Erythremia (Vaquez disease, polycythemia vera). What is polycythemia vera and is it treated? How to treat polycythemia

Polycythemia vera (erythremia, Vaquez 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 primarily affects the erythroblastic germ, so an excess number of red blood cells is detected in the blood. An increase in the number of neutrophilic leukocytes and platelets is also observed.

ICD-10	D45
ICD-9	238.4
ICD-O	M9950/3
MedlinePlus	000589
MeSH	D011087

An increased number of red blood cells increases blood viscosity, 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

Polycythemia vera was first described in 1892 by French and Vaquez. Vaquez suggested that the hepatosplenomegaly and erythrocytosis detected in his patient arose as a result of increased proliferation of hematopoietic cells, and identified erythremia as a separate nosological form.

In 1903, W. Osler used the term “Vaquez 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 disorder 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 proven in 1980 by P. J. Fialkov. He discovered one type of enzyme, glucose-6-phosphate dehydrogenase, in red blood cells, granulocytes and platelets. In addition, both types of this enzyme were detected in the 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 the neoplastic clone from normal cells. It has been experimentally proven that polycythemia produces a population of erythroid committed precursors that are pathologically highly sensitive to even small amounts of erythropoietin (a kidney hormone). According to scientists, this contributes to increased formation 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 component of hemostasis, which play a major role in the development of hemorrhagic and thrombotic complications in polycythemia.

Polycythemia vera is detected mainly in older people, but can be observed 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 become 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 slightly 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 is isolated data on the influence of racial factors (above the average among Jews and below the average among representatives of the Negroid race), but at the moment this assumption has not been confirmed.

Forms

Polycythemia vera 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 erythrocyte mass 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), to which this disease belongs.

Based on epidemiological observations, a theory was put forward about the connection 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 in the enzyme Janus kinase-tyrosine kinase, synthesized in the liver, which is involved in the transcription of certain genes by phosphorylating 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 older people (mainly women) with low levels of hemoglobin and platelets.
• Loss of function of the LNK gene protein SH2B3, 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.

With a mutation of the JAK2 gene 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 of TET2, IDH, ASXL1, DNMT3A, etc. are also often detected, but their pathogenetic significance has not yet been studied.

There were no differences in 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 proliferation (cell production) of the myeloid lineage. At the same time, proliferation and an increase in the number of red blood cells 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 the cause of erythremia may be viruses (15 types of such viruses have been identified), which, in the presence of predisposing factors and weakened immunity, penetrate into immature bone marrow cells or lymph nodes. Cells affected by the virus begin to actively divide instead of maturing, thus starting the pathological process.

Factors that provoke the disease include:

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

Secondary erythremia develops under the influence of favorable factors when:

• 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 adrenal tumors;
• liver diseases (cirrhosis, hepatitis, hepatoma, Budd-Chiari syndrome);
• tuberculosis.

Pathogenesis

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

Polycythemia vera is characterized by the formation of erythroid 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 disruption in the implementation of regulatory signals that the myeloid cell receives from the external environment.

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

A decrease in oxygen concentration in the blood causes a reaction in the interstitial cells of the kidneys that synthesize erythropoietin. The process occurring 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 normal limits, proline residues (the heterocyclic amino acid of the freely existing HIF-1 molecule) are hydroxylated under the influence of the regulatory enzyme PHD2 (molecular oxygen sensor). Thanks 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 forming covalent bonds with other proteins, are sent to the proteasome and destroyed there.

During hypoxia, hydroxylation of the HIF-1 molecule does not occur; the subunits of this protein combine and form the heterodimeric HIF-1 protein, which travels from the cytoplasm to the nucleus. Once in the nucleus, the protein binds to special DNA sequences in the promoter regions of genes (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.

By myelopoiesis precursor cells, the genetic program embedded in them is carried out as a result of the stimulating effect of cytokines (these small peptide control (signal) molecules bind to the corresponding receptors on the surface of the precursor cells).

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

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

Due to the activation of Jak2-kinase, phospholation of a number of cytoplasmic target proteins occurs, which includes 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 thrombopoietin receptor MPL is detected, which is compensatory in nature. The reduction 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 is caused by defects in the VHL gene (for example, representatives of the population of Chuvashia are characterized by a homozygous mutation 598C>T of this gene).

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

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

When JAK2V617F and STAT5 are active, the level of reactive oxygen species increases, resulting in a transition of the cell cycle from the G1 to S phase. The adapter protein STAT5 and reactive oxygen species transmit a regulatory signal from JAK2V617F to the cyclin D2 and p27kip genes, which causes an accelerated transition of the cell cycle from phase G1 to S. As a result, the proliferation of erythroid cells that carry a mutant form of the JAK2 gene increases.

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 fairly low ratio of mutant to 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

Symptoms of polycythemia vera are associated with excess production of red blood cells, which increase blood viscosity. In most patients, the level of platelets, which cause vascular thrombosis, also increases.

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

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

Plethoric syndrome is accompanied by:

• Headaches.
• Feeling of heaviness in the head;
• Dizziness.
• Attacks of pressing, squeezing pain behind the sternum, which occurs during physical activity.
• Erythrocyanosis (redness of the skin to a cherry tint and a bluish tint of the tongue and lips).
• Redness of the eyes, which occurs as a result of dilation of blood vessels in them.
• A feeling of heaviness in the upper abdomen (left), which occurs as a result of 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 red blood cells of the nerve endings.
• An increase in blood pressure, which decreases well with bloodletting and decreases slightly with standard treatment.
• Erythromelalgia (sharp, burning pain in the fingertips that is relieved by taking blood thinners, 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;
• increase in body temperature.

Varicose veins are also observed, especially noticeable in the neck area, Cooperman's sign (change in color of the soft palate with normal coloration of the hard palate), duodenal ulcer and, in some cases, stomach, bleeding of the gums and esophagus, and increased uric acid levels. The development of heart failure and cardiosclerosis is possible.

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; 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 severe 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 red blood cells, platelets and leukocytes. Scar changes are observed in the bone marrow. Form II B is characterized by 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. Red blood cells take on different sizes and shapes, and immature blood cells appear. Scar 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 enlargement of the liver and spleen, extensive scar changes in the bone marrow, circulatory disorders, a decrease in the number of red blood cells, platelets and leukocytes. Transformation into acute or chronic leukemia is possible.

Diagnostics

Erythremia is diagnosed based on:

• Analysis of complaints, medical history 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.
• Data from a physical examination, which pays attention to the color of the skin. During palpation and with the help of percussion (tapping), the size of the liver and spleen is determined, pulse and blood pressure are also measured (may be elevated).
• A blood test that determines the number of red blood cells (the norm is 4.0-5.5x109 g/l), leukocytes (can be normal, increased or decreased), platelets (at the initial stage does not deviate from the norm, then an increase in the level is observed, and then a decrease ), hemoglobin level, color indicator (usually the norm is 0.86-1.05). ESR (erythrocyte sedimentation rate) is reduced in most cases.
• Urinalysis, which allows you to identify concomitant diseases or the presence of renal bleeding.
• A biochemical blood test that reveals the increased level of uric acid characteristic of many cases of the disease. To identify organ damage accompanying the disease, the level of cholesterol, glucose, etc. is also determined.
• Data from a bone marrow study, which is performed using a puncture in the sternum and reveals increased production of red blood cells, platelets and leukocytes, as well as the formation of scar tissue in the bone marrow.
• Trepanobiopsy data, which most fully reflect the condition of the bone marrow. For examination, using a special trephine device, a column of bone marrow is taken from the wing of the ilium along with the bone and periosteum.

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

Since chronic erythremia is accompanied by an enlargement of the liver and spleen, an ultrasound of the internal organs is performed. Ultrasound also detects the presence of hemorrhages.

To assess the extent of the tumor process, SCT (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 goals of treatment for polycythemia vera are:

• prevention and treatment of thrombohemorrhagic complications;
• elimination of symptoms of the disease;
• reducing the risk of complications and 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 case of concomitant heart diseases or in the elderly. The course consists of 3 procedures, which are carried out at intervals of 2-3 days. Before the procedure, the patient takes medications that reduce blood clotting. Bloodletting is not performed in the presence of recent thrombosis.
• Hardware treatment methods (erythrocytapheresis), which remove excess red blood cells and platelets. 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 internal organs or blood vessels. Chemotherapy is carried out according to a special regimen.
• Symptomatic therapy, including antihypertensive drugs for high blood pressure (ACE inhibitors are usually prescribed), antihistamines to reduce skin itching, antiplatelet agents that reduce blood clotting, hemostatic drugs for bleeding.

To prevent thrombosis, anticoagulants are used (usually acetylsalicylic acid is prescribed at 40-325 mg/day).

Nutrition for erythremia must meet the requirements of the treatment table according to Pevzner No. 6 (the amount of protein foods is reduced, red fruits and vegetables and foods containing dyes are excluded).

Found a mistake? Select it and click Ctrl + Enter

print version

Content

Hematologists know that this disease is difficult to treat and has dangerous complications. Polycythemia is characterized by changes in the composition of the blood that affect the patient's health. How does the pathology develop, what symptoms is it characterized by? Find out diagnostic methods, treatment methods, medications, life prognosis for the patient.

What is polycythemia

Men are more susceptible to the disease than women; middle-aged people are more often affected. Polycythemia is an autosomal recessive pathology in which, for various reasons, the number of red blood cells in the blood increases. The disease has other names - erythrocytosis, multiblood, Vaquez disease, erythremia, its ICD-10 code is D45. The disease is characterized by:

• splenomegaly – a significant increase in the size of the spleen;
• increased blood viscosity;
• significant production of leukocytes, platelets;
• increase in circulating blood volume (CBV).

Polycythemia belongs to the group of chronic leukemias and is considered a rare form of leukemia. True erythremia (polycythemia vera) is divided into types:

• Primary is a malignant disease with a progressive form associated with hyperplasia of the cellular components of the bone marrow - myeloproliferation. The pathology affects the erythroblastic germ, which causes an increase in the number of red blood cells.
• Secondary polycythemia is a compensatory reaction to hypoxia caused by smoking, high altitude climbing, adrenal tumors, and pulmonary pathology.

Vaquez disease is dangerous due to complications. Due to high viscosity, blood circulation in peripheral vessels is impaired. Uric acid is released in large quantities. All this is fraught with:

• bleeding;
• thrombosis;
• oxygen starvation of tissues;
• hemorrhages;
• hyperemia;
• hemorrhage;
• trophic ulcers;
• renal colic;
• ulcers in the gastrointestinal tract;
• kidney stones;
• splenomegaly;
• gout;
• myelofibrosis;
• iron deficiency anemia;
• myocardial infarction;
• stroke;
• fatal.

Types of disease

Vaquez disease, depending on development factors, is divided into types. Each has its own symptoms and treatment features. Doctors highlight:

• polycythemia vera, which is caused by the appearance of a tumor substrate in the red bone marrow, leading to an increase in the production of red blood cells;
• secondary erythremia - its cause is oxygen starvation, pathological processes occurring in the patient’s body and causing a compensatory reaction.

