Investigation and Management of Hemolytic Uremic Syndrome in Children

Initial Emergency Assessment

• The American Academy of Pediatrics recommends immediate obtaining of a complete blood count with platelet count, peripheral blood smear for schistocytes, LDH, haptoglobin, indirect bilirubin, direct Coombs test, comprehensive metabolic panel with creatinine, and urinalysis when HUS is suspected in a child, while simultaneously collecting stool for culture and Shiga toxin testing 1
• Thrombocytopenia is defined as platelets <150,000/mm³ or 25% reduction from baseline, according to the American College of Clinical Pathology 1
• The presence of schistocytes, burr cells, or helmet cells in a peripheral blood smear indicates microangiopathic hemolysis, as stated by the International Society of Thrombosis and Haemostasis 1
• Elevated LDH levels, reduced or absent haptoglobin, and elevated indirect bilirubin are markers of hemolysis, as recommended by the National Institute of Diabetes and Digestive and Kidney Diseases 1
• A negative direct Coombs test is necessary to confirm non-immune hemolytic anemia, according to the American Association of Blood Banks 1
• Serum creatinine ≥1.0 mg/dL in children <13 years indicates acute kidney injury, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 1
• Urinalysis should be checked for hematuria and/or proteinuria, as recommended by the American Academy of Pediatrics 1
• ADAMTS13 activity must be tested urgently when thrombotic microangiopathy is confirmed, as severely deficient activity (<10 IU/dL) indicates TTP requiring immediate plasmapheresis rather than HUS, according to the International Society of Thrombosis and Haemostasis 1, 2

Etiologic Workup

• Stool culture and Shiga toxin testing should be performed to diagnose Typical (STEC-HUS), as recommended by the Centers for Disease Control and Prevention (CDC) 1, 3
• The CDC recommends testing for both STEC O157 culture AND Shiga toxin/genes to diagnose Typical (STEC-HUS) 1, 3
• The presence of stx2 is more potent and associated with higher HUS risk, as stated by the European Centre for Disease Prevention and Control (ECDC) 3
• If stool testing is negative but HUS is present, serologic testing for STEC (CDC-validated testing for serogroups O157 and O111) may aid in diagnosing antecedent infection, according to the CDC 1
• Clinical history is essential in distinguishing between Typical and Atypical HUS, as Typical STEC-HUS appears 4-5 days after diarrhea onset, as recommended by the American Academy of Pediatrics 1, 3

Treatment Decision Algorithm

• The American College of Rheumatology recommends initiating eculizumab within 4-8 hours of suspected aHUS diagnosis, as delays are associated with increased morbidity and mortality 4, 2
• Before eculizumab administration, the patient should receive quadrivalent A, C, W, Y meningococcal conjugate vaccine and B meningococcal vaccine, as recommended by the Advisory Committee on Immunization Practices (ACIP) 4
• Long-term antimicrobial prophylaxis with penicillin (or macrolides for penicillin-allergic patients) should be initiated for the duration of treatment, as recommended by the Infectious Diseases Society of America (IDSA) 4
• For Typical (STEC) HUS, supportive care only is recommended, including IV fluid resuscitation during the diarrhea phase to reduce the risk of oligoanuric renal failure, as stated by the American Academy of Pediatrics 3
• Antibiotics should be avoided in Typical (STEC) HUS, as they may worsen outcomes and potentially increase HUS risk, according to the CDC 3