Symptoms of sickle-cell anemia

Sickle-cell anemia occurs in the form of episodes of painful attacks (crises) associated with the occlusion of capillaries as a result of spontaneous "cirrus" erythrocytes alternating with periods of remission. Crises can be provoked by intercurrent diseases, climatic conditions, stresses, spontaneous emergence of crises is possible.

[1], [2], [3]

Symptoms of sickle-cell anemia

Symptoms of sickle-cell anemia usually appear by the end of the first year of life. Fetal hemoglobin (HbF) prevails in newborns, as the concentration of HbS increases in the postnatal period of HbF. Intravascular "surplus" and signs of hemolysis can be detected already at the age of 6-8 weeks, however, clinical manifestations of the disease, as a rule, are not typical until 5-6 months of age.

Sickle-cell anemia patients have a typical appearance only for this disease: an elongated lower segment of the body, dorsal kyphosis and lumbar lordosis, a gothic sky, protruding forehead, a tower skull, a significant elongation of the limbs, which depends on the slowing of ossification in the epiphyses, bones. Characteristic lag in physical and sexual development. At the age of up to 2 years, the indices of physical development correspond to the norm, then at the age of 2-6 years, the height and weight are significantly slowed, and the lag in weight is more pronounced than in growth. By the end of the adolescent period, sick children usually catch up with the healthy ones, the lag in weight remains. There is a delay in puberty, boys have puberty at 16-18, and girls at 15-17. The level of intellectual development in patients is normal.

All patients have pale skin and mucous membranes, icterus, which increases with age. Since the 6th month of life, the spleen is palpable in patients with spleen, at the beginning of the disease, the size of the spleen is significantly increased, at later stages, due to the development of fibrosis against repeated infarcts, the spleen decreases in size (autosplenectomy) and in children older than 6 years, splenomegaly is rarely detected. Although the size of the spleen at the onset of the disease is significantly increased, the functional hyposplenism is clinically noted. Laboratory with functional hypersplenism in peripheral blood is possible transient thrombocytosis, in erythrocytes, Jolly's body is found. Mishenide cells and acanthocytes appear in patients with autosplenectomy. Some children have hepatomegaly. Cardiomegaly is often diagnosed. Adenopathy is typical, the involution of the tonsils in these children is slow. In patients already at the age of 3-4 years, the development of cholelithiasis is possible, the incidence of cholelithiasis in patients aged 2-4 years is 12%, at the age of 1-5 - 1-8 years - 42%; Quite often there is peptic ulcer of the duodenum.

The disease proceeds chronically, patients with severe sickle-cell anemia live for about 20 years. Periodically marked acute states - crises. There are two types of crises: clinical (painful or vaso-occlusive), in which the hemoglobin and reticulocyte composition parameters are basically not different from the norm; hematological, with a sharp decrease in the level of hemoglobin and reticulocytosis. Quite often crises are combined.

Clinical crises of sickle-cell anemia

Clinical crises (pain, vaso-occlusive, rheumatoid and abdominal) are the most frequent variant of sickle cell anemia. They can be triggered by infections or occur spontaneously. Pain syndrome is associated with the occurrence of infarctions due to the occlusion of vessels with sickle erythrocytes. Infarctions can be in the bone marrow, bones and periosteum, periarticular tissues of the joints. The main sign of vaso-occlusive crises is pain of different intensity, accompanied by a temperature reaction, edema in the area of lesion, inflammatory reaction. The first manifestation of the disease in infancy can be a symmetric painful swelling of the hands and feet (due to the occlusion of metatarsal and metacarpal bones) - sickle-cell dactylitis. X-ray reveals the destruction of bone tissue, accompanied by periosteal reaction. In elderly patients, tenderness and swelling of large joints and surrounding tissues are noted. Infarctions of anatomical structures located in the abdominal cavity, lead to the appearance of abdominal pain resembling a clinic of an acute abdomen. Serious danger is represented by acute neurologic disorders, which are noted in about 25% of patients, including seizures, thrombotic and hemorrhagic strokes, transient ischemic attacks. Cerebral strokes are the result of occlusion of a large vessel, mainly in children (approximately 7% of patients, the average frequency is 1.7% per year for the first 20 years of life, with a maximum incidence of stroke 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 they recur within 3 years. In adults, acute hemorrhagic strokes may occur as a result of neovascularization and the formation of cerebral aneurysms. Lung infarctions develop that are difficult to differentiate from pneumonia, the patient has shortness of breath, hemoptysis. In children, acute thoracic syndrome is more severe and is the most common cause of death of patients. 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 lung and manifests itself as breathing disorders, pain in the chest or abdomen, and fever. Chest x-ray data at the time of the syndrome, as a rule, normal, but subsequently often reveal infiltrates (in severe cases, several fractures are affected). In 50% of cases, upper respiratory tract infections caused by Streptococcus pneumoniae, Mycoplasma, Chlamydia are predisposing factors; In 15% of cases, the cause of OTC development can be fat pulmonary embolism. In the bone marrow there are necrosis, heart attacks, fat embolism, which is characterized by fever, anxiety, anxiety, frustration, coma and other disorders of the psychoneurological status. There may be thrombocytopenia and a clinical picture of DIC syndrome. Great importance is attached to the study of the fundus - fat emboli are found in the vessels of the retina. The manifestation of vaso-occlusive crisis is also acute pathology of the genitourinary system. Recurrent priapism is observed in more than 50% of men with sickle cell anemia. Predisposing to the occurrence of priapism factors are sexual intercourse, masturbation, infection, local trauma. Treatment of priapism should be started within the first 12 hours, appoint a replacement blood transfusion to reduce erection, prevent scarring and develop impotence. If conservative treatment is ineffective, resort to a surgical intervention that provides decompression of the cavernous bodies. The appearance of sickle cells in the medulla of the kidney causes the appearance of necrosis of the renal papillae and hematuria. Occlusion of sickles with sickle-shaped erythrocytes is manifested by a pain syndrome that simulates acute cholecystitis or viral hepatitis, expressed by hepatomegaly, a sharp increase in bilirubin (mainly direct), and aminotransferase activity. Possible fulminant liver failure, massive cholestasis, the development of encephalopathy and shock, which requires a replacement blood transfusion.

