TROMBOTsITEMYYa (thrombocyte[s] + Greek haima blood; synonym: primary trombotsitemiya, a trombo-cytemia hemorrhagic, a trombotsitemiya essential, a trombotsitemiya idiopathic, a chronic megakariotsitarny leukosis, a hyper-platelet myelosis) — the rare pathological process which is relating to group of leukoses and shown sharp increase in blood of quantity of thrombocytes (hyperthrombocytosis) and trombogemorragichesky complications.
For many years place of T. among other diseases of system of blood it was not defined. A number of researchers carried to T. iatol. the processes proceeding with a hyperthrombocytosis and shown by tendency to bleedings and a thrombogenesis. In 1951 Mr. W. Dameshek carried T. to myeloproliferative diseases (see). I. A. Kassirsky and
G. A. Alekseev (1970), M. S. Dultsin et al. (1965) considered T. one of options of an osteomyelofibrosis (see), as at gistol. a research of bodies of a hemopoiesis at T. quite often fibrosis comes to light. In a crust, time most of hematologists consider T. as the leukosis relating to myeloproliferative diseases.
Increase in quantity of thrombocytes is quite often noted at a number of diseases of the tumoral and not tumoral nature, napr, at a subleykemi-chesky myelosis (with a myelofibrosis and without it), polycythemias (ShM.), hron. myeloleukemia, nek-ry forms of an acute leukosis, etc. However excess proliferation of a platelet sprout of a hemopoiesis
with strengthening of products of thrombocytes, edges can be observed within several years, and also feature a wedge, pictures of a disease allow to allocate T. in a separate nozol. a form within myeloproliferative diseases. Does not contradict it and quite often revealed at gistol. a research fibrosis of the hemopoietic bodies as fibrosis of red marrow is rather often noted at other leukoses carried to myeloproliferative diseases. T. usually develops at the age of 50 — 60 years with an identical frequency at men and women.
Etiology and pathogeny. Disease polietiologichno. On a pathogeny of T., as well as other leukoses (see), treats tumoral diseases, emergence to-rykh is connected with emergence in an organism of a clone of leukemic cells. Klopovy nature of T. Gaetani (G. F. Gaetani, 1982) with soavg is proved. at a glyukozo-6-phosphate-dehydrogenase research in various blood cells of the patient, heterozygous on a gene of this enzyme. At the same time it was shown that erythroidal, granulotsitarny and megakariotsitar-ny elements had a monoclonal origin while lymphocytes of blood and fibroblasts were not directly involved in patol. process.
Clinical picture. One of characteristic signs of T. the sharp increase in quantity of thrombocytes in blood which is quite often reaching several million in 1 mkl and combined with changes of morphology and function of thrombocytes is. Extent of functional changes of thrombocytes considerably defines features a wedge, pictures, in a cut the manifestations caused by a trombogemorragichesky syndrome dominate (hemorrhages and fibrinferments). Bleedings (nasal, gingival, uterine, from a mucous membrane went. - kish. a path and urinary tract, etc.) quite often arise spontaneously or after small injuries and operative measures; they difficult stop and can lead to development of a posthemorrhagic iron deficiency anemia (see). Existence of ecchymomas and hypodermic hemorrhages is characteristic, petechias meet seldom.
Trombotichesky complications are most often shown by changes of microcirculation (see). Quite often microcirculator disturbances can be the only thing a wedge, T. Tipichna's sign of disturbance of microcirculation in finger-tips of legs (more often) and hands, the skin which are shown an itch, severe pains, sinyush-nostyo and a gangrenosis. Disturbances of microcirculation can lead also to heavy visual disturbances, changes from c. N of page and kidneys. These changes are connected with the increased ability of thrombocytes to aggregation at an intact vascular wall. Quite often the course of a disease is complicated by development of thromboses of large vessels, is more often than veins (portal, splenic, hepatic, hypodermic, etc.). Formation of blood clots and in arteries is possible (mesenteric, sleepy, coronal, brain, pulmonary, etc.). At the heart of development of thromboses (see) and hemorrhages the same mechanisms — the increased tendency of thrombocytes to aggregation with the subsequent release from them a large amount of biologically active agents (thromboxane, ADF, an anti-heparin factor, serotonin, etc.) increasing fibrillation (thrombophilia) and a vascular tone lie; in development of thromboses of large vessels local changes of an endothelium have essential value; developing of hemorrhagic diathesis (see. Hemorrhagic diathesis) it is caused by the disseminated intravascular coagulation. Extent of disturbances in system of a hemostasis widely varies at various patients and is not always combined with changes of quantity of thrombocytes. At a number of patients the disease can proceed asymptomatically for a long time.
At an objective research moderate increase in a spleen often comes to light. The hepatomegalia is noted rather seldom. Limf, nodes do not increase.
The diagnosis is established on the basis by a wedge, pictures and data of a blood analysis and marrow.
The research of red marrow reveals the moderate increase in quantity of megacaryocytes which is combined with increase in quantity of elements of a leykotsitopoez and Erie-trotsitopoeza (panmyelosis) and reduction of amount of fatty tissue.
