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Definition HUS, is a disease characterized by :
Acute kidney failure
Hemolytic anemia Thrombocytopenia (low platelet count)
It predominantly, but not exclusively, affects children.
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Types HUS Typical HUS
Atypical HUS
HUS due to Complement abnormalities
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CLASSIFICATION OF HUS / TTP ACCORDING
TO ETIOPATHOGENESISType of HUS / TTP Specific Cause
Infection related Shiga toxin producing E.coli/ShigellaPneumococcal infection
HIV Typical
Other viral or bacterial infections
Complement factor abnormality Factor H deficiency
CTD Factor I deficiency Miscellaneous Drugs Atypical
Malignancy
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ETIOPATHOGENESIS Typical/Diarrhea associated/Shiga Toxin
associated HUS
Enterohaemorrhagic E. coli
Shigella dysenteriae type 1
Rarely, HUS can occur with E. coli UTI
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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 transmissionVegetables, salads and drinking water may be
contaminated by bacteria shed in animal wastes
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Atypical/Non-Diarrhea Related HUSPneumococcal 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
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Other infections associated with HUS Includeviruseslike :
Influenza
Cytomegalovirus Infectious mononucleosis
Bacteria like:
Streptococcii
Salmonella
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Pathophysiology The typical pathophysiology involves the shiga-toxin
binding to proteins on the surface of glomerularendothelium and inactivating a metalloproteinasecalledADAMTS13, which is also involved in the closelyrelated TTP
http://en.wikipedia.org/wiki/ADAMTS13http://en.wikipedia.org/wiki/ADAMTS138/10/2019 Hemolytic Uremicsyndrome
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CONTI.. The arteriolesand capillariesof the body become
obstructed by the resulting complexes of activatedplateletswhich have adhered to endothelium via largemultimeric vWF.
The growing thrombi lodged in smaller vessels destroyRBCs as they squeeze through the narrowed bloodvessels, forming schistocytes, or fragments of shearedRBCs.
http://en.wikipedia.org/wiki/Plateletshttp://en.wikipedia.org/wiki/Platelets8/10/2019 Hemolytic Uremicsyndrome
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CONTI The consumption of platelets as they adhere to the
thrombi lodged in the small vessels typically leads tomildor moderatethrombocytopaenia
However, in comparison to TTP, the kidneys tend tobe more severely affected in HUS, and thecentral
nervous system is less commonly affected
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CLINICAL FEATURES The commonest clinical presentation of HUS is :
Acute pallor
Oliguria Diarrhea or dysentery
It occurs commonly in children between 1-5yearsof age
HUS develops about 5-10 days after onset of diarrhea
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CONTI.. Hematuria and hypertension are common.
Complications of fluid overload may present with: Pulmonary edema
Hypertensive encephalopathy
Despite thrombocytopenia, bleeding manifestationsare rare
Neurological symptoms like: Irritability
Encephalopathy
Seizures
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INVESTIGATIONS CBC
Peripheral blood smears
Reticulocyte count
LDH
Bilirubin unconjugated
Cr & BUN
Urine analysis
Hemoglobinuria
Hematuria
Proteinuria
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Schistocytes
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Investigations to Identify Cause In patients with dirrhea, the identification of
pathogenic EHECor Shigellais performed by:
Stool culture
Further serotyping by agglutination or enzymeimmunoassay
Rarely HUS can occur with E. coli UTI:
Urine cultures are indicated in non-diarrheal patients
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Conti.. Bacteriological cultures of body fluids are indicated in
suspected pneumococcal disease.
Sputum
CSF
Blood
Pus
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Diagnosis Clinically, HUS can be very hard to distinguish from
TTP
The laboratory features are almost identical, and notevery case of HUS is preceded by diarrhea
HUS is characterized by the triad of:
Hemolytic anemia
ThrombocytopeniaAcute renal failure
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MANAGEMENT Supportive Therapy
Antibiotics
Plasma Therapy
Miscellaneous
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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
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Antibiotics E. coli
Shigellosis
pneumococcal HUS
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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-associatedHUS, who generally recover with supportive care only,
plasma exchange must be initiated as soon as thediagnosis of TMA is suspected
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Plasma Therapy In aHUS due to :
complement factor abnormality
ADAMTS13 deficiency
The replacement of the deficient factor with FFP
Daily plasma infusions (10to20 mL/kg/day)
Exchange of 1.5 times plasma volume (60 to 75mL/kg/day) using FFP
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. Plasma exchange usually is administered once dailyuntil the platelet count and LD have returned tonormal for at least 2 days, after which the frequency of
treatments may be tapered slowly while the plateletcount and LD are monitored for relapse.
In cases of insufficient response to once-daily plasmaexchange, twice-daily treatments should be given.
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Fresh frozen plasma (FFP) may be administered ifimmediate access to plasma exchange is not available or incases of familial TMA.
Platelet transfusions are contraindicated in the treatmentof TMAs due to reports of worsening thromboticmicroangiopathy, possibly due to propagation of platelet-rich microthrombi. In cases of documented life-
threatening bleeding, however, platelet transfusions maybe given slowly and after plasma exchange is underway.
Red blood cell transfusions may be administered in cases ofclinically significant anemia.
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In cases of relapse following initial treatment, plasmaexchange should be reinstituted
. If ineffective, or in cases of primary refractoriness,second-line treatments may be considered includingrituximab, corticosteroids, IVIG, vincristine,cyclophosphamide, and splenectomy.
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Cases of atypical HUS may respond to plasma infusioninitially, and serial infusions of the anticomplement C5antibody eculizumabhave produced sustained
remissions in some patients. If irreversible renal impairment has occurred,
hemodialysis or renal transplantation may benecessary
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Miscellaneous In infants with HUS associated with cobalaminabnormalities:
Treatment with hydroxycobalamin
Oral Folic acid
Normalizes the metabolic abnormalities can help toprevent further episodes.
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CONTI.. In patients with persistent ADAMTS13 antibodies andpoor response to plasma exchange:
Immunosuppressive therapy with high dose
steroids/cyclophosphamide/ cyclosporin/rituximab Splenectomy
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Prognosis With aggressive treatment, more than 90% survive theacute 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 lifelongcomplications, such as : High blood pressure Seizures Blindness Paralysis
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KEY MESSAGES Good sanitationand maintenance of food hygiene canprevent diarrhea associated HUS.
Supportive carewith early dialysis support remains thecornerstone of management.
Non-infective atypical HUS should be treated rapidlywith plasma therapy.
Efforts should be made to make an etiologicaldiagnosis in cases of atypical HUS as treatment andprognosis is affected.
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