Erythropoietin recombinant human. Recombinant erythropoietin. Recombinant human erythropoietin Erythropoietin structural formula

On the eve of the last Olympics in Beijing, the head of the Russian anti-agency RusADA, Alexander Drevevoedov, answering the question of what drugs the domestic laboratory catches most often, named first of all diuretics, steroids and marijuana, the fascination for which has recently become a real scourge in many sports around the world . But all the loudest of this winter brought to light the abbreviation EPO, which is much more mysterious for the layman. Traces of this particular substance were found in the analyzes of the three leaders of the national biathlon team Albina Akhatova, Ekaterina Yurieva and Dmitry Yaroshenko. And a little later, a number of fairly well-known athletes - biathletes Andrei Prokunin and Veronika Timofeeva, multiple winners of the World Cup stages according to Natalia Matveeva, as well as athletes Vladimir Yezhov and Elena Canales.

By the way, even before the 2006 Winter Olympics in Turin, the then head of the Anti-Doping Service of Rossport, Nikolai Durmanov, spoke of EPO as a real nightmare for world sports. According to him, due to the fact that the drug was elusive for many years, he, in fact, “determined the design of sports pedestals”: ​​who is at the top, who is a little lower, and who did not make it to the number of winners. This was especially true of sports such as cycling, skiing, many people talked about ... But even today, when the drug has already been learned to catch, experts in the field of pharmacology still emphasize that in the list of prohibited substances of the World Anti-Doping Agency (WADA) EPO stands apart .

In the body of each person there is this very erythropoietin - a hormone that makes up for the lack of blood cells. If a person climbs into the mountains, then there he begins mountain sickness - there is not enough oxygen. At this point, EPO begins to be produced as a response. If you prick EPO below, at a normal height, then the body will respond as if a person were in the mountains. The amount of hemoglobin in the blood will increase dramatically in a few hours, therefore, the blood will be better saturated with oxygen, muscles will work better, endurance will increase ... This drug was invented in the USA in 1983 for the treatment of kidney patients and is almost an exact copy of the natural hormone, which, in fact , made and continues to make it difficult to catch. EPO entered the sport two years after the invention of the drug. Moreover, with reasonable use, it is practically harmless to the body. As one of the authoritative experts in the field of sports medicine told NI, if the word “humane” is applicable to doping, then, unlike the same anabolic steroids, EPO can be called humane doping. The danger lies in the fact that in large doses and with severe dehydration of the body (imagine how much moisture a cyclist loses during a race in the mountains), it poses a real threat to health, and sometimes life due to an increase in blood viscosity and the possibility of thrombosis, especially in those whose body is naturally inclined to it. The former head of the Russian anti-doping laboratory, Vitaly Semenov, once said that he personally did not know cases of death among athletes after the use of EPO, but at one time he had to observe three cyclists who played for professional Italian clubs. One of them, weighing 80 kg, after taking five cycles of EPO within a year, lost half the weight, and he developed serious health problems.

Few people know that the international Olympic movement first sounded the alarm about EPO back in 1988 during the Calgary Olympics. However, a substantial amount of 400 million dollars had to be invested in the program for its “development”, and Juan Antonio Samaranch, the then president of the IOC, could not go to such expenses. Saying "thank you" for the discovery of EPO should be two French specialists from the laboratory in Chatenot-Malabri, who in 2001 learned to distinguish artificial EPO from natural. And the result was not slow to tell. Despite the fact that cyclists were considered the discoverers of miracle doping, the first high-profile EPO scandal broke out at the 2001 World Ski Championships, when traces of the drug were found in six athletes of the Finnish national team at once. A year later, at the 2002 Olympics in Salt Lake City, Russian skiers Larisa Lazutina and Olga Danilova, as well as Spanish rider Johan Myulegg, caught on it. Two years ago, a talented Russian skier, Sergei Shiryaev, was charged with using the drug, and his two-year ban just ended this winter. And last summer, we recall, a loud scandal shook the holy of holies of cycling - the Tour de France.

