From the Guidelines
In atypical hemolytic uremic syndrome (aHUS), the diagnostic work-up should include a comprehensive set of tests, prioritizing those that help distinguish aHUS from other thrombotic microangiopathies and guide treatment decisions, as outlined in the most recent and highest quality study 1. The initial testing should include:
- Complete blood count with peripheral smear to look for schistocytes, thrombocytopenia, and anemia
- Renal function tests, such as serum creatinine, to assess kidney function
- Liver function tests to evaluate for any liver involvement
- Lactate dehydrogenase (LDH) and haptoglobin to assess for hemolysis
- Urinalysis to evaluate for any urinary abnormalities Specific tests for aHUS include:
- ADAMTS13 activity to rule out thrombotic thrombocytopenic purpura (TTP) 1
- Complement levels, such as C3, C4, and CH50, to assess for complement activation
- Genetic testing for mutations in complement regulatory proteins, such as CFH, CFI, MCP, C3, CFB, and THBD, as these are commonly associated with aHUS 1
- Anti-factor H antibodies, particularly in children, as these can be associated with aHUS Additional tests that may be necessary include:
- Stool cultures and Shiga toxin testing to exclude typical HUS
- Coagulation studies to evaluate for any coagulopathy
- Direct Coombs test to assess for any immune-mediated hemolysis
- Antiphospholipid antibodies to evaluate for any underlying antiphospholipid syndrome
- Kidney biopsy may be necessary in unclear cases to provide a definitive diagnosis These tests are crucial because aHUS is a complement-mediated disorder with high mortality if untreated, and early diagnosis enables prompt initiation of complement inhibitor therapy, such as eculizumab or ravulizumab, which can significantly improve outcomes 1.
From the FDA Drug Label
In Study C10-004, patients with aHUS received SOLIRIS and were required to have ADAMTS13 activity level above 5%; observed range of values in the trial were 28%-116%. In Study C10-003, patients with aHUS received SOLIRIS and were required to have ADAMTS13 activity level above 5%; observed range of values in the trial were 38%-121%. In Study C08-002A/B, patients with aHUS received SOLIRIS and were required to have ADAMTS13 activity level above 5%; observed range of values in the trial were 70%-121%.
The test to be done in atypical HUS is ADAMTS13 activity level. This test is used to differentiate aHUS from other types of thrombotic microangiopathy, such as thrombotic thrombocytopenic purpura (TTP).
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From the Research
Diagnostic Tests for Atypical HUS
To diagnose atypical Hemolytic Uremic Syndrome (aHUS), several tests can be performed, including:
- Microangiopathic hemolysis tests, such as schistocytes, elevated lactate dehydrogenase, low haptoglobin, and low hemoglobin 3
- Thrombocytopenia tests 3, 4
- ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) enzyme activity measurement to distinguish aHUS from thrombotic thrombocytopenic purpura (TTP) 3, 4
- Testing for Shiga toxin-producing E. coli to exclude Shiga toxin-producing Escherichia coli (STEC)-HUS 4
- Complement genetic variants and autoantibodies tests to identify the etiology of the dysregulated complement system 5
- Antigenic, functional, and biomarker analyses to establish the significance of genetic variants and determine the duration of treatment 5
Laboratory Signs and Symptoms
The laboratory signs and symptoms of aHUS include:
- Microangiopathic hemolysis 3, 4
- Thrombocytopenia 3, 4
- Organ system involvement, such as acute kidney injury 3, 4, 6
- End-organ injury, such as anemia and thrombocytopenia 5, 7
Differential Diagnosis
aHUS can be distinguished from other thrombotic microangiopathies, such as: