POLYCYTHEMIA (grech, poly is a lot of + kytos a cell + haima blood; synonym: Osler's disease, Vakez's polycythemia, erythremia — Oslera, an erythremia) — the tumoral myeloproliferative disease of the hemopoietic system, a cut is characterized by significant increase in quantity of mature erythrocytes (and also mature granulocytes and thrombocytes at the same time or consistently), the progressing current, lack of spontaneous remissions and spontaneous treatment. Items carry to to hemoblastoses (see), to group hron, leukoses of a myeloid origin (see. Leukoses ).
In 1892 A. Vakez for the first time described the syndrome which is characterized by dark red coloring of skin, a resistant hyperglobulia (see. Hyperglobulias ), increase in a hemoglobin content, increase in the sizes of a liver and spleen. In 1903 U. Osler gave the detailed description of P. as new a wedge, forms. In 1902 — 1904. W. Turk introduced the idea of the hyperplastic nature of disturbance of a hemopoiesis at this disease and by analogy with leukemia called a disease an erythremia.
The item meets rather seldom, according to Silverstein (M. of N. Silverstein, 1971), its frequency makes 0,6 — 1,8: 100 000. Average age of sick 55 — 60 years, sometimes a disease meets at children's and youthful age. Men are ill a little more often than women.
The etiology and the Pathogeny
the Aetiology is unknown. Significance of genetic predisposition to a disease P.
Patogenez is attached. The clonal neoplastic nature of a miyeloprolifera-tion at P. is proved Violet (P. J. Fialkov, 1980) which found one type of enzyme glyukozo-6-fosfatdegidrogenazy in erythrocytes, granulocytes and thrombocytes and both types of this enzyme in lymphocytes in two sick women, heterozygous on this enzyme. Thus, the target of neoplastic process should be considered a cell-predshestven-nitsu of a myelopoiesis. In culture these cells at addition erythropoetin (see) contain as one, and both types of enzyme of glyukozo-6-fosfatde-hydrogenase. It follows from this that at P. a part of the healthy stem cells which are normally reacting to erythropoetin remains, but in vivo they depressirutsya unknown, perhaps humoral, by mechanisms. In 1980 a number of researchers separated a neoplastic clone of cells from normal. In an experiment it is also shown that at P. there is population of the committed erythroidal predecessors having patholologically high sensitivity even to trace amounts of erythropoetin that, probably, and defines the increased formation of erythrocytes at this disease.
In a blood plasma of a half of sick P. it is found, except erythropoetin, the humoral stimulator of all three sprouts of a hemopoiesis demanding presence of erythropoetin which is not identified yet. Its participation in a pathogeny of a disease is supposed.
In 25 — 30% of cases of P. in cells of a hemogenesis aberation chromosomes are established (see. Mutation ) — an aneuploidy, deletion of a chromosome of the F (couple 19 — 20) group, a trisomy in
group C, restructurings of chromosomes. However Fialkov of chromosomal changes at two sick P., heterozygous on a glyukozo-6-phosphate-dehydrogenase, did not find and considers that they are not required for initial proliferation of a neoplastic clone. The fact of frequency of chromosomal anomalies noted prior to cytopathic therapy at all their not specificity is confirmation of the neoplastic nature of a disease.
Vascular complications at P. (fibrinferments, bleedings) are caused by increase in viscosity of blood, delay of a blood-groove, increase in quantity of thrombocytes, excess of erythrocyte thromboplastic substances, functional inferiority of thrombocytes, deficit of blood-coagulation factors, napr, fibrinogen. The researches conducted in 1981. L. To D. Sidorova et al., showed that the main role in a pathogeny of trombotichesky and hemorrhagic complications is played by quantitative and qualitative changes in platelet a link of a hemostasis.
During the opening of the dead from P. in the developed stage of a disease the most characteristic signs are the expressed plethora of bodies and fabrics, a sharp hyperplasia red marrow (see), increase in a spleen (see. Splenomegaly ), liver (see). Skin, especially faces, mucous membranes have red and cyanochroic coloring. The xanthopathy of the lower extremities, trophic ulcers of shins is quite often observed. Red marrow of flat bones juicy, red and cherry color, in tubular bones yellow marrow is replaced by red. The sizes and mass of a spleen and liver, as a rule, are considerably increased. Tissue of a spleen on a section of dark red color, with the erased drawing, quite often contains fresh and old heart attacks. The hypertrophy of a myocardium, hl is possible. obr. left ventricle. Sometimes on a mucous membrane of a stomach, a duodenum multiple ulcerations are observed. Quite often find fresh and organized blood clots in large and small vessels of the lower extremities, abdominal cavity, heart, brain and other bodies. Along with it hemorrhages in skin, mucous and serous membranes, fabric of various bodies can be noted.
