Recombinant human erythropoietin. Functions of erythropoietin in the human body

Composition and release form of the drug

1 ml - ampoules (5) - contour cell packaging (1) - cardboard packs.
1 ml - ampoules (5) - contour cell packaging (2) - cardboard packs.

pharmachologic effect

Recombinant human erythropoietin (purified glycoprotein), which is a hematopoietic growth factor. Obtained by genetic engineering. Increases the number of red blood cells, reticulocytes, stimulates hemoglobin synthesis in cells. Does not affect leukopoiesis. It is believed that erythropoietin interacts with specific erythropoietin receptors on the surface of cells.

Pharmacokinetics

Anemia due to bone marrow lesions and some chronic diseases (including aplastic anemia, anemia due to myelodysplastic diseases, chronic inflammatory diseases, AIDS, cancer).

Prevention of anemia in premature newborns born with a body weight of 750-1500 g before the 34th week of pregnancy.

To increase the volume of donor blood intended for subsequent autotransfusion in order to avoid blood transfusions.

Contraindications

Uncontrolled, myocardial infarction or cerebral stroke within the previous month, unstable angina, history of thromboembolism, hypersensitivity to epoetin beta.

Dosage

Doses, regimen and duration of treatment are determined individually and depend on the severity of anemia, the severity of the patient’s condition, and the nature of the disease. Injected subcutaneously and intravenously. Initial doses are 50-150 IU/kg, frequency of administration is an average of 3 times a week.

Side effects

From the cardiovascular system: Arterial hypertension and hypertensive crisis are possible.

From the side of the central nervous system: encephalopathy (more often during hypertensive crises) and confusion are possible.

From the blood coagulation system: rarely - thrombocytosis, thrombotic complications.

From the side of metabolism: rarely - hyperkalemia.

Allergic reactions: rarely - anaphylactoid reactions.

Drug interactions

With the simultaneous use of drugs that affect hematopoiesis (for example, iron supplements), the stimulating effect of epoetin beta may be enhanced.

special instructions

Use with caution for epilepsy, thrombocytosis, liver failure, vascular insufficiency, and malignant neoplasms; in patients with nephrosclerosis not receiving hemodialysis, since a more rapid deterioration of renal function is possible.

The effectiveness of treatment decreases with iron deficiency in the body, with infectious and inflammatory diseases, and hemolysis.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, you should refrain from activities that require increased attention and speed of psychomotor reactions.

Pregnancy and lactation

During pregnancy and lactation, epoetin beta is used only when the expected benefit of treatment for the mother outweighs the potential risk of side effects in both the mother and the fetus or child.

IN experimental studies no teratogenic effect was detected.

For impaired renal function

Use with caution in case of liver failure.

For liver dysfunction

Use with caution in patients with nephrosclerosis who are not receiving hemodialysis, as a more rapid deterioration of renal function is possible.

People first learned about what erythropoietin is in 1905 thanks to the work of the French doctor of medicine Paul Carnot. He discovered this hormone together with his assistant, Clotildo Deflander.

Erythropoietin is an active biological substance produced primarily by kidney cells and to a lesser extent by liver tissue. By its structure, this hormone is a glycoprotein.

The hormone erythropoietin stimulates the production of red blood cells. An increase in the production of this active substance occurs in the following cases:

Blood loss.
Decreased oxygen content in the inhaled air.
Stressful situations.

This hormone also performs another function. It prevents excessive destruction of red blood cells under normal conditions. As a result, thanks to erythropoietin, they live for approximately 120 days. In addition, this active substance stimulates the release of additional red blood cells from their depot.

In addition, doctors have established a certain positive effect of this hormone on the process of platelet production.

About the features of production

This hormone, produced by the human body's own body, is called endogenous erythropoietin. About 90% of its total amount is produced in the cells of the proximal tubules and glomeruli of the kidneys. The remaining 10% is produced by liver tissue (at the human embryonic stage, it is the main source of EPO).

The main stages in the production of this hormone are as follows:

Development of hypoxia.
A decrease in oxygen concentration is detected by special sensory cells of the kidneys.
The production of prostaglandins in the renal glomeruli increases.
Erythropoietin is produced and released into the blood.

This diagram is very simplified. At the same time, a number of substances have been identified that increase the level of erythropoietin in the blood. Among them:

somatotropic hormone.

Currently, only 1 group of hormones is known, which helps reduce the concentration of this active substance in a blood test. We are talking about estrogens.