Primary

The disease is characterized by tumor origin. Primary polycythemia - myeloproliferative blood cancer - occurs when pluripotent stem cells of the bone marrow are damaged. When there is a disease in the patient’s body:

• the activity of erythropoietin, which regulates the production of blood cells, increases;
• the number of red blood cells, leukocytes, platelets increases;
• synthesis of mutated brain cells occurs;
• proliferation of infected tissues occurs;
• a compensatory reaction to hypoxia occurs - there is an additional increase in the number of red blood cells.

With this type of pathology, it is difficult to influence mutated cells that have a high ability to divide. Thrombotic and hemorrhagic lesions appear. Vaquez disease has developmental features:

• changes occur in the liver and spleen;
• tissues are filled with viscous blood, prone to the formation of blood clots;
• plethoric syndrome develops - cherry-red color of the skin;
• severe itching occurs;
• blood pressure (BP) increases;
• hypoxia develops.

Polycythemia vera is dangerous due to its malignant development, causing severe complications. This form of pathology is characterized by the following stages:

• Initial – lasts about five years, is asymptomatic, the size of the spleen is not changed. BCC increased slightly.
• The advanced stage lasts up to 20 years. It is characterized by an increased content of red blood cells, platelets, and leukocytes. It has two substages - without changes in the spleen and with the presence of myeloid metaplasia.

The last stage of the disease – post-erythremic (anemic) – is characterized by complications:

• secondary myelofibrosis;
• leukopenia;
• thrombocytopenia;
• myeloid transformation of the liver, spleen;
• cholelithiasis, urolithiasis;
• transient ischemic attacks;
• anemia - the result of bone marrow depletion;
• pulmonary embolism;
• myocardial infarction;
• nephrosclerosis;
• leukemia in acute, chronic form;
• cerebral hemorrhages.

Secondary polycythemia (relative)

This form of Vaquez disease is provoked by external and internal factors. With the development of secondary polycythemia, viscous blood with increased volumes fills the vessels, provoking the formation of blood clots. With oxygen starvation of tissues, a compensation process develops:

• the kidneys begin to intensively produce the hormone erythropoietin;
• active synthesis of red blood cells in the bone marrow is triggered.

Secondary polycythemia occurs in two forms. Each of them has its own characteristics. The following varieties are distinguished:

• stressful – caused by an unhealthy lifestyle, prolonged overexertion, nervous disorders, unfavorable working conditions;
• false, in which the total number of red blood cells, leukocytes, platelets in the tests is within the normal range, an increase in ESR causes a decrease in plasma volume.

Causes

The provoking factors for the development of the disease depend on the form of the disease. Primary polycythemia occurs as a result of a neoplastic neoplasm of the red bone marrow. The predetermining causes of true erythrocytosis are:

• genetic malfunctions in the body - mutation of the tyrosine kinase enzyme, when the amino acid valine is replaced by phenylalanine;
• hereditary predisposition;
• bone marrow cancers;
• oxygen deficiency - hypoxia.

The secondary form of erythrocytosis is caused by external causes. Concomitant diseases play an equally important role in development. Provoking factors are:

• climatic conditions;
• living in high mountains;
• congestive heart failure;
• cancerous tumors of internal organs;
• pulmonary hypertension;
• action of toxic substances;
• overstrain of the body;
• x-ray radiation;
• insufficient oxygen supply to the kidneys;
• infections that cause intoxication of the body;
• smoking;
• bad ecology;
• genetic features - Europeans are more likely to get sick.

The secondary form of Vaquez disease is caused by congenital causes - autonomous production of erythropoietin, high affinity of hemoglobin for oxygen. There are also acquired factors for the development of the disease:

• arterial hypoxemia;
• kidney pathologies - cystic lesions, tumors, hydronephrosis, renal artery stenosis;
• bronchial carcinoma;
• adrenal tumors;
• cerebellar hemangioblastoma;
• hepatitis;
• cirrhosis of the liver;
• tuberculosis.

Symptoms of Vaquez disease

The disease, caused by an increase in the number of red blood cells and blood volume, is distinguished by characteristic symptoms. They have their own characteristics depending on the stage of Vaquez's disease. General symptoms of pathology are observed:

• dizziness;
• visual impairment;
• Cooperman's symptom - a bluish tint of the mucous membranes and skin;
• angina attacks;
• redness of the fingers of the lower and upper extremities, accompanied by pain and burning;
• thrombosis of various localizations;
• severe itching of the skin, aggravated by contact with water.

As the pathology progresses, the patient experiences pain syndromes of various localizations. Disorders of the nervous system are observed. The disease is characterized by:

• weakness;
• fatigue;
• temperature increase;
• enlarged spleen;
• noise in ears;
• dyspnea;
• feeling of loss of consciousness;
• plethoric syndrome - burgundy-red color of the skin;
• headache;
• vomit;
• increased blood pressure;
• pain in the hands from touching;
• chilliness of the limbs;
• redness of the eyes;
• insomnia;
• pain in the hypochondrium, bones;
• pulmonary embolism.

initial stage

The disease is difficult to diagnose at the very beginning of its development. The symptoms are mild, similar to a cold or a condition of elderly people corresponding to old age. Pathology is detected accidentally during tests. Symptoms indicate the initial stage of erythrocytosis:

• dizziness;
• decreased visual acuity;
• attacks of headache;
• insomnia;
• noise in ears;
• soreness of fingers from touching;
• cold extremities;
• ischemic pain;
• redness of mucous surfaces and skin.

Expanded (erythremic)

The development of the disease is characterized by the appearance of pronounced signs of high blood viscosity. Pancytosis is noted - an increase in the number of components in analyzes - red blood cells, leukocytes, platelets. The advanced stage is characterized by the presence of:

• redness of the skin to purple shades;
• telangiectasia - pinpoint hemorrhages;
• acute attacks of pain;
• itching, which intensifies when interacting with water.

At this stage of the disease, signs of iron deficiency are observed - split nails, dry skin. A characteristic symptom is a strong increase in the size of the liver and spleen. Patients experience:

• indigestion;
• breathing disorder;
• arterial hypertension;
• joint pain;
• hemorrhagic syndrome;
• microthrombosis;
• ulcers of the stomach, duodenum;
• bleeding;
• cardialgia – pain in the left chest;
• migraine.

In the advanced stage of erythrocytosis, patients complain of lack of appetite. Investigations reveal stones in the gall bladder. The disease is different:

• increased bleeding from small cuts;
• disturbances of rhythm and conduction of the heart;
• swelling;
• signs of gout;
• pain in the heart;
• microcytosis;
• symptoms of urolithiasis;
• changes in taste, smell;
• bruises on the skin;
• trophic ulcers;
• renal colic.

Anemic stage

At this stage of development, the disease enters the terminal stage. The body does not have enough hemoglobin to function normally. The patient has:

• significant enlargement of the liver;
• progression of splenomegaly;
• thickening of the spleen tissue;
• with hardware examination – cicatricial changes in the bone marrow;
• vascular thrombosis of deep veins, coronary, cerebral arteries.

At the anemic stage, the development of leukemia poses a danger to the patient’s life. This stage of Vaquez's disease is characterized by the occurrence of aplastic iron deficiency anemia, the cause of which is the displacement of hematopoietic cells from the bone marrow by connective tissue. In this case, symptoms are observed:

• general weakness;
• fainting;
• feeling of lack of air.

At this stage, if left untreated, the patient will quickly die. Thrombotic and hemorrhagic complications lead to it:

• ischemic form of stroke;
• pulmonary embolism;
• myocardial infarction;
• spontaneous bleeding – gastrointestinal, esophageal veins;
• cardiosclerosis;
• arterial hypertension;
• heart failure.

Symptoms of the disease in newborns

If the fetus has suffered hypoxia during the period of intrauterine development, its body in response begins to increase the production of red blood cells. The provoking factor for the appearance of erythrocytosis in infants is congenital heart disease and pulmonary pathologies. The disease leads to the following consequences:

• formation of bone marrow sclerosis;
• disruption of the production of leukocytes responsible for the newborn’s immune system;
• development of infections leading to death.

At the initial stage, the disease is detected by test results - the level of hemoglobin, hematocrit, and red blood cells. As the pathology progresses, pronounced symptoms are observed already in the second week after birth:

• the baby cries when touched;
• the skin turns red;
• the size of the liver and spleen increases;
• thrombosis appears;
• body weight decreases;
• tests reveal an increased number of red blood cells, leukocytes, and platelets.

Diagnosis of polycythemia

Communication between a patient and a hematologist begins with a conversation, an external examination, and an anamnesis. The doctor finds out heredity, features of the course of the disease, the presence of pain, frequent bleeding, and signs of thrombosis. During admission, the patient is diagnosed with polycythaemic syndrome:

• purplish-red blush;
• intense coloring of the mucous membranes of the mouth and nose;
• cyanotic (blue) color of the palate;
• change in the shape of the fingers;
• red eyes;
• palpation reveals an increase in the size of the spleen and liver.

The next stage of diagnosis is laboratory tests. Indicators that indicate the development of the disease:

• an increase in the total mass of red blood cells in the blood;
• increased number of platelets, leukocytes;
• significant levels of alkaline phosphatase;
• a large amount of vitamin B 12 in the blood serum;
• increased erythropoietin in secondary polycythemia;
• decrease in situration (blood oxygen saturation) – less than 92%;
• decrease in ESR;
• increase in hemoglobin to 240 g/l.

For differential diagnosis of pathology, special types of studies and analyzes are used. Consultations with a urologist, cardiologist, and gastroenterologist are provided. The doctor prescribes:

• biochemical blood test - determines the level of uric acid, alkaline phosphatase;
• radiological examination - reveals an increase in circulating red blood cells;
• sternal puncture - collection of bone marrow from the sternum for cytological analysis;
• trephine biopsy - histology of tissue from the ilium, revealing three-line hyperplasia;
• molecular genetic analysis.

Laboratory research

Polycythemia disease is confirmed by hematological changes in blood parameters. There are parameters that characterize the development of pathology. Laboratory data indicating the presence of polycythemia:

Index	Units	Meaning
Hemoglobin
Circulating red blood cell mass
Erythrocytosis	cells/liter
Leukocytosis		more than 12x109
Thrombocytosis		over 400x109
Hematocrit
Serum vitamin B 12 level
Alkaline phosphatase		more than 100
Color indicator

Hardware diagnostics

After laboratory tests, hematologists prescribe additional tests. To assess the risk of developing metabolic and thrombohemorrhagic disorders, hardware diagnostics are used. The patient undergoes studies depending on the characteristics of the disease. A patient with polycythemia is given:

• Ultrasound of the spleen, kidneys;
• heart examination - echocardiography.

Hardware diagnostic methods help assess the condition of blood vessels, identify the presence of bleeding and ulcers. Appointed:

• fibrogastroduodenoscopy (FGDS) – instrumental study of the mucous membranes of the stomach and duodenum;
• Doppler ultrasound (USDG) of the vessels of the neck, head, veins of the extremities;
• computed tomography of internal organs.

Treatment of polycythemia

Before starting therapeutic measures, it is necessary to find out the type of disease and its causes - the treatment regimen depends on this. Hematologists are faced with the task of:

• in case of primary polycythemia, prevent tumor activity by affecting the tumor in the bone marrow;
• in the secondary form, identify the disease that provoked the pathology and eliminate it.

