HUS is a disorder characterised by thrombocytopenia, microangiopathic haemololytic anaemia (anaemia secondary to red blood cell fragmentation) and kidney failure | Getty + Stocktrek Images
Contents
Cover image: HUS is a disorder characterised by thrombocytopenia, microangiopathic haemololytic anaemia (anaemia secondary to red blood cell fragmentation) and kidney failure | Getty + Stocktrek Images
Heterogeneous group of disorders characterized by microangiopathic hemolytic anaemia, thrombocytopenia and acute renal insufficiency.
Etiology
D- HUS (Atypical HUS)
Inherent abnormality in Complement Regulatory Pathway
Infection with neuraminidase-producing organisms (Pneumococci)
HIV, Cancer, SLE
Drugs:
TCC: Ticlopidine, Clopidogrel & Cyclosporine
D+ HUS (Typical HUS)
Mostly in children (90%)
Usually, a post-diarrhoeal complication caused by,
Shigella dysentriae Type 1
EHEC/VTEC
Enterohaemorragic E. coli infection and haemolytic–uraemic syndrome. HUS occurs at the 6th day after diarrhoea in EHEC enteritis; with an overall incidence of 6–9% and in STEC-O104:H4’s outbreak of 30%. On the other hand, 70% of HUS cases occur in the context of EHEC enteritis. HUS triad comprises microangiopathic haemolytic anaemia, thrombocytopenia and AKI. Patients who develop AKI, 50% will require RRT and 5–10% will remain with renal sequelae. 5–7% of patients with HUS do not survive. EHEC: enterohaemorragic E. coli; HUS: haemolytic–uraemic syndrome; RRT: renal replacement therapies; STEC: Shiga-like toxin producing E. coli; AKI: acute kidney injury.
Pathophysiology
Pathogenesis of E. coli enteritis and haemolytic–uraemic syndrome. AKI: acute kidney injury; CNS: central nervous system. HUS triad: thrombocytopenia, anaemia and AKI.
Hypothetical model for shared pathophysiology between HUS and TTP. In this proposed model, the inciting event for both HUS and TTP is a similar endothelial insult brought about by any of a variety of sources (or combination of sources) that results in widespread endothelial activation, inflammation, and damage, including the release of VWF and other contents of the Weibel-Palade bodies. The subsequent events may be determined in part by the level of systemic ADAMTS13 activity. In the case of systemic ADAMTS13 deficiency (top), ADAMTS13 is not available to process the newly released VWF, resulting in the widespread formation of VWF and platelet thrombi throughout the arteriolar circulation and the clinical picture of TTP. Conversely, in the case of systemic ADAMTS13 sufficiency (bottom), TTP is avoided by ADAMTS13-mediated release of platelet/VWF thrombi throughout the arteriolar circulation. For reasons that are not understood, circulating ADAMTS13 is not able to cleave efficiently VWF that is released in the glomerular microcapillary circulation, resulting in thrombus formation, increased inflammation, glomerular damage, and the clinical picture of HUS. Potential reasons for the inability of ADAMTS13 to cleave VWF in the glomerular circulation may include unfavorable shear stress not permissive for the proper unfolding of VWF (decreasing access of ADAMTS13 to the sessile bond within the folded VWF A2 domain) and the local presence of molecules that may interfere with ADAMTS13 activity or with its interaction with VWF. | Figure 1. (2022). Journal Of The American Society Of Nephrology. Retrieved from https://jasn.asnjournals.org/content/18/9/2457/F1
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