Erythropoietin, or its alternatives
erythropoetin or
erthropoyetin (icon, ɨ, or ɨˌriːθrɵ-) or
EPO, is a
glycoproteinGlycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
hormoneA hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
that controls
erythropoiesisErythropoiesis is the process by which red blood cells are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin...
, or red blood cell production. It is a
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
for erythrocyte (
red blood cellRed blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
) precursors in the
bone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
.
Also called
hematopoietin or
hemopoietin, it is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and tubular epithelial cells. It is also produced in perisinusoidal Ito cells in the
liverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. While liver production predominates in the fetal and perinatal period, renal production is predominant during adulthood.
Erythropoietin is the
hormoneA hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
that regulates
red blood cellRed blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
production. It also has other known biological functions. For example, erythropoietin plays an important role in the brain's response to neuronal injury. EPO is also involved in the wound healing process.
When
exogenousExogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
EPO is used as a performance-enhancing drug, it is classified as an erythropoiesis-stimulating agent (ESA). Exogenous EPO can often be detected in blood, due to slight difference from the endogenous protein, for example in features of
posttranslational modificationPosttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
.
History
In 1906, Paul Carnot, a professor of medicine in Paris,France, and his assistant DeFlandres proposed the idea that hormones regulate the production of red blood cells. After conducting experiments on rabbits subject to
bloodlettingBloodletting is the withdrawal of often little quantities of blood from a patient to cure or prevent illness and disease. Bloodletting was based on an ancient system of medicine in which blood and other bodily fluid were considered to be "humors" the proper balance of which maintained health...
, Carnot and DeFlandre attributed an increase in red blood cells in rabbit subjects to a hemotropic factor called hemopoietin. Eva Bonsdorff and Eeva Jalavisto continued to study red cell production and later called the hemopoietic substance ‘erythropoietin’. Further studies investigating the existence of EPO by Reissman, and Erslev demonstrated that a certain substance, circulated in the blood, is able to stimulate red blood cell production and increase
hematocritThe hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...
. This substance was finally purified and confirmed as erythropoietin, opening doors to therapeutic uses for EPO in diseases like
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
.
Haematologist John Adamson and nephrologist
Joseph W. EschbachJoseph Wetherill Eschbach was an American doctor and kidney specialist whose twenty years of research starting in the 1960’s led to an improvement in the treatment of anemia....
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
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
in humans. In 1968, Goldwasser and Kung began work to purify human EPO, and managed to purify milligram quantities of over 95% pure material by 1977. Pure EPO allowed the amino acid sequence to be partially identified and the gene to be isolated. Later an NIH-funded researcher at Columbia University discovered a way to synthesize EPO. Columbia University patented the technique, and licensed it to Amgen. Controversy has ensued over the fairness of the rewards that Amgen reaped from NIH-funded work, and Goldwasser was never financially rewarded for his work.
In the 1980s, Adamson,
Joseph W. EschbachJoseph Wetherill Eschbach was an American doctor and kidney specialist whose twenty years of research starting in the 1960’s led to an improvement in the treatment of anemia....
, Joan C. Egrie, Michael R. Downing and Jeffrey K. Browne conducted a clinical trial at the
Northwest Kidney CentersThe Northwest Kidney Centers in Seattle Washington was established in 1962 as the first out-of-hospital outpatient hemodialysis treatment center. The model of providing hemodialysis outside of a hospital setting has spread throughout the world...
for a synthetic form of the hormone, Epogen produced by
AmgenAmgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
. The trial was successful, and the results were published in the
New England Journal of MedicineThe New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
in January 1987.
In 1985, Lin et al. isolated the human erythropoietin gene from a genomic phage library and were able to characterize it for research and production. Their research demonstrated that the gene for erythropoietin encoded the production of EPO in mammalian cells that is biologically active in vitro and in vivo. The industrial production of recombinant human erythropoietin (RhEpo) for treating anemia patients would begin soon after.
In 1989, the U.S. Food and Drug Administration approved the hormone, called Epogen, which remains in use today.
Novel erythropoiesis stimulating protein
More recently, a novel erythropoiesis-stimulating protein (NESP) has been produced. This glycoprotein demonstrates anti-anemic capabilities and has a longer terminal half-life than erythropoietin. NESP offers chronic renal failure patients a lower dose of hormones to maintain normal
hemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
levels.
Regulation
EPO is produced mainly by peritubular capillary lining cells of the
renal cortexThe renal cortex is the outer portion of the kidney between the renal capsule and the renal medulla. In the adult, it forms a continuous smooth outer zone with a number of projections that extend down between the pyramids. It contains the renal corpuscles and the renal tubules except for parts of...
