Risks of therapy include death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence. Risk increases when EPO treatment raises hemoglobin levels over 11 g/dL to 12 g/dL: this is to be avoided. rhEPO has been used illicitly as a performance-enhancing drug.
What are the side effects of erythropoietin?
What are the side effects of Erythropoietin? High blood pressure, muscle and joint pain, flu-like syndrome, rashes and hives. What are the other precautions for Erythropoietin?
What causes high erythropoietin levels?
The risk factors for secondary polycythemia (erythrocytosis) are:
- obesity
- alcohol abuse
- smoking
- high blood pressure (hypertension)
Does erythropoietin have a dark side?
„Does erythropoietin have a dark side? Epo signaling and cancer cells”. Sci. STKE 2007 (395): e38. DOI: 10.1126/stke.3952007pe38. PMID 17636183. Goldwasser, Eugene. A Bloody Long Journey: Erythropoietin and the Person Who Isolated It. Xlibris, 2011.
How can I increase my erythropoietin levels naturally?
how can I increase my erythropoietin levels naturally? Manipulating diet for protein and total calorie adequacy, monitoring hydration, using supplements, timing food combinations, adding weekly hypoxic exercise followed by easy or rest days all increases the release of natural EPO for healthy maximal oxygen carrying capacity.
What happens if you have too much erythropoietin?
Excess erythropoietin results from chronic exposure to low oxygen levels or from rare tumours that produce high levels of erythropoietin. It causes a condition known as polycythaemia which means high red blood cell count. In many people, polycythaemia does not cause any symptoms.
Can EPO be used safely?
EPO medication is very safe. In rare cases, patients feel like they have the flu about 1 hour after an injection. This is not serious and the feeling does go away. EPO medication improves hemoglobin so your blood pressure may go up.
Why do athletes abuse erythropoietin?
By injecting EPO, athletes aim to increase the number of red blood cells and, consequently, their aerobic capacity. If EPO levels are too high the body will produce too many red blood cells which can thicken the blood, leading to clotting, heart attack and stroke.
Why is EPO banned?
Why is EPO prohibited? EPO has a long history of abuse in endurance sports. Blood doping involves the misuse of certain techniques and/or substances like EPO to increase one's red blood cell mass, which allows the body to transport more oxygen to muscles and therefore increase stamina and performance.
What is the effect of erythropoietin on the blood?
Erythropoietin stimulates the bone marrow to produce more red blood cells. The resulting rise in red cells increases the oxygen-carrying capacity of the blood.
What does abnormal erythropoietin mean?
Abnormal erythropoietin levels suggest possible disease of the bone marrow or kidneys. Another possibility is abuse by an athlete to increase the red cell count for better athletic performance. The correct interpretation of an abnormal erythropoietin level depends on the particular clinical situation.
What happens when you replace erythropoietin with synthetic erythropoiet?
Therefore, by replacing the erythropoietin with an injection of synthetic erythropoietin, anemia related to kidney disease may be treated.
What is the meaning of EPO?
Erythropoietin (EPO) definition and facts. Measuring blood levels of erythripoietin, a hormone involved in red blood cell production, can diagnose some medical conditions. Erythropoietin (EPO) is a hormone produced by the kidney. Erythropoietin promotes the formation of red blood cells by the bone marrow. The erythropoietin hormone level can be ...
How much erythropoietin is normal?
Normal levels of erythropoietin range from 4 up to 24 mU/ml (milliunits per milliliter).
Where is erythropoietin produced?
Erythropoietin is produced to a lesser extent by the liver. Only about 10% of erythropoietin is produced in the liver. The erythropoietin gene has been found on human chromosome 7 (in band 7q21). Different DNA sequences flanking the erythropoietin gene act to control liver versus kidney production of erythropoietin.
Is erythropoietin dangerous?
When misused in such situations, erythropoietin is thought to be especially dangerous (perhaps because dehydration due to vigorous exercise can further increase the thickness (viscosity) of the blood, raising the risk for blood clots, heart attacks, and strokes.
What is erythropoietin used for?
Erythropoietin is a type of protein called a growth factor. It is used to treat a low number of red blood cells (anaemia) due to cancer or its treatment.
Where do you inject erythropoietin?
