249: Thalassemia Flashcards
Class lecture was super confusing. Supplemented with BB Thalassemia video.
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:
4 gamma globins
Hemoglobin Bart disease is a severe form of alpha thalassemia
- Complete alpha-globin deficiency (0 working copies) usually results in hydrops fetalis→ cannot form fetal hemoglobin*
- 1 working copy can survive, has HbH disease*
Composition of fetal hemoglobin:
2 alpha chains, 2 gamma chains
Higher O2 affinity than adult hemoglobin
Produced starting at ~10 weeks
What kind of anemia is present in beta-thalassemia?
Microcytic anemia with extravascular hemolysis
Hyercellular marrow
What types of hemoglobin will be present in beta-thalassemia during…
- Newborn screening:
- Post-neonatal testing:
Can’t make normal HbA (required beta globins)
- Newborn screening:
- HbF only
- HbF only
- Post-neonatal testing:
- HbF
- More HbA2 than normal (made of alpha and delta globins)
Is acute hemolysis more prominent in alpha-thalassemia or beta-thalassemia?
Alpha-thalassemia
On which chromosome is the beta-globin locus found?
Chromosome 11
2 copies of beta globin gene (1 on each chromosome)
List 4 treatments for thalassemia
- Transfusions
- Iron chelation
- 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 in RBCs that induce apoptosis
Composition of normal adult hemoglobin:
Hemoglobin A: 2 alph achains, 2 beta chains
- Mutation in beta chain -> more production of HbA2 or HbF*
- HbA2- two alpha, two delta*
Composition of hemoglobin H:
4 beta globins
Hemoglobin H Disease: more severe form of alpha thalassemia, 3 of 4 alpha globins are delete
-> HbH disease, in some normal hemoglobin (HbA, with 2 alpha, 2 beta) and some HbH (4 beta)
What are the two primary mechanisms for anemia in beta thalassemia?
-
Ineffective erythropoiesis
- Reduced or absent beta globin
- -> unpaired alpha-globin, immature RBCs
-
Chronic hemolysis
- Unpaired alpha-globin forms hemichromes that induce RBC apoptosis
- -> sequestered in the spleen
What test is commonly used for diagnosing thalassemias?
Hemoglobin Electrophoresis
Also helpful in sickle cell
What is the consequence of globin chain imbalance within the cell?
The extra chains form hemichromes which induce RBC apoptosis
Which complications of thalassemia can be mitigated by transfusions? (5)
- Facial deformity
- Hypersplenism
- Anemia
- Pathological fractures
- Premature closure of the lower femoral epiphysis