Sickle cell anemia

    • autosomal recessive disorder  (MCQ)
    • abnormal hemoglobin leads to chronic hemolytic anemia
    • A single DNA base change leads to an amino acid substitution of valine for glutamine in the sixth position on the Beta-globin chain. (MCQ)
    • The abnormal Beta chain has a tetramer of alpha2Beta(s)2 is designated hemoglobin S. (MCQ)
    • The rate of sickling is influenced by a number of factors (MCQ)
      • most importantly by the concentration of hemoglobin S in the individual red blood cell. Red cell dehydration makes the cell quite vulnerable to sickling.
      • Hemoglobin F cannot participate in polymer formation, and its presence markedly retards sickling.
      • Other factors that increase sickling are those that lead to formation of deoxyhemoglobin S, eg, acidosis and hypoxemia, either systemic or locally in tissues.
    • Clinical Findings          ‘           ‘
      • The disorder has its onset during the first year of life, when hemoglobin F levels fall as a signal is sent to switch from production of Gamma-globin to Beta-globin. (MCQ)
      • Chronic hemolytic anemia produces jaundice, pigment (calcium bilirubinate) gallstones, splenomegaly, and poorly healing ulcers over the lower tibia.
      • Severe anemia is produced by hemolytic or aplastic crises.
      • Aplastic crises occur when the ability of the bone marrow to compensate is reduced by viral or other infection or by folate deficiency. (MCQ)
      • Hemolytic crises may be related to splenic sequestration of sickled cells (primarily in childhood, before the spleen has been infarcted as a result of repeated sickling) or with coexistent disorders such as G6PD deficiency.
      • Acute painful episodes due to acute vaso-occlusion may occur spontaneously or be provoked by infection, dehydration, or hypoxia.
        • Common sites of acute painful episodes include the bones (especially the back and long bones) and the chest.
        • Acute vaso-occlusion may also cause strokes due to sinus thrombosis and priapism. (MCQ)
        • Vaso-occlusive episodes are not associated with increased hemolysis.
        • Repeated episodes of vascular occlusion affect a large number of organs, especially the heart, lungs, and liver.
        • Ischemic necrosis of bone occurs, rendering the bone susceptible to osteomyelitis due to staphylococci or (less commonly) salmonellae. (MCQ)
        • Infarction of the papillae of the renal medulla causes renal tubular concentrating defects and gross hematuria, more often encountered in sickle cell trait than in sickle cell anemia. (MCQ)
        • Retinopathy similar to that noted in diabetes is often present and may lead to blindness. (MCQ)
        • Pulmonary hypertension may develop and is associated with a poor prognosis.
      • These patients are prone to delayed puberty. (MCQ)
      • An increased incidence of infection is related to hyposplenism as well as to defects in the alternative pathway of complement.
      • On examination, patients are often chronically ill and jaundiced.
      • There is hepatomegaly, but the spleen is not palpable in adult life.
      • The heart is enlarged, with a hyper-dynamic precordium and systolic murmurs. (MCQ)
      • Nonhealing ulcers of the lower leg and retinopathy may be present.
    • Laboratory Findings
      • Chronic hemolytic anemia is present.
      • The hematocrit is usually 20-30%.(MCQ)
      • The peripheral blood smear is characteristically abnormal, with irreversibly sickled cells comprising 5-50% of red cells.
      • Other findings include reticulocytosis (10-25%), nucleated red blood cells, and hallmarks of hyposplenism such as Howell-Jolly bodies and target cells. The white blood cell count is characteristically elevated to 12,000-15,000/mcL(MCQ)
      • thrombocytosis may occur.
      • Indirect bilirubin levels are high.
      • Most clinical laboratories offer a screening test for sickle cell hemoglobin, and the diagnosis of sickle cell anemia is then confirmed by hemoglobin electrophoresis
      • Hemoglobin F levels are variably increased, and high hemoglobin F levels are associated with a more benign clinical course.
    • Treatment
      • Patients are maintained on folic acid supplementation
      • given transfusions for aplastic or hemolytic crises.
      • Pneumococcal vaccination reduces the incidence of infections with this pathogen. (MCQ)
      • The patient should be kept well hydrated, and oxygen should be given if the patient is hypoxic.
      • Acute vaso-occlusive crises can be treated with exchange transfusion. (MCQ)
      • These are primarily indicated for the treatment of intractable pain crises, priapism, and stroke.
      • Long-term transfusion therapy has been shown to be effective in reducing the risk of recurrent stroke in children.
      • Cytotoxic agents increase hemoglobin F levels by stimulating erythropoiesis in more primitive erythroid precursors.
        • Hydroxyurea reduces the frequency of painful crises in patients whose quality of life is dis¬rupted by frequent pain crises. (MCQ)
      • Allogeneic bone marrow transplantation is being studied as a possible curative option for severely affected young patients.
    • Sickle cell trait
      • Patients with the heterozygous genotype (AS) have sickle cell trait.
      • These persons are clinically normal and have acute painful episodes only under extreme conditions such as vigorous exertion at high altitudes (or in unpressurized aircraft).
      • They may, however, have a defect in renal tubular function, causing an inability to concentrate the urine, and experience episodes of gross hematuria. (MCQ)
      • A screening test for sickle hemoglobin will be positive
      • hemoglobin electrophoresis will reveal that approximately 40% of hemoglobin is hemoglobin S
    • Hemoglobin C disorders
      • Hemoglobin C is formed by a single amino acid substitu¬tion at the same site of substitution as in sickle hemoglobin but with lysine instead of valine substituted for glutamine at the Beta 6 position. (MCQ)
      • Hemoglobin C is nonsickling but may participate  in  polymer  formation  in  association  with hemoglobin S.
      • The peripheral blood smear shows generalized red cell targeting and occasional cells with rectangular crystals of hemoglobin C. (MCQ)

    Sickle Cell Disease
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