Anemia: Blood Loss - Thalassemia Flashcards
Thalassemias are due to a mutation of the _____.
B-globin chain genes → decreased production
2 categories of mutation in Beta-thalassemia
- B0: zero beta-globulin synthesis
- B+: some beta-globulin synthesis
MCC of B+ thalassemias
splicing mutations
(AR)
Describe the genetic mutations seen in B- thalassemias
- B0: mutation destroys RNA splice junction
- B+: mutation causes ectopic splice site in intron & promoter region mutations
MCC of B0-thalassemia
chain termination mutation: new stop codon or small frameshift insertion/deletion
Thalassemia syndromes are inherited mutations that decrease the synthesis or either ___ or _____ of HbA (a2b2).
- a-globulin
- b-globulin
Alpha-globin chains → encoded on chromosome _____.
Beta-globin chains → encoded on chromosome _____.
- 16
- 11
How does anemia result from thalassemia syndromes?
Decreased Hgb (relative to other globin chains) → decreased RBC production & lifespan
Which thalassemia syndromes require blood transfusion?
B-thalassemia major (not intermedia)
(due to severity; otherwise you would avoid to protect from iron overload)
Which thalassemia syndromes are severe?
- B-thalassemia major
- B-thalassemia intermedia
- HBH disease (resembles B-thalassemia intermedia)
Which 2 thalassemia syndromes are asymptomatic, but have abnormal RBCs?
- B-thalassemia minor
- A-thalassemia trait
Which thalassemia syndrome is lethal in utero?
Hydrops fetalis
Why is erythropoiesis ineffective in B-thalassemia?
precipitation of unpaired a-globin chains inside RBC precursors damages membrane → apoptosis
(70-85% of them)
Extravascular hemolysis in B-thalassemia occurs due to _______.
alpha-chain inclusions → splenic sequestration & destruction
Uncompensated anemia + erythropoietic drive in B-thalassemia leads to a _______ and extensive ________.
- massive erythroid hyperplasia in the marrow
- extramedullary hematopoiesis
4 Complications of B-thalassemias:
- Skeletal abnormalities
- Extraosseous masses
- Severe cachexia (wasting)
- Excessive absorption of iron → liver damage
B-thalassemia patients have extraosseous masses in the ________ (3).
- chest
- abdomen
- pelvis
Severe cachexia (wasting) in B-thalassemia is due to ______.
active RBC precursors stealing nutrients from already O2-starved tissues
Excessive absorption of dietary iron increases hepcidin (iron absorption inhibitor) → accumulation & liver damage. Risk of this is increased with ____.
iron overload due to repeated blood transfusions (tx)
Beta-thalassemia major (transfusion-dependent anemia) is due to ______.
2 B-thalassemia alleles (some combination of B0 & B+)
Why does B-thalassemia major not present until 6-9 months of age?
HbF is protective; this switches to HbA at that age
Electrophoresis of B-thalassemia major shows ______.
HbA2 and HbF with little or no HbA
B-thalassemia major develops a “crewcut” skull & “chipmunk facies” due to ______.
extramedullary hematopoiesis
Cure for B-thalassemia major
hematopoietic stem cell transplant
(molecular testing can dx baby in utero now; untreated patients die early)
Why are aggregates of unpaired a-globulin not seen in B-thalassemia major?
removed by the spleen
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 → ______
- asymptomatic
- mild anemia, ⇡ RBC
- severe anemia
- hydrops fetalis
In Alpha-thalassemia, cis deletion (both deletions occur on the same chromosome) is associated _______. Seen mostly in _______ (patient population).
- with an increased risk of severe thalassemia in offspring
- Asians
In Alpha-thalassemia, trans deletion (one deletions occur on each chromosome) is seen mostly in _______ (patient population).
African Americans
What is HBH?
- B chains that form tetramers (three alpha genes deleted)
- alpha-thalassemia
Hb barts
tetramer of gamma chains that damage RBCs → hydrops fetalis
(visualized on electrophoresis)
Why is it important to identify alpha-thalassemia trait?
- Superficially resembles iron deficiency (hypochromic, microcytic anemia) → check serum iron/ferritin
- genetic counseling
“crewcut” appearance
