Anemia: Blood Loss - Thalassemia

Question 1

Thalassemias are due to a mutation of the _____.

Answer 1

B-globin chain genes → decreased production

Question 2

2 categories of mutation in Beta-thalassemia

Answer 2

• B0: zero beta-globulin synthesis
• B+: some beta-globulin synthesis

Question 3

MCC of B+ thalassemias

Answer 3

splicing mutations

(AR)

Question 4

Describe the genetic mutations seen in B- thalassemias

Answer 4

• B0: mutation destroys RNA splice junction
• B+: mutation causes ectopic splice site in intron & promoter region mutations

Question 5

MCC of B0-thalassemia

Answer 5

chain termination mutation: new stop codon or small frameshift insertion/deletion

Question 6

Thalassemia syndromes are inherited mutations that decrease the synthesis or either ___ or _____ of HbA (a2b2).

Answer 6

• a-globulin
• b-globulin

Question 7

Alpha-globin chains → encoded on chromosome _____.

Beta-globin chains → encoded on chromosome _____.

Answer 7

• 16
• 11

Question 8

How does anemia result from thalassemia syndromes?

Answer 8

Decreased Hgb (relative to other globin chains) → decreased RBC production & lifespan

Question 9

Which thalassemia syndromes require blood transfusion?

Answer 9

B-thalassemia major (not intermedia)

(due to severity; otherwise you would avoid to protect from iron overload)

Question 10

Which thalassemia syndromes are severe?

Answer 10

1. B-thalassemia major
2. B-thalassemia intermedia
3. HBH disease (resembles B-thalassemia intermedia)

Question 11

Which 2 thalassemia syndromes are asymptomatic, but have abnormal RBCs?

Answer 11

1. B-thalassemia minor
2. A-thalassemia trait

Question 12

Which thalassemia syndrome is lethal in utero?

Answer 12

Hydrops fetalis

Question 13

Why is erythropoiesis ineffective in B-thalassemia?

Answer 13

precipitation of unpaired a-globin chains inside RBC precursors damages membrane → apoptosis

(70-85% of them)

Question 14

Extravascular hemolysis in B-thalassemia occurs due to _______.

Answer 14

alpha-chain inclusions → splenic sequestration & destruction

Question 15

Uncompensated anemia + erythropoietic drive in B-thalassemia leads to a _______ and extensive ________.

Answer 15

• massive erythroid hyperplasia in the marrow
• extramedullary hematopoiesis

Question 16

4 Complications of B-thalassemias:

Answer 16

1. Skeletal abnormalities
2. Extraosseous masses
3. Severe cachexia (wasting)
4. Excessive absorption of iron → liver damage

Question 17

B-thalassemia patients have extraosseous masses in the ________ (3).

Answer 17

1. chest
2. abdomen
3. pelvis

Question 18

Severe cachexia (wasting) in B-thalassemia is due to ______.

Answer 18

active RBC precursors stealing nutrients from already O2-starved tissues

Question 19

Excessive absorption of dietary iron increases hepcidin (iron absorption inhibitor) → accumulation & liver damage. Risk of this is increased with ____.

Answer 19

iron overload due to repeated blood transfusions (tx)

Question 20

Beta-thalassemia major (transfusion-dependent anemia) is due to ______.

Answer 20

2 B-thalassemia alleles (some combination of B0 & B+)

Question 21

Why does B-thalassemia major not present until 6-9 months of age?

Answer 21

HbF is protective; this switches to HbA at that age

Question 22

Electrophoresis of B-thalassemia major shows ______.

Answer 22

HbA₂ and HbF with little or no HbA

Question 23

B-thalassemia major develops a “crewcut” skull & “chipmunk facies” due to ______.

Answer 23

extramedullary hematopoiesis

Question 24

Cure for B-thalassemia major

Answer 24

hematopoietic stem cell transplant

(molecular testing can dx baby in utero now; untreated patients die early)

Question 25

Why are aggregates of unpaired a-globulin not seen in B-thalassemia major?

Answer 25

removed by the spleen

Question 26

a-Thalassemia is usually due to gene deletion; normally, 4 alpha genes are present on chromosome 16.

One gene deletion → ______

Two genes Deleted → ______

Three genes deleted → _____

Four genes deleted → ______

Answer 26

1. asymptomatic
2. mild anemia, ⇡ RBC
3. severe anemia
4. hydrops fetalis

Question 27

In Alpha-thalassemia, cis deletion (both deletions occur on the same chromosome) is associated _______. Seen mostly in _______ (patient population).

Answer 27

• with an increased risk of severe thalassemia in offspring
• Asians

Question 28

In Alpha-thalassemia, trans deletion (one deletions occur on each chromosome) is seen mostly in _______ (patient population).

Answer 28

African Americans

Question 29

What is HBH?

Answer 29

• B chains that form tetramers (three alpha genes deleted)
• alpha-thalassemia

Question 30

Hb barts

Answer 30

tetramer of gamma chains that damage RBCs → hydrops fetalis

(visualized on electrophoresis)

Question 31

Why is it important to identify alpha-thalassemia trait?

Answer 31

1. Superficially resembles iron deficiency (hypochromic, microcytic anemia) → check serum iron/ferritin
2. genetic counseling

Question 32

Answer 32

“crewcut” appearance