Reasons for changes in concentration

Erythropoietin is one of the most active biological compounds. The level of its concentration may also change in the presence of diseases of various organs and tissues.

Erythropoietin is formed in additional quantities in the pathology of the following organs and systems:

Diseases of the blood system.
Kidney diseases.
Lung diseases.

Increased levels of this active substance are often observed in patients with hormone-producing kidney tumors, as well as pheochromocytoma and hemiangioblastoma. Another fact leading to an increase in the level of erythropoietin in the blood is the use of this hormone as a doping.

A pathological decrease in the concentration of this active biochemical compound can result from the development of the following pathology:

Diseases accompanied by the development of chronic or acute renal failure.
Polycythemia vera.

As a result, determining the level of this hormone in a blood test is extremely important.

Diseases of the blood system

Diseases from this group most often cause an increase in the concentration of erythropoietin. The main ones are:

anemia of various etiologies;
initial stages of myelodysplastic syndrome;
leukemia;
red bone marrow aplasia.

All these diseases, one way or another, lead to a decrease in the level of red blood cells in the blood. Increased production of erythropoietin in this case is a response to this situation.

Kidney diseases

This group of ailments includes the following:

renal artery stenosis;
polycystic kidney disease;
urolithiasis disease;
shock conditions accompanied by a decrease in blood supply to the kidneys.

The main reason for increased erythropoietin production in the case of kidney disease is a decrease in blood flow in this organ. At the same time, the receptors that control the concentration of red blood cells in the blood mistakenly assess it as reduced, and in response to this they stimulate an increase in the production of a hormone designed to correct the situation.

Respiratory diseases

We are talking about the following diseases:

chronic obstructive pulmonary disease;
Chronical bronchitis;
silicosis;
pneumoconiosis.

Each of these diseases contributes to a decrease in blood oxygen saturation. As a result, hypoxia develops, which becomes a triggering factor for the body to begin to intensively produce erythropoietin.

The main ailments here are those that lead to a decrease in the concentration of oxygen in the blood. This may be due to the mixing of arterial and venous blood, as in some heart defects, and the occurrence of congestive heart failure, which often occurs in older patients.

About diseases accompanied by a decrease in hormone concentration

Most often, a decrease in the level of production of this active substance occurs as a result of impaired kidney function. This is observed in chronic or acute renal failure. This can be observed with kidney infarction, infectious diseases of this organ, poisoning with certain substances (arsenic, mercury and others), diabetes mellitus, amyloidosis, glomerulonephritis, and other diseases.

In addition, erythropoietin is practically not produced in the presence of polycythemia vera. This disease is accompanied by a significant increase in the production of all blood elements. In this case, the number of red blood cells increases regardless of the concentration of the hormone that stimulates their maturation.

Diagnostics

Most often, an analysis for the content of this important hormone is prescribed by a therapist and hematologist. In this case, the main indication for its implementation is the presence of anemia of unknown etiology in the patient after the initial examination.

It is rational to prescribe an erythropoietin test if the patient has a decrease in the number of red blood cells in the blood with normal levels of serum iron, folic acid and vitamin B12. In addition, such a person should not have had any history of blood loss in the recent past or signs of hemolysis (massive destruction of red blood cells).

Currently, the normal levels of erythropoietin in a blood test are the following indicators:

for men – from 5.6 to 28.9 IU/l;
for women – from 8 to 30 IU/l.

For representatives of the fair half of humanity, this figure is higher due to periodic blood loss during menstruation. This loss of red blood cells must be replenished, which is facilitated by the additional release of erythropoietin.

About medical use

Previously, it was quite difficult to treat people with a deficiency of this hormone. In severe cases, it was necessary to periodically transfuse red blood cells. After lengthy research and practical experiments, medical scientists managed to create a technique that allows the production of so-called recombinant erythropoietin.

Such a drug is obtained from animal tissues that have previously been injected with the genetic code of human EPO. The hormone produced in their body is identical to that produced in the patient’s kidney and liver tissue, so it does not cause absolutely any cytotoxic reactions and performs all the functions assigned to it.

The hormone produced in the body of animals comes in several types. Today, its main types are erythropoietin alpha and beta. In terms of their pharmacological action, they are not fundamentally different. The specific type of hormone depends on which gene strand was used in the pharmaceutical company's production process.

