Hemolytic Uremicsyndrome

8/10/2019 Hemolytic Uremicsyndrome

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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/ADAMTS13


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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/Platelets


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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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Hemolytic Uremicsyndrome