BY: NAILUL MUNA BINTI AHMAD MUSADAD

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
thrombocytopaenia



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
Malignancy
SLE
Radiation
Non-
Diarrhea
Related HUS
Diarrhea
associated/
Shiga Toxin
associated
HUS
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,
poultry,lamb)
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
age
HUS develops about 5-10 days after onset of
diarrhea
Hematuria and hypertension are common.
Complications of fluid overload may present
with:
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
Schistocytes
In patients with diarrhea, the identification
of pathogenic EHEC or Shigella is performed
by:
Stool culture
Further serotyping by agglutination or enzyme
immunoassay
Rarely HUS can occur with E. coli UTI:
Urine cultures are indicated in non-diarrheal
patients
Bacteriological cultures of body fluids are
indicated in suspected pneumococcal
disease.
Sputum
CSF
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
Neurological
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
episodes.

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