From the Guidelines
To check for unconjugated hyperbilirubinemia, order a fractionated bilirubin test (also called a direct/indirect bilirubin test) as it is the most accurate method to differentiate between conjugated and unconjugated bilirubin levels in the blood. This test is crucial for diagnosing conditions such as hemolysis, Gilbert's syndrome, or Crigler-Najjar syndrome, which are associated with elevated unconjugated bilirubin levels 1.
Key Points to Consider
- A total bilirubin test should be ordered simultaneously to provide a complete picture of the patient's bilirubin levels.
- The fractionated bilirubin test measures both conjugated (direct) and unconjugated (indirect) bilirubin levels, allowing for differentiation between the two forms.
- Normal unconjugated bilirubin is typically less than 1.0 mg/dL (17 μmol/L), with elevated levels suggesting conditions like hemolysis, Gilbert's syndrome, or Crigler-Najjar syndrome.
- The test requires a simple blood draw, usually from a vein in the arm, and fasting may be recommended for 4-8 hours before the test for more accurate results.
Clinical Significance
Unconjugated bilirubin is fat-soluble and cannot be excreted in urine, so it appears elevated when there's either increased production from red blood cell breakdown or decreased liver uptake/conjugation. This differentiation is crucial for proper diagnosis and treatment planning, as the causes and management of unconjugated versus conjugated hyperbilirubinemia differ significantly 1.
Recent Guidelines
According to the most recent guidelines, total serum bilirubin (TSB) should be used as the definitive diagnostic test to guide all interventions, and fractionated bilirubin testing can help identify the underlying cause of hyperbilirubinemia 1.
From the Research
Lab Tests for Unconjugated Hyperbilirubinemia
- The lab test used to check for unconjugated hyperbilirubinemia is the measurement of total serum bilirubin (TSB) levels, as well as the calculation of indirect bilirubin by subtracting direct bilirubin from total bilirubin 2, 3, 4.
- However, it has been found that the calculated indirect bilirubin value may not always be accurate, especially in cases of cholestasis, and a more reliable method such as measuring unconjugated bilirubin using a multilayered slide may be needed 5.
- Other parameters such as free unconjugated bilirubin (freeUCB) levels and bilirubin/albumin (B/A) ratios may also be useful in assessing the risk of bilirubin neurotoxicity, but their use in clinical practice is not yet widely established and requires further study 6.
Measurement of Unconjugated Bilirubin
- Unconjugated bilirubin can be measured using a multilayered slide, which has been found to be more accurate than the calculated indirect bilirubin value in cases of cholestasis 5.
- Other methods for measuring unconjugated bilirubin, such as high-performance liquid chromatography (HPLC), may also be used, but are not yet widely available in clinical practice 5.
Clinical Significance
- The measurement of unconjugated bilirubin is important in the diagnosis and management of unconjugated hyperbilirubinemia, as it can help identify infants at risk of bilirubin neurotoxicity and guide treatment decisions 2, 3, 4.
- Further study is needed to establish the clinical utility of parameters such as freeUCB levels and B/A ratios in the management of unconjugated hyperbilirubinemia 6.