Causes of Hemolytic uraemic syndrome in children pathology, investigations and management

1. HEMOLYTIC UREMIC SYNDROME

3. • Hemolytic uremic syndrome is a common cause of community
acquired Acute kidney injury in young children. Characterized
by Triad of
• 》Microangiopathic hemolytic anemia
• 》Thrombocytopenia
• 》Acute kidney injury

4. TYPES OF HUS:
• Typical HUS:
Infection associated HUS which includes Diarrhea ssociated HUS,
HUS associated with strep pneumonae , HIV, influenza, herpes
virus 6, parvovirus B19, malaria
• Atypical HUS:
Associated with systemic disease and genetic(ADAMTS13
,complement dysregulation), acquired causes include Drugs,
pregnancy, transplant associated

6. TYPICAL HUS
• The most common form is caused by Shiga toxin producing E.coli(STEC). In
Asia and south africa- Shigella dysentrae type 1 is causative and in western
countries Shiga Like toxin producing E.coli(O157:H7) and (O104:H4) is
cause. STEC HUS accounts 90%of all childhood cases. Reservoir of STEC is
intestinal tract of domestic animals transmitted via undercooked meat and
unpasteurized Raw milk and apple cider. Cross contamination with
unwashed utensils and cutting boards, contaminated municipal supplies, pet
farms, swimming, contaminated vegetables and person to person contact .
• HUS associated with neuraminidase producing Strep pnemonae is associated
with pneumonia and empyema.

7. ATYPICAL HUS:
• Genetic: inherited deficiency of Von willebrand factor
cleaving protease(ADAMTS13), Complement factor H, I, B.,
cobalamin C mutations.
• The major characteristic feature of genetic form of HUS is
lack of preceding diarrheal prodrome.
• These can have indolent or unremitting course or can have
relapsing pattern precipitated by any infectious illness.
• HUS may be associated with any disease with microvascular
injury including malignant HTN, SLE, antiphospholipd
syndrome
• Drugs- cyclosporin, tacrolimus, quinine, anti-VEGF,

8. PATHOPHYSIOLOGY:
• Microvascular injury with endothelial cell damage is
cahracteristic of Hemoltyic uremic Syndrome.
• In diarrhea associated HUS enteropathogen produce shiga toxin
or shiga like verotoxin which easily absorbs from colon into
systemic circulation, binds to endothelial cells in glomeruli or
cause direct endothelial damage elsewhere enhancing platelet
aggregation and thrombus formation with resultant narrowing
of vascular lumen with increased mechanical injury to RBcs
passing through, and severe anemia which is coombs negative.

9. • In pneumococcal associated HUS, neuraminidase cleaves sialic acid in
membranes of endothelial cells, red blood cells and platelets and
expose underlying Thomson friedreich antigen (T) antigen to which
endogenous IgM Antibodies reacts to trigger hemolysis and anemia with
positive Coombs test.
• Familial recessive and dominant forms of HUS including ADAMTS13 and
regulators of complement cascade predisposes patients to developing
HUS when have some inciting events such as infectious disease which
triggers HUS. The absence of ADAMTS 13 impairs cleavage of von
willebrand factor multimers which enhances platelet aggregation.
• Factor H plays Vital role in regulation of complement cascade deficiency
of which also leads to platelet aggregation and thrombus formation.
• Mild endothelial injury which would have otherwise resolved will convert
into a aggressive microangiopathy because of inherited defects of these
factors.

10. • Capillary and arteriolar endothelial injury in kidney leads to
localized thrombosis in glomeruli and Decreasing GFR.
Progressive platelet aggregation in area of microvascular injury
results in consumptive thrombocytopenia and hemolytic
anemia results from mechanical injury to RBCs through
thrombotic microvasculature.

11. • In E.coli associated- onset of HUS after 5-7dqys of Diarrhoea often
bloody followed by excessive lethargy and pallor which heralds onset
of HUS i-e MAHA. Oliguria is Present which is masked by ongoing
enteritis and Dehydration. May develope volume overload later on.
• In pneumococcal HUS Patient is quite sick with pneumonia, empyema
and bacteremia when they develop HUS.
• Genetic form of HUS onset is insidious triggered by any mild
nonspecific GI or Respiratory illness.
CLINICAL FEATURES

12. LABORATORY FINDINGS
•Complete blood count shows leukocytosis,
normocytic normochromic anemia with schistocytes
or helmet cells in peripheral film and
thrombocytopenia(20,000to 100,000). Anemia
initially is mild and progresses rapidly.
•PT/aPTT normal.
•Coombs test negative except peumococcus induced
HUS where Coombs is positive.

13. • Deranged Renal function tests to anuric Kidney failure.
• HUS causing organism Rapidly clears from Stool So Stool C/S are
usually Normal in diarrhea associated HUS.
• If no history of diarrheal prodrome or pneumococcal infection
obtained evaluation for genetic forms should be considered
because these patients have risk of recurrence and severe
prognosis and can benefit from therapy.

14. MANAGEMENT:
• Early Recognition of disease, monitoring for complications, and supportive care
• Supportive treatment i-e Correction of fluids and electrolytes, control of Hypertension,
and early institution of dialysis if patient becomes oliguric/ anuric with hyperkalemia.
• Red cell concentrates transfusion.
• In peumococcal RCC should be washed before transfusion to remove residual plasma
because endogenous IgM against revealed T antigen can accelerate disease process
further.
• Platelets should not be transfused regardless of count because may be rapidly
consumed and further exacerbate the condition.
• Anticoagulation, antiplatelets and fibrinolytics can cause serious haemorrhage.
• Antibiotics can cause increased toxin release exacerbating the condition except
meropenem, azithromycin, rifaximin which down regulates shiga toxin (strain
O104:H4)release and expression.

15. • Plasmapheresis and plasma infusions for patients with severe
CNS involvement but it is contraindicated in Pneumococcal
associated HUS.
• Ecluzimab an Anti-C5 antibody is FDA approved for atypical
HUS it inhibits complement activation a pathway that
contributes to atypical familial HUS also contributes To STEC
HUS. Has risk of meningococcal disease so prior to treatment
give Meningococcal vaccine.

16. PROGNOSIS:
• Mortality for diarrhea associated HUS is <5%. Upto half of patients may
require dialysis support during acute phase.
• Recovery of platelets count comes first followed by Renal recovery about
5dqys later and finally anemia resolution.
• Mostly Renal function recovers completely but 5% remain dependent on
Dialysis, upto 30% left with Chronic renal insufficiency.
• Prognosis of HUS not associated with diarrhoea is severe. With
pneumococcus associated have morbidity of >80% requiring dialysis and
20% mortality.
• The familial, genetic forms of HUS can have relapsing, insidious course and
poor prognosis.

17. •Thankyou for Listening and
patience!🫡