Diagnostic Testing for Hemolytic Uremic Syndrome (HUS)
The diagnosis of HUS requires demonstrating the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury through specific laboratory tests, with peripheral blood smear examination for schistocytes being essential when HUS is suspected. 1, 2
Core Laboratory Tests (First-Line)
Complete Blood Count with Peripheral Smear
- Obtain hemoglobin and platelet counts with serial monitoring (daily during days 1-14 of illness if STEC infection suspected) to detect evolving HUS, as a single CBC is insufficient to define risk 1
- Examine peripheral blood smear for red blood cell fragmentation (schistocytes, burr cells, helmet cells) - this is mandatory when HUS is suspected, though absence of schistocytes should not exclude early diagnosis due to low sensitivity 1, 2
- Platelet count <150,000/mm³ or 25% reduction from baseline confirms thrombocytopenia; patients with decreasing platelet trends during the diarrheal illness are at higher risk for HUS 1, 2
- Note that near-normal hemoglobin may indicate dehydration rather than absence of anemia 1
Hemolysis Markers
- Elevated lactate dehydrogenase (LDH) and reduced haptoglobin confirm hemolysis 1, 3, 2
- Negative direct Coombs test (direct antiglobulin test) is essential to confirm non-immune hemolytic anemia 1, 3, 2
Renal Function Tests
- Monitor creatinine, blood urea nitrogen, and electrolytes frequently to detect early renal injury 1
- Urinalysis for hematuria and proteinuria - presence of either indicates renal involvement 1, 3, 2
- Acute renal injury defined as creatinine ≥1.0 mg/dL in children <13 years, ≥1.5 mg/dL in those ≥13 years, or ≥50% increase over baseline 2
Etiologic Testing (Critical for Classification)
For Typical (STEC-Associated) HUS
- Stool culture and Shiga toxin testing to identify Shiga toxin-producing E. coli (most commonly O157 serotype) 1
- 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 1
For Atypical HUS (aHUS)
- ADAMTS13 activity level (urgent) - severely deficient (<10%) indicates thrombotic thrombocytopenic purpura (TTP), not aHUS; this is crucial for differential diagnosis 3
- Complement testing: C3, C4, CH50 (classical pathway), and AP50 (alternative pathway) to assess complement activation 1
- Genetic testing for complement pathway mutations should be performed in all suspected aHUS cases for prognosis and treatment decisions; results ideally within a few months 1, 2, 4
- Autoantibody testing for complement factor H and other complement proteins 1, 4
Monitoring Protocol
For Patients with Diagnosed or Suspected STEC Infection
- Daily monitoring of hemoglobin, platelet counts, electrolytes, BUN, and creatinine during the at-risk period (days 1-14) 1
- Monitoring can stop when platelet count begins to increase or stabilize with resolved/resolving symptoms 1
- Patients with increasing creatinine, elevated blood pressure, and volume overload require close monitoring in centers capable of managing acute renal failure 1
White Blood Cell Count Considerations
- High WBC count with neutrophil predominance often occurs in STEC O157 infections that progress to HUS 1
- WBC differential may suggest bacterial vs. viral etiology but should not be used alone to establish diagnosis 1
Important Diagnostic Pitfalls
Do not exclude HUS based on incomplete triad: Up to 50% of aHUS cases may not clearly present with all three clinical signs (hemolytic anemia, thrombocytopenia, renal involvement) at disease onset 2
Timing matters for typical HUS: Typical HUS occurs within 3 weeks after acute or bloody diarrhea; simultaneous onset of diarrhea and HUS suggests aHUS rather than STEC-HUS 2
Platelet count timing: If platelet count obtained within 7 days of acute gastrointestinal illness onset is not below 150,000/mm³, consider alternative diagnoses 2
Special pediatric considerations: In children <1 year with aHUS, consider mutations in non-complement genes (DGKE, WT1) 3