Epidemiology
Etiology
Pathophysiology
- Autosomal Dominant inheritance (most common).
- Defect in RBC membrane scaffolding proteins: ankyrin, band 3, or spectrin.
- This defect uncouples the cytoskeleton from the lipid bilayer, leading to loss of membrane blebs.
- Results in ↓ surface-area-to-volume ratio, causing RBCs to assume a spherical shape (spherocytes).
- Spherocytes are less deformable and are trapped and destroyed by macrophages in the splenic cords of Billroth.
- This leads to extravascular hemolysis.
Clinical features
- Anemia and pallor
- Jaundice (due to ↑ unconjugated bilirubin)
- Splenomegaly with left upper quadrant pain
- Black pigment gallstones (made of calcium bilirubinate), may lead to cholecystitis
Diagnostics
- Peripheral Smear: Presence of spherocytes (small, round RBCs lacking central pallor). Howell-Jolly bodies may be present if post-splenectomy.
- Labs:
- Normocytic anemia (↓ Hgb, ↓ Hct).
- ↑ Mean Corpuscular Hemoglobin Concentration (MCHC) is a classic finding due to cellular dehydration and membrane loss.
- ↑ Reticulocyte count.
- ↑ Unconjugated bilirubin.
- ↑ LDH.
- ↓ Haptoglobin.
- Confirmatory Tests:
- Osmotic fragility test: Positive. Spherocytes are more fragile and lyse more readily in hypotonic solution.
- Eosin-5-maleimide (EMA) binding test: More specific test, shows decreased binding.
- Coombs test: Negative. Differentiates from autoimmune hemolytic anemia, which also presents with spherocytes.
Treatment