Hereditary spherocytosis

Introduction

• Hereditary Spherocytosis (HS) = hereditary hemolytic anemia due to defect in RBC cell membrane (mainly spectrin, ankyrin)
  • 75% Autosomal Dominant, 25% Autosomal Recessive

Pathophysiology

• Deficient/Nonfunctional RBC cell membrane proteins that connect the cell membrane skeleton to the lipid bilayer

Clinical Presentation

• Classic triad: Anemia, Jaundice, Splenomegaly

• Mild HS:
  • No anemia, normal retic count, little or no jaundice/splenomegaly
  • No RBC transfusions
  • Dx’d later in life
• Moderate HS:
  • Anemic, elevated retic, elevated bili, maybe splenomegaly
  • May require RBC transfusions
  • Dx’d in infancy or early childhood
• Severe HS:
  • Marked hemolysis, anemia, hyperbili, splenomegaly
  • Require regular RBC transfusions
  • Dx’d in infancy

Work-Up

• Low Hb, elevated retic count, spherocytes on peripheral smear
• Elevated MCHC (RBC membrane leaky causing RBC dehydration)
• Osmotic fragility test, AGLT, EMA binding test, cryohemolysis
  • One study showed AGLT + EMA binding test identified all HS pts
• Negative Coombs test

Complications

• Cholelithiasis secondary to intravascular hemolysis causing development of bilirubin gallstones
• Pseudohyperkalemia: K+ leaks out of RBCs after blood draw

Treatment

• Folic acid
• RBC transfusion
• EPO
• Splenectomy
  • As late as possible, preferably >6 yo
  • Post-op need encapsulated bacteria prophy: Strep Pneumo, H Influenza, Neiserria Meningitidis
  • Possible higher risk of arterial/venous thrombosis in HS after splenectomy
• Hematopoietic cell transplant (most agree risks outweigh benefits)

See Also

• DIC, TTP, HUS, Microangiopathic Hemolytic Anemia (MAHA)
• HELLP, HIT, Paroxysmal Nocturnal Hemoglobinuria (PNH)