Enzimopenichesky hemolitic anemias — group of the diseases which are characterized by deficit of activity of erythrocyte enzymes are more often than glyukozo-6-fosfatdegidrogenazy (G-6-FD).
Epidemiology Deficit of activity of this enzyme is eurysynusic among inhabitants of tropical and subtropical belts of the globe, especially in the countries of the Mediterranean and Africa therefore there were names of the Mediterranean and African options of deficit of activity 7-6-FD. In some regions of Italy and Greece deficit of activity of enzyme occurs at 36% of the population, on the island of Sardinia the percent of distribution reaches it 48%. In Armenia the frequency of deficit of activity of G-6-FD among men fluctuated from 0,12 to 0,94%, among residents of Azerbaijan and Tajikistan there are from 4,6 to 37,3% and from 1 to 5,7% respectively.
There is quite large number of the oxidizers capable to cause increase of hemolysis in persons (is more often at children) with deficit of activity of G-6-FD (antimalarial means of a quinolinic row, streptocides, sulphones, anesthetics and antitubercular drugs, antibiotics, some bean plants, viruses of hepatitis and flu, etc.). The oxidizing action is connected in their structure of phenolic group.
Etiology and pathogeny More than 250 various mutant G-6-FD forms differing on electrophoretic mobility, affinity to glyukozo-6-phosphate, a nikotinamid-dinukleotidfosfata (NADF) are known. Insufficient activity of enzyme is a consequence of the lowered affinity.
Insufficiency of G-6-FD is inherited as the sign linked to X-chromosome. At men because of existence at them only one X-chromosome controlling formation of G-6-FDG, its defect in the form of deficit of enzyme is shown in all cases.
Women, heterozygous on this sign, have two populations of erythrocytes: with normal activity of G-6-FD controlled by normal X-chromosome and with the reduced activity caused by defective X-chromosome ("mosaicism") at them at high percent of maintenance of enzimodefitsitny population of erythrocytes the hemolitic crises provoked by medicinal and other factors are observed. At deficit of G-6-FD when recovery of NADF is broken, the recovered glutathione cannot resist to their action. It is led to hemoglobin oxidation, loss by gem from its molecule.
Classification WHO experts allocate 4 options (class) of deficit G-6-FD taking into account clinical shows and level of activity of enzyme in erythrocytes: 1) the options which are followed by chronic hemolitic anemia; 2) options with the level of activity of enzyme of 0 — 10% of norm which carriage proceeds without anemia out of crisis and are caused by development of crises at drug intake or the use of horse beans; 3) options with the level of activity of enzyme of 10 — 60% at which the rare clinical manifestations connected with drug intake can be observed; 4) options with the level of activity of enzyme, normal or close to norm, in erythrocytes without clinical manifestations.
Clinic Weight of clinical manifestations of insufficiency of G-6-FD not always correlates with the level of activity of enzyme in erythrocytes. More often crises do not arise without provocation at all.
Approximate formulation of the diagnosis: The Enzimopenichesky hemolitic anemia provoked by drugs oxidizers with deficit of activity of G-6-FD, proceeding with yellowness of skin, periodic darkening of urine, increase of free fraction of bilirubin in blood serum and plasma hemoglobin, a reticulocytosis, a leukocytosis, shift of a leukocytic formula to myelocytes, irritation of an erythrogenesis in marrow, increase in a spleen and liver, development of the IDCS, a renal failure.
The clinical symptomatology of medicamentally provoked hemolysis at persons with deficit of activity of G-6-FD is shown on 3 — the 5th day after receipt in an organism of drugs oxidizers. Deep hemolitic crisis sometimes proceeds with fervescence, symptoms of the general intoxication, short wind, abdominal pains, yellowness of integuments, urine of black or brown color, extremity pains, vomiting, a diarrhea, development of a renal failure; level of hemoglobin and quantity of erythrocytes are reduced, the reticulocytosis, a leukocytosis with shift to myelocytes, the expressed irritation eritro-and a normoblastic sprout of marrow are observed; can come to light increase of free fraction of bilirubin of blood serum and hemoglobin of plasma, fibrinferment. The severe disease often is followed by increase in a spleen, sometimes a liver. The massive erythrocytolysis promotes in some cases emergence of an intravascular blood coagulation that can lead to the microcirculation block in kidneys with development of an acute renal failure.
At some options of insufficiency G-6-FD (which are found, for example, among Blacks) hemolitic crises break though patients continue to accept the medicines which caused their development. Hemolitic crises at deficit of G-6-FD can meet at flu, a viral hepatitis and other infectious diseases, irrespective of use of medicines; the hemolitic illness of newborns caused by deficit of activity of G-6-FD. arises at once after the birth. Its clinical symptomatology is in essence identical to the hemolitic anemia which arose owing to an immunological havoc on antigens of the AVO and Rh system.
At individuals with insufficiency of G-6-FD hemolitic anemia after the use develops in food of horse beans (favism). Assume that at this illness the combination of the deficit of G-6-FD to insufficiency of the enzyme (inherited autosomno), neutralizing in a liver the toxic substances which are contained in horse beans which, apparently, exert negative impact on a membrane of erythrocytes takes place. Development of hemolitic crisis is followed by a febricula, weakness, fervescence, a fever, nausea, vomiting and abdominal pains. There are anemia, jaundice with a haemoglobinuria.
The erythrogenesis is characterized by sharp decrease in quantity of erythrocytes and level of hemoglobin, a reticulocytosis, emergence of normoblasts. Erythrocytes have tendency to a macrocytosis. The hyperleukocytosis with shift is noted to the left (to myelocytes). At height of hemolitic crisis in a miyelogramma comes to light erythroblastic, in the subsequent — normoblastic reaction. In marrow and in peripheral blood a significant amount of eosinophils is found. A favism more often than other forms of hemolitic anemia connected with deficit of G-6-FD is complicated by a renal failure, occasionally development of an anury.
Verification of the diagnosis The diagnosis of the hemolitic anemia connected with deficit of activity of G-6-FD of erythrocytes is based on the described anamnestic data, clinical symptomatology and disturbances of a hemogenesis.
In diagnosis of a disease also use of coloring of erythrocytes crystal violet in the period of the expressed hemolitic crisis (a large number of little bodies of Heinz) matters. Among methods of determination of activity G-6-FD of erythrocytes the greatest recognition was gained a qualitative method of Bernstein. However more exact is quantitative definition of this enzyme in erythrocytes (in our country Mogulsky's method in Idelson's modification and Zhukovsky is applied).
Treatment In treatment of the enzimopenichesky hemolitic anemia caused by deficit of activity of G-6-FD of erythrocytes transfusions of the washed or defrozen erythrocytes generally are used. And at an asymptomatic carriage of a gene of this disease use of oxidizers of various origin is contraindicated to this patients. At emergence of signs of a favism and for the purpose of prevention of its further development the use in food of horse beans in any kind stops. From medical actions for indications transfusions of the washed or defrozen erythrocytes, a plasma exchange and other means of fight against uraemia are used.