Asian Journal of Transfusion Science
Home About Journal Editorial Board Search Current Issue Ahead of print Back Issues Instructions Subscribe Login  Users: 397 Print this page  Email this page Small font sizeDefault font sizeIncrease font size 

CASE REPORT Table of Contents   
Year : 2013  |  Volume : 7  |  Issue : 1  |  Page : 84-85
Hemolytic disease of the fetus and newborn caused by anti-E

1 Department of Hematology and Transfusion Medicine Unit, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia
2 Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia

Click here for correspondence address and email

Date of Web Publication2-Feb-2013


Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother's red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.

Keywords: Allo-antibody, anti-E, hemolytic disease of the fetus and newborn

How to cite this article:
Usman AS, Mustaffa R, Ramli N, Diggi SA. Hemolytic disease of the fetus and newborn caused by anti-E. Asian J Transfus Sci 2013;7:84-5

How to cite this URL:
Usman AS, Mustaffa R, Ramli N, Diggi SA. Hemolytic disease of the fetus and newborn caused by anti-E. Asian J Transfus Sci [serial online] 2013 [cited 2022 Sep 25];7:84-5. Available from:

   Introduction Top

Maternal red cell allo-immunization occurs when the fetus is positive for an antigen that is absent on maternal red cells. The mother is stimulated to produce immunoglobulin G (IgG) antibodies against the positive fetal red cells which pass through the placenta and destroy the antigen-positive fetal red cells. Clinically significant allo-antibodies other than anti-D such as anti-E, anti-K, and anti-c occur in 1:300 pregnancies and risk of hemolytic disease of the fetus and newborn (HDFN) caused by these antibodies is 1:500. [1] Anti-E is the most common clinically significant allo-antibody detected in the Malaysian population. [2] We report here two cases of anti-E HDFN in two Malay infants.

   Case Reports Top

Case 1

A full-term male neonate born to a 32-year-old G2P2 Malay lady was noticed to have jaundice on day 1 after birth. His birth weight was 2.96 kg. The mother and the baby were grouped AB and B, respectively, both being positive for RhD antigen. The baby was shifted to neonatal intensive care unit (NICU) on the following day with hepatomegaly 3 cm and splenomegaly 5 cm below the costal margin. Direct antiglobulin test (DAT) on the neonate's red cells was strongly positive (4+). Hemoglobin was 6.2 g/dL. A sudden rise of total serum bilirubin (TSB) level from 102 μmol/L on day 1 to 401 μmol/L within 24 h prompted to double volume exchange transfusion (ET). The hyperbilirubinemia was mainly of conjugated bilirubin 1 day post-ET [Figure 1].
Figure 1: Concentration of direct and indirect bilirubin (μmol/L) in the infant's serum from the time of admission to day 6

Click here to view

Investigations for infectious causes such as blood culture, urine microscopy, and culture were negative. Liver enzymes such as alkaline phosphatase, alanine transaminase, and aspartate amino transferase were also within the normal ranges. G6PD screening was negative. No evidence of biliary atresia was found. Anti-E was detected and identified in the mother's serum and eluate from the baby's red cells. Rh genotype was performed for the mother, father, and the neonate. The mother was typed as R1R1 (DCe/DCe), father R1R2 (DCe/ DcE). Although the baby's red cells reacted with all the Rh subtype reagents there by typing as R1R2 (DCe/ DcE), the results could not be validated as the auto-control test was positive as well. The neonate was placed on single phototherapy and was given intravenous immunoglobulin (IVIG) at a dose of 0.5 g/kg over 4 h.

The peripheral blood film of the neonate showed evidence of hemolysis such as polychromasia, nucleated red blood cells (NRBCs), and red cell fragments. The baby also presented with thrombocytopenia that was not associated with any known infection. We presumed this could be allo-immune in nature, though no attempt to test for platelet-specific antibodies was made due to lack of facility. He was clinically fit at day 8 of life with slightly lower total serum bilirubin of 230 μmol/L at the time of discharge. The baby was discharged on day 8 of life hale and hearty.

Case 2

A male neonate was delivered via spontaneous vaginal delivery (SVD) at 30 weeks of gestation by a 33 year-old Malay lady G7P7. The mother had a history of premature deliveries in all but one of her previous pregnancies. Her blood group was O RhD positive and was Rh-subtyped as R1R1 (DCe/DCe). Post-SVD antibody screen test in her serum was positive with antibodies identified as anti-c and anti-E. The neonate's birth weight was 1.8 kg. He was transferred to NICU. He was noticed to have jaundice (serum bilirubin 138 μmol/L) at 14 h after birth. His blood group was B RhD positive with Rh-subtype R1R2 (DCe/DcE). DAT was positive (2+). As in the first case, the Rh-subtype results may be interpreted with caution in light of the DAT being positive. A possibility of the ABO HDFN was opened but was ruled out with an extent that the eluate preparation from the baby's red cells showed anti-E only (not anti-c). The neonate became moderately anemic on day 5, with a hemoglobin level of 10.2 g/dL. No evidence of hemolysis was seen on the blood film. The patient was managed with phototherapy, IVIG, and transfusion of 30 cc of red cell concentrate. In light of underlying coagulopathy noticed at 6 h of life (with activated partial thromboplastin time 93.70 s, prothrombin time 20.8 s, and INR 1.80), a dose of 20 cc of fresh frozen plasma was also administered. He was discharged on day 14 of life as requested by the parents. His follow-up visit showed normal developmental milestones with consistent increase in body weight.

