A 28-year-old woman in her third trimester of pregnancy undergoes routine antenatal blood typing. She is found to be Rh-negative. Which is the most common blood group antigen responsible for haemolytic disease of the newborn (HDN) in Rh-negative mothers?

Explanation

## Haemolytic Disease of the Newborn (HDN) — Rh Incompatibility ### Most Common Cause in Rh-Negative Mothers **Key Point:** The D antigen of the Rh system is the most immunogenic and most common cause of HDN in Rh-negative mothers who deliver Rh-positive infants. ### Pathophysiology 1. **Sensitization mechanism**: Rh-negative mother carrying an Rh-positive fetus 2. **Fetal-maternal haemorrhage (FMH)** occurs during pregnancy (especially third trimester) or delivery 3. **Maternal IgG antibodies** develop against D antigen (usually after first pregnancy) 4. **Subsequent pregnancies**: Maternal IgG crosses placenta → haemolysis in fetal RBCs → HDN ### Why D Antigen is Most Common | Feature | D Antigen | Other Rh Antigens | ABO Incompatibility | |---------|-----------|-------------------|--------------------| | **Immunogenicity** | Very high (most antigenic) | Lower | Lower | | **Frequency of sensitization** | ~15% after first Rh+ delivery | Rare | ~20% naturally occurring | | **Severity of HDN** | Severe (2nd+ pregnancies) | Mild | Mild (1st pregnancy) | | **Prevention** | Anti-D prophylaxis (RhIG) | Not routinely given | Not needed | | **Clinical significance** | Most important in transfusion | Occasional | Common but milder | **High-Yield:** D antigen accounts for **>90% of all Rh-incompatibility HDN cases**. This is why anti-D immunoglobulin (RhIG) is given to Rh-negative mothers at 28 weeks and within 72 hours of delivery. ### Clinical Pearl **Prevention strategy**: All Rh-negative non-sensitized pregnant women receive: - **500 IU/kg anti-D at 28 weeks** (standard dose: 500 IU in UK, 300 μg in US) - **Additional dose within 72 hours of delivery** if infant is Rh-positive or D-antigen status unknown - **Kleihauer–Betke test or flow cytometry** to quantify FMH and calculate additional RhIG needed ### Why Other Antigens Are Rare - **Kell antigen (K)**: Second most common cause of HDN after D, but much less frequent (~1% of cases) - **Duffy, MNS, Kidd antigens**: Rarely cause clinically significant HDN - **ABO incompatibility**: More common overall but causes milder disease (naturally occurring IgM antibodies, limited placental crossing) [cite:Harrison 21e Ch 183]