Overview

Haemolytic uraemic syndrome (HUS) is characterised by a triad of:

It is described as microangiopathic due to thrombosis in small blood vessels and subsequent shearing of red blood cells (RBCs) and haemolysis. In simple terms, clots form in small blood vessels and shred RBCs.

Thrombi form in small blood vessels:

  • This consumes platelets leading to thrombocytopenia
  • Thrombi shear and shred RBCs causing haemolytic anaemia – microangiopathic haemolytic anaemia
  • Thrombi reduce blood flow to the kidneys leading to AKI

It may be helpful to look at the chapter on Anaemia: Data Interpretation alongside reading this section to help wrap your head around when to suspect what type of anaemia.

Epidemiology

  • More commonly seen in children (around <5 years old), but can happen at any age 
  • Most cases are due to E.coli O157:H7

Causes

  • Escherichia coli O157:H7 is the most common cause of HUS
    • It produces a toxin called the Shiga toxin or verotoxin
    • The circulating toxin binds to endothelial receptors in blood vessels leading to thrombosis
  • Streptococcus pneumonia
  • Shigella dysenteriae
  • Systemic lupus erythematosus

Risk Factors

  • Contaminated food or water
  • Exposure to infected individuals
  • Young age and older age

Example History

A 15-year-old girl has lethargy and reduced urine output. She has had diarrhoea with blood for the last week. She appears dehydrated.

Investigations:

Haemoglobin:105 g/L(115 – 165 g/L)
Platelets:70.0 x 109/L(150 – 450 x 109/L)
Mean cell volume (MCV):85.0 fL(76.0 – 98.0 fL)
White blood cells (WBC):15.4 x 109/L(3.0 – 10.0 x 109/L)
Urea:10.3 mmol/L(2.0 – 7.0 mmol/L)
Creatinine:186 µmol/L(55 – 120 µmol/L)

Presentation

HUS is characterised by a triad of:

  • Microangiopathic haemolytic anaemia which may present with:
  • Thrombocytopenia which may present with:
  • Acute kidney injury (AKI)

Other features are:

  • Diarrhoea that turns bloody after 1-3 days
  • Fever
  • Abdominal pain
  • Vomiting

Differential Diagnoses

Thrombotic thrombocytopenic purpura (TTP)

  • In TTP, the central nervous system is affected more than the kidneys
  • There is usually no bloody diarrhoea
  • ADAMTS-13 activity is lower

Disseminated intravascular coagulation (DIC)

  • Patients usually have a predisposing serious condition (e.g. sepsis)
  • Unlike HUS, coagulation assays are usually abnormal in DIC because clotting factors are consumed and exhausted in DIC, but not in HUS:
    • Decreased fibrinogen
    • Increased PT and APTT
    • Increased fibrinogen degradation products

Investigations

Overview

Investigations include:

  • Full blood count (FBC):
    • Haemoglobin – reduced
    • Platelets – reduced
    • Reticulocyte count – increased
  • Blood film:
    • Schistocytes
  • Urea and electrolytes (U&Es):
  • Coagulation assay:
    • Prothrombin time (PT) and activated partial thromboplastin time (APTT) are normal
  • Markers of haemolysis:
    • Bilirubin – elevated
    • Lactate dehydrogenase (LDH) – increased
    • Haptoglobins – low
  • Direct Coomb’s test:
  • Stool culture:
    • May detect Shiga toxin-producing E. coli
  • Polymerase chain reaction (PCR):
    • May detect Shiga toxin

Management

All patients

Treatment is mainly supportive:

  • 1st-line: supportive management with fluids and electrolytes
  • Blood transfusions may be needed
  • Dialysis may be considered

Antibiotics are not typically used as they may cause the death of Shiga toxin-producing cells and release more of the toxin into the bloodstream, worsening HUS.

Complications

Prognosis

  • Mortality rates are highest in infants, young children, and the elderly

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