Secondary polycythemia symptoms and treatment. Polycythemia (erythremia, Vaquez disease): causes and development, manifestations, treatment, prognosis

Today we will talk about a blood disease called polycythemia vera. This disease is a pathology in which there is an increased number of red blood cells in the circulating blood. Polycythemia poses a great, sometimes irreversible danger to human life and health, so it is important to recognize the disease by its first signs for timely medical care and competent treatment. Typically, this syndrome is characteristic of people over the age of 50, and is more often diagnosed in males. Let's take a closer look at the disease in all its aspects: etiology, types, diagnosis and main methods of treating polycythemia.

General information about the disease

IN modern medicine Polycythemia has several names, such as Vaquez's disease, and is also sometimes called erythrocytosis. The pathology belongs to the section of chronic leukemia and represents an active increase in the concentration of red blood cells, leukocytes and platelets in the blood; most often, experts classify this disease as a rare type of leukemia. Medical statistics says that polycythemia vera is diagnosed annually in only 5 cases per 1 million patients; usually the development of pathology is typical for older men (from 50 to 65 years).

To the very dangerous complications diseases include the risk of developing thrombosis and hemorrhagic strokes, as well as the transition of polycythemia to the acute stage of myeloblastic leukemia or to chronic stage myeloid leukemia. This disease is characterized by a number of reasons, which we will consider below. All causes of erythremia are divided into two types: primary and secondary.

Causes of the disease

In modern medicine, the root causes of this pathology include the following:

• genetic predisposition to increased production of red blood cells;
• failures at the genetic level;
• cancer bone marrow;
• Oxygen deprivation also affects increased production of blood cells.

Most often, erythremia has a tumor factor, characterized by damage to stem cells produced in the red bone marrow. The result of the destruction of these cells is an increase in the level of red blood cells, which directly leads to disruption of the functioning of the entire body. The disease is malignant, difficult to diagnose and takes a long time to treat, and not always with a positive effect, complex therapy due to the fact that no treatment methods can affect stem cell, which has undergone a mutation and has a high ability to divide. Polycythemia vera is characterized by the presence of plethora, this is due to the fact that in vascular bed increased concentration of red blood cells.

Patients with polycythemia have purplish-red skin, and patients often complain of itchy skin.

Co. secondary causes Experts attribute diseases to factors such as:

• obstructive pulmonary pathologies;
• pulmonary hypertension;
• chronic heart failure;
• there is not enough oxygen supply to the kidneys;
• a sharp change in climate, and the development of this syndrome is typical for the population living in high mountain areas;
• various infections leading to high intoxication of the body;
• harmful working conditions, especially for work carried out at height;
• the disease also affects people living in environmentally polluted areas, or in close proximity to industries;
• excessive smoking;
• experts have revealed high risk the development of polycythemia is typical for people with Jewish roots, this is due to the genetic characteristics of the function of the red bone marrow;
• sleep apnea;
• Hypoventilation syndromes lead to polycythemia.

All these factors lead to the fact that hemoglobin is endowed with the ability to actively absorb oxygen, with virtually no return to the tissues of internal organs, which, accordingly, leads to the active production of red blood cells.

It is worth noting that some oncological diseases can also provoke the development of erythremia, for example, tumors of the following organs affect the production of red blood cells:

• liver;
• kidney;
• adrenal glands;
• uterus.

Some kidney cysts and obstruction of this organ can increase the secretion of blood cells, leading to the development of polycythemia. Polycythemia sometimes occurs in newborns, this disease is transmitted through the maternal placenta, and there is insufficient oxygen supply to the fetus, as a result of which pathology develops. Next, we will consider the course of polycythemia, its symptoms and treatment, what are the complications of polycythemia disease?

Symptoms of polycythemia

This disease is dangerous because polycythemia vera at the initial stage is practically asymptomatic, the patient does not have any complaints about deteriorating health. Most often, pathology is detected during a blood test; sometimes the first “bells” of polycythemia are associated with colds or just with general decline performance in older people.

The main signs of erythrocytosis include:

• a sharp drop in visual acuity;
• frequent migraines;
• dizziness;
• noise in ears;
• sleep problems;
• “icy” fingers.

