Diagnosis and Management of Hemolytic Uremic Syndrome (HUS)

Core Diagnostic Criteria

The diagnosis of HUS requires all three components of the classic triad: microangiopathic hemolytic anemia, thrombocytopenia, and acute renal involvement, with immediate laboratory testing required to distinguish between atypical HUS (aHUS), STEC-HUS, and thrombotic thrombocytopenic purpura (TTP) to guide life-saving treatment 1, 2
Microangiopathic hemolytic anemia is confirmed by negative direct Coombs test, elevated LDH, reduced haptoglobin, and elevated indirect bilirubin 1, 2
Thrombocytopenia is defined as platelet count <150,000/mm³ or a 25% reduction from baseline 1, 3
Renal involvement is evidenced by hematuria, proteinuria, and/or elevated creatinine levels 1, 2

When any patient presents with anemia plus thrombocytopenia in the emergency setting, immediately order complete blood count with peripheral blood smear for schistocytes, haptoglobin, LDH, and indirect bilirubin levels, direct Coombs test, ADAMTS13 activity, stool testing for verocytotoxin-producing E. coli (VTEC/STEC), creatinine, and urinalysis for hematuria and proteinuria 1, 2
Schistocytes >1% favor TMA diagnosis, but their absence should NOT exclude early TMA diagnosis due to low test sensitivity 1, 2, 3

ADAMTS13 activity <10 IU/dL indicates TTP 1
STEC-HUS is diagnosed by positive stool VTEC testing AND diarrhea onset 4-5 days before HUS symptoms 1
aHUS is diagnosed by negative VTEC testing OR short diarrhea period OR simultaneous onset of diarrhea and HUS 1, 3
Key timing distinction: STEC-HUS typically appears 4-5 days after diarrhea onset; if diarrhea and HUS appear simultaneously or with shorter interval, suspect aHUS 1

In pediatric patients, particularly newborns, HUS may be present even if one of the three parameters is absent in up to 50% of cases at disease onset 2, 3
In infants <1 year old, test for complement-unrelated genes (DGKE, WT1) 1
Consider methylmalonic acidemia with homocystinuria (MMACHC) causing cobalamin deficiency 1, 4

If neurological symptoms present (occurs in 10-20% of aHUS cases), obtain neurology consultation, perform electroencephalogram (EEG), and brain MRI with FLAIR and T2-weighted sequences 1, 4
Look for bilateral symmetric hyperintensities in basal ganglia, cerebral peduncles, caudate nuclei, putamen, thalami, hippocampi, insulae, or brainstem 1
Neurological manifestations to recognize: motor symptoms, generalized weakness, vision changes, seizures, encephalopathy 1

Do not delay treatment while awaiting confirmatory testing - aHUS is a medical emergency requiring immediate intervention 2