What are the characteristic laboratory findings in hemolytic‑uremic syndrome?

Laboratory Findings in Hemolytic Uremic Syndrome

The diagnostic triad of HUS consists of microangiopathic hemolytic anemia with schistocytes on peripheral smear, thrombocytopenia (platelets <150,000/mm³), and acute kidney injury with elevated creatinine, hematuria, or proteinuria. 1

Core Laboratory Abnormalities

Hematologic Findings

• Thrombocytopenia is defined as platelet count <150,000/mm³ or a 25% reduction from baseline, typically detected early in the illness 1, 2
• Microangiopathic hemolytic anemia is characterized by the presence of schistocytes, burr cells, or helmet cells on peripheral blood smear 1, 2
• Hemoglobin levels are decreased, though near-normal values may indicate dehydration masking the anemia 1
• A negative direct and indirect Coombs test confirms non-immune hemolysis, distinguishing HUS from autoimmune hemolytic conditions 1, 2

Hemolysis Markers

• Elevated lactate dehydrogenase (LDH) is a consistent finding associated with red blood cell destruction 1, 2
• Reduced or absent haptoglobin levels result from hemoglobin binding and clearance 1, 2
• Elevated indirect (unconjugated) bilirubin reflects increased red blood cell breakdown 1, 2

Renal Function Abnormalities

• Elevated serum creatinine: ≥1.0 mg/dL in children <13 years or ≥1.5 mg/dL in individuals ≥13 years, or ≥50% increase over baseline 1
• Urinalysis reveals hematuria and/or proteinuria 1, 2
• Blood urea nitrogen (BUN) is elevated, with azotemia present in all cases 3

Additional Laboratory Findings

Electrolyte Disturbances

• Hyperkalemia occurs in approximately 55% of cases 3
• Hyponatremia or hypernatremia may be present depending on fluid status 3

White Blood Cell Count

• High WBC count with neutrophil predominance often occurs in STEC O157 infections that progress to HUS 1

Complement Studies (for Atypical HUS)

• C3, C4, CH50 (classical pathway), and AP50 (alternative pathway) should be measured when atypical HUS is suspected 1
• Elevated sC5b-9 indicates complement overactivation 4
• Approximately 40-50% of atypical HUS cases have normal complement levels despite disease activity 1

Critical Differential Testing

• ADAMTS13 activity must be tested urgently when thrombotic microangiopathy is confirmed, as severely deficient activity (<10 IU/dL) indicates thrombotic thrombocytopenic purpura (TTP) requiring immediate plasmapheresis rather than HUS management 1, 2

Etiologic Testing

• Stool culture and Shiga toxin testing (or genes encoding them) should be performed to identify STEC, particularly E. coli O157:H7 1, 2
• If stool testing is negative but HUS is present, serologic testing for STEC (CDC-validated testing for serogroups O157 and O111) may aid diagnosis 1, 2

Important Clinical Caveats

• Not all three clinical signs may be clearly present at disease onset in up to 50% of atypical HUS cases 1
• The absence of schistocytes on peripheral smear should not exclude early diagnosis due to low sensitivity, though their presence is highly specific 1, 2
• Serial monitoring is essential, as a single CBC is insufficient to define risk—daily hemoglobin and platelet counts should be obtained during the at-risk period (days 1-14) 1
• Evidence of disseminated intravascular coagulation (DIC) may be present in severe cases, with decreased fibrinogen, increased fibrinogen degradation products, and deranged clotting studies 3