• Atypical HUS Proposed Physiology
  1. Loss-of-function mutation in regulatory gene (CFH) AND gain-of-function mutation in effector gene
  2. Trigger event (often infection)
  3. Uninhibited continuous activation of alternative pathway (C5) --> MAC
  4. Endothelium damage --> activation of the coagulation cascade and TMA
  **Mutations in complement factor H are most common**
  
  

  Posted 03/09/17 09:09:45 AM by Matthew Cummings

• PLEX vs FFP for TTP
  • PLEX superior to FFP (NEJM 1991) 
    • HOWEVER -- if in resource-limited setting without access to PLEX -- FFP is best option prior to transfer for PLEX
  
  

  Posted 03/09/17 09:26:40 AM by Matthew Cummings

• Eculizimab for atypical HUS
  • First-line therapy: humanized monoclonal antibody to C5
    • Binds to C5 --> prevents its cleavage --> inhibits production of C5a and then MAC
  • IV infusion -- induction followed by maintenance dosing
    • Unclear whether should be discontinued if positive response or if should be continued indefinitely
  • Adverse effects: Severe meningococcal infections (should be vaccinated!)
  
  

  Posted 03/09/17 09:32:09 AM by Matthew Cummings

• For further reading...

  Comparison of Plasma Exchange with Plasma Infusion in the Treatment of TTP (NEJM 1991)
  Clinical differentiation and initial treatment of adult patients with atypical HUS (Blood: How I treat)
  Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies (Nature)
  Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome (NEJM)
  
  

  Posted 03/09/17 10:02:51 AM by Matthew Cummings

Created by Christopher Kelly

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