Hereditary spherocytosis

Background

• 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 Features

• Classic triad: Anemia, Jaundice, Splenomegaly

Mild

• No anemia, normal retic count, little or no jaundice/splenomegaly
• No RBC transfusions
• Dx’d later in life

Moderate

• Anemic, elevated retic, elevated bili, maybe splenomegaly
• May require RBC transfusions
• Dx’d in infancy or early childhood

Severe

• Marked hemolysis, anemia, hyperbili, splenomegaly
• Require regular RBC transfusions
• Dx’d in infancy

Differential Diagnosis

Microangiopathic Hemolytic Anemia (MAHA)

• Disseminated Intravascular Coagulation (DIC)
• Thrombotic Thrombocytopenic Purpura (TTP)
• Hemolytic Uremic Syndrome (HUS)
• HELLP syndrome
• Heparin-Induced Thrombocytopenia (HIT)
• Hereditary spherocytosis
• Paroxysmal nocturnal hemoglobinuria
• Malignant hypertension
• Antiphospholipid syndrome
• Scleroderma
• Antiphospholipid Syndrome (APS)
• Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Other medical causes: malignancy, renal allograft rejection, vasculitides like polyarteritis nodosa and Wegener's granulomatosis
• Drugs: chemotherapy; Clopidogrel (Plavix) associated with TTP
• Nonvascular causes: prosthetic valve (more common with mechanical, more common at aortic valve), LVAD, TIPS, coil embolization, patched AV shunt, AVM

Evaluation

• Low hemoglobin, 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 patients
• Negative Coombs test

Management

• Folic acid
• RBC transfusion
• EPO
• Splenectomy
  • As late as possible, preferably >6 yo
  • Post-op need encapsulated bacteria prophylaxis: 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)

Complications

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

See Also

Authors

Ross Donaldson