Ekaterina Yurieva fell for the EPO.
Photo: AP

Currently, there are several types of EPO and its derivatives. For example, American-made - darbopoetin, because of which Lazutina and Danilova suffered, or the Swiss drug sera, discovered on the Tour de France ... In addition to American and European analogues, three types of EPO are produced in China, two - in our country. Versions that some of them are detected better, and some worse, as one of the employees of the Russian anti-doping center confirmed to NI, do not correspond to reality. Although, as the next novelty appeared on the market, there was talk of its elusiveness. All types of EPO are about the same in effectiveness, and all are detected. But they differ in structure, time of action in the body and price. Russian EPO, for example, will cost less, but to conclude that it was for this reason that those who injected the substance to our biathletes were pierced (in the analyzes of Akhatova, Yuryeva and Yaroshenko, according to some reports, a drug of handicraft Russian production was found) is not costs. Today, a domestic drug is presented as a synonym for the poor work of home-grown pharmacologists, but if it is produced in a normal, non-artisanal way, there will be no significant difference compared to its counterparts in terms of efficiency, and the speed (or vice versa) of detection will not have any. There are long-playing EPO, there are those that act for a short time. Pharmacologists say that if you make an injection once, but more powerful, then the chances that the drug will be caught increase significantly. So those who are trying to cover their tracks prefer to inject more often, but less.

Such a popular use of EPO in sports is also due to the fact that artificial erythropoietin quickly breaks down. It can be detected in the body of an athlete within two to three days, a maximum of four, but this is already considered an exception. By the way, I also heard a version that it was for this reason that Matveeva was released to international competitions, which, as it turns out now, has not passed internal Russian control. Hoped for a chance, but did not carry. From a purely medical point of view, one of the most popular questions about doping today can also be answered: why do some people get caught and others do not? Different people have different periods of elimination of this drug, and there are those who have the presence of EPO in the body to identify and prove 100% impossible. That is why, as a rule, a test for erythropoietin is sent for analysis only when there are serious grounds to suspect the athlete of using this drug. Changes in the blood, for example. It is for this reason that a special dossier is created for athletes, where all blood parameters are entered - even if EPO leaves the body in two days, the effect on the blood remains noticeable for weeks, which gives the laboratory reason to suspect something was wrong. Although, as an authoritative source noted in a conversation with NI, sometimes the presence of a desire or, conversely, unwillingness to catch someone specifically from representatives of the anti-doping services cannot be denied either. Research on EPO, by the way, is very expensive, requires a long time, and sometimes, to be completely sure, and the help of colleagues from other laboratories.

From the list that is on the WADA list today, the Moscow Anti-Doping Laboratory determines everything, including EPO. True, only the last two months in the Federal State Unitary Enterprise "Anti-Doping Center" testing for EPO is carried out on a regular basis. During this time, four positive samples were identified. But if you look at the example of the same Matveeva, sometimes the internal control does not stop either athletes, or coaches, or heads of federations. Doping, to be honest, today still remains an integral part of the sports world. There is a demand for it. The danger is that the specifics of the illegal sports market are such that there is no need to wait for certificates and approval from the Russian Ministry of Health. Experimental drugs can easily penetrate sports, and darbopoetin, which began to be used in sports earlier than in medicine, confirms this. The same can happen with gene doping - the new headache of big sport. By the way, Durmanov has repeatedly said that even a small, well-equipped laboratory can set up its production. At the same time, it is useless to frighten athletes - they are not afraid of anything. This is the profession of desperate people. They are used to living in a risk zone.

According to experts, there is only one way out - to offer an alternative to doping. The most annoying thing is that even now in Russia, where the level of sports medicine remains weak, primarily not because of the lack of good doctors, but because after the collapse of the USSR, a new system of medical control and provision of athletes has not been built, alternative programs, doping-free achievement results exist. These are, for example, a range of physical, chemical and pharmacological methods in any combination with the use of approved drugs that came from previously closed areas - extreme activities, military training and space. It's just that for some reason they don't get the attention they deserve. Although one of the reasons lies on the surface. These methods are more expensive, and you won’t earn much on them. True, there are already those who are not afraid to "risk". For example, there are several successful examples of such programs in the national swimming team. But within the framework of big Russian sports, this is a drop in the ocean. Those who today undertook to reform Russian sports should think that such training has become the norm.

