Erythropoietin is a renal hormone that controls and regulates the process of red blood cell formation (erythropoiesis) in the red bone marrow. 90% of erythropoietin is synthesized in the capillary cells of the renal glomeruli and 10% is produced by liver cells. The release of erythropoietin into the blood is subject to a circadian rhythm; its level in the blood is higher in the morning than in the afternoon or evening. The production of this hormone increases under conditions of hypoxia (lack of oxygen). In pregnant women, the level of erythropoietin in the blood is increased. Some hormones regulate the synthesis of erythropoietin.

Hormones that enhance erythropoietin production:

• Somatotropic hormone(GH, growth hormone) is a pituitary hormone (the pituitary gland is the main endocrine gland, located at the base of the brain, regulates the action of the hormonal system).

• Adrenocorticotropic hormone(ACTH) – pituitary hormone
• Prolactin– pituitary hormone
• Thyroxine (T4) – thyroid hormone
• Cortisol– hormone of the adrenal cortex (the adrenal glands are a pair of small endocrine glands located above the kidneys)
• Testosterone– male sex hormone

Hormones that cause a decrease in erythropoietin production

• Estrogens– female sex hormones

Erythropoietin stimulates the formation and maturation of not only red blood cells (erythropoiesis), but also platelets (blood cells that participate in blood clotting). Determining the level of erythropoietin in the blood is important for differential diagnosis between primary (true) and secondary polycythemia.

• - Primary polycythemia, true - a malignant disease of the hematopoietic system, leukemia, with an increase in the content of hemoglobin and red blood cells in the blood, cherry red coloration of the face and other signs
• - Secondary polycythemia is not associated with disorders of the hematopoietic organ. The number of red blood cells in the blood can be increased due to loss of water due to heavy diarrhea, oxygen deficiency in the mountains, as well as heart defects and pulmonary emphysema.

In primary polycythemia, the level of erythropoietin is reduced, in secondary polycythemia it is increased.

A decrease in erythropoietin levels can be detected:

• - in patients with anemia developed as a result of oncological and hematological diseases (hematological diseases are a large group of diseases associated with impaired function or structure of blood cells)
• - in patients with anemia due to chronic inflammatory diseases
• - in patients after extensive surgical interventions
• - in patients with rheumatoid arthritis
• - in patients with chronic renal failure

Due to a lack of the hormone erythropoietin, patients develop severe normochromic anemia (with a low number of red blood cells in the blood, but a normal hemoglobin content in the red blood cells). Due to the low number of red blood cells, the level of hemoglobin in the blood decreases to 50-80 g/l, while the norm in women is 110-152 g/l and men 120-172 g/l. Such patients are indicated for treatment with recombinant human erythropoietin preparations. The effectiveness of such treatment decreases with iron deficiency in the body.

An increase in erythropoietin levels can be detected:

• - in patients with various types of anemia (iron deficiency, folate deficiency, B12 deficiency, aplastic)
• - in patients with chronic obstructive pulmonary diseases (obstructive - associated with narrowing of the lumens of the cavities)
• - in patients with tumors that secrete erythropoietin, such as kidney tumors, pheochromocytoma(benign adrenal tumor), cerebellar hemangioblastoma (tumor originating from blood vessels).
• - in patients with polycystic kidney disease (a disorder of the development of renal tissue, leading to the appearance of cysts in it; combined with pathology of the urinary system).

Erythropoietin is an important element in the body. This hormone performs many important functions. So, it is involved in the production of red blood cells in the blood and in maintaining their work, this process is called erythropoiesis. The synthesis of the hormone in an adult occurs directly in the kidneys, in newborns in the liver. A healthy body produces an almost identical volume of red blood cells on a constant basis, so the slightest change in their concentration can be harmful to the patient. Erythropoietin what is it?

The hormone erythropoietin helps increase the production of red cells, and this is especially important in cases of large blood loss, hypoxia and stressful situations. In the normal state of the body, destruction of red blood cells may occur; in the case of sufficient synthesis of erythropoietin, strong destruction will not occur, erythropoiesis will be active. The lifespan of blood cells increases to 120 days.

In addition, the hormone affects the release of the additional required amount from their depot. As a result of modern research, it has been found that this hormone also has a positive effect on platelet synthesis.

The hormone that is produced in the human body is called endogenous erythropoietin. The kidneys produce up to 90% of all erythropoietin. About 10% is synthesized in the liver tissue, but the fetus in the womb produces this hormone 100% by the liver.

