Background
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