249 - Thalassemia Flashcards

1
Q

What defines thalassemia major vs. intermedia?

A
  • 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

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2
Q

Composition of hemoglobin Bart:

A

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*
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3
Q

Composition of fetal hemoglobin:

A

2 alpha chains, 2 gamma chains

Higher O2 affinity than adult hemoglobin

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4
Q

What kind of anemia is present in beta-thalassemia?

A

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

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5
Q

What types of hemoglobin will be present in beta-thalassemia during…

  • Newborn screening:
  • Post-neonatal testing:
A
  • Newborn screening:
    • HbF only
  • Post-neonatal testing:
    • HbF
    • More HbA2 than normal (two alpha globins + two delta globins)
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6
Q

What is the significance of Hemoglobin E?

(Severe phenotype?)

A

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
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7
Q

Is acute hemolysis more prominent in alpha-thalassemia or beta-thalassemia?

A

Alpha-thalassemia

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8
Q

On which chromosome is the beta-globin locus found?

A

Chromosome 11

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9
Q

List 4 treatments for thalassemia

A
  • 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

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10
Q

What causes chronic hemolysis in beta-thalassemia?

A

Unpaired alpha-globin forms hemichromes and inclusion bodies in RBCs that induce apoptosis

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11
Q

Composition of normal adult hemoglobin:

A

2 alph achains, 2 beta chains

  • Mutation in beta chain -> more production of HbA2 or HbF*
  • (HbF is functional, HbA2 is not)*
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12
Q

Composition of hemoglobin H:

A

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)*
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13
Q

What are the two primary mechanisms for anemia in thalassemia?

A
  • 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
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14
Q

For thalassemias, what testing is used for:

  • Newborn screening (2):
  • Postnatal testing (2):
A
  • Newborn screening:
    • High Performance Liquid Chromatography (HPLC)
    • Hemoglobin electrophoresis
  • Postnatal testing:
    • CBC
    • Hemoglobin electrophoresis
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15
Q

What is the consequence of globin chain imbalance within the cell?

A

The extra chains form hemichromes which induce RBC apoptosis

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16
Q

Which complications of thalassemia can be mitigated by transfusions? (5)

A
  • Facial deformity
  • Hypersplenism
  • Anemia
  • Pathological fractures
  • Premature closure of the lower femoral epiphysis
17
Q

What types of hemoglobin will be present in alpha-thalassemia during…

  • Newborn screening:
  • Post-neonatal testing:
A
  • Newborn screening:
    • Hb Bart’s (gamma tetramers)
  • Post-neonatal testing
    • HbH (beta tetramers)
18
Q

What causes hepatosplenomegaly in thalassemia?

A

Globin chain imbalance, extra chains form hemichromes

  • > Tags RBCs for apoptosis
  • > Sequestered in spleen

Also exramedullary hematopoiesis -> hepatosplenomegaly