Pathophysiology and clinical complications of atypical-HUS

Review how TMA manifests in atypical-HUS and can lead to resulting organ damage.1


Chronic, uncontrolled complement activity can result in continuous endothelial damage and ongoing risk of TMA1,6,18

Scan through the cyclical stages of endothelial injury that result from TMA lesions to understand how irreversible tissue damage can progress.5,18,19


In individuals with atypical-HUS, uncontrolled complement activity causes ongoing vascular endothelial injury, resulting in TMA lesions and progressive organ damage4,18,19

The assembly of multiple C5b-9 complexes on the surface of endothelial cells causes endothelial injury, leukocyte recruitment, and platelet activation.6,20-22

Binding of C5a to the C5a receptor results in a decrease in the endothelium’s anticomplement and antithrombogenic properties.6,21,24

Disrupted endothelial cells:

  • Release complement-activating microparticles, resulting in a vicious cycle of endothelial activation, complement amplification, and ongoing endothelial injury6,25
  • Release prothrombotic coagulation proteins, activate platelets, and recruit leukocytes, resulting in the formation of thrombi in small blood vessels throughout the body6

Biomarkers of complement activation, inflammation, endothelial cell activation and damage, coagulation, and renal damage (eg, Ba, sTNFR1, sVCAM-1, D-dimer, U-cystatin C) are similarly elevated among patients with atypical-HUS receiving or not receiving plasma exchange or plasma infusion.26

Ba=complement factor Ba; sTNFR1=soluble tumor necrosis factor receptor-1; sVCAM-1=soluble vascular cell adhesion molecule-1; U-cystatin C=urinary cystatin C.

Learn about complement system amplification in atypical-HUS.

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