When the pathology enters an advanced stage, the following may be observed with polycythemia:

• muscle and bone pain;
• Ultrasound often reveals an enlarged spleen or changes in the contours of the liver;
• bleeding gums;
• for example, when a tooth is removed, the bleeding may not stop for a long time;
• Patients often discover new bruises on their body, the origin of which they cannot explain.

Doctors also highlight specific symptoms of the specified disease:

• severe skin itching that increases after taking water procedures;
• burning sensation in fingertips;
• the appearance of spider veins;
• skin of the face, neck and chest may acquire a purplish-red hue;
• lips and tongue, on the contrary, may have a bluish tint;
• the whites of the eyes tend to turn red;
• the patient constantly feels weak.

If we talk about a disease that affects newborns, polycythemia develops a few days after birth. Most often, the pathology is diagnosed in twins; the main signs include:

• the baby's skin turns red;
• when touching the skin, the child experiences unpleasant sensations and therefore begins to cry;
• the baby is born with low weight;
• a blood test reveals an increased level of leukocytes, platelets and red blood cells;
• Ultrasound shows changes in the size of the liver and spleen.

It is worth noting that if polycythemia is not diagnosed in a timely manner, the development of the disease can be missed, and the lack of therapy can lead to the death of the newborn.

Diagnosis of the disease

As mentioned above, most often polycythemia vera is detected during a preventive blood test. Experts diagnose erythrocytosis if blood tests show levels above normal:

• hemoglobin level increased to 240 g/l;
• the level of red blood cells is increased to 7.5x10 12 /l;
• leukocyte level increased to 12x10 9 /l;
• platelet level increased to 400x10 9 /l.

To study the function of red bone marrow, a trephine biopsy procedure is used, because it is the disruption of the production of stem cells that provokes the development of polycythemia. To exclude other diseases, specialists can use studies such as ultrasound, urinalysis, FGDS, ultrasound, etc. The patient is also prescribed consultations with specialized specialists: neurologist, cardiologist, urologist, etc. If a patient is diagnosed with polycythemia, what is the treatment? of this disease, let's look at the main methods.

Treatment of erythrocytosis

This disease is one of those types of pathology that are treated with myelosuppressive drugs. Polycythemia vera is also treated using bloodletting methods, this type therapy can be prescribed to patients who have not reached 45 years of age. The essence of the procedure is that up to 500 ml of blood per day is taken from the patient; elderly people with polycythemia also undergo phlebotomy, but no more than 250 ml of blood is taken per day.

If a patient with this disease experiences severe skin itching and hypermetabolic syndrome, then specialists prescribe a myelosuppressive method of treating polycythemia vera. It includes the following drugs:

• radioactive phosphorus;
• anagrelide;
• interferon;
• Hydroxyurea.

In case of remission with polycythemia, the patient is prescribed repeat tests blood no more than once every 14 days, then the study is carried out once a month. When the level of red blood cells returns to normal, the drugs begin to be gradually discontinued, drug therapy alternates with a rest from the drugs, and the course of the disease is strictly monitored. But it is worth noting that the use of myelosuppressive drugs for polycythemia can lead to the development of leukemia, so specialists prescribe them after lengthy detailed studies. Sometimes side effects such as skin ulcers, gastrointestinal disturbances, and fever occur; if this occurs, the medications are immediately discontinued.

The patient should also take Aspirin daily to reduce the risk of thrombosis, which often complicates the course of this disease.

Another procedure for a patient with polycythemia is erythrocytophoresis, which consists of a device pumping out the patient’s blood while simultaneously removing excess red blood cells from it. Afterwards, in order to restore the previous volume, the patient is infused with saline solution. This procedure is a modern type of bloodletting, but it is carried out no more than once every 2-3 years. Treatment of polycythemia will not protect the patient from possible complications that may develop against the background of this pathology.

Complications of polycythemia

Experts note the following complications that accompany the development of polycythemia vera:

• urine may acquire a strong and unpleasant odor;
• often patients with polycythemia suffer from gout;
• with polycythemia, kidney stones can form;
• renal colic becomes chronic;
• erythrocytosis is often accompanied by a stomach or duodenal ulcer;
• impaired circulatory function can lead to the formation of skin ulcers;
• often this disease provokes thrombosis;
• bleeding gums, frequent nosebleeds.

