Atypical hemolytic-uremic syndrome: Difference between revisions

Latest revision as of 13:50, 20 April 2023

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

@@ Line 1: / Line 1: @@
+==Background==
-== Pathophysiology ==
+*One of the [[thrombotic microangiopathy|thrombotic microangiopathies]]
-* Congenital defect leading to dysregulation of the alternative complement pathway, which leads to increased complement activity
+*Different pathophysiology and treatment from [[hemolytic-uremic syndrome|typical hemolytic-uremic syndrome]] (after STEC diarrhea) and [[secondary hemolytic-uremic syndrome]]
+===Pathophysiology===
-== Investigations ==
+*Congenital defect leading to dysregulation of the alternative complement pathway, which leads to increased complement activity
-* Diagnosis with genetic mutation analysis of complement regulatory proteins (CFH, CFI, MCP, C3, CFB, THBD) and anti-CFH antibodies
+*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)
-== Management ==
+==Diagnosis==
+*Genetic mutation analysis of complement regulatory proteins (CFH, CFI, MCP, C3, CFB, THBD) and anti-CFH antibodies
-* 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 aHUS-specific treatment
+==Management==
-* Eculizumab
+*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]]