Patients with sickle cell anemia detect changes in the system of hemostasis. Hypercoagulation, pronounced intravascular platelet aggregation and activation, increased von Willebrand factor level, increased fibrinogen concentration, deficiency of prothrombin C and S, markedly increase the risk of thrombosis. Changes in the hemostasis system are important in the genesis of vaso-occlusive crises.

Vazocclusive (painful) crisis

The most frequent manifestation of sickle-cell anemia. Basically bones and muscles are affected. Provoking factors are infections, dehydration, cold and hypoxia. Dactylitis (hand-foot syndrome) - painful swelling of the dorsal surfaces of the hands and feet - is typical for children under 5 years old. Bony, clinically similar to osteomyelitis, often begin at the age of 3-4 years. Abdominal symptoms (shin syndrome) develop as a result of occlusion of mesentery vessels and liver infarction, spleen or lymph nodes, in these cases differential diagnosis with a sharp abdomen is necessary. Pulmonary syndrome (acute chest syndrome) occurs quite often, mainly in adolescents and adults, and is the main cause of chronic lung diseases and death, resulting from 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, in some cases leading to impotence. Painful hematuria of moderate degree develops due to papillary necrosis of the kidneys. Crises of the central nervous system may be accompanied by:

• convulsions;
• meningeal signs;
• blindness;
• retinopathy;
• dizziness;
• acute violation of cerebral circulation;
• a cerebral infarction.

The frequency of occurrence of crises of the central nervous system is 7-29%, the average age of their development is 7.7 years. The risk of subarachnoid hemorrhage is high.

Sequestration crisis

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

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

Hepatic sequestration manifests itself:

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

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

Aplastic crisis

The most common cause of parvovirus infection is B19. Signs characteristic of the clinical picture:

• a sharp deep decrease in the level of hemoglobin (up to 10 g / l) with the absence of reticulocytes and normoblasts in peripheral blood;
• the number of platelets and white blood cells, as a rule, is not changed;
• a significant reduction in serum bilirubin levels.

It is most often copied on its own within 10 days. With a sharp decrease in the content of Hb, a transfusion of the erythrocyte mass is indicated.

Hemolytic crisis

It is accompanied by a sharp weakness, pallor, icteric sclera, there may be abdominal pain. In the general blood test, a decrease in hematocrit is observed to 15% and lower, reticulocytosis. After a few days the hemolysis gradually stops. In case of severe anemia, a transfusion of the erythrocyte mass is indicated.

Stroke

Frequent complication of sickle-cell anemia in children. It develops due to the occlusion of large vessels of the brain, often several. The likelihood of repeated strokes is high. Regular transfusions of erythrocyte mass, which maintain a Hb S level of no more than 30%, significantly reduce the risk of recurrent strokes. In acute disorders of cerebral circulation, urgent exchange transfusion is necessary with the use of erythrocyte mass, dehydration with alkalization.

Megaloblastic crisis

Caused by increased need for folic acid as a result of enhanced erythropoiesis, prevented by the preventive intake of folic acid inside.

With sickle-cell anemia due to repeated vaso-occlusive crises and chronic hemolysis, pronounced chronic changes in many organs are noted. Disturbances from the heart are manifested by tachycardia, dyspnea. The heart is resistant to occlusal 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 chronic hypoxia (chronic anemia), cardiomegaly develops, secondary fibrosis and hemosiderosis of the myocardium progressively progress. When examining the results of an ECG, sinus tachyarrhythmia, levogram, left ventricular hypertrophy, T wave inversion are detected; X-ray revealed an increase in all cavities of the heart, swelling of the pulmonary artery; with echocardiography, dilatation of both the left and right ventricles is revealed. In older patients, pulmonary hypertension and pulmonary heart develop. Recurrent pulmonary infarctions in a number of patients cause pulmonary fibrosis. The emergence of acidosis and hyperosmolarity of the medulla of the kidneys is associated with the formation of sickle-shaped cells, therefore in all patients sickle cell anemia, chronic kidney pathology occurs early. 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 kidney function (the first manifestation of obliteration of the vessels of the medulla of the kidneys is hypostenuria, which is already detectable by the age of 10); a violation of the concentration ability of the kidneys makes patients with sickle cell anemia especially sensitive to dehydration. Defects of the tubules can manifest in the form of tubular acidosis and hyperkalemia. In some cases, a nephrotic syndrome is observed. The defeat of the liver is manifested by chronic hepatomegaly; zones of necrosis in the liver are subsequently fibrotic, hepatopathy can go to cirrhosis. Possible development of posttransfusion hepatitis. Owing to the occlusion of the brain vessels, neurological disorders are noted: speech defects, gait disorders, hemiparesis. Often, eye damage with complications in the form of retinal detachment. Developing pathological processes depend on the localization of the lesion. In younger children, due to the development of anastomosis in the subcutaneous tissue, skin lesions (trophic ulcers of the lower limbs) are not found, in older children and adults, blood loss 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. In all age groups, serious infections are frequent - pneumonia, meningitis, osteomyelitis, sepsis, including urosepsis. The period of maximum risk of death from severe infections is the first 5 years of life.

[4], [5], [6], [7], [8], [9], [10]