Polycythemia is a chronic hemoblastosis, which is based on the unlimited proliferation of all myelopoiesis sprouts, mainly erythrocyte. Clinically, polycythemia is manifested by cerebral symptoms (heaviness in the head, dizziness, tinnitus), thrombohemorrhagic syndrome (arterial and venous thrombosis, bleeding), microcirculatory disorders (limb chilliness, erythromelalgia, hyperemia of the skin and mucous membranes). Basic diagnostic information is obtained by examining peripheral blood and bone marrow. For the treatment of polycythemia, bloodletting, erythrocytopheresis, and chemotherapy are used.
Meaning
Polycythemia (Vaquez disease, erythremia, erythrocytosis) is a disease of the group of chronic leukemias characterized by increased production of erythrocytes, platelets and leukocytes, increased BCC, 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 thrombotic and hemorrhagic complications, as well as the likelihood of transformation into acute myeloblastic leukemia, erythromyelosis, chronic myeloid leukemia.
Causes
The development of polycythemia is preceded by mutational changes in the polypotent hematopoietic stem cell, which gives rise to all three bone marrow cell lines. The mutation of the JAK2 tyrosine kinase gene with the replacement of valine with phenylalanine in position 617 is most often detected. 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 progenitor cells of erythroid hematopoiesis 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 an autonomous cell population is nothing more than a mutant clone – the main substrate of polycythemia.
Pathogenesis
In the pathogenesis of erythremia, the leading role belongs to enhanced erythropoiesis, the consequence of which is absolute erythrocytosis, violation of rheological and clotting 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 filling of internal organs. At the end of polycythemia, hematopoiesis depletion and myelofibrosis are noted.
Classification
In hematology, there are 2 forms of polycythemia – true and relative. Relative polycythemia develops with a normal level of red blood cells and a decrease in plasma volume. This condition is called stress or false polycythemia and is not considered in this article.
True polycythemia (erythremia) by origin can be primary and secondary. The primary form is an independent myeloproliferative disease, which is based on the defeat of the myeloid germ of hematopoiesis.
Secondary polycythemia usually develops with an increase in the activity of erythropoietin; this condition is a compensatory reaction to general hypoxia and can occur with chronic pulmonary pathology, “blue” heart defects, adrenal tumors, hemoglobinopathies, when climbing or smoking, etc. True polycythemia in its development goes through 3 stages: initial, expanded and terminal.
Stage I (initial, low–symptomatic) – lasts about 5 years; proceeds asymptomatically or with minimal clinical manifestations. It is characterized by moderate hypervolemia, small erythrocytosis; the size of the spleen is normal.
Stage II (erythremic, expanded) is divided into two sub–stages:
- IIA – without myeloid transformation of the spleen. Erythrocytosis, thrombocytosis, and sometimes pancytosis are noted; according to the myelogram– hyperplasia of all hematopoietic sprouts, pronounced megakaryocytosis. The duration of the expanded stage of erythremia is 10-20 years.
- IIB – with the presence of myeloid metaplasia of the spleen. Hypervolemia, hepatomegaly and splenomegaly are expressed; in peripheral blood – pancytosis.
Stage III (anemic, posterythremic, terminal). Anemia, thrombocytopenia, leukopenia, myeloid transformation of the liver and spleen, secondary myelofibrosis are characteristic. Possible outcomes of polycythemia in other hemoblastoses.
Symptoms
Erythremia develops for a long time, gradually and can be detected by chance during a blood test. Early symptoms, such as heaviness in the head, tinnitus, dizziness, blurred vision, chilly limbs, sleep disorder, etc., are often “written off” as old age or concomitant diseases.
The most characteristic feature of polycythemia is the development of a plethoric syndrome caused by pancytosis and an increase in CBV. Evidence of fullness are telangiectasia, cherry-red coloring of the skin (especially the face, neck, hands and other exposed areas) and mucous membranes (lips, tongue), hyperemia of the sclera. A typical diagnostic sign is the Kuperman’s symptom – the color of the hard palate remains normal, and the soft palate acquires a stagnant cyanotic hue.
Another distinctive symptom of polycythemia is skin itching, which increases after water procedures and sometimes has an unbearable character. The 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, arterial hypertension may occur. In 80% of patients, moderate or severe splenomegaly is detected; the liver increases somewhat less frequently. Many patients with polycythemia notice increased bleeding of the gums, the appearance of bruises on the skin, 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.
Complications
The result of microthrombosis and trophic disorders of the skin and mucous membranes are trophic ulcers of the lower leg, stomach ulcers and duodenal ulcers. Complications in the form of vascular thrombosis of deep veins, mesenteric vessels, portal veins, cerebral and coronary arteries are the most frequent in polycythemia clinic. Thrombotic complications (PE, ischemic stroke, myocardial infarction) are the leading causes of death in patients with polycythemia. At the same time, along with thrombosis, polycythemia patients are prone to hemorrhagic syndrome with the development of spontaneous bleeding of various localization (gingival, nasal, esophageal veins, gastrointestinal, etc.).
Diagnostics
Hematological changes characterizing polycythemia are decisive in the diagnosis. Blood tests reveal erythrocytosis (up to 6.5-7.5 x 1012 / l), increased hemoglobin (up to 180-240 g / l), leukocytosis (over 12×109 / l), thrombocytosis (over 400×109/ l). The morphology of erythrocytes, as a rule, is not changed; with increased bleeding, microcytosis may be detected. A reliable confirmation of erythremia is an increase in the mass of circulating erythrocytes of more than 32-36 ml/kg.
For the study of the bone marrow in polycythemia, it is more informative to conduct not a sternal puncture, but a trepanobiopsy. Histological examination of the biopsy revealed panmyelosis (hyperplasia of all hematopoietic sprouts), in the late stages of polycythemia – secondary myelofibrosis.
To assess the risk of developing complications of erythremia, additional laboratory tests (functional liver tests, urinanalysis) and instrumental studies (ultrasound of the kidneys, ultrasound of the veins of the extremities, EchoCG, ultrasound of the vessels of the head and neck, EGD, etc.) are carried out. In case of a threat of thrombohemorrhagic and metabolic disorders, consultations of relevant narrow specialists are required: neurologist, cardiologist, gastroenterologist, urologist.
Treatment
In order to normalize the volume of BCC and reduce the risk of thrombotic complications, the first measure is bloodletting. Blood exfusions are carried out in a volume of 200-500 ml 2-3 times a week, followed by replenishment of the removed blood volume with saline or rheopolyglucine. The consequence of frequent bloodletting may be the development of iron deficiency anemia. Bloodletting in polycythemia can be successfully replaced by erythrocytapheresis, which allows only the erythrocyte mass to be extracted from the bloodstream, returning plasma.
In the case of pronounced clinical and hematological changes, the development of vascular and visceral complications, myelodepressive therapy with cytostatics (busulfan, mitobronitol, cyclophosphamide, etc.) is resorted to. Sometimes therapy with radioactive phosphorus is carried out. To normalize the aggregate state of the blood, heparin, acetylsalicylic acid, dipyridamole are prescribed under the control of a coagulogram; platelet transfusion is indicated for hemorrhages; allopurinol is indicated for urate diathesis.
Forecast
The course of erythremia is progressive; the disease is not prone to spontaneous remissions and spontaneous cure. Patients are forced to be under the supervision of a hematologist for life, undergo courses of hemoexfusion therapy. Polycythemia has a high risk of thromboembolic and hemorrhagic complications. The frequency of transformation of polycythemia into leukemia is 1% in patients who did not undergo chemotherapy treatment, and 11-15% in those who received cytostatic therapy.
Literature
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