Erythropoietin, also known as EPO, is a glycoprotein hormone that controls erythropoiesis, or the production of red blood cells. It is a cytokine (a signaling protein molecule) for the precursors of erythrocytes (red blood cells) in the bone marrow. Human EPO has a molecular weight of 34 kDa. It is also called hematopoietin or hematopoietin; it is produced by interstitial fibroblasts in the kidney in close association with peritubular capillaries and proximal convoluted tubules. It is also produced in the perisinusoidal cells of the liver. While liver production is predominant in the fetus and perinatal period, renal 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 pharmaceutical preparations are available with various glycosylation configurations, collectively referred to as erythropoiesis stimulating agents (ESAs). Specific details for use vary depending on the product label, however, ESAs have also been used to treat anemia in chronic kidney disease, anemia in myelodysplasia, and anemia due to cancer chemotherapy. Warnings on the instructions include risk of death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence. Exogenous erythropoietin is illegally used as a performance enhancing drug; it can often be detected in the blood due to small differences with endogenous proteins, for example, during 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, the final erythropoiesis will not take place. Under conditions of hypoxia, the kidneys will produce and secrete erythropoietin to increase red blood cell production by engulfing CFU-E, proerythroblasts, and basophilic erythroblast differentiation subunits. Erythropoietin has a primary effect on progenitors and precursors of red blood cells by promoting their survival by protecting these cells from apoptosis. Erythropoietin is the main 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 cell erythroid unit (BFU-E) burst formation begins with the expression of the erythropoietin receptor, being erythropoietin sensitive. After completion of this stage, the erythroid colony forming unit (CFU-E) expresses the maximum density of erythropoietin receptors, completely dependent on erythropoietin for further differentiation. The progenitors of erythrocytes, namely proerythroblasts and basophilic erythroblasts, also express the erythropoietin receptor, and hence they are affected by it.

Non-hematopoietic roles

Erythropoietin exhibits a number of actions, including hypertension dependent on vasoconstriction, stimulation of angiogenesis, including the proliferation of smooth muscle fibers. It can increase absorption by inhibiting the hormone hepcidin. EPO levels up to 100 times baseline in brain tissue have been identified as a natural response to hypoxic injury. In rats, erythropoietin pretreatment has been associated with neuronal protection during induced cerebral hypoxia. Human trials have not been conducted. Numerous studies have shown that EPO improves memory. This effect is independent of its effect on hematocrit. This is most likely due to increased hippocampal response and effects on synaptic connections, neural plasticity, and memory-related neural networks. EPO can 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 blood half-life of about five hours. The half-life of EPO may differ between endogenous and various recombinant versions. Additional glycosylation or other changes in EPO due to recombinant technology have resulted in increased EPO persistence 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. Erythropoietin receptor expression occurs in a number of tissues such as bone marrow and peripheral/central nervous tissue. In the circulation, red blood cells do not themselves express the erythropoietin receptor, so they cannot respond to EPO. However, the indirect relationship between red blood cell longevity and plasma erythropoietin levels has been reported to be termed neocytolysis.

Synthesis and regulation

Erythropoietin levels in the blood 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 IU per ml in blood. EPO is produced primarily by interstitial cells in the peritubular capillary beds of the renal cortex. It is synthesized in the renal peritubular cells in adults; a small part of it is produced in the liver. The regulation is thought to rely on a feedback mechanism to measure blood oxygenation. The continuously synthesized EPO transcription factors, known as hypoxia-induced factors, are hydroxylated and proteasomally digested in the presence of oxygen.

medical application

Erythropoietins available for therapeutic use are produced by recombinant DNA technology in cell culture, including Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa); they are used to treat anemia due to chronic kidney disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), and myelodysplasia due to cancer treatment (chemotherapy and radiation). Instructions for use of medicinal products include warnings regarding the risk of death, myocardial infarction, stroke, venous thromboembolism and tumor recurrence, in particular when used to increase hemoglobin levels in excess of 11-12 g per dl.

Available shapes

Recombinant erythropoietin has a variety of glycosylation configurations that result in alpha, beta, delta, and omega forms. Often referred to as a novel erythropoiesis-stimulating protein (NESP) in the original literature during his research, darbepoetin alfa 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, which means it can be administered less frequently.

