Sickle cell anemia is a hereditary hemoglobinopathy caused by the synthesis of abnormal hemoglobin S, a change in the shape and properties of red blood cells. Disease is manifested by hemolytic, aplastic, sequestration crises, vascular thrombosis, bone and joint pain and swelling of the extremities, skeletal changes, splenic and hepatomegaly. The diagnosis is confirmed by the peripheral blood and bone marrow punctate examination. Treatment is symptomatic, aimed at preventing and relieving crises; transfusion of erythrocytes, taking anticoagulants, splenectomy may be indicated.
Sickle cell anemia (S-hemoglobinopathy) is a type of hereditary hemolytic anemia characterized by a violation of the structure of hemoglobin and the presence of sickle-shaped erythrocytes in the blood. The incidence of pathology is widespread mainly in the countries of Africa, the Near and Middle East, the Mediterranean basin, and India. Here, the frequency of carrying hemoglobin S among the indigenous population can reach 40%. It is curious that sickle cell anemia patients have increased innate resistance to malaria infection, since malarial plasmodium cannot penetrate into sickle-shaped red blood cells.
Sickle cell anemia causes
Sickle cell anemia is based on a gene mutation that causes the synthesis of abnormal hemoglobin S (HbS). The defect in the hemoglobin structure is characterized by the replacement of glutamic acid with valine in the β-polypeptide chain. The resulting hemoglobin S, after the loss of the attached oxygen, acquires the consistency of a high-polymer gel and becomes 100 times less soluble than normal hemoglobin A. As a result, red blood cells carrying deoxyhemoglobin S are deformed and acquire a characteristic semilunar (crescent-shaped) shape. Altered erythrocytes become rigid, low-plastic, can clog capillaries, causing tissue ischemia, and are easily subjected to autohemolysis.
Inheritance of disease occurs in an autosomal recessive type. At the same time, heterozygotes inherit a defective sickle cell anemia gene from one of the parents, therefore, along with altered red blood cells and HbS, they also have normal red blood cells with HbA in the blood. In heterozygous carriers of the sickle cell anemia gene, signs of the disease occur only under certain conditions. Homozygotes inherit one defective gene each from their mother and father, so only sickle-shaped erythrocytes with hemoglobin S are present in their blood; the disease develops early and proceeds heavily.
Thus, depending on the genotype, a heterozygous (HBAs) and homozygous (HbSS, drepanocytosis) form of disease is distinguished in hematology. The rare variants of the disease include intermediate forms of this pathology. They usually develop in double heterozygotes carrying one sickle cell anemia gene and another defective gene – hemoglobin C (HbSC), sickle β-plus (HbS/β +) or β-0 (HbS/β0) thalassemia.
Sickle cell anemia symptoms
Homozygous sickle cell anemia usually manifests itself in children by 4-5 months of life, when the number of HbS increases, and the percentage of sickle-shaped erythrocytes reaches 90%. In such cases, the early occurrence of hemolytic anemia in a child causes a delay in physical and mental development. Disorders of skeletal development are characteristic: a tower skull, thickening of the frontal sutures of the skull in the form of a ridge, kyphosis of the thoracic or lordosis of the lumbar spine.
There are three periods in the development of this disease: I – from 6 months to 2-3 years, II – from 3 to 10 years, III – older than 10 years. Early signals of sickle cell anemia are arthralgia, symmetrical swelling of the joints of the extremities, chest, abdominal and back pain, jaundice of the skin, splenomegaly. Children with this pathology belong to the category of those who are often ill. The severity is closely correlated with the concentration of HbS in red blood cells: the higher it is, the more severe the symptoms are.
In conditions of intercurrent infection, stress factors, dehydration, hypoxia, pregnancy, etc. sickle cell crises may develop in patients with this type of hereditary anemia: hemolytic, aplastic, vascular-occlusive, sequestration, etc.
