Symptoms of sickle cell anemia

Sickle cell anemia occurs in the form of episodes of pain attacks (crises) associated with capillary occlusion as a result of spontaneous "sickle formation" of erythrocytes, alternating with periods of remission. Crises can be provoked by intercurrent diseases, climatic conditions, stress, and spontaneous occurrence of crises is possible.

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Symptoms of Sickle Cell Anemia

Symptoms of sickle cell anemia usually appear by the end of the first year of life. In newborns, fetal hemoglobin (HbF) predominates; as HbF decreases in the postnatal period, the concentration of HbS increases. Intravascular "sickle formation" and signs of hemolysis can be detected as early as 6-8 weeks of age, but clinical manifestations of the disease are usually not characteristic until 5-6 months of age.

Patients with sickle cell anemia have an appearance typical only for this disease: an elongated lower body segment, dorsal kyphosis and lumbar lordosis, gothic palate, prominent forehead, tower skull, significant elongation of the limbs, which depends on the slowing of the ossification processes in the epiphyses, a general delay in bone maturation. A lag in physical and sexual development is characteristic. At the age of up to 2 years, physical development indicators correspond to the norm, then at the age of 2-6 years, growth and weight slow down significantly, and the lag in weight is expressed to a greater extent than in height. By the end of adolescence, sick children usually catch up with healthy children in height, the lag in weight remains. Delayed puberty is noted, in boys puberty occurs at 16-18 years, in girls - at 15-17 years. The level of intellectual development in patients is normal.

All patients have pale skin and mucous membranes, jaundice, which increases with age. Starting from 6 months of life, the spleen is palpable in patients; at the onset of the disease, the spleen is significantly enlarged; at later stages, due to the development of fibrosis against the background of repeated infarctions, the spleen decreases in size (autosplenectomy) and splenomegaly is rarely detected in children over 6 years old. Although the spleen is significantly enlarged at the onset of the disease, functional hyposplenism is clinically noted. In the laboratory, with functional hyposplenism, transient thrombocytosis is possible in the peripheral blood, and Jolly bodies are found in erythrocytes. In patients with autosplenectomy, target cells and acanthocytes appear. Some children have hepatomegaly. Cardiomegaly is often detected. Adenopathy is characteristic; involution of the tonsils in such children occurs slowly. In patients already by the age of 3-4 years, gallstone disease may develop; the frequency of cholelithiasis in patients aged 2-4 years is 12%, in patients aged 1.5-1.8 years - 42%; ulcerative disease of the duodenum is quite common.

The disease is chronic, patients with severe sickle cell anemia live about 20 years. Acute conditions - crises - are observed periodically. There are two types of crises: clinical (painful or vaso-occlusive), in which the hemoglobin and reticulocyte composition indicators generally do not differ from the norm; hematological, with a sharp decrease in hemoglobin levels and reticulocytosis. Crises are often combined.

