Management of Elevated Bilirubin
The appropriate management of elevated bilirubin requires determining whether the hyperbilirubinemia is predominantly conjugated or unconjugated through fractionated bilirubin levels and comprehensive liver function tests to guide targeted interventions. 1
Initial Diagnostic Evaluation
- Obtain fractionated bilirubin levels to determine if hyperbilirubinemia is predominantly conjugated or unconjugated 1
- Order complete liver function tests including ALT, AST, ALP, GGT, and albumin to assess for liver injury and synthetic function 1
- Measure prothrombin time (PT) and INR to evaluate liver synthetic capacity 2, 1
- Perform complete blood count with peripheral smear to assess for hemolysis if unconjugated hyperbilirubinemia is suspected 1
Management Based on Bilirubin Type
Unconjugated Hyperbilirubinemia
- Consider Gilbert's syndrome, which is the most common cause of isolated elevated bilirubin 2, 3
- Evaluate for hemolysis with reticulocyte count, haptoglobin, and LDH if clinically indicated 1
- For neonates with unconjugated hyperbilirubinemia, consider phototherapy based on age-specific thresholds:
- For TSB levels ≥25 mg/dL in neonates, immediate admission for intensive phototherapy is required 1
Conjugated Hyperbilirubinemia
- Perform abdominal ultrasound as the initial imaging study to evaluate for biliary obstruction 1
- For infants with conjugated bilirubin >25 μmol/L, urgent referral to a pediatrician is essential 1
- Consider preoperative biliary drainage if total bilirubin is >12.8 mg/dL (218.75 μmol/L) and major hepatic resection is planned 1
- For suspected cholestatic disorders (e.g., choledocholithiasis), more advanced biliary imaging may be needed 5
Special Populations
Neonates
- Use bilirubin/albumin (B/A) ratio as an additional factor in determining the need for exchange transfusion, but not in lieu of the TSB level 2
- For isoimmune hemolytic disease, administer intravenous immunoglobulin (0.5-1 g/kg over 2 hours) if TSB is rising despite intensive phototherapy 1
- Exchange transfusion should be performed only by trained personnel in a neonatal intensive care unit 1
- Screen for G6PD deficiency in infants with significant hyperbilirubinemia, as they may develop sudden increases in TSB 2
Adults
- For adults with jaundice, evaluate for underlying causes including viral hepatitis, alcoholic liver disease, medication effects, and biliary obstruction 5
- In patients on antiviral therapy with hyperbilirubinemia, assess whether it's due to hemolysis, impaired bilirubin conjugation, or hepatocellular injury 6
Pitfalls to Avoid
- Do not subtract direct (conjugated) bilirubin from total bilirubin when making treatment decisions 1
- Avoid overinterpreting albumin concentrations as a marker of liver disease severity, as albumin can be reduced in many clinical situations including sepsis and malnutrition 2
- Do not delay appropriate imaging in patients with conjugated hyperbilirubinemia, as early identification of biliary obstruction is critical 1
- Remember that in the presence of hemolysis, G6PD levels can be elevated, which may obscure the diagnosis in the newborn period 2
- Be aware that standard laboratory tests for hemolysis have poor specificity and sensitivity 1
Red Flags Requiring Urgent Attention
- Jaundice presenting within the first 24 hours after birth 4
- Total serum bilirubin rising by more than 5 mg/dL (86 μmol/L) per day 4
- TSB level ≥25 mg/dL at any time in neonates 1
- Failure of bilirubin to decrease during phototherapy, suggesting hemolysis 2
- Signs of acute liver failure (encephalopathy, coagulopathy) accompanying hyperbilirubinemia 2