What lab test should be ordered to measure direct bilirubin?

Laboratory Testing for Direct Bilirubin

To measure direct bilirubin, order a "Total and Direct Bilirubin" test, which will provide both the total bilirubin and direct (conjugated) bilirubin fractions. 1

Understanding Direct Bilirubin Testing

• Direct bilirubin testing is performed as part of a comprehensive bilirubin panel that includes both total and direct (conjugated) bilirubin measurements 1
• The direct bilirubin fraction includes both conjugated bilirubin and delta bilirubin (which is bound to albumin) 1
• This test is particularly important for identifying cholestasis and differentiating between different causes of hyperbilirubinemia 1

Clinical Indications for Direct Bilirubin Testing

• Jaundice present at or beyond 3 weeks of age 1
• Sick infants with jaundice 1
• Infants receiving phototherapy or with rapidly rising total serum bilirubin (TSB) levels 1
• Suspected cholestatic liver disease 1
• Evaluation of drug-induced liver injury (DILI) 1

Technical Aspects of Direct Bilirubin Measurement

• Direct bilirubin is typically measured using colorimetric methods where bilirubin reacts with diazotized sulfanilic acid in an acidic medium 2, 3
• More recent methods include enzymatic assays using bilirubin oxidase 4
• The accuracy of direct bilirubin measurement can be affected by the specific methodology used 5
• Modern automated chemistry analyzers can perform this test with as little as 20 μL of serum, which is particularly beneficial for testing infants 2

Interpretation of Results

• Direct bilirubin levels ≥10 μmol/L (approximately 0.6 mg/dL) should be considered abnormal when total bilirubin is also elevated 6
• In drug-induced liver injury, the direct bilirubin fraction is usually greater than 35% of the total bilirubin 1
• In Gilbert's syndrome (a benign condition), conjugated bilirubin should be less than 20-30% of the total bilirubin 1
• When evaluating jaundiced infants, it's important to interpret bilirubin levels according to the infant's age in hours 1

Important Considerations

• Do not subtract direct bilirubin from total bilirubin when making clinical decisions about phototherapy or exchange transfusion in newborns 1
• In cases where direct bilirubin is 50% or more of the total bilirubin, consultation with a specialist is recommended 1
• If the etiology of prolonged hyperbilirubinemia is uncertain, consider requesting a breakdown of the direct bilirubin fraction into conjugated and delta bilirubin components 1
• Be aware that some direct bilirubin measurement methods may yield falsely high values, particularly when high levels of unconjugated bilirubin are present 5

Follow-up Testing When Direct Bilirubin is Elevated

• For elevated direct bilirubin in infants: perform urinalysis, urine culture, and evaluate for sepsis if clinically indicated 1
• For jaundice at or beyond 3 weeks: check results of newborn thyroid and galactosemia screening 1
• For suspected cholestatic liver disease: evaluate for causes of cholestasis 1
• For suspected drug-induced liver injury: monitor liver function tests and consider drug interruption 1