Epidemiology


Etiology


Pathophysiology


FeatureABO HDNRh HDN
FrequencyCommon (Most common cause of HDN)Rare (due to RhoGAM prophylaxis)
ScenarioMom Type O / Baby A or BMom Rh(-) / Baby Rh(+)
First Pregnancy?Yes (Pre-existing IgG)No (Requires sensitization)
SeverityMild (Jaundice within 24h)Severe (Hydrops fetalis, death)
MechanismIgG Anti-A/B cross placentaIgG Anti-D cross placenta
Smear/LabsSpherocytes, Weak CoombsStrong + Coombs, No spherocytes
PreventionNoneRhoGAM (Anti-D IgG)

1. The “Sponge” Effect (Antigen Distribution)

  • ABO Antigens: Found on RBCs AND other tissues (endothelium, platelets, fetal tissues).
    • Result: Maternal Anti-A/B antibodies crossing the placenta bind to these other tissues, effectively “soaking up” or neutralizing the antibodies before they can significantly destroy RBCs.
  • Rh Antigens: Found ONLY on RBCs.
    • Result: Every maternal Anti-D antibody that crosses the placenta targets red blood cells specifically, leading to focused and massive hemolysis.

2. Antigen Maturity

  • ABO Antigens: Weakly expressed on fetal RBCs compared to adult RBCs.
    • Result: Less binding sites for antibodies → less hemolysis.
  • Rh Antigens: Fully expressed at birth.
    • Result: High density of binding sites allows for rapid destruction (extravascular hemolysis in the spleen).

ABO incompatibility

  • Highest risk: mother with blood group O; newborn with blood group A or B
  • Maternal antibodies (anti-A and/or anti-B) against nonself antigens of the ABO system are present even if sensitization has not occurred, so fetal hemolysis may occur during the first pregnancy.
    • Combination of predominantly IgM antibodies and late expression of fetal ABO antigens reduces the chances of significant disease.

Clinical features


Diagnostics


Treatment

  • Prevention (Rh only): Administer Rho(D) immune globulin (RhoGAM) to Rh-negative mothers at 28 weeks gestation and within 72 hours of delivery of an Rh-positive infant.
    • Administered anti-D IgG binds to fetal Rh(+) RBCs in maternal circulation. Opsonized fetal RBCs are cleared by maternal splenic macrophages before maternal B-cells can recognize the D-antigen.
  • Fetal Tx: Intrauterine blood transfusion if severe anemia is detected via Doppler of the middle cerebral artery (↑ peak systolic velocity).
  • Neonatal Tx:
    • Phototherapy: Converts unconjugated bilirubin to water-soluble isomers.
    • Exchange Transfusion: Used if bilirubin levels are dangerously high despite phototherapy.