What is the optimal timing for initiating eculizumab (eculizumab) with plasmapheresis in the treatment of atypical Hemolytic Uremic Syndrome (aHUS) or Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Eculizumab and Plasmapheresis Timing in aHUS/PNH

Plasmapheresis should be discontinued immediately once eculizumab is initiated in atypical hemolytic uremic syndrome (aHUS), as continuing plasma exchange removes the therapeutic antibody and undermines treatment efficacy. 1

Critical Timing Principles

Stop Plasmapheresis When Starting Eculizumab

• Plasma exchange/plasmapheresis should be avoided once eculizumab is started, unless specifically treating thrombotic thrombocytopenic purpura (TTP) with ADAMTS13 activity <5%. 1
• Continuing plasmapheresis after eculizumab initiation is counterproductive because plasma exchange physically removes the therapeutic monoclonal antibody from circulation, negating its complement-blocking effect. 1

Initiate Eculizumab Rapidly

• Eculizumab should be initiated within 4-8 hours of diagnosis in patients with severe aHUS/TMA, even without a hematologist physically present. 1
• Early eculizumab initiation is critical to prevent irreversible organ damage—delays result in permanent renal injury that cannot be reversed even with subsequent treatment. 2, 3
• The standard dosing regimen is 900 mg IV weekly for 4 doses, followed by 1,200 mg at week 5, then 1,200 mg every 2 weeks for maintenance. 1, 4

Pre-Treatment Safety Requirements (Do Not Delay Eculizumab)

Meningococcal Protection

• Administer both quadrivalent meningococcal A, C, W, Y conjugate vaccine AND meningococcal B vaccine immediately upon suspecting aHUS. 1, 4
• If eculizumab cannot be delayed for the standard 2-week post-vaccination period, start antimicrobial prophylaxis (penicillin or macrolides such as ciprofloxacin) immediately and continue throughout treatment. 1, 4
• Never delay eculizumab initiation to wait for vaccination—the risk of irreversible organ damage from untreated aHUS far exceeds the meningococcal infection risk when prophylactic antibiotics are used. 1, 4

Clinical Sequence in Practice

Diagnostic Confirmation (Concurrent with Treatment Initiation)

• Obtain ADAMTS13 activity level to exclude TTP—a level >5% indicates aHUS rather than TTP. 1
• Perform complement testing (C3, C4, CH50) and stool testing for Shiga toxin/E. coli O157 to exclude STEC-HUS. 5
• Do not delay eculizumab while awaiting genetic testing results, as genetic mutations are found in only 50-60% of aHUS cases. 5

Transitioning from Plasmapheresis to Eculizumab

• If plasmapheresis has already been initiated before aHUS diagnosis is confirmed, stop it immediately when starting eculizumab. 1
• Patients who were plasmapheresis-dependent can achieve complete remission with eculizumab monotherapy—continuing plasma exchange is unnecessary and harmful. 6, 3
• In one reported case, a patient receiving plasma exchange three times weekly with frequent allergic reactions achieved complete disease control when transitioned to eculizumab alone. 7

Monitoring After Eculizumab Initiation

• Perform daily complete blood count, LDH, and creatinine for the first week after initiating eculizumab. 1
• Monitor for platelet count normalization (target >150,000/mm³), resolution of hemolysis (LDH normalization, disappearance of schistocytes), and stabilization or improvement in renal function. 5
• Watch continuously for signs of meningococcal infection including fever, headache, neck stiffness, confusion, or flu-like symptoms throughout treatment. 4

Common Pitfalls to Avoid

• Never continue plasmapheresis after starting eculizumab—this is the single most important timing principle, as plasma exchange removes the therapeutic antibody. 1
• Avoid delaying eculizumab initiation for genetic testing, vaccination completion, or specialist availability—irreversible renal damage occurs rapidly. 5, 2, 3
• Do not transfuse platelets unless life-threatening bleeding occurs, as platelet transfusions may worsen thrombotic microangiopathy. 1, 5

Special Consideration for PNH

While the evidence provided focuses primarily on aHUS, the same principle applies to paroxysmal nocturnal hemoglobinuria (PNH): plasmapheresis is not indicated in PNH management, and eculizumab should be initiated promptly once diagnosis is established with appropriate meningococcal prophylaxis. 4