Basic drugs

Currently, there are several drugs that are a recombinant form of erythropoietin. All of them are available in ampoules. The medicine is administered subcutaneously or intravenously. The main ones among these drugs are:

Epoetin;
erythrostim;
recormon;
vero-epoetin.

All of these drugs are commercial names of recombinant erythropoietin produced by various pharmaceutical companies and have the same indications for their use. The main ones among them are the following:

benign tumor diseases of the kidneys;
condition after chemotherapy for malignant neoplasms;
anemia of various types, especially in combination with chronic renal failure;
for prophylactic purposes before major surgical interventions;
for preventive purposes for a child weighing less than 1.5 kg and born before 34 weeks of pregnancy.

Unfortunately, there are some contraindications to taking such medications. Chief among them are:

Unstable angina.
Decrease in the amount of iron in the blood.
Individual increase in sensitivity to the components of the drug.

Such drugs are prescribed with great caution during pregnancy. If the benefits of taking them are greater than the possible negative consequences, then they can be prescribed. It is recommended to start using them during pregnancy in a hospital, where doctors will quickly provide all the necessary assistance if the patient’s condition worsens.

The selection and correction of the doses of this drug used should be carried out by the attending physician. Most often, the patient is initially prescribed 20 IU/kg of recombinant erythropoietin 3 times a week subcutaneously. After 4 weeks, a general blood test is performed. If the hematocrit level (the ratio of the volume of formed elements to the total volume of blood) increases by less than 2%, then the dose is increased by 2 times. You can increase it up to 720 IU/kg per week.

About side effects

The use of such medications does not always occur without negative consequences. Side effects when using them may have the following manifestations:

headache;
dizziness;
nausea;
vomit;
joint pain;
asthenic condition;
diarrhea;
convulsions;
swelling, redness at the injection site;
increase in body temperature.

The occurrence of such side effects while using erythropoietin must be reported to your doctor.

Application in sports

Currently, this hormone cannot be used by professional athletes. Back in 1990, the International Olympic Committee banned the use of erythropoietin - doping of this type until that time was most widely used by cyclists. From 1987 to 1990, several deaths were reported in such athletes due to overdose of recombinant erythropoietin.

Unfortunately, neither these tragedies nor the IOC bans stopped the use of this drug for non-medical purposes. One of the most high-profile scandals in recent years is the lifelong disqualification in 2012 of the legendary American cyclist Lance Armstrong, who used erythropoietin in sports for many years.

Currently, there are several methods that indirectly stimulate the production of erythropoietin by the athlete’s body. One example is xenon inhalation. Such techniques are also prohibited for use by athletes.

Bibliography

Glycosylated hemoglobin and free fatty acids in the diagnosis of diabetes and metabolic syndrome: New opportunities for diagnosis, therapy and risk assessment. – Moscow: [b. i.], 2014. – 100 p. : Fig., table. – Bibliography at the end of the chapters.
Bessonov P.P., Bessonova N.G. Syndromic diagnosis of chronic liver diseases.
Vinogradov A.V. Differential diagnosis of internal diseases. M.: MIA. 2001.
Diseases of the endocrine system: hands. on internal diseases / ed. I. I. Dedov. – M.: Medicine, 2000. – 568 p. : ill.
Makarov V.M., Khorunov A.N., Argunova A.N., Asthma school. Methodological manual Yakutsk, YSU Publishing House, 2005.

Erythropoietin

Erythropoietin– a hormone from the group of glycoproteins, synthesized in the kidneys and stimulating the production of red blood cells. The test for erythropoietin has an independent diagnostic value, but is more often prescribed with a general blood test (hematocrit, erythrocyte index). A study of the level of erythropoietin in plasma is used to establish a diagnosis of anemia or polycythemia, determine the etiology of diseases of the blood system and evaluate the effectiveness of treatment. Blood for the test is taken from a vein. A unified research method is ELISA. The normal steroid indicators are 4.3-29 mIU/ml. The analysis period ranges from 1 to 8 days.

Erythropoietin is a steroid that enhances the production of red blood cells, which transport iron and oxygen to the body's tissues. The main share of this hormone is synthesized in the kidneys in response to oxygen starvation and only about 10% is produced in the liver by hepatocytes. Once in the bone marrow, erythropoietin stimulates the transformation of stem cells into red blood cells of the same shape and size. In healthy adult patients, the lifespan of red blood cells is about 4 months. Normally, the body contains approximately the same number of red blood cells circulating in the blood. If the balance between the synthesis and destruction of red blood cells is disturbed, anemia occurs. With insufficient production of red blood cells in the bone marrow, with hemolysis or bleeding, the level of red blood cells decreases, and accordingly, the transport of oxygen to all organs decreases. In response to oxygen starvation of kidney cells, they synthesize erythropoietin, which is delivered through the circulatory system to the bone marrow, where the formation of red blood cells is stimulated.

