Epidemiology
Mainly children < 5 years of age
Etiology
- Typical HUS (>90%): Associated with Shiga toxin-producing Escherichia coli (STEC), most commonly serotype O157:H7.
- Transmission: Undercooked beef (hamburgers), unpasteurized milk, contaminated water.
- Toxin: Shiga-like toxin (verotoxin).
- Atypical HUS: Genetic mutations (e.g., Complement Factor H deficiency) or drug-induced (e.g., Cyclosporine, Tacrolimus).
Pathophysiology
- Toxin Entry: Ingestion of bacteria → bloody diarrhea prodrome → Shiga-like toxin (verotoxin) enters circulation.
- Endothelial Damage: Toxin binds to Gb3 receptors on endothelial cells, particularly in the glomerulus of the kidney and CNS.
- Microthrombi Formation: Endothelial injury triggers platelet activation and aggregation → formation of platelet-fibrin microthrombi (thrombotic microangiopathy).
- Thrombocytopenia: Systemic consumption of platelets in microthrombi leads to ↓ platelet count (usually <60,000).
- Microangiopathic Hemolytic Anemia (MAHA): RBCs are mechanically sheared while passing through narrowed, thrombus-occluded vessels → formation of schistocytes (helmet cells).
- Acute Kidney Injury (AKI): Microthrombi occlude renal afferent arterioles/glomerular capillaries → ↓ GFR, oliguria/anuria, and uremia.
Clinical features
Diagnostics
- Peripheral Blood Smear: Schistocytes (fragmented RBCs), helmet cells.
- CBC: ↓ Hb, ↓ Platelets.
- Hemolysis Labs: ↑ LDH, ↑ Indirect Bilirubin, ↓ Haptoglobin, ↑ Reticulocytes.
- Coagulation Studies: Normal PT/PTT (Key differentiator from DIC).
- Renal Function: ↑ BUN, ↑ Creatinine.
- Coombs Test: Negative (non-immune hemolysis).
- Stool Culture: Positive for E. coli O157:H7 or Shiga toxin.