Atypical hemolytic-uremic syndrome

Background

• One of the thrombotic microangiopathies
• Different pathophysiology and treatment from typical hemolytic-uremic syndrome (after STEC diarrhea) and secondary hemolytic-uremic syndrome

Pathophysiology

• Congenital defect leading to dysregulation of the alternative complement pathway, which leads to increased complement activity
• Mutations can occur anywhere in the complement pathway or, occasionally, in unrelated proteins
  • Complement factor H (CFH), C3, factor B, factor I, CD46
  • Diacylglycerol kinase ε, plasminogen, factor XII (in the presence of anti-factor H autoantibodies), and thrombomodulin (CD141)

Diagnosis

• Genetic mutation analysis of complement regulatory proteins (CFH, CFI, MCP, C3, CFB, THBD) and anti-CFH antibodies

Management

• Often unable to distinguish from TTP, so plasma exchange should be initiated promptly
• If no improvement on PLEX and there is significant renal involvement, consider:
  • Eculizumab to inhibit C5 complement
  • Ideally with full meningococcal vaccination beforehand