You have erythropoietin as an injection under the skin (subcutaneously). It is usually given into the thigh or tummy. A nurse can teach you, or a person caring for you, how to inject it. If you or a carer cannot give the injections, a district or practice nurse may do it for you.
What does EPO mean in medical terms?
Erythropoietin (EPO) is a treatment for anaemia. This means having too few red cells in the blood. Anaemia is also sometimes called having low haemoglobin (low Hb). Red blood cells carry oxygen round the body. If you have too few, you may feel very tired, lack energy and get cold or breathless easily.
Why are blood transfusions not good for you?
blood transfusions are not suitable for you, because you have other health conditions. People who have a bone marrow condition called myelodysplasia are also sometimes given erythropoietin. This is to increase their red blood cell numbers.
Can erythropoietin injections cause side effects?
When you have erythropoietin injections, the amount of the protein in your body becomes much higher than normal. This may cause side effects, but these are usually mild or moderate.
Can you take iron before or after treatment?
Your doctor may give you iron tablets, or injections of iron, before or during your treatment. Your body uses iron to make red blood cells. Your doctor can tell you if this will be helpful for you. You will have regular blood tests to check how your red cells and haemoglobin level are responding to treatment.
Can cancer cause anemia?
Many people with cancer develop anaemia at some point during their illness. This can be caused by the cancer or by chemotherapy . If you have anaemia and cancer, doctors usually treat the anaemia with a blood transfusion. But they may use erythropoietin if:
How low is erythropoietin in blood?
Erythropoietin levels in blood are quite low in the absence of anemia, at around 10 mU/mL. However, in hypoxic stress, EPO production may increase up to 1000-fold, reaching 10 000 mU/mL of blood. In adults, EPO is synthesized mainly by interstitial cells in the peritubular capillary bed of the renal cortex, with additional amounts being produced in the liver, and the pericytes in the brain. Regulation is believed to rely on a feedback mechanism measuring blood oxygenation and iron availability. Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors, are hydroxylated and proteosomally digested in the presence of oxygen and iron. During normoxia GATA2 inhibits the promoter region for EPO. GATA2 levels decrease during hypoxia and allow the promotion of EPO production.
What is the mechanism of action of erythropoietin?
Mechanism of action. Erythropoietin has been shown to exert its effects by binding to the erythropoietin receptor (EpoR). EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signalling cascade. This initiates the STAT5, PIK3 and Ras MAPK pathways.
What is the mechanism of regulation of EPO?
Regulation is believed to rely on a feedback mechanism measuring blood oxygenation and iron availability. Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors, are hydroxylated and proteosomally digested in the presence of oxygen and iron.
Why is EPO elevated?
Common causes of cellular hypoxia resulting in elevated levels of EPO (up to 10 000 mU/mL) include any anemia, and hypoxemia due to chronic lung disease.
What is the hemotropic factor in rabbits?
After conducting experiments on rabbits subject to bloodletting, Carnot and his graduate student Clotilde-Camille Deflandre attributed an increase in red blood cells in rabbit subjects to a hemotropic factor called hemopoietin. Eva Bonsdorff and Eeva Jalavisto called the hemopoietic substance 'erythropoietin'.
What is the name of the hormone that makes up erythropoietin?
Erythropoietin ( / ɪˌrɪθroʊˈpɔɪ.ɪtɪn, - rə -, - pɔɪˈɛtɪn, - ˈiːtɪn /; EPO ), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidney in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in the bone marrow.
What is the name of the drug that is produced by erythropoietin?
Erythropoietin. Erythropoietin ( / ɪˌrɪθroʊˈpɔɪ.ɪtɪn, - rə -, - pɔɪˈɛtɪn, - ˈiːtɪn /; EPO ), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidney in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in the bone marrow.
What is erythropoietin alpha?
Erythropoietin alpha: Epoetin alpha is an isoform of recombinant DNA-derived erythropoietin (rEPO), synthesized in Chinese hamster ovary (CHO) cells. It differs from the beta isoform in its migration on isoelectric focusing (IEF) and in a range of lectin-binding assays.[13]
What is recombinant human erythropoietin?
