What antibodies destroy red blood cells in a fetus?

Antibodies That Destroy Red Blood Cells in a Fetus

The main antibodies that destroy fetal red blood cells are maternal alloantibodies, primarily anti-D (Rh) antibodies, as well as antibodies against other Rh system antigens (c, C, e, E), Kell (K, k), Duffy (Fya), and Kidd (Jka, Jkb) antigens. 1

Maternal Alloimmunization and Hemolytic Disease of the Fetus and Newborn (HDFN)

• HDFN occurs when maternal antibodies cross the placenta, enter fetal circulation, and attack fetal red blood cells, causing hemolysis and anemia 2
• The RhD antigen is detectable in fetuses as early as 38 days and is well developed by 6 weeks' gestation 1
• Maternal alloimmunization can occur when as little as 0.1 mL of incompatible fetal blood enters maternal circulation 1
• Fetomaternal hemorrhage occurs in 7% of pregnancies in the first trimester, 16% in the second trimester, and 29% in the third trimester 1

Common Alloantibodies Causing HDFN

• Anti-D (Rh) antibodies were historically the most common cause, but with Rh immunoprophylaxis, other antibodies have increased in relative importance 1
• Other significant red cell antibodies include:
  • Other Rh system antibodies (anti-c, anti-C, anti-e, anti-E) 1
  • Anti-Kell (K, k) antibodies 1
  • Anti-Duffy (Fya) antibodies 1
  • Anti-Kidd (Jka, Jkb) antibodies 1
• In rare cases, ABO incompatibility can cause HDFN, typically with group O mothers having antibodies against group A or B infants 3
• Unusually, a group B mother can develop anti-A IgG antibodies that cause HDFN in a group A fetus 3

Pathophysiology and Clinical Manifestations

• Maternal antibodies cross the placenta, bind to fetal red blood cells, and cause their destruction 4
• The severity of fetal anemia can be categorized based on hemoglobin concentrations as mild, moderate, or severe 1
• Clinical manifestations range from asymptomatic mild anemia to hydrops fetalis (severe fluid accumulation) or stillbirth 5
• Severe anemia can lead to hydrops fetalis when hemoglobin concentrations fall below 5 g/dL 1

Diagnosis of Alloimmune Fetal Anemia

• Maternal blood typing and antibody screening are routinely performed early in pregnancy 2
• If a mother is Rh-negative, non-invasive blood testing can determine if the fetus is Rh-positive 2
• Serial ultrasound measurements can detect signs of fetal anemia 5
• Fetal hemoglobin concentration can be measured through fetal blood sampling when necessary 1
• Reference ranges for normal fetal hemoglobin have been established from 18 to 40 weeks gestation 1

Other Causes of Fetal Anemia

• Parvovirus B19 infection is the most common infectious cause of fetal anemia 1
• Other infectious causes include toxoplasmosis, cytomegalovirus, coxsackie virus, and syphilis 1
• Inherited disorders like alpha-thalassemia can cause severe fetal anemia 1
• Twin anemia-polycythemia sequence can occur in 3-5% of monochorionic twin pregnancies 1

Prevention and Management

• Anti-D immunoglobulin prophylaxis has dramatically reduced Rh alloimmunization 5
• Prophylaxis is given for any event associated with potential fetomaternal hemorrhage and at delivery of an Rh-positive infant 5
• Routine prophylaxis at 28 (and sometimes 34) weeks gestation has reduced alloimmunization to <1% in Rh-negative women carrying Rh-positive fetuses 5
• For already sensitized pregnancies, management may include:
  • Serial monitoring of maternal antibody levels 5
  • Ultrasound assessment for signs of fetal anemia 5
  • Intrauterine transfusion when indicated 2
  • Intravenous immunoglobulin (IVIG) as a potential non-invasive treatment for high-risk cases 2

Clinical Pitfalls and Considerations

• False-negative results in maternal antibody testing can occur due to delayed appearance of antibodies or low-affinity antibodies 6
• When certain antigens (HPA-1, -3, or -5) are implicated, antibody testing should be repeated 2-8 weeks later to catch delayed antibodies 1
• Some antibodies may require specific testing methods to detect, as they can be missed with standard techniques 1
• Laboratory confirmation requires identification of antigen incompatibility between mother and father/fetus and identification of a maternal alloantibody 1
• Testing should be performed in specialized reference laboratories due to the expertise required 1