Is polycythemia dangerous for a partner? Polycythemia vera. Causes, symptoms, diagnosis, treatment. Complications and consequences

Polycythemia vera is a rare disease that is more common in the elderly (over 60 years old) and is characterized by a violation of hematopoietic processes. Refers to benign neoplasms. The causes of the disease are still unknown. There is a version that uncontrolled cell division begins as a result of the mutation of their precursor cell. Despite the good quality of the tumor and the weak progression of the process, the disease can lead to severe complications.

True polycythemia. What it is?

This is a blood disease that refers to benign tumor diseases. The precursor cell of myelopoiesis is primarily affected, which manifests itself in uncontrolled, unlimited division and growth of blood cells. As a result of this process, the number of erythrocytes, platelets, and leukocytes sharply increases in the peripheral blood, which leads to an increase in blood viscosity and an increase in hematocrit.

The disease is more common in adults over 60 years of age, but can occur in children and even newborns. The childhood form of Wakez disease is the most severe. Among full-term newborns, about 2 - 5% are affected by the disease, in premature infants, the incidence increases to 15%.

An increase in the number of red blood cells in the blood is called erythrocytosis, it is a characteristic sign of polycythemia. There are true erythrocytosis (primary polycythemia), which occurs with Wakez's disease, and false erythrocytosis (or relative), which occurs when the amount of the liquid part of the blood decreases during burns, vomiting, diarrhea, and dehydration.

Secondary erythrocytosis is also isolated (this is the so-called secondary polycythemia), when an increase in the number of red blood cells is caused by a lack of oxygen in the tissues. Hypoxia stimulates the production of erythropoietin, which stimulates the growth of red blood cells. This type of pathology occurs in smokers, with lung diseases, in people who are in the mountains at heights or with hemoglobinopathies, as well as in violation of the production of erythropoietin, a hormone that controls the production of red blood cells.

Symptoms and manifestations of the disease

The clinical picture of the disease will depend on the stage, there are three of them.

Treatment and prognosis of polycythemia

Treatment of the disease is carried out only in the conditions of the hematology department under close control of blood counts.

1. Bloodletting is a method of treatment in which a part of blood (about 500 ml) is taken from a patient with a frequency of 1-2 days to reduce the number of red blood cells and hemoglobin in it. Bloodletting is successful if erythrocytes have decreased to 4.5 - 5.0 × 1012 / l, and hemoglobin - up to 150 g / l. With a patient weighing up to 55 kg, erythrocytopheresis is used, when, after blood sampling, centrifugation is performed, the erythrocyte mass is separated from the plasma and the liquid part of the blood is returned to the patient.
2. Cytostatics (Myelosan, Imifos) are prescribed to suppress the growth of tumor cells.
3. Interferon is prescribed simultaneously with cytostatics, increases the body's immune properties.

Treatment of the disease with folk remedies is possible, but only when combined with the main medical methods. It is recommended to follow a diet that promotes blood thinning, and the use of lemon-garlic infusion. It is also very important to observe the drinking regimen. The amount of fluid you drink should be 50 ml/kg of body weight per day.

The prognosis of the disease depends on the stage at which the disease was detected. If this is the third stage, then the outcome of the disease will depend on what form of leukemia erythrocytosis transforms into. On average, patients after the diagnosis of polycythemia live 10 to 15 years.

Polycythemia is a tumor process in which the cellular elements of the bone marrow increase (hyperplasia). The overwhelming majority of the process is benign, although under certain conditions a transition to a malignant form is possible.

This pathology, called erythremia, is singled out as a separate nosological form (disease). The name Wakez's disease is also used, after the doctor who first described it in 1892.

More often the disease is diagnosed in older men. But for young and middle age, the predominance of women is characteristic. Polycythemia manifests itself in different ways, but in terms of external effects, skin veins dilate and skin color changes. Changes in the neck, on the face and hands are especially clearly visible.

The disease is dangerous, in particular, thrombosis and increased bleeding (for example, from the gums).

Polycythemia (erythremia, Wakez's disease, polycythemia vera) is a chronic neoplastic myeloproliferative clonal disease in which there is an uncontrolled proliferation of erythroid, megakaryocytic, granulocytic myelopoiesis sprouts with predominant proliferation of erythroid sprout (panmyelosis), an increase in the concentration of erythrocytes, an increase in hemoglobin levels, a high content of platelets, leukocytes (pancytosis).

Important! With erythremia, erythropoiesis does not depend on normal regulatory mechanisms.

The most common disease occurs in men in middle and old age, but in general, erythremia is a rare disease.

For reference. True polycythemia is most common among Jews, and the most “resistant” inhabitants of our planet to such a disease are the Negroid race and the inhabitants of Japan (the exception is those who survived atomic attacks).

Erythremia - cancer or not

Polycythemia vera belongs to the group of chronic leukemias, the course of which can be either benign or malignant. Since the blood system is affected, this disease cannot be called cancer, since cancer is a malignant neoplasm that develops from the epithelial tissues of various organs.

However, erythremia is a highly differentiated neoplastic process that affects the human hematopoietic system.

Wakez disease - causes and risk factors

The main cause of true (primary) polycythemia is hereditary genetic mutations, which is proved by the fact that almost all patients with this disease are carriers of the JAK2V617F mutation or other functionally similar mutations.

In such cases, specific genes are determined that are responsible for the synthesis of red blood cells and show high sensitivity to erythropoietin. This phenomenon is often recorded in relatives and is family.

Another option for a genetic mutation is that pathological genes begin to capture a lot of oxygen without giving it to the tissues.

Secondary polycythemia is the result of pathological changes in chronic long-term diseases that stimulate the production of erythropoietin. These diseases and conditions include:

• Emphysema of the lungs.
• Bronchial asthma.
• Obstructive bronchitis.
• Heart defects in the stage of compensation and decompensation.
• Thromboembolism of any localization.
• Increased pressure in the pulmonary artery.
• Heart rhythm disorders.
• Heart failure.
• Cardiac ischemia.
• Kidney cysts.
• Renal ischemia due to atherosclerotic lesions of the vessels of the kidneys.
• Tumors of the red bone marrow.
• Renal cell carcinoma.
• Liver carcinoma.
• Tumor processes in the uterus.
• Tumors of the adrenal glands.
• Smoking.
• Ionizing radiation.
• Exposure to toxic and chemical substances.
• Some drugs - chloramphenicol, azathioprine, methotrexate, cyclophosphamide.

There are also a number of genetic diseases that increase the risk of developing polycythemia. Such diseases have nothing to do with the blood system, but gene instability leads to the fact that blood cells become more susceptible to various external and internal influences, which can cause the development of erythremia. Such diseases are:

• Down Syndrome.
• Klinefelter syndrome.
• Bloom Syndrome.
• Marfan syndrome.

With polycythemia, the leading manifestation is an increase in the number of red blood cells in the blood plasma, but the causes of this process directly depend on the type of erythremia:

• Absolute type- in this case, there is an increase in the concentration of erythrocytes in the bloodstream due to their increased formation. This phenomenon is typical for:
  • True polycythemia.
  • Polycythemia in case of hypoxia.
  • Lung obstructions.
  • Hypoxia that occurs with damage to the kidneys, adrenal glands.
• Relative type- at the same time, the volume of erythrocytes increases due to a decrease in plasma volume. The indicators of erythrocytes do not change at the same time, but the ratio of erythrocytes / plasma changes and therefore this phenomenon is called relative. This type of process occurs due to the occurrence of the following diseases:
  • Salmonellosis.
  • Cholera.
  • Dysentery, as well as other infectious diseases, which are accompanied by severe vomiting and diarrhea.
  • Burns.
  • Exposure to high temperatures, which is accompanied by increased sweating.

In addition to the immediate causes of the development of Wakez's disease, there are also risk factors that can, under certain conditions, trigger the pathological process:

• Stressful situations, prolonged exposure to stress.
• Activities associated with constant exposure to carbon dioxide, which leads to changes in the gas composition of the blood.
• Living in the highlands for a long time.

How the disease develops

• The V617F point mutation occurs in the Jak2 gene, which leads to a disruption in the structure of the gene itself.
• As a result, the activity of tyrosine kinase significantly increases, which is transformed into increased proliferation of mature cells of myeloid germs. In this case, a complete blockade of apoptosis (natural cell death) occurs.
• In addition, an increased sensitivity of pathological progenitor cells to erythropoietin, even at its reduced concentrations, leads to an increased synthesis of formed elements, in particular, erythrocytes. Moreover, there is also a second type of cells - the precursors of erythrocytes, which behave absolutely independently and autonomously, their division does not depend on erythropoietin. This population is mutant and is one of the main substrates of erythremia.
• As a result of such a reaction, hyperplasia of hematopoietic germs occurs with a significant increase in the production of red blood cells in the bone marrow in the first place, as well as platelets and granulocytes. At the same time, absolute erythrocytosis develops, the rheological properties of the blood are disturbed.
• Organs and tissues overflow with blood, the viscosity of which increases significantly, which leads to the development of blood clots inside the vessels, changes in the liver, spleen of varying severity (myeloid metaplasia of the spleen and liver), hypoxia and hypervolemia.
• In the final stages, hematopoiesis is depleted, myelofibrosis develops.

Important! An abnormal cell clone is able to transform into any blood cell - erythrocyte, leukocyte and / or platelet.

The result of all pathogenetic reactions is the emergence of two types of cells - precursors:

• Normal.
• Mutant.

Since the process of formation of mutant cells is uncontrollable, the number of erythrocytes significantly exceeds the body's needs for them. This leads to inhibition of the synthesis of erythropoietin in the kidneys, which further aggravates the pathological process, since erythropoietin loses its effect on normal erythropoiesis, and it has no effect on tumor cells.

In addition, the constant growth of mutant cells leads to the displacement of normal ones, which at a certain point in time leads to the fact that all erythrocytes are produced from mutant precursor cells.

Disease classification

As mentioned above, depending on the reasons that led to the development of polycythemia, it is divided into two types:

• True polycythemia.
• Relative.

True erythremia, in turn, can be:

• Primary - the basis of this process is the defeat of the myeloid germ of hematopoiesis.
• Secondary - the basis of this variety - an increase in the activity of erythropoietin.

The disease goes through three stages of development:

• Stage 1 - oligosymptomatic, initial, height - during this period, there are practically no clinical manifestations of erythremia. This stage lasts for a long time, up to 5 years or more. During this period, the following processes develop:
  • Moderate hypervolemia.
  • moderate erythrocytosis.
  • Changes in the size of the spleen are not detected.
• Stage 2 - deployed, erythremic - at this stage, all relevant clinical signs are expressed. This period of the disease is divided in turn into 2 stages:
  • IA - no myeloid degeneration of the spleen. Erythrocytosis, thrombocytosis, and in some cases pancytosis develops. The myelogram shows hyperplasia of all hematopoietic lineages and severe megakaryocytosis. This stage can last up to 20 years.
  • IIB - here the spleen is already actively involved, which undergoes myeloid metaplasia. Severe hypervolemia develops, the spleen and liver increase in size, and pancytosis is recorded in the blood plasma.
• Stage 3 - terminal, anemic, posterythremic - the final stage of the disease. It develops:
  • Anemia.
  • thrombocytopenia.
  • Leukopenia.
  • Myeloid transformation of the liver, spleen.
  • Secondary myelofibrosis.
  • It is possible to degenerate into other hemoblastoses, much more dangerous than polycythemia itself.

Important! At the last stage of the disease, cells lose their ability to differentiate, which in most cases leads to the development of acute leukemia.

