hus, pediatric diarrhoea with thrombocytopenia

1. Haemolytic Uremic Syndrome
(HUS)
Dr. Virendra Kumar Gupta
Assistant Professor
Department Of Pediatric Gastroentero-hepatology & Liver Transplantation
NIMS Medical College & Hospital , Jaipur

2. DEFINITION
• HUS is a clinical syndrome that destroys red blood
cells, is the most common cause of sudden,
short-term acute kidney failure in children.
It is a triad of:
• Micro-angiopathic hemolytic anemia (MAHA)
• Thrombocytopenia.
• Acute kidney injury (acute renal failure)
• A clinical syndrome

3. • Most common cause of acute renal failure in
children and is increasingly recognized in
adults.
• First described by Gasser et al in 1955.

4. CLASSIFICATION OF HUS / TTP ACCORDING TO
ETIOPATHOGENESIS
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

5. Two main categories of HUS
• Shiga-like toxin associated HUS
(Stx-HUS)
• Non-shiga-like toxin associated HUS
(non-Stx-HUS)

6. • Stx-HUS: (tHUS)
D+ HUS
D- HUS
• Non-StxHUS: (aHUS)
Sporadic
Familial

7. Stx-associated HUS
In developed countries:
• Escherichia coli serotype O157:H7 (EHEC)
most common.
In developing countries:
• Shigella dysenteriae serotype 1.

9. Source of infection
• Human feco-oral transmission.
• Milk and animal products (incompletely
cooked)
• Veges, salads,drinking water contaminated by
bacteria shed in animal wastes.

10. Pathogenesis
Shiga-like toxin affects endothelial cells and initiates intravascular
thrombo-genesis. After entering the circulation via the
gastrointestinal mucosa, the toxin preferentially localizes to
the kidneys, inhibiting protein synthesis and eventually
leading to cell necrosis or apoptosis.
Endothelial cell damage subsequently potentiates renal
microvascular thrombosis by promoting activation of the
blood coagulation cascade.
Platelet aggregation results in a consumptive thrombocytopenia.
Microangiopathic hemolytic anemia results from mechanical
damage to red blood cells circulating through partially
occluded microcirculation.

12. Histopathological hallmark of HUS
• Thrombotic microangiopathy (TMA)
Characterized by:
• Capillary endothelial damage.
• Microvascular formation of platelet/fibrin plugs.
• This induces tissue ischemia
• Damage to erythrocytes
• Consumptive thrombocytopenia.

13. ADAMTS-13 deficiency
Familial:
• usually in children.
• rare.
Acquired:
• more common in adults and older children.
• Associated with presence of anti-ADAMTS13
antibodies.
• Manifestation classically of frank TTP.

14. 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

15. 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

16. INVESTIGATIONS
• CBC
• Peripheral blood smears
• Reticulocyte count
• LDH
• Bili unconjigated
• Cr & BUN
• Urine analysis
Hemoglobinuria
Hematuria
Proteinuria

17. Schistocytes

18. 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

19. Conti..
• Bacteriological cultures of body fluids are
indicated in suspected pneumococcal disease.
Sputum
CSF
Blood
Pus

20. 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

21. Cont…
– The only distinguishing feature is that in TTP fever
and neurological symptoms are often present, but
this is not always the case
– A pericardial friction rub can also sometimes be
heard on auscultation
– The two conditions are sometimes treated as a single
entity called TTP/HUS.

22. MANAGEMENT
• Supportive Therapy
• Antibiotics
• Plasma Therapy
• Miscellaneous

23. 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

24. 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

25. Antibiotics
• E. coli
• Shigellosis
• pneumococcal HUS

26. 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

27. 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.

28. CONTI..
• In patients with persistent ADAMTS13
antibodies and poor response to plasma
exchange:
 Immunosuppressive therapy with high dose
steroids/cyclophosphamide/
cyclosporin/rituximab
 Splenectomy

29. Prevention
• Once patient infected with EHEC, attempts to
prevent progression from bloody diarrheal phase to
postdiarrheal phase of HUS have been unsuccessful.
• Antibiotics and anti-motility drugs not
recommended.
• Vigorous fluid repletion during diarrheal phase of
illness is associated with less severe renal
involvement.

30. Prognosis
• Hematologic manifestation resolve usually
within one to two weeks.
• Mortality rate <5%.
• Causes of death include hyperkalemia, CHF,
pulmonary hemorrhage.

31. Markers of poor prognosis
• WCC>20 on presentation
• Persistent oliguria/anuria.
• Renal histology showing a glomerular
microangiopathy affecting >50% of glomeruli,
arterial microangiopathy +/- cortical necrosis.

32. Complications
GASTROINTESTINAL NEUROLOGIC RENAL
• Intestinal
strictures/perforations
• Intussusception
• Pancreatitis
• Severe colitis
• Altered mental status
• Focal neurologic signs
• Seizures
• Chronic renal failure
• Hematuria
• Hypertension
• Proteinuria

33. DIFFERNTIAL DIAGNOSIS
• Acute abdomen
• Acute gastroenteritis
• Appendicitis
• Colitis
• Disseminated intravascular coagulation
• Inflammatory bowel disease
• Lupus
• Thrombotic thrombocytopenia

34. summary
• HUS is a clinical syndrome characterized by MAHA, ARF and
Thrombocytopenia.
• Thrombotic Microangiopathy (TMA) is the hallmark of disease
pathogenesis.
• Stx or Non-Stx associated HUS.
• E.coli O157:H7 most common cause for Stx HUS.
• Strep pneumoniae for non-STx HUS.
• Familial form of HUS usually associated with complement dysregulation.
• Treatment of StxHUS mainly supportive with a good prognosis.

35. 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.