Erythropoietin functions in the bloodstream for a short time, after which the hormone is excreted in the urine. With the development of certain neoplasms, the steroid is produced in large quantities, which causes polycythemia (increased number of red blood cells). This pathology contributes to an increase in blood volume, an increase in its viscosity and surges in blood pressure. Artificially created erythropoietin preparations are used to treat anemia in patients suffering from chronic renal failure or bone marrow dysfunction. The study is most often prescribed in surgery, endocrinology, nephrology or hematology in combination with CBC (qualitative and quantitative analysis of blood cells). Also, tests for the concentration of erythropoietin are used in sports medicine to detect doping in the blood, which increases the concentration of oxygen in tissues, as a result of which the athletes’ body becomes more resistant to high physical activity.

Indications

A study of the level of erythropoietin in the blood is prescribed for diagnostic purposes to determine pathology (anemia or polycythemia), identify tumors of the kidneys and adrenal glands, as well as monitor cases of erythropoietin use by athletes before competitions. Symptoms for which a test for erythropoietin concentration is indicated to exclude an increase in the level of the hormone are dizziness, migraines, itching, blurred vision, enlarged spleen upon palpation, facial redness, heart attack, stroke, thrombosis of the veins of the lower extremities or bleeding.

Signs indicating a decrease in hormone concentration (pale face, weakness, fatigue, severe shortness of breath even at rest) are also important to confirm using analysis. The indication for the test may be the result of the CBC, confirming the presence of anemia (decreased number of red blood cells and reticulocytes, low hemoglobin). Contraindications for the study include gestation, previous blood transfusion, use of anabolic steroids that stimulate the thyroid gland, or administration of erythropoietin several days before blood sampling.

Preparing for the test and drawing blood

The study of erythropoietin concentration is carried out in the morning before meals (the break should be at least 10 hours). In the morning, the hormone level approaches maximum levels. An hour before the test, it is important to avoid stress, physical activity, drinking alcohol and smoking. It is necessary to interrupt drug treatment several days in advance; if it is impossible to stop drug therapy, you should inform the laboratory assistant about taking medications. Blood for analysis is taken from a vein. Transportation to the laboratory is carried out in sterile containers at a temperature of +2 to +8 degrees.

A unified method for detecting the level of erythropoietin in plasma is ELISA. Enzyme immunoassay allows you to determine the concentration of hormones in the bloodstream due to the reaction between the antibody and antigen, which bind to each other. To form an antigen-antibody reaction, enzymes are used (as a labeled reagent). The concentration of erythropoietin in the blood depends on the intensity of staining of the complexes. The advantage of the test is its high sensitivity and specificity (about 100%). The analysis period can vary from 1 to 8 days.

Normal indicators

Normal erythropoietin values in healthy adults range from 4.3 to 29 mIU/ml. If the patient’s hormone concentration is higher than normal, but the level of red blood cells is low, anemia is most likely due to inhibition of the hematopoietic function of the bone marrow. With normal levels or a slight decrease in the amount of erythropoietin in the blood, anemia is caused by insufficient synthesis of the steroid in the kidneys. An increased concentration of erythropoietin and red blood cells indicates the production of excess of this hormone by the liver or kidneys. If the level of red blood cells is increased, and the amount of erythropoietin is within the reference values or is decreased, then polycythemia is not caused by the synthesis of a steroid.

Level up

The main reason for the increase in the concentration of erythropoietin in plasma is considered to be pathologies of the circulatory system: anemia (aplastic, iron deficiency, sickle cell and folate deficiency), acute and chronic blood loss, bone marrow malformations (the synthesis of only red blood cells decreases, and the level of platelets and leukocytes is within the norms). The second reason for an increase in the concentration of erythropoietin in plasma is pathological processes in the kidneys, including narrowing of the renal artery, polycystic disease, and urolithiasis.

