Haemolytic Uraemic Syndrome

Disclaimer

These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.

Read the full CAHS clinical disclaimer.

Aim

To guide Emergency Department (ED) staff with the assessment and management of Haemolytic Uraemic Syndrome (HUS).

Risk

Misdiagnosis of HUS will lead to undertreatment and significant morbidity and mortality secondary to renal failure.

Background^1,2

HUS is among the commonest causes of acute renal failure in children. It is estimated to affect 1-2/100,00 children per year with peak incidence <5years of age.

HUS is a disease characterised by:

Microangiopathic haemolytic anaemia (destruction of red blood cells).
Acute renal failure.
Thrombocytopaenia.
HUS is among the commonest causes of acute renal failure in children.
Mortality of 5-10%.

Causes¹:

Secondary infectious causes:

Post diarrhoeal illness (usually bloody):
- Shiga toxin producing Escherichia coli (STEC)
  - Accounts for 90% of cases.
- Shigella, Campylobacter and other viruses.
Non-diarrhoeal
- Streptococcus pneumoniae
  - Approximately 10% of all paediatric HUS.
  - Usually present with pneumonia with effusion.
  - May be Coombes positive.

Secondary non-infectious causes:

Medications (e.g. chemotherapy, tacrolimus, ciclosporin, oral contraceptives, valaciclovir, quinine).
Immune mediated.
Malignancy.
Connective tissue disease (e.g., systemic lupus erythematosus (SLE), scleroderma, antiphospholipid antibody syndrome).
Other glomerulonephritides (e.g., acute post-infectious glomerulonephritis (APIGN), membranoproliferative glomerulonephritis (GN)).

Primary causes:

Complement defects.
Familial cases.
Hereditary (e.g. inborn error of cobalamin deficiency).

Assessment^2,3

History

Most children with HUS (STEC) present 5-10 days after the onset of a bloody diarrhoea with:
- Fatigue and Pallor
- Anaemia
- Oliguria
- Haematuria
- Oedema
- Hypertension
- Renal failure
History taking should explore recent illnesses, foreign travel and animal contact.
20% of cases have extra-renal manifestations secondary to microthrombi formation including:
- Respiratory: -> pneumonia and effusions, especially associated with Pneumococcal HUS
- Cardiac: -> Myocardial Infarction, Myocarditis and Pericardial Effusions
- Cerebral: -> Stroke, Seizures, Visual Disturbance and Encephalopathy
- Gastrointestinal: -> GI Haemorrhage, Cholestasis, Liver Necrosis
- Pancreatic: -> Pancreatitis and Diabetes secondary to Pancreatic Dysfunction

Examination

Full set of vital signs including accurate blood pressure.
Full system examination.
Assessment of cardiovascular and intravascular volume status is very important.

Consider:

Thirst, restlessness and confusion
Capillary refill
Skin turgor
Warmth of peripheries
Urine output
Oliguria
Fontanelle tension
Blood pressure
Heart rate
Evidence of oedema.

Investigations

Full blood picture
Blood film
Electrolytes, Urea and Creatinine (EUC)
Liver function tests (LFT)
C-Reactive Protein (CRP)
Blood glucose level (BGL)
Coagulation profile
Group and hold
Blood cultures if pneumococcal cause suspected +/- pneumococcal PCR
Stool microscopy, culture and sensitivity (MC&S)
Stool – Shigella-toxin producing E-Coli PCR
Urinalysis and urine MC&S.
Other investigations as clinically indicated (e.g. Chest X-ray, renal ultrasound, electrocardiogram (ECG), head computerised tomography (CT) or magnetic resonance imaging (MRI), electroencephalogram (EEG)).

Investigation	Rationale
Blood tests
Full Blood Count	Demonstrating anaemia
Blood Film	Demonstrating fragmented red cells and schistocytes
Group and Hold x2, plus Coombs	Differentiating from autoimmune and preparing for treatment
Electrolyte, Urea and Creatinine (EUC)	Demonstrating acute kidney injury
Liver Function Test (LFT)	Demonstrating raised bilirubin
CRP	Differentiating from sepsis/DIC
Coagulation Profile	Differentiating from sepsis/DIC
Blood Glucose Level
Microbiology
Blood Culture (If Pneumococcal suspected)
Stool Microscopy, Culture and Sensitivity (MC+S)
Stool Shigella Toxin Producing E-Coli PCR
Urine Dip and Culture (MC+S)
Other investigations as clinically indicated
e.g. Chest X-ray, renal ultrasound, electrocardiogram (ECG), head computerised tomography (CT) or magnetic resonance imaging (MRI), electroencephalogram (EEG).

