249: Thalassemia Flashcards

Class lecture was super confusing. Supplemented with BB Thalassemia video.

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

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*
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3
Q

Composition of fetal hemoglobin:

A

2 alpha chains, 2 gamma chains

Higher O2 affinity than adult hemoglobin

Produced starting at ~10 weeks

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4
Q

What kind of anemia is present in beta-thalassemia?

A

Microcytic anemia with extravascular hemolysis

Hyercellular marrow

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5
Q

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

  • Newborn screening:
  • Post-neonatal testing:
A

Can’t make normal HbA (required beta globins)

  • Newborn screening:
    • HbF only
  • Post-neonatal testing:
    • HbF
    • More HbA2 than normal (made of alpha and delta globins)
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6
Q

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

A

Alpha-thalassemia

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7
Q

On which chromosome is the beta-globin locus found?

A

Chromosome 11

2 copies of beta globin gene (1 on each chromosome)

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8
Q

List 4 treatments for thalassemia

A
  • Transfusions
  • Iron chelation
  • Splenectomy
  • Bone marrow/stem cell transplant

Must manage both anemia and iron overload

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9
Q

What causes chronic hemolysis in beta-thalassemia?

A

Unpaired alpha-globin forms hemichromes in RBCs that induce apoptosis

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10
Q

Composition of normal adult hemoglobin:

A

Hemoglobin A: 2 alph achains, 2 beta chains

  • Mutation in beta chain -> more production of HbA2 or HbF*
  • HbA2- two alpha, two delta*
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11
Q

Composition of hemoglobin H:

A

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)

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12
Q

What are the two primary mechanisms for anemia in beta thalassemia?

A
  • 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
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13
Q

What test is commonly used for diagnosing thalassemias?

A

Hemoglobin Electrophoresis

Also helpful in sickle cell

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14
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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15
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
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16
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

Thank you @Zach Cross!

17
Q

How many copies of the alpha globin gene are there? Where are they located?

A

4 copies, chromosome 16

(2 copies on each chromosome)

18
Q

In alpha-thalassemia, the alpha globin genes are __________________.

A

In alpha-thalassemia, the alpha globin genes are DELETED.

Severity of disease determined by number of deletions

2 deletions→ Alpha Thal Minor/Trait

3 Deletions→ Hemoglobin H Disease

4 Deletions→ Hemoglobin Bart Disease, incompatible with life

19
Q

In beta-thalassemia the beta globin genes are __________

A

In beta-thalassemia the beta globin genes are MUTATED

Beta Thal Minor: one gene mutated

Beta Thal Major: both genes mutated

Gene variants can be B+ (some function) or B0 (non-functional)

Wide variance in presentation

20
Q

What globin genes make up each Hemoglobin molecule?

HbA

HbA2

HbF

HbH

HbBart

A
  • HbA: 2 alpha, 2 beta
  • HbA2: 2 alpha, 2 delta
    • increased in beta-thalassemia
  • HbF: 2 alpha, 2 gamma
  • HbH: 4 betas
    • seen in Hemoglobin H, severe kind of alpha thalassemia (1 functional alpha gene)
  • HbBart: 4 gamma
    • seen in Hemoglobin Bart, most severe kind of alpha thalassemia (no functional alpha globin genes)
    • cannot make any functional fetal hemoglobin
    • incompatible with life