Hemolytic Disease of the Fetus and Newborn (HDFN) Practive Flashcards

Hemolytic Disease of the Fetus and Newborn (HDFN): Definition and Etiology

  • Hemolytic Disease of the Fetus and Newborn (HDFN) is also commonly referred to as erythroblastosis fetalis.
  • The condition is characterized by the destruction of fetal or newborn red blood cells (RBCs) by maternal immunoglobulin G (IgG) antibodies.
  • The etiology follows a specific sequence of events:
    • The mother lacks a specific RBC antigen that the fetus possesses; this antigen is inherited from the biological father.
    • Maternal IgG antibodies cross the placenta and sensitize the fetal RBCs, leading to a shortened RBC survival rate.
  • Role of the Placenta:
    • It serves as the primary site for the exchange of oxygen, nutrients, and waste products.
    • It acts as a barrier between maternal and fetal circulations, which normally reduces the chance of maternal exposure to fetal antigens.
    • If ABO incompatibility exists, any fetal cells that cross into maternal circulation are typically lysed, further preventing antigenic exposure.
  • Causes of Fetomaternal Hemorrhage: HDFN typically occurs when fetal cells escape into maternal circulation during specific events:
    • Delivery of the infant.
    • Invasive procedures such as amniocentesis or cordocentesis.
    • Miscarriage or abortion.
    • Ectopic pregnancy.
    • Abdominal trauma to the mother.
  • Mechanism of Destruction: Fetal RBC antigens stimulate the mother to produce antibodies. These antibodies bind to fetal antigens, and the sensitized cells are destroyed in the fetal liver and spleen.

Bilirubin Metabolism and Pathophysiology

  • Metabolism Before Birth:
    • Fetal RBC destruction leads to the production of indirect (unconjugated) bilirubin.
    • The maternal liver conjugates this indirect bilirubin for excretion, so the fetus remains relatively protected from bilirubin toxicity in utero.
    • Compensatory Erythropoiesis: As destruction continues, the fetus increases RBC production. Immature nucleated RBCs (erythroblasts) are released into circulation (erythroblastosis fetalis).
    • Complications: Severe anemia leads to edema in the peritoneal and pleural cavities, a condition known as hydrops fetalis. This can ultimately result in fetal cardiac failure.
  • Metabolism After Birth:
    • The newborn liver is immature and cannot effectively conjugate bilirubin.
    • Unconjugated bilirubin binds first to albumin; when albumin levels are exceeded, it binds to tissues, resulting in jaundice.
    • Bilirubin Toxicity: If unconjugated bilirubin binds to the tissues of the central nervous system, it causes permanent brain damage known as kernicterus.

Classifying Types of HDFN

  • Necessary Factors for HDFN:
    • The maternal antibody must be of the IgG class (as only IgG crosses the placenta).
    • The fetus must possess an antigen the mother lacks (inherited from the father).
    • The antigen must be well-developed at the time of birth.
  • Rh HDFN (Anti-D):
    • This is the most severe form of the disease.
    • Typically, a D-negative woman is sensitized during her first pregnancy with a D-positive infant.
    • Subsequent pregnancies with D-positive fetuses are affected by the established maternal antibody.
    • Serological findings include a positive Direct Antiglobulin Test (DAT).
    • Clinical findings include jaundice, severe anemia, and the potential need for exchange transfusion.
  • ABO HDFN:
    • This is the most common type, occurring in approximately 11 in 150150 births.
    • It most frequently occurs when the mother is blood group O and the baby is group A or B.
    • Unlike Rh HDFN, the first pregnancy can be affected.
    • Symptoms are usually mild, possibly because A or B substances in fetal tissues neutralize the antibodies, or because A/B antigen sites are poorly developed/reduced on fetal RBCs.
    • Jaundice may occur and is often treated with phototherapy.
  • Other Antibody HDFN:
    • Any IgG antibody can cause the disease.
    • Anti-c and anti-K (Kell) are the most common causes after anti-D.
    • Less common causes include other Kell antibodies, Kidd, Duffy, S, and U antigens.
    • A clue to a low-frequency antigen is when maternal serum agglutinates paternal cells despite negative screening cells.

