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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 221-224

A rare case of immune hydrops in an “Elevated D” pregnancy


1 Department of IH and BT, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Transfusion Medicine, Bharatiya Vidhya Peeth University, Pune, Maharashtra, India

Date of Submission20-Aug-2020
Date of Decision23-Sep-2020
Date of Acceptance06-Oct-2020
Date of Web Publication13-Nov-2020

Correspondence Address:
Amit Kumar Biswas
Department of IH and BT, Armed Forces Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_89_20

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  Abstract 


The D-/-phenotype is a rare variant of the Rh system, in which red blood cells express only D antigen. Sensitized D-/-women carry a risk of hemolytic disease of fetus and newborn (HDFN) and pose a challenge in management due to nonavailability of antigen negative blood for intra-uterine/exchange-transfusion. A 23y old G2P1L1A0, blood group “A” Rh D+C-c-E-e- presented at 20 weeks' period of gestation (POG) with a positive indirect antiglobulin test. Cordocentesis at 23 weeks' POG revealed fetal's blood group as “B” Rh D+, Direct Coombs Test 4+, Hemoglobin 2.8 g/dL. USG with MCA-PSV indicated rapid development of fetal anemia and hydrops. Patient's sibling had D-/-phenotype, but was ABO-incompatible with the fetus. Rapidity of progression of case resulted in intrauterine fetal demise at 27 weeks' POG. HDFN, in rare blood groups, leads to problems in arranging compatible units in developing countries due to lack of centralized rare donor registries.

Keywords: Antibody screening, elevated D, hemolytic disease of fetus and newborn


How to cite this article:
Biswas AK, Bajaj AK, Philip J, Kushwaha N. A rare case of immune hydrops in an “Elevated D” pregnancy. Glob J Transfus Med 2020;5:221-4

How to cite this URL:
Biswas AK, Bajaj AK, Philip J, Kushwaha N. A rare case of immune hydrops in an “Elevated D” pregnancy. Glob J Transfus Med [serial online] 2020 [cited 2020 Nov 26];5:221-4. Available from: https://www.gjtmonline.com/text.asp?2020/5/2/221/300643




  Introduction Top


The D-/-phenotype, a very rare variant of the Rh system was first described by Race and Sanger in 1950.[1] Red cells of such individuals express the D antigens, but no C, c, E, e antigens. The lack of RhCE encoded proteins is associated with an over-expression of the D antigen, known as “Elevated D.”[1],[2] Individuals may become sensitized to high-frequency Rh system antigen (Rh 17) by transfusion or pregnancy.[1] Sensitized women carry a major risk of hemolytic disease of fetus and Newborn (HDFN).[2]

D-/-has been reported especially in populations with a high consanguinity rate.[1],[2] There have been reported cases of HDFN due to anti-Rh 17, but the rapidity of progression of the disease and the difficulty in its management has not been addressed to a great extent. We present a case of a severe HDFN in an “Elevated D” pregnancy, its progression and the difficulties faced in management.


  Case Report Top


A 23-year-old female, (G2P1L1), a booked case at our hospital, reported at 20 weeks' period of gestation (POG) for ABO grouping and indirect coombs test (ICT). There was a history of pre-eclampsia in her first pregnancy, an uneventful delivery followed by a single double-volume exchange transfusion (ET) in her first-born child, but later had normal developmental milestones and offered no complaints till wdate. The patient's blood group was A Rh D+, ICT positive (3+) by column agglutination technology using BioRad (Switzerland) ID gel cards. Her titer at 20 weeks' POG was 1:128.

