What is the management approach for a patient with a condition requiring eculizumab (eculizumab) treatment when a hematologist (hematologist) is not readily available?

Management When Hematologist is Not Readily Available

When a hematologist is not immediately accessible for a patient requiring eculizumab treatment, frontline providers must initiate diagnostic workup and stabilization measures immediately, as delays beyond 4-8 hours from diagnosis are associated with increased morbidity and mortality. 1

Immediate Actions for Suspected aHUS/TMA

Diagnostic Workup to Perform Immediately

• Complete blood count with peripheral blood smear - specifically look for schistocytes >1% (though absence does not exclude early TMA), platelet count <150,000/mm³ or 25% reduction from baseline 1
• Hemolysis markers: LDH (elevated), haptoglobin (reduced), direct and indirect Coombs test (must be negative), reticulocyte count, bilirubin 1
• Renal function: serum creatinine (elevated), urinalysis for hematuria and/or proteinuria 1
• ADAMTS13 activity level - must be >5% to distinguish from TTP; this should be available as an urgent test within hours 1
• Complement testing: C3, C4, CH50 to assess complement pathway activation 1
• Infectious workup: stool for Shiga toxin/E. coli O157 (especially in pediatrics), viral studies (EBV, CMV, HHV6) 1

Critical Stabilization Measures

• Admit the patient immediately for continuous monitoring 1
• Establish IV access and prepare for potential transfusion support 1
• Type and screen for blood products - notify blood bank that transfusions may need to be irradiated and filtered depending on final diagnosis 1
• Avoid platelet transfusions unless life-threatening bleeding, as they may worsen thrombotic complications 1

Establishing Specialist Consultation

When Hematology is Not On-Site

Immediately initiate telephone or telemedicine consultation with a hematologist at a referral center while beginning diagnostic workup. 1 If consultation or transfer to a specialist center is not immediately possible, investigation and treatment should be initiated while liaison is being established. 1

• Contact nephrology as well, since aHUS requires multidisciplinary management involving both hematology and nephrology 1, 2
• Consider transfer to a tertiary center with expertise in TMA management if patient deteriorates or diagnosis remains uncertain 1
• Document all findings and timeline for specialist review, including exact time of symptom onset and diagnostic test results 1

Pre-Eculizumab Safety Measures

Mandatory Infection Prevention (Do Not Delay Treatment)

Administer meningococcal vaccines immediately - quadrivalent A, C, W, Y conjugate vaccine AND meningococcal B vaccine 1, 3 The FDA label notes that patients should ideally be immunized at least 2 weeks before eculizumab, but the risks of delaying therapy outweigh the risks of meningococcal infection in acute life-threatening situations. 1, 4

• Start antimicrobial prophylaxis immediately: penicillin (or macrolides for penicillin-allergic patients) for the duration of eculizumab treatment 1, 3
• This prophylaxis must continue long-term throughout complement inhibitor therapy 1, 3

Initiating Eculizumab Without On-Site Hematologist

Grade 3-4 TMA (Life-Threatening)

For severe cases with renal failure, CNS involvement, or hemodynamic compromise, eculizumab should be initiated within 4-8 hours of diagnosis even without hematologist present. 1

Dosing regimen for aHUS/HUS:

• 900 mg IV weekly for 4 doses 1
• 1,200 mg on week 5 1
• 1,200 mg every 2 weeks thereafter 1

Supportive Care Concurrent with Eculizumab

• Red blood cell transfusions according to existing guidelines for symptomatic anemia 1
• Avoid plasma exchange/plasmapheresis once eculizumab is started unless specifically treating TTP (ADAMTS13 <5%) 1
• Monitor for infusion reactions - have methylprednisolone available for premedication if needed 5

Critical Pitfalls to Avoid

Do Not Wait for Genetic Testing Results

The absence of identified complement mutations or antibodies cannot exclude aHUS - approximately 50% of cases have no identified genetic abnormality, and treatment should not be delayed pending genetic results. 1, 2

Do Not Confuse with STEC-HUS in Pediatrics

In children, distinguish timing of diarrhea: STEC-HUS typically appears 4-5 days after diarrhea onset, while aHUS may have concurrent diarrhea or very short prodrome. 1 However, when in doubt in severe cases, treat as aHUS since delays cause irreversible organ damage. 6

Do Not Discontinue Eculizumab Without Specialist Input

Stopping eculizumab carries 10-20% risk of disease recurrence and renal failure - this decision requires thorough risk assessment by specialists. 1, 2

Monitoring After Initiation

• Daily CBC, LDH, creatinine for first week 1
• Platelet count should improve within 1 week (mean increase from ~88 to ~281 × 10⁹/L) 4
• Hematologic normalization typically occurs within 1-2 doses (7-14 days) 7
• Renal recovery takes longer - median 28-35 days (5-6 doses) 7
• Watch for meningococcal infection signs throughout treatment - fever, headache, neck stiffness require immediate evaluation 1, 4