Preventive measures

The development of a disease such as polycythemia can be prevented; it is necessary to adhere to the following preventive measures:

• completely abandon bad habits, especially from smoking cigarettes, it is nicotine that harms the body and provokes this disease;
• if the area is unfavorable for living, then it is better to change your place of residence;
• the same applies to work;
• regularly take preventive blood tests, which can show whether the patient has polycythemia;
• It is necessary to take a responsible approach to your diet, it is better to limit your meat consumption, include in your diet those foods that stimulate the function of hematopoiesis, and give preference to fermented milk and plant products.

Remember that timely diagnosis and proper treatment of polycythemia can prevent the development of complications with this disease, but, unfortunately, with this disease there is no guarantee of a complete cure.

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Polycythemia vera (primary polycythemia, Vaquez disease, erythremia) is the most common disease of the group of chronic myeloproliferative diseases. The pathological process primarily affects the erythroblastic sprout of the bone marrow, which causes an increase in the number of red blood cells in the peripheral blood, as well as an increase in the viscosity and mass of circulating blood (hypervolemia).

The disease occurs predominantly in older people (the average age of onset is approximately 60 years), but is also diagnosed in young people and children. For patients young a more severe course of the disease is typical. Men are slightly more susceptible to polycythemia vera than women, but for young patients the inverse proportionality is typical.

Causes and risk factors

The reasons contributing to the occurrence of polycythemia vera have not been definitively established. Pathology can be both hereditary and acquired. A family predisposition to the disease was discovered. In patients with polycythemia vera, gene mutations, which are inherited in an autosomal recessive manner.

Risk factors include:

• influence of toxic substances on the body;
• ionizing radiation;
• X-ray irradiation;
• extensive burns;
• long-term use of a series medicines(gold salts, etc.);
• advanced forms of tuberculosis;
• distress;
• viral diseases;
• tumor neoplasms;
• smoking;
• endocrine disorders caused by adrenal tumors;
• heart defects;
• liver and/or kidney diseases;
• extensive surgical interventions.

Forms of the disease

Polycythemia vera is of two types:

• primary (not a consequence of other pathologies);
• secondary (develops against the background of other diseases).

Without adequate treatment for polycythemia vera, 50% of patients die within 1-1.5 years from the time of diagnosis.

Stages of the disease

The clinical picture of polycythemia vera is divided into three stages:

1. Initial (asymptomatic) – clinical manifestations are minor, duration is about 5 years.
2. The erythremic (advanced) stage lasting 10–20 years, in turn, is divided into substages: IIA – no myeloid metaplasia of the spleen; IIB – presence of myeloid metaplasia of the spleen;
3. Post-erythraemic myeloid metaplasia stage (anemic) with or without myelofibrosis; capable of becoming chronic or acute leukemia.

Symptoms

Polycythemia vera is characterized by a long asymptomatic course. The clinical picture is associated with increased production of red blood cells in the bone marrow, which is often accompanied by an increase in the number of other cellular elements of the blood. An increase in platelet content leads to vascular thrombosis, which can cause strokes, myocardial infarction, transient ischemic attacks, etc.

For more later stages diseases can be observed:

• skin itching, worsened by exposure to water;
• attacks of pressing pain in the chest during physical activity;
• weakness, increased fatigue;
• memory disorder;
• headaches, dizziness;
• erythrocyanosis;
• redness of the eyes;
• visual impairment;
• increased blood pressure;
• spontaneous bleeding, ecchymosis, gastrointestinal bleeding;
• dilated veins (especially neck veins);
• short-term intense pain in the fingertips;
• stomach and/or duodenal ulcer;
• joint pain;
• heart failure.

Diagnostics

The diagnosis of polycythemia vera is established on the basis of data obtained during the examination:

• taking anamnesis;
• objective examination;
• general and biochemical blood test;
• general urine analysis;
• trephine biopsy followed by histological analysis of the biopsy;
• ultrasound examination;
• computed tomography or magnetic resonance imaging;
• molecular genetic analysis.