Microscopically the trekhrostkovy hyperplasia of marrow of different degree depending on duration and a stage of a disease is characteristic of P. In the developed stage of a disease in red marrow significant increase in quantity of nuclear forms of an erythroidal row, megacaryocytes, granulocytes at different stages of maturing in combination with reduction of lipoblasts is defined, up to their total disappearance (tsvetn. fig. 4). Sine are considerably expanded, filled with blood (tsvetn. fig. 5). Megacaryocytes differ in the expressed polymorphism, existence of unripe forms, often are located in the form of accumulations (tsvetn. fig. 6). Among granulocytes quite often there are a lot of eosinophils. With the small duration of a disease the hyperplasia of red marrow, in particular megakariotsitoz, is expressed moderately, yellow marrow is partially kept. After use of cytostatic drugs the ratio of red and yellow marrow, close to norm, formation of sites of an aplasia can be observed.
At P. quite often note development of a secondary myelofibrosis, a precursory symptom to-rogo is focal or diffusion increase in amount of argentofilny fibers of a stroma against the background of the expressed hyperplasia of marrow that is found by means of a trepanobiopsiya at impregnation of cuts silver salts. In process of progressing of fibrosis the quantity of cells of marrow decreases, bunches of reticulin and collagenic fibers diffuzno fill marrowy cavities (tsvetn. fig. 7).
In a spleen and a liver in the developed P.'s stage and at an outcome in a myelofibrosis find the sharp plethora, fibrous changes expressed in various degree and the centers of a trekhrostkovy hemopoiesis with dominance of cells of an erythrocytopoiesis (tsvetn. fig. 8) which can be observed also in other bodies, napr, in limf, nodes, kidneys. Vascular complications — thrombosis are the main reasons for death of sick P. (tsvetn. fig. 9), thromboembolisms (see), hemorrhages (see), the causing deep disturbances of blood circulation and development of heart attacks of vitals. At P.'s transformation in a leukosis reveal morfol. the changes typical for this group of diseases (see. Leukoses ).
The clinical picture
Conditionally a number of researchers allocates three stages of the Item. The first (initial) stage is characterized by moderate increase in volume of the circulating blood (see. Plethora ) with normal quantity of leukocytes, thrombocytes and with a focal hyperplasia of red marrow; the second And (developed, without myeloid metaplasia of a spleen) — the expressed plethora moderated gepato-and a splenomegaly, a pan-cytosis; the second B (developed, with a myeloid metaplasia of a spleen) — a pan-cytosis with shift leukocytic formula (see) to the left and expressed gepato-and a splenomegaly; the third stage (terminal, anemic) is characterized by the expressed anemia, an outcome in a myelofibrosis, a myeloleukemia is more rare in an acute leukosis or hron.
The disease begins usually slowly and imperceptibly. Patients complain of fatigue, headaches, dizziness, pains in heart, in bones, a skin itch, feeling of heat, weight loss. Red and cyanochroic coloring of skin and visible mucous membranes is characteristic of sick P.; the sharp redness of a soft palate contrasting with pale coloring of a hard palate (Kupperman's symptom). Vessels of scleras are usually injected (a symptom of «rabbit eyes»). On cheeks and a tip of a nose are often formed teleangiectasias (see). P.'s symptom, the second for frequency — a splenomegaly — comes to light, by data A. V. Demidova (1965), at 78,5% of patients and is caused by the increased deposition and sequestration of uniform elements of blood, participation of a spleen in myeloproliferative process, and also sometimes a vnut-ripechenochny and extrahepatic (trombotichesky) portal hypertension. Increase in a liver is observed at 68% of patients in connection with the raised krovenapolneniye and growth of connecting fabric (up to development of cirrhosis) owing to stagnation of blood. Disintegration of the increased quantity of erythrocytes and a pleyokhromiya of bile (the increased maintenance of bilious pigments) can lead to a complication — cholelithiasis (see).
At many patients pletorichesky arterial hypertension with increase preferential systolic and to a lesser extent diastolic pressure develops. Increase in mass of the circulating blood and increase in the ABP lead to increase in load of cardiovascular system, however heart failure for P. is not inherent, except for cases of a coronarothrombosis. A respiratory organs at P. is surprised rather seldom. Tendency to the diseases connected with delay of a blood flow in vessels of lungs, napr to bronchitis is noted. Overflow by blood of abdominal organs breaks a trophicity of a mucous membrane went. - kish. a path that can lead to its ulceration; stomach ulcer and a duodenum, by data A. V. Demidova (1965), come to light at 14% of sick Items.
