From the Guidelines
The workup for hyperbilirubinemia should begin with a thorough history, physical examination, and laboratory tests to determine if the elevation is predominantly unconjugated (indirect) or conjugated (direct) bilirubin, with initial laboratory tests including complete blood count, liver function tests, fractionated bilirubin levels, and coagulation studies, as recommended by recent guidelines 1. The initial step in managing hyperbilirubinemia involves identifying the type of bilirubin elevation, which guides further testing and treatment.
- For unconjugated hyperbilirubinemia, additional tests may include reticulocyte count, peripheral blood smear, Coombs test, and genetic testing for conditions like Gilbert's syndrome.
- For conjugated hyperbilirubinemia, imaging studies such as ultrasound, CT, or MRCP should be performed to evaluate the biliary tract. Treatment depends on the underlying cause, with options including:
- Corticosteroids for autoimmune hemolytic anemia
- Splenectomy for hereditary spherocytosis
- No treatment for Gilbert's syndrome
- Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement or surgical intervention for obstructive causes
- Antiviral medications or discontinuation of the offending agent for hepatocellular causes like viral hepatitis or drug-induced liver injury. In neonatal hyperbilirubinemia, phototherapy is the mainstay of treatment for moderate elevations, while exchange transfusion is reserved for severe cases to prevent kernicterus, with the decision to discontinue phototherapy individualized based on the TSB level, cause of hyperbilirubinemia, and risk of rebound hyperbilirubinemia 1. The urgency and aggressiveness of treatment depend on the bilirubin level, rate of rise, and patient factors such as age and comorbidities.
- For infants receiving intensive phototherapy, TSB should be measured to verify efficacy, with the timing guided by the TSB trajectory and infant age 1.
- Care should be escalated when an infant’s TSB level is at or above the exchange transfusion threshold or within 0 to 2 mg/dL below the exchange transfusion threshold, with intravenous hydration and emergent intensive phototherapy initiated as soon as possible 1.
From the Research
Hyperbilirubinemia Workup
The workup for hyperbilirubinemia involves a combination of clinical evaluation, laboratory tests, and imaging studies.
- A comprehensive medical history, review of systems, and physical examination are essential for differentiating potential causes of hyperbilirubinemia 2, 3, 4.
- Initial laboratory evaluation should include:
- Bilirubin (total and fractionated) to determine whether the hyperbilirubinemia is conjugated or unconjugated 2, 3.
- Complete blood cell count to evaluate for hemolysis or other hematological disorders 2, 3.
- Liver function tests, such as aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, and alkaline phosphatase, to assess liver damage or dysfunction 2, 3.
- Prothrombin time and international normalized ratio to evaluate coagulation status 2, 3.
- Imaging studies, such as ultrasonography, computed tomography, or magnetic resonance cholangiopancreatography, may be necessary to evaluate the biliary tree and liver 2, 3, 4.
- In some cases, liver biopsy may be required to establish the diagnosis, prognosis, and management of the disease 2, 4.
Approach to Hyperbilirubinemia in Newborns
For newborns presenting with hyperbilirubinemia, the approach is slightly different.
- The American Academy of Pediatrics' clinical practice guidelines for "Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation" provide a helpful framework for evaluation and management 5.
- A careful history and physical examination are essential for assessing the risk factors associated with pathologic bilirubin levels 5.
- Indirect and direct bilirubin levels should be measured to evaluate the severity of hyperbilirubinemia 5.
- Transcutaneous bilirubin measuring devices may be used to non-invasively estimate bilirubin levels 5.
Diagnostic Algorithm
A diagnostic algorithm for hyperbilirubinemia should take into account the patient's clinical presentation, laboratory results, and imaging studies.
- The algorithm should consider the different causes of conjugated and unconjugated hyperbilirubinemia, such as hemolytic disorders, liver disease, and biliary obstruction 3, 6.
- The algorithm should also consider the patient's age, medical history, and other relevant factors to guide further evaluation and management 2, 3, 4.