The production of erythropoietin follows a certain pattern. According to the most simplified system, hormone synthesis occurs, first starting with oxygen starvation or hypoxia, then the kidney tissues begin to be irritated from lack of nutrition and the production of prostaglandins begins in the glomeruli, and finally erythropoietin is released into the blood.

The above diagram does not fully disclose the entire system of erythropoietin formation. In addition to the above principles of formation, the synthesis of this hormone is influenced by several substances:

1. Testosterone.
2. Cortisol.
3. Prolactin.
4. Thyroxine.
5. Adrenocorticotropic hormone.
6. Somatotropic hormone.

Estrogens have been proven to directly affect low erythropoietin levels. The level of this hormone can change under the influence of certain factors and diseases.

Reasons for deviations from the norms

The concentration can be increased by diseases of various organs and systems in the human body. It can be elevated for various reasons: pathologies of the circulatory system, diseases of the kidneys, lungs, heart.

Hormone-producing kidney tumors often cause the hormone to be elevated. This phenomenon also occurs with pheochromocytoma and hemiangioblastoma. Erythropoietin is used as a doping in sports; a blood test will help find out; when deciphered, the erythropoietin level will be significantly increased.

A decrease in the hormone occurs as a result of certain pathological processes such as diseases of the kidneys or other organs, causing chronic or renal failure, polycythemia vera. Therefore, to exclude the development of pathology, it is necessary to take a biochemical blood test to determine the level of erythropoietin. Based on a blood test, as a rule, additional differential diagnosis of all body systems is required in order to find out which system is affected.

Kidney disease is the most common cause of decreased erythropoietin concentrations. A deviation from the norm occurs when diagnosing the following kidney pathologies: renal artery stenosis, polycystic kidney disease, kidney stones, a condition in which the blood supply to the kidneys is reduced.

In kidney disease, it is the deterioration of blood circulation that causes increased production of erythropoietin. Red blood cells and erythropoiesis in the blood are controlled by special receptors that are responsible for the perception of these components. With reduced blood circulation, the receptors do not perceive red blood cells in full concentration, and to replenish, a hormone is actively produced that will actively stimulate erythropoiesis.

Polycythemia vera is characterized by the fact that erythropoietin is produced in minimal quantities. All components of the blood with this pathology are produced at increased levels. In this case, erythropoietin does not control erythropoiesis, and they are increased even without an increase in this hormone.

Other diseases

Pathologies of the blood system often cause an increase in the volume of erythropoietin in the blood. The most common disease provocateurs are anemia, myelodysplastic syndrome at the first stage, leukemia, and red bone marrow aplasia.

Diseases of this type lead to varying degrees of reduction in red blood cells. Therefore, the body, as a defense, has to produce the hormone in an enhanced mode in order to restore red cells in the required quantity.

Various respiratory diseases can also cause changes in erythropoietin levels. Such diseases are: chronic obstructive pulmonary disease, chronic bronchitis, silicosis and pneumoconiosis.

Pathologies of the respiratory system reduce the volume of oxygen and the blood becomes less saturated with it; accordingly, cell nutrition becomes insufficient. This is hypoxia and causes increased production of the hormone, which will be elevated when analyzed in the blood.

Those heart diseases that are directly related to a decrease in oxygen in the blood also cause an increase in the concentration of erythropoietin. Heart defect or congestive heart failure is characterized by mixing of arterial and venous blood, resulting in oxygen deficiency. This pathology is most typical for people in old age.

In medicine

After visiting a general practitioner or hematologist, the patient may receive a referral for a blood test for erythropoietin. This examination is prescribed to a patient if he has signs of anemia. And also if, when conducting a blood test to determine the level of red blood cells, folic acid and vitamin B 12, a decrease in these indicators is revealed.

At the same time, it is important to exclude from the patient the fact that the level of red blood cells is lowered not due to large blood loss and he does not suffer from hemolysis, that is, massive destruction of red blood cells. However, there are established indicators that must be considered normal for men, these are indicators at the level of 5.6 to 28.9 IU/l, and for women - from 8 to 30 IU/l.

The female body loses a certain amount of blood every month during menstruation, so the norm is higher for women than for men. Even the loss of such a small volume of red blood cells, as during menstruation, is felt by the body, so it is necessary to make up for this decrease.