A commercial 3-cell panel for antibody screening showed pan-agglutination. Antibody confirmation done using a BioRad (Switzerland) antibody identification 11-cell panel also showed pan-agglutination with a negative autocontrol. Rh-Kell typing of the patient's red cells showed no C, c, E, e antigens [Figure 1]. Sample from the patient's husband was also evaluated to look for any red cell antigens, which may have been inherited by the fetus. The husband's blood group was B with a Rh phenotype of D+, C +, c +, e+ [Figure 2]. Although the antibody suspected was anti-Rh17, its confirmation was not possible due to unavailability of anti-Rh 17 antisera.
Figure 1: Rh-Kell typing of the patient's red cells showed no C, c, E, e antigens

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Figure 2: Rh-Kell phenotype gel card of the patient's husband showing C+, c+, E-, e + phenotype

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The patient was advised antenatal ultrasonography, which showed a single live intrauterine pregnancy and no fetal abnormality. Middle cerebral artery peak systolic velocity (MCA-PSV) at 20 weeks POG was normal-31.9 cm/s (cut off– 40 cm/s) with no evidence of fluid accumulation in any body cavity of the fetus. The patient was advised a follow-up after 2 weeks.

Due to a lack of a centralized rare donor registry, a proactive search for a compatible blood was carried out at our center foreseeing any possibility of intrauterine transfusion (IUT)/ET. Initially, multiple O Rh D negative blood units from our blood bank inventory and O Rh D-negative donors registered at our center were phenotyped but were found to be Rh phenotype incompatible with the mother's blood. Family members of the patient were tested for blood group and phenotype. The patient's brother was found to be A Rh D+, D-/-phenotype and was compatible with that of the patient. The patient's brother was reserved as a potential donor for IUT/ET.

Repeat ultrasound at 23 weeks' POG showed fluid in all the body cavities of the fetus and features of hydrops fetalis [Figure 3]. The MCA-PSV was now 43 cm/s (cut off 40 cm/s) and the patient also developed peripheral edema and hypertension. The repeat ICT titer of the patient's was 1: 512. Cordocentesis performed at 23 weeks' POG revealed (baby's blood sample) Hb of 2.8 g/dL, DCT 4+, blood group B Rh D + and cord blood bilirubin 4.6 mg/dL (Indirect bilirubin– 2.9 mg/dL). Adsorption elution studies on the cord blood red cells showed pan-agglutination in the 3 and 11 cell panel with a negative auto control.
Figure 3: Ultrasonography of the fetus at 23 weeks' period of gestation showing features of Hydrops in the form of ascites and cutaneous edema

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The blood group of the fetus was ABO incompatible with the probable donor, i.e., the patient's brother and the Hb of the mother was 9.8 gm/dL. Other blood banks in the city were also contacted but a compatible blood for IUT could not be found.

The patient was admitted at 24 weeks' POG as a case of preeclampsia but was unwilling for an ABO incompatible IUT. Despite all our efforts to arrange for a compatible blood for IUT, the patient had an intrauterine fetal demise at 27 weeks' POG.

The samples from the patient were sent for confirmatory testing at the reference-testing center. The offending antibody was confirmed to be anti-Rh 17. Molecular studies were not done due to a resource constraint. Although the case could not be salvaged, it brought to light the rapid progression of the disease in the fetus and the unavailability of rare blood groups in such situations due to a lack of a dedicated centralized rare donor registry.


  Discussion Top


The Rh blood group system is one of the highly polymorphic systems in transfusion medicine.[3] Two genes on chromosome 1 (the RhD gene and the RhCE gene) code for the D antigen and the CcEe antigens, respectively.[4] Little is known about the genetic defect that is responsible for the D-/-phenotype.[5],[6] These individuals can become immunized by pregnancy or any previous transfusion.[1],[2] Our patient was most probably sensitized during her first pregnancy.

