What is the initial treatment for atypical Hemolytic Uremic Syndrome (aHUS)?

Initial Treatment for Atypical Hemolytic Uremic Syndrome (aHUS)

Begin eculizumab therapy immediately upon diagnosis of aHUS at 900 mg weekly for 4 weeks, followed by 1200 mg at week 5, then 1200 mg every 2 weeks thereafter for adults, as this is the FDA-approved standard of care that inhibits complement-mediated thrombotic microangiopathy. 1

Critical Pre-Treatment Requirements

Vaccination and prophylaxis must be addressed urgently but should not delay life-saving therapy:

• Vaccinate against meningococcal infection (serogroups A, C, W, Y, and B) at least 2 weeks prior to eculizumab initiation according to ACIP recommendations 1
• If urgent therapy is required before vaccination completion, provide antibacterial prophylaxis (penicillin or macrolides for penicillin-allergic patients) immediately and administer vaccines as soon as possible 1, 2
• Continue long-term antimicrobial prophylaxis with penicillin throughout the duration of eculizumab treatment 2

Treatment Initiation Algorithm

For Adults (≥18 years or ≥40 kg):

• Loading phase: 900 mg IV weekly for 4 weeks 1
• Transition dose: 1200 mg IV at week 5 (one week after fourth dose) 1
• Maintenance: 1200 mg IV every 2 weeks thereafter 1

For Pediatric Patients:

Weight-based dosing is essential 1:

• 40 kg and over: Same as adult dosing
• 30 to <40 kg: 600 mg weekly × 2 doses, then 900 mg at week 3, then 900 mg every 2 weeks
• 20 to <30 kg: 600 mg weekly × 2 doses, then 600 mg at week 3, then 600 mg every 2 weeks
• 10 to <20 kg: 600 mg weekly × 1 dose, then 300 mg at week 2, then 300 mg every 2 weeks
• 5 to <10 kg: 300 mg weekly × 1 dose, then 300 mg at week 2, then 300 mg every 3 weeks

Critical Timing Considerations

Treatment delays are associated with increased morbidity and mortality; initiate therapy within 4-8 hours of diagnosis 2

aHUS should be treated as a medical emergency with urgent supportive measures 3

Alternative Complement Inhibitor Option

Ravulizumab (ULTOMIRIS) is an FDA-approved alternative with less frequent dosing 4:

• Loading dose varies by weight (3000-3600 mg for adults ≥40 kg) 4
• Maintenance dosing every 8 weeks (versus every 2 weeks for eculizumab) 4
• Same meningococcal vaccination and prophylaxis requirements apply 4

Concurrent Supportive Management

While initiating complement inhibitor therapy, provide:

• Immediate hematology consultation 5
• Stabilization of critical organ dysfunction 5
• Red blood cell transfusions according to existing guidelines for symptomatic anemia 5
• Avoid platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombotic microangiopathy (general medical knowledge)
• Renal replacement therapy if indicated for acute kidney injury 3

Diagnostic Confirmation Requirements

Before or concurrent with treatment initiation, obtain:

• ADAMTS13 activity level to exclude thrombotic thrombocytopenic purpura (TTP) 5
• Complement testing: C3, C4, CH50, and complement inhibitory antibodies 5
• Stool testing for Shiga toxin/E. coli O157 to exclude STEC-HUS 5, 3
• Complete blood count with peripheral smear demonstrating schistocytes >1% 5, 3
• Serum creatinine, LDH, haptoglobin, and reticulocyte count 5

Critical Pitfalls to Avoid

Do not delay eculizumab/ravulizumab therapy while awaiting genetic testing results, as genetic mutations are found in only 50-60% of cases 5

Do not use plasma exchange as primary therapy for aHUS—this is appropriate for TTP but not for complement-mediated aHUS 3, 1

Do not discontinue complement inhibitor therapy prematurely, as this carries 10-20% risk of relapse with potential renal failure 5, 2

Recognize that in pediatric patients, particularly newborns, aHUS may present without all three classic features (thrombocytopenia, anemia, elevated creatinine) 3

Special Clinical Contexts

For pregnancy-triggered aHUS:

• C5 inhibitors (eculizumab/ravulizumab) are instrumental in resolving TMA and should be initiated immediately 5, 3

For patients of Chinese or Japanese descent:

• Be aware of potential resistance to C5 inhibitors due to C5 gene polymorphisms (c.2654 G→A, c.2653 C→T) 5, 3

For patients requiring plasmapheresis, plasma exchange, or IVIG:

• Supplemental dosing of eculizumab/ravulizumab is required as these procedures reduce drug levels 4, 1

Monitoring During Initial Treatment

Assess response to therapy by monitoring:

• Platelet count normalization (target >150,000/mm³) 5
• Resolution of hemolysis (LDH normalization, disappearance of schistocytes) 5
• Stabilization or improvement in renal function (serum creatinine) 5
• Complete blood count every 2-4 weeks until doses stabilized 5

Monitor for meningococcal infection signs throughout treatment, as risk remains elevated despite vaccination 4, 1