blood dope

Erythropoiesis stimulants (ESAs) have been used as blood doping agents to promote endurance sports in boxing, cycling, rowing, running, race walking, snowshoeing, skiing, biathlon, mixed martial arts, and triathlon. The overall oxygen delivery system (oxygen content in the blood as well as heart rate, vascularity, and lung function) is one of the main factors that limits the ability of muscles to be resistant to endurance exercise. Thus, the main reason why athletes use ESA 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 autologous and homologous blood transfusion was partly replaced by the administration of erythropoietin for the body to naturally produce red blood cells. The increased hematocrit (% of blood volume that makes up the mass of red blood cells) with ESA and the total mass of red blood cells in the body provide an advantage in sports, due to which this practice has become banned. In addition to ethical considerations in sports, providing an increased mass of red blood cells (above natural levels) reduces blood flow due to increased viscosity, contributing to an increased 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 return to normal hemoglobin levels (as opposed to exceeding normal levels, when the risk of death increases). Although EPO was considered to be widely used in some sports in the 1990s, until 2000 there was no method to test its use, until researchers at the French National Anti-Doping Laboratory (LNDD) developed specific testing approved by the World Anti-Doping Agency ( WADA); it has been used to detect pharmaceutical EPO by identifying it among nearly identical natural hormones present in athlete's urine. The first use of EPO as a doping agent was discovered by the Swiss Doping Laboratory. In 2002, at the Salt Lake City Winter Olympics, 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 sports history. In 2012, at the 2012 Summer Olympics in London, Alex Schwaser, who won a gold medal in the 50 km race walk at the 2008 Summer Olympics in Beijing, tested positive for EPO, after which he was disqualified. Since 2002, testing for EPO by US sports authorities has been based on a urinalysis or "direct" test only. From 2000-2006, testing for EPO at the Olympics was based on blood and urine tests. However, some substances have been identified that, when taken orally, can stimulate endogenous EPO production. Most of the 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. Inhalation of the xenon/oxygen mixture activates the production of the transcription factor HIF-1-alpha, resulting in increased production of erythropoietin and improved 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. Theoretically, the use of EPO can significantly increase VO2max, making it useful for endurance sports such as cycling. Italian anti-doping lawyer Sandro Donati claims the cycling doping story could lead to Italian doctor Francesco Conconi of the University of Ferrara. During the 1980s, Conconi worked on the idea of ​​giving athletes their own blood through transfusions. Donati suggested that this development "paved the way for EPO, since blood doping was a way to understand the role of EPO." Dr. Michel Ferrari, a former student and ward of Conconi, gave a controversial interview in 1994 mentioning the drug, just after the Gewiss-Ballan team showed amazing results in the La Flèche Wallonne race. Ferrari told l'Equipe journalist Jean-Michel Rouet that the EPO has no "impressive" effect on the performance of athletes, and if cyclists used it, it would not cause a "scandal." After the journalist began to suspect that the death of several athletes was 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 has been widely quoted Ferrari was fired shortly thereafter, continuing to work in the industry with professional cyclists, which included Lance Armstrong.The 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 that all athletes who had a hematocrit above 50%, n They were not only disqualified immediately, but also suspended from racing for two weeks. Robert Millar, a former racer, wrote to Cycling News some time later that the 50% limit was "an open proposal for doping to a certain extent", pointing out that typically hematocrit levels should be "about 40-42% ”, after which they should fall in the course of the “big tour”; after EPO, the level should be maintained at 50% "within a few weeks". By 1998, the use of EPO had become widespread, and the Festin case surfaced during the 1998 Tour de France. One manager offered 270,000 francs a month to Christophe Basson 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, becoming the second most points with 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 on massive doping by the American Postal Service cycling team, captained by Lance Armstrong. The report included testimonies 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 substances that improved performance during the Tour de France, especially the EPO, when Armstrong won seven consecutive victories. Johan Brunel forced other members of the team to dope. the roots of their doping network are known, including shadow participants, doctors and other professionals who helped cyclists use drugs; high-ranking executives were identified who helped avoid doping controls and cover up 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 incidents date back more than 8 years, USADA felt that this restriction could not apply to Armstrong's "fraudulent cover-up". Years of precedent in US law has shown that the statute of limitations does not apply in cases of fraudulent behavior by the defendant. In accordance with this decision, the tour organizers removed Armstrong's name and results. Witnesses said that the code words for EPO were "Edgar", "Po", Edgar Allan Poe, "Zumo" (translated from Spanish as "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 been bled, Carnot and Deflandre considered the increase in red blood cells in rabbits to be a hemotrophic factor called hematopoietin. Eva Bonsdorf and Eva Zhalavisto continued their research on the production of red blood cells, then calling the hematopoietic substance "erythropoietin". Further research regarding the existence of EPO by the scientist K.R. Reissman (residence unknown) and Allan J. Earsley (of the Thomas Jefferson Medical College) have shown that a certain substance circulating in the blood can stimulate the production of red blood cells, while increasing hematocrit. This substance was eventually isolated and confirmed to be erythropoietin, which led to the therapeutic use of EPO in diseases such as anemia. Hematologist John Adamson and nephrologist Joseph W. Eshbach have studied various forms of kidney failure and the role of the natural hormone EPO in the formation of red blood cells. A study of sheep and other animals in the 1970s by these two scientists established that EPO stimulates the production of red blood cells in the bone marrow, which may help treat anemia in humans. In 1968, Goldwaser and Kung began work on isolating the human EPO; in 1977 they were able to purify a milligram of this substance, which was 95% pure. Pure EPO made it possible to partially determine the amino acid sequence and isolate the gene. Later, an NIH-funded researcher at Columbia University discovered a way to synthesize EPO. Columbia University has patented the technology by licensing it to Amgen. After that, there was controversy regarding the fairness of awarding Amgen with NIH-funded work, with Goldwaser never receiving any financial reward for this research. In the 1980s at Northwestern Kidney Center, Adamson, Joseph W. Eshbach, Joan C. Egree, Michael R. Downing, and Jeffrey C. Brown conducted a clinical trial of a synthetic form of the hormone, commercially named Epogen, from Amgen. The trial was successful and the results were published in January 1987 in the New England Journal of Medicine. In 1985, Lin and colleagues isolated the human erythropoietin gene from the genomic phage database, allowing them to characterize it for further research and release. Their research identified a gene that codes for erythropoietin for EPO production in mammalian cells that are biologically active in vitro and in vivo. Shortly thereafter, recombinant human erythropoietin (rhEpo) was commercialized for the treatment of anemic patients. In 1989, the US Food and Drug Administration approved the hormone Epogen, which is still used today.

