From the Guidelines
Hemolytic Uremic Syndrome (HUS) is a serious condition characterized by three key features: hemolytic anemia, thrombocytopenia, and acute kidney injury, and its diagnosis involves laboratory tests showing microangiopathic hemolytic anemia, thrombocytopenia, and evidence of kidney dysfunction. HUS is a disorder characterized by a form of thrombotic microangiopathy with renal failure, hemolytic anemia, and severe thrombocytopenia, as defined in the study by 1. The signs and symptoms of HUS can include bloody diarrhea, decreased urination or blood in the urine, abdominal pain, vomiting, and occasionally fever, among others.
Key Features of HUS
- Hemolytic anemia (destruction of red blood cells)
- Thrombocytopenia (low platelet count)
- Acute kidney injury The diagnosis of HUS involves laboratory tests, including:
- Complete blood count
- Peripheral blood smear to show schistocytes
- Reticulocyte count
- Haptoglobin levels (typically low)
- Lactate dehydrogenase (elevated)
- Urinalysis showing proteinuria and hematuria
- Stool cultures for STEC and Shiga toxin testing, as recommended by 1. Early diagnosis of HUS is crucial, as it can lead to serious complications, including kidney failure requiring dialysis, neurological damage, and even death if not promptly identified and treated. In atypical HUS, genetic testing and complement studies may be necessary, as stated in the study by 1. 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, as suggested by 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 a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytia, and acute kidney injury 3, 4, 5, 6, 7.
- It is defined by the simultaneous occurrence of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure 4.
- HUS represents a heterogeneous group of disorders with variable etiologies that result in differences in presentation, management, and outcome 5.
Causes of HUS
- The most common cause of HUS is Shiga toxin-producing Escherichia coli (EHEC) strains 3, 4, 6, 7.
- Other causes include Streptococcus pneumoniae infections, genetic dysregulation of the alternative complement pathway or coagulation cascade, and rarely, a hereditary disorder of cobalamin C metabolism 6.
- Atypical HUS (aHUS) is associated with complement dysregulation due to mutations or autoantibodies 4.
Diagnosis of HUS
- Diagnosis of HUS involves identifying the underlying thrombotic microangiopathy trigger, which can be challenging but is imperative for personalized disease-specific treatment 7.
- Biochemical, microbiological, immunological, and genetic investigations are used to diagnose HUS 4.
- Understanding the underlying mechanisms of the different subtypes of HUS enables tailoring of appropriate treatment and management 4.
Clinical Features of HUS
- HUS is characterized by the triad of haemolytic anaemia, thrombocytopenia, and acute renal failure 3.
- Patients with HUS may develop some degree of renal insufficiency, and approximately two-thirds of children with HUS will require dialysis therapy 3.
- Extra-renal involvement and haematological complications can occur in HUS 3.