Disturbances from c. N of page are caused by delay of a blood flow, and also fibrinferments (see) or punctulate and macrofocal hemorrhages in substance of a brain.
Increase in a hemoglobin content within 180 — 200 g/l and quantity of erythrocytes to 6 — 8*10 is characteristic of P. 12 in 1 l with an indicator of a hematocrit of 60 — 70% and above (see. Gematokritny number ). A reliable symptom of a disease is increase in mass of the circulating erythrocytes up to 32 — 36 ml/kg and above that leads to delay of ROE up to 1 — 3 mm/hour and to increase in viscosity of blood. The quantity of leukocytes usually fluctuates from 9000 to 15 000 in 1 mkl, the neutrocytosis (neutrophils contain the increased quantity of an alkaline phosphatase) and band shift of a leukocytic formula is noted. At most of patients the thrombocytosis from 400 000 to 1 000 000 in 1 mkl comes to light above. At 25 — 30% of patients a long time the quantity of leukocytes and thrombocytes does not change. At development of a myeloid metaplasia of a spleen it is observed polychromatophilia (see), anizo-and poikilocytosis, basphilic stippling erythrocytes (see), normoblasts. In to a miyelogramma (see) — reduction of a leykoeritroblastichesky index, increase in quantity of megacaryocytes.
At P. the periods which are characterized by a quiet current (kliniko-hematologic compensation after treatment), and the periods with expressed a wedge, manifestations (eritremichesky crises) can be observed.
The albuminuria almost constantly is found in sick P. (see. Proteinuria ), sometimes hamaturia (see) that is connected, as a rule, with heart attacks of kidneys (fibrinferments of renal arteries). At P., as well as at other myeloproliferative diseases, the nephrolithiasis can develop, the cut is the cornerstone disturbance of purine exchange (see. Urate diathesis ), shown a hyperuricemia and a hyper uricosuria (the increased contents uric to - you in blood and urine).
The item, as a rule, proceeds from the outcome in a secondary myelofibrosis that is followed by disappearance of external symptoms of a disease, the progressing increase in a spleen, anemia, increase of a leukocytosis with shift of a blood count to the left, normoblastozy and qualitative changes of erythrocytes; note an outcome in an acute leukosis and in hron, a myeloleukemia less often.
Among complications vascular pathology — vein thromboses of extremities, coronal (coronary) and brain vessels, tendency to bleedings which can arise spontaneously or (most often) after any, even small, operative measures, napr, extractions of teeth figures prominently. At P. peculiar functional vascular complications are often observed — eritromelalgiya (see) and an acroparesthesia (see. Angiotrofonevroza ), shown burning pristupoobrazny extremity pains, erubescence and hypostases.
the Diagnosis the wedge, pictures and data establish on the basis of the anamnesis, a lab. researches — blood test and gistol, researches of marrow. At gistol, a research of the marrow received by method trepanobiopsiya (see), reveal a characteristic hyperplasia of all three sprouts with expressed megakariotsitozy and reduction of quantity of lipoblasts.
Differential diagnosis carry out with symptomatic (secondary) hyperglobulias (see), at to-rykh the strengthened erythrocytopoiesis without characteristic trekhrostkovy hyperplasia of marrow is observed; with myeloproliferative diseases, e.g. primary myelofibrosis (see. Osteomyelofibrosis ), at Krom the plethora is short-term, a splenomegaly, changes of a leukocytic formula, normoblastoz in blood, growths of fibrous fabric prevail. Items differentiate also from primary trombotsitemiya (see), characterized by bleedings, thromboses and the increased quantity of thrombocytes (2 000 000 — 5 000 000 in 1 mkl); with hron, a myeloleukemia, at Krom Ph '-a chromosome in cells of marrow comes to light and the granulotsitarny sprout with the broken maturing of cells prevails (see. Leukoses ).