Clinical crises of sickle cell anemia

Clinical crises (pain, vaso-occlusive, rheumatoid and abdominal) are the most common variant of sickle cell anemia. They can be provoked by infections or occur spontaneously. Pain syndrome is associated with the occurrence of infarctions due to vascular occlusion by sickle-shaped erythrocytes. Infarctions can occur in the bone marrow, bones and periosteum, periarticular tissues of the joints. The main symptom of vaso-occlusive crises is pain of varying intensity, accompanied by a temperature reaction, edema in the affected area, and an inflammatory reaction. The first manifestation of the disease in infancy can be symmetrical painful swelling of the hands and feet (due to occlusion of the metatarsal and metacarpal bones) - sickle cell dactylitis. X-rays reveal destruction of bone tissue, accompanied by a periosteal reaction. In older patients, pain and swelling of large joints and surrounding tissues are observed. Infarctions of anatomical structures located in the abdominal cavity lead to abdominal pain, resembling the clinical picture of acute abdomen. Acute neurological disorders, observed in approximately 25% of patients, including seizures, thrombotic and hemorrhagic strokes, transient ischemic attacks, pose a serious danger. Cerebral strokes are the result of occlusion of a large vessel, occur mainly in children (approximately 7% of patients; the average incidence is 1.7% per year during the first 20 years of life, and the incidence of strokes is maximum in children aged 5-10 years), can leave behind irreversible consequences in the form of hemiplegia and in 70% of cases, in the absence of treatment, recur within 3 years. In adult patients, acute hemorrhagic strokes may occur as a result of neovascularization and formation of cerebral vascular aneurysms. Pulmonary infarctions develop, which are difficult to differentiate from pneumonia; the patient experiences dyspnea and hemoptysis. In children, acute thoracic syndrome is more severe and is the most common cause of death. Death occurs as a result of progressive respiratory failure and multiple infarctions of internal organs. Acute thoracic syndrome is caused by the appearance of sickle cells in the microvascular bed of the lungs and is manifested by respiratory failure, chest or abdominal pain, and fever. Chest X-ray data at the time of syndrome onset are usually normal, but infiltrates are often detected later (in severe cases, several lobes are affected). In 50% of cases, predisposing factors are upper respiratory tract infections caused by Streptococcus pneumoniae, Mycoplasma, Chlamydia; in 15% of cases, the cause of the development of OTS may be pulmonary fat embolism. Necrosis and infarctions occur in the bone marrow, fat embolism develops, which is characterized by fever, anxiety, restlessness, and loss of consciousness,coma and other disorders of the psychoneurological status. Thrombocytopenia and the clinical picture of DIC syndrome may be observed. Great importance is attached to the examination of the fundus - fat emboli are found in the retinal vessels. Acute pathology of the genitourinary system is also a manifestation of vaso-occlusive crisis. Recurrent priapism is observed in more than 50% of men with sickle cell anemia. Predisposing factors for the development of priapism are sexual intercourse, masturbation, infections, local trauma. Treatment of priapism should be started within the first 12 hours, replacement blood transfusions are prescribed to reduce erection, prevent scarring and the development of impotence. If conservative treatment is ineffective, surgical intervention is resorted to, providing decompression of the cavernous bodies. The appearance of sickle cells in the renal medulla causes necrosis of the renal papillae and hematuria. Occlusion of the liver vessels by sickle erythrocytes is manifested by a pain syndrome simulating acute cholecystitis or viral hepatitis, severe hepatomegaly, a sharp increase in bilirubin (mainly direct) and aminotransferase activity. Fulminant liver failure, massive cholestasis, development of encephalopathy and shock are possible, which requires replacement blood transfusion.

In patients with sickle cell anemia, changes in the hemostasis system are detected. Hypercoagulation, pronounced intravascular activation and aggregation of platelets, increased levels of von Willebrand factor, increased fibrinogen concentration, deficiency of prothrombins C and S are noted, which significantly increases the risk of thrombosis. Changes in the hemostasis system are important in the genesis of vaso-occlusive crises.

Vaso-occlusive (pain) crisis

The most common manifestation of sickle cell anemia. Mainly bones and muscles are affected. Provoking factors are infections, dehydration, cold and hypoxia. Dactylitis (hand-foot syndrome) - painful swelling of the dorsum of the hands and feet - is typical for children under 5 years old. Bone, clinically similar to osteomyelitis, often begins at the age of 3-4 years. Abdominal symptoms (girdle syndrome) develop as a result of occlusion of the mesenteric vessels and infarction of the liver, spleen or lymph nodes, in these cases differential diagnosis with acute abdomen is necessary. Pulmonary syndrome (acute chest syndrome) is quite common, mainly in adolescents and adults, and is the main cause of chronic lung diseases and death, occurring as a result of progressive respiratory failure and multiple infarctions of internal organs. Acute chest syndrome must be differentiated from pneumonia. Treatment is symptomatic (antibacterial and infusion therapy, analgesics, oxygen). Factors such as sexual intercourse, masturbation, infection and local trauma contribute to the development of priapism, which in some cases leads to impotence. Painful hematuria of moderate severity develops due to papillary necrosis of the kidneys. CNS crises may be accompanied by:

• convulsions;
• meningeal signs;
• blindness;
• retinopathy;
• dizziness;
• acute cerebrovascular accident;
• cerebral infarction.

The incidence of CNS crises is 7-29%, the average age of their development is 7.7 years. The risk of developing subarachnoid hemorrhages is high.

Sequestration crisis

Most often localized in the spleen (splenic sequestration), develops rarely, at the age of 5-24 months, often leads to death. Signs characteristic of the clinical picture:

• splenomegaly (discharge of a large amount of blood into the spleen);
• sudden, severe abdominal pain accompanied by nausea and vomiting;
• a sharp decrease in Hb levels, leading to hypovolemic shock and death.