; which are highly specialized epithelial-like cells. It is synthesized by renal peritubular cells in adults, with a small amount being produced in the liver. 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 hydroxylated and proteosomally digested in the presence of oxygen. It binds to the
erythropoietin receptorThe erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...
(EpoR) on the red cell surface and activates a
JAK2Janus kinase 2 is a human protein that has been implicated in signaling by members of the type II cytokine receptor family , the GM-CSF receptor family , the gp130 receptor family , and the single chain receptors...
cascade. This receptor is also found in a large number of tissues such as bone marrow cells and peripheral/central nerve cells, many of which activate intracellular biological pathways upon binding with Epo.
Primary role in red cell blood line
Erythropoietin has its primary effect on red blood cells by promoting red blood cell survival through protecting these cells from
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. It also cooperates with various growth factors involved in the development of precursor red cells. Specifically, the colony forming unit-erythroid (
CFU-ECFU-E is a colony forming unit.It arises from CFU-GEMMUnderstanding the murine CFU-e assay :CFU-e is a stage of erythroid development between the BFU-e stage and the pro-erythroblast stage...
) is completely dependent on erythropoietin. The burst forming unit-erythroid (BFU-E) is also responsive to erythropoietin.
Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E, pro-erythroblast and basophilic erythroblast subsets in the differentiation.
It has a range of actions including vasoconstriction-dependent
hypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, stimulating
angiogenesisAngiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
, and inducing proliferation of
smooth muscleSmooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
fibers. It has also been shown that erythropoietin can increase iron absorption by suppressing the hormone
hepcidinHepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...
.
Uses
Erythropoietin is available as a therapeutic agent produced by recombinant DNA technology in mammalian
cell cultureCell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
. It is used in treating
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
resulting from chronic kidney disease and myelodysplasia, from the treatment of
cancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
(
chemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and
radiationIn physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
). Current research suggests that, aminoacid R103 to E mutation in Erythropoietin makes it Neuroprotective and non-erythropoietic.
Available forms as biomedicine
- Erypro Safe, made by Biocon Ltd.
- Repoitin, made by Serum Institute of India Limited
- Eprex, made by Janssen-Cilag
Janssen-Cilag is a subsidiary of the Johnson & Johnson pharmaceutical company. The company was founded in the early 1950s by a merger between Janssen Pharmaceutica and Cilag....
- NeoRecormon, made by Hoffmann–La Roche
- Vintor, made by Emcure Pharmaceuticals
__NOEDITSECTION__Emcure Pharmaceuticals headquartered at Pune in West India is a vertically integrated Indian pharmaceutical company. The company's products include Tablets, Capsules , and injectables...
- Epofit, made by Intas pharma
- Erykine, made by Intas Biopharmaceutica
- Wepox, made by Wockhardt Biotech
- Epogen, made by Amgen
- Espogen, made by LG life sciences.
- ReliPoietin, made by Reliance Life Sciences
- Shanpoietin, made by Shantha Biotechnics Ltd
- Zyrop, made by Cadila Healthcare Ltd.
- Epotrust, made by Panacea Biotec
Anemia due to chronic kidney disease
In patients who require
dialysisIn medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
(have stage 5 chronic kidney disease(CKD)), iron should be given with erythropoietin. Dialysis patients in the US are most often given Epogen; outside of 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 who are not on dialysis (those in stage 3 or 4 CKD and those living with a kidney transplant). There are two types of erythropoietin for people with anemia due to chronic kidney disease (not on dialysis):
Brands in Epoetin Alpha are:
- Epofit (Intas pharma)
- Epoetin (Procrit (also known as Eprex),
- Darbepoetin (Aranesp)
Brands in Epoetin Beta are:
- NeoRecormon is Epoetin Beta
- MIRCERA is Methoxy Polyethylene Glycol-Epoetin Beta
Anemia due to treatment for cancer
In March 2008, a panel of advisers for the U.S. Food and Drug Administration (FDA) supported keeping ESAs from
AmgenAmgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
and
Johnson & JohnsonJohnson & Johnson is an American multinational pharmaceutical, medical devices and consumer packaged goods manufacturer founded in 1886. Its common stock is a component of the Dow Jones Industrial Average and the company is listed among the Fortune 500....
on the market for use in cancer patients. The FDA has focused its concern on study results showing an increased risk of death and
tumorA tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
growth in chemo patients taking the anti-anemia drugs. According to the FDA, evidence for increased rates of mortality exist in various cancers, including breast, lymphoid, cervical, head and neck, and non-small-cell lung cancer.
