Calculating Fractionated Bilirubin from Direct Bilirubin
Fractionated bilirubin can be calculated by determining the percentage of conjugated (direct) bilirubin relative to total bilirubin, with hyperbilirubinemia classified as predominantly unconjugated when conjugated bilirubin is <20-30% of total bilirubin, and predominantly conjugated when it is >35% of total bilirubin. 1
Calculation Method
To calculate fractionated bilirubin from direct bilirubin:
- Measure both direct (conjugated) bilirubin and total bilirubin levels
- Calculate the percentage: (Direct bilirubin ÷ Total bilirubin) × 100%
- Interpret based on the following classification:
| Percentage of Conjugated Bilirubin | Type of Hyperbilirubinemia |
|---|---|
| <20-30% | Predominantly Unconjugated |
| >35% | Predominantly Conjugated |
Clinical Significance of Fractionation
The fractionation of bilirubin has important diagnostic implications:
Predominantly unconjugated hyperbilirubinemia (<20-30% conjugated) suggests:
- Gilbert's syndrome
- Hemolytic disorders
- Neonatal jaundice
Predominantly conjugated hyperbilirubinemia (>35% conjugated) suggests:
- Biliary obstruction
- Hepatocellular disease
- Cholestatic disorders
Laboratory Considerations
Several important factors affect the accuracy of bilirubin fractionation:
- Different laboratory methods may yield varying results, especially with mild hyperbilirubinemia (<5 mg/dL) 2
- High-performance liquid chromatography (HPLC) is considered the gold standard for bilirubin fractionation but is impractical for routine use 3
- Direct spectrophotometry provides measurements of unconjugated bilirubin and the sum of bilirubin conjugates, offering similar information to HPLC 3
Clinical Pitfalls to Avoid
- Do not rely solely on bilirubin fractionation for diagnosis without considering other liver function tests and clinical context 1
- Be aware that direct bilirubin measurements include both conjugated bilirubin and delta bilirubin (albumin-bound bilirubin) 4
- Laboratory variability can significantly impact results, particularly with total bilirubin levels below 5 mg/dL 2
- Fractionation is most useful when hepatobiliary disease has been established as unlikely beforehand 5
Additional Considerations
- Delta bilirubin (albumin-bound bilirubin) can comprise 8-90% of total bilirubin in patients with hepatocellular and cholestatic jaundice 4
- Delta bilirubin persists longer in circulation due to albumin binding, which can delay the resolution of jaundice 4
- For comprehensive evaluation, bilirubin fractionation should be interpreted alongside other laboratory tests including complete blood count, liver enzymes, and coagulation studies 1