D-/-phenotype occurs in the Japanese population at a relatively high frequency (1 in 100,000).[2],[7],[8],[9] More than 50 cases of HDFN have been reported in Japan due to anti Rh17.[2],[10] Hirose et al. compared 8 cases out of all reported cases of HDFN due to anti-Rh 17 in English and Japanese literature in which a prenatal diagnosis was made. All 8 patients had a preterm delivery with titers between 1:128 and 1:4000 with an adverse outcome in 2 of the cases (fetal hydrops). In the reported cases from Japan D-/-donors are registered at a centralized rare donor registry, which makes the availability of this rare blood group for transfusion possible.[2]

In our case study, the preexisting antibody caused an abrupt deterioration in the fetus over 2 weeks without any external trigger, showing that the antibody has a high hemolytic potential. Aref et al. support this in their case study where despite a high ΔOD 450 and high antibody titer in their patient at 20 weeks POG, no fetal hydrops or anemia was present on USG study. At 33 weeks POG, there was an abrupt increase in MCA-PSV (>1.5 times multiples of median) with USG suggestive of fetal hydrops. They used frozen group O Rh D negative (D-/-) RBCs for an ET in the newborn.[11] Shahverdi et al. have also mentioned in their study that a centralized rare donor registry in Iran made the availability of D-/-blood possible for an IUT, when required.[12] It is a challenge to acquire compatible blood for patients who have clinically important alloantibodies to high-prevalence/rare antigens in our set up due to the lack of a centralized dedicated rare donor registry.

Mari et al. reported that elevations of antibody titer and MCA-PSV in D-/-phenotype women strongly suggests the presence of fetal anemia, which needs monitoring using an invasive intervention, including cordocentesis until the early third trimester and immediate delivery in the middle to late third trimester.[13] Cordocentesis should be introduced timely in such cases, even if it may provoke an anamnestic immune response, which was reported by Hirose et al.[2],[14] One previous study reported successful management with an IUT for fetal hemolytic anemia in a sensitized D-/-woman.[15] Another management option is by transfusing washed maternal RBCs for IUT. Serial maternal blood donations can be used to treat these high-risk pregnancies.[16] Denomme et al. reported a case of an immunized anti-Rh 17 woman whose ABO mis-matched fetus received serial maternal blood for IUTs. During her affected pregnancy, the woman donated blood at 12, 19, 28, 32, and 36 weeks' POG and seven IUTs were done by the 36th week of gestation. The authors reported no adverse effects to the mother or fetus.[17]

Our patient was counseled for an ABOi IUT using the patient's brother's blood. The potential risk associated with a maternal-to-fetal ABO-mismatched transfusion was less than the benefit because anti-A and anti-B are not detected in a large proportion of fetuses and are absent or weakly detectable in cord serum.[18] However, the patient did not consented for the procedure due to lack of proven benefits and guidelines for the same.

HDFN due to anti-Rh 17 has a dramatic clinical course and leads to sudden deterioration of the fetus. A proactive monitoring with serial antibody titers and USG MCA-PSV is required to ensure early intervention. This case highlights the importance of including an ICT as a part of routine prenatal work up to detect rare antibodies early in the pregnancy.

Apart from the above, there is also an urgent requirement of having a rare donor program (RDP) or a centralized rare donor registry in developing countries like ours due to the increasing demand on the transfusion medicine services to provide compatible blood in such difficult scenarios. Except for Japan and China, a rare donor registry program is yet to be in place in Asia. With respect to Indian perspective, even though there is a well-established Immunohematology Reference Laboratory at the National Institute of Immunohematology (NIH), Mumbai, where few rare donor phenotypes have been identified, but a fully functional RDP is presently not available.[19]

Further case reports and studies are needed on serial maternal blood donations during pregnancy and on the safety of ABO incompatible IUTs such that guidelines can be laid down that can help the clinicians and the patients to take an informed decision.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. The patient understand that name 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.
Race RR, Sanger R. Blood Groups in Man. 6th ed. London: Blackwell; 1975. p. 215.  Back to cited text no. 1
    
2.
Hirose M, Nakanishi K, Kaku S, Moro H, Hodohara K, Aotani H, et al. Fetal hemolytic disease due to anti-Rh17 alloimmunization. Fetal Diagn Ther 2004;19:182-6.  Back to cited text no. 2
    