Recombinant human erythropoietin (rhEPO) is arguably the most successful therapeutic application of recombinant DNA technology till date. It was isolated in 1977 and the gene decoded in 1985. Since then, it has found varied applications, especially in stimulating erythropoiesis in anemia due to chronic conditions like renal failure, myelodysplasia, infections like HIV, in prematurity, and in reducing peri-operative blood transfusions. The discovery of erythropoietin receptor (EPO-R) and its presence in non-erythroid cells has led to several areas of research. Various types of rhEPO are commercially available today with different dosage schedules and modes of delivery. Their efficacy in stimulating erythropoiesis is dose dependent and differs according to the patient's disease and nutritional status. EPO should be used carefully according to guidelines as unsolicited use can result in serious adverse effects. Because of its capacity to improve oxygenation, it has been abused by athletes participating in endurance sports and detecting this has proved to be a challenge.
What does EPO do?
EPO acts synergistically with other cytokines to promote the proliferation, differentiation, and survival of progenitor cells in the erythroid lineage and boosts the production of erythrocytes. It does not influence the fate of the pluripotent stem cell, but acts on the colony forming unit-erythroid (CFU-E) cells to prevent their apoptosis and induce expression of erythroid specific proteins. The EPO-R polypeptide is a 66-kDa membrane protein belonging to the cytokine receptor superfamily.[9]
What is the effect of EPO on the receptor?
The EPO binding to its receptor results in homodimerization of the receptor , followed by activation of several signal transduction pathways: JAK2/STAT5 system, G-protein (RAS), calcium channel, and kinases [Figure 1]. A gain of function mutation in JAK2 has been reported in patients with polycythemia vera and other myeloproliferative diseases.[10] EPO also acts on angiogenesis, vasculogenesis, regulation of vascular resistance, and neuroprotection.[11]
How often can you give rhepo?
rhEPO can be given once, twice, or thrice weekly depending on the clinical status of the patient as per the level of hemoglobin maintained .
Which cell line synthesizes epoetin beta?
Erythropoietin beta: Epoetin beta is also synthesized by CHO cell lines and differs from epoetin alpha in containing:
Where does EPO come from?
The main site of production of EPO is from the kidney and to a much lesser extent from the liver. In the kidney, certain interstitial fibroblasts appear to be a major source of EPO; however, other studies suggest an important role of proximal tubular cells as well.[5,6]
What is the purpose of erythropoietin?
Erythropoietin-Stimulating Agents. Erythropoietin (EPO) is produced by the kidney and used to make red blood cells. Erythropoetin-stimulating agents are used often for people with long-term kidney disease and anemia. Appointments & Access.
How is erythropoietin produced?
It is produced by cloning the gene for erythropoietin. Recombinant erythropoietin drugs are known as erythropoietin-stimulating agents (ESAs). These drugs are given by injection (shot) and work by stimulating the production of more red blood cells. These cells are then released from the bone marrow into the bloodstream.
Why do people get ESAs?
These patients usually have lower hemoglobin levels because they can't produce enough erythropoietin.
Why do red blood cells raise hemoglobin?
Having more red blood cells raises your hemoglobin levels. Hemoglobin is the protein in red blood cells that helps blood carry oxygen throughout the body. Anemia is a disorder that occurs when there is not enough hemoglobin in a person's blood. There are several different causes of anemia.
When is it necessary to give a patient recombinant erythropoietin?
In cases where transfusions are not an option—for example, when the patient cannot have, or refuses, a transfusion— it may be necessary to give the patient recombinant erythropoietin. Recombinant erythropoietin is a man-made version of natural erythropoietin. It is produced by cloning the gene for erythropoietin.
Can antibodies cause anemia?
If this happens, the antibodies will block or lessen the body's ability to make red blood cells. This could result in an anemia. It is important that the patient keep the health care provider informed of any unusual tiredness, lack of energy, dizziness, or fainting.
Who should consult before taking ESA?
In addition, women who are pregnant, planning to become pregnant, or breastfeeding should consult with their health care provider before taking an ESA.
Why is EPO used in endurance athletes?
Consequently EPO is most generally utilized among endurance athletes as a means to increasing their RBC count which in turn results in better oxygen transportation along these lines and a vast improvement in aerobic respiration.
What is EPO used for?
