Haemolytic Uraemic Syndrome

OVERVIEW

  • Haemolytic uraemic syndrome (HUS) is a clinically similar condition to TTP
  • in HUS (unlike TTP): renal failure > neurological symptoms
  • typical and atypical forms

HUS VERSUS TTP

  • TTP has predominantly neurological features, in HUS renal failure predominates.
  • TTP has a distinct molecular pathogenesis – most cases either have inherited ADAMTS13 mutations or acquired antibodies against ADAMST13 (a von Willebrand’s Factor-cleaving metalloproteinase).
  • TTP and aHUS can coexist!

TYPES OF HUS

Diarrhoea-associated (D+ HUS)

  • >90% of HUS cases
  • caused by preceding infection with a verocytotoxin-producing bacteria, typically E.coli O157:H7

Non-diarrhoeal/ atypical (D- or aHUS)

  • rare
  • possibly familial
  • only about 50% of those with the genetic predisposition develop aHUS
  • poorer prognosis
  • often results from complement dysregulation — 50% involve complement regulatory genes: factor H, membrane cofactor protein (MCP) and factor I

TRIGGERS

D+ HUS

  • verocytotoxin-producing bacteria, typically E.coli O157:H7

aHUS

  • Streptococcus pneumoniae (40%) (also known as P-HUS, a subtype of aHUS)
  • Pregnancy (term or post-partum)
  • Drugs – quinine, mitomycin, ciclosporin, tacrolimus, ticlopidine, caboplatinum, gemcitabine
  • Transplantation – renal, haematological stem cell transplantation
  • HIV
  • Combined methylmalonic aciduria and homocystinuria (a vitamin B12 metabolism disorder)

P-HUS

  • occurs because S. pneumoniae has a neuraminidase that removes N-acetylneuraminic acid from cell-surface glycoproteins
  • this  exposes the normally hidden T antigen (Thomsen-Friedenreich antigen) on red blood cells, platelets, and glomeruli
  • Anti-T immunoglobulin M (IgM) in the serum reacts with the antigen causing hemolysis, thrombocytopenia and renal damage

CLINICAL FEATURES

  • childhood: bloody diarrhoea post E.coli infection
  • adulthood: same but also HIV, antiphospholipid syndrome, malignant hypertension
  • bone transplant
  • CMV infection

Classic pentad: (FAT R/N)

  • fever
  • anaemia (microangiopathic haemolytic)
  • thrombocytopenia
  • renal problems (88% have renal problems, 15% haematuria) – more likely in HUS
  • neurological problems (headaches, confusion, seizures) – more likely in TTP

INVESTIGATIONS

-> microangiopathic haemolytic anaemia, ARF, thrombocytopenia

  • low platelets
  • low Hb with polychromasia, schistocytes and spherocytes
  • increased reticulocytes
  • reduced haptoglobins
  • increased LDH
  • unconjugated hyperbilirubinaemia with urinary urobilinogen
  • variable neutrophilia
  • increased urea and creatinine levels (greater in HUS)

Renal biopsy (may be contra-indicated by thrombocytopenia) — histological findings include:

  • Thrombotic microangiopathy with swollen glomerular endothelial cells and red cells and platelets in the capillaries
  • Accumulation of fibrin-like material in the subendothelial space resulting in thickened capillary walls
  • Thrombi in the glomerular capillaries and arterioles
  • There may be acute cortical necrosis involving both glomeruli and convoluted tubules

Other tests to confirm aHUS and identify the underlying cause include:

  • genetic testing
  • C3 levels are low in Factor H and I deficiency
  • FDP/ D-dimer is high but the coagulation profile is otherwise normal.

MANAGEMENT

Supportive care and monitoring are the mainstays:

  • antibiotics may worsen toxin production
  • platelets are contra-indicated
  • plasmapheresis if unsure
  • seek and treat the underlying cause and any complications

Specific therapies

  • Plasma exchange and plasma infusion
    • Efficacy is uncertain given the absence of any randomised controlled trials in aHUS
    • Mortality has decreased from 50% to 25% since their introduction to clinical practice
    • Avoided in S. pneumoniaeassociated HUS (P-HUS) because anti-T IgM in the administered plasma may exacerbate the disease.
  • There is no good evidence for:
    • Steroids
    • Heparin
    • Aspirin
    • Antioxidants

General treatment of acute renal failure

  • Fluid restriction and diuretics
  • Anti-hypertensives
  • Avoidance of nephrotoxins where possible
  • RRT if necessary

References and Links

LITFL

Journal articles

  • Amirlak I, Amirlak B. Haemolytic uraemic syndrome: an overview. Nephrology(Carlton). 2006 Jun;11(3):213-8. PMID: 16756634.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.