Hemolytic Uremicsyndrome

Definition
HUS, is a disease characterized by :

Acute kidney failure
Hemolytic anemia
Thrombocytopenia (low platelet count)
It predominantly, but not exclusively, affects children.
Types HUS
Typical HUS
Atypical HUS
HUS due to Complement abnormalities
CLASSIFICATION OF HUS / TTP ACCORDING

TO ETIOPATHOGENESIS
Type of HUS / TTP
Infection related
Specific Cause
Shiga toxin producing E.coli/Shigella
Pneumococcal infection
HIV
Typical
Other viral or bacterial infections
Complement factor abnormality

CTD
Miscellaneous
Drugs
Malignancy
Factor H deficiency
Factor I deficiency
Atypical
ETIOPATHOGENESIS
Typical/Diarrhea associated/Shiga Toxin
associated HUS
Enterohaemorrhagic E. coli
Shigella dysenteriae type 1
Rarely, HUS can occur with E. coli UTI
CONTI..
The common serotype of E coli:0157:H7
However, only about 10-15% patients with E. coli
0157:H7 infection will develop HUS

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
Atypical/Non-Diarrhea Related HUS

Pneumococcal HUS
HUS due to Complement abnormalities
Miscellaneous Causes of HUS / TTP

Abnormalities in intracellular vitamin B12 metabolism
HIV
Systemic lupus erythromatosus
Malignancies
Radiation
Certain drugs
Other infections associated with HUS

Include viruses like :
Influenza
Cytomegalovirus
Infectious mononucleosis
Bacteria like:
Streptococcii
Salmonella
Pathophysiology
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
CONTI..
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.
CONTI
The consumption of platelets as they adhere to the
thrombi lodged in the small vessels typically leads to

mild or moderate thrombocytopaenia
However, in comparison to TTP, the kidneys tend to
be more severely affected in HUS, and the central

nervous system is less commonly affected
CLINICAL FEATURES
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
CONTI..
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
INVESTIGATIONS
CBC
Peripheral blood smears
Reticulocyte count
LDH
Bilirubin unconjugated
Cr & BUN
Urine analysis
Hemoglobinuria
Hematuria
Proteinuria
Schistocytes
Investigations to Identify Cause

In patients with dirrhea, 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
Conti..
Bacteriological cultures of body fluids are indicated in
suspected pneumococcal disease.

Sputum
CSF
Blood
Pus
Diagnosis
Clinically, HUS can be very hard to distinguish from
TTP
The laboratory features are almost identical, and not
every case of HUS is preceded by diarrhea
HUS is characterized by the triad of:
Hemolytic anemia
Thrombocytopenia
Acute renal failure
MANAGEMENT
Supportive Therapy
Antibiotics
Plasma Therapy
Miscellaneous
Supportive Therapy
In all patients, supportive treatment is primary.
Close clinical monitoring of :
Fluid status
Blood pressure
Neurological
Ventilatory parameters
Blood levels of glucose, electrolytes, creatinine and
hemogram need frequent monitoring
CONTI..
The use of antimotility therapy for diarrhea has been
associated with a higher risk of developing HUS

With the onset of acute renal failure :
Fluid restriction
Diuretics
Antibiotics
E. coli
Shigellosis
pneumococcal HUS
Plasma Therapy
Immediate administration of plasma exchange is
essential in most cases due to the mortality rate of >

95% without treatment. With the exception of
children or adults with endemic diarrhea-associated
HUS, who generally recover with supportive care only,
plasma exchange must be initiated as soon as the
diagnosis of TMA is suspected
Plasma Therapy
In aHUS due to :
complement factor abnormality
ADAMTS13 deficiency
The replacement of the deficient factor with FFP
Daily plasma infusions (10 to 20 mL/kg/day)

Exchange of 1.5 times plasma volume ( 60 to 75
mL/kg/day) using FFP
. Plasma exchange usually is administered once daily
until the platelet count and LD have returned to

normal for at least 2 days, after which the frequency of
treatments may be tapered slowly while the platelet
count and LD are monitored for relapse.
In cases of insufficient response to once-daily plasma
exchange, twice-daily treatments should be given.
Fresh frozen plasma (FFP) may be administered if
immediate access to plasma exchange is not available or in

cases of familial TMA.
Platelet transfusions are contraindicated in the treatment
of TMAs due to reports of worsening thrombotic
microangiopathy, possibly due to propagation of plateletrich microthrombi. In cases of documented lifethreatening bleeding, however, platelet transfusions may
be given slowly and after plasma exchange is underway.
Red blood cell transfusions may be administered in cases of
clinically significant anemia.
In cases of relapse following initial treatment, plasma
exchange should be reinstituted

. If ineffective, or in cases of primary refractoriness,
second-line treatments may be considered including
rituximab, corticosteroids, IVIG, vincristine,
cyclophosphamide, and splenectomy.
Cases of atypical HUS may respond to plasma infusion
initially, and serial infusions of the anticomplement C5

antibody eculizumab have produced sustained
remissions in some patients.
If irreversible renal impairment has occurred,
hemodialysis or renal transplantation may be
necessary
Miscellaneous
In infants with HUS associated with cobalamin
abnormalities:
Treatment with hydroxycobalamin
Oral Folic acid
Normalizes the metabolic abnormalities can help to
prevent further episodes.
CONTI..
In patients with persistent ADAMTS13 antibodies and
poor response to plasma exchange:

Immunosuppressive therapy with high dose
steroids/cyclophosphamide/ cyclosporin/rituximab
Splenectomy
Prognosis
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 longterm dialysis.
Another 8% of persons with HUS have other lifelong
complications, such as :
High blood pressure
Seizures
Blindness
Paralysis
KEY MESSAGES
Good sanitation and maintenance of food hygiene can
prevent diarrhea associated HUS.

Supportive care with early dialysis support remains the
cornerstone of management.
Non-infective atypical HUS should be treated rapidly
with plasma therapy.
Efforts should be made to make an etiological
diagnosis in cases of atypical HUS as treatment and
prognosis is affected.

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Definition

HUS, is a disease characterized by :

CLASSIFICATION OF HUS / TTP ACCORDING

Other viral or bacterial infections

Complement factor abnormality

0157:H7 infection will develop HUS

Atypical/Non-Diarrhea Related HUS

Miscellaneous Causes of HUS / TTP

Other infections associated with HUS

binding to proteins on the surface of glomerular

obstructed by the resulting complexes of activated

thrombi lodged in the small vessels typically leads to

be more severely affected in HUS, and the central

It occurs commonly in children between 1-5 years

Investigations to Identify Cause

pathogenic EHEC or Shigella is performed by:

Rarely HUS can occur with E. coli UTI:

suspected pneumococcal disease.

Acute renal failure

hemogram need frequent monitoring

associated with a higher risk of developing HUS

essential in most cases due to the mortality rate of >

diagnosis of TMA is suspected

The replacement of the deficient factor with FFP

Daily plasma infusions (10 to 20 mL/kg/day)

mL/kg/day) using FFP

. Plasma exchange usually is administered once daily

until the platelet count and LD have returned to

exchange, twice-daily treatments should be given.

Fresh frozen plasma (FFP) may be administered if

immediate access to plasma exchange is not available or in

In cases of relapse following initial treatment, plasma

exchange should be reinstituted

Cases of atypical HUS may respond to plasma infusion

initially, and serial infusions of the anticomplement C5

Normalizes the metabolic abnormalities can help to

prevent further episodes.

poor response to plasma exchange:

prevent diarrhea associated HUS.

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