SICKEMIA (synonym: S-gemoglobinonatiya, sickle cell disease, drepanocytosis, drepanotsitarny anemia) — the hemoglobinopathy proceeding with hemolitic anemia for a cut existence in blood of crescent erythrocytes and periodic obstruction of a microcirculator bed by them in various bodies and fabrics is characteristic (especially with the slowed-down blood-groove).
The term «sickemia» designate heterogeneous group hemoglobinopathies (see), to a cut carry actually S. and., or a homozygous SS hemoglobinopathy, and the combined heterozygous forms on hemoglobin S and various options of a thalassemia (microdrepanocytosis), on hemoglobin S and hemoglobin F (a so-called hemoglobinosis of SF), on hemoglobin S and hemoglobin C and D and other haemo globins, abnormal on structure (see. Gemoglobin ). In this group a little especially there is a so-called drepanocytic anomaly of erythrocytes, edges is a heterozygous state on hemoglobin S, characterized by existence in blood of approximately equal proportions of hemoglobin A and S and absence a wedge, manifestations in usual conditions. The pregnancy, childbirth, flight in the unpackaged airplane which are stressful situations can cause the symptomatology similar to S. in nek-ry such heterozygous carriers and.
For the first time S. and. Herrick described (J. Century of Herrick) in 1910. Molecular bases of pathology L. Polingom, H. A. Itano and sotr were open in 1949. In 1956 Mr. V. Ingram found out that anomaly of hemoglobin S is caused by substitution glutaminic to - you in a beta and polypeptide chain of a globin valine.
Hemoglobin S represents system from the balanced polymorphism (see. Population ), the so-called malarial belt of the globe and the hemoglobin S providing protection of heterozygous carriers against tropical existing in populations malaria (see), the caused Plasmodium falciparum. In the local centers of malaria (e.g., in nek-ry districts of the Central Africa) hemoglobin S occurs at 40% of representatives in population; with a smaller frequency — at Blacks of the Western Africa, and also among populations of North Africa, the countries of the Mediterranean, the Middle East, India. In the USA 8% of Blacks are heterozygous carriers of hemoglobin S. In the USSR, according to R. Sh. Rustamov and sotr. (1981), the carriage of hemoglobin S at 3% of Azerbaijanians is revealed.
Etiology and pathogeny
Prichina S. and. is gene mutation (see), leading finally to synthesis of abnormal hemoglobin S, to-ry in a deoksigenirovanny state has property of polymerization and by 100 times we will dissolve less, than hemoglobin A. Thereof erythrocytes with deoksigemoglobiny S get a characteristic crescent form (fig.), in their membrane calcium is laid. They become rigid, lose plastic properties, cork capillaries and are hemolyzed. Speed and extent of formation of crescent erythrocytes depend on a ratio deoksi-and oxyhemoglobin S. This process is most intensive at a homozygous form C. and., at heterozygous S.'s combination of ampere-second a beta a °-thalassemia (see. Thalassemia ), and also at hemoglobinoses of SC and SD; haemo globins of C and D strengthen it, and others, napr, hemoglobin F, oppress. Formation of crescent erythrocytes also amplifies at undervoltage of oxygen in fabrics, increase in osmolarity of plasma, increase in contents 2,3 diphosphoglycerates in erythrocytes, decrease in pH of blood, delay of a blood-groove, a hypoxia and an anoxemia, at dehydration of an organism and fervescence. Weight hemolysis (see) correlates with number of the circulating crescent erythrocytes.
Long obstruction of capillaries crescent erythrocytes causes ischemia of fabrics up to formation of multiple heart attacks (see. Heart attack ), to-rye are especially often localized in a spleen, bones, marrow, and also in marrow of kidneys.
As well as majority of hemoglobinopathies of S. and. it is transferred on a codominant mode of inheritance.
At S. and. pathoanatomical changes same as at others it is long the proceeding hemolitic anemias (see. Hemolitic anemia ). Along with signs of hemolysis (jaundice, an eritrofagiya, a hemosiderosis of a liver, spleen, kidneys and limf, nodes) at sick S. and. note stagnation or, on the contrary, an extraordinary anemia of internals owing to blockade of vessels the agglutinated erythrocytes. Also thrombosis of vessels and heart attacks of internals as a result of disturbance of microcirculation are characteristic. Owing to Multiple heart attacks the spleen at children is more senior than 5 — 7 years and adults decreases in sizes, shrivels (a small siderofibrotichesky spleen).
The clinical picture
the Clinical picture depends on a number of factors: a heterozygous or homozygous state, the joined infection, a hypoxia, a stress, pregnancy, existence of aggravations (crises), complications, etc.
At adults the homozygous form at quiet disease is characterized by the moderate anemia which is only slightly reducing working ability of patients. Anemia is usually normokhromny, with gematokritny number apprx. 25%; content of the general hemoglobin makes 80 r/l, quantity of reticulocytes of 10%, is irreversible crescent erythrocytes of 12%, average life expectancy of erythrocytes apprx. 17 days, Aggravation of anemia can be connected with hypoplastic crisis (oppression of erythropoietic function of marrow), giiyergemolitiches-ky crisis (an increased hemolysis under the influence of the joined infection, a hypoxia, a stressful factor, etc.) and sekvestratsionny crisis (disintegration of a considerable part of erythrocytes in internals, in particular in a spleen). The painful crises which are characterized by an acute pain in the site of an eritrostaz or a heart attack, a leukocytosis and fever are the most specific. These crises are provoked by infections (at children), a hypoxia, dehydration, cold, etc. Sometimes their reason does not manage to be established. During painful crises distinguish three phases: ischemic (duration of 2 — 6 hours), infarctive (duration from 24 to 72 hours), micro embolic (lasting up to 1 week and more). The ischemic phase is characterized by tubular bone, backbone and joints pains.