The development of modern medicine is at a stage when treatment of patients with impaired production of this hormone is much easier. In the past, treatment relied on red blood cell transfusions. At the moment, recombinant human erythropoietin is the main substitute. For this purpose, a special therapy technique is used.

This type of substitute is produced from animal tissues containing the genetic code of human EPO. There are several types of this hormone, which do not differ in their effect on the patient - erythropoietin alpha and beta. This type of hormone is absolutely identical to those that are formed naturally in the tissues of the liver and kidneys, so no rejection reactions occur, so in some cases alpha can be replaced with beta, but only with the agreement of a doctor. The composition of the drugs includes the components epoetin alfa, beta.

It is strictly prohibited to use this hormone in sports, no matter what type is used, alpha or beta. Cases of death after taking recombinant erythropoietin are known for certain. The use of any method that will artificially produce additional erythropoietin is strictly prohibited for athletes and threatens with disqualification.

Medications

What is erythropoietin in medicine? Several drugs that contain recombinant erythropoietin are used in medicine. Medicines are produced in ampoules, as they are administered subcutaneously or intravenously. The following synonyms of erythropoietin, which are INNs, are most often used in treatment:

1. Epoetin.
2. Erythrostim.
3. Recormon.
4. Vero-epoetin.

All drugs contain the same recombinant erythropoietin alpha, beta and the indications for use do not differ, however, they have different names, but the instructions for use practically do not change in any case.

Main indications for use:

1. Chronic renal failure.
2. Renal neoplasms of benign origin.
3. Rehabilitation after chemotherapy used to treat malignant lesions.
4. Anemia.
5. Postoperative recovery period.
6. For premature babies weighing less than 1.5 kg.

This medicine cannot be used for all groups of patients. Thus, the following features are contraindicated: uncontrolled arterial hypertension, unstable angina, decreased iron concentration in the blood, individual intolerance to some components of the drug.

It is also necessary to take into account the possible risks when using such drugs by pregnant women.. If the use is advisable and does not entail a negative effect on the fetus, then such treatment is possible, but it should only be carried out under the supervision of specialists in a hospital setting.

For some patients, taking the drugs goes away without a trace, however, cases of side effects have been reported. The most common manifestations are headache, dizziness, nausea and vomiting, joint pain, asthenic condition, diarrhea, cramps, swelling and redness after the injection, and fever. The specialist will warn about possible manifestations, however, if side effects are present during an appointment with a doctor, you must notify about this.

Erythropoietin, also known as EPO, is a glycoprotein hormone that controls erythropoiesis, or the production of red blood cells. It is a cytokine (signaling protein molecule) for red blood cell precursors in the bone marrow. EPO human has a molecular weight of 34 kDa. It is also called hematopoietin or hemopoietin; it is produced by interstitial fibroblasts in the kidney in close association with the peritubular capillaries and proximal convoluted tubules. It is also produced in the perisinusoidal cells of the liver. While liver production predominates in the fetus and perinatal period, kidney production is dominant in adulthood. In addition to erythropoiesis, erythropoietin also has other known biological functions. For example, it plays an important role in the brain's response to neuronal damage. EPO is also involved in the wound healing process. Exogenous erythroethin is produced using recombinant DNA technology in cell culture. Several different pharmaceuticals are available with different glycosylation configurations, collectively referred to as erythropoiesis-stimulating agents (ESAs). Specific details for use vary depending on the prescribing information for the drug, but ESAs have also been used to treat anemia of chronic kidney disease, anemia of myelodysplasia, and anemia caused by cancer chemotherapy. Warnings on the instructions include the risk of death, myocardial infarction, stroke, venous thromboembolism and tumor recurrence. Exogenous erythropoietin is used illegally as a performance-enhancing drug; it can often be detected in the blood due to small differences with endogenous proteins, for example, post-translational modification.

Functions

Production of red blood cells

The main role of erythropoietin is that it is an essential hormone for the production of red blood cells. Without his participation, final erythropoiesis will not take place. Under hypoxic conditions, the kidneys will produce and secrete erythropoietin to increase red blood cell production by recruiting CFU-E, proerythroblast, and basophilic erythroblast differentiation subunits. Erythropoietin has a primary effect on red blood cell progenitors and precursors by promoting their survival by protecting these cells from apoptosis. Erythropoietin is a major erythropoietic factor that interacts with various other growth factors (eg, IL-3, IL-6, glucocorticoids, and SCF) involved in the development of the erythroid lineage from pluripotent progenitors. The burst cell formation erythroid unit (BFU-E) begins with the expression of the erythropoietin receptor, being sensitive to erythropoietin. After completion of this stage, the erythroid colony-forming unit (CFU-E) expresses a maximum density of erythropoietin receptors, completely dependent on erythropoietin for further differentiation. Red blood cell precursors, namely proerythroblasts and basophilic erythroblasts, also express the erythropoietin receptor and are therefore affected by it.