Anemia in critically ill patients
There are two types of erythropoietin (and several brands) for people with anemia, due to critical illness. These are:
- Epoetin (Procrit (also known as Eprex) or NeoRecormon)
- Darbepoetin (Aranesp)
- Epoetin delta (Dynepo)
- PDpoetin (an erythropoietin produced in Iran by Pooyesh Darou pharmaceuticals)
- Methoxy polyethylene glycol-epoetin beta
Methoxy polyethylene glycol-epoetin beta is the active ingredient of a drug marketed by Hoffmann-La Roche under the brand name Mircera. Mircera is a long-acting erythropoietin receptor activator indicated for the treatment of patients with anaemia associated with chronic kidney disease. It is the...
(Mircera) by Roche
In a
randomized controlled trialA randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
, 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 reduction in patients receiving erythropoietin. This result was
statistically significantIn statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
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 hypotheses for potential etiologies of this reduced mortality, but, given the known increase in thrombosis and increased benefit in trauma patients as well as marginal nonsignificant benefit (adjusted hazard ratio of 0.9) in surgery patients, it could be speculated 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 any, might benefit from administration of erythropoeitin. Any benefit of erythropoetin must be weighed against the 50% increase in
thrombosisThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, which has been demonstrated in numerous trials .
Treating anemia in patients undergoing cardiac surgery
In anemic patients undergoing valvular cardiac surgery, with anemia being defined as hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men, patients who received recombinant human erythropoietin 16-24 hr before surgery received approximately 1 less unit of blood; of those who were transfused, they received about 1.5 less units of blood, and ten fewer patients needed a transfusion. Furthermore, in the recombinant human erythropoietin group, the lowest postoperative hemoglobin concentration was higher on postoperative days 2, 3 and 4; additionally, reticulocyte count drop was less and erythropoiesis enhancement was greater.
Blood doping
ESAs have a history of use as
blood dopingBlood doping is the practice of boosting the number of red blood cells in the bloodstream in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentration in the blood can improve an athlete’s aerobic capacity and...
agents in endurance
sportA Sport is all forms of physical activity which, through casual or organised participation, aim to use, maintain or improve physical fitness and provide entertainment to participants. Sport may be competitive, where a winner or winners can be identified by objective means, and may require a degree...
s such as horseracing,
cyclingCycling, also called bicycling or biking, is the use of bicycles for transport, recreation, or for sport. Persons engaged in cycling are cyclists or bicyclists...
,
rowingRowing is a sport in which athletes race against each other on rivers, on lakes or on the ocean, depending upon the type of race and the discipline. The boats are propelled by the reaction forces on the oar blades as they are pushed against the water...
, distance running,
race walkingRacewalking, or race walking, is a long-distance athletic event. Although it is a foot race, it is different from running in that one foot must appear to be in contact with the ground at all times...
, cross country skiing,
biathlonBiathlon is a term used to describe any sporting event made up of two disciplines. However, biathlon usually refers specifically to the winter sport that combines cross-country skiing and rifle shooting...
, and
triathlonA triathlon is a multi-sport event involving the completion of three continuous and sequential endurance events. While many variations of the sport exist, triathlon, in its most popular form, involves swimming, cycling, and running in immediate succession over various distances...
s.
Though EPO was believed to be widely used in the 1990s in certain sports, there was no way at the time to directly test for it, until in 2000, when a test developed by scientists at the French national anti-doping laboratory (LNDD) and endorsed by the World Anti-Doping Agency (WADA) was introduced to detect pharmaceutical EPO by distinguishing it from the nearly identical natural hormone normally present in an athlete’s urine.
In 2002, at the Winter Olympic Games in Salt Lake City,
Don CatlinDon H. Catlin, M.D. is an anti-doping scientist and one of the founders of modern drug-testing in sport. -Career:Catlin has overseen testing for performance-enhancing drugs at the three most recent Olympics held in the United States since the 1984 Summer Games in Los Angeles, as well as testing...
, MD, the founder and then-director of the UCLA Olympic Analytical Lab, reported finding darbepoetin alfa, a form of erythropoietin, in a test sample for the first time in sports.
In 2010,
Floyd LandisFloyd Landis is an American retired cyclist who after initially being awarded victory in the 2006 Tour de France was stripped of his title for a doping offense. He was an all-around rider, with special skills in climbing and time-trialing, and is also known to be a very fast descender.Landis...
admitted to using performance-enhancing drugs, including EPO, throughout the majority of his career as a professional cyclist.
Since 2002, EPO tests performed by U.S. sports authorities have consisted of only a urine or “direct” test. From 2000–2006, EPO tests at the Olympics were conducted on both blood and urine.
Neurological diseases
Erythropoietin has been shown to be beneficial in certain neurological diseases like schizophrenia. Research has suggested that EPO improves the survival rate in children suffering from cerebral malaria, caused by the malaria parasite's blocking of blood vessels in the brain.
