9.18 SFGH am report pearls: atypical HUS

Atypical HUS:

  • Thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, AKI
  • Cardiac complications occur in 3-10% of patients with complement-mediated aHUS, due to microangiopathic injury in the coronary microvasculature
  • Primary causes due to complement dysregulation (atypical HUS)
    • complement gene mutations: (including complement factor H, complement factor I, membrane cofactor protein)
    • antibodies to complement factor H
  • Send ADAMST13 activity to distiguish from TTP (In TTP, ADAMST13 activity usually <5-10%; although malignancy/infection may cause marked reductions),
  • Treatment:
    • first line: eculizumab: a monoclonal antibody to C5 that blocks terminal complement cascade
      • initially a weekly infusion dose
      • optimal duration of therapy unknown
      • associated with meningococcal infections
        • vaccinate for neisseria meningitis, strep pneumo, and H flu type B
    • Oftentimes difficult to distinguish at presentation from TTP; given high mortality for TTP, practice oftentimes is to initiate plasma exchange while genetic and ADAMST13 testing is sent

Legendre et al. Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome. 2013 NEJM. 368 (23) 2169-81.

Davin JC and van de Kar NC.  Advances and challenges in the mangement of complement-mediated thrombotic microangiopathies.  2015 Ther Adv Hematol. 4:171-85.

Noris M and Remuzzi G.  Cardiovascular complications in atypical haemolytic uraemic syndrome.  Nat Rev Nephrol. 2014 10(3):174-80.

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