Haemolytic Uraemic Syndrome (HUS)
Summary
Haemolytic Uraemic Syndrome (HUS) is a Thrombotic Microangiopathy characterized by the Classical Triad of:
- Microangiopathic Haemolytic Anaemia (MAHA).
- Thrombocytopenia.
- Acute Kidney Injury (AKI).
It is the most common cause of acute renal failure in children. 90% of cases are "Typical" (Diarrhoea +ve), caused by Shiga-Toxin producing E. coli (STEC), most commonly serotype O157:H7. [1,2]
Clinical Pearls
Antibiotics are Forbidden: In STEC-HUS, antibiotics are CONTRAINDICATED. Killing the bacteria causes a massive release of Shiga toxin stored within them, precipitating or worsening the HUS ("Herxheimer-like" effect).
Platelets are Forbidden: Do rarely transfuse platelets unless there is life-threatening active bleeding. Giving platelets is "adding fuel to the fire" – they will immediately be consumed into the microthrombi, worsening the vessel occlusion.
Schistocytes: The hallmark on the blood film. These are "helmet cells" or fragmented red cells that have been sliced apart by the fibrin strands in the damaged capillaries.
Demographics
- Age: Peak incidence < 5 years.
- Seasonality: Summer/Autumn peaks (Barbecues, Farm visits).
Transmission
- Source: Undercooked beef (burgers), unpasteurised milk, petting zoos (animal faeces).
- Secondary: Person-to-person faecal-oral spread is common in nurseries.
STEC-HUS (Typical)
- Ingestion: E. coli O157 colonizes gut -> Bloody diarrhoea (Prodrome).
- Toxin: Shiga toxin crosses gut wall -> Bloodstream.
- Binding: Toxin binds Gb3 receptors on glomerular endothelium.
- Thrombosis: Endothelial injury -> Platelet plug formation -> Glomerular occlusion -> AKI.
- Haemolysis: RBCs torn apart passing through blocked vessels (MAHA).
Atypical HUS (aHUS)
- Mechanism: Uncontrolled activation of the Alternative Complement Pathway (Factor H/I deficiency). usually genetic. Poor prognosis.
- Trigger: Streptococcus infection, Drugs, Pregnancy. No diarrhoea prodrome.
| Feature | HUS | TTP (Thrombotic Thrombocytopenic Purpura) |
|---|---|---|
| Patient | Child | Adult (usually female) |
| Dominant Organ | Kidney (Renal failure) | Brain (Neuro signs) |
| Mechanism | Shiga Toxin | ADAMTS13 Deficiency |
| Fever | Rare (after prodrome) | Common (Pentad) |
| Treatment | Supportive | Plasma Exchange |
History
Signs
Bloods
- FBC:
- Hb: Low (less than 80 g/L common).
- Platelets: Low (less than 60 usually).
- WBC: Elevated (Leukocytosis is a predictor of severe disease).
- Blood Film: Schistocytes, Burr cells, Polychromasia (Reticulocytosis).
- U&E: Urea & Creatinine markedly elevated. Hyponatraemia. Hyperkalaemia.
- LDH: Very High (Haemolysis marker).
- Haptoglobin: Low (Consumed).
- Coombs Test: Negative (Non-immune haemolysis).
Microbiology
- Stool Culture: Specifically request O157 / Shiga Toxin PCR.
Urine
- Dipstick: Haematuria, Proteinuria.
Management Algorithm
DIARRHOEA + PALLOR + ANURIA
↓
ADMIT + ISOLATE
(Barrier nursing - Risk of spread)
↓
STOP NEPHROTOXICS
(Stop NSAIDs / ACEi / Antibiotics)
↓
FLUID MANAGEMENT
- If Dehydrated: Gentle rehydration
- If Anuric/Overloaded: Fluid Restrict
(Insensible losses: ~400ml/m2/day)
↓
MONITORING
- 4 hourly BP (Treat Hypertension)
- Daily Wt, U&E, FBC
↓
INDICATIONS FOR DIALYSIS
- Anuria > 24h
- Uncontrollable Hyperkalaemia
- Severe Fluid Overload (Pulm Oedema)
- BUN > 35 mmol/L (Uraemic encephalopathy)
↓
TRANSFUSION?
- RBC: Only if symptomatic (Hb < 60)
- Platelets: NEVER (unless bleeding)
1. Supportive Care
- There is no specific cure for STEC-HUS. The kidneys usually recover if the child is kept alive and balanced during the acute phase.
- Nutrition: High calorie, low protein/salt.
2. Renal Replacement Therapy
- Peritoneal Dialysis or Haemodialysis required in ~50% of cases.
- Usually temporary (few weeks).
3. Atypical HUS Therapy
- Eculizumab: Monoclonal antibody against terminal complement (C5). Transforms prognosis of aHUS from 50% ESRD to recovery.
- Acute:
- Seizures / Encephalopathy (Hypertension or Toxin).
- Colitis / Bowel Perforation.
- Pancreatitis (Toxin affects islet cells -> T1DM).
- Chronic:
- CKD: 5-10% end up with permanent End Stage Renal Disease.
- Proteinuria: Long term follow up required.
- Mortality: 3-5% in acute phase.
- Renal Recovery: >85% recover renal function fully in typical HUS.
- Timeframe: Thrombocytopenia resolves in 1-2 weeks. Renal recovery takes longer.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Renal Failure | NICE / KDIGO | Criteria for dialysis initiation. |
| STEC-HUS | RCPCH | Antibiotic avoidance. Volume expansion in pre-HUS phase may prevent oliguria. |
Landmark Studies
1. Volume Expansion
- Evidence suggests that aggressive IV fluid hydration during the diarrhoeal prodrome (before anuria) protects the kidneys and reduces the severity of HUS ("Washout" effect).
2. Wong et al (NEJM 2000)
- The definitive study confirming that antibiotic treatment of children with E. coli O157:H7 infection increases the risk of HUS.
What is HUS?
It is a serious complication of a tummy bug. The bacteria that caused the diarrhoea release a toxin into the blood. This toxin damages the tiny filters in the kidneys and breaks up red blood cells.
Why is my child pale?
The toxin is destroying their red blood cells faster than they can make new ones (Haemolysis).
Why are they not peeing?
The debris from the broken cells and clotting has clogged up the kidney filters. The kidneys have shut down temporarily. We may need a dialysis machine to clean the blood until the kidneys heal.
Can we give antibiotics?
No. Antibiotics can make the bacteria burst and release even more toxin, making the condition worse. We have to support the body to clear it naturally.
Primary Sources
- Loirat C, Saland J. Bignall G. Hemolytic uremic syndrome: an update. Pediatr Nephrol. 2021.
- Tarr PI, et al. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005.
- Wong CS, et al. Risk of hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infection. N Engl J Med. 2000.
Common Exam Questions
- Diagnosis: "Triad of HUS?"
- Answer: MAHA + Thrombocytopenia + AKI.
- Microbiology: "Causative organism?"
- Answer: E. coli O157:H7.
- Management: "Contraindicated drugs?"
- Answer: Antibiotics and Anti-motility agents.
- Haematology: "Coombs test result?"
- Answer: Negative (Non-immune).
- Pathology: "Smear finding?"
- Answer: Schistocytes.
Viva Points
- TTP vs HUS: TTP is caused by ADAMTS13 deficiency (can't cleave vWF). HUS is caused by Toxin. TTP is commoner in adults, HUS in kids.
- Eculizumab: Why use it? For Atypical HUS only. It blocks the complement cascade which is overactive in aHUS.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.