:Tags

List of used literature:

The hormone erythropoietin, little known to ordinary people, performs vital functions for a person. The secretion of erythropoietin (cytokine) occurs in the kidneys, from where it enters the bone marrow. To clarify - 90% of the hormone is produced by the kidneys, 10% - by the liver.

With the help of a hormone based on stem cells, red blood cells are formed, which many have heard of, since its content is often determined in a general blood test. Red blood cells contain hemoglobin, which is responsible for transporting oxygen in the body.

Every day, the cytokine has to form 200 billion red blood cells, since there is no supply of these cells in the blood and internal organs.

A few words about erythrocytes

Red blood cells are important cells found in the blood. The period of their existence is 120 days. All these cells are exactly the same in shape and size. If there are not enough red blood cells in the blood, the human body will lack oxygen. And it is needed for the performance of its functions by all internal organs and tissues.

A lack of red blood cells occurs as a result of injury after increased blood loss. Also, these cells can be destroyed for various reasons. In these cases, the brain signals the kidneys to produce erythropoietin, and the hormone starts producing new red blood cells.

The described process is very important for athletes, because during large physical overloads the body spends a lot of oxygen. In people engaged in hard physical work, the body is tuned to the timely production of erythropoietin. But to supply the organs with a sufficient amount of oxygen, not only red blood cells are needed, it is also necessary to eat iron-containing foods, take vitamin B12 and folic acid.

Erythropoietin, the norm and deviations from it

What is it - erythropoietin? The substance is formed from amino acids of a certain type. It includes 4 glucose fragments, which differ from each other in physical and chemical characteristics. If there is not enough cytokine in the body, most likely the person has problems with the kidneys. This may be renal failure, and hormone deficiency also occurs after hemodialysis (extrarenal blood purification).

When the amount of this hormone exceeds the norm, the doctor can make a preliminary diagnosis - a disease of the kidneys or other internal organs. Although, an increased rate can be observed in pregnant women, and, in this case, an excess of the norm is not a sign of illness.

Hormone content table:

The hormone is synthesized in the body with a lack of oxygen. As soon as the problem disappears, the secretion of the cytokine stops.

Men have less erythropoietin in their blood because they have more testosterone, which also stimulates the formation of red blood cells. Men require less hormone. Women have much less testosterone, but there is estrogen, which inhibits the secretion of cytokines. Therefore, the described hormone is produced more actively in them, taking into account the counteraction of estrogen.