Treating patients with chronic pain
Certain analogs of erythropoietin, e.g., ARA290, an 11-amino-acid peptide that mimics the tertiary structure of erythropoietin, can activate the erythropoietin receptor but not erythrocyte precursor cells. In one study, mice and rats underwent either spared nerve injury (lesion of two of the three terminal branches of the sciatic nerve) or a sham operation. Those animals that underwent spared nerve injury were assigned to one of three groups and received intraperitoneal injections and then maintenance, intraperitoneal injections and no maintenance, or sham injection of ARA290. Spared nerve injury caused tactile and cold allodynia (increased sensitivity to non-painful stimuli) and animals that also received ARA290 had long-term relief of tactile and cold allodynia. A decrease in nociceptive and cold threshold was seen in the opposite paw and that response was lesser in animals treated with ARA290. There was less progression of tactile and cold allodynia in rats also treated with maintenance ARA290. There were no ARA290 effects in animals that lacked the EPOR-ßcR complex. If the same is found in humans, this would represent a novel way to treat this debilitating condition.
Adverse effects
Erythropoietin is associated with an increased risk of adverse cardiovascular complications in patients with kidney disease if it is used to increase
hemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
levels above 13.0 g/dl.
Early treatment with erythropoietin correlated with an increase in the risk of
Retinopathy of prematurityRetinopathy of prematurity , previously known as retrolental fibroplasia , is an eye disease that affects prematurely-born babies. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve...
in premature infants who had anemia of prematurity, raising concern that the angiogenic actions of erythropoietin may exacerbate retinopathy. However, since anemia itself increases the risk of retinopathy, the correlation with erythropoietin treatment may be incidental, and merely reflect that anemia induces retinopathy.
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-labelOff-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
indication with caution.
Amgen advised the U.S. Food and Drug Administration (FDA) regarding the results of the
DAHANCAThe Danish Head and Neck Cancer Group is a permanent working group operating under the authority of the Danish Society for Head and Neck Oncology...
10 clinical trial. The DAHANCA 10 data monitoring committee found that 3-year loco-regional cancer 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
on March 9, 2007, and a clinical alert for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents (ESAs) 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 warningIn the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects...
s 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.
Several publications and FDA communications have increased the level of concern related to adverse effects of ESA therapy in selected groups. In a revised Black Box Warning, the FDA notes significant risks associated with ESA use. ESAs should be used only in patients with cancer when treating anemia specifically caused by chemotherapy, and not for other causes of anemia. Further, it states that ESAs should be discontinued once the patient's chemotherapy course has been completed.
Interactions
Erythropoietin has been shown to
interactProtein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with the
Erythropoietin receptorThe erythropoietin receptor is a protein that in humans is encoded by the EPOR gene. EpoR is a 59 kDa peptide and is a member of the cytokine receptor family. EpoR pre-exists as dimers...
as its mechanism of action within the body.
Drug interactions with Erythropoietin include:
Major interaction:
LenalidomideLenalidomide , initially known as CC-5013 and marketed as Revlimid by Celgene, is a derivative of thalidomide introduced in 2004....
--risk of thrombosis
Moderate interaction:Cyclosporine--risk of high blood pressure may be greater in combination with EPO. EPO may lead to variability in blood levels of cyclosporine.
Minor interactions: ACE inhibitors may interfere with hematopoiesis by decreasing the synthesis of endogenous erythropoietin or decreasing bone marrow production of red blood cells.
See also
- Erythropoiesis
Erythropoiesis is the process by which red blood cells are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin...
- Hemopoietic growth factors
Hemopoietic growth factors regulate the differentiation and proliferation of particular progenitor cells. Made available through recombinant DNA technology, they hold tremendous potential for medical uses when a person's natural ability to form blood cells is diminished or defective...
- Amgen
Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...
, producer of artificial EPO (Brand Names: Epogen and Aranesp)
- Dynepo
Dynepo is a form of pharmaceutical erythropoietin under development as a pharmaceutical product by Shire Pharmaceuticals. The first development steps were performed by HMR and Aventis. Aventis obtained the license in Europe in 2002. The company expects to launch the product in Europe in 2006,...
, trademark name for an erythropoiesis stimulating protein, by TKT
- Blood doping
Blood doping is the practice of boosting the number of red blood cells in the bloodstream in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentration in the blood can improve an athlete’s aerobic capacity and...
, transfusions and EPO use as doping methods; testing and enforcement
- Jehovah's Witnesses and blood transfusions
Jehovah's Witnesses believe that the Bible prohibits ingesting blood and that Christians should therefore not accept blood transfusions or donate or store their own blood for transfusion...
Additional images
External links