Also, the level of the hormone increases with hypoxia (decreased blood oxygen saturation), which occurs with venous stagnation, heart defects, chronic bronchitis, or with neoplasms that synthesize erythropoietin (pheochromocytoma, kidney adenocarcinoma, breast tumor, hemangioblastoma). In some cases, the cause of high levels of the steroid is its intake from the outside as a doping (athletes can take the hormone before competitions). A slight increase in erythropoietin, which does not require treatment, occurs after chemotherapy, being at altitude, or during pregnancy (the pituitary hormone prolactin increases the synthesis of erythropoietin).

Level reduction

The reason for the decrease in the level of erythropoietin in the blood is chronic renal failure, in which the physiological inverse linear relationship between the amount of steroid and hemoglobin level is disrupted. As a result, erythropoietin production does not increase in proportion to the severity of the anemia, and ineffective erythropoiesis occurs, which is accompanied by hemolysis within the bone marrow and a reduction in the lifespan of red blood cells. This erythropoietin deficiency anemia persists in patients with chronic renal failure on program hemodialysis or outpatient dialysis and disappears only after kidney allotransplantation. The second reason for a decrease in the level of erythropoietin in plasma is considered to be polycythemia vera, caused by intensive proliferation (growth) of erythrocyte, leukocyte and platelet lineages in the bone marrow.

Treatment of abnormalities

The study of the concentration of erythropoietin in plasma has an important diagnostic value in clinical medicine, as it helps to track the dynamics of neoplasms and differentiate anemia from polycythemia. To determine the cause of deviations from the reference values, you should contact your attending physician: nephrologist, endocrinologist, oncologist, hematologist or therapist, who will prescribe additional tests and instrumental diagnostic studies. Typically, therapy is carried out after a full examination and assessment of the hormone level over time. To normalize the patient’s condition, the doctor prescribes a diet, recommends normalizing the drinking regime (at least 2 liters of water per day), and determines a treatment regimen.

Erythropoietin (EPO) is a glycoprotein hormone that controls the rate of erythropoiesis in the human body. The substance presented is synthesized mainly in the kidneys, a small amount (about 10 percent) is formed in the liver. The hormone erythropoietin activates the division and differentiation of erythroid precursors. The level of endogenous hormone in the blood plasma of healthy people varies over a wide range and is inversely related to the concentration of hemoglobin and the degree of tissue oxygenation. The work on isolating and producing this hormone for medical purposes is very useful.

Structure and significance of the hormone

The hormone molecule consists of amino acids. With a deficiency of endogenous erythropoietin, a sharp decrease in the level of hemoglobin and red blood cells in the blood is observed, and the so-called erythropoietin deficiency anemia develops. Until recently, drug correction of such anemia remained impossible due to the lack of appropriate pharmaceuticals. Nowadays, when there is a deficiency of the above hormone in the human body, doctors prescribe recombinant erythropoietin. The drug is obtained from animal cells into which the gene code for human EPO is introduced. Recombinant human erythropoietin is identical in amino acid and carbohydrate composition to the natural hormone, increases the number of red blood cells, reticulocytes, and activates hemoglobin biosynthesis in cells. The biological activity of the resulting substance is no different from the endogenous hormone. Recombinant erythropoietin does not exhibit cytotoxic effects and does not affect leukopoiesis. Scientists suggest that EPO interacts with specific erythropoietin-sensitive receptors that are localized on the cell surface.

Method for purifying recombinant human erythropoietin

Recombinant human EPO is one of the most common proteins produced by many biological and pharmaceutical companies around the world for drug therapy. The presented compound is synthesized by Chinese hamster ovary (CHO) cells using the recombinant DNA method. One polypeptide chain of recombinant EPO contains 165 amino acids, the calculated molecular weight of which is 24,000 Da, and the observed molecular weight of the glycosylated protein is 30,400 Da. Separation of erythropoietin from impurities is carried out using ion exchange and Human recombinant EPO has a purity of 98%.

Recombinant erythropoietins and their analogues

To stimulate the processes of erythropoiesis, doctors use different drugs:

"Aranesp";
"Aeprin";
"Epobiocrine";
"Bioein";
"Vepox";
"Binocrit";
"Epocrine";
"Gemaks";
"Epogen"
"Eprex";
"Epovitan";
"Epomax";
"Hypercrit";
"Eralfon";
"Erytrostim";
"Recormon";
"Epostim";
"Eposino";
Epoetin Beta.

Before replacing recombinant erythropoietin with analogs, you should consult with your doctor.