Non-hematopoietic roles

Erythropoietin exhibits a number of actions, including vasoconstriction-dependent hypertension, stimulation of angiogenesis, including smooth muscle proliferation. This may increase absorption by inhibiting the hormone hepcidin. EPO levels up to 100 times baseline have been detected in brain tissue as a natural response to hypoxic injury. In rats, erythropoietin pretreatment has been associated with neuronal protection during induced cerebral hypoxia. No human trials have been conducted. Numerous studies have shown that EPO improves memory. This effect is independent of its effect on hematocrit levels. This is likely due to increased hippocampal responsiveness and effects on synaptic connections, neural plasticity, and memory-related neural networks. EPO may affect mood.

Mechanism of action

Erythropoietin appears to exert its effects by binding to the erythropoietin receptor (EpoR). EPO can be glycosylated (40% of total molecular weight) with a half-life in the blood of approximately five hours. The half-life of EPO may differ between endogenous and different recombinant versions. Additional glycosylation or other changes to EPO due to recombinant technology have resulted in increased persistence of EPO in the blood (requiring less frequent injections). EPO binds to the erythropoietin receptor on the surface of red blood cell precursors, thereby activating the JAK2 signaling cascade. Expression of erythropoietin receptors occurs in a number of tissues, such as bone marrow and peripheral/central nervous tissue. In the bloodstream, red blood cells themselves do not express the erythropoietin receptor, so they cannot respond to EPO. However, an indirect relationship between red blood cell duration and plasma erythropoietin levels has been reported to be called neocytolysis.

Synthesis and regulation

Blood levels of erythropoietin are quite low in the absence of anemia, amounting to about 10 mU per ml. However, under hypoxic conditions, EPO production can increase 1000-fold, reaching 10,000 mU per ml in the blood. EPO is produced primarily by interstitial cells in the peritubular capillary beds of the renal cortex. It is synthesized in renal peritubular cells in adults; a small part of it is produced in the liver. Regulation is thought to rely on a feedback mechanism to measure blood oxygenation. Constantly synthesized EPO transcription factors, known as hypoxia-induced factors, are hydroxylated and proteasomally digested in the presence of oxygen.

Medical use

Available for therapeutic use, erythropoietins are produced using recombinant DNA technology in cell culture, including Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa); They are used to treat anemia caused by chronic kidney disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), and myelodysplasia caused by cancer treatment (chemotherapy and radiation). Prescribing information for medications includes warnings regarding the risk of death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence, particularly when used to increase hemoglobin levels greater than 11 to 12 g per dL.

Available forms

Recombinant erythropoietin has a variety of glycosylation configurations that result in alpha, beta, delta and omega forms. Darbepoetin alfa, which was often identified as a novel erythropoiesis-stimulating protein (NESP) in the original research literature, is a form created by five substitutions (Asn-57, Thr-59, Val-114, Asn-115 and Thr-117) , which create two new N-glycosylation localizations. This glycoprotein has a longer half-life, meaning it can be administered less frequently.