Treatment of polycythemia includes drawing up a rehabilitation and prevention plan for a specific patient. Therapy involves:

• bloodletting, reducing the number of red blood cells to normal - 500 ml of blood is taken from the patient every two days;
• maintaining physical activity;
• erythocytophoresis – taking blood from a vein, followed by filtration and return to the patient;
• diet;
• transfusion of blood and its components;
• chemotherapy to prevent leukemia.

In difficult situations that threaten the patient’s life, a bone marrow transplant is performed, splenectomy is the removal of the spleen. In the treatment of polycythemia, much attention is paid to the use of medications. The treatment regimen includes the use of:

• corticosteroid hormones - in severe cases of the disease;
• cytostatic agents - Hydroxyurea, Imifos, which reduce the proliferation of malignant cells;
• antiplatelet agents, blood thinners - Dipyridamole, Aspirin;
• Interferon, which increases defenses and enhances the effectiveness of cytostatics.

Symptomatic treatment involves the use of drugs that reduce blood viscosity, prevent thrombosis, and the development of bleeding. Hematologists prescribe:

• to exclude vascular thrombosis - Heparin;
• for severe bleeding - Aminocaproic acid;
• in case of erythromelalgia - pain in the fingertips - non-steroidal anti-inflammatory drugs - Voltaren, Indomethacin;
• for itchy skin - antihistamines - Suprastin, Loratadine;
• in case of infectious genesis of the disease - antibiotics;
• for hypoxic reasons - oxygen therapy.

Phlebotomy or erythrocytopheresis

An effective treatment for polycythemia is phlebotomy. When performing bloodletting, the volume of circulating blood decreases, the number of red blood cells (hematocrit) decreases, and skin itching is eliminated. Features of the process:

• before phlebotomy, the patient is administered Heparin or Reopoliglucin to improve microcirculation and blood fluidity;
• excess is removed using leeches or an incision is made to puncture the vein;
• up to 500 ml of blood is removed at a time;
• the procedure is carried out at intervals of 2 to 4 days;
• hemoglobin is reduced to 150 g/l;
• hematocrit is adjusted to 45%.

Another method of treating polycythemia, erythrocytopheresis, is more effective. During extracorporeal hemocorrection, excess red blood cells are removed from the patient’s blood. This improves hematopoietic processes and increases iron consumption by the bone marrow. Scheme for performing cytopheresis:

1. They create a vicious circle - the patient’s veins of both arms are connected through a special device.
2. Blood is taken from one.P
3. It is passed through a machine with a centrifuge, separator, and filters, where some of the red blood cells are removed.
4. The purified plasma is returned to the patient and injected into a vein in the other arm.

Myelosuppressive therapy with cytostatics

In severe cases of polycythemia, when bloodletting does not produce positive results, doctors prescribe drugs that suppress the formation and reproduction of brain cells. Treatment with cytostatics requires constant blood tests to monitor the effectiveness of therapy. Indications are factors accompanying polycythaemic syndrome:

• visceral, vascular complications;
• skin itching;
• splenomegaly;
• thrombocytosis;
• leukocytosis.

Hematologists prescribe medications taking into account test results and the clinical picture of the disease. Contraindications for cytostatic therapy are childhood. The following medications are used to treat polycythemia:

• Myelobramol;
• Imifos;
• Cyclophosphamide;
• Alkeran;
• Myelosan;
• Hydroxyurea;
• Cyclophosphamide;
• Mitobronitol;
• Busulfan.

Preparations for normalizing the state of blood aggregation

The objectives of treatment for polycythemia: normalization of hematopoiesis, which includes ensuring the liquid state of the blood, its coagulation during bleeding, and restoration of the walls of blood vessels. Doctors face a serious choice of drugs so as not to harm the patient. Prescribed medications that help stop bleeding - hemostatics:

• coagulants – Thrombin, Vikasol;
• fibrinolysis inhibitors – Kontrikal, Ambien;
• stimulators of vascular aggregation – Calcium chloride;
• drugs that reduce permeability - Rutin, Adroxon.

The use of antithrombotic agents is of great importance in the treatment of polycythemia to restore the aggregative state of the blood:

• anticoagulants - Heparin, Girudin, Phenilin;
• fibronolytics – Streptolyasis, Fibrinolysin;
• antiplatelet agents: platelet - Aspirin (Acetylsalicylic acid), Dipyridamole, Indobrufen; erythrocytes - Reogluman, Reopoliglucin, Pentoxifylline.

Recovery prognosis

What awaits a patient diagnosed with polycythemia? Forecasts depend on the type of disease, timely diagnosis and treatment, causes, and the occurrence of complications. Vaquez disease in its primary form has an unfavorable development scenario. Life expectancy is up to two years, which is associated with the complexity of therapy, high risks of strokes, heart attacks, and thromboembolic consequences. Survival can be increased by using the following treatments:

• local irradiation of the spleen with radioactive phosphorus;
• lifelong phlebotomy procedures;
• chemotherapy.

A more favorable prognosis for the secondary form of polycythemia, although the disease can result in nephrosclerosis, myelofibrosis, and erythrocyanosis. Although a complete cure is impossible, the patient’s life is extended for a significant period - over fifteen years - provided:

• constant monitoring by a hematologist;
• cytostatic treatment;
• regular hemocorrection;
• undergoing chemotherapy;
• eliminating factors that provoke the development of the disease;
• treatment of pathologies that caused the disease.

Video

Stage 1 - low-symptomatic, duration up to 5 years or more.

Stage 2A - erythraemic advanced stage without myeloid metaplasia of the spleen - duration 10-20 years.

Stage 2B – erythraemic with myeloid metaplasia of the spleen.

Stage 3 – post-erythemic myeloid metaplasia with or without myelofibrosis.

Vascular complications in polycythemia vera .

Microvascular thrombophilic complications with clinical manifestations in the form of erythromelalgia, headache, transient visual disturbances, angina pectoris.

Thrombosis of arterial and venous vessels, local and multiple.

Hemorrhages and bleeding, spontaneous and provoked by any, even minor, surgical interventions.

DIC syndrome with clinical manifestations in the form of local and multiple thromboses and bleeding (thrombohemorrhagic syndrome).

Diagnostic criteria for polycythemia vera (pvsc, USA).

Increase in the mass of circulating red blood cells: for men more than 36 ml/kg, for women more than 32 ml/kg.

Normal arterial blood oxygen saturation (more than 92%).

Splenomegaly.

Leukocytosis over 12.0x10 9 /l in the absence of infections and intoxications.

Thrombocytosis (over 400.0x10 9 /l).

The phosphatase activity of neutrophils is more than 100 units. (in the absence of intoxication).

Increase in unsaturated vitamin B 12 - binding capacity of blood serum (more than 2200 pg/l).

Classification.

I. Polycythemia vera (erythremia).

II. Secondary absolute erythrocytosis (A, B, C).

A. Based on generalized tissue hypoxia.

1. With arterial hypoxemia.

altitude sickness,

Chronic obstructive pulmonary diseases,

Congenital (blue) heart defects,

Arteriovenous shunts (aneurysms) in the lungs,

Primary pulmonary hypertension, Ayersa–Arrilaghi disease,

Alveolar-capillary blocks of a different origin,

Pickwick syndrome,

Carboxyhemoglobinemia (erythrocytosis of tobacco smokers).

2. Without arterial hypoxemia:

Hemoglobinopathies with increased oxygen affinity (hereditary erythrocytosis),

Congenital deficiency of 2,3-diphosphoglycerate in erythrocytes.

B. Paraneoblastic erythrocytosis:

Kidney cancer

Cerebellar hemangiblastoma,

Common hemangioblastosis (Hippel-Lindau syndrome),

Hepatoma,

Fibroids,

Atrial myxoma,

Tumors of the endocrine glands,

Rarely other tumors.

C. Nephrogenic erythrocytosis (based on local renal hypoxia).

Hydronephrosis,

Polycystic,

Renal artery stenosis,

Anomaly of kidney development and other diseases.

Post-transplant erythrocytosis.

III. Relative (hemoconcentration) erythrocytosis.

IV. Primary erythrocytosis.

Clinical picture – The history includes indications of skin itching associated with taking water procedures, slightly elevated red blood counts, duodenal ulcer, and sometimes the first manifestations are vascular complications (erythromelalgia, venous thrombosis, necrosis of the fingers of the lower extremities, nosebleeds).

Clinical symptoms are divided into:

caused by an increase in the mass of circulating red blood cells (plethora),

caused by the proliferation of granulocytes and platelets (myeloproliferative).

An increase in the mass of circulating erythrocytes and hematocrit leads to an increase in blood viscosity, a slowdown in blood flow and stasis at the microcirculation level, and an increase in peripheral vascular resistance. Characteristic is erythrocyanotic coloration of the skin of the hands and face, visible mucous membranes, especially the soft palate (Cooperman's symptom). The limbs are hot to the touch, patients cannot tolerate heat well. The cause of splenomegaly in stage 2A is increased deposition and sequestration of blood cells, in stage 2B is the progressive development of myeloid metaplasia. Liver enlargement in stage 2A is due to increased blood supply, in stage 2B – the progressive development of myeloid metaplasia. Both stages are characterized by the development of liver fibrosis, cholelithiasis, and a characteristic complication is liver cirrhosis. At the time of diagnosis, 35-40% of patients have arterial hypertension:

symptomatic (pletoric) hypertension associated with increased blood viscosity, well corrected by bloodletting,

concomitant essential hypertension, aggravated by plethora,

renovascular hypertension caused by sclerotic or thrombophilic stenosis of the renal arteries.

Sometimes nephrogenic hypertension develops (complication of urate diathesis and chronic pyelonephritis).

50-55% of patients have skin itching associated with taking water procedures. Visceral complications include ulcers/erosions of the stomach and duodenum. Disorders of uric acid metabolism - renal colic, gout, gouty polyarthralgia.

The simultaneous tendency to hemorrhagic and thrombotic complications is a unique feature of this disease. Microcirculatory vascular diseases account for 58-80% of all complications.

Microcirculatory thrombophilic complications - erythromelalgia (attacks of acute burning pain in the tips of the fingers of the extremities, accompanied by their sharp redness or blueness and swelling. The pain is relieved by taking aspirin.

Thrombosis of the veins of the lower extremities occurs with the clinical picture of thrombophlebitis, in untreated patients it is prone to recurrence, after which brown spots remain, often melasma of the lower third of the leg, trophic ulcers.

Possible myocardial infarction, pulmonary embolism, thrombosis in the portal vein system with the development of portal hypertension.

Hemorrhagic syndrome is manifested by spontaneous bleeding of the gums, nosebleeds, ecchymosis, and the development of massive bleeding during minor surgical interventions is possible. Thrombocytosis increases the risk of developing all thrombophilic complications. In 50% of patients there is spontaneous aggregation of platelets in the bloodstream, very often with thrombocytosis of more than 900 thousand.

Erythrocytosis causes difficulties in differential diagnosis with erythremia in cases where there is no splenomegaly; about 30% of patients do not have leukocytosis and thrombocytosis.

