Hereditary hemolytic anemia, caused by deficiency of activity of glucose-6-phosphate dehydrogenase of erythrocytes
Activity deficiency of glucose-6-phosphate dehydrogenase( G-6-PD) is the most common hereditary anomaly of erythrocytes, resulting in hemolytic crises( exacerbation due to intense destruction of red blood cells) associated with the administration of a number of drugs. Outside the crisis( exacerbation), the state of health and the condition of a person with this disease is fully compensated. It is known that a number of drugs, especially antimalarials, can cause acute hemolytic anemia in some individuals. Intolerance to drugs is often observed in members of the same family. It is established that after hemolytic crisis in humans in erythrocytes large inclusions appear which are called Heinz's bodies. After the placement of red blood cells of persons who underwent an acute hemolytic crisis, caused by the taking of a drug, into a test tube with acetylphenylhydrazine, many Heinz bodies appear in the erythrocytes( much more than in healthy people).The first description of the deficiency in the activity of the G-6-FD enzyme dates back to 1956. A low activity of the enzyme was found in people taking antimalarial medication with a preventive purpose primaquine. At the same time, an acute hemolytic crisis developed. Irrespective of these studies, another scientist in 1957 found a deficiency of the same enzyme in the erythrocytes of a young man from Iran, who periodically had hemolytic crises without taking any medications.
The activity deficit of this enzyme is always linked to the X chromosome. The linkage of the mutant gene with the sex gives a significant predominance of men among persons with this disease. It manifests itself in men who inherited this pathology from the mother with her X chromosome, in women who inherited the disease from both parents, and in part of women who inherited the disease from one of the parents.
The most common deficiency of G-6-FD is found in Europe, located on the Mediterranean coast - in Greece, in Italy. A deficiency of enzyme activity is widespread in some countries of Latin America and Africa.
In our country, the lack of activity of G-6-FD is distributed unevenly. A high concentration of pathological gene was found in Azerbaijan, among various nationalities of Dagestan, in Uzbekistan, Armenia and Georgia. Perhaps the high accumulation of an abnormal gene in these communities is facilitated by the custom of related marriages that has survived to the present day. This leads to the accumulation in the population of women with two mutant X chromosomes, in which the decay of erythrocytes after taking medications is more severe than that of carriers of one mutant X chromosome. In addition, the probability of the birth of men with a mutant X chromosome increases. This was also facilitated by the large spread of tropical malaria in the past. There is a hypothesis that the deficiency of G-6-FD gives some advantages in the fight against tropical malaria, and those who have such a deficit died less often from this disease. This hypothesis is supported by the heterogeneous distribution of the parasite among the erythrocytes of the heterozygous woman: in normal parasite cells there is much more than in the pathologically changed ones.
The first stage of drug exchange in the body is its transition into an active form, which can cause changes in the structure of the erythrocyte membrane. The active form of the drug interacts with hemoglobin. This produces a certain amount of hydrogen peroxide. In healthy people, an acute hemolytic crisis develops with the administration of a significant amount of the drug( toxic dose).A crisis can arise when the recovery systems are unable to cope with the excess of hydrogen peroxide formed in the red blood cells. In this case, the body of Heinz appears in red blood cells. The spleen releases erythrocytes from these bodies, while a part of the erythrocyte surface is lost, which leads to their premature death.
Experts of the World Health Organization subdivide G-6-FD enzyme deficiency variants into 4 classes in accordance with the emerging manifestations and level of enzyme activity in erythrocytes.
1st class - variants that are accompanied by chronic hemolytic anemia.
2nd class - variants with a level of enzyme activity in erythrocytes 0-10% of the norm, the carriage of which causes the absence of hemolytic anemia without exacerbation, and exacerbations are associated with taking medications or eating horse beans.
3rd class - variants with a level of enzyme activity in erythrocytes 10-60% of the norm, at which there may be mild signs of hemolytic anemia associated with taking medications.
4th class - variants with a normal or close to normal level of enzyme activity without any manifestations.
Hemolytic anemia at the birth of a child happens with a deficiency of the enzyme G-6-FD both 1st and 2nd class. The activity of G-6-PD in erythrocytes does not always correspond to the severity of the emerging manifestations of the disease. In many variants of the 1st class, 20-30% activity of the enzyme is determined, and at zero activity, some manifestations of the disease are not observed in some carriers. This is due, first, to the properties of the mutant enzymes themselves, and secondly, to the rate of neutralization of drugs in the liver.
The most often deficiency of the activity of the enzyme G-6-FD does not give any manifestations without provocation. In most cases, hemolytic crises begin after the administration of certain drugs, primarily sulfonamide drugs( norsulfazole, streptocide, sulfadimethoxin, sodium albucide, ethazole, biseptol), antimalarials( primaquine, quinine, acrichine), nitrofuran derivatives( furazalidone, furadonin, furagin,5-NOC, Negroes, nevigramon), drugs for the treatment of tuberculosis( tubazid, ftivazid), anthelminthic drug niridazole( ambibilhar).When the activity of the enzyme G-6-PD is deficient, you can use the antimalarial drug delagil, and from sulfanilamide preparations - only phthalazole. Some drugs in high doses cause hemolytic crises, and in small doses can be used in the deficiency of the activity of the enzyme G-6-FD.Such drugs include acetylsalicylic acid( aspirin), amidopyrine, phenacetin, levomycetin, streptomycin, artan, antidiabetic sulfanilamide preparations.