Analysis for erythropoietin

To determine the content of the hormone, blood is taken for analysis. Typically, the analysis is combined with a clinical blood test, in which they pay increased attention to the number of red blood cells.

When is a study ordered?

A blood test for erythropoietin is prescribed for patients with renal insufficiency. Also, the study is carried out during hemodialysis. An increase in the hormone content can be suspected with the following symptoms:

• Frequent dizziness;
• Severe headaches;
• Excruciating shortness of breath in a horizontal position;
• visual impairment;
• Itching of the skin after a shower;
• Bleeding that is difficult to stop
• Thrombosis and their consequences (stroke, heart attack);
• bluish skin tone;
• Red complexion;
• Swelling of the spleen.

These symptoms are a reason to do a study of the hormone content.

Preparation for analysis

Preparation for venous blood sampling is standard. The patient is shown:

1. Do not eat and drink 8 hours before the analysis, clean water without gas can be drunk;
2. Do not use tobacco in any form the day before and on the day of the study;
3. Do not take medications on the eve and on the day of the analysis, except for life support;
4. Refuse heavy physical work a day before the analysis;
5. Try to protect yourself from stress the day before the study and in the morning before the analysis.

Usually, along with the study of the level of erythropoietin, analyzes are prescribed for the amount of hemoglobin, determination of the volume of folic acid, vitamin B12, hematocrit and erythrocyte indices. The last 2 indicators determine the number of red blood cells in the heme. If necessary, other indicators of health in the blood are also examined.

When is the amount of erythropoietin increased?

The reason for the increase in the level of the hormone can be diseases of various organs and systems of the human body:

• Circulatory system
  • The analysis may indicate a disease in which the number of red blood cells in the bone marrow is reduced, and white blood cells and platelets are within the normal range.
  • Also, the level of the hormone can be reduced due to large blood loss.
  • Another decrease in this indicator can be caused by various anemias - lack of iron, vitamin B12, folic acid, aplastic anemia (a disease in which blood formation in the bone marrow is reduced, the production of leukocytes, erythrocytes and platelets is reduced). This also includes sickle cell anemia and thalassemia, which are expressed in the pathological structure of hemoglobin.
  • Stem cell mutations.
  • Oncological diseases of the blood.

• kidney disease
  • Failures in the blood supply to organs.
  • Narrowing of the renal artery.
  • Formation of stones in the kidneys and bladder.
  • Multiple cysts of the kidneys.

• Diseases resulting from a lack of oxygen in the blood
  • Diseases of the respiratory tract and organs.
  • allergic bronchitis.
  • Pneumoconiosis, silicosis (lung diseases that occur when inhaling dusty air and lead to fibrotic processes in the lungs).
  • Acquired heart defects, expressed in incomplete closure of the heart valves.
  • Heart failure due to lack of oxygen and metabolic disorders in the heart muscle.

• Tumor diseases of the nervous system, adrenal glands, kidneys.
• The use of erythropoietin as a stimulant (doping) by athletes.

All of these diseases require additional studies - ultrasound, MRI and so on. You should not make a diagnosis on the basis of one indicator. The doctor will decide what you are sick with.

Decreased erythropoietin level

• Renal failure, most often wearing a chronic form. It is expressed in a decrease in the ability of the kidneys to perform their functions.
• Condition after hemodialysis.
• Bone marrow growth due to active cell division.
• Myeloma (malignant disease).
• Rheumatoid arthritis.

The result of the analysis is influenced by the following factors: pregnancy, which increases the rate; the use of anabolic steroids; blood transfusions; taking hormonal drugs.

Kidney failure is sometimes treated with artificially synthesized erythropoietin. But you need to be treated under the supervision of a specialist so as not to harm your health.

Erythropoietin in sports

Athletes are well aware of the substance erythropoietin. In sports, it is called EPO. Since hemoglobin, which is part of erythrocytes, increases the amount of oxygen carried to the organs and systems of the human body, and erythropoietin stimulates the production of erythrocytes, the hormone was identified as a doping agent. It is clear that physical activity is easier for an oxygenated body. Doping began to be considered a substance after the discovery by scientists of ways to stimulate the secretion of the hormone. In addition, a synthetic preparation was obtained.