Differential diagnosis - measurement of the mass of circulating erythrocytes (Cr 51), the volume of circulating plasma (serum albumin, labeled I 131) - with a normal mass of circulating erythrocytes and a decrease in the volume of circulating plasma - a diagnosis of relative erythrocytosis. The main reason for this erythrocytosis is taking diuretics and smoking. Typically, patients with elevated blood counts have normal coloration of the skin and mucous membranes.

With an increase in the mass of circulating erythrocytes, differential diagnosis between erythremia and absolute erythrocytosis: artoxihemometry and pO2 measurement (several times a day). If arterial hypoxemia is excluded, p50 O2 and the oxyhemoglobin dissociation curve are determined. When it shifts to the left - hemoglobinopathy with increased affinity for oxygen or congenital deficiency of 2,3 diphosphoglycerate in erythrocytes.

In smokers, carboxyhemoglobin is examined in the morning, afternoon and evening 5 days after stopping smoking.

Gaisbeck syndrome is essential arterial hypertension, excess body weight, neurotic personality, activation of the sympathetic-adrenal system and erythrocytosis in the blood with a normal mass of circulating red blood cells and a decrease in the volume of circulating plasma.

If hypoxic erythrocytosis is excluded, the kidneys are examined, then other organs and systems.

Trephine biopsy is about 90% informative. Neoplastic proliferation is distinguished from reactive proliferation (bleeding, sepsis, cancer of certain localizations, renovascular hypertension). Rarely, there may be no changes in the bone marrow with erythremia; the diagnosis is made during long-term observation.

To differentiate between erythremia and symptomatic erythrocytosis, the level of erythropoietin in the blood serum and the colony-forming ability of erythroid precursors in blood and bone marrow in vitro are determined. With erythremia, the level of endogenous erythropoietin and the ability of erythroid precursors to spontaneously form colonies in culture are reduced (without the addition of erythropoietin).

Erythremia is confirmed by large forms of platelets, a violation of their aggregation properties, an increase in the number of neutrophils more than 7 thousand, an increase in the content of alkaline phosphatase in them, the detection of a high content of IgG receptors on the neutrophil membrane, an increase in the content of lysozyme and B 12-binding protein (a product of neutrophil secretion in plasma), an increase in the absolute number of basophils (acrylic blue staining) more than 65 in 1 μl, an increase in the content of histamine in the blood and urine (basophil secretion product)

IP outcomes – posterythremic myeloid metaplasia and myelofibrosis, transformation into acute leukemia.

Treatment of polycythemia vera.

Bloodletting– unloading of the vascular bed is achieved, which quickly gives a symptomatic effect, does not affect thrombocytosis and leukocytosis. Repeated bloodletting contributes to the development of iron deficiency and can cause reactive thrombocytosis. Bloodletting is carried out to a hematocrit level of less than 0.45% and hemoglobin 140-150 g/l and maintained at this level. Bloodletting is prescribed for:

benign erythremia.

its erythrocythemic variant.

reproductive age patient.

relapses of erythremia after cytostatic therapy with a decrease in the level of leukocytes and platelets.

Bloodletting does not have a leukemic effect; it quickly normalizes the mass of circulating cells and blood viscosity, which prevents hemorrhagic and thrombotic complications. Bloodletting reduces skin itching, urate diathesis, visceral complications, has little effect on the size of the spleen, and is sometimes complicated by vascular thrombosis.

Bloodletting is carried out in a volume of 500 ml every other day in the hospital or every 2 days on an outpatient basis. In old age, with diseases of the cardiovascular system, poor tolerance - 350 ml, the intervals between procedures are increased. On the eve of bloodletting, during the treatment period and 1-2 days after it (depending on reactive thrombocytosis), antiplatelet agents (aspirin or ticlid) are prescribed, and before bloodletting, rheopolyglucin is prescribed. Before bloodletting - heparin IV 5 thousand units. and 5 thousand units each. x 2 times a day s/c for several days after.

Then every 6-8 weeks the blood picture is monitored; in case of relapse of plethoric syndrome and hemoglobin more than 140 g/l - repeated bloodletting.

For erythromelalgia(especially in the presence of thrombocytosis) - aspirin 40-80 mg daily, annually - examination by an ophthalmologist, neurologist. For the prevention of thromboembolic complications - ticlid, Plavix, pentoxifylline.

Cytostatic therapy – with erythrocytosis with leukocytosis and thrombocytosis, skin itching that persists against the background of bloodletting, splenomegaly, visceral and vascular complications, serious condition of the patient, insufficient effect of bloodletting, poor tolerance and complications of thrombocytosis, age over 50 years, inability to organize bloodletting therapy and control it.

With erythremia with thrombocythemia, young patients - hydrea orally 30 mg/kg per day in two doses for a week, then 15 mg/kg daily until leukocytosis is above 3.5 thousand, thrombocytosis is more than 100 thousand, if necessary, the maintenance dose is increased to 20 mg/kg per day.

INF-ά - 3-5 IU x 3 times a week, especially with hyperthrombocytosis.

For hyperthrombocytosis - anagrelide (affects the ripening of megakaryocytes).

Cytostatic therapy is usually combined with bloodletting.

Treatment monitoring is carried out weekly, and towards the end of treatment - every 5 days. Leukocytes should not be allowed to drop below 5 thousand, platelets - below 100 thousand. The results are assessed after 2-3 months. Maintenance therapy with cytostatics is not recommended due to low efficiency and leukemic effect. Timely course treatment in full or reduced volume is preferable if there is a tendency to relapse.

For urate diathesis, allopurinol is prescribed. When treated with bloodletting and cytostatics, it is prescribed prophylactically in a daily dose of 200-500 mg.

For acute vascular thrombosis - antiplatelet agents, heparin, FFP.

Prednisolone is prescribed for suspected autoimmune origin of anemia and thrombocytopenia, in order to reduce the size of the spleen:

90-120 mg/day for 2 weeks with transition to medium and small doses if effective and discontinuation if ineffective.

20-30 mg, then 15-10 mg for 2-3 months with mandatory cancellation.

For post-erythraemic myelofibrosis, increasing leukocytosis (more than 30 thousand), progression of splenomegaly - short courses of myelosan (4-2 mg/day for 2-3 weeks)

In the anemic stage of erythremia, splenectomy is possible:

with severe hemolytic anemia that does not respond to conservative therapy and requires frequent transfusions.

deep thrombocytopenia with hemorrhagic syndrome with ineffective conservative therapy.

recurrent splenic infarctions and mechanical compression phenomena.

extrahepatic portal block.

For postoperative thrombocytosis, antiplatelet agents are prescribed.

Prevention of vascular complications in erythremia - aspirin 40 mg/day. During the period of remission, there is no need to take medications, except for the presence of other risk factors for vascular complications. The danger of hemorrhagic complications disappears when the hematocrit level is normalized.

For vascular thrombosis - aspirin 0.5-1 g for 5-7 days under control (risk of internal bleeding), at the same time - heparin in mini doses, fraxiparin, with a decrease in ATIII levels during heparin therapy - FFP 400 ml IV in a bolus 1 once every 3 days, the duration of anticoagulant therapy is 1-2 weeks. For myocardial infarction, ischemic stroke, deep vein thrombosis of the thigh - thrombolytic therapy.

Treatment of microcirculatory vascular complications (erythromelalgia, angina, migraine) – aspirin – 0.3-0.5 g/day. or other disaggregants. Bleeding after tooth extraction usually stops spontaneously.

Surgeries for untreated erythremia are dangerous (there may be fatal hemorrhagic or thrombotic complications). If urgent surgical intervention is necessary, the patient is prepared using bloodletting and transfusion of FFP. Aspirin is discontinued 7 days before any operation, with high thrombocytosis - hydrea 2-3 g/day + bleeding. To prevent postoperative complications - heparin in mini doses, for patients with thrombocytosis - aspirin in small doses.

In case of arterial hypertension, nifedipine is poorly tolerated and responds well to β-blockers, ACE inhibitors, and Arifon.

Symptomatic therapy for skin itching - periactin (cyproheptadine) - has an antihistamine, antiserotonin effect, but gives a strong hypnotic effect and is poorly tolerated.

Iron-deficiency anemia- clinical-hematological syndrome, characterized by impaired hemoglobin synthesis due to iron deficiency developing as a result of various pathological (physiological) processes and manifested by symptoms of anemia and sideropenia.

Along with the developed symptom complex of iron deficiency anemia, there is a hidden iron deficiency, characterized by a decrease in the iron content in blood stores and serum with normal hemoglobin levels. Latent iron deficiency is a prestage of iron deficiency anemia (latent anemia, “anemia without anemia”) and is manifested by anemic syndrome with progression and lack of compensation of the iron deficiency state.

Iron deficiency anemia is the most common anemic syndrome and accounts for approximately 80% of all anemias. According to WHO (1979), the number of people with iron deficiency worldwide reaches 200 million people. The groups most vulnerable to the development of iron deficiency anemia include children of younger age groups, pregnant women and women of childbearing age.

Etiology and pathogenesis The question of the etiology of iron deficiency anemia is resolved quite simply. As the name itself says, the main etiological aspect of the disease is iron deficiency in the human body. However, the ways in which this deficiency occurs are very, very different: more often it is blood loss (menstrual blood loss, microblood loss from the gastrointestinal tract), an increase in the body's need for iron, which cannot be replenished by homeostatic mechanisms.

Clinical manifestations Iron deficiency anemia is caused, on the one hand, by the presence of anemic syndrome, and on the other, by iron deficiency (hyposiderosis), to which various organs and tissues are sensitive.

Anemic syndrome is manifested by symptoms nonspecific to anemia of any origin. The main complaints of patients are weakness, increased fatigue, dizziness, tinnitus, spots before the eyes, palpitations, shortness of breath during exercise. The severity of anemia depends on the rate of decrease in hemoglobin levels and the patient’s physical activity.

Sideropenic syndrome. Its clinical manifestations are associated with tissue deficiency of iron, which is necessary for the functioning of organs and tissues. The main symptoms are observed in the skin and mucous membranes. There is dry skin and a violation of the integrity of the epidermis. Ulcerations and cracks with an inflammatory shaft appear in the corners of the mouth. Typical clinical manifestations are brittleness and layering of nails, the appearance of transverse striations. Hair falls out and splits. Some patients report a burning sensation on the tongue. Taste distortions are possible in the form of an irrepressible desire to eat chalk, toothpaste, ashes, etc., as well as an addiction to certain odors (acetone, gasoline).

One of the signs of hyposiderosis is difficulty swallowing dry and solid food - Plummer-Vinson syndrome. In girls, less often in adult women, dysuric disorders and sometimes urinary incontinence when coughing or laughing are possible. Children may experience symptoms of nocturnal enuresis. Symptoms associated with iron deficiency include muscle weakness, which is associated not only with anemia, but also with a deficiency of iron-containing enzymes.

When examining patients, attention is drawn to the pallor of the skin, often with a greenish tint. Hence the old name for this type of anemia - chlorosis (greenness). Often in patients with iron deficiency anemia there is a distinct “blue” appearance of the sclera (a symptom of blue sclera).

