What is the workup for hyperbilirubinemia (elevated bilirubin levels)?

From the Guidelines

The workup for hyperbilirubinemia should begin with a thorough history, physical examination, and laboratory tests to determine whether the elevated bilirubin is predominantly unconjugated (indirect) or conjugated (direct), with total and direct bilirubin levels being the definitive diagnostic test used to guide all interventions 1. The initial laboratory evaluation should include total and direct bilirubin levels, complete blood count, liver function tests (ALT, AST, alkaline phosphatase, GGT), and a peripheral blood smear.

• For unconjugated hyperbilirubinemia, additional tests may include reticulocyte count, haptoglobin, LDH, and direct Coombs test to evaluate for hemolysis.
• For conjugated hyperbilirubinemia, ultrasound of the liver and biliary tract is essential to assess for biliary obstruction. Further testing may include viral hepatitis serologies (HAV, HBV, HCV), autoimmune markers (ANA, ASMA, AMA), ceruloplasmin for Wilson's disease, iron studies, and alpha-1 antitrypsin levels. In neonates with hyperbilirubinemia, blood type and Rh factor of both mother and infant should be checked, along with direct Coombs testing to evaluate for hemolytic disease of the newborn, and the rate of rise of total serum bilirubin (TSB) concentrations should be used to identify possible hemolysis, with a rapid rate of rise (≥0.3 mg/dL per hour in the first 24 hours or ≥0.2 mg/dL per hour thereafter) being suggestive of ongoing hemolysis 1. If the diagnosis remains unclear after initial evaluation, more specialized tests such as MRCP, ERCP, liver biopsy, or genetic testing may be necessary. The specific workup should be tailored to the patient's age, clinical presentation, and pattern of bilirubin elevation, as the causes of hyperbilirubinemia range from benign conditions like Gilbert syndrome to serious disorders like biliary obstruction, hepatitis, or hemolytic anemia. Phototherapy is an essential intervention for severe hyperbilirubinemia, especially in neonates at high risk, and the timing of intervention is guided by performing serial measurements of TSB concentrations and screening for the presence of intrinsic risk factors for bilirubin neurotoxicity 1.

From the Research

Workup for Hyperbilirubinemia

• The workup for hyperbilirubinemia typically involves evaluating the level of bilirubin in the blood and assessing for any underlying conditions that may be contributing to the elevated levels 2.
• This may include tests such as blood type, Rh, Coombs' test, and glucose-6-phosphate dehydrogenase to detect hemolytic diseases 3.
• Transcutaneous bilirubin measurement can also be used to monitor the rise of serum bilirubin levels and distinguish between physiological and non-physiological hyperbilirubinemia 3.

Risk Factors for Hyperbilirubinemia

• Premature infants and those with hemolytic diseases are at higher risk of developing hyperbilirubinemia and kernicterus 3, 4.
• Infants who do not feed well and lose more than 10% of their body weight are also at increased risk 3.
• The American Academy of Pediatrics (AAP) recommends universal neonatal hyperbilirubinemia screening in newborns 35 weeks' gestational age or greater 4.

Treatment Options for Hyperbilirubinemia

• Phototherapy is a common treatment for hyperbilirubinemia, but it has potential short- and long-term adverse effects, including diarrhea and increased risk of seizures 4.
• Ursodeoxycholic acid (UDCA) has been shown to be effective in reducing bilirubin levels and may be used as an adjuvant to phototherapy 5, 6.
• Other pharmacological therapies, such as metalloporphyrins, clofibrate, and bilirubin oxidase, may also be effective in treating hyperbilirubinemia, but further research is needed to confirm their efficacy and safety 2.
• The AAP recommends using phototherapy only for newborns who exceed thresholds recommended by the current hour-specific phototherapy nomograms 4.