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Pathology - Thalassemias
Definition • A collection of hereditary erythrocyte diseases resulting from the insufficient synthesis of alpha or beta globin chains. Pathogenesis • Insufficient production of either A- or B-globin chains results in the accumulation of surplus unpaired chains. • This culminates in the destruction of developing erythrocytes and the premature elimination of circulating erythrocytes in the spleen. The anemia in thalassaemia results from a combination of inadequate erythropoiesis and splenic haemolysis. Beta-thalassemia major • Resulting from mutations in both B-globin genes.
• Complications arise within the initial months of life as HbF levels diminish and surplus A-chains start to build in erythrocytes. • Deteriorating anaemia results in heightened erythropoietic stimulation, causing an increase in the bone marrow volume and the reactivation of extramedullary haematopoiesis.
• Manifestations in infancy include pallor, inadequate feeding, and growth failure. • The complete blood count indicates hypochromic, microcytic anemia. • The diagnosis is corroborated by the nearly absent HbA on hemoglobin electrophoresis. Beta-thalassemia minor • Resulting from mutations in a single B-globin gene.
• Asymptomatic silent carriers exhibit moderate microcytic anemia. • An elevated HbA2 level on hemoglobin electrophoresis is a critical diagnostic indicator. Alpha-thalassemia • A-chains are essential for both adult and fetal hemoglobin. • In the fetus, surplus G-chains aggregate to form tetramers referred to as Hb Bart's. In adulthood, surplus B-chains aggregate to form tetramers referred to as HbH. The deletion of all four A-globin genes results in severe fetal anemia, widespread edema, major hepatosplenomegaly, and fetal demise between 28 and 40 weeks of gestation. The deletion of three alpha-globin genes results in HbH illness, characterized by varying degrees of persistent hemolysis. The majority of individuals experience moderate chronic hemolytic anemia throughout their lives (Hb 7–10 g/dL) accompanied by splenomegaly. Deletion of one or two alpha-globin genes results in alpha-thalassemia minor, which is typically asymptomatic. A minor case of microcytic anemia may be present.
Definition • A collection of hereditary erythrocyte diseases resulting from the insufficient synthesis of alpha or beta globin chains. Pathogenesis • Insufficient production of either A- or B-globin chains results in the accumulation of surplus unpaired chains. • This culminates in the destruction of developing erythrocytes and the premature elimination of circulating erythrocytes in the spleen. The anemia in thalassaemia results from a combination of inadequate erythropoiesis and splenic haemolysis. Beta-thalassemia major • Resulting from mutations in both B-globin genes.
• Complications arise within the initial months of life as HbF levels diminish and surplus A-chains start to build in erythrocytes. • Deteriorating anaemia results in heightened erythropoietic stimulation, causing an increase in the bone marrow volume and the reactivation of extramedullary haematopoiesis.
• Manifestations in infancy include pallor, inadequate feeding, and growth failure. • The complete blood count indicates hypochromic, microcytic anemia. • The diagnosis is corroborated by the nearly absent HbA on hemoglobin electrophoresis. Beta-thalassemia minor • Resulting from mutations in a single B-globin gene.
• Asymptomatic silent carriers exhibit moderate microcytic anemia. • An elevated HbA2 level on hemoglobin electrophoresis is a critical diagnostic indicator. Alpha-thalassemia • A-chains are essential for both adult and fetal hemoglobin. • In the fetus, surplus G-chains aggregate to form tetramers referred to as Hb Bart's. In adulthood, surplus B-chains aggregate to form tetramers referred to as HbH. The deletion of all four A-globin genes results in severe fetal anemia, widespread edema, major hepatosplenomegaly, and fetal demise between 28 and 40 weeks of gestation. The deletion of three alpha-globin genes results in HbH illness, characterized by varying degrees of persistent hemolysis. The majority of individuals experience moderate chronic hemolytic anemia throughout their lives (Hb 7–10 g/dL) accompanied by splenomegaly. Deletion of one or two alpha-globin genes results in alpha-thalassemia minor, which is typically asymptomatic. A minor case of microcytic anemia may be present.
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