Chronic, uncontrolled complement activity and endothelial damage puts patients with aHUS at risk of life-threatening complications1-4

TMA lesions from repeated endothelial injury can progress toward irreversible tissue damage2,4,5

  • Elevated Baseline of
    Complement Activity

  • Chronic
    Complement Activity

  • Complement Mediated
    TMA

  • Ischemia

  • Progressive Organ
    Damage

Individual with aHUS

  • The assembly of multiple C5b-9 complexes on the surface of endothelial cells causes endothelial injury and platelet activation3,6-8
  • Binding of C5a to the C5a receptor results in a decrease in the endothelium's anticomplement and antithrombogenic properties3,7,9,10
  • Disrupted endothelial cells3,11:
    • Release complement-activating microparticles, resulting in a vicious cycle of endothelial activation, complement amplication, and ongoing endothelial injury
    • Release prothrombotic coagulation proteins, activate platelets, and recruit leukocytes, resulting in the formation of thrombi in small blood vessels throughout the body
  • Effects of aHUS are a result of response to endothelial injury4
    • aHUS can result in damage to glomeruli, arterioles, and arteries
  • 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 elevated in patients with aHUS12

Patients with aHUS experiencing a TMA manifestation can develop organ damage rapidly1,13,14

1. Laurence J, et al. Clin Adv Hematol Oncol. 2016;14 Suppl 11(11):2-15. 2. Legendre CM, et al. N Engl J Med. 2013;368(23):2169-2181. 3. Noris M, et al. Nat Rev Nephrol. 2012;8(11):622-633. 4. Goodship THJ, et al. Kidney Int. 2017;91(3):539-551. 5. Nester CM, Thomas CP. Hematology Am Soc Hematol Educ Program. 2012;2012:617-625. 6. Barbour T, et al. Nephrol Dial Transplant. 2012;27(7):2673-2685. 7. Fang CJ, et al. Br J Haematol. 2008;143(3):336-348. 8. Loirat C, Fremeaux-Bacchi V. Orphanet J Rare Dis. 2011 ;6 :60. 9. Gastoldi S, et al. lmmunobiology. 2012;217(11):1145-1146. 10. Salant DJ. J Am Soc Nephrol. 2011 ;22(1):7-9. 11. Renner B, et al. J Am Soc Nephrol. 2013;24(11):1849-1862. 12. Cofiell R, et al. Blood. 2015;125(21):3253-3262. 13. Campistol JM, et al. Nefrologia. 2015;35(5):421-447. 14. Azoulay E, et al. Chest. 2017;152(2):424-434.