Haemolytic uraemic syndrome

Overview & Definition

A previously well toddler who had bloody diarrhoea a week ago and now arrives pale, listless, and passing very little urine has haemolytic uraemic syndrome. The name describes the three things going wrong at once: red blood cells are being destroyed inside narrowed blood vessels (haemolytic anaemia), platelets are being consumed as clots form in those vessels (thrombocytopenia), and the vessels that are most affected are in the kidneys, where the clots block the filtering surface and shut down urine production (uraemia). This triad, caused by widespread thrombotic microangiopathy in small vessels, defines the syndrome regardless of the trigger. [1]

The trigger is usually an intestinal infection. About 90 percent of paediatric HUS follows gastroenteritis caused by Shiga toxin-producing Escherichia coli, most commonly the O157:H7 strain, and this form is called typical or STEC-HUS. A much smaller but far more dangerous group, accounting for 5 to 10 percent of cases, has no diarrhoeal prodrome and is driven by uncontrolled activation of the body's complement immune pathway. This is atypical HUS, and the distinction between the two is the single most consequential decision in the disease because atypical HUS requires urgent treatment with eculizumab, a complement-blocking drug, while typical STEC-HUS is managed with supportive care alone. [3]

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1. [1]Tarr PI, Gordon CA, Chandler WL Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet, 2005.PMID 15781103
2. [2]Noris M, Remuzzi G Atypical hemolytic-uremic syndrome. N Engl J Med, 2009.PMID 19846853
3. [3]Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, et al An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol, 2016.PMID 25859752
4. [4]Keir LS, Saleem MA Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome. Pediatr Nephrol, 2014.PMID 23843163
5. [5]Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, et al Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis, 2012.PMID 22412065
6. [6]Schaefer F, Ardissino G, Ariceta G, Fakhouri F, Scully M, Isbel N, et al Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int, 2018.PMID 29907460
7. [7]Le Clech A, Simon-Tillaux N, Provôt F, et al. Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors. Kidney Int, 2019.PMID 30982675
8. [8]Lapeyraque AL, Malina M, Fremeaux-Bacchi V, Boppel T, Kirschfink M, Oualha M, et al Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med, 2011.PMID 21612462
9. [9]Percheron L, Gramada R, Tellier S, et al. Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study. Pediatr Nephrol, 2018.PMID 29572749
10. [10]de Zwart PL, Mueller TF, Spartà G, Luyckx VA Eculizumab in Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: a systematic review. Pediatr Nephrol, 2024.PMID 38057431
11. [11]Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, et al Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med, 2011.PMID 21696328
12. [12]Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, et al Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol, 2013.PMID 23431077