   Discussion Top

With the introduction of anti-D prophylaxis, the incidence of Rh HDFN has been reduced. ABO foeto-maternal blood group incompatibility is the main cause of HDFN. [3] Other red cell allo-antibodies such as anti-c, anti-C, anti-E, and anti-e of the Rh blood group system and anti-K of the Kell blood group system have been reported occasionally as rare causes of HDFN. [4],[5] Previous study [6] reported that most cases of HDFN caused by Rh antibodies other than anti-D have been detected in RhD-positive women. The two cases we report here were also in RhD-positive women. Here we described two cases of HDFN due to anti-E. Both the babies showed a positive DAT and corroborating findings of anti-E being present in serum samples of the respective mothers. Eluates obtained from the babies' red cells showed anti-E antibody specificity thus providing evidence for a cause of HDFN in both cases. In case 1, there is evidence of hemolysis seen on blood picture (anemia, polychromasia, NRBCs), whereas in the second case no evidence of hemolysis was seen on blood picture. The Rh genotypes in both cases were supportive of the hypothesis on anti-E as the cause of HDFN.

It has been reported previously that the risk of allo-antibody production is unknown during pregnancy, but foeto-maternal hemorrhage at the time of delivery is a frequent stimulus. [7] Both mothers in the present report were probably sensitized during previous pregnancies. Presentations of case 1 (anemia, conjugated hyperbilirubinemia, thrombocytopenia) are consistent with two earlier reported cases of HDFN caused by Rh antibodies other than anti-D. [8],[9]

   Conclusion Top

This case report shows that HDFN caused by anti-E may be moderate or severe in its presentation and brings to attention the necessity of introducing antibody screening for pregnant women as part of the antenatal care to look for significant allo-antibodies other than anti-D. Those mothers found to be allo-immunized should be monitored closely for measurement of maternal antibody titer and, in more severe conditions, for amniotic fluid analysis to monitor the fetus.

   Acknowledgments Top

We wish to acknowledge Universiti Sains Malaysia (USM) fellowship scheme for providing necessary support. We also acknowledge Mrs. Suzana Abu and Mr. Saw Teik Hock from the blood transfusion unit for bringing our attention to one of the cases.

   References Top

1.Koelewijn JM, Vrijkotte TG, van der Schoot CE, Bonsel GJ, de Haas M. Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: A population study in the Netherlands. Transfusion 2008;48:941-52.  Back to cited text no. 1
2.Al-Joudi Fawwaz F, Ali Anuar Bin AB, Ramli Majdan Bin MB, Ahmed Suhair S, Ismail Mohd M. Prevalence and specificities of red cell alloantibodies among blood recipients in the Malaysian state of Kelantan. Asian J Transfus Sci 2011;5:42.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.Kaplan M, Hammerman C. Understanding severe hyperbilirubinemia and preventing kernicterus: Adjuncts in the interpretation of neonatal serum bilirubin. Clin Chim Acta 2005;356:9-21.  Back to cited text no. 3
4.Armstrong B, Smart E. Haemolytic diseases. ISBT Sci Series 2008;3:93-109.  Back to cited text no. 4
5.Smits-Wintjens V, Walther F, Lopriore E. Rhesus haemolytic disease of the newborn: Postnatal management, associated morbidity and long-term outcome. Netherlands: Elsevier; 2008.  Back to cited text no. 5
6.Basu S, Kaur R, Kaur G. Hemolytic disease of the fetus and newborn: Current trends and perspectives. Asian J Transfus Sci 2011;5:3.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.Heddle NM, Klama L, Frassetto R, O'Hoski P, Leaman B. A retrospective study to determine the risk of red cell alloimmunization and transfusion during pregnancy. Transfusion 1993;33:217-20.  Back to cited text no. 7
8.Allgood C, Bolisetty S. Severe conjugated hyperbilirubinaemia and neonatal haemolysis. Int J Clin Pract 2006;60:1513-4.  Back to cited text no. 8
9.McAdams RM, Dotzler SA, Winter LW, Kerecman JD. Severe hemolytic disease of the newborn from anti-e. J Perinatol 2008;28:230-2.  Back to cited text no. 9

Correspondence Address:
Adiyyatu Sa'idu Usman
Department of Hematology and Transfusion Medicine Unit, School of Medical Sciences, Health Campus, University Sains Malaysia (USM), 16150 Kubang Kerian, Kelantan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-6247.106750

Rights and Permissions


  [Figure 1]

This article has been cited by
1 Management of severe hyperbilirubinemia in the cholestatic neonate: a review and an approach
Jon F. Watchko, M. Jeffrey Maisels
Journal of Perinatology. 2022;
[Pubmed] | [DOI]
2 A genetic polymorphism of IL17F rs763780 associated with anti-E production in the Han Chinese population
Sitian Chen, Jie Xiao, Ning Song, Haixia Xu, Li Tian, Zhong Liu
Transfusion and Apheresis Science. 2020; 59(4): 102745
[Pubmed] | [DOI]



    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Reports
    Article Figures

 Article Access Statistics
    PDF Downloaded78    
    Comments [Add]    
    Cited by others 2    

Recommend this journal

Association Contact us | Sitemap | Advertise | What's New | Copyright and Disclaimer | Privacy Notice

2006 - Asian Journal of Transfusion Science | Published by Wolters Kluwer - Medknow
Online since 10th November, 2006