Hepatic sequestration is manifested by:

• sudden painful enlargement of the liver;
• a marked increase in the level of bilirubin due to its direct fraction;
• increased activity of transaminases (ALT, AST).

It can develop at any age with fibrosis of the spleen. Treatment consists of immediate replenishment of the BCC and correction of anemia, as well as removal of the spleen.

Aplastic crisis

Most often caused by parvovirus infection B19. Signs characteristic of the clinical picture:

• a sharp, deep decrease in hemoglobin levels (up to 10 g/l) with the absence of reticulocytes and normoblasts in the peripheral blood;
• the number of platelets and leukocytes is usually unchanged;
• significant reduction in serum bilirubin levels.

It usually resolves on its own within 10 days. If the Hb content drops sharply, a transfusion of red blood cells is indicated.

Hemolytic crisis

Accompanied by severe weakness, pallor, icteric sclera, and possible abdominal pain. A general blood test shows a decrease in hematocrit to 15% or less, reticulocytosis. After a few days, hemolysis gradually stops. In severe anemia, red blood cell transfusion is indicated.

Stroke

A common complication of sickle cell anemia in children. Develops due to occlusion of large vessels of the brain, often several. The probability of repeated strokes is high. Regular transfusions of red blood cells, maintaining the Hb S level of no more than 30%, significantly reduce the risk of repeated strokes. In acute cerebrovascular accidents, urgent exchange transfusion using red blood cells, dehydration with alkalization are necessary.

Megaloblastic crisis

Caused by an increased need for folic acid as a result of increased erythropoiesis, it is prevented by prophylactic oral administration of folic acid.

In sickle cell anemia, due to repeated vaso-occlusive crises and chronic hemolysis, pronounced chronic changes are observed in many organs. Cardiac disorders are manifested by tachycardia and dyspnea. The heart is resistant to occlusive lesions due to the fact that myocardial contraction facilitates the passage of defective erythrocytes through the vessels that feed the organ, and this prevents the development of blood clots. However, as a result of constant hypoxia (chronic anemia), cardiomegaly develops, secondary fibrosis and hemosiderosis of the myocardium gradually progress. An ECG examination reveals sinus tachyarrhythmia, levogram, left ventricular hypertrophy, T wave inversion; radiological examination reveals an increase in all cardiac cavities, bulging of the pulmonary artery; echocardiography reveals dilation of both the left and right ventricles. In older patients, pulmonary hypertension and pulmonary heart disease develop. Recurrent pulmonary infarctions cause pulmonary fibrosis in some patients. The development of acidosis and hyperosmolarity of the renal medulla is associated with the formation of sickle cells, so chronic renal pathology develops early in all patients with sickle cell anemia. The kidneys are affected by secondary glomerulonephritis due to ischemia, diffuse fibrosis of the tubules and glomeruli of the kidneys leads to progressive deterioration of renal function (the first manifestation of obliteration of the vessels of the renal medulla is hyposthenuria, which is detected by the age of 10); impaired renal concentrating ability makes patients with sickle cell anemia especially sensitive to dehydration. Tubular defects can manifest as tubular acidosis and hyperkalemia. In some cases, nephrotic syndrome is observed. Liver damage is manifested by chronic hepatomegaly; necrosis zones in the liver subsequently become fibrotic, hepatopathy can develop into cirrhosis. Post-transfusion hepatitis may develop. Due to cerebral vascular occlusion, neurological disorders are observed: speech defects, gait disturbances, hemiparesis. Eye lesions with complications in the form of retinal detachment are common. Developing pathological processes depend on the location of the lesion. In younger children, due to the development of anastomoses in the subcutaneous tissue, skin lesions (trophic ulcers of the lower extremities) do not occur, in older children and adults, circulatory disorders can cause skin necrosis. Functional hyposplenism in sickle cell anemia increases susceptibility to bacterial infections caused by pneumococci, meningococci, H. influenzae, salmonella and E. coli. Severe infections are common in all age groups - pneumonia, meningitis, osteomyelitis, sepsis, including urosepsis. The period of maximum risk of death from severe infections is the first 5 years of life.

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