A blood test for polycythemia vera shows an increase in the number of red blood cells

Diagnostic criteria for polycythemia vera:

• increased mass of circulating erythrocytes: in men – more than 36 ml/kg, in women – more than 32 ml/kg;
• leukocytes – 12 × 10 9 /l or more;
• platelets – 400 × 10 9 /l or more;
• increase in hemoglobin to 180–240 g/l;
• increase in oxygen saturation in arterial blood– 92% or more;
• increase in the serum content of vitamin B 12 – 900 pg/ml or more;
• increase in leukocyte alkaline phosphatase activity to 100;
• splenomegaly.

The disease occurs predominantly in older people (the average age of onset is approximately 60 years), but is also diagnosed in young people and children.

Differential diagnosis with absolute and relative (false) erythrocytosis, neoplasms, and hepatic vein thrombosis is necessary.

Treatment

Treatment of polycythemia vera is aimed primarily at preventing the development of leukemia, as well as prevention and/or treatment of thrombohemorrhagic complications. Symptomatic therapy is carried out to improve the patient’s quality of life.

To reduce blood viscosity in hyperviscosity syndrome, a course of phlebotomies (exfusions, bloodlettings) is performed. However, with initially high thrombocytosis, phlebotomy may contribute to the occurrence of thrombotic complications. For patients who do not tolerate bloodletting well, as well as in childhood and adolescence, myelosuppressive therapy is indicated.

Interferon drugs are prescribed for a long course (2-3 months) to reduce myeloproliferation, thrombocythemia, and also to prevent the development of vascular complications.

Using hardware therapy methods (erythrocytapheresis, etc.), excess blood cellular elements are removed. To prevent thrombosis, anticoagulants are prescribed. To reduce symptoms skin itching apply antihistamines. In addition, patients are advised to adhere to a dairy-vegetable diet and limit physical activity.

With a pronounced increase in the size of the spleen (hypersplenism), splenectomy is indicated for patients.

Possible complications and consequences

Polycythemia vera can be complicated by:

• myelofibrosis;
• splenic infarction;
• anemia;
• nephrosclerosis;
• cholelithiasis and/or urolithiasis;
• gout;
• myocardial infarction;
• ischemic stroke;
• liver cirrhosis;
• pulmonary embolism;
• acute or chronic leukemia.

Forecast

At timely diagnosis and treatment, survival rate exceeds 10 years. Without adequate therapy, 50% of patients die within 1-1.5 years from the moment of diagnosis.

Prevention

Since the exact causes of the disease are unclear, effective methods Prevention of polycythemia vera has not yet been developed.

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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. Metabolic disorder uric acid– 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 with small surgical interventions X. 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 pronounced hemolytic anemia, not amenable conservative therapy and requiring 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 iron deficiency anemia There is a hidden iron deficiency, characterized by a decrease in iron content in blood stores and serum with normal hemoglobin levels. Hidden 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 (erythrocytes with iron granules) is sharply reduced down to 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 periodic administration of iron supplements to patients with high level the risk of relapse of iron deficiency anemia - for 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 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 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 during their excessive growth: condition after gastrointestinal anastomosis, diverticula jejunum, 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 need: 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.

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, called “polycythemia vera.”

Features of the disease

Primary (true) polycythemia is a blood disease from the leukemia group that occurs idiopathically (without visible reasons), proceeds for a long time (chronically) and is characterized by an increase in the number of red blood cells, an increase in hematocrit and blood viscosity. Synonyms for the name of the pathology are 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 in the blood huge amount red blood cells, 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 they were identified various defects, 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 on high altitude 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;
• serious 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 red blood cells, white blood cells, there are red blood cells different sizes, forms, 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 registered approximately 10-20 years after the development of the pathology.

