Can schistocytes be present in Hemolytic Uremic Syndrome (HUS)?

Schistocytes in Hemolytic Uremic Syndrome

Yes, schistocytes are not only present but are a required diagnostic feature of Hemolytic Uremic Syndrome (HUS). According to the Centers for Disease Control and Prevention (CDC) guidelines, the presence of microangiopathic changes, specifically schistocytes (fragmented red blood cells), is one of the essential laboratory criteria for diagnosing HUS 1.

Diagnostic Criteria for HUS

The CDC defines the laboratory criteria for HUS diagnosis as requiring both:

1. Anemia (acute onset) with microangiopathic changes - specifically schistocytes, burr cells, or helmet cells on peripheral blood smear
2. Renal injury (acute onset) - evidenced by hematuria, proteinuria, or elevated creatinine levels 1

Pathophysiology of Schistocytes in HUS

Schistocytes form in HUS due to the underlying thrombotic microangiopathy:

• Red blood cells become fragmented when passing through small vessels partially occluded by microthrombi
• These microthrombi form due to endothelial damage in the microcirculation
• In typical HUS, this is often triggered by Shiga toxin-producing bacteria
• In atypical HUS (aHUS), this results from dysregulation of the complement system 2

Quantification and Significance

• Automated fragmented red blood cell percentage (FRC%) has shown high sensitivity (95.4%) for detecting schistocytes in pediatric HUS patients 3
• Studies show that schistocytes are consistently present in HUS/TTP patients, with residual schistocytosis (persistent schistocytes) occurring in approximately 35.6% of patients even after treatment 4

Differentiating HUS from Other Conditions

Schistocytes help differentiate HUS from other conditions:

• HUS vs. TTP: Both conditions show schistocytes, but can be differentiated by ADAMTS13 activity (severely deficient in TTP, normal or slightly reduced in HUS) 5
• Typical vs. atypical HUS: Both show schistocytes, but atypical HUS is associated with complement dysregulation rather than Shiga toxin 2
• Other microangiopathic conditions: Schistocytes may be present in various thrombotic microangiopathies, requiring additional clinical and laboratory features for differentiation 6

Clinical Implications

The presence of schistocytes in HUS has important clinical implications:

• Requires monitoring during treatment to assess response
• May persist even after platelet count normalization 4
• Helps guide treatment decisions, particularly regarding plasma exchange or complement inhibitors like eculizumab 7

Important Caveats

• Schistocyte evaluation by manual microscopy is subjective and requires expertise
• Automated methods may provide more consistent results but have lower specificity (50%) 3
• The absence of schistocytes should prompt consideration of alternative diagnoses
• The number of schistocytes does not necessarily correlate with disease severity or predict relapse 4

In conclusion, schistocytes are a fundamental diagnostic feature of HUS, reflecting the underlying microangiopathic hemolytic process. Their presence is required for diagnosis according to established guidelines, though their quantification and persistence after treatment may vary between patients.