Atypical Hemolytic Uremic Syndrome (aHUS) Treatment
First-Line Treatment
Initiate eculizumab (or ravulizumab) immediately upon clinical suspicion of aHUS without waiting for genetic test results, as delays are associated with increased morbidity and mortality. 1, 2
- Start eculizumab within 4-8 hours of diagnosis, as treatment delays worsen outcomes 3
- Do not wait for genetic confirmation—mutations are only identified in 50-60% of cases 1, 2
- Both eculizumab and ravulizumab have equivalent efficacy, but ravulizumab offers longer duration of effect and less frequent infusions 3
Dosing Schedule
Eculizumab Standard Dosing (Adults):
- Induction phase: 900 mg weekly for 4 weeks 4
- Maintenance phase: 1200 mg at week 5, then every 14 days 4, 5
- Treatment duration: Minimum 6 months 2, 6
Individualized Dosing Strategy:
- Monitor classical complement pathway (CCP) activity to guide dosing intervals 4
- Target CCP activity <30% to prevent relapses 4
- Extend dosing intervals (21-28 days) based on CCP suppression once stable remission achieved 4
- Free eculizumab levels inversely correlate with CCP activity (r = -0.690, p = 0.0001) 4
Mandatory Vaccination Requirements
Complete meningococcal vaccination at least 2 weeks before eculizumab initiation (or immediately if treatment cannot be delayed): 3, 6
- Quadrivalent meningococcal conjugate vaccine (serogroups A, C, W, Y) 3
- Meningococcal B vaccine 3
- Long-term antimicrobial prophylaxis with penicillin (or macrolides if penicillin-allergic) for the entire duration of complement inhibitor therapy 3, 6
Monitoring Protocol
Laboratory Monitoring:
- Complete blood count with peripheral blood smear (monitor for schistocytes >1%) 2
- Lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, reticulocyte count 2
- Serum creatinine, urinalysis for hematuria/proteinuria 3, 2
- Platelet count (target >150,000/mm³ or <25% reduction from baseline) 3
- Classical complement pathway activity (CCP) to guide dosing intervals 4
Clinical Monitoring:
- Monitor for signs of disease recurrence: hemolysis, thrombocytopenia, rising creatinine, proteinuria 2, 6
- Assess for meningococcal infection symptoms throughout treatment 3
Alternative Treatments
If Eculizumab Contraindicated or Unavailable:
Plasma exchange remains the historical alternative, though significantly inferior to complement inhibition: 5, 7
- Plasma exchange: 150% plasma volume, 3 times weekly 5
- Plasma infusions: 10-20 mL/kg if plasma exchange unavailable 7
- Glucocorticosteroids as adjunctive therapy 7
- Critical limitation: 67% of adult patients progress to end-stage renal disease or death within 3 years without eculizumab 7
If Eculizumab Ineffective:
- Verify adequate complement suppression with CCP activity and free eculizumab levels 4, 8
- Consider increased dosing frequency (every 7-10 days instead of 14) if breakthrough activity occurs 8
- Some patients show persistent C3d and sC5b-9 elevation despite maximal complement suppression, indicating incomplete response 8
- Evaluate for alternative diagnoses or concurrent triggers (infection, pregnancy) 1
Treatment Discontinuation Considerations
Eculizumab discontinuation carries 10-20% recurrence risk with potential for renal failure: 1, 6
- Restrictive treatment protocols show safety when combined with close monitoring 9
- If discontinuation attempted, monitor weekly for 4 weeks, then monthly for signs of recurrence 9
- Restart eculizumab immediately if recurrence detected—early intervention prevents clinical sequelae 9
- Genetic risk stratification should inform discontinuation decisions (though absence of mutations does not exclude risk) 3, 1
Critical Supportive Care
- Transfuse RBCs only for symptomatic anemia or hemoglobin <7-8 g/dL 2
- Avoid platelet transfusions unless life-threatening bleeding—they worsen microangiopathic thrombosis 1, 2, 6
- Provide folic acid 1 mg daily supplementation 2
- Coordinate with blood bank before any transfusions regarding complement-mediated TMA 2
Genetic Testing and Counseling
- Order next-generation sequencing of complement genes (CFH, CFHR1-5, C3, CD46, CFI, THBD, DGKE, CFB) after treatment initiation 2
- Provide genetic counseling once diagnosis confirmed due to possible genetic transmission 2
- Results should not delay treatment but inform long-term management and family screening 1, 2