Treatment, as a rule, complex. For a degrowth of erythrocytes appoint bloodlettings (see) and various cytostatic means (see), the activities of marrow directed to suppression. The indication to bloodletting as to independent remedy is the plethora (hemoglobin higher than 180 g/l and an indicator of a hematocrit higher than 55%) without high leukocytosis and a thrombocytosis, and also youthful age of patients. They are repeated in 1 — 2 day, the amount of hemoglobin or an indicator of a hematocrit is not normalized yet. Prolonged use of bloodlettings can cause deficit of iron, in such cases they are stopped and appoint iron preparations; at development of a reactive thrombocytosis dezagregant recommend (acetilsalicylic to - that on 0,5 g or trental on 200 — 300 mg a day). For obtaining more bystry effect combine bloodlettings with cytostatic means which appoint the patient, as a rule, at advanced age (50 years are more senior) in the presence of a pan-cytosis, a splenomegaly and a skin itch. The most effective is Myelosanum which is applied on 4 — 6 mg a day, on a course 250 — 300 mg; in process of decrease in leukocytes and thrombocytes the daily dose is reduced. Duration of a course of treatment is 2 — 3 months. Such course allows to exercise control of reaction of a hemopoiesis and gives the chance to avoid overdose. Imiphosum is appointed on 50 mg a day, to a course 450 — 550 mg. Drug has the expressed leu-kopenichesky and especially thrombocytopenic effect. Miyelobro-mol it is shown at a high leukocytosis and a splenomegaly on 250 mg a day, on a course 7,5 — 10 g. Chlorbutinum (a daily dose of 10 mg, on a course 400 — 500 mg) is used at low indicators of leukocytes and thrombocytes. Assessment of effect of cytostatic drugs at P. is carried out in 2 — 3 months after an initiation of treatment (according to life expectancy of erythrocytes). Blood is investigated in 7 days. During the falling of quantity of leukocytes lower than 5000 and thrombocytes lower than 100 000 in 1 mkl cytostatic drugs cancel.
At P.'s outcome in a secondary myelofibrosis with the advent of anemia appoint androgens or anabolic hormones, transfusions eritrotsitny weight (see). The hemolitic nature of anemia is the indication for use of steroid hormones. In rare instances recommend splenectomy (see).
In the presence of complications carry out a symptomatic treatment: at fibrinferments appoint heparin; at an erit-romelalgiya — acetilsalicylic to - that or a metindol (indometacin); at urate diathesis — Miluritum (Allopyrinolum), plentiful drink of alkaline waters; at a skin itch — antihistaminic drugs (Dimedrol, Diazolinum, Pipolphenum).
Restriction of the food rich with iron, proteins and cholesterol is reasonable. Dignity. - hens. treatment during remission is not contraindicated (without change of a climatic strip). The physical therapy is categorically contraindicated.
Due to the emergence of effective cytostatic pharmaceuticals radiation therapy at P. has limited value that is caused by increase of acute leukoses after its use.
The indication to purpose of radiation therapy is advanced age (50 years are more senior), the developed stage of the disease proceeding with a pan-cytosis and a splenomegaly, lack of effect of bloodlettings and cytostatic therapy. As a contraindication serve youthful and childbearing age, initial, and also terminal (anemic) stages of a disease with leykotsito-and (or) thrombocytopenia, existence of fresh vascular thromboses, an acute hepatitis.
The main means of radiation therapy is radioactive phosphorus which is applied in the form of water solution of disubstituted sodium phosphate. There are two ways of treatment: single introduction 32P in a vein in number of 3 — 5 mkyur and intake 1 — 2 mkyur each 4 — 10 days, on a course 6 — 8 mkyur. At the choice of a dose consider the weight of the patient, a picture of blood and disease severity. Improvement of health is usually observed on 3 — 4th week of treatment. Kliniko-gematologichesky remission occurs in 2 — 4 months. In the absence of therapeutic effect carry out additional treatment. At a recurrence treatment is repeated.
At forms, resistant to 32P, and existence of contraindications to chemotherapy it is possible to use remote radiation therapy. Patients are subjected to total or subtotal radiation in a single focal dose 20 — 25 I am glad (0,2 — 0,25 Gr), at the same time the total dose in certain sites of a skeleton brought for 5 — 6 sessions shall not exceed 150 is glad (1,5 Gr).
the Forecast for life without treatment adverse. Cytostatic means can prolong life of patients for 20 years and more. Average survival of patients at treatment with cytostatic means makes 11 — 15 years. The main hazard to life of the patient is posed by vascular complications. Dispensary observation behind sick P. (constant control behind blood, timely carrying out courses of cytopathic therapy) considerably reduces danger of vascular complications. Rational employment (release from heavy exercise stresses, rises on big height, works in gas-polluted rooms, hot workshops) creates premises for long working capacity of the persons suffering from a polycythemia.
See also Myeloproliferative diseases .
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L. I. Krasyukova; A. V. Demidov (etiol., patog.), G. D. Baysogolov (medical I am glad.); M. P. Khokhlova (stalemate. An.).