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Blood Bank

HDFN

Hemolytic Disease of the Fetus and Newborn (HDFN) is a condition where maternal antibodies destroy fetal/newborn red blood cells (RBCs). We’ll look at how it happens (Pathophysiology), how we find it (Detection), how we fix it (Treatment), and how we stop it before it starts (Prevention)

Pathophysiology: How HDFN Happens

  • Incompatibility & Sensitization: The mother lacks an RBC antigen (e.g., D, K, c) that the fetus inherits from the father. During pregnancy or delivery, fetal RBCs can enter the maternal circulation (Fetal-Maternal Hemorrhage - FMH). The mother’s immune system sees the fetal antigen as foreign and becomes sensitized, producing antibodies (initially IgM, then IgG) and memory cells
  • Subsequent Pregnancy & Anamnestic Response: In a later pregnancy with a fetus positive for the same antigen, even a small FMH triggers a rapid secondary immune response, producing large amounts of high-affinity IgG antibodies
  • Placental Transfer: Maternal IgG (the only Ig class that does this) actively crosses the placenta into the fetal circulation
  • Fetal Hemolysis: Maternal IgG binds to fetal RBCs possessing the target antigen. These antibody-coated cells are destroyed primarily by macrophages in the fetal spleen (Extravascular Hemolysis)
  • Fetal Consequences
    • Anemia: Leads to increased fetal RBC production (erythropoiesis), including in the liver/spleen (extramedullary hematopoiesis -> hepatosplenomegaly) and release of immature RBCs (erythroblastosis fetalis)
    • Bilirubin: Increased RBC breakdown produces bilirubin, but it’s cleared by the mother’s liver in utero
    • Hydrops Fetalis: In severe cases, profound anemia leads to heart failure, liver damage (low albumin), and massive fluid accumulation (edema, effusions) – often fatal if untreated
  • Neonatal Consequences
    • Hyperbilirubinemia: After birth, the immature newborn liver cannot cope with the ongoing bilirubin load from continued hemolysis (maternal IgG persists for weeks). Unconjugated bilirubin accumulates
    • Kernicterus: If bilirubin levels get too high, it crosses the blood-brain barrier, causing permanent brain damage
    • Anemia: Can persist for weeks/months after birth

Detection: Finding the Problem

  • Antenatal (During Pregnancy)
    • Screening (All Mothers): ABO/RhD typing, Antibody Screen (IAT) at first visit & ~28 weeks
    • If Screen Positive: Antibody Identification, Titers (for significant IgG)
    • Monitoring (If Clinically Significant Antibody)
      • Assess Fetal Antigen Status (Paternal testing, Fetal DNA from maternal plasma - cffDNA)
      • Monitor for Fetal Anemia: Middle Cerebral Artery Peak Systolic Velocity (MCA-PSV) Doppler (key non-invasive tool). Values >1.5 MoM suggest significant anemia
      • Selective Use: Amniotic fluid ΔOD 450, Fetal Blood Sampling (Cordocentesis)
  • Postnatal (After Birth)
    • Cord/Neonatal Blood: ABO/RhD typing, Direct Antiglobulin Test (DAT) (key diagnostic test - detects IgG/complement on newborn RBCs)
    • Monitoring: Hemoglobin/Hematocrit, Bilirubin levels (total & unconjugated), Reticulocyte count
    • Confirmation (If needed): Antibody elution from infant RBCs to identify coating antibody

Treatment: Managing the Condition

  • Antenatal
    • Intrauterine Transfusion (IUT): Mainstay for severe fetal anemia. Transfusion of compatible RBCs (O neg, Ag-neg for maternal Ab, irradiated, fresh, high Hct, CMV-safe, compatible with maternal plasma) directly into fetal circulation (umbilical vein)
    • Timing of Delivery: Balancing risks of prematurity vs. ongoing hemolysis
    • Adjunctive: Maternal IVIg or plasmapheresis (rarely used)
  • Postnatal
    • Hyperbilirubinemia Management
      • Phototherapy: Primary treatment; uses light to make bilirubin excretable
      • Exchange Transfusion: For severe cases; removes bilirubin, maternal antibody, and coated cells, while providing compatible blood
    • Anemia Management: Simple RBC transfusion if needed later; IVIg may reduce hemolysis

Prevention: Stopping Sensitization (Primarily for Anti-D)

  • Rh Immune Globulin (RhIG): The cornerstone! Concentrated IgG anti-D given to RhD-negative, unsensitized mothers
    • Mechanism: Passive anti-D clears fetal RhD+ cells from maternal circulation before the mother mounts her own active immune response
    • Administration
      • Routine antenatal dose (~28 weeks)
      • Routine postnatal dose (within 72 hrs of delivering an RhD+ infant)
      • After any potential sensitizing event (miscarriage, amnio, trauma, etc.)
    • Large FMH: Screen (Rosette test) and quantify (KB stain/Flow Cytometry) post-delivery to determine if >1 standard dose of RhIG is needed
  • Other Antibodies: No specific immune globulin exists. Prevention relies on judicious transfusion policies for women of childbearing potential (avoiding unnecessary transfusion, providing antigen-negative blood like K-negative when feasible)