Haemolytic Uraemic Syndrome

Question 1

Definition

Answer 1

• HUS is characterised by a triad of:

o Microangiopathic haemolytic anaemia (MAHA)
o Thrombocytopenia
o Acute renal failure

Question 2

Types

Answer 2

• There are TWO forms of HUS:

o D+ = diarrhoea-associated – prodrome of diarrhoea
o D- = no prodromal illness identified

Question 3

Association with TTP (thrombotic thrombocytopenic purpura)

Answer 3

• HUS overlaps with TTP (thrombotic thrombocytopenia purpura), which has 2 additional features to make a pentad:
o Fever
o Fluctuating CNS/neurological signs

• Many consider TTP and HUS as a spectrum of disease
• All with TTP have HUS, along with the additional features
• Even though HUS and TTP are similar, they have DIFFERENT aetiologies that lead to MAHA

Question 4

Aetiology

Answer 4

• In HUS, a toxin (Shiga toxin) causes endothelial damage which leads to platelet
activation
• Endothelial injury results in platelet aggregation and the release of unusually large
vWF multimers and activation of platelets and the clotting cascade
• There is also fibrin deposition in small vessels, leading to microthrombi
• Damaged RBCs and microthrombi clog up vessels
o The glomerular-afferent arteriole and capillaries are particularly vulnerable - they undergo fibrinoid necrosis
o This leads to renal ischaemia and acute renal failure
• The thrombi also promote intravascular haemolysis

• Atypical HUS: Abnormalities in alternative complement regulatory pathway →
endothelial cell damage → microvascular thrombosis

Question 5

Causes

Answer 5

Infection - HUS only
• Escherichia coli O157:H7 (Shiga toxin-producing E. coli – STEC) – 90%
• Produces a verotoxin that attacks endothelial cells
• Contaminated food/water (undercooked meat, cheese, poultry), community outbreaks, infected close contacts are RFs
• Shigella
• Neuraminidase-producing infections (Streptococcus)
• HIV

Drugs - both HUS and TTP
• COCP
• Ciclosporin
• Mitomycin
• Quinine
• 5-fluorouracil
• Some chemotherapy/targeted cancer drugs eg monoclonal antibodies, TKIs

Other
• Malignant hypertension
• Malignancy
• Bone marrow transplant – both
• Pregnancy / post-partum – both
• SLE
• Scleroderma
• Genetic predisposition for atypical HUS – FHx of HUS

Question 6

Epidemiology

Answer 6

• UNCOMMON
• D+ HUS often affects YOUNG CHILDREN (<5 years) – 90% of HUS due to STEC in young
children, decreasing frequency in older children and adults
• Can have outbreaks but may occur sporadically or in small clusters
• It is the most common cause of acute renal failure in children

Question 7

Presenting symptoms (GI)

Answer 7

o Severe abdominal colic
o Watery diarrhoea, esp bloody (prodrome for STEC HUS) – diagnosis occurs 5-10
days post onset

Question 8

Presenting symptoms (general)

Answer 8

o Malaise
o Fatigue
o Nausea
o Fever < 38 degrees (D+ or TTP)

Question 9

Presenting symptoms (renal)

Answer 9

o Oliguria or anuria

o Haematuria

Question 10

Signs on physical examination

Answer 10

• General
o Pallor
o Slight jaundice (due to haemolysis)
o Bleeding: bruising/purpura/ecchymoses, menorrhagia
o Generalised oedema
o Hypertension
o Retinopathy

• GI
o Abdominal tenderness

Question 11

Investigations (bloods)

Answer 11

o Normocytic anaemia (low Hb) – haemolysis
o High neutrophils
o Very low platelets – thrombocytopenia

Question 12

Investigations (U&Es)

Answer 12

o High urea!!
o High creatinine
o High K+
o Low Na+
o Electrolyte abnormalities may be due to diarrhoea (in HUS) and AKI

Question 13

Investigations (LFTs)

Answer 13

o High unconjugated bilirubin
o High LDH from haemolysis
o Evaluate hepatic involvement in STEC HUS (may have raised ALT/AST)

Question 14

Investigations (other)

Answer 14

• Haptoglobin – decreased during haemolysis
• LDH – high during haemolysis (released from RBC)

• ABG
o Low pH (due to bicarbonate loss)
o Low bicarbonate
o Low PaCO2
o Normal anion gap

• Blood Film
o Schistocytes / fragments
o High reticulocytes and spherocytes

• Urinalysis/dipstick
o 1+ g protein/24 hrs – mild proteinuria
o Haematuria

• Blood cultures – presence of STEC

• Stool culture – presence of STEC (may be -ve if not done early in diarrhoeal illness);
MC&S

• PCR – to detect Shiga toxin 1/2

• Proteins involved in complement regulation – abnormal levels of
complement (eg low
C3/C4) in familial and atypical HUS

• ADAMTS-13 level – deficiency in TTP
• Serum amylase, lipase and glucose – evaluate pancreatic involvement in STEC HUS

• Renal Biopsy
o Can distinguish between D+ and D- HUS