From the Guidelines
Hemolytic Uremic Syndrome (HUS) is a disorder characterized by thrombotic microangiopathy with renal failure, hemolytic anemia, and severe thrombocytopenia, and its diagnosis requires laboratory testing including a complete blood count, stool cultures, and urinalysis, as well as clinical evaluation for signs and symptoms such as bloody diarrhea, decreased urination, and abdominal pain 1.
Key Features of HUS
- Hemolytic anemia (destruction of red blood cells)
- Thrombocytopenia (low platelet count)
- Acute kidney injury
Diagnosis of HUS
- Laboratory testing:
- Complete blood count showing anemia with schistocytes (fragmented red blood cells) on peripheral blood smear
- Decreased platelet count
- Elevated creatinine and BUN indicating kidney dysfunction
- Stool cultures for Shiga toxin-producing Escherichia coli (STEC)
- Urinalysis showing hematuria and proteinuria
- Sometimes kidney biopsy in unclear cases
- Lactate dehydrogenase (LDH) is typically elevated while haptoglobin is decreased, confirming hemolysis
Clinical Evaluation
- Signs and symptoms:
- Bloody diarrhea
- Decreased urination or blood in the urine
- Abdominal pain, vomiting, and occasionally fever
- Pallor
- Small, unexplained bruises or bleeding from the nose and mouth
- Fatigue and irritability
- Confusion or seizures
- High blood pressure
- Swelling of the face, hands, feet, or entire body
- Diagnosis should be pursued urgently in patients presenting with bloody diarrhea followed by pallor, decreased urine output, petechiae, or unusual bleeding, particularly in children, as recommended by the Infectious Diseases Society of America 1.
Importance of Early Diagnosis
- Early diagnosis is crucial as HUS can lead to serious complications including kidney failure requiring dialysis, neurological damage, and even death if not properly managed.
- Frequent monitoring of hemoglobin and platelet counts, electrolytes, and blood urea nitrogen and creatinine is recommended to detect hematologic and renal function abnormalities that are early manifestations of HUS and precede renal injury 1.
From the FDA Drug Label
Hemolytic Uremic Syndrome (HUS) is not directly defined in the provided drug label, but it is mentioned as a condition being treated with eculizumab. The diagnosis of HUS is not explicitly described in the label, but parameters such as platelet count, LDH (lactate dehydrogenase) levels, serum creatinine levels, and eGFR (estimated glomerular filtration rate) are mentioned as being used to assess disease activity and response to treatment in patients with atypical HUS (aHUS). Key diagnostic criteria mentioned in the label for patients enrolled in the studies include:
- Platelet count < lower limit of normal range (LLN)
- Evidence of hemolysis, such as elevation in serum LDH above the upper limits of normal
- Serum creatinine level ≥97 percentile for age without the need for chronic dialysis
- ADAMTS13 activity level above 5% It is essential to note that the label does not provide a comprehensive definition or diagnostic criteria for HUS, and diagnosis should be based on a combination of clinical presentation, laboratory tests, and other diagnostic evaluations 2.
From the Research
Definition of Hemolytic Uremic Syndrome (HUS)
- Hemolytic Uremic Syndrome (HUS) is characterized by the simultaneous occurrence of nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure 3, 4, 5, 6, 7.
- It is a clinical syndrome defined by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury 5, 6, 7.
Diagnosis of HUS
- The diagnosis of HUS is based on clinical, pathological, hematological, and biochemical features, as well as epidemiology and pathogenetic mechanisms 4.
- Laboratory data shows hemolytic anemia with schistocytes, elevated LDH values, thrombocytopenia, and elevated creatinine concentrations 3.
- Renal biopsy may show thrombotic microangiopathy, with varying degrees of glomerular, arteriolar, and cortical involvement 3.
- Biochemical, microbiological, immunological, and genetic investigations are also important in diagnosing HUS and distinguishing between different subtypes 4, 5, 6, 7.
Subtypes of HUS
- HUS can be classified into different subtypes, including:
- STEC-HUS (associated with Shiga toxin-producing Escherichia coli) 4, 5, 6, 7.
- Atypical HUS (aHUS, associated with complement dysregulation due to mutations or autoantibodies) 4, 5, 6.
- Secondary HUS (arising from cancer, chemotherapy, solid organ and hematopoietic stem cell transplant, pregnancy, or autoimmune disorders) 6.
- Each subtype has distinct clinical, pathological, and genetic features, and requires tailored treatment and management approaches 4, 5, 6, 7.