The main laboratory sign allowing one to suspect the iron deficiency nature of anemia is a low color indicator, which reflects the hemoglobin content in the erythrocyte and is a calculated value. Since in iron deficiency anemia the synthesis of hemoglobin is impaired due to a lack of “building material”, and the production of red blood cells in the bone marrow decreases slightly, the calculated color index is always below 0.85, often 0.7 and below (all iron deficiency anemias are hypochromic).

The following erythrocyte indices are calculated:

Average hemoglobin concentration in erythrocyte (MCHC) – represents the ratio of the Hb content in g/l to the hematocrit level in %. Normal is 30-38 g/dl.

These indicators are analogous to the color indicator.

Average red blood cell volume (MCV) is the ratio of Ht in 1 mm3 to the number of red blood cells in 1 mm3 (μm3 or femtoliter - fl) or Ht in 1 mm3 x 10 and divided by the number of red blood cells (million cells/mm3).

RDW– width of distribution of erythrocytes by volume. It is calculated from the coefficient of variation of the erythrocytometric curve and expressed as a percentage. Normal is 11.5-14.5%. This indicator more accurately reflects the heterogeneity of red blood cells

In a peripheral blood smear, hypochromic erythrocytes predominate, microcytes - the hemoglobin content in them is less than in erythrocytes of normal size. Along with microcytosis, anisocytosis (unequal value) and poikilocytosis (various forms) of erythrocytes are noted. The number of siderocytes (red blood cells with iron granules) is sharply reduced to the point of complete absence. The content of reticulocytes is within normal limits.

The iron content in the blood serum tested before the start of iron therapy is reduced, often significantly. Along with the determination of serum iron, the study of the total iron-binding capacity of serum (TIBC), which reflects the degree of “starvation” of the serum or saturation of transferrin with iron, is of diagnostic importance. In patients with iron deficiency anemia, there is an increase in CVS and a decrease in the transferrin saturation coefficient.

Due to the fact that iron reserves in iron deficiency anemia are depleted, there is a decrease in the serum content of ferritin - an iron-containing protein, which, along with hemosiderin, reflects the amount of iron reserves in the depot.

Assessment of iron reserves can be carried out by determining the iron content in the urine after the administration of certain complexes that bind iron and excrete it in the urine, in particular desferal, as well as by staining blood and bone marrow smears for iron and counting the number of siderocytes and sideroblasts. The number of these cells in iron deficiency anemia is significantly reduced.

Treatment. There are 3 stages of treatment for iron deficiency anemia. The first stage is relief therapy, replenishing hemoglobin levels and peripheral iron reserves; the second is therapy that restores tissue reserves; the third is anti-relapse treatment. Pharmacy now provides a number of excellent oral medications for the treatment of iron deficiency anemia. These include: hemostimulin, conferon, tardiferon, fenyuls, ferramide, ferrograd-500, ferrogradument, ferrofolic-500, ferrocal, ferroplex, ferroceron, fesovit, sorbifer-durules and some others. All of them are available in capsules or in the form of tablets and dragees. As a rule, relief therapy requires 20 to 30 days. During this time, hemoglobin is restored, the level of fatty acids increases, and the blood volume and lifespan decreases. However, the iron depot is not completely replenished. In this regard, a second stage of treatment, replenishing iron reserves, is necessary. This is best achieved by taking any of the above iron supplements orally for 3-4 months. Anti-relapse treatment consists of periodically prescribing iron supplements to patients with a high risk of relapse of iron deficiency anemia - women with heavy and prolonged periods, other sources of blood loss, long-term nursing mothers, etc.

AT 12 - DEFICIENCY ANEMIA.

B12-deficiency anemia belongs to the group of megaloblastic anemias. Megaloblastic anemia is a group of diseases characterized by weakened DNA synthesis, as a result of which the division of all rapidly proliferating cells (hematopoietic cells, skin cells, gastrointestinal cells, mucous membranes) is disrupted. Hematopoietic cells are among the most rapidly multiplying elements, so anemia, as well as often neutropenia and thrombocytopenia, come to the fore in the clinic. The main cause of megaloblastic anemia is a deficiency of cyanocobalamin or folic acid.

Etiology and pathogenesis. The role of cyanocobalamin and folic acid in the development of megaloblastic anemia is associated with their participation in a wide range of metabolic processes and metabolic reactions in the body. Folic acid in the form of 5,10-methylenetetrahydrofolate is involved in the methylation of deoxyuridine necessary for the synthesis of thymidine, resulting in the formation of 5-methyltetrahydrofolate.

Cyanocobalamin is a cofactor in the methyltransferase catalytic reaction that resynthesizes methionine and simultaneously regenerates 5-methyltetrahydrofolate into tetrahydrofolate and 5,10 methylenetetrahydrofolate.

With a deficiency of folate and (or) cyanocobalamin, the process of incorporation of uridine into the DNA of developing hematopoietic cells and the formation of thymidine are disrupted, which causes DNA fragmentation (blocking its synthesis and disrupting cell division). In this case, megaloblastosis occurs, accumulation of large forms of leukocytes and platelets occurs, their early intramedullary destruction and shortening of the life of circulating blood cells. As a result, hematopoiesis is ineffective, anemia develops, combined with thrombocytopenia and leukopenia,

In addition, cyanocobalamin is a coenzyme in the conversion of methylmalonyl-CoA to succinyl-CoA. This reaction is necessary for the metabolism of myelin in the nervous system, and therefore, with cyanocobalamin deficiency, along with megaloblastic anemia, damage to the nervous system is noted, while with folate deficiency, only the development of megaloblastic anemia is observed.

Cyanocobalamin is found in food products of animal origin - liver, kidneys, eggs, milk. Its reserves in the body of an adult (mainly in the liver) are large - about 5 mg, and if we take into account that the daily loss of the vitamin is 5 mcg, then complete depletion of reserves in the absence of intake (malabsorption, with a vegetarian diet) occurs only after 1000 days . Cyanocobalamin in the stomach binds (against the background of an acidic reaction of the environment) with an internal factor - a glycoprotein produced by the parietal cells of the stomach, or other binding proteins - K-factors present in saliva and gastric juice. These complexes protect cyanocobalamin from destruction during transport through the gastrointestinal tract. In the small intestine, at an alkaline pH, under the influence of pancreatic juice proteinases, cyanocobalamin is cleaved from K-proteins and combines with intrinsic factor. In the ileum, the intrinsic factor complex with cyanocobalamin binds to specific receptors on the surface of epithelial cells, the release of cyanocobalamin from intestinal epithelial cells and transport to tissues occurs with the help of special blood plasma proteins - transcobalamins 1/2,3.

Folic acid found in green plant leaves, fruits, liver, and buds. Folate stores are 5-10 mg, the minimum requirement is 50 mcg per day. Megaloblastic anemia can develop after 4 months of complete lack of dietary folate intake.

Various etiological factors can cause deficiency of cyanocobalamin or folic acid (less commonly, combined deficiency of both) and the development of megaloblastic anemia.

Shortage cyanocobalamin may be due to the following reasons:

intrinsic factor deficiency: pernicious anemia, gastrectomy, damage to the gastric epithelium by chemicals, infiltrative changes in the stomach (lymphoma or carcinoma), Crohn's disease, celiac disease, resection of the ileum, atrophic processes in the stomach and intestines,

Increased utilization of vitamin B-12 by bacteria due to their overgrowth: condition after gastrointestinal anastomosis, jejunal diverticula, intestinal stasis or obstruction due to strictures,

Helminthic infestation: wide tapeworm,

Absorbing site pathology: ileal tuberculosis, small intestinal lymphoma, sprue, regional enteritis,

Other causes: congenital absence of transcobalamin 2 (rare), malabsorption caused by the use of neomycin, colchicine.

Causes of folate deficiency may include:

1. Insufficient intake: poor diet, alcoholism, anorexia nervosa, parenteral nutrition, unbalanced nutrition in the elderly

2. Malabsorption: malabsorption, changes in the intestinal mucosa, celiac disease and sprue, Crohn's disease, regional ileitis, intestinal lymphoma, decreased reabsorbing surface after resection of the jejunum, taking anticonvulsants 3.Increasing demand: pregnancy, hemolytic anemia, exfoliative dermatitis and psoriasis

4. Violation of disposal: alcoholism, folate antagonists: trimethoprim and methotrexate, inborn errors of folate metabolism.

A classic example of megaloblastic anemia is pernicious (B 12 deficiency anemia) anemia. More often, people over 40-50 years old suffer from this anemia.

Clinical picture: anemia develops relatively slowly and may be asymptomatic. Clinical signs of anemia are nonspecific: weakness, fatigue, shortness of breath, dizziness, palpitations. Patients are pale and subicteric. There are signs of glossitis - with areas of inflammation and atrophy of the papillae, a varnished tongue, and there may be an enlargement of the spleen and liver. Gastric secretion sharply decreases. Fibrogastroscopy reveals atrophy of the gastric mucosa, which is confirmed histologically. Symptoms of damage to the nervous system (funicular myelosis) are also observed, which do not always correlate with the severity of anemia. The neurological manifestations are based on demyelination of nerve fibers. Distal paresthesia, peripheral polyneuropathy, sensitivity disorders, and increased tendon reflexes are noted. Thus, B 12 deficiency anemia is characterized by a triad: blood damage, gastrointestinal damage, and nervous system damage.

Basic diagnostic information is obtained from the study of peripheral blood and bone marrow. To treat polycythemia, bloodletting, erythrocytapheresis, and chemotherapy are used.

Polycythemia

Polycythemia (Vaquez disease, erythremia, erythrocytosis) is a disease of the group of chronic leukemias, characterized by increased production of red blood cells, platelets and leukocytes, an increase in blood volume, and splenomegaly. The disease is a rare form of leukemia: 4-5 new cases of polycythemia per 1 million population are diagnosed annually. 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 myeloblastic leukemia, erythromyelosis, and chronic myeloid leukemia.

Causes of polycythemia

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

In polycythemia, there are 2 types of erythroid hematopoietic precursor cells in the bone marrow: some of them behave autonomously, their proliferation is not regulated by erythropoietin; others, as expected, are erythropoietin-dependent. It is believed that the autonomous population of cells 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 coagulation properties of blood, 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 supply to 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 normal red blood cell counts and decreased plasma volume. This condition is called stress or false polycythemia and is not discussed within the scope of this article.

Polycythemia vera (erythremia) can be primary or secondary in origin. The primary form is an independent myeloproliferative disease, which is based on damage to the myeloid lineage of hematopoiesis. Secondary polycythemia usually develops with increased erythropoietin activity; this condition is a compensatory reaction to general hypoxia and can occur with chronic pulmonary pathology, “blue” heart defects, adrenal tumors, hemoglobinopathies, when climbing to altitude or smoking, etc.

Polycythemia vera goes through 3 stages in its development: initial, advanced and terminal.

Stage I (initial, asymptomatic) – lasts about 5 years; is asymptomatic or with minimally expressed clinical manifestations. Characterized by moderate hypervolemia, slight erythrocytosis; The size of the spleen is normal.