With the development of a hemolytic crisis, the patient’s condition deteriorates sharply: febrile fever occurs, indirect bilirubin increases in the blood, jaundice and pallor of the skin increases, hematuria appears. Rapid disintegration of red blood cells can lead to an anemic coma. Aplastic crises are characterized by inhibition of the erythroid growth of the bone marrow, reticulocytopenia, and a decrease in hemoglobin.
Sequestration crises are the consequence of depositing blood in the spleen and liver. They are accompanied by hepatomegaly and splenomegaly, severe abdominal pain, severe arterial hypotension. Vascular-occlusive crises occur with the development of renal vascular thrombosis, myocardial ischemia, spleen and lung infarction, ischemic priapism, retinal vein occlusion, mesenteric vascular thrombosis, etc.
Heterozygous carriers of the sickle cell anemia gene feel practically healthy under normal conditions. Morphologically altered erythrocytes and anemia occur only in situations associated with hypoxia (with heavy physical exertion, air travel, climbing mountains, etc.). At the same time, an acutely developed hemolytic crisis with a heterozygous form of this disease can be fatal.
The chronic course of sickle cell anemia with repeated crises leads to the development of a number of irreversible changes, often causing the death of patients. About a third of patients have autosplenectomy – shrinking and reduction in the size of the spleen caused by the replacement of functional scar tissue. This is accompanied by a change in the immune status of sickle cell anemia patients, more frequent occurrence of infections (pneumonia, meningitis, sepsis, etc.).
The outcome of vascular-occlusive crises can be ischemic strokes in children, subarachnoid hemorrhages in adults, pulmonary hypertension, retinopathy, impotence, renal failure. In women with sickle cell anemia, there is a late formation of the menstrual cycle, a tendency to spontaneous termination of pregnancy and premature birth. The consequence of myocardial ischemia and hemosiderosis of the heart is the occurrence of chronic heart failure; kidney damage – chronic renal failure.
Prolonged hemolysis, accompanied by excessive bilirubin formation, leads to the development of cholecystitis and cholelithiasis. Patients often have aseptic necrosis of bones, osteomyelitis, ulcers of the shins.
The diagnosis of sickle cell anemia is made by a hematologist on the basis of characteristic clinical symptoms, hematological changes, family genetic research. The fact that a child inherits sickle cell anemia can be confirmed even at the stage of pregnancy with a chorionic villus biopsy or amniocentesis.
In peripheral blood, normochromic anemia is noted (1-2 x1012 / l), a decrease in hemoglobin (50-80 g / l), reticulocytosis (up to 30%). Sickle-shaped red blood cells, cells with Jolly bodies and Kabo rings are found in the blood smear. Hemoglobin electrophoresis makes it possible to determine the form of sickle cell anemia – homo- or heterozygous. Changes in biochemical blood samples include hyperbilirubinemia, an increase in serum iron content. When examining the bone marrow punctate, an expansion of the erythroblastic germ of hematopoiesis is revealed.
Sickle cell anemia treatment
Sickle cell anemia belongs to the category of incurable blood diseases. Such patients require lifelong supervision of a hematologist, carrying out measures aimed at preventing crises, and with their development – carrying out symptomatic therapy.
During the development of sickle cell crisis, hospitalization is required. In order to quickly relieve the acute condition, oxygen therapy, infusion dehydration, administration of antibiotics, painkillers, anticoagulants and disaggregants, folic acid are prescribed. In severe exacerbations, transfusion of erythrocyte mass is indicated. Splenectomy cannot affect the course of sickle cell anemia, but it can temporarily reduce the manifestations of the disease.
Prognosis and prevention
The prognosis of the homozygous form is unfavorable; most patients die in the first decade of life from infectious or thromboocclusive complications. The course of heterozygous forms of pathology is much more encouraging.
To prevent the rapidly progressing course of disease, provoking conditions (dehydration, infections, overstrain and stress, extreme temperatures, hypoxia, etc.) should be avoided. Children suffering from this form of hemolytic anemia are required to be vaccinated against pneumococcal and meningococcal infections. If there are sickle cell anemia patients in the family, a medical and genetic consultation is necessary to assess the risk of developing the disease in the offspring.
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