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).

HUS is a thrombotic microangiopathy, a condition characterized by the formation of microthrombi occluding the microvasculature.

Infection with enterohemorrhagic E. coli (EHEC) or another causative organism
Mucosal inflammation facilitates bacterial toxins entering systemic circulation.
- Most commonly Shiga-like toxin from enterohemorrhagic E. coli (EHEC) strain O157:H7
Toxins cause endothelial cell damage (especially in the glomerulus ).
Damaged endothelial cells secrete cytokines that promote vasoconstriction and platelet microthrombus formation at the site of damage (intravascular coagulopathy) → thrombocytopenia (consumption of platelets)
RBCs are mechanically destroyed as they pass through the platelet microthrombi occluding small blood vessels (i.e., arterioles, capillaries) → hemolysis (schistocytes), and end-organ ischemia and damage, especially in the kidneys → decreased glomerular filtration rate (GFR)

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.