Indications for use

Medical practitioners quite often have to deal with erythropoietin deficiency anemia (EDA). This group includes the following pathologies:

anemia in malignant neoplasms;
early anemia of premature babies (up to 34 weeks of pregnancy) with body weight from 750 to 1500 g;
nephrogenic anemia;
anemia in chronic diseases (hepatitis C, rheumatoid arthritis, HIV infection, diseases of the digestive canal).

A distinctive feature of the above anemias is that they are not treated with iron supplements. Until recently, the only effective treatment method was blood transfusions. Due to the fact that this type of therapy has a huge number of side effects and a high risk of transmitting pathogens of a number of dangerous infectious diseases (HIV, hepatitis viruses, etc.) through the blood, this method is practically not used in modern medicine. Recombinant human erythropoietin helps improve the quality of life in patients diagnosed with erythropoietin deficiency anemia. The biosynthesis and introduction into practice of recombinant human EPO has opened a new era in the treatment of erythropoietin-dependent anemia.

Contraindications

thromboembolism;
hypersensitivity to the drug;
inability to carry out effective anticoagulant therapy;
previous cerebral stroke or myocardial infarction;
unstable angina;
uncontrolled arterial hypertension;
the period of bearing a child and breastfeeding;
refractory arterial hypertension.

Dosage regimen

The dosage, regimen and duration of treatment are established on a strictly individual basis, depending on the severity of anemia, the general condition of the patient and the nature of the pathology. The drugs are intended for parenteral use. Initial doses range from 50 to 150 IU/kg. The dose must be adjusted depending on the patient's age. Recombinant erythropoietin is usually administered 3 times a week. In case of an overdose of the drug, increased side effects are observed. The result becomes more or less noticeable after 2-3 weeks of use.

Side effect

Are you prescribed recombinant human erythropoietin? Instructions for use do not exclude the development of side effects. This:

myalgia;
dizziness;
hyperthermia;
drowsiness;
vomit;
headache;
diarrhea;
arthralgia;
hypertension;
chest pain;
thrombocytosis;
tachycardia;
hypertensive crisis;
convulsions;
hepatosis;
increased activity levels of AST, ALT in the blood;
erythrocyte lineage aplasia;
eczema;
angioedema;
skin rash and itching;
asthenia;
urticaria, hyperemia and burning at the injection site;
hyperkalemia;
decreased concentration of ferritin protein in blood plasma;
hyperphosphatemia.

Erythropoiesis stimulants in sports

Recently, the drug Epovitan (recombinant human erythropoietin) is often used. The presented product is often used in sports (athletics, bodybuilding, swimming, biathlon). This drug activates the biosynthesis of red blood cells, which, in turn, leads to an increase in the oxygen content per unit volume of blood and, accordingly, to an increase in the oxygen capacity of the blood and the delivery of O 2 to organs and tissues. This mechanism of action increases the athlete’s aerobic endurance. A similar effect is observed when an athlete trains in mid-altitude conditions, when a lack of O 2 in the air provokes the development of hypoxia, which, in turn, activates the biosynthesis of endogenous erythropoietin. EPO preparations are used in combination with insulin, somatotropin (GH, growth hormone) and stanazolol.

Excessive, uncontrolled use of the drug "Erythropoietin" in sports can provoke the formation of blood clots, which is usually fatal. It is quite difficult to detect recombinant EPO, since the structure of the synthetic compound is identical to its physiological counterpart, therefore this biocompound is still used illegally in professional sports as a doping.

What's happened erythropoietin? Erythropoietin (EPO) is a glycopeptide hormone that controls the formation of red blood cells (erythrocytes) from bone marrow stem cells depending on oxygen consumption. Myself Erythropoietin mainly produced by kidney tissue.

The erythropoietin molecule consists of amino acids. In four sections, glycosidic fragments are attached to the protein chain using appropriate bonds. They are different sugars, so there are several varieties of EPO with the same biological activity, but slightly different in their physicochemical properties.

Recombinant (synthetic) human erythropoietin, obtained by genetic engineering (the abbreviations generally accepted in the scientific literature are rHuEPO, r-HuEPO, rhuEPO, rEPO), is identical in amino acid composition to natural human EPO. However, there are minor differences in the composition of the glycosidic fragments. These differences determine the acid-base properties of the entire hormone molecule.