Blood doping

Erythropoiesis stimulating agents (ESAs) have been used as blood doping drugs to promote endurance performance in sports such as boxing, cycling, rowing, running, race walking, snowshoeing, skiing, biathlon, mixed martial arts and triathlon. The overall oxygen delivery system (blood oxygen content as well as heart rate, vascularity, and lung function) is one of the major factors limiting the ability of muscles to withstand endurance exercise. Thus, the main reason why athletes use ESAs is to improve oxygen delivery to the muscles, which directly improves their endurance. With the advent of recombinant erythropoietin in the 1990s, the practice of autogenous and homologous blood transfusions was partially replaced by the introduction of erythropoietin to allow the body to naturally produce red blood cells. The increased hematocrit (% of blood volume that makes up the mass of red blood cells) and the total mass of red blood cells in the body, which is increased by taking ESA, provide an advantage in sports, due to which this practice has become prohibited. In addition to ethical considerations in sport, providing increased red blood cell mass (above natural levels) reduces blood flow through increased viscosity, increasing the risk of thrombosis and stroke. Because of the dangers associated with the use of ESAs, their use should be limited to clinical use only when anemic patients are brought back to normal hemoglobin levels (as opposed to above normal levels, where the risk of death increases). Although EPO was thought to be widely used in some sports in the 1990s, there was no method to test its use until 2000, until researchers at the French National Anti-Doping Laboratory (LNDD) developed special testing approved by the World Anti-Doping Agency ( WADA); it was used to detect pharmaceutical EPO by identifying it among essentially similar naturally occurring hormones present in athlete's urine. The first cases of EPO being used as a doping agent were discovered by the Swiss doping laboratory. In 2002, at the Winter Olympics in Salt Lake City, Dr. Don Catlin, founder and then director of the UCLA Olympic Analytical Laboratory, reported the discovery of darbepoetin alfa (a form of erythropoietin) in one of the test samples for the first time in the history of the sport. At the 2012 London Summer Olympics, Alex Schwazer, who won the 50-kilometer race walking gold medal at the 2008 Beijing Summer Olympics, tested positive for EPO and was disqualified. Since 2002, testing for EPO by US sports authorities has been based only on urine analysis or a “direct” test. From 2000-2006, testing for EPO at the Olympic Games was based on blood and urine tests. However, the existence of certain substances has been identified that, when taken orally, can stimulate endogenous EPO production. Most compounds stabilized hypoxia-induced transcription factors that activated the EPO gene. These compounds include oxo-glutarate competitors, however they also include simple ions, including cobalt chloride ions. Inhaling a xenon/oxygen mixture activates the production of the transcription factor HIF-1-alpha, resulting in increased erythropoietin production and increased overall performance. This method has been used in Russia since 2004.

Cycling

Synthetic EPO is believed to have come into use in cycling around 1990. In theory, using EPO can significantly increase VO2max, making it beneficial for endurance sports such as cycling. Italian anti-doping lawyer Sandro Donati claims the cycling doping story could trace back to Italian doctor Francesco Conconi of the University of Ferrarra. In the 1980s, Conconi worked on the idea of ​​providing athletes with their own blood through transfusions. Donati suggested that this development "opened the way to EPO, since blood doping was the way to understand the role of EPO." Dr. Michel Ferrari, Conconi's former student and mentee, gave a controversial interview in 1994 that mentioned the drug, immediately after the Gewiss-Ballan team achieved an astonishing performance in the La Flèche Wallonne race. Ferrari told l'Equipe journalist Jean-Michel Rouet that EPO does not have a "impressive" effect on the performance of athletes, and if cyclists used it, it would not cause a "scandal." After the journalist became suspicious that the deaths of several athletes were most likely due to EPO, Ferrari stated that EPO is not dangerous, while stating that "it is also dangerous to drink 10 liters of orange juice at once."The "orange juice" comment was widely quoted Ferrari was fired soon after, continuing to work in the industry with professional cyclists, including Lance Armstrong.That same year, Sandro Donati, working for the Italian National Olympic Committee, presented a report in which he accused Conconi of that it is associated with the use of EPO in sports... In 1997, the International Cycling Union (UCI) introduced a new rule under which all athletes who were detected with a hematocrit above 50% were not only immediately disqualified, but also suspended from racing for two weeks. Robert Millar, a former racing competitor, later wrote for Cycling News that the 50% limit was "an open invitation to doping at a certain level", pointing out that hematocrit levels should typically be "around 40-42%". ”, after which they should fall as the “grand tour” progresses; after EPO, levels should remain at 50% "for several weeks." By 1998, the use of EPO had become widespread, and Festin's case came to light during the 1998 Tour de France. One manager offered Christophe Basson 270,000 francs a month if he would use EPO, but he refused. In the 1998 Tour de France, Stuart O'Grady won one of the stages, receiving the Tour de France yellow jersey for three days, finishing second in points using EPO. In 2010, Floyd Landis admitted to using performance-enhancing drugs, including EPO , throughout his career as a cyclist. In 2012, USADA released a report regarding the massive doping of the US Postal Service cycling team, captained by Lance Armstrong. The report contained testimony from numerous team cyclists, including Frankie Andreu, Tyler Hamilton, George Hincapie , Floyd Landis, Levi Leipheimer and others, who admitted that they and Armstrong used cocktails of performance-enhancing substances during the Tour de France, especially EPO, when Armstrong won seven consecutive victories. It became known that Armstrong and the team manager Johan Bruyneel forced other team members to dope and the roots of their doping network came to light, including shady members, doctors and other professionals who helped cyclists take drugs; High-ranking executives were identified who helped avoid doping controls and hide positive results. Armstrong was subsequently stripped of all victories since 1998, including victories at the Tour de France and appearances at the 2000 Summer Olympics. The UCI agreed with the decision. While some of the doping cases occurred more than 8 years ago, USADA felt that this limitation could not be applied to Armstrong's "fraudulent cover-up." Long-standing precedent in US law has shown that the statute of limitations does not apply in cases of fraudulent conduct by the defendant. In accordance with this decision, the tour organizers removed Armstrong's name and his results. Witnesses said the code words for EPO were "Edgar", "Poe", Edgar Allan Poe", "Zumo" (Spanish for "juice").

