Journal of Clinical Neonatology

: 2020  |  Volume : 9  |  Issue : 2  |  Page : 146--148

Hemolytic disease of the newborn due to anti-e

Hammam A H. Ali1, Osayd Samer Zohud2,  
1 Department of Medical Laboratory Sciences, Faculty of Health Professions, Al-Quds University, Jerusalem; Department of Laboratory and Blood Bank, Yaser Arafat Hospital, Palestinian Ministry of Health, Salfit, State of Palestine
2 Department of Laboratory and Blood Bank, Yaser Arafat Hospital, Palestinian Ministry of Health, Salfit, State of Palestine

Correspondence Address:
Dr. Hammam A H. Ali
Department of Medical Laboratory Sciences, Faculty of Health Professions, Al-Quds University, Jerusalem; Department of Laboratory and Blood Bank, Yaser Arafat Hospital, Palestinian Ministry of Health, Salfit, State of Palestine


In Palestine, antibody screening is done antenatally only for pregnant women who are Rh-D negative. However, we report the first hemolytic disease of the newborn (HDN) due to anti-e in Palestine, illustrating the importance of alloantibodies other than anti-D as a cause of HDN. A pregnant woman had e-antigen negative and her blood group was B positive developed alloantibody against her infant erythrocyte e-antigen that lead to severe jaundice due to fetal erythrocyte destruction by this maternal alloantibody. Postnatal workup for the severe hyperbilirubinemia indicated that the newborn' erythrocytes were sensitized by the maternal anti-e alloantibody. Furthermore, the positive direct Coombs test was reported. This case highlights the importance of antibody screening for all pregnant women irrespective of the D antigen status to detect and manage erythrocyte alloimmunization to any other clinically significant blood group antigens.

How to cite this article:
Ali HA, Zohud OS. Hemolytic disease of the newborn due to anti-e.J Clin Neonatol 2020;9:146-148

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Ali HA, Zohud OS. Hemolytic disease of the newborn due to anti-e. J Clin Neonatol [serial online] 2020 [cited 2020 Dec 4 ];9:146-148
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In addition to Rh-D antigen incompatibilities, subgroup incompatibilities may rarely play a role among the causes of hemolytic anemia and hyperbilirubinemia in newborns. This case is the first reported hemolytic disease of the newborn (HDN) case due to anti-e in Palestine.

Little e-antigens are extremely common worldwide. This high frequency could be up to 98% in some countries such as India.[1] There is no available data about the exact frequency of e-antigen in the Palestinian population, but its frequency is expected to be very high. The presence of anti-e in patients who need blood transfusions makes the provision of compatible blood units difficult due to this high frequency.

Pregnant women with negative e-antigen have a very high probability to form anti-e against e-antigen in their infant's erythrocytes, which could lead to HDN.

HDN due to anti-e alone is rare globally,[2] but there are HDN cases reported due to anti-e which were reported in Japan in 2008 by McAdams < i>et al.[3] and in London in 1981 by Chapman and Waters.[2]

Alloimmunization is an immune response against foreign erythrocyte antigens. This immune response occurs after blood transfusion, solid-organ transplantation, or pregnancy. The first exposure to a foreign antigen leads to the stimulation of the immune system and the corresponding production of antibodies against this foreign antigen. The second exposure to the same foreign antigen leads to the sensitization of erythrocytes which carry this antigen by the corresponding alloantibody. These sensitized red blood cells (RBCs) are destroyed by the monocyte–macrophage system in the spleen in a mechanism, which is called extravascular hemolysis.[4]

At delivery, an enormous number of fetal RBCs enter the mother's circulation. When the fetus inherits certain antigens from the father, the fetal RBCs stimulate the maternal immune system to produce the corresponding alloantibody, which is mostly immunoglobulin G (IgG). The IgG antibody class is actively transported across the placenta. All subsequent offspring who inherit the antigen will be affected. The maternal IgG alloantibody crosses the placenta and binds to the fetal antigen-positive cells, leading to the sensitization of fetal erythrocytes which are detectedin vitro by the direct antiglobulin test (direct Coombs test [DCT]). These sensitized fetal RBCs are destroyed in the spleen which causes anemia. This process of fetal RBC destruction due to maternal alloantibodies is called HDN.[5] Hemolytic disease of the newborn is reported as the most commonly identified pathologic cause of hyperbilirubinemia.[6]

Anti-D is the most common cause of death due to severe HDN.[6]

In Palestine, antibody screening is done antenatally only for pregnant women who are Rh-D negative to detect the presence of anti-D. Pregnant women could form alloantibodies either within Rh-systems such as anti-C, anti-c, anti-E, and anti-e or other systems. This could lead to serious delays in diagnosing HDN.