3.
Flegel W, Wagner F. Molecular genetics of RH. Vox Sang 1999;78:109-15.  Back to cited text no. 3
    
4.
Raynal V, D'ambrasio AM, Carton JP, Colin Y. Molecular analysis of the structure and expression of RH locus in individuals with D, Dc and Dcw gene complex. Blood 1994;5:62-5.  Back to cited text no. 4
    
5.
Chérif-Zahar B, Raynal V, D'Ambrosio AM, Cartron JP, Colin Y. Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes. Blood 1994;84:4354-60.  Back to cited text no. 5
    
6.
Race RR, Sanger R. A probable deletion in a human Rh chromosome. Nature 1950;166:520.  Back to cited text no. 6
    
7.
Race RR, Sanger R, Selwyn JG. A possible deletion in a human Rh chromosome: A serological and genetic study. Br J Exp Pathol 1951;32:124-8.  Back to cited text no. 7
    
8.
Mora ML, Botti G, Lomas C. Ten homozygous-D-individuals in one Italian village. Hum Hered 1990;40:278-84.  Back to cited text no. 8
    
9.
Olafsdottir S, Jensson O, Thordarson G, Sigurdardottir S. An unusual Rhesus haplotype,-D-, in Iceland. Forensic Sci Int 1983;22:183-7.  Back to cited text no. 9
    
10.
Okubo Y. Pre-transfusion testing with special reference to blood groups (in Japanese). Tokyo: Ishiyaku Publishers; 1991. p. 40-1.  Back to cited text no. 10
    
11.
Aref K, Boctor F, Pande S, et al. Successful perinatal management of hydrops fetalis due to hemolytic disease associated with D–maternal phenotype. J Perinatol 2002;22:667-8.  Back to cited text no. 11
    
12.
Shahverdi E, Moghaddam M, Abolghasemi H. First report of the rare RhCE-depleted D–phenotype in sixteen people of Iranian origin. Vox Sang 2019;114:256-61.  Back to cited text no. 12
    
13.
Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman R, Moise KJ Jr, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler assessment of the blood velocity in anemic fetuses. N Engl J Med 2000;342:9-14.  Back to cited text no. 13
    
14.
Rodeck CH, Deans A. Red cell alloimmunisation. In: Rodeck CH, Whittle MJ, editors. Fetal Medicine: Basic Science and Clinical Practice. London: Churchill-Livingstone; 1999. p. 785-804.  Back to cited text no. 14
    
15.
Deitenbeck R, Tutschek B, Crombach G, Stannigel H. Successful management of pregnancy and hemolytic disease of the newborn due to anti-HrO in a woman of the D–phenotype. Transfusion 1999;39:1151-2.  Back to cited text no. 15
    
16.
Gonsoulin WJ, Moise KJ Jr, Milam JD, Sala JD, Weber VW, Carpenter RJ Jr. Serial maternal blood donations for intrauterine transfusion. Obstet Gynecol 1990;75:158-62.  Back to cited text no. 16
    
17.
Denomme GA, Ryan G, Seaward PGR, Kelly EN, Fernandes BJ. Maternal AB0-mismatched blood for intrauterine transfusion of severe hemolytic disease of the newborn due to anti-Rh 17. Transfusion 2004;44:1357-60 (PMID: 15318861 DOI: 10.1111/j.1537-2995.2004.04082.x).  Back to cited text no. 17
    
18.
Mollison PL, Engelfriet CP, Contreras M. Blood transfusion in clinical medicine. 9th ed. Oxford: Blackwell Scientific Publications; 1992.  Back to cited text no. 18
    
19.
Ahuja K, Surinder S. Review: Rare donor registry: Need of the hour. Int J Tech Research and Appl 2015;3:104-5.  Back to cited text no. 19
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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