Obstetric Topic 49. Hemolytic disease. Rh isoimmunisation

I. Rh Alloimmunization

Definition

• Rh alloimmunization: RhD-negative mother becomes sensitized against RhD-positive fetal RBCs.
• Sensitization: fetal RBCs enter maternal blood → maternal anti-D IgG formation.
• Hemolytic disease of fetus/newborn (HDFN): maternal IgG crosses placenta → fetal RBC hemolysis.

Pathophysiology

• Hemolysis → anemia → hypoxia → extramedullary hematopoiesis.
• Severe anemia → high-output heart failure → hydrops fetalis → fetal death.
• Hydrops fetalis: fluid in ≥2 compartments, e.g. skin edema, ascites, pleural/pericardial effusion or placental edema.
• First sensitizing pregnancy: often mild; later RhD-positive pregnancies are more dangerous because memory B cells rapidly produce IgG.
• Important antibodies causing HDFN: anti-D, anti-Kell, anti-Duffy.
• Usually harmless: anti-Lewis. Memory aid: D deadly, Kell kills, Duffy dies, Lewis lives.

II. Sensitizing Events and Screening

Fetomaternal Hemorrhage Events

• Delivery: vaginal or cesarean.
• Pregnancy loss: miscarriage/abortion, incomplete abortion or ectopic pregnancy.
• Bleeding: threatened abortion, placenta previa bleeding or placental abruption.
• Procedures/trauma: CVS, amniocentesis, cordocentesis/fetal surgery, abdominal trauma or external cephalic version.

Screening

• All pregnant patients: ABO/RhD type + antibody screen at first prenatal visit.
• RhD-negative, unsensitized patient: repeat antibody screen around 28 weeks before prophylaxis.
• Positive antibody screen → identify antibody + quantify titer.
• Critical or rising titer, often ≥1:16 → risk of significant fetal anemia.
• Anti-Kell: severe disease may occur at lower titers because it suppresses fetal erythropoiesis.

III. Unsensitized RhD-Negative Mother

Anti-D Immunoglobulin Prophylaxis

1. 28 weeks: if antibody screen is negative → give anti-D immunoglobulin.
2. After delivery: test newborn RhD status.
3. RhD-negative newborn → no postpartum anti-D.
4. RhD-positive newborn → anti-D within 72 h postpartum.
5. Any sensitizing event → anti-D as soon as possible.

• Kleihauer-Betke test/flow cytometry: estimates fetomaternal hemorrhage volume → adjust dose after large hemorrhage.
• Anti-D prevents sensitization only; it does not treat an already sensitized mother.

IV. Sensitized Pregnancy

Monitoring Algorithm

1. Identify antibody and baseline titer.
2. Titer stable below critical level and no previous affected fetus → repeat titers about every 4 weeks.
3. Critical/rising titer or previous affected fetus → determine fetal antigen risk and start fetal anemia surveillance.
4. Serial US: hydrops, placentomegaly, hepatosplenomegaly, ascites.
5. MCA Doppler: middle cerebral artery peak systolic velocity (MCA-PSV) screens for anemia.
   • MCA-PSV >1.5 MoM → moderate/severe fetal anemia likely.
6. Hydrops or MCA-PSV >1.5 MoM → fetal therapy center; cordocentesis/PUBS if delivery is not safer.

Treatment and Delivery

• PUBS/cordocentesis: confirms fetal Hb/Hct and allows intrauterine transfusion.
• Early severe anemia → intrauterine transfusion.
• Late gestation or worsening condition → delivery may be safer than fetal therapy.
• Stable mild disease → plan delivery around 37-38 weeks.
• Preterm delivery likely → antenatal corticosteroids; magnesium sulfate if very preterm.

V. Newborn and Differential

Neonatal Management

• At birth: cord blood RhD type, direct antiglobulin test (Coombs), Hb/Hct, bilirubin.
• Risks: anemia, jaundice, kernicterus, heart failure, hydrops.
• Treatment: phototherapy, selected IVIG, RBC transfusion or exchange transfusion if severe.

Non-Immune Differential of Fetal Anemia/Hydrops

• Infections: parvovirus B19, CMV, syphilis.
• Twin-to-twin transfusion, fetal arrhythmia/heart disease, alpha-thalassemia major, metabolic disease or malformations.