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

• IA – without myeloid transformation of the spleen. Erythrocytosis, thrombocytosis, and sometimes pancytosis are noted; according to the myelogram - hyperplasia of all hematopoietic germs, pronounced megakaryocytosis. Duration of the advanced stage of erythremia.
• IIB – with the presence of myeloid metaplasia of the spleen. Hypervolemia, hepato- and splenomegaly are pronounced; 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 into other hemoblastoses.

Symptoms of polycythemia

Erythremia develops over a long period of time, gradually, and can be detected accidentally during a blood test. Early symptoms, such as heaviness in the head, tinnitus, dizziness, blurred vision, chilly limbs, sleep disturbance, etc., are often attributed to old age or concomitant diseases.

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

Another distinctive symptom of polycythemia is skin itching, which intensifies after water procedures and sometimes becomes unbearable. Specific manifestations of polycythemia also include 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 enlarges somewhat less frequently. 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 disruption of the trophism of the skin and mucous membranes are trophic ulcers of the leg, gastric and duodenal ulcers. The most common complications in the polycythemia clinic are vascular thrombosis of the 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 thrombus formation, patients with polycythemia are prone to hemorrhagic syndrome with the development of spontaneous bleeding of various locations (gingival, nasal, from the esophageal veins, gastrointestinal, etc.).

Diagnosis of polycythemia

Hematological changes characterizing polycythemia are decisive in the diagnosis. A blood test reveals erythrocytosis (up to 6.5-7.5x10 12 /l), increased 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. Reliable confirmation of erythremia is an increase in the mass of circulating red blood cells (more than ml/kg).

To study the bone marrow in polycythemia, it is more informative to perform a trepanobiopsy rather than a sternal puncture. Histological examination of the biopsy specimen reveals panmyelosis (hyperplasia of all hematopoietic germs), and 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 - liver function tests, general urine analysis, ultrasound of the kidneys, ultrasound of the veins of the extremities, echocardiography, ultrasound of the vessels of the head and neck, EGD, etc. If there is a threat of thrombohemorrhagic and metabolic disorders, consultations with the appropriate narrow specialists: neurologist, cardiologist, gastroenterologist, urologist.

Treatment and prognosis of polycythemia

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

In case of pronounced clinical and hematological changes, the development of vascular and visceral complications, they resort to myelosuppressive therapy with cytostatics (busulfan, mitobronitol, cyclophosphamide, etc.). Radioactive phosphorus therapy is sometimes given. To normalize the state of aggregation of the blood, heparin, acetylsalicylic acid, dipyridamole are prescribed under the control of a coagulogram; for hemorrhages, platelet transfusions are indicated; for 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 and undergo courses of hemoexfusion therapy. With polycythemia there is a high risk of thromboembolic and hemorrhagic complications. The incidence of transformation of polycythemia into leukemia is 1% in patients who have not undergone chemotherapy treatment, and 11-15% in those receiving cytotoxic therapy.

Symptoms of polycythemia vera and prognosis for life with erythremia

Erythremia (polycythemia vera, Vaquez disease) is a hereditary disease of the blood system, occurring mainly in older women.

This pathology is characterized by malignant bone marrow hypertrophy. 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 blood, a decrease in the speed of blood flow through the vessels, and, as a consequence, an increase in thrombus formation and a 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 somewhat less frequently; the incidence of this pathology is approximately 3:2.

On average, Vaquez disease occurs around 40 years of age, with symptoms peaking between 60 and 70 years of age. There is a hereditary predisposition to the disease. In the population, erythremia is quite rare - about 30 cases per million population.

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 reasons are blood stagnation and hemoglobin restoration. Due to reduced blood flow, red blood cells remain in one place longer, which leads to the restoration of the hemoglobin they contain, 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 intensely cherry-colored neck. In addition, visible swollen veins are clearly visible under the skin. When studying the mucous membranes, one can observe a characteristic Kuperman symptom - a change in the color of the soft palate while the color of the hard palate remains unchanged.
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. Spleno- and hepatomegaly. An increase in these organs is observed in most hematological diseases. If a patient develops erythremia, then the increased concentration of cells in the blood can lead to increased blood flow in these organs, and as a result, their enlargement. This can be determined by palpation or instrumental studies. Megalia syndrome is eliminated on its own after the hemogram parameters are normalized, that is, when the blood test returns to normal.
5. Thrombosis. Due to the high concentration of cells in the blood and decreased blood flow, a large number of blood clots form in places where the vascular intima is damaged, which leads 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 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 certain metabolic disorders. With polycythemia, there may be an increase in the level of uric acid in the blood and its deposition in the joint area. In rare cases, pain occurs when 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 come first (all symptoms are caused by decreased tissue oxygenation, impaired blood circulation in certain parts of the body). When diagnosing, they are not used as mandatory criteria, since they can correspond to any systemic disease.

Stages and degrees of polycythemia

Polycythemia vera occurs in three stages (phases):

• stage of initial manifestations. At this stage, the patient does not make specific complaints. He is worried about general weakness, increased fatigue, and 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;
• advanced stage (clinical stage). This stage is characterized by the appearance of headaches and changes in the color of the skin and mucous membranes. Pain syndrome develops quite late and indicates advanced disease;
• terminal stage. At this stage, damage to internal organs due to ischemia and dysfunction of all body systems are maximally manifested. Death may occur due to secondary pathology.

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

Diagnosis of Vaquez disease

To make a diagnosis, a general blood test plays a decisive role. It exhibits pronounced erythrocytosis, an increase in hemoglobin levels 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 the concomitant pathology, it is recommended to conduct a biochemical analysis, which provides information about the condition of the liver and kidneys. In case of massive thrombosis, the state of blood coagulation factors is assessed by analyzing its coagulability - a coagulogram.

Other studies (ultrasound, CT, MRI) provide 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 Vaquez disease, there are relatively few treatments for it. It depends on what the hemogram analysis showed, whether a cytological syndrome has developed and what symptoms the patient has.

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

1. Bloodletting. This method appeared quite a long time ago, however, despite its primitiveness, it is still used to this day. The essence of the procedure is to remove excess blood from the patient’s body. This method can effectively reduce plethora syndrome (plethora), reduce the concentration of red blood cells in the patient’s blood, and 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 4.5x10^12 degrees). During one procedure, about 300-400 ml of the patient’s blood is removed, previously diluted with a solution of rheopolyglucins and heparin.
2. Erythrocytopheresis– a procedure aimed at hardware removal of excess red blood cells from the patient’s body. The procedure is based on the principle of creating an artificial blood circulation with a so-called filter for red blood cells. Their excess remains on the filter membranes, and purified blood is returned 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 red blood cell removal is a normal blood test.

Such treatment should be accompanied by the prescription 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 to the treatment regimen (if the cause of bone marrow hyperplasia is cancer), interferons (if secondary viral complications develop) or hormones (mainly dexamethasone and prednisolone are used), which can improve the prognosis of the disease.

Complications, consequences and prognosis

All complications of the disease are caused by the development of vascular thrombosis. As a result of their blockage, infarctions of internal organs (heart, liver, spleen, brain) and obliterating atherosclerosis (when thrombosis of the vessels of the lower extremities affected by atherosclerotic plaques) can develop. Excess hemoglobin in the blood provokes the development of hemochromatosis, urolithiasis or gout.

All of them develop secondaryly and require elimination of the underlying cause - erythrocytosis, for the most effective treatment.

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 is malignant, that is, the prognosis is unfavorable, and secondary complications develop much faster. Accordingly, the later the development of the disease is observed, the more benign it is. When adequately prescribed medications are used, the lifespan 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 of what the outcome of erythremia could be, it should be noted that it all depends on:

• what secondary processes have developed
• what are their reasons
• how long have they been around
• 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, a transition from polycythemia to the chronic form of myeloblastic leukemia is observed. The lifespan with it remains almost the same, and with the correct selection of drugs can reach tens of years (the prognosis is relatively

Polycythemia (erythremia, Vaquez'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 also carry out 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 Vaquez 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 last long. Various reasons can cause sudden redness of the face: fever, increased blood pressure, hot flashes during menopause, recent tanning, an awkward situation, and emotionally labile people generally tend to blush often, even if those around them do not see any prerequisites for this.

Polycythemia is different. Here the redness is persistent, not transient, evenly distributed throughout the face. The color of excessively “healthy” plethora is rich, bright cherry.

What kind of disease is polycythemia?

Polycythemia vera (erythremia, Vaquez disease) belongs to the group of hemoblastoses (erythrocytosis) or chronic leukemia with a benign course. The disease is characterized by the proliferation of all three germs of hematopoiesis with a significant advantage of the erythrocyte and megakaryocyte, due to which there is an increase not only in the number of red blood cells - red blood cells, but also the rest of the blood cells that originate from these sprouts, where the source of the tumor process is the affected myelopoiesis precursor cells. They are the ones who begin uncontrolled proliferation and differentiation into mature forms of red blood cells.

The ones that suffer the most under such conditions are immature red blood cells, which are hypersensitive to erythropoietin even in small doses. With polycythemia, an increase in leukocytes of the granulocytic series (primarily band and neutrophils) and platelets. 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 path of reproduction and maturation.

Cancer or not cancer?

Erythremia is not to say that it occurs all the time, but in a town of 25 thousand people there are a couple of people, and for some reason this disease “loves” men aged 60 or so more, although anyone can encounter such a pathology age. True, polycythemia vera is absolutely not typical for newborns and young children, so if erythremia is detected in a child, then most likely it will be secondary character and be a symptom and consequence of another disease (toxic dyspepsia, stress erythrocytosis).

For many people, the disease classified as leukemia (and it does not matter: acute or chronic) is primarily associated with blood cancer. Here it is interesting to figure out: 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 polycythemia vera 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.

Vaquez disease refers to malignant tumors, but is characterized by high cell differentiation. 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, when significant changes occur in erythropoiesis, the disease becomes acute and acquires more “evil” features and manifestations. This is what it is like – true polycythemia, the prognosis of which will depend entirely on how quickly it progresses.

Why do sprouts grow incorrectly?

Any patient suffering from erythremia sooner or later asks the question: “Why did this “disease” happen to me?” Finding 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 stated unambiguously. There can only be one clue for a doctor to find out 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 Vaquez disease may be associated with trisomy 8 and 9 pairs (47 chromosomes) or another disorder of the chromosomal apparatus, for example, loss of a section (deletion) of the long arm C5, C20, but these are still guesses, although based on conclusions of scientific research.