1977 For the first time, purified EPO was isolated from human urine.
1988 Start of mass production of recombinant EPO.
1988-1990 Several deaths among Dutch and Belgian cyclists have been linked to the use of EPO.
1990 The use of EPO is banned by the IOC.
1993-1994 The IAAF is implementing a blood sampling procedure at eight Grand Prix events.
1998 Use cases exposed EPO The Tour de France cycling race receives widespread media coverage.

Action of EPO. EPO stimulates the transformation of reticulocytes into mature red blood cells as part of the hematopoietic sprout of the bone marrow. An increase in the number of red blood cells leads to an increase in oxygen content per unit volume of blood and, accordingly, to an increase in oxygen capacity and oxygen delivery to tissues. Ultimately, the body's endurance increases. Similar effects are achieved when training in mid-mountain areas.

For what purposes is rhEPO used in medicine? In the body, EPO is produced in the kidneys. Therefore, patients with chronic renal failure always suffer from anemia. Before the advent of recombinant EPO Such patients regularly received blood transfusions of both whole blood and red blood cells. However, since 1989, the need for such procedures has ceased, as they have been replaced by the administration of EPO drugs. In some cases, anemia of other origins is also successfully treated with recombinant EPO. As an alternative to red blood cell transfusion, high-dose EPO therapy appears to be an effective antianemic measure in the treatment of chronic polyarthritis, AIDS, some tumors, as well as during surgical interventions and blood loss.

In what sports is recombinant EPO used as a doping? Due to the significant effect of EPO on the oxygen capacity of the blood and the delivery of oxygen to tissues, this drug helps to increase performance in sports that require aerobic endurance - these are all types of athletics running, starting from 800 m, as well as skiing and cycling.

What is the risk associated with the use of recombinant EPO? Rh-EPO is a well-tolerated pharmacological drug that has virtually no side effects. However, an overdose of EPO and uncontrolled use can lead to an increase in blood viscosity and, consequently, an increased risk of disorders in the vascular blood supply system of the heart and brain. The risk of these side effects of EPO increases when training in mid-altitude areas, as well as when the body is dehydrated.

Is it possible to detect traces of the use of recombinant EPO?

Currently, there are no proven methods for reliably detecting traces of EPO used by athletes as doping. Because natural and recombinant erythropoietins have identical amino acid structures, rh-EPO is virtually indistinguishable from its natural counterpart.

The modern arsenal of methods designed to determine EPO includes direct and indirect approaches. The direct method is based on the separation of natural EPO and genetically engineered EPO based on the minor differences that were found when studying them. In particular, the method of electrophoretic separation can show the distribution of different isoforms of erythropoietin having different glycosidic fragments. Natural EPO is predominantly associated with glycosidic moieties that are more acidic, while recombinant EPO is associated with moieties that are more alkaline. The method of purifying a urine sample and separating it itself is quite complex and requires large quantities of urine (up to 1 liter). As a result, indirect methods that require only small volumes of blood or urine samples are now favored.

Examples of indirect EPO detection method:

Deviations from the normal level of content in the biofluid. This fact means that the established excess of EPO levels must differ from acceptable variations of a physiological or pathological nature. However, the use of this criterion is possible only if the range of fluctuations in the indicator is small compared to the values that are found after exogenous administration of the drug. The latter is only possible when using blood as a sample for a doping test.

Registration of biochemical parameters, the value of which depends on the concentration of EPO. This approach could be based on measuring serum levels of soluble transferrin receptor (sTfR), the level of which increases after administration of recombinant EPO. However, this indicator undergoes similar changes after training in mid-altitude conditions.

Determination of fibrin and fibrinogen breakdown products in urine after administration EPO.

Doping control of EPO abuse cases.

At present, it is practically impossible to reliably identify cases of exogenous administration of EPO into the body. Therefore, changes in physiological blood parameters that are detected after EPO administration are used for preliminary control. Thus, the International Cycling Union uses the criterion of the maximum hematocrit value (50 volume % for men). The International Ski Federation has established the maximum permissible hemoglobin values as such a criterion (16.5 g% for women and 18.5 g% for men).

In case of exceeding the specified limit values established during the control procedure before the competition, the corresponding athlete is suspended from participation in the competition in order to protect his health. However, both hemoglobin and hematocrit are indicators that are influenced by many factors.

In particular, they can change significantly after even one moderate-volume endurance workout. In addition, these indicators are characterized by significant individual variability. Therefore, even an excess of the hematocrit value of more than 50 volume % cannot serve as evidence of EPO abuse.