Polycythemia. Symptoms

• Plethoric (plethora) The main symptoms of this syndrome are:
  • Change in the volume of erythrocytes in the circulating blood in the direction of increase.
  • The occurrence of dizziness, headaches.
  • Visual disorder.
  • Development of itchy skin.
  • Angina pectoris.
  • The appearance of a bluish tint on the skin and visible mucous membranes, which is called a positive symptom of Cooperman.
  • Thrombosis of any level of localization.
  • Redness of the fingers of the upper and lower extremities, which is accompanied by extremely painful attacks and a burning sensation, which is called erythromelalgia.
• Myeloproliferative- occurs due to hyperplasia of all three hematopoietic sprouts, with which there are:
  • Sweating.
  • Skin itching.
  • Marked weakness.
  • Increase in body temperature.
  • Violation of purine metabolism, which causes uric acid diathesis, the occurrence of kidney stones, gout and gouty arthritis.
  • The development of extramedullary hematopoiesis (foci of the formation of pathological blood cells no longer appear in the bone marrow, but outside it).
  • Enlargement of the spleen.
  • Frequent infections.

If we talk about each stage of polycythemia, then they are characterized by their own special clinical signs, which are signs of the stages of the disease:

• initial stage- there are practically no manifestations here, they are nonspecific and can be attributed to many other diseases of various organs and systems:
  • Redness of the mucous membranes and skin - this symptom occurs due to an increase in the concentration of red blood cells. It appears in all parts of the human body. at the beginning of the disease may be mild.
  • Headaches - develop in violation of microcirculation processes in the vessels of the brain of small caliber.
  • Soreness in the toes, hands - since during this period the blood flow through small vessels is already disturbed, this leads to an increase in blood viscosity, which leads to a decrease in oxygen delivery to the organs. This leads to the development of ischemia and the appearance of ischemic pain.
• Expanded stage- at this stage of the disease, polycythemia causes a significant increase in the number of blood cells, which leads to an increase in its viscosity, their increased destruction in the spleen and disturbances in the activity of the blood coagulation system. Clinically, this is manifested by such signs:
  • Redness of the skin and mucous membranes intensifies up to the appearance of a purple, blue tint.
  • Teleaniectasias (spot hemorrhages on the skin).
  • Bilateral erythromelalgia intensifies, which is complicated by necrosis of the fingers of the upper and lower extremities. Such a process with the progression of polycythemia can completely cover the entire hand and foot. Attacks of acute pain can last up to several hours, and exposure to cold water may provide some relief.
  • An increase in the liver (sometimes up to 10 kg) is expressed by the development of pain in the right hypochondrium, a disorder in the act of breathing and disorders of the digestive process.
  • Enlargement of the spleen - excessive filling of the spleen with blood leads not only to its enlargement, but also to the thickening of the spleen.
  • Arterial hypertension appears due to an increased volume of circulating blood, high blood viscosity. This causes the development of vascular resistance to blood flow.
  • The severity of skin itching becomes stronger - this is because the increased formation of blood elements, in particular, leukocytes, leads to their high concentrations. This leads to their massive destruction, as a result of which histamine is actively released from them, which is the culprit of skin itching, which is further enhanced by contact with water.
  • Increased bleeding - even minor cuts and injuries can lead to bleeding due to high blood pressure, increased blood volume and excessive platelet activity.
  • Ulcerative lesions of the digestive tract, which is accompanied by such dyspeptic symptoms of varying severity.
  • Pain in the joints of any localization.
  • Ischemic stroke due to massive thrombosis.
  • Myocardial infarction.
  • Signs of iron deficiency - exfoliating nails, dry skin and mucous membranes, cracks in the corners of the mouth, poor appetite, impaired smell, taste, increased susceptibility to the development of infectious diseases.
  • Dilated cardiomyopathy - gradually all the chambers of the heart are more and more filled. The heart is stretched. This occurs as a protective, compensatory reaction of the body to maintain a sufficient level of blood circulation. Gradually, the constant stretching of the heart leads to the loss of its ability to contract normally. Clinically, this is expressed by rhythm and conduction disturbances, edematous syndrome, pain in the heart, fatigue and severe general weakness.
• anemic stage- the main symptom of this stage is a decrease in the production of all blood cells, which transforms into the following symptoms:
  • Aplastic iron deficiency anemia - develops as a result of inhibition of hematopoietic processes in the bone marrow due to myelofibrosis - the displacement of hematopoietic cells from the bone marrow by the connective tissue. Paleness of the skin, increased fatigue, general pronounced weakness, fainting, a feeling of lack of air appear.
  • Bleeding - occurs with the smallest injuries on the skin and mucous membranes due to reduced production of platelets and the synthesis of platelets that lose their functions.

Important! In the absence of treatment, the terminal stage occurs very quickly with the development of a lethal outcome.

Erythremia in children, features

• Hypoxia.
• Toxic dyspepsia.
• Feto - placental insufficiency.

Important! Twins have congenital polycythemia due to genetic defects, which manifests itself from birth.

Basically, the disease manifests itself at 2 weeks of a child's life.

The staging of the disease in children is completely identical to that in adults, but in children the disease is much more severe, with the development of severe bacterial infections, heart defects, bone marrow sclerosis, which leads to early death. Treatment for polycythemia is the same as for adults, as discussed below.

Diagnosis of Wakez disease

When diagnosing polycythemia, a well-defined diagnostic plan is used, which includes the following steps:

• Collection of anamnestic data.
• Visual inspection.
• Blood test, which should include:
  • The number of red blood cells and other blood cells.
  • Hematocrit.
  • Mean volume of erythrocytes - MCV.
  • The average content of hemoglobin in erythrocytes - MCH.
  • The average concentration of hemoglobin in erythrocytes is MCHC.
  • The distribution width of erythrocytes by volume is RDW.
  • Erythropoietin in blood serum.
  • Molecular genetic testing of blood to detect mutations.
• Ultrasound examination of the abdominal organs.
• A biochemical blood test, especially for uric acid, an increase in the levels of which indicates the development of gout.
• Fibrogastroduodenoscopy.
• Abdominal CT scan in vascular mode.
• Bone marrow biopsy.
• Assessment of the functions of external respiration.
• Determination of the content of oxygen and carbon dioxide in the blood.
• large arteries.
• EchoCG.
• General urine analysis.

To make a diagnosis of true polycythemia, after all the manipulations, certain criteria are applied, according to which the diagnosis of polycythemia is made:

• Big Criteria:
  • Hemoglobin levels above 185 g/l for men and 165 g/l for women, as well as other signs of increased mass of red blood cells - hematocrit > 52% in men, > 48% in women.
  • Detection of mutations in the JAK2V617F gene.
• Small Criteria:
  • Panmyelosis in a bone marrow biopsy is an increase in the proliferation of erythroid, granulocytic and megakaryocytic hematopoietic sprouts.
  • Low erythropoietin values.
  • The formation of endogenous erythrocyte colonies without the participation of erythropoietin in the study of biopsy of bone marrow cultures.

Important! The diagnosis is fully confirmed in the presence of two major and one minor criteria.

Treatment

• Bloodletting - performed to reduce the number of red blood cells and hemoglobin. The procedure is carried out once every 1-2 days with the collection of up to 500 ml of blood.
• Cytopheresis is the passage of blood through special filters, with the help of which some of the red blood cells are eliminated.
• Reception of cytostatics - cyclophosan, cyclophosphamide, hydroxyurea, etc.
• Antiplatelet therapy with aspirin, dipyridamole.
• Interferons.
• symptomatic treatment.

Important! It is strictly forbidden to independently treat the disease without medical intervention, as well as to use dubious methods and types of treatment.

Important in the treatment of polycythemia is a diet that completely excludes the intake of foods that increase blood formation. With the addition of gout, meat and fish in general can be excluded from the diet of patients and replaced with plant foods.

In general, the basis of treatment is the distinction between the primary process and the secondary, since in secondary polycythemia, the condition that caused the development of erythremia is primarily treated.

Complications

Polycythemia is characterized by a high probability of such formidable complications as:

• Arterial hypertension in severe form.
• Hemorrhagic strokes.
• Myocardial infarction.
• Acute myeloid leukemia.
• Chronic myeloid leukemia.
• Erythromyelosis.

In some cases, even timely treatment leads to the development of such dangerous situations that can end in death at any time.

Forecast

The prognosis of polycythemia directly depends on its type, course, timeliness and correctness of treatment.

Important! Without appropriate treatment, about 50% of patients die within a year and a half from the time of diagnosis.

With timely therapy, the prognosis in patients with erythremia is quite favorable and demonstrates a 10-year survival rate in more than 75% of cases.

The main diagnostic information is obtained from the study of peripheral blood and bone marrow. Bloodletting, erythrocytapheresis, and chemotherapy are used to treat polycythemia.

Polycythemia

Polycythemia (Vakez's disease, erythremia, erythrocytosis) is a disease of the group of chronic leukemias, characterized by increased production of red blood cells, platelets and white blood cells, an increase in BCC, and splenomegaly. The disease is a rare form of leukemia: 4-5 new cases of polycythemia are diagnosed annually per 1 million population. Erythremia develops mainly in patients of the older age group (50-60 years), somewhat more often in men. The relevance of polycythemia is due to the high risk of developing thrombotic and hemorrhagic complications, as well as the likelihood of transformation into acute myeloid leukemia, erythromyelosis, and chronic myeloid leukemia.

Causes of polycythemia

The development of polycythemia is preceded by mutational changes in the pluripotent stem hematopoietic cell, which gives rise to all three cell lines of the bone marrow. The most frequently detected mutation of the JAK2 tyrosine kinase gene with the replacement of valine by phenylalanine at position 617. Sometimes there is a family incidence of erythremia, for example, among Jews, which may indicate in favor of a genetic correlation.

With polycythemia in the bone marrow, there are 2 types of precursor cells of erythroid hematopoiesis: some of them behave autonomously, their proliferation is not regulated by erythropoietin; others, as expected, are erythropoietin-dependent. It is believed that an autonomous cell population is nothing more than a mutant clone - the main substrate of polycythemia.

In the pathogenesis of erythremia, the leading role belongs to enhanced erythropoiesis, which results in absolute erythrocytosis, impaired rheological and blood coagulation properties, and myeloid metaplasia of the spleen and liver. High blood viscosity causes a tendency to vascular thrombosis and hypoxic tissue damage, and hypervolemia causes increased blood filling of internal organs. At the end of polycythemia, depletion of hematopoiesis and myelofibrosis are noted.

Classification of polycythemia

In hematology, there are 2 forms of polycythemia - true and relative. Relative polycythemia develops with a normal level of erythrocytes and a decrease in plasma volume. This condition is called stress or false polycythemia and is not considered within the scope of this article.

True polycythemia (erythremia) by origin can be primary and secondary. The primary form is an independent myeloproliferative disease, which is based on the defeat of the myeloid germ of hematopoiesis. Secondary polycythemia usually develops with an increase in erythropoietin activity; this condition is a compensatory response to general hypoxia and can occur with chronic pulmonary pathology, "blue" heart defects, adrenal tumors, hemoglobinopathies, when climbing to a height or smoking, etc.

True polycythemia in its development goes through 3 stages: initial, advanced and terminal.

Stage I (initial, asymptomatic) - lasts about 5 years; asymptomatic or with minimal clinical manifestations. It is characterized by moderate hypervolemia, slight erythrocytosis; the size of the spleen is normal.

