Absolute Criteria and Indications for Exchange Transfusion in Neonatal Jaundice
Exchange transfusion should be performed when total serum bilirubin (TSB) reaches specific hour- and risk-stratified thresholds despite intensive phototherapy, or immediately if any signs of acute bilirubin encephalopathy appear regardless of bilirubin level. 1, 2, 3
TSB Thresholds for Exchange Transfusion
The decision for exchange transfusion is based on gestational age-specific TSB levels that vary by risk category 1:
For Term Infants (≥38 weeks gestation):
- Low risk infants: TSB ≥25 mg/dL (428 μmol/L) 1
- Medium risk infants: TSB ≥20-25 mg/dL depending on age in hours 1
- High risk infants (isoimmune hemolytic disease, G6PD deficiency): Lower thresholds apply 1
For Late Preterm Infants (35-37 6/7 weeks):
- 35-37 6/7 weeks with risk factors: TSB thresholds are 2-3 mg/dL lower than term infants 1
- Higher risk or hemolytic disease: Even lower thresholds apply 1
Critical Action Point:
If TSB is at or approaching exchange level, immediately send blood for type and crossmatch while initiating escalation of care 1.
Bilirubin-to-Albumin (B/A) Ratio as Additional Criterion
The B/A ratio should be used together with, but not in lieu of, TSB levels as an additional factor 1:
| Risk Category | B/A Ratio Threshold (mg/dL per g/dL) |
|---|---|
| Infants ≥38 weeks | 8.0 |
| Infants 35-36 6/7 weeks (well) or ≥38 weeks with higher risk | 7.2 |
| Infants 35-37 6/7 weeks with higher risk or hemolytic disease | 6.8 |
The B/A ratio correlates with unbound bilirubin and helps identify infants at higher risk for neurotoxicity, particularly in sick infants where albumin binding is impaired 1.
Absolute Indication: Acute Bilirubin Encephalopathy
Immediate exchange transfusion is mandatory if any signs of acute bilirubin encephalopathy are present, regardless of TSB level 2, 4, 3. These signs include:
- Intermediate stage (BIND-M score 3-6): Moderate lethargy, hypotonia, high-pitched cry 3
- Advanced stage (BIND-M score 7-12): Severe lethargy, inability to feed, fever, hypertonia with retrocollis and opisthotonus 3
The BIND-M scoring protocol demonstrates significant association with need for exchange transfusion and supports immediate intervention for intermediate-to-advanced ABE 3.
Escalation of Care Protocol
When TSB is within 0-2 mg/dL below exchange threshold, immediate escalation is required 1:
- Initiate intensive phototherapy emergently with irradiance ≥30 μW/cm²/nm in blue-green spectrum (430-490 nm) 1, 5
- Provide intravenous hydration to correct any fluid deficit 1
- Line bassinet/incubator with aluminum foil or white material to maximize surface area exposure 1
- Measure TSB every 2 hours until escalation period ends 1
- Consult neonatology for NICU transfer if TSB continues rising despite intensive phototherapy 1
Risk Factors Requiring Lower Thresholds
Exchange transfusion thresholds are lowered in the presence of neurotoxicity risk factors 1:
- Isoimmune hemolytic disease (ABO, Rh incompatibility with positive DAT) 1
- G6PD deficiency (particularly if TSB rises suddenly or despite intensive phototherapy) 1
- Gestational age 35-37 6/7 weeks 1
- Sepsis or clinical instability 1
- Acidosis 6
- Hypoalbuminemia (<3.0 g/dL) 1
During Birth Hospitalization vs. Readmission
For infants still hospitalized: Exchange transfusion is recommended if TSB rises to threshold levels despite intensive phototherapy 1.
For readmitted infants: If TSB is above exchange level, repeat TSB measurement every 2-3 hours and consider exchange if TSB remains above indicated levels after 6 hours of intensive phototherapy 1.
Critical Pitfalls to Avoid
- Do NOT subtract direct/conjugated bilirubin from TSB when making exchange transfusion decisions, even in cholestatic jaundice 1
- Do NOT delay exchange transfusion waiting for phototherapy response if signs of encephalopathy are present 2, 3
- Do NOT rely on visual assessment alone to determine severity; always measure TSB 2, 7
- Recognize that G6PD levels may be falsely elevated during active hemolysis, potentially obscuring diagnosis 1
Procedure Requirements
Exchange transfusion carries significant risks with mortality of approximately 3 per 1000 procedures and morbidity in up to 5% of cases (apnea, bradycardia, thrombosis, necrotizing enterocolitis) 1. Therefore: