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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 117-119

Late-onset hyporegenerative anemia in an infant with rhesus isoimmunization


1 Department of Pediatrics, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India
2 Department of Pathology, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India

Date of Submission08-Feb-2021
Date of Acceptance12-Mar-2021
Date of Web Publication15-May-2021

Correspondence Address:
Ramesh Srinivasan
Department of Pediatrics, PSG Institute of Medical Sciences and Research, Avinashi Road, Peelamedu, Coimbatore - 641 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.jcn_24_21

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  Abstract 


Late-onset anemia is a complication of hemolytic disease of fetus and newborn. It includes late hemolytic anemia and late hyporegenerative anemia. This case report is to discuss an Rh isoimmunized infant who presented with late-onset hyporegenerative anemia. The infant had low reticulocyte count, negative direct antiglobulin test, high erythropoietin, and high ferritin levels. She was treated with repeated blood transfusions and improved after 4 months of age. The follow-up of infants with Rh isoimmune hemolytic disease is needed for identification of late-onset anemia.

Keywords: Hydrops fetalis, hyporegenerative anemia, late-onset anemia, Rh hemolytic disease


How to cite this article:
Velumani SR, Srinivasan R, Kumar PN. Late-onset hyporegenerative anemia in an infant with rhesus isoimmunization. J Clin Neonatol 2021;10:117-9

How to cite this URL:
Velumani SR, Srinivasan R, Kumar PN. Late-onset hyporegenerative anemia in an infant with rhesus isoimmunization. J Clin Neonatol [serial online] 2021 [cited 2022 Dec 2];10:117-9. Available from: https://www.jcnonweb.com/text.asp?2021/10/2/117/316186




  Introduction Top


Rhesus D isoimmunization is a common cause for severe hemolytic disease of fetus and newborn (HDFN). Late-onset anemia occurring after 1st week of life is found in 71%–83% of neonates with Rh hemolytic disease, and the incidence is highest among infants who received intrauterine transfusion. It commonly develops between 2 and 6 weeks after birth and usually resolves by the 3rd month of life.[1] This case report discusses an Rh isoimmunized infant who presented during the 2nd month of life with severe anemia.


  Case Report Top


A female neonate was delivered at 35 weeks gestational age by cesarean section to a fourth gravida mother. The mother's blood group was A-negative with positive indirect antiglobulin test (IAT). Anti-D was given in the first two pregnancies but not in the third pregnancy. In the current pregnancy, antenatal ultrasound scan at 31 weeks of gestational age showed features of hydrops fetalis with ascites, pleural effusion, and hepatosplenomegaly. Intrauterine transfusion was done twice at 32 and 34 weeks of gestational age. The baby had normal transition at birth. On examination, the baby had hepatosplenomegaly but no pallor or icterus. Double-volume exchange transfusion was done at 7 h of life in view of in utero hydrops fetalis. Serum bilirubin sequentially monitored was not in treatment range. Packed red blood cell (PRBC) transfusion was done on day 3 of life for anemia with hemoglobin 9.1 g/dl, and the baby was discharged on day 8 of life [Table 1].
Table 1: Hematological parameters during the course of illness

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At review on day 50 of life, the infant showed adequate weight gain but had hemoglobin of 4.2 g/dl. Peripheral smear showed severe normocytic normochromic anemia with normal leukocyte and platelets. Reticulocyte count was low (0.2%). Direct antiglobulin test (DAT) was negative, but IAT was positive. Serum erythropoietin level was high. Parvovirus B19 DNA polymerase chain reaction was negative. Work-up for iron deficiency and megaloblastic anemia showed normal reports, except for increased serum ferritin level. Bone marrow study showed normoblastic erythroid hyperplasia; the myeloid series and megakaryocytes were normal. Hemoglobin electrophoresis was normal. Hence, late-onset hyporegenerative anemia of rhesus hemolytic disease was diagnosed. The baby received PRBC transfusions on day 52, 60, and 84 of life. The baby was on folate and multivitamin supplements. Intravenous immunoglobulin (IVIg) was given on day 85 of life. At 4 months of age, the baby's hemoglobin level stabilized with increase in reticulocyte count. Liver span became normal, while spleen was not palpable. The infant did not require further transfusions. Follow-up showed hemoglobin in improving trend. At 7 months of age, IAT became negative, and DAT was positive. The Rh type that was hitherto reported as equivocal due to mixed field reaction was now reported as O-positive.