Stage II (erythremic, expanded) is divided into two substages:

• IA - without myeloid transformation of the spleen. There is erythrocytosis, thrombocytosis, sometimes pancytosis; according to the myelogram - hyperplasia of all hematopoietic sprouts, pronounced megakaryocytosis. The duration of the extended stage of erythremia.
• IIB - with the presence of myeloid metaplasia of the spleen. Hypervolemia, hepato- and splenomegaly are expressed; in peripheral blood - pancytosis.

Stage III (anemic, posterythremic, terminal). Characterized by anemia, thrombocytopenia, leukopenia, myeloid transformation of the liver and spleen, secondary myelofibrosis. Possible outcomes of polycythemia in other hemoblastoses.

Symptoms of polycythemia

Erythremia develops for a long time, gradually and can be detected by chance in a blood test. Early symptoms, such as heaviness in the head, tinnitus, dizziness, blurred vision, chilliness of the extremities, sleep disturbance, etc., are often “written off” to advanced age or concomitant diseases.

The most characteristic feature of polycythemia is the development of a plethoric syndrome caused by pancytosis and an increase in BCC. Telangiectasia, cherry-red coloration of the skin (especially the face, neck, hands and other open areas) and mucous membranes (lips, tongue), hyperemia of the sclera serve as evidence of plethora. A typical diagnostic sign is Cooperman's symptom - the color of the hard palate remains normal, and the soft palate acquires a stagnant cyanotic hue.

Another distinguishing symptom of polycythemia is pruritus, aggravated after water procedures and sometimes unbearable. Among the specific manifestations of polycythemia is also erythromelalgia - a painful burning sensation in the fingertips, which is accompanied by their hyperemia.

In the advanced stage of erythremia, painful migraines, bone pain, cardialgia, and arterial hypertension may occur. 80% of patients have moderate or severe splenomegaly; the liver increases a little less often. Many patients with polycythemia notice increased bleeding of the gums, bruising of the skin, and prolonged bleeding after tooth extraction.

The consequence of ineffective erythropoiesis in polycythemia is an increase in the synthesis of uric acid and a violation of purine metabolism. This finds clinical expression in the development of the so-called urate diathesis - gout, urolithiasis, renal colic.

The result of microthrombosis and violation of the trophism of the skin and mucous membranes are trophic ulcers of the lower leg, gastric and duodenal ulcers. The most frequent complications in the clinic of polycythemia are vascular thrombosis of deep veins, mesenteric vessels, portal veins, cerebral and coronary arteries. Thrombotic complications (PE, ischemic stroke, myocardial infarction) are the leading causes of death in patients with polycythemia. At the same time, along with thrombosis, patients with polycythemia are prone to hemorrhagic syndrome with the development of spontaneous bleeding of various localizations (gingival, nasal, from the veins of the esophagus, gastrointestinal, etc.).

Diagnosis of polycythemia

Hematological changes that characterize polycythemia are decisive in the diagnosis. A blood test reveals erythrocytosis (up to 6.5-7.5x10 12 / l), an increase in hemoglobin (dog / l), leukocytosis (over 12x10 9 / l), thrombocytosis (over 400x10 9 / l). The morphology of erythrocytes, as a rule, is not changed; with increased bleeding, microcytosis may be detected. A reliable confirmation of erythremia is an increase in the mass of circulating erythrocytes over ml / kg.

For the study of the bone marrow in polycythemia, it is more informative to conduct not a sternal puncture, but a trepanobiopsy. Histological examination of the biopsy revealed panmyelosis (hyperplasia of all hematopoietic sprouts), in the later stages of polycythemia - secondary myelofibrosis.

To assess the risk of developing complications of erythremia, additional laboratory tests and instrumental studies are carried out - functional liver tests, general urinalysis, ultrasound of the kidneys, ultrasound of the veins of the extremities, echocardiography, ultrasound of the vessels of the head and neck, FGDS, etc. If there is a threat of thrombohemorrhagic and metabolic disorders, consultations of the relevant narrow specialists: neurologist, cardiologist, gastroenterologist, urologist.

Treatment and prognosis of polycythemia

In order to normalize the volume of BCC and reduce the risk of thrombotic complications, bloodletting is the first measure. Blood exfusions are carried out in volume 2-3 times a week, followed by replenishment of the removed blood volume with saline or rheopolyglucin. The consequence of frequent bloodletting may be the development of iron deficiency anemia. Bloodletting in polycythemia can be successfully replaced by erythrocytepheresis, which allows you to remove only the red blood cell mass from the bloodstream, returning the plasma.

In the case of pronounced clinical and hematological changes, the development of vascular and visceral complications, myelosuppressive therapy with cytostatics (busulfan, mitobronitol, cyclophosphamide, etc.) is resorted to. Sometimes radioactive phosphorus therapy is performed. To normalize the aggregate state of the blood, heparin, acetylsalicylic acid, dipyridamole are prescribed under the control of a coagulogram; at hemorrhages transfusions of thrombocytes are shown; with urate diathesis - allopurinol.

The course of erythremia is progressive; the disease is not prone to spontaneous remissions and spontaneous cure. Patients are forced to be under the supervision of a hematologist for life, undergo courses of hemoexfusion therapy. With polycythemia, the risk of thromboembolic and hemorrhagic complications is high. The incidence of transformation of polycythemia into leukemia is 1% in patients who have not received chemotherapy, and 11-15% in those receiving cytostatic therapy.

Symptoms of polycythemia vera and prognosis for life with erythremia

Erythremia (polycythemia vera, Wakez's disease) is a hereditary disease of the blood system, occurring mainly in elderly women.

This pathology is characterized by malignant hypertrophy of the bone marrow. Most often, this pathology is known to patients as blood cancer (although such a judgment is erroneous) and leads to a progressive increase in the number of blood cells, primarily red blood cells (the number of other elements also increases). As a result of an increase in their number, an increase in hematocrit is observed, which leads to a decrease in the rheological properties of the blood, a decrease in the rate of blood flow through the vessels, and as a result, an increase in thrombus formation and deterioration in tissue supply.

These reasons lead to the fact that most tissues experience oxygen starvation, which reduces their functional activity (ischemic syndrome). Polycythemia vera occurs mainly in women. Men get sick a little less often, the frequency of occurrence of this pathology is approximately 3:2.

On average, Wakez disease occurs around the age of 40, and the peak of symptoms occurs in the 60s and 70s. There is a hereditary predisposition to the disease. In the population, erythremia is quite rare - about 30 cases per million population.

The main symptoms of the disease

Erythremia is an excessive saturation of the blood with red blood cells, which leads to various tissue and vascular disorders. Among the most common symptoms are:

1. Change in skin color. The main causes are stagnation of blood and restoration of hemoglobin. Due to reduced blood flow, red blood cells stay in one place longer, which leads to the restoration of the hemoglobin contained in them, and as a result, a change in the color of the skin. Patients suffering from this disease have a characteristic appearance - a reddened face and an intensely cherry-colored neck. In addition, swollen veins are clearly visible under the skin. When studying the mucous membranes, one can observe the characteristic symptom of Kuperman - a change in the color of the soft palate with an unchanged color of the hard palate.
2. Itching. This syndrome develops due to an increase in the number of immune cells that have the ability to release specific inflammatory mediators, in particular, serotonin and histamine. Itching intensifies after mechanical contact (most often after a shower or bath).
3. Erythromelalgia - discoloration of the distal phalanges of the fingers with the appearance of pain. This syndrome is caused by an increased content of platelets in the blood, which leads to clogging of small capillaries of the distal phalanges, the development of an ischemic process and pain in their tissues.
4. Splenitis and hepatomegaly. An increase in these organs is observed in most hematological diseases. If a patient develops erythremia, then an increased concentration of cells in the blood can lead to an increase in blood flow in these organs, and as a result, their increase. This can be determined by palpation or instrumental studies. The megalia syndrome is eliminated on its own after the normalization of the hemogram, that is, when the blood test returns to normal.
5. Thrombosis. Due to the high concentration of cells in the blood and a decrease in blood flow, a large number of blood clots form in the areas of damage to the intima of blood vessels, which lead to blockage of blood vessels in all parts of the body. The development of thrombosis of mesenteric, pulmonary or cerebral vessels is especially dangerous. In addition, blood clots in the small vessels of the gastric mucosa lead to a decrease in its protective properties and the appearance of gastritis and ulcers. DIC syndrome may also occur.
6. Pain. It can develop as a result of vascular disorders, for example, with obliterating endarteritis, and as a result of some metabolic disorders. With polycythemia, there may be an increase in the level of uric acid in the blood, its deposition in the joints. In rare cases, pain is observed during percussion or tapping of flat bones containing bone marrow (due to its hyperplasia and stretching of the periosteum).

Among the general symptoms, if erythremia occurs, headache, dizziness, a feeling of heaviness in the head, tinnitus, general weakness syndrome (all symptoms are due to a decrease in tissue oxygenation, impaired blood circulation in certain parts of the body) come first. When diagnosing, they are not used as mandatory criteria, since they can correspond to any systemic disease.

Stages and degrees of polycythemia

True polycythemia occurs in three stages (stages):

• stage of initial manifestations. At this stage, the patient does not present specific complaints. He is concerned about general weakness, increased fatigue, a feeling of discomfort in the head. All these symptoms are most often attributed to overwork, social and life problems, which is why the disease itself is diagnosed quite late;
• extended stage (clinical stage). At this stage, the appearance of a headache, discoloration of the skin and mucous membranes is characteristic. The pain syndrome develops quite late and indicates the neglect of the disease;
• terminal stage. At this stage, damage to internal organs due to their ischemia, dysfunction of all body systems are most pronounced. There may be a lethal outcome due to secondary pathology.

All stages proceed sequentially, and the diagnosis of the disease (blood test) becomes informative from the stage of clinical signs.

Diagnosis of Wakez disease

To make a diagnosis, a complete blood count plays a decisive role. It shows pronounced erythrocytosis, an increase in hemoglobin and hematocrit. The most reliable is the analysis of bone marrow punctate, which reveals signs of hyperplasia of the erythroid germ, and also calculates how many cells are present in it and what is their morphological distribution.

To clarify the nature of concomitant pathology, it is recommended to conduct a biochemical analysis, which provides information about the state of the liver and kidneys. With massive thrombosis, the state of blood coagulation factors is assessed by analyzing it for coagulability - a coagulogram.

Other studies (ultrasound, CT, MRI) give only an indirect idea of ​​the state of the body and are not used in making a diagnosis.

Treatment of erythremia

Despite the variety and severity of the manifestations of Wakez disease, there are relatively few treatments for it. It depends on what the analysis of the hemogram showed, whether a cytological syndrome has developed and what symptoms the patient has.

As mentioned above, the cause of the disease is an increased concentration of blood cells (especially red blood cells), which develops due to bone marrow hyperplasia. In this regard, the correct analysis of the paths of the development of the disease allows us to determine the basic principles of pathogenetic treatment, which include a decrease in the number of blood cells and an impact directly on the places of their formation. This is achieved through the following treatments:

1. bloodletting. This method appeared quite a long time ago, however, despite its primitiveness, it is used to this day. The essence of the procedure is the removal of excess blood from the patient's body. This method allows you to effectively reduce the syndrome of plethora (plethora), reduce the concentration of erythrocytes in the patient's blood, improve the rheological properties of his blood. The procedure is carried out several times until the required hematological parameters are achieved (hemoglobin level is about 140 and the number of red blood cells is at the level of 4.5x10^12 degrees). In one procedure, about 300-400 ml of the patient's blood is removed with a pre-diluted solution of rheopolyglucins and heparin.
2. Erythrocytopheresis- a procedure aimed at the hardware removal of excess red blood cells from the patient's body. The procedure is based on the principle of creating an artificial circulatory circuit with a so-called erythrocyte filter. Their excess remains on the filter membranes, and purified blood returns to the patient's body. This method of treatment is painless, and the indications and necessary symptoms for its implementation are the same as for bloodletting. However, erythrocytopheresis does not cause vascular damage. The criterion for the effectiveness of the removal of red blood cells is a normal blood test.

