Diagnostic Approach to Hemolytic Uremic Syndrome (HUS) and Thrombotic Microangiopathy (TMA)

Initial Evaluation and Differential Diagnosis

The American College of Physicians recommends distinguishing between atypical HUS (aHUS), thrombotic thrombocytopenic purpura (TTP), STEC-HUS, and secondary causes of TMA when a patient presents with microangiopathic hemolytic anemia, thrombocytopenia, and renal involvement 1, 2
The European Renal Association suggests that TTP is distinguished by severely deficient ADAMTS13 activity (<10 IU/dL) 1, 2
The American Society of Nephrology notes that STEC-HUS typically follows bloody diarrhea by 4-5 days 3, 2
The International Society of Nephrology recommends considering systemic lupus erythematosus/lupus nephritis, antiphospholipid syndrome, and disseminated intravascular coagulation (DIC) as secondary causes of TMA 4

The American College of Physicians recommends obtaining a complete blood count with platelet count, peripheral blood smear, LDH, haptoglobin, indirect bilirubin, and direct Coombs test to confirm TMA 1, 2
The European Renal Association suggests performing ADAMTS13 activity assay, stool culture, and Shiga toxin testing to distinguish among TMA causes 1, 2
The American Society of Nephrology notes that complement studies, genetic screening, and anti-factor H antibodies may be necessary for aHUS diagnosis 5, 6

The American College of Physicians recommends initiating eculizumab within 4-8 hours of suspected aHUS diagnosis, as delays are associated with worse outcomes 5
The European Renal Association suggests providing supportive care, including IV fluid resuscitation, monitoring of hemoglobin, platelets, and renal function, and blood pressure control 4, 6
The American Society of Nephrology notes that plasma exchange may be considered for TTP, but is less effective in aHUS compared to eculizumab 2, 6