Comparison of alpha and beta thalassemia pathophysiology and clinical features

Pathophysiology	Alpha thalassemia	Beta thalassemia
Genes affected	Alpha locus 1 and/or 2	Beta locus and sometimes delta locus
Globin chains in excess	Gamma chains (fetus through early infancy), which form HbBarts* Beta chains (child and adult), which form HbH* Beta chains can also form aggregates during erythropoiesis but to a lesser extent than free alpha chains	Alpha chains, which aggregate and precipitate, beginning early in erythropoiesis* Some alpha chains persist in circulating RBCs as inclusion bodies
Effect on RBCs and erythroblasts	Membrane damage Hyperhydration	Membrane damage Dehydration
Mechanisms of anemia^¶	Peripheral blood hemolysis predominates Component of ineffective erythropoiesis	Ineffective erythropoiesis predominates Component of peripheral blood hemolysis
Clinical features
Geographic origins	Malaria belt^Δ	Malaria belt^Δ
Age of onset	Before birth	6 to 9 months
Physical findings	Pallor and jaundice Growth retardation Bony and facial deformities (lesser in alpha thalassemia than beta thalassemia) Hepatosplenomegaly	Pallor and jaundice Growth retardation Bony and facial deformities (more in beta thalassemia than in alpha thalassemia) Hepatosplenomegaly
CBC and blood smear	Findings consistent with hemolytic anemia^◊ Microcytosis and hypochromia Anisocytosis and poikilocytosis	Findings consistent with hemolytic anemia^◊ Microcytosis and hypochromia Anisocytosis and poikilocytosis NRBCs
Complications	Iron overload and associated organ damage (with or without transfusions) Extramedullary hematopoiesis VTE Leg ulcers Pathologic fractures (less-so in alpha than in beta thalassemia)	Iron overload and associated organ damage (with or without transfusions) Extramedullary hematopoiesis VTE Leg ulcers Pathologic fractures (more-so in beta than in alpha thalassemia)

The severity of all of these features depends on how many of the globin genes are affected (beta thalassemia: 1 or 2; alpha thalassemia: 1, 2, 3, or 4) and the specific variant(s) within the affected gene(s). Persistence of HbF after birth can mitigate the clinical severity of beta thalassemia. Refer to UpToDate for additional information.

HbH: hemoglobin H; RBCs: red blood cells; CBC: complete blood smear: NRBC: nucleated red blood cells; VTE: venous thromboembolism.
* HbBarts (tetramers of gamma globin) and HbH (tetramers of beta globin) are somewhat soluble homotetrameric hemoglobins that behave like unstable hemoglobins. They bind oxygen but cannot release it to tissues. Unpaired alpha chains cannot form hemoglobin and instead aggregate and form insoluble precipitates.
¶ Alpha and beta thalassemia both have components of ineffective erythropoiesis and peripheral blood hemolysis.
Δ The malaria belt consists of tropical and subtropical regions in which malaria is (or was) endemic, including the Mediterranean basin, Africa, the Middle East, and Southern Asia.
◊ In addition to anemia, hemolysis can cause low haptoglobin, increased lactate dehydrogenase (LDH), increased indirect bilirubin, and increased reticulocyte count.

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Comparison of alpha and beta thalassemia pathophysiology and clinical features