View source for Atypical hemolytic-uremic syndrome

==Background==

*One of the [[thrombotic microangiopathy|thrombotic microangiopathies]]
*Different pathophysiology and treatment from [[hemolytic-uremic syndrome|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

[[Category:Hematology]]
[[Category:Nephrology]]
[[Category:Thrombosis]]