 Hemolytic-uremic syndrome (HUS) is a
clinical syndrome characterized by
progressive renal failure that is associated
with :
 microangiopathic (nonimmune, Coombs-
negative) Hemolytic anemia
 Uremia
 Thrombocytopenia (Low platelet count)

 The pathologic lesion of HUS
 E. Coli Shigatoxin damages
endothelial cells
 Endothelial swelling narrows
vessel lumen
 Platelet/fibrin clots form blocking
blood flow
 Poor blood flow(microcirculation
in kidney)
 Low tissue oxygen (hypoxia)
 Hypoxia
 Cell dysfunction
 Cell necrosis (death)
The typical pathophysiology involves the shiga-toxin binding to proteins on
the surface of glomerular endothelium and inactivating a metalloproteinase
called ADAMTS13, which is also involved in the closely related TTP
 The arterioles and capillaries of the body become obstructed by the
resulting complexes of activated platelets which have adhered to
endothelium via large multimeric vWF.
 The growing thrombi lodged in smaller vessels destroy RBCs as they
squeeze through the narrowed blood vessels, forming schistocytes, or
fragments of sheared RBCs.
 The consumption of platelets as they adhere to the thrombi lodged in
the small vessels typically leads to mild or moderate

Type of HUS / TTP Specific Cause

 Infection related Shiga toxin producing E.coli/Shigella***
Pneumococcal infection
HIV Typical
Other viral or bacterial infections

• Complement factor abnormality Factor H deficiency
CTD Factor I deficiency
• Miscellaneous Drugs Atypical
Related HUS
Shiga Toxin
 Typical/Diarrhea associated/Shiga Toxin
associated HUS
 Enterohaemorrhagic E. coli
 Shigella dysenteriae type 1
 Rarely, HUS can occur with E. coli UTI
 Sources of infection are :
 Milk and animal products (incompletely cooked beef, pork,
 Human feco-oral transmission
 Vegetables, salads and drinking water
may be contaminated by bacteria
shed in animal wastes

 The commonest clinical presentation of HUS
is :
 Acute pallor
 Oliguria
 Diarrhea or dysentery

 It occurs commonly in children between 1-5 years of
 HUS develops about 5-10 days after onset of
 Hematuria and hypertension are common.
 Complications of fluid overload may present
 Pulmonary edema
 Hypertensive encephalopathy
 Despite thrombocytopenia, bleeding
manifestations are rare
 Neurological symptoms like:
 Irritability
 Encephalopathy
 Seizures

 Full Blood Count (FBC)
 Anaemia
 thrombocytopenia
 Peripheral blood smears
 schistocytes
 Reticulocyte count
 reticulocytosis
 Features of intravascular hemolysis
 Raised unconjugated Bilirubin
 Raised Lactate Dehydrogenase(LDH)
 Decreased circulating level of haptoglobin
 Creatinine
 Urine analysis
 Hemoglobinuria
 Hematuria
 Proteinuria
 In patients with diarrhea, the identification
of pathogenic EHEC or Shigella is performed
 Stool culture
 Further serotyping by agglutination or enzyme
 Rarely HUS can occur with E. coli UTI:
 Urine cultures are indicated in non-diarrheal
 Bacteriological cultures of body fluids are
indicated in suspected pneumococcal
 Sputum
 Blood
 Pus

 Supportive Therapy
 Antibiotics
 Plasma Therapy
 Miscellaneous
1. Supportive Therapy
 In all patients, supportive treatment is primary.
 Close clinical monitoring of :
Hydration status
Blood pressure
Ventilatory parameters
 Blood levels of glucose, electrolytes, creatinine
and full blood count need frequent monitoring
2. Antibiotics
 E. coli
 Shigellosis
 pneumococcal HUS

3. Plasma Therapy
 In aHUS due to :
 complement factor abnormality
 ADAMTS13 deficiency
▪ The replacement of the deficient factor with Fresh Frozen Plasma
 Daily plasma infusions (10 to 20 mL/kg/day)
 Exchange of 1.5 times plasma volume ( 60 to 75 mL/kg/day) using FFP
 With the onset of acute renal failure :
 Fluid restriction
 Diuretics
4. Miscellaneous
 In infants with HUS associated with cobalamin abnormalities:
 Treatment with hydroxycobalamin
 Oral betaine
 Folic acid
 Normalizes the metabolic abnormalities can help to prevent further

 In patients with persistent ADAMTS13 antibodies and poor response to
plasma exchange:
 Immunosuppressive therapy with high dose
steroids/cyclophosphamide/ cyclosporin/rituximab
 Splenectomy

 Recently, impressive results have been reported with the anti-C5
monoclonal antibody, eculizumab, which binds to C5, thereby
preventing activation of the terminal complement cascade.

 With aggressive treatment, more than
90% survive the acute phase.
 About 9% may develop end stage
renal disease.
 About one-third of persons with HUS
have abnormal kidney function many
years later, and a few require long-
term dialysis.
 Another 8% of persons with HUS have
other lifelong complications, such as :
 High blood pressure
 Seizures
 Blindness
 Paralysis