Manifestations of the disease can occur on the 2-3rd day from the beginning of the medication. At first, a slight yellow coloration of the eyes appears, the urine becomes dark. If during this period to stop taking the medication, then a heavy hemolytic crisis does not develop, otherwise on the 4th or 5th day a hemolytic crisis may occur with the release of urine black, sometimes brown, which is associated with the disintegration of red blood cells inside the blood vessels. The hemoglobin content during this period can decrease by 20-30 g / l and more. In severe illness, the temperature rises, there is a sharp headache, pain in the extremities, vomiting, and sometimes diarrhea. There is shortness of breath, blood pressure decreases. The spleen is often enlarged, sometimes the liver.
In rare cases, massive decay of erythrocytes provokes intravascular coagulation of blood with the formation of thrombi closing the lumen of blood vessels. This, in turn, can lead to impaired blood circulation in the kidneys and the development of acute renal failure.
In the study of blood, anemia is detected with an increase in the number of immature forms of red blood cells( reticulocytes).The number of white blood cells increases. Sometimes, especially in children, the number of white blood cells can become very large( 100 x 109 / L and higher).The level of platelets usually does not change. In the special study of erythrocytes in the period of severe exacerbation of the disease, a large number of Heinz bodies are detected. As a result of pronounced destruction of erythrocytes in the serum, the content of free hemoglobin increases, bilirubin content is often increased. In the urine also appears hemoglobin.
Children are more likely to experience severe hemolytic crises than adults. When the activity of the enzyme G-6-FD is expressed, hemolytic crises sometimes appear immediately after birth. This is a hemolytic disease of the newborn, not related to the immunological conflict between him and his mother. It can proceed as hard as hemolytic anemia associated with Rh-incompatibility of the mother and child, it can provoke severe jaundice with severe damage to the central nervous system.
Hemolytic crises in the presence of a deficiency in the activity of the enzyme G-6-PD sometimes occur in infectious diseases( influenza, salmonellosis, viral hepatitis), regardless of medications, may be triggered by exacerbation in diabetes mellitus or the development of renal insufficiency.
A small proportion of people with a deficiency in the activity of the enzyme G-6-PD have permanent hemolytic anemia associated with taking medications. In these cases, a small increase in the spleen occurs, hemoglobin does not decrease so much, the level of bilirubin in the blood increases slightly. In such people, the disease can worsen either after taking the above medicines, or for infectious diseases.
Some people with G-6-FD deficiency develop hemolytic anemia associated with eating horse beans - favism. Manifestations of favism are formed from signs of rapid destruction of red blood cells, which occurs more rapidly than after taking medications, and digestive disorders associated with the direct influence of horse beans on the intestine. Hemolytic crises occur several hours after the consumption of beans, less often after 1-2 days, their severity depends on the number of beans eaten. Favism is often complicated by renal insufficiency. Mortality is higher in favism than in forms caused by taking medications. When inhaling flower pollen, haemolytic crises are more likely to be light, but occur several minutes after exposure to pollen.
Single hemolytic crises due to the intake of male fern, eating blueberries, blueberries are described.
The basis for detecting the deficiency of the enzyme G-6-FD is the determination of enzyme activity by means of special research methods.
Treatment of deficiency of the enzyme G-6-FD is necessary only with the expressed signs of acute destruction of erythrocytes. With persistent hemolytic anemia, with a deficiency of G-6-PD 1-st grade activity, spleen removal is sometimes performed. With moderate hemolytic crises with a slight darkening of the urine, slight yellowing of the sclera and a slight decrease in hemoglobin, it is necessary to cancel the drug that caused the crisis, taking riboflavin 0.015 g 2-3 times a day, xylitol 5-10 g 3 times a day, vitamin E preparations.
expressed signs of intravascular decay of erythrocytes, especially in favism, it is necessary to prevent acute renal failure. Prophylaxis of renal failure is carried out only in a hospital or intensive care unit and depends on the severity of the condition.
Erythrocytes transfuse only with severe anemia.
Prevention of hemolytic crises is reduced to the rejection of drugs that can exacerbate the disease. In this case, such drugs must be replaced with analogs, which should be done by the attending physician.
Forecast of .Individuals with a deficiency of the enzyme G-6-FD are practically healthy, and with the observance of preventive measures can be healthy throughout life. The working capacity of such people does not suffer. Chronic hemolytic anemia associated with deficiency of G-6-PD is usually not severe. As a rule, the working capacity is fully preserved. The prognosis for acute hemolytic crises depends on the speed of withdrawal of the drug that caused the hemolytic crisis, age, and the state of the cardiovascular system. With favism the forecast is worse, but preventive measures make the lethality small even in cases complicated by acute renal failure.