- 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.
- 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
sickle cell anemia 1
Sickle Cell Anemia: A Patient’s Journey
As a young child, Alexandria, now age 17, endured near-constant feelings of exhaustion and general sickness, which turned into severe pain at night. After experiencing a “silent stroke” as a young girl, Alexandria was diagnosed with sickle cell anemia, a disease in which the blood cells become deformed and unable to function properly.
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What is sickle cell anemia? What is malaria? And how can one be linked to the other? Answer these questions for your students using this educational video on human evolution
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What is Sickle Cell Anemia
What is Sickle Cell Anemia? Learn what causes Sickle Cell Anemia and donate to www.fudgefoundation.com today. Let’s find a cure for Sickle Cell together
Pathophysiology of Sickle Cell Anemia