Such treatment should be accompanied by the appointment of antiplatelet drugs such as aspirin, chimes, clopidogrel or anticoagulants (heparin). The use of these drugs with one of the procedures significantly increases the effectiveness of therapy than using them separately.

It is also recommended to add some cytostatic drugs (if the cause of bone marrow hyperplasia is cancer), interferons (with the development of secondary viral complications) or hormones (mainly dexamethasone and prednisolone are used) to the treatment regimens, which improves the prognosis of the disease.

Complications, consequences and prognosis

All complications of the disease are due to the development of vascular thrombosis. As a result of their blockage, infarcts of internal organs (heart, liver, spleen, brain), obliterating atherosclerosis (with thrombosis of vessels of the lower extremities affected by atherosclerotic plaques) can develop. An excess of hemoglobin in the blood provokes the development of hemochromatosis, urolithiasis or gout.

All of them develop secondarily and require the elimination of the main cause - erythrocytosis, for the most effective cure.

As for the prognosis of the disease, much depends on the age at which treatment was started, what methods were used, and whether they were effective.

As mentioned at the beginning, polycythemia vera tends to develop later. If the appearance of the main symptoms in young people (aged 25 to 40 years) is observed, then the disease proceeds malignantly, that is, the prognosis is unfavorable, and secondary complications develop much faster. Accordingly, the later the development of the disease is observed, the more benignly it proceeds. In the case when adequately prescribed drugs are used, the period and life of patients is significantly improved. Such patients can live normally with their disease for quite a long time (up to several decades).

Answering the question, what could be the outcome of erythremia, it should be noted that it all depends on:

• what secondary processes have developed
• what are their reasons
• how long have they existed
• whether polycythemia vera was diagnosed in a timely manner and the necessary treatment was started.

Most often, due to damage to the liver and spleen, there is a transition from polycythemia to the chronic form of myeloid leukemia. The life expectancy with it remains almost the same, and with the right selection of drugs it can reach tens of years (forecast regarding

Polycythemia (erythremia, Wakez's disease): causes, signs, course, therapy, prognosis

Polycythemia is a disease that can be assumed just by looking at the patient's face. And if you still conduct the necessary blood test, then there will be no doubt at all. In reference books, it can also be found under other names: erythremia and Wakez's disease.

Redness of the face is quite common and there is always an explanation for this. In addition, it is short-term and does not linger for a long time. Various reasons can cause sudden reddening of the face: fever, high blood pressure, hot flashes during menopause, a recent tan, an awkward situation, and emotionally labile people tend to blush often, even if others do not see any prerequisites for this.

Polycythemia is different. Here, the redness is persistent, not transient, evenly distributed over the entire face. The color of an overly “healthy” plethora is saturated, bright cherry.

What kind of disease is polycythemia?

True polycythemia (erythremia, Wakez's disease) belongs to the group of hemoblastoses (erythrocytosis) or chronic leukemia with a benign course. The disease is characterized by the growth of all three hematopoietic lineages with a significant advantage of erythrocyte and megakaryocytic, due to which there is an increase not only in the number of red blood cells - erythrocytes, but also other blood cells that originate from these germs, where the source of the tumor process is the affected precursor cells of myelopoiesis. It is they who begin uncontrolled proliferation and differentiation into mature forms of erythrocytes.

Most affected under such conditions are immature red blood cells, which are hypersensitive to erythropoietin even at low doses. With polycythemia, the growth of leukocytes of the granulocytic series (primarily stab and neutrophils) and platelets. The cells of the lymphoid series, which include lymphocytes, are not affected by the pathological process, since they come from a different germ and have a different way of reproduction and maturation.

Cancer or not cancer?

Erythremia - not to say that it occurs all the time, however, there are a couple of people in a town of 25 thousand people, while for some reason men of 60 years or so “love” this disease more, although any person can meet with such a pathology age. True, for newborns and young children, true polycythemia is absolutely not typical, so if erythremia is found in a child, then most likely she will wear secondary character and be a symptom and consequence of another disease (toxic dyspepsia, stress erythrocytosis).

For many people, a disease classified as leukemia (whether acute or chronic) is primarily associated with blood cancer. Here it is interesting to understand: is it cancer or not? In this case, it would be more expedient, clearer and more correct to talk about the malignancy or benignity of true polycythemia in order to determine the boundary between "good" and "evil". But, since the word "cancer" refers to tumors from epithelial tissues, then in this case this term is inappropriate, because this tumor comes from hematopoietic tissue.

Wakez disease refers to malignant tumors, but it is characterized by high differentiation of cells. The course of the disease is long and chronic, for the time being qualified as benign. However, such a course can only last up to a certain point, and then with proper and timely treatment, but after a certain period of time, when significant changes in erythropoiesis occur, the disease becomes acute and acquires more “evil” features and manifestations. Here it is - true polycythemia, the prognosis of which will completely depend on how quickly its progression occurs.

Why do sprouts grow incorrectly?

Any patient suffering from erythremia, sooner or later asks the question: "Why did this" illness happen "to me?". The search for the cause of many pathological conditions is usually useful and gives certain results, increases the effectiveness of treatment and promotes recovery. But not in the case of polycythemia.

The causes of the disease can only be assumed, but not definitely stated. Only one clue can be for the doctor when determining the origin of the disease - genetic abnormalities. However, the pathological gene has not yet been found, so the exact localization of the defect has not yet been determined. There are, however, suggestions that Wakez's disease may be associated with trisomy 8 and 9 pairs (47 chromosomes) or other violation of the chromosomal apparatus, for example, the loss of a section (deletion) of the long arm C5, C20, but this is still guesswork, although built on conclusions of scientific research.

Complaints and clinical picture

If there is nothing to say about the causes of polycythemia, then we can talk about clinical manifestations for a long time and a lot. They are bright and varied, since already from the 2nd degree of development of the disease, literally all organs are drawn into the process. Subjective sensations of the patient are of a general nature:

• Weakness and constant feeling of fatigue;
• Significant decrease in performance;
• increased sweating;
• Headaches and dizziness;
• Marked memory loss;
• Visual and auditory disorders (decrease).

Complaints characteristic of this disease and characterized by it:

• Acute burning pain in the fingers and toes (the vessels are clogged with platelets and red blood cells, which form small aggregates there);
• Soreness, though not so burning, in the upper and lower limbs;
• Itching of the body (a consequence of thrombosis), the intensity of which increases markedly after a shower and a hot bath;
• Periodic appearance of a rash such as urticaria.

It's obvious that cause all these complaints microcirculation disorder.

reddening of the skin with polycythemia

As the disease progresses, more and more new symptoms are formed:

1. Hyperemia of the skin and mucous membranes due to the expansion of capillaries;
2. Pain in the region of the heart, resembling angina pectoris;
3. Pain in the left hypochondrium caused by overload and enlargement of the spleen due to the accumulation and destruction of platelets and red blood cells (it is a kind of depot for these cells);
4. Enlargement of the liver and spleen;
5. Peptic ulcer of the stomach and 12 duodenal ulcer;
6. Dysuria (difficulty urinating) and pain in the lumbar region due to the development of uric acid diathesis, which was caused by a shift in the blood buffer systems;
7. Pain in bones and joints as a result hyperplasia(overgrowth) bone marrow;
8. Gout;
9. Manifestations of a hemorrhagic nature: bleeding (nose, gums, intestinal) and skin hemorrhages;
10. Injections of the vessels of the conjunctiva, which is why the eyes of such patients are called "rabbit eyes";
11. Telangiectasias;
12. Tendency to thrombosis of veins and arteries;
13. Varicose veins of the lower leg;
14. Thrombophlebitis;
15. Possible thrombosis of the coronary vessels with the development of myocardial infarction;
16. Intermittent claudication, which may result in gangrene;
17. Arterial hypertension (almost 50% of patients), giving rise to a tendency to strokes and heart attacks;
18. Respiratory damage due to immune disorders, which cannot adequately respond to infectious agents that cause inflammation. In this case, red blood cells begin to behave like suppressors and suppress the immunological response to viruses and tumors. In addition, they are in the blood in an abnormally high amount, which further aggravates the state of the immune system;
19. The kidneys and urinary tract suffer, so patients have a tendency to pyelonephritis, urolithiasis;
20. The central nervous system does not remain aloof from the events taking place in the body, when it is involved in the pathological process, symptoms of cerebrovascular accident, ischemic stroke (with thrombosis), hemorrhage (less often), insomnia, memory impairment, mnestic disorders appear.

Asymptomatic to end stage

Due to the fact that polycythemia in the early stages is characterized by an asymptomatic course, the above manifestations do not occur in one day, but accumulate gradually and for a long time, it is customary to distinguish 3 stages in the development of the disease.

Initial stage. The patient's condition is satisfactory, the symptoms are moderately severe, the duration of the stage is about 5 years.

Stage of developed clinical manifestations. It takes place in two stages:

II A - proceeds without myeloid metaplasia of the spleen, subjective and objective symptoms of erythremia are present, the duration of the period is years;

II B - myeloid metaplasia of the spleen appears. This stage is characterized by a clear picture of the disease, the symptoms are pronounced, the liver and spleen are significantly enlarged.

The terminal stage, which has all the signs of a malignant process. Complaints of the patient are diverse, "everything hurts, everything is wrong." At this stage, cells lose their ability to differentiate, which creates a substrate for leukemia, which replaces chronic erythremia, or rather, it turns into acute leukemia.

The terminal stage is characterized by a particularly severe course (hemorrhagic syndrome, rupture of the spleen, infectious and inflammatory processes that cannot be treated due to deep immunodeficiency). It usually ends in death soon after.

Thus, the life expectancy for polycythemia is years, which may be not bad, especially considering that the disease can overtake after 60. And this means that there is a certain prospect of living up to 80 years. However, the prognosis of the disease still depends most of all on its outcome, that is, on what form of leukemia erythremia is transformed into at stage III (chronic myeloid leukemia, myelofibrosis, acute leukemia).

Diagnosis of Wakez disease

The diagnosis of polycythemia vera is mainly based on laboratory data with the determination of the following indicators:

• Complete blood count, in which you can notice a significant increase in red blood cells (6.0-12.0 x / l), hemoglobin (g / l), hematocrit (ratio of plasma and red blood). The number of platelets can reach levels of 10 9 /l, while they can significantly increase in size, and leukocytes - up to 9.0-15.0 x 10 9 /l (due to rods and neutrophils). ESR with true polycythemia is always reduced and can reach zero.

Morphologically, erythrocytes do not always change and often remain normal, but in some cases, erythremia can be observed anisocytosis(erythrocytes of different sizes). Platelets indicate the severity and prognosis of the disease with polycythemia in the general blood test (the more there are, the more severe the course of the disease);

• BAC (biochemical blood test) with the determination of the level of alkaline phosphatase and uric acid. For erythremia, the accumulation of the latter is very characteristic, which indicates the development of gout (a consequence of Wakez's disease);
• Radiological examination using radioactive chromium helps to determine the increase in circulating red blood cells;
• Sternal puncture (bone marrow sampling from the sternum) followed by cytological diagnosis. In the preparation hyperplasia of all three sprouts with a significant predominance of red and megakaryocytic;
• Trepanobiopsy(histological examination of material taken from the ilium) is the most informative method that allows you to most reliably identify the main symptom of the disease - three-growth hyperplasia.