Complaints and clinical picture

If there is nothing to say about the causes of polycythemia, then a lot can be said about the clinical manifestations. They are bright and varied, since already from the 2nd stage of development of the disease, literally all organs are involved in the process. The patient’s subjective sensations are of a general nature:

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

Complaints characteristic of this disease and characterized by it:

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

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

redness of the skin due to polycythemia

As the disease further develops, 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 heart area, reminiscent of angina pectoris;
3. Painful sensations 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. Enlarged liver and spleen;
5. Peptic ulcer of the stomach and duodenum;
6. Dysuria (difficulty urinating) and pain in the lumbar region due to the development of uric acid diathesis, caused by a shift in the buffer systems of the blood;
7. Pain in bones and joints as a result hyperplasia(excessive growth) bone marrow;
8. Gout;
9. Manifestations of a hemorrhagic nature: bleeding (nose, gum, intestinal) and skin hemorrhages;
10. Injections of conjunctival vessels, which is why the eyes of such patients are called “rabbit eyes”;
11. Telangiectasia;
12. Tendency to thrombosis of veins and arteries;
13. Varicose veins of the leg;
14. Thrombophlebitis;
15. Thrombosis of coronary vessels with the development of myocardial infarction is possible;
16. Intermittent claudication, which may result in gangrene;
17. Arterial hypertension (almost 50% of patients), creating a tendency to strokes and heart attacks;
18. Damage to the respiratory system due to immunity disorders, which cannot adequately respond to infectious agents that cause inflammatory processes. In this case, red blood cells begin to behave like suppressors and suppress the immunological response to viruses and tumors. In addition, they are found in abnormally high quantities in the blood, which further aggravates the condition of the immune system;
19. The kidneys and urinary tract suffer, so patients have a tendency to pyelonephritis and urolithiasis;
20. The central nervous system does not remain aloof from the events occurring 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, and mnestic disorders appear.

From asymptomatic period to terminal stage

Due to the fact that polycythemia in the first stages is characterized by an asymptomatic course, the above manifestations do not occur in one day, but accumulate gradually and over a long period of 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 moderate, the duration of the stage is about 5 years.

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

II A – occurs 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. The patient’s complaints are varied, “everything hurts, everything is wrong.” At this stage, cells lose the ability to differentiate, thereby creating 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 profound immunodeficiency). Usually it soon ends in death.

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

Diagnosis of Vaquez disease

The diagnosis of polycythemia vera is primarily based on laboratory data, measuring the following indicators:

• A general blood test, 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 in polycythemia vera is always reduced and can reach zero.

Morphologically, red blood cells do not always change and often remain normal, but in some cases, erythremia can be observed anisocytosis(red blood cells of different sizes). The severity and prognosis of the disease with polycythemia in a general blood test is indicated by platelets (the more of them, the more severe the course of the disease);

• BAC (biochemical blood test) with 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 Vaquez's disease);
• Radiological testing using radioactive chromium helps determine the increase in circulating red blood cells;
• Sternal puncture (bone marrow collection from the sternum) followed by cytological diagnosis. In the preparation - hyperplasia of all three lineages with a significant predominance of red and megakaryocytic;
• Trephine biopsy(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-line hyperplasia.

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

So, the diagnosis has been made... What next?

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

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

The treatment regimen for erythremia is prescribed by the doctor individually for each case, so our task is only to briefly introduce the reader to the drugs used to treat Vaquez disease.

Nutrition, diet and folk remedies

A significant role in the treatment of polycythemia is given to the regime of work (reducing 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 to table No. 15 (general), albeit with some reservations. The patient is not recommended to consume foods that enhance hematopoiesis (liver, for example) and is asked to reconsider the diet, giving preference to dairy and plant products.

In the second stage of the disease, the patient is prescribed table No. 6, which corresponds to the diet for gout and limits or completely excludes fish and meat dishes, legumes and sorrel. After being discharged from the hospital, the patient must adhere to the recommendations given by the doctor during outpatient observation or treatment.

Question: “Can it be treated with 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 patient’s life expectancy depend entirely on timely treatment, the goal of which is to achieve a long and stable remission and delay the third stage for as long as possible.

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

Treatment with folk remedies for blood diseases should not be generalized, and if there are many recipes for increasing hemoglobin levels or for thinning the blood, this does not mean at all that they are suitable for treating polycythemia, for which, in general, no medicinal herbs have yet been found. Vaquez's disease is a delicate matter, and in order to control the function of the bone marrow and thus influence 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 say a few words to the readers about relative erythremia, which should not 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 is 90% water, decreases.

Prognosis for polycythemia vera

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

Features of the disease

Primary (true) polycythemia is a blood disease from the leukemia group that occurs idiopathically (for no apparent reason), has a long-term (chronic) course 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 Vaquez-Osler disease, erythremia, primary erythrocytosis. The consequences of erythrocytosis and blood thickening in this myeloproliferative disease can be serious and relate to the risk of thrombosis, an increase in size and disruption of the spleen, an increase in the volume of circulating blood, etc.

Erythremia is considered a malignant tumor process, which is caused by increased proliferation (hyperplasia) of bone marrow cells. The pathological process is especially strong in 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 of a huge number of red blood cells in the blood, as well as with a slight increase in the number of platelets and neutrophils (neutrophilic leukocytes). 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 flow of blood, the formation of blood clots, disruption of the local blood supply to tissues and their hypoxia.

If initially the patient most often experiences primary erythrocytosis, that is, only the number of red blood cells increases, then further changes begin to affect 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 - the process of formation of red blood cells - is also localized. 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 bloodstream without maturing. In approximately 10% of cases, the pathology develops into acute leukemia.

The study and first description of erythrocytosis was made in 1892 by Vaquez, and in 1903 the scientist Osler suggested that the cause of the disease was a malfunction of the bone marrow. Polycythemia vera is observed somewhat more often than other similar pathologies, but is still quite rare. It is diagnosed in approximately 5 people per year per 1 million population. Most often, the disease occurs in people over 50 years of age, the average age of detection is 60 years. In children, such a diagnosis is made very rarely, mainly after 12 years. On average, only 5% of cases 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 ranks 4th. Sometimes it is inherited, so there are familial cases.

Causes of pathology

The primary form of the disease is considered hereditary and is transmitted in an autosomal recessive manner. In this case, it is often referred to as “familial 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 the clonal origin of the pathology in many patients, since the same enzyme was detected in leukocytes, platelets, and erythrocytes. The clonal theory is also confirmed by ongoing cytological studies regarding the karyotype of chromosome groups, where various defects were identified, similar in different patients. There is also a viral-genetic theory, according to which up to 15 types of viruses can invade the body and, with the participation of a number of provoking factors, lead to a malfunction of the bone marrow. They penetrate the precursors of blood cells, which then, instead of maturing normally, begin to divide and form new red blood cells and other cells.

As for the risk factors for the development of polycythemia vera, presumably they may be the following:

• lung diseases;
• long stay at high altitudes above sea level;
• pulmonary hypoventilation syndromes;
• various hemoglobinopathies;
• long history of smoking;
• tumors of 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 by chemical vapors, penetration through the skin;
• entry of toxic substances into the gastrointestinal tract;
• treatment with gold salts;
• advanced tuberculosis;
• major surgical interventions;
• “blue” heart defects;
• kidney pathologies - hydronephrosis, stenosis of the renal arteries.

Thus, the main cause of secondary erythrocytosis are all conditions that in one way or another 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 its production of additional blood cells.

Classification of polycythemia vera

The disease is classified into the following stages:

1. The first, or initial stage. It can last more than 5 years and represents the development of plethoric syndrome, that is, increased blood supply to organs. At this stage, symptoms may be moderate, and no complications arise. A general blood test reflects a slight increase in the number of red blood cells, a bone marrow puncture shows an increase in erythropoiesis or the production of all the main elements of blood, with the exception of lymphocytes.
2. The second is stage A, or polycythemic stage. Duration - from 5 to 15 years. Plethoric syndrome is more pronounced, an enlargement of the spleen and liver (blood-forming organs) is observed, and thrombus formation in the veins and arteries is often recorded. No tumor growth was observed in the peritoneal organs. If this stage ends with a decrease in the number of platelets - thrombocytopenia, then the patient may experience various bleedings. Frequent hemorrhages cause a lack of iron in the body. A general blood test reflects an increase in red blood cells, platelets, and leukocytes; in advanced cases, a decrease in platelets. The myelogram shows increased formation of most blood cells (with the exception of lymphocytes), and scar changes in the brain are formed.
3. The second is stage B, or polycythemic stage with myeloid metaplasia of the organ - the spleen. The patient's spleen and often the liver continue to increase in size. Puncture of the spleen reveals tumor growth. Frequent thromboses interspersed with bleeding are observed. In the general analysis, there is an even greater increase in the number of erythrocytes, leukocytes, there are erythrocytes of different sizes, shapes, and immature precursors of all blood cells are present. The number of scar changes in the bone marrow increases.
4. Third, or anemic stage. It is the outcome of a disease in which the activity of blood cells is depleted. The number of red blood cells, white blood cells, and platelets is greatly reduced, the liver and spleen are enlarged with myeloid metaplasia, and extensive scarring occurs 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 patient’s disease manifests itself in one way or another, and the specific symptoms can be varied. Basically, the symptom complex includes the following main signs:

1. Change in skin tone, dilation of veins. Most often, in the neck area of ​​an adult, the veins begin to become very visible; their pattern becomes stronger due to swelling and overfilling with blood. But the skin signs become the most obvious: the skin color becomes dark red, literally cherry. This is most noticeable in the neck, arms, and face, which is associated with overfilling of the subcutaneous arteries with blood. At the same time, many patients mistakenly think that blood pressure rises due to hypertension, and therefore often continue to take blood pressure medications and do not consult a doctor. If you pay close attention to your health, you will notice that your lips and tongue have also changed their color and become red-blue. The blood vessels of the eyes also become engorged, 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. Itchy skin. All described changes in the skin in approximately 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, patients release histamine, as well as prostaglandins, itching of the skin may become even more pronounced after a bath or shower.
3. Pain in the 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, and at first they are often perceived as a symptom of fatigue in an elderly person. Pain is also observed with palpation and tapping of flat bones, which reflects the process of hyperplasia and cicatricial changes in the bone marrow. The next type of pain in a person with polycythemia vera is persistent burning pain in the area of ​​large and small joints of the legs, which resemble gouty pain and are caused by the same cause 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 and blue spots appear on it. These pains are caused by an increase in the number of platelets and the appearance of capillary microthrombosis.
4. Splenomegaly. An increase in size of the spleen is observed in almost every person with polycythemia vera, but at different stages of the disease. This occurs due to increased filling of the spleen with blood and the development of myeloproliferative phenomena. Somewhat less frequently, but still occurring, is a strong increase in the size of the liver - hepatomegaly.
5. Peptic ulcer disease. About one in ten people with Vaquez-Osler disease develop ulcers in the small intestine (usually the duodenum) and 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 develop a tendency to thrombosis, and until recently, patients died from such complications at an early stage of the disease. Modern treatment currently being carried out can prevent the appearance of blood clots in the brain, spleen, and legs, which threaten embolism and death. Increased blood viscosity characterizes polycythemia vera 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 very specific and can be characteristic of different pathologies:

• fatigue;
• head goals;
• tinnitus;
• nausea;
• dizziness;
• feeling of pulsation in the temples, ears;
• decreased appetite and 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 low-grade fever;
• insomnia;
• numbness, tingling of fingers;
• epileptiform seizures and paralysis (rare).

In general, the disease is characterized by a long and sometimes benign course, especially with adequate treatment. But some people, especially those not receiving therapy, may experience early onset of various effects of polycythemia vera.

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 blood clot and the affected area. Transient ischemic attacks, strokes, thrombophlebitis and phlebothrombosis of superficial and deep veins, blockage of retinal vessels and blindness, infarction of internal organs, and myocardial infarction may occur.

