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  • In this disease, there is fetal to maternal transfer of red cells that results in immunization of the mother. Then, transplacental transfer of maternal anti–red cell antibodies to the fetus shortens the life span of fetal or newborn red cells.

  • Manifestations include fetal hemolytic anemia, jaundice, and hepatosplenomegaly; in more severe cases, anasarca and kernicterus also occur.


  • Asymptomatic transplacental passage of fetal red cells occurs in 75% of pregnancies.

  • If there is blood group incompatibility between mother and fetus, the chance of maternal immunization increases with the volume of any transplacental hemorrhage.

  • Approximately 95% of pregnant women have fetomaternal hemorrhage of less than 1.0 mL at delivery.

  • Intrapartum fetomaternal hemorrhage of more than 30 mL occurs in approximately 1.0% of deliveries.

  • Larger volume transplacental hemorrhages are more likely to occur at delivery or during invasive obstetric procedures.

  • The risk of sensitization increases with each trimester of pregnancy and is greatest (65%) at delivery.

  • Fetomaternal transfusion can occur at the time of chorionic villous sampling, amniocentesis, therapeutic abortion, cesarean section, abdominal trauma, and other situations.

  • Prior blood transfusions or abortions also can immunize the mother.

  • Maternal red cell antibodies fall into three classes: antibodies directed against the D antigen in the Rh blood group, antibodies directed against the A or B antigens, and antibodies directed against any of the remaining red cell antigens.

  • The D antigen of the Rh blood group system is involved in most serious cases.

  • Without prophylaxis, immunization occurs in approximately 12% of those at risk with an RhD-positive, ABO-compatible fetus and 2% of these with an RhD-positive, ABO-incompatible fetus.

  • Anti-D immunoglobulin G (IgG) crosses the placenta and leads to a positive antiglobulin test and hemolysis in the infant.

  • In ABO hemolytic disease, the mother is usually type O and the fetus is either type A or B.

  • Anti-A and anti-B antibodies ordinarily cause mild, rarely severe, hemolysis. Numerous other causal antibodies have been described but are less common (see “Epidemiology”).


  • The distribution of blood group antigens among different ethnic groups determines their risk of alloimmune hemolytic disease.

  • Approximately 16% of Americans of European descent are RhD negative, compared to 8% of Americans of African ancestry, 5% of persons of Asian Indian ancestry, and 0.3% of those of Chinese ancestry.

  • More than 50 different red cell antigens have been associated with maternal alloimmunization and with alloimmune hemolytic disease with varying degrees of severity.

  • Women have naturally occurring antigens to blood group A or B (eg, mother type O) or may develop other antibodies not screened for prior to blood transfusion.

  • Antenatal screening programs detect antibodies in approximately 0.2% of pregnant women.

  • After anti-RhD, the following blood groups are most often involved in alloimmunization: Rh (C, e, E, e), Kell, Duffy, Kidd, and the MNS.

  • The presence of maternal antibodies is not predictive of alloimmune hemolytic disease because (1) they ...

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