Haemolytic Uraemic Syndrome

What is HUS?

Haemolytic Uraemic Syndrome is a combination of findings which involves the triad of:

• Microangiopathic haemolytic anaemia with red blood cell fragmentation on blood film
• Acute renal failure
• Thrombocytopenia

 What causes HUS?

About 90% of cases follow an infection, most commonly with entero-haemorrhagic E. Coli (EHEC). Other infective causes to be considered include Shigella and Streptococcus pneumoniae.

These infections are commonly contracted by the ingestion of contaminated food or water sources. In the US and UK, E. Coli 0.157 forms part of the natural intestinal microflora of cattle and sheep, therefore infection can be caused by direct contact with animal faeces. This can take place at farms or petting zoos, or via undercooked contaminated meat or dairy products.

The other 10-15% of cases represent atypical HUS and are due to a variety of causes, which will not be discussed here.

How do children present?

In children infected with EHEC about 10-15% of them will go on to develop HUS.

The common presentation includes bloody diarrhoea +/- cramping abdominal pain, fever and/or vomiting. The average onset of HUS after development of diarrhoea is about 7-10 days, with children under the age of 5 at highest risk.

Dependent on the extent of HUS progression, children may present with pallor, oedema, lethargy, or reduced urine output.

How to approach the examination

As with any unwell child, an A to E assessment is critical to rule out any immediate, life threatening complications.

Specific attention should be paid to assessing their fluid status, especially for evidence of dehydration.

*Although they may be oedematous, it is important to assess if they are intra-vascularly dry.

Things to examine for:

• Prolonged capillary refill time
• Observations: Tachycardia; hypotension or hypertension
• Are they are cool peripherally?
• Assess fontanelle tension (if applicable)
• Dry mucus membranes/reduced skin turgor
• Oedema (common locations in children include lower limbs, sacral and peri-orbital)

Is there evidence of neurological sequelae?

• Irritable/restlessness
• Confusion
• Reduced GCS

Key investigations to perform

A. Initial blood samples:

• Full blood count with blood film to assess for RBC fragmentation
• Coagulation
• Group and Save +/- cross match if haemoglobin low
• Biochemistry: U&Es, calcium, phosphate, magnesium, bicarbonate
• Glucose
• CRP
• Liver function including albumin
• Amylase/Lipase (hospital dependent)
• LDH
• Blood gas
• Blood cultures

B. Stool MC&S + E. Coli PCR

C. Urinalysis + MC&S

How to approach the management of HUS

Management should always be discussed with your local paediatric nephrologist in order to individualise/optimise management.

This is a generalised framework for the approach to management. Treatment involves supportive therapy to allow time for the infection to clear and the HUS process to cease.

1. Fluid Management:

• IV access
• Assess fluid status
• Monitor for electrolyte disturbances and correct as per local guidelines
• Daily weight, In/Out fluid balance, close monitoring of patient observations

*Fluid rehydration should be administered cautiously and in the setting of oliguria/anuria and oedema, fluids given should not exceed insensible loss + urine output.

*Evidence has shown that children presenting to hospital with dehydration in the prodromal phase of EHEC-induced HUS have a higher risk of developing an oliguric AKI and the requirement for dialysis. The administration of isotonic fluid in this phase has shown to be nephroprotective. 

2. Hypertension:

• Can be secondary to fluid overload or as a result of the HUS process
• Trial of diuretics or if receiving dialysis, fluid can be offloaded
• If unresponsive to diuretics, consider a vasodilator (For example, amlodipine/ nifedipine *hospital dependent)

3. Anaemia:

• Target Haemoglobin: 70-100g/L
• Avoid excessive transfusion due to the associated risk of development of hyperkalaemia or fluid overload

4. Thrombocytopenia:

• Consideration for platelet transfusion if platelets <10 x10⁹
• If undergoing surgery may require platelets > 50 x 10⁹

5. Abdominal pain/vomiting:

• Secondary to colitis
• Regular paracetamol for pain relief
• Avoid opiates if possible due to constipating side effects

*NSAIDS like Ibuprofen should not be prescribed*

6. Nutrition:

• All patients should be reviewed by a dietician
• NG tube and feeding regime

7. Dialysis (Peritoneal Dialysis or Haemodialysis) Indications:

• Intractable acidosis
• Diuretic resistant fluid overload
• Electrolyte abnormalities  Hyperkalaemia
• Symptoms of uraemia

In children with HUS, peritoneal dialysis is the preferred treatment option as it is a gentler form of dialysis.

Haemodialysis is indicated for children with severe colitis, severe electrolyte abnormalities and those with neurological complications.

 HUS Complications

• AKI:  Oliguria/anuria; hyperkalaemia; hypertension
• Neurological: Irritable, confusion, seizures
• Bleeding Risk
• Cardiac: Hypertensive cardiomyopathy/myocarditis
• Gastrointestinal: Severe colitis with bleeding/perforation
• Pancreatitis
• Pulmonary oedema

Selected references

Mayer CL, Leibowitz CS, Kurosawa S and Stearns-Kurosawa DJ. Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals. Toxins (Basel). Nov 2012. [Cited June 2020]; 4 (11): 1261-1287. doi: 10.3390/toxins4111261

Kausman. J 517 Haemolytic uraemia syndrome. Royal Hospital for Children- Nephrology. Dec 2013. [Cited June 2020]; Available from:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509707/

Hughes D. Management and investigation of bloody diarrhoea and haemolytic uraemic syndrome [draft].  GG&C Paediatric Guidelines- Kidney Diseases. Oct 30 2019. [Cited June 2020]; Available from: https://www.clinicalguidelines.scot.nhs.uk/ggc-paediatric-guidelines/ggc-guidelines/kidney-diseases/management-and-investigation-of-bloody-diarrhoea-and-haemolytic-uraemic-syndrome-draft/

Balestracci A et al. Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children. Pediatr Nephrol. 2012. [ Cited June 2020];27: 1407-1410. Doi: 10.1007/s00467-012-2158-0

Scheiring J. Andreoli SP. Zimmerhackl LB. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Ped Neprhrol. 2008. [Cited June 2020]; 23: 1749-1760. Doi: 10.1007/s00467-008-0935-6

Grisaru Silviu. Management of hemolytic-uremic syndrome in children. Int J Nephrol Renovasc Dis. 2014 [Cited June 2020]; 7: 231-239. Doi: 10.2147/IJNRD.S41837.