At many patients, especially at the long course of a disease, the myelofibrosis, a pathogeny to-rogo is observed at T., as well as at other myeloproliferative diseases, finally it is not found out. Value of the platelet growth factor (a mitogenetic factor) allocated to megacarat of an iotsitama and having ability to strengthen proliferation of both smooth muscle cells of a vascular wall, and fibroblasts is widely discussed. This polypeptide also stimulates synthesis of collagen and glikozamino-glycanes. Increase in its concentration in marrow can be connected with increase in number of megacaryocytes and with defect and - granules, in to-rykh the platelet growth factor (the acquired megakariotsitopatiya) is deposited.
At T., as well as at other leukoses, chromosomal disturbances are observed. So, at a number of patients in cells of marrow deletion of a part of a long shoulder of one of chromosomes of the 21st couple — del (21) (qll) is noted.
In blood the quantity of thrombocytes (see), usually more than 800 000 in 1 mkl, at certain patients — 8 000 000 — 12 000 000 in 1 mkl is sharply increased. It is connected with increase in products of thrombocytes, sometimes by 15 times, at normal terms of their circulation in blood. The quantity of leukocytes is usually increased moderately (10 000 — 15 000 in
1 mkl). The leukocytic formula is not changed a thicket though the shift is possible to the left (to myelocytes). Activity of an alkaline phosphatase in neutrophils of blood normal or is a little increased. At nek-ry patients in blood the quantity of progenitors of a gra-nulomonotsitopoez is increased. At certain patients, especially at the beginning of a disease, the quantity of erythrocytes and hemoglobin can be a little increased. In blood smears thrombocytes form large units. Existence of huge thrombocytes, and also thrombocytes of a bizzare shape with the expressed vacuolation is typical. Quite often megacaryocytes and especially their fragments come to light. At electronic microscopic examination, in addition to vacuolation of thrombocytes, their excessive granulation with sharp disturbances of a form of granules is observed (rhabdoid, triangular shape, etc.). However many thrombocytes have normal ultrastructure. Changes of function of thrombocytes come down to strengthening of aggregation of in vitro in response to collagen and ADF, to in vivo and deficit expressed to spontaneous aggregation in thrombocytes of a factor 3. At the same time adhesion of thrombocytes to collagen is significantly not changed. In a blood plasma increase in quantity uric to - you and B12 vitamin quite often comes to light.
T. differentiate with symptomatic, or secondary, a thrombocytosis, to-ry meets at physiological (the physical tension, a hyperadrenalemia) and morbid conditions of an organism. The symptomatic thrombocytosis is possible at intensive regeneration of blood (e.g., after bleedings, hemolitic crises). Besides, it is quite often observed after removal of a spleen or at its atrophy, at inflammatory diseases (tuberculosis, osteomyelitis, rheumatism, acute inf. diseases, etc.), tumors, hron. a myeloleukemia, a polycythemia, an osteomyelofibrosis, a polycystosis of kidneys, Itsenko's disease — Cushing, etc. Increase in quantity of thrombocytes in these cases is connected with redistribution of thrombocytes (physical tension, a post-adrenalinic thrombocytosis) or strengthening of their otshnurovka from megacaryocytes. At a symptomatic thrombocytosis the quantity of thrombocytes seldom reaches 1 OOO OOO in 1 mkl, the morphology and their function are usually not changed, and a bleeding time normal. However at sharp increase in quantity of thrombocytes disturbances of microcirculation, and also development of trombogemorragichesky complications are possible.
Treatment is carried out by cytostatic means, preferential Myelosanum (a daily dose apprx. 4 mg) within several weeks. Use also other drugs — miyelobrokhmol, Chlorbutinum, radioactive phosphorus, etc. At disturbances of microcirculation purpose of antiagregant is necessary (acetilsalicylic to - you, curantyl, trental, an anturan). In need of immediate reduction of quantity of thrombocytes the plateletpheresis is shown (see the Plasma exchange).
The forecast is rather favorable. Cytostatic therapy usually leads to permanent decrease in quantity of thrombocytes and involution of the changes caused by disturbances of microcirculation. Remissions, as a rule, long, and most of patients does not need a maintenance therapy. Outcomes of T are described. in an osteomyelofibrosis. Trombotichesky complications are the main reason for death.
Bibliography: Dulcin M. C., Kass
sirsky I. A. and Rausch of N - and x M. O. Leukoses, M., 1965; Ista-makova T. Page, Diamonds B. And, and Kanayev S. V. Functional hematology, L., 1973; Dameshek W, Some speculations on the myeloproliferative syndromes, Blood, v. 6, p. 372, 1951; G an e t a n i G. F. a. o. Primary throm-boeythemia, clonal origin of platelets, erythrocytes, and granulocytes in A GdB/Gd mediterranean subjects, ibid., v. 59, p. 76, 1982; Petit P. Van den Ber-g h e H. A chromosomal abnormality (21 q) of in primary thrombocytosis, Hum. Genet., v. 50, p. 105, 1979; Zaccaria A. T u r a S. A chromosomal abnormality in primary thrombocythemia, New Engl. J. Med., v. 298, p. 1422, 1978.
V. A. Almazov.