Comparison of Clinical and Laboratory Findings (Table 12.1)

  • Jaundice: Mild to moderate in ABO HDFN; Moderate to severe in Rh HDFN.
  • Edema: Absent in ABO HDFN; ranges from mild to severe in Rh HDFN.
  • Serology:
    • ABO HDFN: Mother is O, Baby is A or B; DAT is negative or weakly positive; Antibodies involved are Anti-A, Anti-B, and Anti-A,B.
    • Rh HDFN: Mother is D-negative, Baby is D-positive; DAT is strongly positive; Antibody is Anti-D.
  • Hematology Results:
    • Anemia: Mild in ABO; Moderate to severe in Rh.
    • Reticulocyte Count: Mild increase in ABO; Greatly increased in Rh.
    • RBC Morphology: Spherocytes are characteristic of ABO HDFN; Macrocytes and hypochromia are characteristic of Rh HDFN.
    • Nucleated RBCs: Mild increase in ABO; Greatly increased in Rh.
  • Chemistry Results (Bilirubin):
    • ABO HDFN: Mild increase, peaks at 2424 to 4848 hours postpartum.
    • Rh HDFN: Moderate to severe increase.

Prenatal Diagnostic Procedures and Monitoring

  • Initial Prenatal Workup:
    • Includes ABO/Rh typing and an antibody screen. If an antibody is identified, its identity and titer are determined.
    • History: Accurate obstetric and transfusion history is essential for risk assessment.
  • Antibody Titration:
    • Aids in determining the necessity of invasive procedures.
    • A baseline titer is established in the first trimester, and the sample is frozen.
    • Testing is repeated at 44 to 66 week intervals.
    • Significance: A rise of 22 dilutions (compared to baseline) is significant. A titer of 1616 or 3232 is generally considered the critical threshold for anti-D and other Rh antibodies.
  • Ultrasound (Color Doppler):
    • Detects fetal anemia by measuring peak systolic velocity in the middle cerebral artery.
    • Fetal anemia causes increased cardiac output and low blood viscosity.
  • Amniocentesis:
    • Amniotic fluid is scanned spectrophotometrically from 350350 to 700 nm700\,nm.
    • The change in optical density (\Delta OD) at 450 nm450\,nm measures bilirubin pigments.
    • Results are plotted on a Liley graph according to gestational age:
      • Zone 3 (Upper): Severe disease and potential fetal death.
      • Zone 2 (Middle): Moderate disease; requires monitoring.
      • Zone 1 (Lower): Mild disease.
    • Fetal Lung Maturity: Before inducing early labor, the lecithin-sphingomyelin (L:SL:S) ratio is checked; it must be greater than 2:12:1.
  • Cordocentesis:
    • A fetal blood sample is drawn to test Hemoglobin (Hgb), Hematocrit (Hct), bilirubin, and RBC genotype.
    • Mortality rate for the procedure is low (1%1\% to 2%2\%).
    • It can be used for intravascular transfusions.
  • Fetal Genotyping: Fetal DNA can be typed from maternal plasma in the second trimester, potentially avoiding invasive tests if the fetus lacks the target antigen.