Symptoms of manifestation

Often this pathology It 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 most obvious ones are skin signs: 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. However, many patients mistakenly think that blood pressure increases due to hypertension, which is why they 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. Solid sky remains the same color, but the soft sky 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 patients release histamine as well as prostaglandins after taking water treatments, 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 strong painful sensations 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 legs, which resemble gouty pain and are caused by the same cause as gout - an increase in uric acid levels. 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 spleen size is observed in almost every person with polycythemia vera, but different stages diseases. 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 in duodenum) and in the stomach. This is due to the activation Helicobacter bacteria pylori, 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 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 late stages pathologies often appear kidney stones ( urolithiasis disease), gout, nephrosclerosis, liver cirrhosis. 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 common symptoms. However, the totality of data from hematological and biochemical tests, as well as some distinctive features appearance the patient, together with his complaints, will help the doctor establish the cause of the changes occurring.

The main indicators for establishing the diagnosis of polycythemia vera are: general analysis blood - 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. The indicated figures are typical for early stages 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. Increases blood viscosity by 500-800%.
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. Presence of gene abnormalities, if tested genetic testing 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 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 layer is layered tumor process For 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 a volume of 100-400 ml (according to indications) and 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 to 10-15 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 vera (primary polycythemia) is an idiopathic chronic myeloproliferative disease, which is characterized by an increase in the number of red blood cells (erythrocytosis), an increase in hematocrit and blood viscosity, which can lead to the development of thrombosis. With this disease, hepatosplenomegaly may develop. In order to establish a diagnosis, it is necessary to determine the number of red blood cells and exclude other causes of erythrocytosis. Treatment consists of periodic bloodletting, and in some cases myelosuppressive drugs are used.

ICD-10 code

D45 Polycythemia vera

Epidemiology

Polycythemia vera (PV) is more common than other myeloproliferative diseases; the incidence is 5 cases per 1,000,000 people, men are more likely to get sick (ratio about 1.4:1). Average age patients at the time of diagnosis are 60 years old (from 15 to 90 years old; this disease is rare in children); at the time of onset of the disease, 5% of patients are under 40 years of age.

Causes of polycythemia vera

Pathogenesis

Polycythemia vera is characterized by increased proliferation of all cell lineages, including erythrocyte, leukocyte and platelet lineages. An isolated increase in erythrocyte proliferation is termed “primary erythrocytosis.” In polycythemia vera, increased red blood cell production occurs independently of erythropoietin (EPO). Extramedullary hematopoiesis is observed in the spleen, liver and other sites with the potential for hematopoiesis. The life cycle of peripheral blood cells is shortened. In the later stages of the disease, approximately 25% of patients have reduced erythrocyte lifespan and inadequate hematopoiesis. Anemia, thrombocytopenia, and myelofibrosis may develop; precursors of erythrocytes and leukocytes can enter the systemic circulation. Depending on the treatment, the frequency of transformation of the disease into acute leukemia varies from 1.5 to 10%.

With polycythemia vera, the volume and viscosity of the blood increases, which creates a predisposition to thrombosis. Because platelet function is impaired, the risk of bleeding is increased. A sharp intensification of metabolism is possible. Reduction life cycle cells leads to hyperuricemia.

Symptoms of polycythemia vera

Polycythemia vera is often asymptomatic. Sometimes increased blood volume and viscosity are accompanied by weakness, headaches, dizziness, visual disturbances, fatigue and shortness of breath. Itching is common, especially after a hot shower/bath. Facial hyperemia and congestion of retinal veins may be observed. The lower extremities may be hyperemic, hot to the touch and painful, and digital ischemia (erythromelalgia) is sometimes observed. An enlarged liver is characteristic; in addition, 75% of patients also have splenomegaly, which can be very pronounced.

Thrombosis can occur in various vessels, resulting in possible strokes, transient ischemic attacks, deep vein thrombosis, myocardial infarction, retinal artery or vein occlusions, splenic infarctions, or Budd-Chiari syndrome.

Bleeding (usually in the gastrointestinal tract) occurs in 10-20% of patients.

