HDFN Flashcards (Danny)

HDFN
Definition & Causes

• Maternal IgG crosses placenta → fetal RBC destruction

• Requires: antigen-positive fetus, antigen-negative mother, clinically significant antibody

• Antigen must be well developed on fetal RBCs (Rh, Kell, Kidd, Duffy, MNS)

HDFN
Maternal Antibodies

• Severe: anti-D, anti-c, anti-K

• Others: anti-E, anti-C, anti-Fya, anti-Jka, anti-S/s, anti-U

• Usually no HDFN: ABO (mild), anti-Lea/Leb, anti-I, anti-P1 (IgM)

HDFN
Maternal Alloimmunization Mechanism

• Sensitization from delivery, abortion, amniocentesis, trauma, transfusion

• First pregnancy often sensitizes; subsequent at risk

• IgM can’t cross placenta → only IgG causes HDFN

HDFN
Clinical Spectrum

• Mild: jaundice only

• Moderate: anemia + hyperbilirubinemia

• Severe: hydrops fetalis, stillbirth, neonatal death

HDFN
Differential Diagnosis

• Congenital infection (TORCH) – DAT negative

• Hereditary spherocytosis / G6PD deficiency – DAT negative

• Sepsis – positive cultures

• ABO incompatibility – mild, 1st pregnancy affected

HDFN
Prenatal Testing – Antibody Screen & Titers

• Antibody ID if screen positive

• Critical titer: ≥16 or ≥32 (Rh); anti-Kell uses MCA Doppler instead of titer correlation

• Repeat titers q2–4 wks

HDFN
Paternal & Fetal Antigen Testing

• Paternal typing: homozygous → all offspring at risk; heterozygous → 50% risk

• Fetal antigen typing: amniocentesis (PCR) or cell-free DNA from maternal plasma

HDFN
Fetal Anemia Pathophysiology

• IgG hemolysis → ↓ RBC mass → hypoxia → ↑ CO → heart failure → hydrops fetalis

HDFN
Management of At-Risk Pregnancies

• Antibody present & fetus antigen-positive → MCA Doppler if at/above critical titer

• Cordocentesis for Hgb/Hct if anemia suspected

• Intrauterine transfusion if Hct <30%

HDFN
Intrauterine Transfusion (IUT) Requirements

Antigen-negative, crossmatch-compatible, irradiated, CMV-neg, HbS-neg, high HbA, O neg packed cells

HDFN
Neonatal Management

• Phototherapy: converts unconjugated bilirubin → soluble form

• Exchange transfusion: removes antibody-coated RBCs + bilirubin

• Simple transfusion: corrects anemia only

HDFN
RhIg Prophylaxis

• 300 µg at 28 wks & ≤72 hrs postpartum (if infant D+)

• Also after abortion, ectopic, amnio, trauma

• Coats fetal D+ RBCs before maternal immune recognition

HDFN
Diagnostic Criteria

• Maternal: positive antibody screen, specificity matches fetal/paternal antigen

• Fetal/neonatal: positive DAT (IgG), anemia, hyperbilirubinemia, other causes excluded

• Rh HDFN: severe, later pregnancies; ABO HDFN: mild, 1stborn possible

HDFN
Follow-Up Testing

• Maternal: antibody ID, titers, paternal typing, fetal antigen typing

• Neonatal: DAT, bilirubin, Hgb/Hct, retic count

• DAT+ → eluate for antibody ID

HDFN
Eluate Use in HDFN

• dentifies antibody bound to neonatal RBCs

• Compare with maternal antibody ID for confirmation

HDFN
Testing Pathway – Maternal Antibody Detected

• Perform antibody identification (IAT)

• Determine clinical significance

• If clinically significant & IgG → paternal antigen typing

• Paternal homozygous → fetus at risk; heterozygous → 50% risk → consider fetal antigen typing

• Establish baseline titer & repeat q2–4 wks until critical

HDFN
Testing Pathway – Screen Negative, High Risk History

• If prior affected pregnancy → monitor regardless of screen

• MCA Doppler monitoring begins earlier

• Consider non-invasive fetal antigen typing via cell-free DNA

HDFN
Testing Pathway – Critical Titer Reached

• Initiate MCA Doppler surveillance

• Abnormal velocity (>1.5 MoM) → cordocentesis to confirm fetal anemia

• If Hct <30% → intrauterine transfusion

HDFN
Testing Pathway – Newborn with Positive DAT

• Evaluate for anemia (Hgb/Hct, retic) and hyperbilirubinemia

• Eluate from newborn RBCs → test against antibody ID panel (IAT)

• Compare eluate result with maternal antibody profile

• Rule out other causes (infection, membrane defects)

HDFN
Testing – Cordocentesis

• Direct measurement of fetal Hgb/Hct & blood type

• Used if MCA Doppler suggests anemia

• Risk: fetal loss, infection, worsening alloimmunization

HDFN
Testing – Paternal Antigen Typing

• Determines zygosity (homo vs heterozygous)

• Guides risk assessment for fetus

• If heterozygous → non-invasive fetal antigen typing considered

HDFN
Testing – Fetal Antigen Typing

• Amniocentesis (PCR) or maternal plasma cell-free DNA

• Determines if fetus carries target antigen

• Avoids unnecessary surveillance if antigen-negative

HDFN
Testing – Elution Studies

• Purpose: identify antibody coating neonatal RBCs

• Performed on DAT-positive cord blood

• Compare with maternal antibody ID for confirmation

HDFN
Testing – DAT in Newborn

• Positive in immune-mediated hemolysis

• Strength does not always correlate with severity

• Negative DAT possible in ABO HDFN due to rapid RBC destruction