In addition to hematological parameters, to establish the diagnosis of polycythemia vera, the patient is sent for an ultrasound examination (ultrasound) of the abdominal organs (enlargement of the liver and spleen).

So, the diagnosis is established ... What's next?

And then the patient is waiting for treatment in the hematological department, where tactics are determined by clinical manifestations, hematological parameters and the stage of the disease. Therapeutic measures for erythremia usually include:

1. Bloodletting, which allows to reduce the number of red blood cells to 4.5-5.0 x / l and Hb (hemoglobin) to 150 g / l. To do this, with an interval of 1-2 days, 500 ml of blood is taken until the number of erythrocytes and Hb drops. The bloodletting procedure is sometimes replaced by hematologists with erythrocytopheresis, when, after sampling by centrifugation or separation, red blood is separated, and the plasma is returned to the patient;
2. Cytostatic therapy (myelosan, imifos, hydroxyurea, hydroxycarbamide);
3. Antiplatelet agents (aspirin, dipyridamole), which, however, require caution in their use. So, acetylsalicylic acid can enhance the manifestation of hemorrhagic syndrome and cause internal bleeding if the patient has a stomach ulcer or duodenal ulcer;
4. Interferon-α2b, which is successfully used with cytostatics and increases their effectiveness.

The treatment regimen for erythremia is signed by the doctor for each case individually, so our task is only to briefly acquaint the reader with the drugs used to treat Wakez's disease.

Nutrition, diet and folk remedies

A significant role in the treatment of polycythemia is assigned to the regime of work (reduction of physical activity), rest and nutrition. In the initial stage of the disease, when the symptoms are not yet expressed or are weakly manifested, the patient is assigned table number 15 (general), however, with some reservations. The patient is not recommended to consume foods that enhance hematopoiesis (liver, for example) and are offered to revise the diet, giving preference to dairy and vegetable products.

In the second stage of the disease, the patient is assigned table number 6, which corresponds to the gout diet and limits or completely excludes fish and meat dishes, legumes and sorrel. Having been discharged from the hospital, the patient must adhere to the recommendations given by the doctor during outpatient observation or treatment.

Question: "Is it possible to treat folk remedies?" sounds with the same frequency for all diseases. Erythremia is no exception. However, as already noted, the course of the disease and the life expectancy of the patient depend entirely on timely treatment, the purpose of which is to achieve a long and stable remission and delay the third stage for the longest possible time.

During the calm period of the pathological process, the patient must still remember that the disease can return at any time, therefore, he must discuss his life without exacerbation with the attending physician, in whom he is observed, periodically take tests and undergo an examination.

Treatment of blood diseases with folk remedies should not be generalized, and if there are many recipes to increase hemoglobin levels or to thin the blood, this does not mean at all that they are suitable for the treatment of polycythemia, for which, in general, medicinal herbs have not yet been found. Wakez's disease is a delicate matter, and in order to control the function of the bone marrow and thus affect the hematopoietic system, you need to have objective data that can be assessed by a person with certain knowledge, that is, the attending physician.

In conclusion, I would like to tell the readers a few words about relative erythremia, which cannot be confused with the true one, since relative erythrocytosis can occur against the background of many somatic diseases and successfully end when the disease is cured. In addition, erythrocytosis as a symptom can accompany prolonged vomiting, diarrhea, burn disease and hyperhidrosis. In such cases, erythrocytosis is a temporary phenomenon and is associated primarily with dehydration of the body, when the amount of circulating plasma, which consists of 90% water, decreases.

Prognosis for polycythemia vera

Among blood diseases, there are many that cause a decrease in various elements - erythrocytes, leukocytes, platelets. But in some pathologies, on the contrary, there is an uncontrolled increase in the number of blood cells. The condition in which there is a chronic increase in the number of red blood cells, and other pathological changes occur, is called "true polycythemia".

Features of the disease

Primary (true) polycythemia is a blood disease from the leukemia group that occurs idiopathically (for no apparent reason), proceeds for a long time (chronically) and is characterized by an increase in the number of red blood cells, an increase in hematocrit and blood viscosity. Synonyms for the name of the pathology are Wakez-Osler disease, erythremia, primary erythrocytosis. The consequences of erythrocytosis and blood clotting in this myeloproliferative disease can be serious and relate to the risk of thrombosis, enlargement and malfunction of the spleen, an increase in circulating blood volume, etc.

Erythremia is considered a malignant tumor process, which is caused by increased proliferation (hyperplasia) of bone marrow cells. Especially strongly the pathological process covers the erythroblastic germ - a part of the bone marrow, consisting of erythroblasts and normoblasts. The pathogenesis of the main manifestations is associated with the appearance in the blood of a huge number of red blood cells, as well as with a certain increase in the number of platelets and neutrophils (neutrophilic leukocytes). The blood cells are morphologically normal, but their number is abnormal. As a result, blood viscosity and the amount of blood in the circulating bloodstream increase. The result is a slower blood flow, the formation of blood clots, a violation of the local blood supply to tissues and their hypoxia.

If initially the patient most often has primary erythrocytosis, that is, only the number of erythrocytes increases, then further changes begin to cover other blood cells. Extramedullary hematopoiesis (pathological formation of blood outside the bone marrow) occurs in the organs of the peritoneum - in the liver and spleen, where part of erythropoiesis is also localized - the process of formation of red blood cells. At a late stage of the disease, the life cycle of erythrocytes is shortened, anemia, thrombocytopenia, myelofibrosis may develop, and the precursor cells of leukocytes and erythrocytes enter the general circulation without maturing. In about 10% of cases, the pathology flows into acute leukemia.

The study and first description of erythrocytosis was made in 1892 by Vakez, and in 1903 the scientist Osler suggested that the cause of the disease is a violation of the bone marrow. True polycythemia is observed somewhat more often than other similar pathologies, but still it is quite rare. It is diagnosed in approximately 5 people per year per 1 million population. Most often, the disease occurs in people older than 50 years, the average age of detection is 60 years. In children, a similar diagnosis is made very rarely, mainly after 12 years. On average, only 5% of patients are under 40 years of age. Men suffer from this pathology more often than women. In the general structure of chronic myeloproliferative diseases, polycythemia vera takes the 4th place. Sometimes it is inherited, so there are family cases.

Causes of pathology

The primary form of the disease is considered hereditary, transmitted in an autosomal recessive manner. In this case, it is often referred to as "family polycythemia". But most often, erythremia is a secondary condition, representing one of the manifestations of a general pathological process. The exact causes have not been established, but there are several theories about the appearance of polycythemia vera. Thus, there is a connection between the development of the disease and the transformation of stem cells, when a tyrosine kinase mutation occurs, which occurs in polycythemia vera more often than in other blood diseases.

Studies of cells in erythremia revealed in many patients the clonal origin of the pathology, since the same enzyme was detected in leukocytes, platelets, erythrocytes. The clonal theory is also confirmed by ongoing cytological studies in relation to the karyotype of chromosome groups, where various defects were identified that are similar in different patients. There is also a virus-genetic theory, according to which up to 15 types of viruses can enter the body and, with the participation of a number of provoking factors, lead to a malfunction in the bone marrow. They penetrate into the precursors of blood cells, which then, instead of normal maturation, begin to divide and form new red blood cells and other cells.

As for the risk factors for the development of true polycythemia, then, presumably, they may be as follows:

• lung diseases;
• long stay at high altitude above sea level;
• hypoventilation syndromes;
• various hemoglobinopathies;
• long smoking history;
• tumors of the bone marrow, blood;
• hemoconcentration with long-term use of diuretics;
• burns of a large part of the body;
• severe stress;
• diarrhea;
• exposure to x-rays, radiation;
• poisoning with vapors of chemicals, their ingress through the skin;
• the intake of toxic substances in the digestive tract;
• treatment with gold salts;
• advanced tuberculosis;
• major surgical interventions;
• "blue" heart defects;
• kidney pathology - hydronephrosis, stenosis of the arteries of the kidneys.

Thus, the main cause of secondary erythrocytosis are all conditions that somehow provoke tissue hypoxia, stress for the body or its intoxication. In addition, oncological processes, endocrine pathologies, and liver diseases can have a great impact on the brain and the production of additional blood cells.

Classification of true polycythemia

The disease is classified into the following stages:

1. The first or initial stage. It can last more than 5 years, is the development of plethoric syndrome, that is, increased blood supply to organs. At this stage, the symptoms can be expressed moderately, complications do not occur. A complete blood count reflects a slight increase in the number of erythrocytes, a bone marrow puncture shows an increase in erythropoiesis or the production of all the main blood elements, with the exception of lymphocytes.
2. The second is the A stage, or polycythemic stage. Duration - from 5 to 15 years. The plethoric syndrome is more pronounced, there is an increase in the spleen, liver (hematopoietic organs), thrombosis is often recorded in the veins and arteries. Tumor growth in the organs of the peritoneum is not observed. If this stage ends with a decrease in the number of platelets - thrombocytopenia, then the patient may experience various bleeding. Frequent hemorrhages cause a lack of iron in the body. A general blood test reflects an increase in erythrocytes, platelets, leukocytes, with a running course - a decrease in platelets. In the myelogram, there is an increased formation of most blood cells (with the exception of lymphocytes), cicatricial changes in the brain are formed.
3. The second - stage B, or polycythemic stage with myeloid metaplasia of the organ - the spleen. The patient continues to increase the size of the spleen, and often the liver. Puncture of the spleen reveals tumor growth. There are frequent thromboses interspersed with bleeding. In the general analysis, there is an even greater increase in the number of erythrocytes, leukocytes, there are erythrocytes of different sizes, shapes, there are immature precursors of all blood cells. In the bone marrow, the number of cicatricial changes increases.
4. The third, or anemic stage. It is the outcome of a disease in which the activity of blood cells is depleted. The number of erythrocytes, leukocytes, and platelets is greatly reduced, the liver and spleen are enlarged with myeloid metaplasia, extensive cicatricial changes occur in the bone marrow. A person becomes disabled, most often due to the consequences of thrombosis or the addition of acute leukemia, myelofibrosis, hematopoietic hypoplasia or chronic myeloid leukemia. This stage is recorded approximately one year after the development of the pathology.