Postpartum Testing and Results Interpretation

  • Maternal Sample Testing (at delivery):
    • ABO/D typing and an antibody screen to determine the need for RhIG and pretransfusion needs.
    • Fetal screen (rosette test) and Kleihauer-Betke (if the rosette test is positive) to determine RhIG dosage.
  • Cord or Infant Sample Testing:
    • ABO/D Typing: Only forward grouping is performed for ABO (antibodies are not yet produced).
    • Weak D Test: Not required if the mother is D-negative and the infant appears D-negative initially, unless checking for RhIG eligibility. If the mother is D-negative and the infant is D-positive, RhIG is indicated.
    • Direct Antiglobulin Test (DAT): Routinely performed. If positive, an elution is performed.
    • Elution: The eluate is tested against A cells, B cells, and panel cells. If positive with A or B cells only, ABO HDFN is indicated. If negative with all, a low-frequency antigen is suspected.
  • Technical Considerations:
    • Wharton’s Jelly: Cord blood must be washed thoroughly to prevent false-positive results from Wharton’s jelly.
    • Blocking Phenomenon: If D-antigen sites are heavily coated (blocked) by maternal anti-D, the infant may type as D-negative (false negative). An eluate will demonstrate the anti-D.
    • False Positives: A weak D test on coated RBCs may yield a false positive; the Rh control will be positive at the AHG phase.

Rh Immune Globulin (RhIG) Prevention and Calculations

  • Purpose: RhIG prevents alloimmunization in D-negative mothers by preventing the formation of anti-D. It does not prevent other antibodies.
  • Administration Schedule:
    • Antepartum: A 300 μg300\,\mu g dose is administered at 2828 weeks' gestation.
    • Postpartum: Nonimmunized D-negative women with D-positive infants receive one dose within 7272 hours of delivery.
  • Fetomaternal Hemorrhage (FMH) Screening:
    • The Rosette Test: Maternal RBCs are incubated with anti-D, and D-positive indicator cells are added.
    • Interpretation: If there is less than 11 rosette per 33 low-power fields, one dose of RhIG is given. If more than 11 rosette per 33 low-power fields is found, the bleed must be quantified.
  • Quantifying FMH (Kleihauer-Betke Test):
    • Principle: Fetal hemoglobin resists acid and retains dye (appears dark), while adult hemoglobin is acid-sensitive (appears as "ghost" cells).
    • Calculation Steps:
      1. Determine the percentage of fetal cells in a count of 20002000 total cells.
      2. Calculate fetal whole blood ($ ext{mL}$) = $\text{Percentage} \times 5000\,\text{mL}$ (estimated maternal volume).
      3. Determine vials: $\text{vials} = \frac{\text{fetal blood (mL)}}{30}$.
      4. Rounding: Round up if the decimal is ≥0.5\ge 0.5; round down if <0.5< 0.5.
      5. Safety Margin: Add 11 vial to the calculated whole number.
    • Example:
      • Count: 16 fetal cells2000 total cells=0.008\frac{16\,\text{fetal cells}}{2000\,\text{total cells}} = 0.008.
      • Volume: 0.008×5000 mL=40 mL0.008 \times 5000\,\text{mL} = 40\,\text{mL}.
      • Vials: 4030=1.3\frac{40}{30} = 1.3.
      • Rounding: 1.3→11.3 \rightarrow 1.
      • Final Dose: 1+1=21 + 1 = 2 vials of RhIG.

Therapeutic Interventions and Transfusion

  • Intrauterine Transfusion:
    • Purpose: Corrects fetal anemia and prevents heart failure.
    • Blood Selection: Group O, D-negative RBCs; fresh (collected within 77 days); irradiated to prevent graft-versus-host disease; CMV-negative and/or leukocyte-reduced; Hemoglobin S negative.
  • Phototherapy:
    • Uses fluorescent blue light (420420 to 475 nm475\,nm) to treat hyperbilirubinemia.
    • It converts bilirubin into isomers excreted in the bile.
  • Exchange Transfusion:
    • Involves replacement of 11 to 22 whole blood volumes.
    • Goals: Corrects anemia without volume expansion, removes the newborn's coated cells, reduces bilirubin (threshold is usually 1818 to 20 mg/dL20\,mg/dL) to prevent kernicterus, and reduces circulating maternal antibody.
    • Blood Selection: The infant is typed for ABO and D; maternal or infant serum/plasma is used for the antibody screen to ensure antigen-negative units are provided.