In terms of modern medicine, EPO is harvested from cell cultures and is used to treat anemia (a decrease in the bodies RBC count). EPO is also used in the treatment of Myelodysplasia, which is a type of cancer that inhibits the bone marrows ability to produce healthy RBCs.
What is EPO in sports?
EPO (Erythropoietin), its advantages and disadvantages for endurance athletes. For the purposes of this essay an understanding of what EPO (Erythropoietin) is will be established. An understanding of how EPO works in the body will also be established. EPO’s use in medicinal practice is wide and varied and will be referred to also.
Where is EPO produced?
Its function is as a protein signaling molecule for RBC precursors in the bone marrow. EPO is produced naturally in the body by interstitial fibroblasts in the kidneys and by perisinusoidal cells present in the liver. Production of EPO in adults is most common in the kidneys.
Is EPO good for athletes?
A further study by Prof. Max Gassmann from the University of Zurich stated that EPO usage had massive psychological benefits to an athlete. He found that there were serious gains to be made in terms of motivation after treating genetically modified mice that produced human EPO solely in their brains. He surmised that EPOs possible mental health benefits were limitless given proper dosage and that it could be used to potentially alleviate the devastating symptoms suffered by Schizophrenics.
Does EPO cause heart attacks?
Most EPO prescribed to patients contain major health warnings about increased risk of heart attack, stroke and even the reoccurrence of certain tumors. Put simply, athletes who harness the power of EPO can go harder for longer. EPO allows bone marrow to create RBCs and thus extra hemoglobin.
When did athletes use EPO?
Athlete’s use of artificial EPO became a very popular method of performance enhancement, specifically for cyclists in the 1980s and has been linked with many champion athletes being stripped of titles and banned from the sport. The most famous case of admitted EPO use was by seven times Tour De France Champion, Lance Armstrong.
What are the arrows on the erythropoietin receptor?
The structure of the receptor dimer is outlined; docking sites for several intracellular proteins are marked with P and linked with black-dotted arrow to individual pathway components. Positive interactions are presented with full black arrows, negative with dotted red.
What is the hemoglobin level of Darbepoetin Alfa?
Transfusion risk in cancer patients with chemotherapy-induced anemia when initiating darbepoetin alfa therapy at a baseline hemoglobin level of <9 g/dL versus 9 to <10 g/dL versus >/= 10 g/ dL: an exploratory analysis of a phase 3 trial
What is the purpose of EPO?
Until 1990, erythropoietin (EPO) was considered to have a single biological purpose and action, the stimulation of red blood cell growth and differentiation. Slowly, scientific and medical opinion evolved, beginning with the discovery of an effect on endothelial cell growth in vitro and the identification of EPO receptors (EPORs) on neuronal cells. We now know that EPO is a pleiotropic growth factor that exhibits an anti-apoptotic action on numerous cells and tissues, including malignant ones. In this article, we present a short discussion of EPO, receptors involved in EPO signal transduction, and their action on non-hematopoietic cells. This is followed by a more detailed presentation of both pre-clinical and clinical data that demonstrate EPO’s action on cancer cells, as well as tumor angiogenesis and lymphangiogenesis. Clinical trials with reported adverse effects of chronic erythropoiesis-stimulating agents (ESAs) treatment as well as clinical studies exploring the prognostic significance of EPO and EPOR expression in cancer patients are reviewed. Finally, we address the use of EPO and other ESAs in cancer patients.
How many amino acids are in rHuepo?
Commercially available rHuEPO has the same 165 amino acid sequence as naturally occurring hormone ( 29 ). However, the level of glycosylation in rHuEPO depends on the expression system used ( 30 ). Glycosylation pattern can be analyzed by isoelectric focusing enabling, thus distinguishing endogenous EPO (eEPO) from rHuEPO ( 31 ). Also, urinary and serum EPO have some minor heterogeneity in glycosylation levels ( 32 ).
What is the EPO receptor?
EPO receptor is a member of the type I cytokine receptor superfamily ( 43 ). During post-translation modification, the N-terminal 24-amino acid signal peptide is cleaved and the protein is modified by glycosylation, phosphorylation, and ubiquitination to a mature 66–105 kDa protein ( 38, 44, 45 ). Mature human receptor consists of extracellular, single transmembrane, and cytoplasmic regions ( 46) (Figure (Figure11 ).
