HDFN

• Hemolytic Disease of the Fetus and Newborn (HDFN)


  The destruction of the red blood cells (RBCs) of a fetus and neonate by antibodies produced by the mother
• Causes of HDFN


  • Mother can be stimulated to form RBC antibodies naturally (ABO), by previous pregnancy, or transfusion (RBC alloimmunization)
• Pathogenesis of HDFN


  1. Hemorrhage of D-positive fetal RBCs into D-negative mother

  2. Maternal antibody formed against paternally inherited D antigen

  3. Placental passage of maternal IgG anti-D

  4. Maternal antibody attaches to fetal RBCs

  5. Hemolysis of fetal RBCs
• Important factors for HDFN to occur

  • The red cell antibody produced by the mother must be of the
  • The fetus must possess an antigen that is
  • The antigen must be
• Antibodies Identified in Prenatal Specimens That Can Cause of HDFN


  • Anti-D
  • Anti-Fya
  • Anti-Lea
  • Anti-D + C
  • Anti-s
  • Anti-Leb
  • Anti-D + E
  • Anti-M
  • Anti-I
  • Anti-C
  • Anti-N
  • Anti-IH
  • Anti-E
  • Anti-S
  • Anti-P₁
  • Anti-c
  • Anti-Jka
  • Anti-e
  • Anti-K
• Pathogenesis


  • Occurs when maternal IgG attaches to specific antigens of the fetal RBCs
  • Destruction of red cells
  • Increased production of red cells
• Neonatal Manifestations of HDFN-Induced Anemia by Time of Onset

  • Early-Onset Anemia (Within 7 days of birth, Antibody-mediated hemolysis, Elevated bilirubin)
  • Late Hemolytic Anemia (>2 Weeks of age, 1. Antibody-mediated hemolysis, 2. Natural decline of Hb levels, 3. Expanding intravascular volume of growing infant, Normal bilirubin, Reticulocyte count usually elevated)
  • Late Hyporegenerative Anemia (>2 Weeks of age, 1. Antibody destruction of RBC precursors and RBCs, 2. Marrow suppression by IUT and transfusions, 3. Erythropoietin deficiency, 4. Expanding intravascular volume of growing infant, Normal or high bilirubin, Low or absent reticulocyte count)
• Severe anemia and hypoproteinemia (caused by decreased hepatic production of plasma proteins) lead to the development of high-output cardiac failure with generalized edema, effusions, and ascites, a condition known as hydrops fetalis
• The antibody-coated cells are removed from the circulation by the macrophages of the spleen
• When the bone marrow fails to produce enough RBCs to keep up with the rate of RBC destruction, erythropoiesis outside the bone marrow is increased in the hematopoietic tissues of the spleen and liver. These organs become enlarged (hepatosplenomegaly), resulting in portal hypertension and hepatocellular damage
• RBC destruction releases hemoglobin, which is metabolized to bilirubin. This bilirubin is called indirect because indirect methods are required to measure the bilirubin in the laboratory. - if left untreated can cause kernicterus or permanent damage to parts of the brain
• Diagnosis and Management


  1. Serologic testing of the mother - ABO Typing, Rh Typing, Antibody Screening and Identification, Antibody Titration

  2. Fetal genetic testing to determine fetal inheritance

  3. Cordocentesis - highly specialized prenatal test in which a sample of the baby's blood is removed from the umbilical cord for testing

  4. Amniocentesis - process of collecting amniotic fluid from the mother

  5. Intrauterine transfusion - performed by accessing the fetal umbilical vein and injecting donor RBCs directly into the vein
• Most centers treating HDFN use group O RBCs for intrauterine and neonatal transfusions
• RHOGAM


  • Mechanism of action - attaches to the fetal Rh positive red cells in the maternal circulation
  • Regular-dose vial - sufficient anti-D to protect against RhD negative RhD positive
• RHOGAM administration


  1. Given in 28th week of gestation, 72 hours after birth

  2. Rh(-) without anti-D

  3. Rh(-) with complicated pregnancy

  4. Rh(-) with Rh (+) baby
• Anti-D present: Rhig not indicated if anti-D not due to previous Rhig
• Fetal Screen (Rosette Test)

  1. Screening test

  2. D positive indicator cells

  3. D positive fetal RBCs
• Kleihauer-Betke Acid Elution Test

  • Quantitative test
  • Ghost Cell: Intact Cell:
  • Formula: %FRC = FMH