Symptoms of manifestation

Often this pathology is asymptomatic, but only in its initial stages. Later, the disease in a patient manifests itself in one way or another, while specific symptoms can be varied. Basically, the symptom complex includes the following main signs:

1. Change in skin tone, dilated veins. Most often, in the neck of an adult, the veins begin to shine through strongly, their pattern becomes stronger due to swelling, overfilling with blood. But the skin signs become the most obvious: the skin color becomes dark red, literally cherry. Most of all, this is noticeable in the neck, arms, face, which is associated with overfilling of the subcutaneous arteries with blood. At the same time, many patients mistakenly think that blood pressure rises against the background of hypertension, and therefore they often continue to take drugs for pressure and do not go to the doctor. With a careful attitude to health, you can see that the lips and tongue also changed their shade, became red-blue. The vessels of the eyes are also filled with blood, their plethora leads to hyperemia of the sclera and conjunctiva of the organs of vision. The hard palate remains the same color, but the soft palate also becomes brighter, burgundy.
2. Skin itching. All described changes in the skin in about half of the cases are complemented by severe discomfort and itching. This symptom is very characteristic of erythremia, both primary and secondary. Since after taking water procedures in patients, histamine is released, as well as prostaglandins, itching of the skin may become even more pronounced after a bath or shower.
3. Pain in limbs. Many people develop obliterating endarteritis, which results in persistent and severe pain in the legs. They can intensify with exercise, long walking, in the evening, at first they are often perceived as a symptom of fatigue in an elderly person. Pain is also observed during palpation and tapping of flat bones, which reflects the process of hyperplasia and scarring in the bone marrow. The next type of pain in a person with polycythemia vera is persistent burning pain in the large and small joints of the legs, which resemble gouty pains and are caused by the same reason as gout - an increase in the level of uric acid. Another type of pain is severe, poorly tolerated pain in the fingers and toes, in which the skin becomes bluish-red, blue spots appear on it. These pains are caused by an increase in the number of platelets and the appearance of microthrombosis of capillaries.
4. Splenomegaly. The growth of the spleen in size is observed in almost every person with polycythemia vera, but at different stages of the disease. This is due to increased filling of the spleen with blood and the development of myeloproliferative phenomena. Somewhat less often, but still there is a strong increase in the size of the liver - hepatomegaly.
5. Ulcer disease. Approximately one in ten people with Wackez-Osler disease develop ulcers in the small intestine (often in the duodenum) and in the stomach. This is due to the activation of Helicobacter pylori bacteria, as well as the development of microthrombosis in the gastrointestinal tract.
6. thrombosis and bleeding. Almost all patients at a certain stage have a tendency to thrombosis, and until recently, patients died from such complications at an early stage of the disease. Now ongoing modern treatment can prevent the appearance of blood clots in the brain, spleen, legs, which threaten embolism and death. Increased blood viscosity characterizes true polycythemia in the initial stages, and later, against the background of depletion of the platelet formation system, bleeding develops - it is observed in the gums, nose, uterus, and gastrointestinal tract.

There are other signs of polycythemia vera that a person may complain about, but they are not specific and may be inherent in various pathologies:

• fatigue;
• head goals;
• tinnitus;
• nausea;
• dizziness;
• feeling of pulsation in the temples, ears;
• decreased appetite, performance;
• the appearance of "flies" before the eyes;
• other visual impairments - loss of fields, loss of visual acuity;
• shortness of breath, coughing;
• increased blood pressure;
• unexplained weight loss;
• prolonged subfebrile condition;
• insomnia;
• numbness, tingling of the fingers;
• epileptiform seizures and paralysis (rare).

In general, the disease is characterized by a long and sometimes benign course, especially when adequate treatment is carried out. But in some people, especially those who are not receiving therapy, various consequences of polycythemia vera may appear early.

Possible Complications

Most often, complications are associated with thrombosis and embolism of the veins and vessels of the spleen, liver, legs, brain, and other areas of the body. This leads to different consequences depending on the size of the thrombus, the affected area. Transient ischemic attacks, strokes, thrombophlebitis and phlebothrombosis of superficial and deep veins, blockage of retinal blood vessels and blindness, heart attacks of internal organs, myocardial infarction may occur.

In the most advanced stages of the pathology, kidney stones (urolithiasis), gout, nephrosclerosis, and cirrhosis of the liver often appear. Complications are likely due to tissue bleeding - bleeding from gastrointestinal ulcers, anemia. From the side of the heart, in addition to myocardial infarction, signs of myocardiosclerosis and heart failure are also possible. There is also the possibility of the transition of true polycythemia to acute leukemia, chronic leukemia and other oncopathologies.

Carrying out diagnostics

It is not easy to make a diagnosis of this disease, especially in the absence of a characteristic clinical picture and in the presence of only general symptoms. Nevertheless, the totality of data from hematological and biochemical analyzes, as well as some distinctive features of the patient's appearance, coupled with his complaints, will help the doctor determine the cause of the changes.

The main indicators for establishing the diagnosis of polycythemia vera are the indicators of the general blood test - the number of erythrocytes and hematocrit. In men, the development of this disease can be suspected if the number of red blood cells is more than 5.7 * 10 * 9 / l, hemoglobin is more than 177 g / l, hematocrit was above 52%. In women, an excess of indicators is noted if they are more than 5.2 * 10 * 9 / l, 172 g / l, 48-50%, respectively. These figures are typical for the early stages of pathology, and as it develops, they become even higher. In addition, it is important to assess the mass of circulating erythrocytes, which is normally up to 36 ml/kg for men and up to 32 ml/kg for women.

Other blood parameters (according to biochemistry, general analysis and other tests), which, in combination with the described disorders and in combination with each other, reflect the picture of the development of primary or secondary erythrocytosis:

1. Moderate or severe thrombocytosis (above 400 * 10 * 9 l), neutrophilic leukocytosis (above 12 * 10 * 9 l) with the presence of an increased number of basophils and eosinophils.
2. Increase in the number of reticulocytes.
3. The appearance in the blood of myelocytes, metamyelocytes.
4. Increase in blood viscosity by %.
5. A strong decrease in ESR.
6. Increase in the mass of circulating red blood cells.
7. Increase in alkaline phosphatase, vitamin B12 in serum.
8. An increase in the amount of uric acid in the serum.
9. The saturation of blood in the arteries with oxygen is above 92%.
10. The appearance of erythrocyte colonies in a test tube.
11. Decrease in erythropoietin.
12. Change in color index less than 1.

At the stage of myelofibrosis, hemoglobin and erythrocyte indicators can return to normal, but the number of leukocytes increases greatly, their immature forms appear, and the presence of erythroblasts is diagnosed. As for the myelogram, which is obtained by puncturing the bone marrow, the following changes are revealed in it:

• reduction in the presence of fatty inclusions;
• increase in erythroblasts, normoblasts;
• hyperplasia of myelopoiesis sprouts.

There are other criteria by which the doctor can draw a conclusion about the ongoing changes characteristic of polycythemia vera:

1. Hepatosplenomegaly.
2. Tendency to thrombosis.
3. Increased sweating combined with weight loss, weakness.
4. The presence of gene abnormalities, if genetic testing has been performed, when it comes to primary erythremia.
5. Increase in the average amount of circulating blood.

All the criteria described above, except for the three main ones, which are considered large, are small. As for the major diagnostic criteria, this is an increase in the mass of circulating erythrocytes, splenomegaly, supersaturation of arterial blood with oxygen. To establish a diagnosis, it is usually sufficient to have three of these major criteria, which are combined with two or three minor ones. Differential diagnosis is carried out by a hematologist between conditions that are accompanied by erythrocytosis - heart defects, tuberculosis, tumors, etc.

Treatment Methods

The earlier a person seeks help, the more effective the therapy can be. At the third stage, or when layering another tumor process on erythremia, symptomatic therapy is performed in combination with chemotherapy treatment. Chemotherapeutic treatment may be recommended at other stages of the disease, but the body does not always give an adequate response to it. Of the symptomatic means that improve the quality of life, the following are used:

1. Drugs against high blood pressure, mainly from the group of ACE inhibitors.
2. Antihistamines for itching, skin irritation, and other allergic reactions.
3. Antiplatelet agents and anticoagulants for blood thinning with a tendency to thrombosis.
4. Local and systemic hemostatic agents for bleeding tissues.
5. Medications to lower uric acid.

Treatment options for polycythemia vera may include:

1. Bloodletting, or removing a small amount of blood from the bloodstream (phlebotomy). As a rule, they are done in volume (according to indications) and a break of 3-4 days in a course of several sessions. The blood after such manipulations becomes more liquid, but they cannot be done if there is a recent history of blood clots. Before treatment with bloodletting, the patient is given a solution of Reopoliglyukin, as well as Heparin.
2. Erythrocytapheresis. It is used to clean the blood from excess red blood cells, as well as from platelets. Such sessions are done once a week.
3. Chemotherapy. It is used, as a rule, when the disease reaches the tumor stage - the second B. Other indications for chemotherapy are the presence of complications from the peritoneal organs, the general plight of a person, and an increase in the number of all blood elements. For chemotherapy, or cytoreductive therapy, cytostatics, antimetabolites, alkylating drugs, biological drugs are used. The most commonly prescribed drugs are Leukeran, Hydroxyurea, Mielosan, recombinant interferon.
4. Treatment of iron deficiency with androgens, erythropoietin, which are most often used in combination with glucocorticosteroids.
5. Radiation therapy. It is used to irradiate the spleen area and stop the cancer process in it, it is used with a strong increase in the size of the organ.
6. Transfusion of erythrocyte mass from purified erythrocytes. Used for severe anemia up to coma. If thrombocytopenia increases in the final stages of polycythemia vera, a platelet mass transfusion from a donor may be necessary.

Bone marrow transplantation for a disease such as erythremia often leads to adverse results, so it is rarely used. In some cases, splenectomy is indicated, but with the development of acute leukemia, such an operation is not performed even with severe splenomegaly.

Features of treatment in pregnant women

During pregnancy, this pathology occurs rarely. However, if there is a predisposition (hereditary or from secondary factors), pregnancy, childbirth and abortion can become a trigger for the development of polycythemia vera. Pregnancy always worsens the course of this disease, and its outcome may be more serious than outside of gestation. However, in 50% of cases, pregnancy ends in a successful birth. The remaining half is accounted for by miscarriages, developmental delay, anomalies in the structure of the fetal body.

Treatment of the disease in pregnant women is not easy. Most drugs are strictly contraindicated, as they have a pronounced teratogenic property. Therefore, during pregnancy, bloodletting therapy and, if necessary, glucocorticosteroids are mainly performed. To prevent complications and early detection of the disease in pregnant women, blood tests should be carried out regularly according to the schedule indicated by the observing obstetrician-gynecologist.

What Not to Do

It is strictly forbidden to use diuretics, which additionally thicken the blood. Also in our time, the use of radioactive phosphorus preparations is limited, which seriously inhibit myelopoiesis and often lead to the development of leukemia. Also, you can not save the old nutrition system: the diet must change. All foods that enhance blood formation, such as the liver, are prohibited. It is better to form a diet as a dairy-vegetable one, and refuse excess meat.

The patient should not overload the body, engage in heavy sports, ignore regular rest. Treatment with folk remedies can be used, but only after a thorough study of all the remedies by the doctor in terms of composition, in order to prevent an increase in the production of red blood cells. Most often, symptomatic therapy is used to remove uric acid, reduce pain and itching of the skin, etc.

Prevention and prognosis

Methods of prevention have not yet been developed. The prognosis for life varies depending on the severity of the course of the disease. Without treatment, up to a third of patients die within the first 5 years of diagnosis. If you carry out a full-fledged therapy, then you can extend the life of a person for a flight or more. The most common cause of death is thrombosis, and only occasionally do people die from blood cancer (leukemia) or heavy bleeding.

Polycythemia vera (erythremia, Wakez's disease or primary polycythemia) is a progressive malignant disease belonging to the group of leukemias, which is associated with hyperplasia of the cellular elements of the bone marrow (myeloproliferation). The pathological process affects mainly the erythroblastic germ, therefore, an excess number of red blood cells is detected in the blood. There is also an increase in the number of neutrophilic leukocytes and platelets.

An increased number of red blood cells increases the viscosity of the blood, increases its mass, causes a slowdown in blood flow in the vessels and the formation of blood clots. As a result, patients develop impaired blood supply and hypoxia.

General information

True polycythemia was first described in 1892 by French and Vaquez. Vakez suggested that the hepatosplenomegaly and erythrocytosis revealed in his patient arose as a result of increased proliferation of hematopoietic cells, and singled out erythremia as a separate nosological form.

