HDFN Overview and Pathogenesis

HDFN Overview

• HDFN is a rare condition that results from the destruction of fetal and newborn RBCs by maternal antibodies.
• Maternal antibodies can be either naturally occurring ABO antibodies or develop after exposure to foreign RBCs called alloantibodies.
• Most maternal alloimmunization occurs due to previous pregnancy (83%), while only 4% is due to previous transfusion.
• Before the advent of Rh immune globulin (RhIG), 95% of HDFN cases were caused by maternal antibodies directed against the Rh antigen D.
• Recently, ABO incompatibility has become the most frequent cause of HDFN.

Pathogenesis of HDFN

• ABO HDFN:
  • ABO antibodies are present in the plasma of individuals lacking the corresponding antigen.
  • ABO antibodies are predominantly IgM class, which cannot efficiently cross the placenta.
  • IgG ABO antibodies can cross the placenta and attach to fetal RBCs.
  • Group O individuals are most likely to form high-titer IgG anti-ABO antibodies.
  • ABO HDFN is primarily limited to A or B infants of group O mothers with potent anti-A, B antibodies.
  • ABO HDFN is often limited to A or B infants of group O mothers.
  • Tetanus toxoid administration and helminth parasite infections during pregnancy have been linked to higher IgG ABO antibody levels and severe HDFN.
  • The mild course of ABO HDFN is associated with the incomplete development of ABO antigens on fetal RBCs.
  • ABO antigens are not fully developed until after the first year of life.

FMH (Fetal-Maternal Hemorrhage)

• Maternal alloimmunization occurs from exposure to foreign RBCs through pregnancy, transfusions, or organ transplants.
• FMH allows spontaneous mixing of fetal and maternal blood during pregnancy.
• The mixing increases throughout pregnancy, with a higher risk in the third trimester.
• Physical disturbances during pregnancy (trauma, abortion, etc.) increase the risk of FMH.

Maternal Factors

• Individuals' ability to produce antibodies varies based on complex genetic factors.
• Rh-negative individuals who receive Rh-positive blood have an 85% chance of developing anti-D antibodies.

Antibody Identification

• If the antibody screen is reactive, the antibody identity must be determined.
• Cold reactive IgM antibodies, such as anti-1, anti-IH, and anti-Lea, are generally not significant.
• Antibodies such as anti-M and anti-N can cause moderate HDFN, although rarely.
• A sulfhydryl reagent can be used to differentiate between IgG and IgM antibodies.

Management of the Infant

• Cord blood testing is important for ABO grouping and RhD typing.
• DAT (Direct Antiglobulin Test) is the primary serologic test for HDFN.
• Elution is sometimes necessary to confirm the cause of HDFN.
• Exchange transfusion is used to replace the neonate's blood and remove bilirubin and maternal antibodies.
• The selection of blood products for the transfusion requires careful consideration of the infant's blood type and potential antigens.

Rh Immune Globulin (RhIG)

• RhIG reduces the risk of alloimmunization in RhD-negative mothers.
• The mechanism of RhIG is unclear but likely involves interfering with B-cell priming to produce anti-D antibodies.
• RhIG doses are given at 28 weeks’ gestation or after trauma, and again after delivery of an RhD-positive infant.
• RhIG offers no benefit if the mother has already formed anti-D antibodies.
• RhIG is not indicated if the infant is D-negative.
• RhIG is recommended for abortions, stillbirths, and ectopic pregnancies, even if fetal blood type cannot be determined.
• Repeated administration of RhIG does not necessarily correlate with effectiveness.
• RhIG is available in IV and intramuscular forms with specific considerations for administration.
• RhIG is contraindicated for individuals with anti-IgA or IgA deficiency and a history of anaphylactic reactions to blood products.
• A maternal sample should be obtained within 1 hour of delivery for screening for massive fetomaternal hemorrhage.

This quiz covers the overview and pathogenesis of Hemolytic Disease of the Fetus and Newborn (HDFN). It delves into the causes and mechanisms of maternal antibody effects on fetal red blood cells, including ABO incompatibility and Rh antigen interactions. Test your knowledge on this rare medical condition!