Story

In 1905, Paul Carnot, a professor of medicine in Paris, and his assistant Clotilde Deflandre, suggested that hormones regulate the production of red blood cells. After conducting experiments on rabbits that had undergone bloodletting, Carnot and Deflandre believed that the increase in red blood cells in rabbits was a hemotrophic factor called hematopoietin. Eva Bonsdorf and Eva Žalavisto continued their research into the production of red blood cells, then naming the hematopoietic substance “erythropoietin.” Further research into the existence of EPO by scientist K.R. Reissman (location unknown) and Allan J. Earsley (of Thomas Jefferson Medical College) showed that a substance circulating in the blood can stimulate the production of red blood cells, thereby increasing the hematocrit. This substance was eventually isolated and confirmed to be erythropoietin, allowing EPO to be used therapeutically for conditions such as anemia. Hematologist John Adamson and nephrologist Joseph W. Eschbach studied various forms of kidney failure and the role of the natural hormone EPO in the formation of red blood cells. Studies of sheep and other animals in the 1970s by these two scientists helped establish that EPO stimulates the production of red blood cells in the bone marrow, which may help treat anemia in humans. In 1968, Goldwasser and Kung began work on isolating human EPO; in 1977 they were able to purify a milligram of this substance that was 95% pure. Pure EPO allowed partial amino acid sequence determination and gene isolation. Later, an NIH-funded researcher at Columbia University discovered a way to synthesize EPO. Columbia University patented the technology and licensed it to Amgen. There has since been controversy over the fairness of Amgen awarding NIH-funded work, with Goldwasser never receiving financial compensation for the research. In the 1980s, at the Northwestern Kidney Center, Adamson, Joseph W. Eschbach, Joan C. Egri, Michael R. Downing, and Jeffrey K. Brown conducted a clinical trial of a synthetic form of the hormone, commercially known as Epogen, marketed by Amgen. The trial was successful and the results were published in January 1987 in the New England Journal of Medicine. In 1985, Lin and his colleagues isolated the human erythropoietin gene from a genomic phage database, allowing them to characterize it for further research and release. Their studies identified a gene that encoded erythropoietin to produce EPO in mammalian cells that was biologically active in vitro and in vivo. Shortly thereafter, commercial production of recombinant human erythropoietin (rhEpo) began to treat patients with anemia. In 1989, the US Food and Drug Administration approved the hormone Epogen, which is still used today.

:Tags

List of used literature:

1 ml of solution for subcutaneous and intravenous administration contains 500 IU or 2000 IU Epoetin beta .

Release form

1 ml of solution in a glass ampoule; 5 ampoules in contour packaging; 1 or 2 packs in a paper pack.

pharmachologic effect

Stimulating effect on hematopoiesis .

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

– this is purified glycoprotein , a recombinant analogue of natural human Erythropoietin, which is a growth factor hematopoiesis . Produced using genetic engineering methods.

Increases the quantity reticulocytes, activates synthesis in red blood cells . Does not affect leukopoiesis . The drug is believed to interact with erythropoietin receptors on cell walls.

Pharmacokinetics

After subcutaneous administration, the highest concentration is recorded after 14-26 hours. The half-life is 15-26 hours, with intravenous administration - up to 12 hours.

Indications for use

• To increase the amount of blood for subsequent autotransfusion , to avoid blood transfusions donor blood.
• Heavy anemia against the background of the chronic type.
• Anemia in bone marrow diseases and a number of chronic diseases (, myelodysplastic diseases, oncological diseases ).
• Warning anemia in premature babies (up to the 34th week) with a birth weight of 0.75-1.5 kg.