In 1903, W. Osler used the term "Wakez's disease" to describe patients with splenomegaly (enlarged spleen) and severe erythrocytosis and gave a detailed description of the disease.

Turk (W. Turk) in 1902-1904 suggested that in this disease, the violation of hematopoiesis is hyperplastic in nature, and called the disease erythremia by analogy with leukemia.

The clonal neoplastic nature of myeloproliferation, which is observed in polycythemia, was proved in 1980 by P. J. Fialkov. He found in erythrocytes, granulocytes and platelets one type of enzyme glucose-6-phosphate dehydrogenase. In addition, both types of this enzyme were detected in lymphocytes of two patients heterozygous for this enzyme. Thanks to Fialkov's research, it became clear that the target of the neoplastic process is the precursor cell of myelopoiesis.

In 1980, a number of researchers managed to separate a neoplastic clone from normal cells. It has been experimentally proven that in polycythemia, a population of erythroid committed precursors is formed, which have a pathologically high sensitivity to even a small amount of erythropoietin (kidney hormone). According to scientists, this contributes to the increased production of red blood cells in polycythemia vera.

In 1981, L. D. Sidorova and co-authors conducted studies that made it possible to detect qualitative and quantitative changes in the platelet link of hemostasis, which play a major role in the development of hemorrhagic and thrombotic complications in polycythemia.

Polycythemia vera occurs predominantly in the elderly, but can also occur in young people and children. In young people, the disease is more severe. The average age of patients varies from 50 to 70 years. The average age of those who fell ill for the first time is gradually increasing (in 1912 it was 44 years, and in 1964 - 60 years). The number of patients under 40 years of age is about 5%, and erythremia in children and patients under 20 years of age is detected in 0.1% of all cases of the disease.

Erythremia is somewhat less common in women than in men (1: 1.2-1.5).

It is the most common disease in the group of chronic myeloproliferative diseases. It is quite rare - according to various sources, from 5 to 29 cases per 100,000 population.

There are sporadic data on the influence of racial factors (above average among Jews and below average among representatives of the Negroid race), but at the moment this assumption has not been confirmed.

Forms

True polycythemia is divided into:

• Primary (not a consequence of other diseases).
• Secondary. It can be triggered by chronic lung disease, hydronephrosis, the presence of tumors (uterine fibroids, etc.), the presence of abnormal hemoglobins, and other factors associated with tissue hypoxia.

An absolute increase in the mass of erythrocytes is observed in all patients, but only in 2/3 the number of leukocytes and platelets also increases.

Reasons for development

The causes of polycythemia vera have not been definitively established. Currently, there is no single theory that would explain the occurrence of hemoblastoses (blood tumors), which include this disease.

Based on epidemiological observations, a theory was put forward about the relationship of erythremia with the transformation of stem cells, which occurs under the influence of gene mutations.

It has been established that most patients have a mutation of the Janus kinase tyrosine kinase enzyme synthesized in the liver, which is involved in the transcription of certain genes by phosphorylation of many tyrosines in the cytoplasmic part of the receptors.

The most common mutation discovered in 2005 is in exon 14 JAK2V617F (detected in 96% of all cases of the disease). In 2% of cases, the mutation affects exon 12 of the JAK2 gene.

Patients with polycythemia vera also have:

• In some cases, mutations in the thrombopoietin receptor gene MPL. These mutations are of secondary origin and are not strictly specific for this disease. They are detected in elderly people (mainly in women) with low levels of hemoglobin and platelets.
• Loss of function of the LNK gene of the SH2B3 protein, which reduces the activity of the JAK2 gene.

Elderly patients with a high JAK2V617F allelic load are characterized by elevated hemoglobin levels, leukocytosis, and thrombocytopenia.

When the JAK2 gene is mutated in exon 12, erythremia is accompanied by a subnormal serum level of the hormone erythropoietin. Patients with this mutation are younger.
In polycythemia vera, mutations in TET2, IDH, ASXL1, DNMT3A, and others are often also detected, but their pathogenetic significance has not yet been studied.

There were no differences in the survival of patients with different types of mutations.

As a result of molecular genetic disorders, the JAK-STAT signaling pathway is activated, which is manifested by the proliferation (production of cells) of the myeloid germ. At the same time, proliferation and an increase in the number of erythrocytes in the peripheral blood increase (an increase in the number of leukocytes and platelets is also possible).

The identified mutations are inherited in an autosomal recessive manner.

There is also a hypothesis according to which viruses can be the cause of erythremia (15 types of such viruses have been identified), which, in the presence of predisposing factors and weakened immunity, penetrate immature bone marrow cells or lymph nodes. Instead of maturation, cells affected by the virus begin to actively divide, thus starting the pathological process.

Disease-causing factors include:

• x-ray exposure, ionizing radiation;
• paints, varnishes and other toxic substances that penetrate the human body;
• long-term use for medicinal purposes of certain drugs (gold salts for rheumatoid arthritis, etc.);
• viral and intestinal infection, tuberculosis;
• surgical interventions;
• stressful situations.

Secondary erythremia develops under the influence of favorable factors with:

• high innate affinity of hemoglobin for oxygen;
• low levels of 2,3-diphosphoglycerate;
• autonomous production of erythropoietin;
• arterial hypoxemia of a physiological and pathological nature (“blue” heart defects, smoking, adaptation to high altitude conditions and chronic lung diseases);
• kidney diseases (cystic lesions, hydronephrosis, renal artery stenosis and diffuse diseases of the renal parenchyma);
• the presence of tumors (possibly influenced by bronchial carcinoma, cerebellar hemangioblastoma, uterine fibroids);
• endocrine diseases associated with tumors of the adrenal glands;
• liver diseases (cirrhosis, hepatitis, hepatoma, Budd-Chiari syndrome);
• tuberculosis.

Pathogenesis

The pathogenesis of polycythemia vera is associated with a violation of the process of hematopoiesis (hematopoiesis) at the level of the progenitor cell. Hemopoiesis acquires the unlimited proliferation of a progenitor cell characteristic of a tumor, the descendants of which form a specialized phenotype in all hematopoietic lineages.

Polycythemia vera is characterized by the formation of erythrocyte colonies in the absence of exogenous erythropoietin (the appearance of endogenous erythropoietin-independent colonies is a sign that distinguishes erythremia from secondary erythrocytosis).

The formation of erythroid colonies indicates a violation of the implementation of regulatory signals that the myeloid cell receives from the external environment.

The basis of the pathogenesis of true polycythemia are defects in the genes encoding proteins that are responsible for maintaining myelopoiesis within the normal range.

A decrease in the concentration of oxygen in the blood causes a reaction of the interstitial cells of the kidneys that synthesize erythropoietin. The process that takes place in interstitial cells concerns the work of many genes. The main regulation of this process is carried out by factor-1 (HIF-1), which is a heterodimeric protein consisting of two subunits (HIF-1alpha and HIF-1beta).

If the oxygen concentration in the blood is within the normal range, proline residues (a heterocyclic amino acid of the free-existing HIF-1 molecule) are hydroxylated under the influence of the regulatory enzyme PHD2 (molecular oxygen sensor). Due to hydroxylation, the HIF-1 subunit acquires the ability to bind to the VHL protein, which provides tumor prevention.

The VHL protein forms a complex with a number of E3 ubiquitin ligase proteins, which, after the formation of covalent bonds with other proteins, are directed to the proteasome and degraded there.

Under hypoxia, hydroxylation of the HIF-1 molecule does not occur, the subunits of this protein combine and form a heterodimeric HIF-1 protein, which is directed from the cytoplasm to the nucleus. The protein that has entered the nucleus binds in the promoter regions of genes with special DNA sequences (the conversion of genes into protein or RNA is induced by hypoxia). As a result of these transformations, erythropoietin is released into the bloodstream by the interstitial cells of the kidneys.

Myelopoiesis precursor cells carry out their genetic program as a result of the stimulating effect of cytokines (these small peptide control (signal) molecules bind to the corresponding receptors on the surface of precursor cells).

When erythropoietin binds to the EPO-R erythropoietin receptor, this receptor dimerizes, which activates the kinase associated with intracellular EPO-R domains Jak2.

Jak2 kinase is responsible for signal transduction from erythropoietin, thrombopoietin and G-CSF (it is a granulocyte colony stimulating factor).

The activation of Jak2 kinase results in phosphorylation of a number of cytoplasmic target proteins, which include adapter proteins of the STAT family.

Erythremia was detected in 30% of patients with constitutive activation of the STAT3 gene.

Also, with erythremia, in some cases, a reduced level of expression of the MPL thrombopoietin receptor, which is compensatory in nature, is detected. The decrease in MPL expression is secondary and is caused by a genetic defect responsible for the development of polycythemia vera.

A decrease in degradation and an increase in the level of the HIF-1 factor are caused by defects in the VHL gene (thus, representatives of the population of Chuvashia are characterized by a homozygous mutation 598C>T of this gene).

Polycythemia vera can be caused by chromosome 9 abnormalities, but the most common is a deletion of the long arm of chromosome 20.

In 2005, a point mutation of exon 14 of the Jak2 kinase gene (mutation JAK2V617F) was identified, which causes the replacement of the amino acid valine by phenylalanine in the JH2 pseudokinase domain of the JAK2 protein at position 617.

The JAK2V617F mutation in hematopoietic precursor cells in erythremia is presented in a homozygous form (the formation of the homozygous form is affected by mitotic recombination and duplication of the mutant allele).

With the activity of JAK2V617F and STAT5, the level of reactive oxygen species increases, resulting in a transition of the cell cycle from G1 to S phase. phase G1 in S. As a result, the proliferation of erythroid cells that carry the mutant form of the JAK2 gene is enhanced.

In JAK2V617F-positive patients, this mutation is detected in myeloid cells, B- and T-lymphocytes, and natural killer cells, which proves the proliferative advantage of defective cells compared to the norm.

Polycythemia vera in most cases is characterized by a rather low ratio of the mutant and normal allele in mature myeloid cells and early precursors. In the presence of clonal dominance, patients have a more severe clinical picture compared to patients without this defect.

Symptoms

The symptoms of polycythemia vera are associated with an overproduction of red blood cells, which increase the viscosity of the blood. In most patients, the level of platelets also increases, which cause vascular thrombosis.

The disease develops very slowly and is asymptomatic at the initial stage.
In later stages, polycythemia vera manifests itself:

• plethoric syndrome, which is associated with increased blood supply to organs;
• myeloproliferative syndrome, which occurs when there is an increased production of red blood cells, platelets and white blood cells.

Plethoric syndrome is accompanied by:

• Headaches.
• Feeling of heaviness in the head;
• Vertigo.
• Attacks of pressing, squeezing pain behind the sternum, which occurs during physical exertion.
• Erythrocyanosis (reddening of the skin to a cherry hue and a bluish tint of the tongue and lips).
• Redness of the eyes, which occurs as a result of the expansion of blood vessels in them.
• Feeling of heaviness in the upper abdomen (left) due to an enlarged spleen.
• Skin itching, which is observed in 40% of patients (a specific sign of the disease). It intensifies after water procedures and occurs as a result of irritation by the breakdown products of erythrocytes of nerve endings.
• An increase in blood pressure, which is well reduced with bloodletting and slightly reduced with standard treatment.
• Erythromelalgia (acute, burning pain in the fingertips that improves with blood-thinning drugs, or painful swelling and redness of the foot or lower third of the leg).