Where is EPO produced?
In adult human beings, the hormone is produced mainly by the renal cortex ( 24, 25 ), while in the developing fetus, the liver is the principal source ( 26 ). EPO is secreted into the bloodstream, circulates to the bone marrow, and binds to EPOR situated on the cell surface of erythroid progenitors promoting their survival, proliferation, and differentiation ( 27 ). EPO is also produced by numerous non-hematopoietic cells and may act in endocrine, autocrine, and paracrine manner ( 28 ).
Is EPO safe for cancer patients?
Erythropoietin (EPO) was first considered to have a single biological purpose and action – the stimulation of RBC growth and differentiation and, as such safe, for use in cancer patients. Slowly, scientific and medical opinion evolved, beginning with the discovery of an effect on endothelial cell growth in vitro ( 9) and the identification of EPO receptors (EPORs) on neuronal cells ( 10 ). We now know that EPO is a pleiotropic growth factor that exhibits an anti-apoptotic action on numerous cells and tissues, including malignant ones [reviewed in Ref. ( 11 – 13 )]. In this article, we present a short discussion of EPO, its signaling, and its action on non-hematopoietic cells. This is followed by a more detailed presentation of both pre-clinical and clinical data that demonstrate EPO’s diverse actions on cancer cells as well as possible receptors involved in the response of cancer cells to EPO/ESA therapy. Finally, we review current recommendations for the use of rHuEPO and other ESAs as supportive therapy in cancer patients with anemia that often develops during the radio- or chemotherapy.
Overview
Erythropoietin , also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. Low levels of EPO (around 10 mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Comm…
Pharmacology
EPO is highly glycosylated (40% of total molecular weight), with half-life in blood around 5 h. EPO's half-life may vary between endogenous and various recombinant versions. Additional glycosylation or other alterations of EPO via recombinant technology have led to the increase of EPO's stability in blood (thus requiring less frequent injections).
Function
Erythropoietin is an essential hormone for red blood cell production. Without it, definitive erythropoiesis does not take place. Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E, proerythroblast and basophilic erythroblast subsets in the differentiation. Erythropoietin has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in humans) by prom…
Mechanism of action
Erythropoietin has been shown to exert its effects by binding to the erythropoietin receptor (EpoR). EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signalling cascade. This initiates the STAT5, PIK3 and Ras MAPK pathways. This results in differentiation, survival and proliferation of the erythroid cell. SOCS1, SOCS3 and CIS are also expressed which act as negative regulators of the cytokine signal.
Synthesis and regulation
Erythropoietin levels in blood are quite low in the absence of anemia, at around 10 mU/mL. However, in hypoxic stress, EPO production may increase up to 1000-fold, reaching 10 000 mU/mL of blood. In adults, EPO is synthesized mainly by interstitial cells in the peritubular capillary bed of the renal cortex, with additional amounts being produced in the liver, and the pericytes in the brain. Regulation is believed to rely on a feedback mechanism measuring blood oxygenation and iron …
Medical uses
Erythropoietins available for use as therapeutic agents are produced by recombinant DNA technology in cell culture, and include Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa); they are used in treating anemia resulting from chronic kidney disease, chemotherapy induced anemia in patients with cancer, inflammatory bowel disease (Crohn's disease and ulcerative colitis) and myelodysplasia from the treatment of cancer (chemotherapy and radiation). The package inserts
History
In 1905, Paul Carnot proposed the idea that a hormone regulates the production of red blood cells. After conducting experiments on rabbits subject to bloodletting, Carnot and his graduate student Clotilde-Camille Deflandre attributed an increase in red blood cells in rabbit subjects to a hemotropic factor called hemopoietin. Eva Bonsdorff and Eeva Jalavisto called the hemopoietic substance 'erythropoietin'. K.R. Reissman and Allan J. Erslev demonstrated that a certain substa…
Usage as doping product
As a performance-enhancing drug, EPO has been banned since the early 1990s, but a first test was not available until the 2000 Summer Olympics. Before this test was available, some athletes were sanctioned after confessing to having used EPO, for example in the Festina affair, when a car with doping products for the Festina cycling team was found.
The first doping test in cycling was used in the 2001 La Flèche Wallonne. The first rider to test p…