Doping tests take the athlete's blood or urine. It is easier to determine the presence of this type of doping in the blood. Erythropoietin breaks down 5-9 hours after entering the body, so it is difficult to determine the presence of the hormone in the blood 2 days after taking the drug. To mask doping, dishonest athletes take heparin. It is an anticoagulant (a drug that prevents blood clots from clogging blood vessels).

Another protease is injected into the bladder through the catheter. The drug cleaves peptide bonds between amino acids. Because erythropoietin is made up of a bunch of amino acids, its presence in the blood is smeared. WADA services (World Anti-Doping Agency) have learned to determine the use of doping by the hormone breakdown products contained in the blood and other signs.

Erythropoietin is a renal hormone that controls and regulates the formation of red blood cells (erythropoiesis) in the red bone marrow. 90% of erythropoietin is synthesized in the cells of the capillaries of the renal glomeruli and 10% is produced by the cells of the liver. The release of erythropoietin into the blood is subject to a daily rhythm, its level in the blood in the morning is higher than in the afternoon or evening. The production of this hormone is enhanced in 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 the production of erythropoietin:

• growth hormone(GH, growth hormone) - pituitary hormone (pituitary - 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 (adrenal glands - 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 are involved in its coagulation). Determining the level of erythropoietin in the blood is important for the differential diagnosis between primary (true) and secondary polycythemia.

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

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

A decrease in the level of erythropoietin can be detected:

• - in patients with anemia that has developed with 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 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 in men 120-172 g / l. Such patients are treated with drugs of recombinant human erythropoietin. The effectiveness of such treatment is reduced with iron deficiency in the body.

An increase in the level of erythropoietin 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 lumen of the cavities)
• - in patients with tumors that secrete erythropoietin, such as kidney tumors, pheochromocytoma(benign tumor of the adrenal glands), hemangioblastoma of the cerebellum (tumor originating from the blood vessels).
• - in patients with polycystic kidney disease (impaired development of the renal tissue, leading to the appearance of cysts in it; combined with the pathology of the urinary system).

Erythropoietin is a glycopeptide hormone produced by the adrenal glands and in small amounts by the liver. It is involved in the regulation of the formation of red blood cells synthesized in the bone marrow. The task of erythrocytes, in turn, is to supply cells with oxygen. The effect of erythropoietin on human hematopoietic ability is of interest to scientists and sports coaches, as it makes it possible to increase the resources of the human body.

Erythropoietin or, as it is commonly referred to in medicine, EPO begins to be produced even with the slightest oxygen deficiency. The hormone is transported throughout the body by a complex iron-containing protein, hemoglobin.

Oxygen is used by the body for a variety of functions. Without it, the synthesis of cholesterol, bile acid, and steroid hormones would be impossible. The constituent elements of amino acids and so on. In addition, oxygen breaks down into harmless elements, toxins, poisons, and unnecessary drugs.

During hypoxia, oxygen starvation, internal organs, the cardiovascular system, and most importantly, the brain are destroyed. That is, severe cases of hypoxia end in the death of a person.

The hormone erythropoietin entering the blood turns reticulocytes into red blood cells, significantly increasing their number, respectively increasing the oxygen they carry. As oxygen levels rise, the pressure in the arteries rises, and the blood becomes more viscous.

EPO is produced not only during hypoxia, but glucocorticoid, synthesized by the adrenal gland, in a stressful situation also becomes a stimulator of its release. This feature of the body allows it to increase the strength and speed of muscle tissue in a few seconds, and the influx of acid provides endurance.

The metabolism working in this way allowed man to survive as a species, since there were plenty of natural enemies in the wild, primitive nature. When attacked by a predator, a person managed to escape or win in a fight with a strong animal.

True, such a surge in the activity of the synthesis of blood cells leads to the depletion of iron, copper, vitamins B9 and B12, therefore, after a stressful situation, it is necessary to restore the balance of these substances in the body. Ancient man replenished his supply of iron and copper by eating a defeated animal.

Causes of deviation from the norm

In the human body, the level of various hormones is extremely precisely balanced, the same applies to erythropoietin. The norm for women is the range of hormone content from 8 to 30 IU / l. In men, respectively, 5.6 to 28.9 IU / l. If there is a deviation from the norm up or down, this may mean the presence of some kind of pathology.