Contraindications

(uncontrollable), or in the month preceding treatment, in the past, unstable , To epoetin beta.

Side effects

• Phenomena from the nervous system: headache, confusion.
• Phenomena from the circulatory system: hypertensive crisis, arterial hypertension.
• Allergic reactions: rash, reactions anaphylactoid type.
• Phenomena related to blood coagulation and effects on blood tests: thrombotic complications, thrombocytosis.
• Metabolic phenomena: hyperkalemia.

Instructions for use (Method and dosage)

The instructions for Erythropoietin advise developing a treatment regimen individually depending on the degree anemia , the patient’s condition and type of disease.

Intravenous and subcutaneous administration is possible. The initial dose is 50-150 IU per kilogram of weight, the recommended frequency of administration is every other day.

Overdose

In case of overdose, effects characteristic of a high degree of activity of the active substance may occur. At very high contents it is possible to produce phlebotomy . Symptomatic treatment is used.

Interaction

Drugs that activate hematopoiesis (drugs gland and others) can enhance the effect Epoetin beta on hematopoiesis .

Terms of sale

Can only be purchased with a prescription.

Storage conditions

• Store in a dark place.
• Store in a temperature range of 2-8 degrees.
• Keep away from children.
• Do not freeze.

Best before date

Three years.

special instructions

It is advised to use the product with caution when thrombocytosis, hepatic or vascular insufficiency , at malignant oncological diseases , in patients with nephrosclerosis.

The effectiveness of therapy decreases with a lack of gland in the body, as well as during infectious and inflammatory lesions or hemolysis .

During treatment, it is advised to refrain from driving mobile mechanisms and vehicles.

Erythropoietin analogues

Other Erythropoietin preparations (analogs): Vero-Epoetin, Epotal, Epostim, Epoetin, Erythrostim, Erythrostim, Shanpoetin, Gemax, Binocrit, Vepox.

During pregnancy and lactation

During these periods it is possible to take medications Epoetin beta in the presence of strict indications.

Not everyone knows what erythropoietin is, but this indicator is important in the human body, especially in an athlete. Erythropoietin is a hormone produced primarily by the kidneys. It appears in the blood when oxygen starvation begins in the human body.

Erythropoietin also enters the bone marrow, where the process of generation of red blood cells, the basis of which are stem cells, is started. It is this blood cell that contains hemoglobin. This is the same protein that has the ability to carry oxygen.

The life span that red blood cells must demonstrate is usually 120 days. They all have the same shape and size. At the same time, human blood contains approximately the same number of these cells on a constant basis, which circulate through the bloodstream. If fewer red blood cells are produced, too many are lost through destruction or blood loss.

In accordance with this, the total volume of oxygen received by internal organs and tissues will be reduced. In response to this process, the above hormone is produced. This hormone is very important for athletes. The fact is that with constant increased physical activity, oxygen starvation is inevitable. Therefore, the hormone is produced in greater quantities to stimulate the bone marrow to produce red blood cells.

Moreover, the production of this blood component depends not only on the functioning of the bone marrow, but also on the presence of sufficient iron, vitamin B12, and folic acid in the body. The education process itself is also very important. If the hormone is reduced, then there will simply be no stimulating effect on the bone marrow.

To determine the hormone and its level, a blood test is prescribed. The reference values ​​demonstrated by a hormone such as erythropoietin should be in the range of 4.3 – 29 mIU/ml. If the analysis shows other indicators, pathology may be present in the human body.

If the hormone is elevated, and the analysis shows a lack of red blood cells, then most likely we are talking about anemia associated with insufficient functionality of the bone marrow type. If the hormone is not increased, but decreased with the same anemia, then we can talk about improper functioning of the kidneys. They are the ones responsible for the production of this component.

When the hormone is elevated along with red blood cells, we can talk about excessive production of erythropoietin by any excretory organ. If only the red blood cell count is increased, with a decrease in hormonal levels, then we can conclude that there is no connection between polycythemia and the production of erythropoietin.

Features of the analysis

A blood test to determine hormonal levels is performed to differentiate, diagnose and confirm anemia in its various manifestations. Despite the fact that the name anemia is used for a number of diseases, its different types are not synonymous.

Such analysis helps in determining how serious the level of pathology is. If endogenous erythropoietin shows low levels, then anemia will show progress.

If a person has chronic kidney disease, it is necessary to carry out analysis with enviable regularity. This is necessary to check the kidneys, their ability to produce the hormone in abundance. However, the test is not required when monitoring for anemia. Sometimes this blood test can help identify the reason why more red blood cells are being produced than necessary.