Here, we report a case of maternal anti-e alloimmunization in an Rh (D)-positive mother, which was detected postnatally by a positive direct antiglobulin test.

 Case Report

A male infant (3 kg) was born at 38 weeks of gestation by normal delivery. The mother was a 27-year-old with a normal healthy pregnancy; her blood group was B and Rh-D was positive. According to the policies of the Palestinian Ministry of Health, antibody screening was not done for the mother in the first trimester because she had Rh-D antigen (positive).

After the birth, routine laboratory tests were done to evaluate the newborn, including complete blood count, blood group (ABO-D), total serum bilirubin (TSB), C-reactive protein (CRP), and blood culture. The hemoglobin (Hb) level was 16.2 g/dl, CRP was negative, the blood culture was negative, ABO-D was B positive, and TSB was 20 mg/dl.

After the elimination of the other causes of newborn hyperbilirubinemia, the DCT, was ordered and the result was positive for DCT. The indirect Coombs test was done for antibody screening for the mother and the result was positive. Antibody identification was done; anti-e was identified. TSB was repeated at 6 h postdelivery with phototherapy and the result was 22.6 mg/dl. At 12 h postdelivery, the TSB level was 23.2 mg/dl. The TSB level was 25.4 at 18 h postdelivery. At 24 h postdelivery, the TSB level was 26.1 mg/dl and the Hb level was 14.5 g/dl, so the first intravenous immunoglobulin (IVIG) shot was ordered. The TSB level was 32.3 mg/dl in the next 4 h after the first IVIG shot (at 28 h postdelivery) and the Hb level decreased to 13.6 g/dl. The newborn was prepared for blood exchange, so compatible blood unit from the mother's brother, who had negative phenotype for little e-antigen, was prepared for blood exchange because no blood units that were negative for e-antigen were found in the blood banks. At 32 h postdelivery, the TSB level was 30.8 mg/dl and the Hb level was 12.9 g/dl. At 36 h postdelivery, the TSB level was 28.9 mg/dl and the Hb level was 12.4 g/dl, so a second IVIG was ordered. After 4, 8, 12, and 24 h after the second dose of IVIG (at 40, 44, 48, and 60 h postdelivery, respectively), the TSB level decreased to 25.8 mg/dl, 22.1 mg/dl, 18.3 mg/dl, and 16.8 mg/dl, respectively, where the Hb level was stable around 12 g/dl; blood exchange was therefore cancelled. At 72 h postdelivery, the TSB level was 14.2. [Figure 1] illustrates the TSB level changing overtime whereas [Figure 2] illustrates the Hb level changing over time.{Figure 1}{Figure 2}


When fetal RBCs are positive for an antigen that is absent in the mother's red cells, maternal alloantibody production is stimulated. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. This process is called HDN.[4] This case was the first HDN case due to anti-e with severe hyperbilirubinemia in Palestine. The peak of serum bilirubin was reported at 28 h postdelivery, with a TSB level of 32.3 mg/dl but hydrops fetalis was not reported in this case. The lowest Hb level was stable around 12 g/dl. The severity of hyperbilirubinemia could be reduced by IVIG without newborn blood exchange.

The most common cause of death from severe HDN cases is anti-D, but since the widespread use of anti-D immunoglobulin prophylaxis in preventing sensitization of Rh-negative mothers, this leads to fall in the incidence of Rh HDN, but it still presents.

Due to the decrease in HDN cases in recent years, pediatricians are less experienced at performing newborn blood exchange, so the morbidity associated with this procedure could increase. IVIG could be used in cases such as the one described to minimize the side effects of HDN without the need for blood exchange to reduce the risks of blood exchange at the hands of inexperienced staff.[3],[5],[6],[7]

HDN due to anti-e alone is very rare. McAdams et al. reported a severe HDN case due to the presence of anti-e in 2008, whereas Chapman and Waters reported another case in 1981.[2],[3] In Turkey, Karagol et al. studied 106 HDN cases due to Kell, C, c, E, and e alloantibodies and HDN due to anti-e was reported in 5 (4.7%) of 106 cases.[8]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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