  Discussion Top


HDFN is caused by the destruction of red blood cells (RBCs) of the fetus or newborn by maternal IgG alloantibodies that have crossed the placenta. Rh isoimmunization may lead to late hyporegenerative anemia. Pathogenesis implicated is antibody-dependent intramedullary destruction of RBCs and its precursors and bone marrow suppression by intrauterine/postnatal RBC transfusion. This anemia is characterized by normal bilirubin level and low or absent reticulocyte count. In contrast, late hemolytic anemia following Rh isoimmunization is characterized by active bone marrow erythropoiesis and elevated reticulocyte counts associated with elevated bilirubin levels.[2]

Low reticulocyte count in the peripheral smear with erythroid hyperplasia in bone marrow suggests antibody-mediated intramedullary destruction of red cell precursors. In addition, negative DAT with positive IAT in the baby suggests severe hemolysis because of the mother's Rh antibody, with the presence of free circulating maternal antibodies and absent baby's native red cells for forming antigen antibody complex.[3] Thus, the baby's circulating RBCs were probably only transfused compatible cells.

Serum erythropoietin level may be low relative to the degree of anemia in babies with late hyporegenerative anemia, but it may not be so always. Moreover, treatment with recombinant erythropoietin (rEPO) may be ineffective when anti-Rh (D) antibody titers are high. Thus, in late hyporegenerative anemia in HDFN, available data are not sufficient to support beneficial effects of rEPO.[4] Hence, erythropoietin therapy may not be essential in all such cases.

IVIg reduces the immune-mediated hemolysis by blocking Fc receptors in the reticuloendothelial system of neonate and enhances maternal antibody clearance. A meta-analysis by Louis et al. on the role of IVIg in isoimmune hemolytic disease of newborn showed that IVIg did not reduce the need for top-up transfusion in both Rh and ABO isoimmunization.[5] A meta-analysis by Li et al. has found that IVIg therapy did not cause any significant difference in the incidence of late anemia among babies with isoimmune hemolytic disease.[6] A study by Al-Alaiyan et al. on effects of IVIg on late hyporegenerative anemia due to rhesus HDFN has stated that there was no significant difference on the incidence of late anemia and requirement of top-up transfusion.[7] Hence, routine use of IVIg should not be encouraged in managing HDFN.

High iron storage as evidenced by increase in serum ferritin level occurs in hyporegenerative anemia due to treatment with multiple intrauterine transfusion and postnatal RBC transfusion. Rath et al. have reported that in neonates with red cell isoimmune hemolytic disease, iron overload occurs in 70% of neonates at birth, and the incidence of iron overload gradually decreases within the first 3 months, once the blood transfusions are discontinued.[8] Hence, iron essential for hemoglobin synthesis by erythroblast has to be supplemented only if serum ferritin levels are low or in normal range.


  Conclusion Top


In infants with HDFN, regular follow-up of hemoglobin, reticulocyte count, and serum ferritin level are advisable till hematological parameters stabilize in normal range. Late-onset anemia can be managed with regular top-up transfusions and the role of rEPO and IVIg is to be decided on case-to-case basis.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Al-Alaiyan S, Al Omran A. Late hyporegenerative anemia in neonates with rhesus hemolytic disease. J Perinat Med 1999;27:112-5.  Back to cited text no. 1
    
2.
Ree IM, Smits-Wintjens VE, van der Bom JG, van Klink JM, Oepkes D, Lopriore E. Neonatal management and outcome in alloimmune hemolytic disease. Expert Rev Hematol 2017;10:607-16.  Back to cited text no. 2
    
3.
Parker V, Tormey CA. The direct antiglobulin test: Indications, interpretation, and pitfalls. Arch Pathol Lab Med 2017;141:305-10.  Back to cited text no. 3
    
4.
Pessler F, Hart D. Hyporegenerative anemia associated with Rh hemolytic disease: Treatment failure of recombinant erythropoietin. J Pediatr Hematol Oncol 2002;24:689-93.  Back to cited text no. 4
    
5.
Louis D, More K, Oberoi S, Shah PS. Intravenous immunoglobulin in isoimmune haemolytic disease of newborn: An updated systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2014;99:F325-31.  Back to cited text no. 5
    
6.
Li ZH, Wang J, Chen C. Meta analysis of the effect of immunoglobulin infusion on neonatal isoimmune hemolytic disease caused by blood group incompatibility. Zhonghua Er Ke Za Zhi 2010;48:656-60.  Back to cited text no. 6
    
7.
Al-Alaiyan S, Ahmad HA, Al-Hazzani F, AlHasan M, Dawoud M, Khadawardi E, et al. Effects of intravenous human immunoglobulin on late hyporegenerative anemia secondary to rhesus hemolytic disease of the newborn. Int J Pediatr Adolesc Med 2014;1:73-7.  Back to cited text no. 7
    
8.
Rath ME, Smits-Wintjens VE, Oepkes D, Walther FJ, Lopriore E. Iron status in infants with alloimmune haemolytic disease in the first three months of life. Vox Sang 2013;105:328-33.  Back to cited text no. 8
    



 
 
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