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
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, hyperbilirubinemia, 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 (PNH)
- Malignant hypertension
- Scleroderma
- Antiphospholipid Syndrome (APS)
- 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
- pRBC 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