Complications and consequences

Diagnosis of polycythemia vera

IP should be excluded in patients with characteristic symptoms(especially in the presence of Budd-Chiari syndrome), however, the first suspicion of this disease often arises when abnormalities in the general blood test are detected (for example, with Ht > 54% in men and > 49% in women). The number of neutrophils and platelets may be increased, and the morphological structure of these cells may be disrupted. Since PV is a panmyelosis, the diagnosis is not in doubt in the case of proliferation of all 3 peripheral blood lineages in combination with splenomegaly in the absence of reasons for secondary erythrocytosis. However, all of the above changes are not always present. In the presence of myelofibrosis, anemia and thrombocytopenia, as well as massive splenomegaly, may develop. In the peripheral blood, precursors of leukocytes and erythrocytes are found, pronounced anisocytosis and poikilocytosis are observed, microcytes, elliptocytes and drop-shaped cells are present. A bone marrow examination is usually performed and reveals panmyelosis, enlarged and aggregated megakaryocytes, and (sometimes) reticulin fibers. Cytogenetic analysis of the bone marrow sometimes reveals an abnormal clone characteristic of myeloproliferative syndrome.

Since Ht reflects the proportion of red blood cells per unit volume of whole blood, an increase in Ht level can also be caused by a decrease in plasma volume (relative or false erythrocytosis, also called stress polycythemia or Gaisbeck syndrome). As one of the first tests that helps distinguish polycythemia vera from an increased hematocrit due to hypovolemia, it was proposed to determine the number of red blood cells. It should be taken into account that in polycythemia vera the plasma volume may also be increased, especially in the presence of splenomegaly, which makes Ht falsely normal despite the presence of erythrocytosis. Thus, for the diagnosis of true erythrocytosis, an increase in the erythrocyte mass is necessary. When determining the erythrocyte mass using erythrocytes labeled with radioactive chromium (51 Cr), the erythrocyte mass is more than 36 ml/kg in men (norm 28.3 ± 2.8 ml/kg) and more than 32 ml/kg in women (norm 25. 4 + 2.6 ml/kg) is considered pathological. Unfortunately, many laboratories do not perform blood volume tests.

Diagnostic criteria for polycythemia vera

Erythrocytosis, absence of secondary polycythemia and characteristic bone marrow changes (panmyelosis, enlarged megakaryocytes with the presence of aggregates) S combined with any of the following factors:

• Splenomegaly.
• Plasma erythropoietin level
• Platelet count > 400,000/µl.
• Positive endogenous colonies.
• Neutrophil count > 10,000/µl in the absence of infection.
• Clonal cytogenetic abnormalities in the bone marrow

It is necessary to think about the causes of erythrocytosis (of which there are quite a few). The most common secondary erythrocytosis due to hypoxia (HbO 2 concentration in arterial blood

The level of serum EPO in patients with polycythemia vera is usually reduced or normal, in erythrocytosis caused by hypoxia - increased, in tumor-associated erythrocytosis - normal or increased. Patients with increased level EPO or microhematuria should be examined using CT to look for renal pathology or other tumors that secrete EPO, which leads to the development of secondary erythrocytosis. Unlike bone marrow healthy people, culture of bone marrow from patients with polycythemia vera can form red blood cell colonies without the addition of EPO (ie, positive endogenous colonies).

Although polycythemia vera may cause a variety of abnormal other laboratory tests, most are unnecessary: ​​vitamin B12 levels and B12-binding capacity are often elevated, but these tests are not cost-effective. A bone marrow biopsy is also usually not necessary: ​​when performed, it usually reveals hyperplasia of all blood lines, accumulations of megakaryocytes, decreased iron stores (best assessed in bone marrow aspirate) and increased reticulin levels. Hyperuricemia and hyperuricosuria occur in more than 30% of patients. New ones have recently been proposed diagnostic tests: determination of increased expression of the PRV-1 gene in leukocytes and decreased expression of C-Mpl (receptor for thrombopoietin) on megakaryocytes and platelets.

Treatment of polycythemia vera

Since polycythemia vera is the only form of erythrocytosis for which myelosuppressive therapy can be indicated, it is very important to accurate diagnosis. Therapy should be individualized, taking into account age, gender, general condition sick, clinical manifestations diseases and hematological parameters.

Phlebotomy. Phlebotomy reduces the risk of thrombosis, improves symptoms and may be the only method of therapy. Bloodletting is the therapy of choice in women of childbearing age and patients under 40 years of age, as it does not have a mutagenic effect. Typically, the indication for phlebotomy is an Ht level greater than 45% in men and greater than 42% in women. At the beginning of therapy, 300-500 ml of blood is exfused every other day. A smaller volume of exfusions (200-300 ml twice a week) is performed in elderly patients, as well as patients with concomitant cardiac and cerebrovascular pathology. Once the hematocrit has been reduced below the threshold value, it should be determined once a month and maintained at this level with additional bloodletting (as needed). Before elective surgical interventions, the red blood cell count should be reduced using phlebotomy. If necessary, intravascular volume can be maintained by infusions of crystal oid or colloid solutions.