At the most advanced stages of pathology, kidney stones (urolithiasis), gout, nephrosclerosis, and cirrhosis of the liver often appear. Complications are likely to occur due to tissue bleeding - bleeding from gastrointestinal ulcers, anemia. On the part of the heart, in addition to myocardial infarction, signs of myocardiosclerosis and heart failure are also possible. There is also a possibility of transition of polycythemia vera to acute leukemia, chronic leukemia and other oncological pathologies.

Carrying out diagnostics

Making a diagnosis of this disease is not easy, especially in the absence of a characteristic clinical picture and in the presence of only general symptoms. However, the totality of data from hematological and biochemical tests, 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 occurring.

The main indicators for establishing the diagnosis of polycythemia vera are the general blood test indicators - the number of red blood cells 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, and the hematocrit is above 52%. In women, excess values ​​are 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 the pathology, and as it develops they become even higher. In addition, it is important to assess the mass of circulating red blood cells, which is normally up to 36 ml/kg for men and up to 32 ml/kg for women.

Other blood parameters (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. Increased reticulocyte count.
3. The appearance of myelocytes and metamyelocytes in the blood.
4. Increase in blood viscosity by%.
5. Severe decrease in ESR.
6. Increase in the mass of circulating red blood cells.
7. Increased alkaline phosphatase, vitamin B12 in serum.
8. Increase in the amount of uric acid in the serum.
9. Blood saturation in the arteries with oxygen is above 92%.
10. The appearance of colonies of erythrocytes in a test tube.
11. Decrease in erythropoietin levels.
12. A change in color index of less than 1.

At the stage of myelofibrosis, hemoglobin and red blood cell levels may return to normal, but at the same time 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:

• reducing 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 changes occurring that are characteristic of polycythemia vera:

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

All the criteria described above, except the three main ones, which are considered large, are small. As for the major diagnostic criteria, these are an increase in the mass of circulating red blood cells, splenomegaly, and oversaturation of arterial blood with oxygen. To make 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 sooner a person seeks help, the more effective therapy can be. At the third stage, or when another tumor process is superimposed on erythremia, symptomatic therapy is carried out in combination with treatment with chemotherapy. Chemotherapy treatment may be recommended at other stages of the disease, but the body does not always respond adequately to it. Among the symptomatic remedies 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 tissue bleeding.
5. Medicines to lower uric acid levels.

Treatment methods 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 with a break of 3-4 days in a course of several sessions. After such manipulations, the blood becomes more fluid, but they cannot be done if there is a recent history of blood clots. Before treatment with bloodletting, the patient is administered a solution of Reopoliglucin, as well as Heparin.
2. Erythrocytapheresis. Used to cleanse the blood of excess red blood cells, as well as platelets. Such sessions are done once a week.
3. Chemotherapy. It is used, as a rule, when the disease reaches the tumor stage - second B. Other indications for chemotherapy are the presence of complications from the peritoneal organs, the general difficult situation of the person, and an increase in the amount of all blood elements. For chemotherapy or cytoreductive therapy, cytostatics, antimetabolites, alkylating drugs, and biological drugs are used. The most commonly prescribed medications are Leukeran, Hydroxyurea, Myelosan, and 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 area of ​​the spleen and stop the cancer process in it; it is used when the organ greatly increases in size.
6. Transfusion of red blood cells from purified red blood cells. Used for severe anemia to the point of coma. If thrombocytopenia increases in the final stages of polycythemia vera, a transfusion of platelet mass from a donor may be necessary.

Bone marrow transplantation for a disease such as erythremia often leads to unfavorable results and is therefore 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 gestation. However, in 50% of cases, pregnancy ends in a successful birth. The remaining half is due to miscarriages, developmental delays, and structural anomalies of the fetus.

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, therapy is predominantly performed with bloodletting and, if necessary, glucocorticosteroids. To prevent complications and early detection of the disease in pregnant women, blood tests should be carried out regularly according to the schedule designated by the observing obstetrician-gynecologist.

What not to do

It is strictly forbidden to use diuretics, which further thicken the blood. Also in our time, the use of radioactive phosphorus preparations, which seriously inhibit myelopoiesis and often lead to the development of leukemia, is limited. You also cannot maintain the same nutritional system: the diet must change. All foods that enhance hematopoiesis, such as liver, are prohibited. It is better to create a dairy-vegetable diet and avoid excess meat.

The patient should not overload the body, engage in strenuous sports, or ignore regular rest. Treatment with folk remedies can be used, but only after a doctor has carefully studied all the remedies according to their 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

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

Polycythemia is a disease that can be identified just by looking at a person's face. And if you carry out a diagnostic examination, then there will be no doubt at all. In the medical literature you can find other names for this pathology: erythremia, Vaquez disease. Regardless of the term chosen, the disease poses a serious threat to human life. In this article we will talk in more detail about the mechanism of its occurrence, primary symptoms, stages and proposed treatment methods.

general information

Polycythemia vera is a myeloproliferative blood cancer that produces red blood cells in excess quantities. To a lesser extent, an increase in other enzyme elements, namely leukocytes and platelets, is observed.

Red blood cells (aka erythrocytes) saturate all cells of the human body with oxygen, delivering it from the lungs to the internal organ systems. They are also responsible for removing carbon dioxide from tissues and transporting it to the lungs for later exhalation.

Red blood cells are continuously produced in the bone marrow. It is a collection of sponge-like tissues, localized inside the bones and responsible for the process of hematopoiesis.

Leukocytes are white blood cells that help fight various infections. Platelets are fragments that are activated when the integrity of blood vessels is disrupted. They have the ability to stick to each other and clog the hole, thereby stopping bleeding.

Polycythemia vera is characterized by excess production of red blood cells.

Prevalence of the disease

This pathology is usually diagnosed in adult patients, but can occur in adolescents and children. For a long time, the disease may not make itself felt, that is, it may be asymptomatic. According to studies, the average age of patients varies from 60 to approximately 79 years. Young people get sick much less often, but their illness is much more severe. According to statistical data, representatives of the stronger sex are diagnosed with polycythemia several times more often.

Pathogenesis

Most of the health problems associated with this disease arise from the continuous increase in the number of red blood cells. As a result, the blood becomes excessively thick.

On the other hand, its increased viscosity provokes the formation of clots (thrombi). They can interfere with normal blood flow through arteries and veins. This situation often causes strokes and heart attacks. The thing is that thick blood flows several times slower through the vessels. The heart has to make more efforts to literally push it through.

Slowing blood flow does not allow internal organs to receive the required amount of oxygen. This entails the development of heart failure, headaches, angina, weakness and other health problems that are not recommended to be ignored.

Classification of the disease

• I. Initial stage.

1. Lasts from 5 years or more.
2. The spleen is of normal size.
3. Blood tests show a moderate increase in the number of red blood cells.
4. Complications are diagnosed extremely rarely.

• II A. Polycythemic stage.

1. Duration from 5 to approximately 15 years.
2. There is an increase in some organs (spleen, liver), bleeding and thrombosis.
3. There are no areas in the spleen itself.
4. Bleeding can cause iron deficiency in the body.
5. The blood test shows a persistent increase in red blood cells, white blood cells and platelets.

• II B. Polycythemic stage with myeloid metaplasia of the spleen.

1. Analyzes show increased levels of all blood cells except lymphocytes.
2. A tumor process is observed in the spleen.
3. The clinical picture includes exhaustion, thrombosis, and bleeding.
4. Gradual scar formation occurs in the bone marrow.

• III. Anemic stage.

1. There is a sharp decrease in red blood cells, platelets and leukocytes in the blood.
2. There is a marked increase in the size of the spleen and liver.
3. This stage usually develops 20 years after confirmation of the diagnosis.
4. The disease can transform into acute or chronic leukemia.

Causes of the disease

Unfortunately, at present experts cannot say which factors lead to the development of a disease such as polycythemia vera.

Most are inclined to the viral-genetic theory. According to it, special viruses (there are about 15 of them in total) are introduced into the human body and, under the influence of certain factors that negatively affect the immune defense, penetrate into the cells of the bone marrow and lymph nodes. Then, instead of maturing as expected, these cells begin to rapidly divide and multiply, forming more and more new fragments.

On the other hand, the cause of polycythemia may be hidden in a hereditary predisposition. Scientists have proven that close relatives of the sick person, as well as people with abnormal chromosome structure, are more susceptible to this disease.

Factors predisposing to the onset of the disease

• X-ray exposure, ionizing radiation.
• Intestinal infections.
• Viruses.
• Tuberculosis.
• Surgical interventions.
• Frequent stress.
• Long-term use of certain groups of medications.

Clinical picture

Starting from the second stage of development of the disease, literally all systems of internal organs are drawn into the pathological process. Below we list the subjective sensations of the patient.

• Weakness and a persistent feeling of fatigue.
• Increased sweating.
• Noticeable decrease in performance.
• Severe headaches.
• Memory impairment.

Polycythemia vera may also be accompanied by the following symptoms. In each specific case, their severity varies.

Diagnostics

First of all, the doctor collects a complete medical history. He may ask a number of clarifying questions: when exactly did the malaise/shortness of breath/painful discomfort appear, etc. It is equally important to determine the presence of chronic ailments, bad habits, and possible contacts with toxic substances.

A physical examination is then performed. The specialist determines the color of the skin. By palpation and tapping, an enlarged spleen or liver is detected.

To confirm the disease, blood tests are required. If the patient has this pathology, the test results may be as follows:

• Increase in the number of red blood cells.
• Elevated hematocrit parameters (percentage of red blood cells).
• High hemoglobin levels.
• Low erythropoietin levels. This hormone is responsible for stimulating the bone marrow to produce new red blood cells.

Diagnosis also involves brain aspiration and biopsy. The first version of the study involves taking the liquid part of the brain, and a biopsy - the solid component.

Polycythemia disease is confirmed by gene mutation tests.

What should the treatment be?

It is not possible to completely overcome a disease such as polycythemia vera. That is why therapy focuses exclusively on reducing clinical manifestations and reducing thrombotic complications.

Patients are first prescribed bloodletting. This procedure involves the removal of a small amount of blood (from 200 to approximately 400 ml) for therapeutic purposes. It is necessary to normalize the quantitative parameters of the blood and reduce its viscosity.

Patients are usually prescribed Aspirin to reduce the risk of developing various types of thrombotic complications.

Chemotherapy is used to maintain a normal hematocrit when severe pruritus or increased thrombocytosis occurs.

Bone marrow transplantation for this disease is performed extremely rarely, since this pathology is not fatal if adequately treated.

It should be noted that the specific treatment regimen is selected individually in each case. The therapy described above is for informational purposes only. It is not recommended to try to cope with this disease on your own.

Possible complications

This disease is quite serious, so its treatment should not be neglected. Otherwise, the likelihood of unpleasant complications increases. These include the following:

Forecast

Vaquez disease is a rare disease. Symptoms that appear in the early stages of its development should be the reason for immediate examination and subsequent therapy. In the absence of adequate treatment, if the disease is not diagnosed in a timely manner, death occurs. The main cause of death is most often vascular complications or transformation of the disease into chronic leukemia. However, competent therapy and strict adherence to all recommendations from the doctor can significantly extend the patient’s life (by 15-20 years).

We hope that all the information presented in this article will be truly useful to you. Be healthy!