A blood test is performed when the cause of anemia is not a deficiency of vitamins or microelements. It is not needed in case of blood loss or hemolysis. It is also important to perform the analysis if separation of erythropoietin deficiency and bone marrow suppression is considered. An EPO test is also required if the red blood cell count is high.

Deviations towards increase

The amount of the hormone in the blood can be either higher or lower than normal, but the first condition is much more common. The level can increase as a result of blood diseases, tumors and a number of other conditions.

If we consider these categories separately, there are several options in the list of blood diseases. Pure red bone marrow aplasia can increase hormone levels. This disease is rare. Within its framework, the production of only red blood cells is reduced, without problems with leukocytes and platelets.

As a result of acute or chronic blood loss, this condition will also occur. Anemia of the aplastic type, due to a deficiency of iron, folic acid and vitamin B12, can affect it. Leukemia should not be excluded as a possible cause.

The following kidney problems can increase hormone levels: impaired blood supply resulting from shock, renal artery stenosis, urolithiasis, or polycystic disease.

A number of diseases characterized by a decrease in the amount of oxygen in the blood should not be ruled out. This may be bronchitis in its chronic form, COPD, pneumoconiosis, heart defects or congestive failure.

If you want to get the correct indicator in the analysis, then you need to exclude taking erythropoietin. By the way, erythropoietin is considered doping in sports.

Reasons for the decline and features of the analysis

There are not many variants of diseases in which the hormone level decreases. That is why such a laboratory result is much less common than an increase. The level of this hormone can decrease as a result of kidney diseases. In particular, when it comes to chronic failure or in patients undergoing dialysis.

Also, do not forget about polycythemia vera. We are talking about increased proliferation of all cell lineages in the bone marrow. There is no dependence on the level of erythropoietin.

Do not forget that any analysis must be carried out taking into account preparatory activities. The reason for the distortion of the results may be blood transfusion, taking analapril, or increased viscosity of blood plasma. All these processes will lead to a decreased hormone level as a result of the analysis.

Maximum levels of the hormone are observed in the morning, during pregnancy, taking steroids of an anabolic nature, as well as using erythropoietin directly in dosage form.

It is worth emphasizing that normal erythropoietin levels do not always indicate the absence of pathologies. In particular, anemia resulting from a lack of vitamin B12 or iron may persist even when the hormone level has returned to normal.

Only patients with anemia and chronic renal failure should use artificially synthesized hormones. This treatment will also be effective for problems with the functioning of the bone marrow.

Medications

Often, if the body produces insufficient hormones on its own, medications are prescribed to help compensate for its deficiency. One of these is recombinant erythropoietin. Recombinant human erythropoietin is a purified glycoprotein that acts as a growth factor of a hematopoietic nature.

This drug was obtained as a result of the work of genetic engineers. After taking it, the level of red blood cells and reticulocytes will be increased to normal levels, and the synthesis of hemoglobin in the cells will be stimulated.

This drug is prescribed for anemia caused by:

• chronic kidney failure;
• bone marrow lesions;
• a number of chronic diseases.

The instructions for use also contain information about the possibility of using it for newborns who were premature. Therefore, they need anemia prevention. Such a drug can also increase the level of donor blood, which is subsequently used for autotransfusion.

Before use, you must read the instructions, which detail the contraindications. However, the use of the drug should initially only be carried out as prescribed by a doctor. Contraindications include sensitivity to any components, severe hypertension of the anterial type. If we are talking about the need to increase the amount of donor blood, then a history of myocardial infarction or stroke should become a restriction on use.

It is worth noting that this drug has synonyms. One of them is epoetin beta. Epoetin beta is a glycoprotein containing more than 150 amino acids. The drug epoetin beta helps in the formation of red blood cells from progenitor cells that have been partially committed.

The composition of epoetin beta is very close to that of the natural human hormone. Epoetin beta can be administered intravenously or subcutaneously. As a result of the work of epoetin beta, the number of red blood cells, reticulocytes, and hemoglobin indicators increases.

In addition, after taking epoetin beta, you should expect an increase in the rate of iron incorporation into cells. If epoetin beta is used for leukocytic leukemia, the effect should be expected two weeks later in comparison with other patients. Speaking of pharmacokinetics, epoetin beta shows the best results when administered intravenously. We are talking about 15 minutes.