Aspirin (at a dose of 81-100 mg orally 1 time per day) reduces the incidence of thrombotic complications. Patients undergoing phlebotomy alone or phlebotomy in combination with myelosuppressive therapy should take aspirin unless contraindicated.

Myelosuppressive therapy. Myelosuppressive therapy may be indicated for patients with platelet levels greater than 1/µl, with a feeling of discomfort due to increased visceral organs, with the presence of thrombosis, despite Ht less than 45%, symptoms of hypermetabolism or uncontrolled itching, as well as patients over 60 years of age or patients with cardiovascular diseases who do not tolerate bloodletting well.

Radioactive phosphorus (32 P) is effective in 80-90% of cases. The duration of remission ranges from 6 months to several years. P is well tolerated, and if the disease is stable, the number of follow-up visits to the clinic can be reduced. However, P therapy is associated with an increased rate of leukemic transformation, and when leukemia develops after phosphorus treatment, it is often resistant to induction chemotherapy. Thus, P therapy requires careful patient selection (eg, only used in patients likely to die from other disorders within 5 years).

Hydroxyurea is an inhibitor of the enzyme ribonucleoside diphosphate reductase - long time has been used for myelosuppression, its leukemic potential continues to be studied. Ht is reduced to less than 45% through phlebotomy, after which patients receive hydroxyurea at a dose of 20-30 mg/kg orally once daily. Patients are monitored weekly with a complete blood count. When a stable condition is achieved, the interval between control blood tests is extended to 2 weeks, and then to 4 weeks. When the level of leukocytes decreases to less than 4000/μl or platelets less than 100,000/μl, hydroxyurea is suspended, and when the levels are normalized, it is resumed at a dose reduced by 50%. In patients with unsatisfactory disease control, requiring frequent phlebotomies, or patients with thrombocytosis (platelet level > 600,000/μl), the dose of the drug may be increased by 5 mg/kg monthly. Acute toxicity is rare, and rash, GI symptoms, fever, nail changes, and skin ulceration may occasionally occur and may require discontinuation of hydroxyurea.

Interferon a2b was used in cases where blood cell levels could not be controlled with hydroxyurea or when the drug was poorly tolerated. The usual starting dose is 3 units subcutaneously 3 times a week.

Anagrelide is a new drug that has a more specific effect on megakaryocyte proliferation than other drugs and is used to reduce platelet levels in patients with myeloproliferative diseases. The safety of this drug during long-term use is currently being studied, but according to available data, it does not contribute to the progression of the disease to acute leukemia. When using the drug, vasodilation may develop with headaches, palpitations and fluid retention. To minimize the indicated side effects The drug is started at an initial dose of 0.5 mg twice daily, then the dose is increased weekly by 0.5 mg until the platelet count decreases to less than 450,000/mcL or until the dose is 5 mg twice daily. The average dose of the drug is 2 mg/day.

Most alkylating agents and, to a lesser extent, radiophosphorus (formerly used for myelosuppression) have leukemoid effects and should be avoided.

Treatment of complications of polycythemia vera

For hyperuricemia, if it is accompanied by symptoms or if the patient is simultaneously receiving myelosuppressive therapy, it is necessary to take allopurinol 300 mg orally once a day. Itching may be relieved after taking antihistamines, however, this does not always happen; the most effective treatment Myelosuppressive therapy is often a complication of this complication. To relieve itching, cholestyramine 4 g orally three times a day, cyproheptadine 4 mg orally 3-4 times a day, cimetidine 300 mg orally 4 times a day, paroxetine 20-40 mg orally once a day can also be used. After bath skin must be wiped carefully. Aspirin relieves the symptoms of erythromelalgia. Elective surgical interventions for polycythemia vera should be performed only after the Ht level has decreased

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