1. With an elevated level of erythropoietin, the number of red blood cells should be high, but if it is low, then this indicates anemia, which suppresses the hematopoietic function of the bone marrow.
2. The level of erythropoietin can be reduced under the influence of the environment, for example, in high altitude conditions, poor in oxygen.
3. Oxygen depletion, despite high levels of erythropoietin, can occur as a result of poisoning the body with smoke, such as from cigarettes.
4. A low level of erythropoietin may be caused by kidney failure or by the presence of a cyst or tumor in the adrenal glands. The kidneys also stop producing the desired hormone in case of urolithiasis or the presence of multiple cysts in the parenchyma of the organ.
5. Tumors can also affect the bone marrow, so a high level of erythropoietin in this situation does not cause an influx of red blood cells.
6. The bone marrow is susceptible to a variety of pathologies from various forms of anemia to leukemia, all of which are accompanied by low levels of red blood cells, white blood cells, or platelets.
7. If, with an elevated level of erythropoietin, oxygen in the blood still does not rise, it may be a disease of the lungs or the cardiovascular system.
8. Damage to the brain by hemangioblastoma leads to a violation of the level of erythropoietin in the blood.
9. Acquired immunodeficiency syndrome.
10. After transplantation of any organ, especially bone marrow, there is a significant hormonal failure, accompanied by a deficiency of red blood cells.
11. Donor blood donation leads to a deficiency of red blood cells despite high levels of erythropoietin.

The presence of all the mentioned pathologies and diseases becomes the reason for a long and laborious therapy, during which not only the hormonal and oxygen balance in the body is put in order, but the very cause of such a situation is eliminated.

The use of erythropoietin in therapy

Many diseases and conditions are treated with hormone therapy, including erythropoietin drugs. Any treatment in this direction is prescribed by an endocrinologist, since even the slightest deviation in the dosage of the drug can lead to a dangerous excess or vice versa, an underestimation of the number of red blood cells.

Treatment is carried out both with the help of subcutaneous and intravenous drugs. During treatment, the patient is regularly checked for blood composition, hemoglobin levels and erythropoietin levels in the blood.

It is important to understand that the course of treatment with erythropoietin implies a gradual decrease in the amount of the drug taken, so that the body itself restores the required amount of hormones. As a result of the correct use of drugs, the work of the endocrine system is fully restored.

For your information, the normal level of hemoglobin is from 110 to 120 g/l, and the ratio of erythrocytes to other blood elements should be at the level of 30-35%.

Along with drugs containing erythropoietin, the patient must take medications containing iron, folic acid and B vitamins, this restores the level of substances used by the hematopoietic system in the body.

Erythropoietin in sports

Erythropoietin has found wide application in sports. Its synthetic analogues are used to give the muscles the ability to do hard work for a long time. Drugs that thus affect the body of an athlete are called doping.

An athlete taking doping based on erythropoietin is able to run, ride a bicycle or row with oars for a long time without feeling tired. In other words, such doping has found application in those sports where a long uniform effort is needed. But for heavyweight athletes, it is not very well suited.

The payoff for the ability to run or pedal for a long time is an accelerated metabolism and the burning of all reserves of iron, folic acid and other elements of the hematopoietic system.

Several fatal cases were registered, just among cyclists, after which drugs with erythropoietin were officially recognized as dangerous doping and they were banned from use. All athletes convicted of using erythropoietin were disqualified for the rest of their lives.

Doping with erythropoietin is very difficult to determine by analyzing the blood or urine of an athlete. Therefore, since 1990, anti-doping laboratories have been developing ways to detect a prohibited drug in athletes' samples. Since the synthetic hormone, in its composition and action, is identical to the natural one, besides, its presence in the blood is explained by the stressful situation caused by the competition, it is extremely difficult to detect it.

Therefore, it was decided not to measure the amount of the hormone in the blood of athletes, but the level of oxygen and hemoglobin. Although this method of measurement is quite subjective, because someone was calm before the start, and rested the day before, and someone trained for a long time and is very nervous.

Despite the controversy of methods for determining doping in the blood of an athlete, the conclusion in connection with the use of the drug with erythropoietin can be made simple - the effect of it can be fatal.

But there is another opinion, born in the light of recent events related to sports competitions of world importance, namely the Olympics. The main thing for sports officials is not to identify an athlete using doping, but to remove athletes from competitions with policies that are wrong from their point of view. And few people in such a situation are interested in what effect the drug creates on a person.