It is reversible, especially at vigorous treatment. Many bone and joints pains, fever, perspiration, a leukocytosis and sometimes strengthening of anemia are inherent to an infarctive phase. At a mikroembo-lichesky phase the obstruction of vessels in various bodies and fabrics resulting from microembolization from iifartsirovan-ny marrow is observed. Depending on localization of thromboses at S. and. it is possible to allocate several syndromes — chest, musculoskeletal, abdominal (including hepatic), brain (is more often at children), etc. E.g., at obstruction of pulmonary capillaries there are pains in a thorax, a pleural exudate, breath is broken.
The homozygous form at children's age differs in heavier current, a high lethality as a result of the joined infection.
Complications of a homozygous form C. and. calculous cholecystitis, ulcers of extremities (is more often than anklebones), various damages of bones, napr are, fractures, osteomyelitis, are often observed aseptic necroses of heads of femoral and humeral bones, and also a retinopathy (see), a hamaturia (a renal origin), a hyperuricemia (see. Lithemia ), etc. Children can have fibrinferments of vessels of a brain (see. Stroke ), and adults have subarachnoidal hemorrhages (see. the Subshell hemorrhages ).
The wedge, a picture at a combination of a heterozygous form C. of ampere-second a beta talassemia has the following features: the splenomegaly is noted, there are targetoid erythrocytes, the hemoglobin content of F or A2 raises; complications in the form of thromboses meet rather seldom.
Vascular new growths, vitreous hemorrhages, ischemia and amotio of a retina are more characteristic of patients with a hemoglobinosis of SC.
the Diagnosis is based on the anamnesis (taking into account an ethnic origin of the patient), this a wedge, pictures, existence of the crescent erythrocytes in blood which are coming to light by means of test with sodium metabisulphite and a characteristic slow strip of hemoglobin S at an electrophoresis (see), and also on results of a family and genetic research.
Differential diagnosis is carried out with an infectious disease (see a viral hepatitis), jaundices of other origin (see Jaundice), other forms of hemolitic anemias, acute rheumatism (see) and pseudorheumatism (see), scurvy (see), rickets (see), tuberculosis of bones at children and teenagers (see Tuberculosis extra pulmonary, bones and joints), primary osteomyelitis (see), a long septic endocarditis (see), inborn heart diseases (see. Heart diseases inborn ), syphilis (see), frambeziya (see) with nek-ry inf. diseases, napr, with a typhoid (see); at abdominal painful crises with an acute abdomen (see).
symptomatic treatment. At painful crises appoint various analgetics, sedatives, in some cases drugs, an oxygenotherapy (see. Oxygen therapy ). In hard cases, napr, at the joined pneumococcal infection (pneumonia, an acute septic state, meningitis) that is often observed at children with S. and., apply antibiotics; in case of an operative measure by the patient with S. and. carry out partial zamenny hemotransfusions (see) for reduction of quantity of crescent erythrocytes (at the same time it is necessary gematol. and biochemical control). In a crust, time for the prevention of a polimeration of hemoglobin S drugs of thiol group are used. For the purpose of prevention or weakening of aggregation of erythrocytes at hemolitic crisis dezagregant apply (small doses of heparin, acetilsalicylic to - that). Preventive hemotransfusions make to the pregnant women suffering from S. and., during the strengthening of weight of a current or increase of crises. At the same time try to obtain reduction of quantity of erythrocytes with hemoglobin S (less than 50%). In especially hard cases during childbirth make partial zamenny hemotransfusions, at the same time whenever possible, it is necessary to avoid anesthesia.
Forecast actually S. and. (homozygous states) adverse; at heterozygous states on SC, SD, SF, 8V hemoglobin + - thalassemias — satisfactory.
Is necessary medicogenetic consultation (see) for the purpose of the prevention of marriages between heterozygous carriers C. and. and the recommendation of failure from posterity.
See also Thalassemia .
Bibliography: Alekseev G. A. and Tokarev Yu. N. Hemoglobinopathies, page 55, M., 1969; To about N about N I am a h e N to about V. A. and Yushkov of H. M. Drepanocytic anemia, M., 1968; Tokarev Yu. N., etc. A drepanocytic disease and other structural hemoglobinopathies, in book: The major hemoglobinopathies, 'under the editorship of O. K. Gavrilov and IO. N. Tokareva, page 36, M., 1979; To ark J. a. Les-s i n L. Sickle cell disease and variants, in book: Hematol. oncol., ed. by M. A. Lichtman, p. 89, N. Y. a. o., 1980; Lehmann H. Hunts m a n R. G. Man's haemoglobins, Amsterdam, 1974; Serjeant G. B. The clinical features of sickle cell disease, Amsterdam — N. Y., 1974, bibliogr.; Sickle cell symposium Arch, intern. Med., v. 133, p. 510, 1974
BB. H. Tokarev.