Myeloproliferative syndrome manifests itself:

• soreness in flat bones and joint pain;
• a feeling of heaviness in the right upper abdomen as a result of an enlarged liver;
• general weakness and increased fatigue;
• an increase in body temperature.

There are also dilated veins, especially noticeable in the neck, Cooperman's symptom (discoloration of the soft palate with normal coloration of the hard palate), duodenal ulcer and in some cases of the stomach, bleeding of the gums and esophagus, increased uric acid levels. Perhaps the development of heart failure and cardiosclerosis.

Stages of the disease

Polycythemia vera is characterized by three stages of development:

• Initial, stage I, which lasts about 5 years (a longer period is possible). It is characterized by moderate manifestations of plethoric syndrome, the size of the spleen does not exceed the norm. A general blood test reveals a moderate increase in the number of red blood cells, an increased formation of red blood cells is observed in the bone marrow (an increase in the number of all blood cells, with the exception of lymphocytes, is also possible). At this stage, complications practically do not arise.
• The second stage, which can be polycythemic (II A) and polycythemic with myeloid metaplasia of the spleen (II B). Form II A, lasting from 5 to 15 years, is accompanied by a pronounced plethoric syndrome, enlargement of the liver and spleen, the presence of thrombosis, and bleeding. Tumor growth in the spleen is not detected. Possible iron deficiency due to frequent bleeding. A general blood test reveals an increase in the number of erythrocytes, platelets and leukocytes. There are cicatricial changes in the bone marrow. Form II B is characterized by a progressive enlargement of the liver and spleen, the presence of tumor growth in the spleen, thrombosis, general exhaustion, and bleeding. A complete blood count can detect an increase in the number of all blood cells, with the exception of lymphocytes. Erythrocytes acquire different sizes and shapes, immature blood cells appear. Cicatricial changes in the bone marrow gradually increase.
• Anemic, stage III, which develops 15-20 years after the onset of the disease and is accompanied by a pronounced increase in the liver and spleen, extensive cicatricial changes in the bone marrow, circulatory disorders, a decrease in the number of red blood cells, platelets and white blood cells. Transformation into acute or chronic leukemia is possible.

Diagnostics

Erythremia is diagnosed based on:

• Analysis of complaints, anamnesis of the disease and family history, during which the doctor clarifies when the symptoms of the disease appeared, what chronic diseases the patient has, whether there was contact with toxic substances, etc.
• Physical examination data, in which attention is drawn to the color of the skin. In the process of palpation and with the help of percussion (tapping), the size of the liver and spleen is determined, the pulse and blood pressure are also measured (may be elevated).
• A blood test, which determines the number of erythrocytes (normal 4.0-5.5x109 g / l), leukocytes (may be normal, increased or decreased), platelets (at the initial stage it does not deviate from the norm, then there is an increase in the level, and then a decrease ), hemoglobin level, color indicator (usually the norm is detected - 0.86-1.05). ESR (erythrocyte sedimentation rate) in most cases is reduced.
• Urinalysis, which allows you to identify concomitant diseases or the presence of renal bleeding.
• A biochemical blood test, which allows to identify an elevated level of uric acid, characteristic of many cases of the disease. To detect concomitant organ damage, the level of cholesterol, glucose, etc. is also determined.
• Data from a bone marrow study, which is carried out using a puncture in the sternum and reveals an increased production of red blood cells, platelets and white blood cells, as well as the formation of scar tissue in the bone marrow.
• Trepanobiopsy data, which most fully reflect the state of the bone marrow. For examination, using a special trephine device, a bone marrow column is taken from the iliac wing along with the bone and periosteum.

A coagulogram, studies of iron metabolism are also carried out, and the level of erythropoietin in the blood serum is determined.

Since chronic erythremia is accompanied by an increase in the liver and spleen, ultrasound of the internal organs is performed. With the help of ultrasound, the presence of hemorrhages is also detected.

To assess the prevalence of the tumor process, CT (spiral computed tomography) and MRI (magnetic resonance imaging) are performed.

To identify genetic abnormalities, a molecular genetic study of peripheral blood is performed.

Treatment

The goal of treatment for polycythemia vera is:

• prevention and therapy of thrombohemorrhagic complications;
• elimination of symptoms of the disease;
• reducing the risk of complications and the development of acute leukemia.

Erythremia is treated with:

• Bloodletting, in which 200-400 ml of blood is removed to reduce blood viscosity in young people and 100 ml of blood in concomitant heart diseases or in the elderly. The course consists of 3 procedures, which are carried out with an interval of 2-3 days. Before the procedure, the patient takes drugs that reduce blood clotting. Bloodletting is not performed in the presence of recent thrombosis.
• Hardware methods of treatment (erythrocytepheresis), with the help of which excess red blood cells and platelets are removed. The procedure is carried out at intervals of 5-7 days.
• Chemotherapy, which is used at stage II B, in the presence of an increase in the number of all blood cells, poor tolerance to bloodletting, or the presence of complications from the internal organs or blood vessels. Chemotherapy is carried out according to a special scheme.
• Symptomatic therapy, including antihypertensive drugs for elevated blood pressure (ACE inhibitors are usually prescribed), antihistamines to reduce skin itching, antiplatelet agents that reduce blood clotting, hemostatic drugs for bleeding.

For the prevention of thrombosis, anticoagulants are used (usually acetylsalicylic acid is prescribed at 40-325 mg / day).

Nutrition for erythremia should comply with the requirements of the treatment table according to Pevzner No. 6 (the amount of protein products is reduced, fruits and vegetables of red color and products containing dyes are excluded).

print version

Polycythemia is a chronic disease in which there is an increase in the number of red cells or red blood cells in the blood. The disease affects people of middle and older age - men are affected several times more often than women. More than half of people have an increase in the number of platelets and leukocytes.

The occurrence of a disease can be due to several reasons for which its species are divided. Primary or true polycythemia is caused mainly by genetic abnormalities or bone marrow tumors, while secondary polycythemia is promoted by external or internal factors. Without proper treatment, it leads to severe complications, the prognosis of which is not always comforting. So, the primary form, if therapy is not started in a timely manner, can be fatal over several years of progression, and the outcome of the secondary depends on the cause of its occurrence.

The main symptoms of the disease are attacks of severe dizziness and tinnitus, it seems to a person that he is losing consciousness. Bloodletting and chemotherapy are used for treatment.

A distinctive feature of this disorder is that it cannot spontaneously disappear and it is also impossible to completely recover from it. A person will need to regularly take blood tests and be under the supervision of doctors until the end of his life.

Etiology

The causes of the disease depend on its form and can be caused by various factors. True polycythemia is formed when:

• hereditary predisposition to violations of production;
• genetic failures;
• malignant neoplasms in the bone marrow;
• exposure to hypoxia (oxygen deficiency) on red blood cells.

Secondary polycythemia is caused by:

• chronic heart failure;
• insufficient supply of blood and oxygen to the kidneys;
• climatic conditions. The most affected are people living in high mountain areas;
• oncological tumors of internal organs;
• various infectious diseases that cause intoxication of the body;
• harmful working conditions, for example, in a mine or at a height;
• living in polluted cities or near factories;
• long-term abuse of nicotine;
• nation. According to statistics, polycythemia manifests itself in people of Jewish origin, this is due to genetics.

The disease itself is rare, but polycythemia is even rarer in newborns. The main way the disease is transmitted is through the mother's placenta. The child's place does not provide a sufficient supply of oxygen to the fetus (inadequate blood circulation).

Varieties

As mentioned above, the disease is divided into several types, which directly depend on the causes of occurrence:

• primary or true polycythemia - caused by blood pathologies;
• secondary polycythemia, which can be called relative - due to external and internal pathogens.

True polycythemia, in turn, can occur in several stages:

• initial, which is characterized by a slight manifestation of symptoms or their complete absence. Can take up to five years
• deployed. It is divided into two forms - without a malignant effect on the spleen and with its presence. The stage lasts one or two decades;
• severe - observed, the formation of cancerous tumors on the internal organs, including the liver and spleen, malignant blood lesions.

Relative polycythemia is:

• stressful - based on the name, it becomes clear that it occurs when the body is affected by prolonged overvoltage, adverse working conditions and an unhealthy lifestyle;
• false - in which the level of erythrocytes, and in the blood is within the normal range.

The prognosis of polycythemia vera is considered unfavorable, life expectancy with this disease does not exceed two years, but the chances of long life increase when used in the treatment of bloodletting. In this case, a person can live fifteen or more years. The prognosis of secondary polycythemia depends entirely on the course of the disease that triggered the process of increasing the number of red cells in the blood.

Symptoms

At the initial stage, polycythemia occurs with little or no symptoms. It is usually discovered during a random examination or during a preventive blood test. The first symptoms may be mistaken for a common cold or indicate a normal condition in the elderly. These include:

• decreased visual acuity;
• severe dizziness and headache attacks;
• noise in ears;
• sleep disturbance;
• cold fingertips.

In the advanced stage, the following symptoms may be observed:

• muscle and bone pain;
• an increase in the size of the spleen, the volume of the liver changes a little less often;
• bleeding gums;
• continuous bleeding for quite a long time after tooth extraction;
• the appearance of bruises on the skin, the nature of which a person cannot explain.

In addition, the specific symptoms of this disease are:

• severe itching of the skin, which is characterized by an increase in intensity after taking a bath or shower;
• painful burning sensations of the tips of the fingers and toes;
• manifestation of veins that were not previously visible;
• the skin of the neck, hands and face takes on a bright red color;
• lips and tongue become bluish;
• the whites of the eyes are filled with blood;
• general weakness of the patient's body.

In newborns, especially twins, the symptoms of polycythemia begin to be expressed a week after birth. These include:

• redness of the skin of the crumbs. The child begins to cry and scream during touching;
• significant weight loss;
• a large number of erythrocytes, leukocytes and platelets are found in the blood;
• enlargement of the liver and spleen.

These signs can lead to the death of the baby.

Complications

The consequences of ineffective or untimely treatment can be:

• excretion of large amounts of uric acid. Urine becomes concentrated and acquires an unpleasant odor;
• education ;
• chronic;
• occurrence and ;
• circulatory disorders, which leads to trophic ulcers on the skin;
• hemorrhages in various places of localization, for example, nose, gums, gastrointestinal tract, etc.

And they are considered the most common causes of death of patients with such an ailment.

Diagnostics

Polycythemia is very often discovered by chance during a blood test for completely different reasons. When diagnosing, the doctor must:

• carefully read the medical history of the patient and his immediate family;
• conduct a complete examination of the patient;
• find out the cause of the disease.

The patient, in turn, must undergo the following examinations:

The treatment of the primary disease is a rather laborious process, which includes the impact on tumors and the prevention of their activity. In drug therapy, the age of the patient plays an important role, because those substances that will help people under fifty will be strictly prohibited for the treatment of patients over seventy.

With a high content of red blood cells in the blood, the best treatment is bloodletting - during one procedure, the blood volume is reduced by about 500 milliliters. Cytopheresis is considered a more modern method of treating polycythemia. The procedure is to filter the blood. To do this, catheters are inserted into the veins of both arms of the patient, through one blood enters the apparatus, and after filtration, the purified blood returns to the other vein. This procedure must be carried out every other day.

For secondary polycythemia, treatment will depend on the underlying disease and the severity of its symptoms.

Prevention

Most causes of polycythemia cannot be prevented, but despite this, there are several preventive measures:

• completely stop smoking;
• change place of work or residence;
• timely treat diseases that can cause this disorder;
• regularly undergo preventive examinations in the clinic and take a blood test.