A single nucleotide change in a codon on chromosome 11 that causes valine to replace glutamic acid at the sixth position of the b chain of hemoglobin.peripheral blood film of the patient is given
Hemoglobin S (Hb S) is formed by the replacement of glutamic acid by valine in the sixth position in the b chain of hemoglobin. On deoxygenation, Hb S polymerizes and the red cells sickle. In patients heterozygous for Hb S (sickle cell trait, Hb AS), there is approximately 45% Hb S and 55% Hb A. Because of the content of Hb A, erythrocytes only sickle at low oxygen tension and symptoms are much milder than in sickle cell disease. Hb F does not react with hemoglobin S, so that patients who have Hb S and large amounts of Hb F, as occurs in newborns with sickle cell disease, are asymptomatic. Clinically, sickle cell disease is characterized by the triad of chronic hemolytic anemia, vascular occlusion, and vulnerability to infection. The severe chronic hemolytic anemia leads to chronic hyperbilirubinemia (jaundice), which leads to pigmented gallstones. Vascular occlusion results in leg ulcers, renal papillary necrosis, and multiple infarcts, which may cause severe bone pain. Repeated splenic infarcts cause progressive fibrosis and splenic atrophy (autoinfarction). Rather than hypersplenism, most adults have a small, functionless, fibrotic spleen. The lack of splenic function along with defects in the alternate complement pathway predispose to infections such as Salmonella osteomyelitis and pneumococcal infections. The vasoocclusive disease also leads to painful crises, hand-foot syndrome in children (consisting of the typical triad of fever, pallor, and symmetric swelling of hands and feet), and infarctive crises. In patients not having yet undergone splenic autoinfarction (usually children), massive splenic sequestration (sequestration crisis) may lead to rapid splenic enlargement, hypovolemia, and shock. Patients with sickle cell disease have a normocytic anemia with a corrected reticulocyte count of greater than 3%. The erythrocyte sedimentation rate (ESR) is zero because the sickled red cells cannot aggregate and settle in the test tube. Hydroxyurea has recently been approved for the treatment of sickle cell disease because it increases the synthesis of hemoglobin F, thus reducing the severity of the disease Reference: Robbins & Cotran Pathologic Basis of Disease, 9edition.
a thalassemia
Hereditary spherocytosis
Paroxysmal nocturnal hemoglobinuria
Sickle cell anemia
Haematology