Differential diagnoses

Sepsis
Acute post-Streptococcal glomerulonephritis
Disseminated intravascular coagulation
Immune thrombocytopaenia (ITP)
Thrombotic thrombocytopaenia purpura
Systemic lupus erythematosis (SLE)
Vasculitis.

Management^1,4

Fluid management

Establish IV access
Hypovolaemia should be treated with sodium chloride 0.9% saline boluses, or packed red blood cells, depending on the clinical status (usually sodium chloride 0.9% saline in the ED setting)
In the presence of oliguria/anuria and fluid overload, fluid should be administered cautiously and should not exceed insensible fluid losses plus urine output (or less)
- Insensible fluids:
  - 0-10kg weight - give 25 mL/kg/day
  - 10-20kg weight - give 12.5 mL/kg/day
  - Then 5 mL/kg/day for each additional kg over 20 kg weight
Hyponatraemia is treated with fluid restriction
Electrolyte abnormalities: please discuss with paediatric renal team
- May require dialysis

Blood products

Packed red blood cell transfusion may be indicated especially if Hb <70 or acutely falling. Discuss with Renal team due to risk of hyperkalaemia.
Avoid platelet transfusions unless active bleeding concerns.
Altered consciousness / focal neurological signs.
If these develop, immediate discussion should be undertaken with a senior colleague (e.g. ED consultant, renal consultant or Paediatric Critical Care (PCC) Unit consultant).

Hypertension

Usually secondary to volume overload.
Treat with diuretics (furosemide) after discussion with renal team.
If unresponsive to diuretics, consider vasodilator treatment after discussion with renal +/- critical care teams.

Medications

Review and discontinue nephrotoxic drugs.
Abdominal pain and vomiting may be due to colitis in post-diarrhoeal HUS.
- Do not prescribe non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen.
- Treat initially with paracetamol (Refer to Paracetamol Monograph – Medication Management Manual (internal WA health only).
- May require opiate analgesia (but this will decrease bowel motility and should be avoided if possible).
- Do not prescribe Loperamide.

Antibiotics

Indicated in pneumonia related HUS. Refer to Acute Respiratory Tract Infection – Empiric Guidelines - ChAMP.
Not required in E Coli related HUS as may increase risk of Shiga Toxin Release.

Further management

All patients diagnosed with HUS must be admitted.
HUS is a notifiable disease and should be reported using the communicable disease notification form. Refer to Notification of infectious diseases and related conditions.
The paediatric renal team (and general surgical team for Haemodialysis line placement / PD catheter placement) should be consulted early as 50% of patients require dialysis for roughly 10 days. Renal replacement therapy will usually be peritoneal dialysis (PD). Exceptions are those with severe colitis, cerebral HUS or profound metabolic abnormalities (where haemodialysis or haemofiltration techniques may be considered).

Indications for dialysis

Fluid overload resistant to diuretic therapy
Hyperkalaemia
Intractable acidosis
Symptoms of uraemia
Likely progression to one of the above

Patients needing dialysis (most) will usually be placed on peritoneal dialysis (PD). Exceptions are those with severe colitis, cerebral HUS or profound metabolic abnormalities (where haemodialysis or haemofiltration techniques may be considered).

All patients diagnosed with HUS must be admitted.

The paediatric renal team (and general surgical team for PD catheter / line placement) should be consulted early.

Nursing

Implement appropriate standard and transmission based precautions for the cause. HUS may be a communicable disease spread through faeco-oral transmission for up 1 month after resolution of colitis.
Complete and record a full set of observations including Blood Pressure on the Observation and Response Tool and record additional information on the Clinical Comments chart.
Complete a full set of neurological observations on the age appropriate chart if clinically indicated.
Maintain an accurate record of fluid balance.
Obtain an accurate patient height and weight.

Bibliography

Niaudet P & Boyer OG, UpToDate: Overview of hemolytic uremic syndrome in children. 2021 Overview of hemolytic uremic syndrome in children - UpToDate (health.wa.gov.au)
Textbook of Paediatric Emergency Medicine 3rd Edition Cameron P, Browne GJ, Mitra B, et al (2018) Publisher: Elsevier Edition updated
Nelson Textbook of Pediatrics: 21st Edition Robert M. Kliegman, St Geme JW, Blum MJ et al. 2020 Publisher: Elsevier
Fleisher and Ludwig’sTextbook of Pediatric Emergency Medicine, 8th Edition. Shaw K and Bachur RG (2020) Publisher: Wolters Kluwer

Endorsed by:	Nurse, Co-director, Surgical Services	Date:	May 2025
		Review date:	May 2028

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