Hemolytic Uremic Syndrome Diagnosis and Management

Introduction to Hemolytic Uremic Syndrome

• The American Academy of Pediatrics recommends that Hemolytic Uremic Syndrome (HUS) be classified into two main types: typical HUS (STEC-HUS) and atypical HUS (aHUS), with STEC-HUS being caused by Shiga toxin-producing Escherichia coli (STEC) and aHUS being a complement-mediated disease 1, 2

Etiological Differences

• Typical HUS (STEC-HUS) is caused by infection with Shiga toxin-producing Escherichia coli (STEC), confirmed by stool testing for STEC, and represents approximately 90% of HUS cases in children 1, 3
• Atypical HUS (aHUS) is a multifactorial disease characterized by genetic or acquired (anti-CFH antibodies) anomalies affecting the alternative complement pathway, with frequent triggers including infections and pregnancy 2

Diagnostic Criteria

• STEC-HUS: Diarrhea precedes HUS by 4-5 days, with a positive test for STEC in stool 1, 3
• aHUS: Suspicion should be raised when diarrhea is absent, when the interval between diarrhea and HUS is short, or when diarrhea and HUS occur simultaneously, with a negative test for STEC or a short interval between diarrhea and HUS 1, 3

Management Differences

• STEC-HUS: Supportive treatment is predominantly used, with avoidance of platelet transfusions, which are contraindicated as they can worsen microangiopathic thrombosis 4, 5
• aHUS: Urgent medical attention is required, with immediate initiation of complement inhibitors (eculizumab or ravulizumab) without waiting for genetic testing results, and treatment should be administered for at least 6 months 1, 4, 5

Special Considerations for aHUS

• Patients receiving complement inhibitors should be vaccinated against meningococcal infection (serogroups A, C, W, Y, and B) and receive long-term antimicrobial prophylaxis 4
• The risk of recurrence after discontinuation of C5 inhibitors is 10-20%, with potential for renal failure, and monitoring should include clinical presentation, laboratory data, and appearance of glomerular proteinuria 4

Clinical Pitfalls to Avoid

• Do not delay treatment with eculizumab while waiting for genetic testing if aHUS is suspected and STEC-HUS is excluded, as genetic mutations are found in only 50-60% of cases 4, 3
• Do not administer platelet transfusions in HUS, as they can worsen microangiopathic thrombosis 5, 4