO, known as hypoxia inducible factors (HIFs), are hydroxylized and proteosomally digested in the presence of oxygen.^[1]

Uses

Erythropoietin is available as a therapeutic agent produced by recombinant DNA technology in mammalian cell culture. It is used in treating anemia resulting from chronic kidney disease, from the treatment of cancer (chemotherapy & radiation) and from other critical illnesses (heart failure).

Anemia due to chronic kidney disease

In patients who require dialysis (have stage 5 chronic kidney disease(CKD)), iron should be given with erythropoietin.^[2] People in the US and on dialysis are most often given Epogen®, outside the US other brands of epoetin may be used.

Outside of people on dialysis, erythropoietin is used most commonly to treat anemia in people with chronic kidney disease and not on dialysis (those in stage 3 or 4 CKD and those living with a kidney transplant). There are two types of erythropoietin (and three brands) for people with anemia due to chronic kidney disease (not on dialysis), these are:

• epoetin (Procrit®(also known as Eprex®), NeoRecormon®)
• darbepoetin (Aranesp®).

Anemia due to treatment for cancer

Anemia in critically ill patients

There are two types of erythropoietin (and three brands) for people with anemia, due to critical illness. These are:

• epoetin (Procrit®(also known as Eprex®), NeoRecormon®)
• darbepoetin (Aranesp®).

In a recent randomized controlled trial^[3], erythropoietin was shown to not change the number of blood transfusions required by critically ill patients. A surprising finding in this study was a small mortality benefit in patients receiving erythropoietin. This result was statistically significant after 29 days but not at 140 days. This mortality difference was most marked in patients admitted to the ICU for trauma. The authors speculate several hypothesis of potential etiologies for reduced mortality, but given the known increase in thrombosis and increase benefit in trauma patients as well as marginal nonsignificant benefit (adjusted hazard ratio of 0.9) in surgery patients, one might speculate that some of the benefit might be secondary to the procoagulant effect of erythropoetin. Regardless, this study suggests further research may be necessary to see which critical care patients, if anyone, might benefit from administration of erythropoeitin. Any benefit of erythropoetin must be weighed against the 50% increase in thrombosis, which has been well substantiated by numerous trials.

Blood doping

It has a history of usage as a blood doping agent in endurance sports such as bicycle racing, triathlons and marathon running.

Adverse effects

Erythropoietin is associated with an increased risk of adverse cardiovascular complications in patients with kidney disease if it is used to increase hemoglobin levels above 13.0 g/dl.^[4]

Safety advisories in anemic cancer patients

Amgen sent a "dear doctor" letter in January, 2007, that highlighted results from a recent anemia of cancer trial, and warned doctors to consider use in that off-label indication with caution.

Amgen advised the United States FDA as to the results of the DAHANCA 10 clinical trial. The DAHANCA 10 data monitoring committee found that 3-year loco-regional control in subjects treated with Aranesp was significantly worse than for those not receiving Aranesp (p=0.01).

In response to these advisories, the FDA released a Public Health Advisory^[5] on March 9, 2007, and a clinical alert^[6] for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as epogen and darbepoetin. The advisory recommended caution in using these agents in cancer patients receiving chemotherapy or off chemotherapy, and indicated a lack of clinical evidence to support improvements in quality of life or transfusion requirements in these settings.

In addition, on March 9, 2007, drug manufacturers agreed to new black box warnings about the safety of these drugs.

On March 22, 2007, a congressional inquiry into the safety of erythropoeitic growth factors was reported in the news media. Manufacturers were asked to suspend drug rebate programs for physicians and to also suspend marketing the drugs to patients.

See also

• Amgen, producer of artificial EPO (Brand Names: Epogen and Aranesp)
• Dynepo, trademark name for an erythropoiesis stimulating protein, by TKT
• Blood doping, transfusions and EPO use as doping methods; testing and enforcement
• Jehovah's Witnesses and blood transfusions
• The german company AplaGen Biopharmaceuticals has developed a new EPO-mimetic peptide, HemoMer™. The active compound is bound to a polysacharid-based polymeric carrier. Comparable to PEGylation by the increase of the molecular weight the half-life, which is limited by renal elimination is increased. The so-called supravalency concept hat significant advantaged. In contrast to PEGylation also the efficacy is increased and because the drug carrier is degraded in the body no accumulation can occur. At the moment the drug is in the preclinical studies.^[7]

Additional images

EPO hematopoiesis (German)	JAK-STAT signaling pathway	EPO structure	EPO sales
Epo blotting

References

External links

• NYT 1987 announcement of Epogen's clinical success
• Patient information on Epogen
• Patient information on Aranesp
• Patient information on Procrit
• EPO F.A.Q.

Endocrine system: hormones/endocrine glands (Peptide hormones, Steroid hormones)
Hypothalamic-pituitary	Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α (FSH, LH, TSH), GH, prolactin, POMC (ACTH, MSH, endorphins, lipotropin)
Adrenal axis	Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA
Thyroid axis	Thyroid: thyroid hormone (T3 and T4) - calcitonin - Parathyroid: PTH
Gonadal axis	Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin (pregnancy)
Other end. glands	Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin
Non-end. glands	Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Target-derived	NGF, BDNF, NT-3

Urinary system, physiology: renal physiology and acid base physiology
Filtration	Ultrafiltration - Countercurrent exchange
Hormones affecting filtration	Antidiuretic hormone (ADH) - Aldosterone - Atrial natriuretic peptide
Endocrine	Renin - Erythropoietin (EPO) - Calcitriol (Active vitamin D) - Prostaglandins
Assessing Renal function / Measures of dialysis	Glomerular filtration rate - Creatinine clearance - Renal clearance ratio - Urea reduction ratio - Kt/V - Standardized Kt/V - Hemodialysis product
Acid base physiology	Fluid balance - Darrow Yannet diagram - Body water - Interstitial fluid - Extracellular fluid - Intracellular fluid/Cytosol - Plasma - Transcellular fluid - Base excess - Davenport diagram - Anion gap
Buffering/compensation	Bicarbonate buffering system - Respiratory compensation - Renal compensation

Cytokines, glycoproteins: colony-stimulating factors
Numbered	Macrophage colony-stimulating factor - Granulocyte macrophage colony-stimulating factor - Granulocyte colony-stimulating factor
Unnumbered	Erythropoietin - Thrombopoietin - Interleukin 3

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)