Which of the following is the PRIMARY mechanism of anemia in β-thalassemia major?
A. Reduced oxygen-carrying capacity due to low hemoglobin synthesis alone
B. Bone marrow infiltration by leukemic cells
C. Hemolysis caused by precipitation of excess α-globin chains forming insoluble inclusions
D. Acute blood loss from gastrointestinal bleeding
Explanation
Pathophysiology of Anemia in β-Thalassemia Major
Key Point
The anemia in β-thalassemia major results from hemolysis due to precipitation of excess α-globin chains, not simply from reduced hemoglobin synthesis.
Mechanism of α-Globin Precipitation
1.
β-globin deficiency → imbalance in globin chain synthesis
2.
Excess α-globin chains accumulate (no β-chains to pair with)
3.
Unpaired α-globin chains precipitate → form insoluble inclusions (Heinz bodies)
4.
RBC membrane damage → hemolysis and ineffective erythropoiesis
5.
Severe hemolytic anemia with reticulocytosis
High-YieldNEET PG
This is why β-thalassemia major is fundamentally a hemolytic anemia, not just a hypoproliferative anemia. The RBCs are destroyed in the bone marrow (ineffective erythropoiesis) and in the spleen (extravascular hemolysis).
Ineffective Erythropoiesis vs. Hemolysis
Table
Process
Contribution to Anemia
Ineffective erythropoiesis
70–80% of RBC loss (destroyed in bone marrow)
Extravascular hemolysis
20–30% of RBC loss (destroyed in spleen)
Clinical Pearl
Patients with β-thalassemia major have:
Marked reticulocytosis (>10%) — bone marrow response
Splenomegaly — from extramedullary hematopoiesis and hemolysis
Elevated indirect bilirubin — from hemolysis
Elevated LDH — from hemolysis and ineffective erythropoiesis
Why Simple Reduced Synthesis Is Insufficient
If anemia were only from reduced β-globin synthesis, patients would have:
Mild-to-moderate anemia (like in iron deficiency)
Normal reticulocyte response
No hemolysis markers
Instead, β-thalassemia major shows severe hemolytic anemia because of the toxic effect of precipitated α-globin chains on RBC membranes.
Mnemonic
ALPHA — Alpha chains accumulate, Lead to precipitation, Precipitates damage membrane, Hemolysis results, Anemia is severe.
Robbins 10e Ch 12
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