249 - Thalassemia Flashcards
What defines thalassemia major vs. intermedia?
- Major: ≥8 transfusions in the last 12 months
- Intermedia: <8 transfusions in the last 12 months
Genotype does not accurately affect phenotype; classify operationally instead of genetically
Composition of hemoglobin Bart:
gamma-globin tetramer
- Formed during gestation due to deficient functional alpha-globin*
- Hb Bart decreases quickly after birth -> beta tetramers form instead (HbH)*
- Complete alpha-globin deficiency (0 working copies) usually results in hydrops fetalis, but if there is 1 working copy of alpha globin, then has HbH disease*
Composition of fetal hemoglobin:
2 alpha chains, 2 gamma chains
Higher O2 affinity than adult hemoglobin
What kind of anemia is present in beta-thalassemia?
Microcytic anemia despite hypercellular marrow
too much alpha chain for the decreased amount of beta chain –> extra alpha chain forms hemichromes and inclusion bodies –> apoptosis
What types of hemoglobin will be present in beta-thalassemia during…
- Newborn screening:
- Post-neonatal testing:
- Newborn screening:
- HbF only
- HbF only
- Post-neonatal testing:
- HbF
- More HbA2 than normal (two alpha globins + two delta globins)
What is the significance of Hemoglobin E?
(Severe phenotype?)
Point mutation in beta-globin splice site
- Homozygous HbE
- Benign clinical course; alpha/beta interface less stable under oxidative stress
- BUT: heterozygous for HbE and beta-thalassemia
- -> Severe phenotype
Is acute hemolysis more prominent in alpha-thalassemia or beta-thalassemia?
Alpha-thalassemia
On which chromosome is the beta-globin locus found?
Chromosome 11
List 4 treatments for thalassemia
- Transfusions
- Iron chelation - too much iron can develop b/c of the transfusions
- Splenectomy
- Bone marrow/stem cell transplant
Must manage both anemia and iron overload
What causes chronic hemolysis in beta-thalassemia?
Unpaired alpha-globin forms hemichromes and inclusion bodies in RBCs that induce apoptosis
Composition of normal adult hemoglobin:
2 alph achains, 2 beta chains
- Mutation in beta chain -> more production of HbA2 or HbF*
- (HbF is functional, HbA2 is not)*
Composition of hemoglobin H:
Beta-globin tetramer
- Only 1 working copy of alpha-globin (alpha-thalassemia)*
- -> HbH disease, where 1 working copy results in some normal hemoglobin (HbA, with 2 alpha, 2 beta) and some HbH (4 beta)*
What are the two primary mechanisms for anemia in thalassemia?
-
Ineffective erythropoiesis
- Reduced or absent beta globin –> can’t make the cells correctly
- -> unpaired alpha-globin, immature RBCs
-
Chronic hemolysis
- Unpaired alpha-globin forms hemichromes that induce RBC apoptosis
- -> sequestered in the spleen
For thalassemias, what testing is used for:
- Newborn screening (2):
- Postnatal testing (2):
- Newborn screening:
- High Performance Liquid Chromatography (HPLC)
- Hemoglobin electrophoresis
- Postnatal testing:
- CBC
- Hemoglobin electrophoresis
What is the consequence of globin chain imbalance within the cell?
The extra chains form hemichromes which induce RBC apoptosis
