From the Guidelines
Diagnosis of Hemolytic Uremic Syndrome (HUS) should be suspected in patients presenting with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, and confirmed through a combination of clinical findings and laboratory tests, including a peripheral blood smear for red blood cell fragmentation, as recommended by the 2017 Infectious Diseases Society of America clinical practice guidelines 1. To diagnose HUS, the following laboratory tests are essential:
- Complete blood count to show hemoglobin reduction and thrombocytopenia
- Peripheral blood smear to reveal schistocytes (fragmented red blood cells)
- Elevated lactate dehydrogenase (LDH)
- Decreased haptoglobin
- Elevated reticulocyte count
- Negative Coombs test
- Renal function tests to show elevated blood urea nitrogen (BUN) and creatinine levels
- Stool cultures or PCR for Shiga toxin-producing E. coli in typical HUS (STEC-HUS)
- Genetic testing for complement pathway mutations and measurement of ADAMTS13 activity to rule out thrombotic thrombocytopenic purpura (TTP) in atypical HUS Frequent monitoring of hemoglobin and platelet counts, electrolytes, and blood urea nitrogen and creatinine is crucial to detect hematologic and renal function abnormalities that are early manifestations of HUS, as recommended by the guidelines 1. The diagnosis of HUS is critical, as prompt intervention can significantly improve outcomes by preventing further organ damage, particularly to the kidneys. In patients with diagnosed E. coli O157 or another STEC infection, especially those that produce Shiga toxin 2 or are associated with bloody diarrhea, frequent monitoring of hemoglobin and platelet counts, electrolytes, and blood urea nitrogen and creatinine is recommended to detect early manifestations of HUS 1.
From the Research
Diagnosis of HUS
- Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury 2.
- The diagnosis of HUS involves identifying the underlying thrombotic microangiopathy trigger, which can be challenging but is imperative for personalized disease-specific treatment 3.
- HUS is classified into two subgroups: typical HUS, which usually occurs after a prodrome of diarrhea, and atypical (sporadic) HUS, which is not associated with diarrhea 4.
- Atypical HUS is a rare variant of thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment, and is associated with poor clinical outcomes 5.
Diagnostic Approaches
- The classical clinical triad of HUS is microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury associated with endothelial cell injury 6.
- Identifying the underlying cause of HUS is crucial for directing therapy, and may involve testing for genetic mutations in the alternative complement pathway or other underlying conditions 6, 4.
- Diagnosis of aHUS may involve genetic testing to identify abnormalities in the complement alternative pathway, as well as testing for autoantibodies against specific complement factors 5.
Challenges in Diagnosis
- The rarity of aHUS makes it challenging to diagnose and treat, and data from multiple patient registries are important for improving clinical practice 6.
- The high cost of anti-complement therapies, such as eculizumab, can limit their use in low-income countries, making diagnosis and treatment of HUS even more challenging 3.