Alloimmunization Against Erythrocytes in Pregnancy: Causes, Diagnosis, and Treatment

Pregnancy and Anti-E Positive Alloimmunization

Anti-e antibodies cause significant fetal and newborn hemolytic disease requiring prenatal intervention. Unlike other non-RhD alloimmunization, anti-e antibodies are not usually associated with prior affected pregnancies and are often found when antibody titers and DOD 450 are high.

Platelet concentrate alloimmunization with non-RhD antibodies is rare and usually accompanied by anti-D or anti-C. We report a case of anti-e alloimmunization following buffy coat-derived platelet concentrates (BC-PCs).


Antibodies produced during pregnancy (either from an incompatibility or blood transfusion) can cross the placenta and bind to fetal red blood cells that have the matching antigen. This causes the destruction of the fetal blood cells and results in a severe form of hemolysis. The resulting bilirubin then builds up in the infant’s system, causing hyperbilirubinemia.

Hemolytic disease of the newborn (HDN) caused by anti-E is extremely rare. Unlike other non-D Rh antibodies, such as anti-D, anti-c and autoantibodies, which can give rise to HDN, hematological abnormalities due to anti-E are not known to increase with subsequent pregnancies.

A 32-year-old woman with anti-E antibodies detected during her first pregnancy had a direct Coombs test titer of 1 : 2 in the second trimester. Her fetus was diagnosed with hydrops at 18 weeks and required a single transfusion. Despite the high indirect Coombs titer, her MCA-PSV remained within the normal range. The fetus was delivered at 33 weeks and had a postnatal hemoglobin of 19.0 g/dL.


Antibody typing for the E antigen is not routinely performed antenatally. However, it should be considered in pregnant women who have a history of prior hemolytic disease due to e-antigen isoimmunization or have high titers of anti-E antibody.

A neonate with severe hyperbilirubinemia was born to an e-antigen negative and Rh positive mother with a blood group O and subtype R1R2. His erythrocyte e-antigen was destroyed by maternal alloantibody, which resulted in the development of HDN. A postnatal workup showed severe hyperbilirubinemia with a positive direct Coombs test.

A multipara woman with an O Rh positive husband developed high titers of anti-E antibodies during her first pregnancy. She was diagnosed with hydrops fetalis by ultrasonography, and a Doppler peak systolic velocity of 0.8 m/sec indicated severe fetal anemia.


Alloimmunization against erythrocytes carries the risk of severe hemolytic disease in the newborn (HDN). The anti-E antibodies can cross the placenta and attack fetal red cells carrying the E antigen. HDN due to anti-E is less common than those caused by other non-D Rh antibodies, such as anti-C or anti-D.

However, even low titers of anti-E alloimmunization can result in HDN. Joy et al. found that of the 19 pregnancies in which maternal titer exceeded 1 : 16, six resulted in fetal Hb below 10 g/dL and two resulted in perinatal death, one of which was due to hydrops fetus.

The treatment of HDN caused by anti-E involves phototherapy and exchange transfusion. Intravenous immunoglobulin can reduce the need for exchange transfusion and shortens the duration of phototherapy. However, the optimum method to treat HDN is to prevent maternal alloimmunization using matched antigen-negative RBC units.

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