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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 7  |  Issue : 1  |  Page : 99-102

Rare Anti-Cw antibody: Two case reports with review of literature


Department of Immunohematology and Blood Transfusion, Sri Balaji Action Medical Institute, New Delhi, India

Date of Submission09-Oct-2021
Date of Decision17-Jan-2022
Date of Acceptance07-Feb-2022
Date of Web Publication29-Apr-2022

Correspondence Address:
Dr. Sadhana Mangwana
Department of Immunohematology and Blood Transfusion, Sri Balaji Action Medical Institute, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/gjtm.gjtm_92_21

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  Abstract 


Introduction: Anti-Cw is a low-frequency antibody against Cw (Rh8) antigen, a low incidence antigen of the Rh system. Anti-Cw antibody may cause mild to moderate hemolytic disease of the fetus and newborn (HDFN) and mild to severe immediate or delayed hemolytic transfusion reactions (HTR). The antigenic frequency of Cw in the Indian population is 1.25%. Two cases of Anti-Cw antibody are being reported which were detected during routine antibody screening, one an oncology patient and the other a healthy blood donor. Case 1: A 30-year-old male, known case of acute myeloid leukemia, with previous history of induction chemotherapy and blood transfusion was admitted for further management and chemotherapy. When three cell antibody screening was performed using an automated platform, the screen was positive with +2 reactions. Antibody identification using 14 cells suggested the presence of an Anti-Cw antibody. On further testing, the patient red blood cell (RBCs) were negative for Cw antigen. Case 2: A 20-year-old male, first-time, voluntary blood donor, with no history of blood transfusion donated whole blood. On performing three cell antibody screening using automated platform, screen was found to be positive with +3 reactions. Antibody identification performed using 14 cell panel suggested the presence of Anti-Cw antibody. On further testing, the donor RBCs were negative for Cw antigen. Conclusion: Antibody screening and identification is recommended in pretransfusion testing, especially in multi-transfused patients and patients belonging to the reproductive age group, so that antibody to low-frequency antigen can be detected and its potential to cause HTR and HDFN can be assessed.

Keywords: Anti-Cw antibody, Antibody screening, pretransfusion testing


How to cite this article:
Mangwana S, Gohel D, Simon N. Rare Anti-Cw antibody: Two case reports with review of literature. Glob J Transfus Med 2022;7:99-102

How to cite this URL:
Mangwana S, Gohel D, Simon N. Rare Anti-Cw antibody: Two case reports with review of literature. Glob J Transfus Med [serial online] 2022 [cited 2022 Sep 26];7:99-102. Available from: https://www.gjtmonline.com/text.asp?2022/7/1/99/344345




  Introduction Top


Anti-Cw is a low-frequency antibody against Cw (Rh8) antigen, a low incidence antigen of the Rh system.[1] Anti-Cw was first described in 1946 in a patient with Lupus and named because of the association with 'C' antigen and 'W' from Willis, the first blood donor whose red blood cells (RBCs) carried the antigen.[2] Most Cw positive RBCs are also positive for the 'C' antigen. Cw positive RBCs exhibit a weaker expression of the 'C' antigen due to molecular changes associated with the Cw antigen. Usually, Anti-Cw occurs naturally, although it may be immune stimulated. Anti-Cw is almost always an IgG antibody, with rare case reports of IgM, and often occurs in association with other antibodies. Anti-Cw may cause mild to moderate hemolytic disease of the fetus and newborn (HDFN) and mild to severe immediate or delayed hemolytic transfusion reactions (HTRs).[3] As multi-transfused patients are more prone to develop red cell antibodies which can be picked up by red cell antibody screen, likewise antibody screen in donors is must to ensure safe transfusion. There is the prevalence of alloantibody in healthy donors, who are transfused previously or female donors with a history of pregnancy. The prevalence of red cell alloantibody is 0.17% in the North Indian population to 0.3% in multi-transfused patients.[4],[5] Two cases of Anti-Cw antibody are being reported which were detected in an oncology patient and a healthy blood donor during routine antibody screening.

Case 1

A 30-year-old male, known case of acute myeloid leukemia, with the previous history of induction chemotherapy and blood transfusion was admitted to the Department of Hemat-Oncology for further management and chemotherapy. Blood samples, received in the Department of Immunohematology and Transfusion Medicine, were processed for pretransfusion testing to ensure random donor platelets transfusion for the patient. On performing serological investigations using the automated platform (Immucor Inc., USA), the blood group of the patient was “O” RhD Positive and Rh and Kell Phenotype was Ccee, Kell Negative. When three cell antibody screen with R1R1, R2R2, and rr was performed using the automated platform (ImmucorInc., USA), the screen was positive with +2 reactions in cell 1 [Table 1]. Direct antiglobulin test (DAT) was performed on the patient's RBCs using polyspecific antiglobulin reagents (anti IgG and C3d) by column agglutination method and was found to be negative along with negative auto control. Antibody identification performed using 14 cell panel suggested the presence of Anti-Cw antibody [Table 2]. On further testing, the patient's RBCs were negative for Cw antigen. As requisition received was for platelet concentrate and not PRBC; hence, major cross-matching was not required. Platelet transfusions were uneventful. The patient was discharged without any complications.
Table 1: Antibody screening using 3 cell panel – Case 1

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Table 2: Antibody identification - Case 1

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Case 2

A 20-year-old male, first-time voluntary blood donor, with no history of blood transfusion donated whole blood in our Blood Center. On performing routine serological investigations using the automated platform (Immucor Inc., USA) blood group was “B” RhD Positive and Rh and Kell phenotype was CCee, Kell positive and single-cell antibody screen was positive. When three cell antibody screen with R1R1, R2R2 and rr was performed using the automated platform (Immucor Inc.), the screen was positive with +3 reactions in cell 01 [Table 3]. DAT performed on donor's RBCs using polyspecific antiglobulin reagents (Anti IgG and C3d) by column agglutination method and showed negative results along with negative auto control. Antibody identification was performed using 14 cell panel, where the pattern suggested the presence of Anti-Cw antibody [Table 4]. On further testing, the donor RBCs were negative for Cw antigen. All components were issued without any adverse events to the recipients.
Table 3: Antibody screening using 3 cell panel - Case 2

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Table 4: Antibody identification - Case 2

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  Discussion Top


Rh blood group is polymorphic in nature with 45 Rh antigens have been identified. Of these, the most significant ones are D, C, c, E, e. These antigens are expressed by RHD and RHCE genes on chromosome 1.[6],[7] Although Cw is also a part of the Rh blood group system, D, C, c, E, e antigens are with higher incidence and so the antibodies against them are formed more frequently than anti-Cw.[3] Mangwana et al. reported 68% of antibodies formed are from the Rh system.[5]

Cw is a low incidence antigen which results from single amino acid change (Gln41Arg) predicted to be located on the first extracellular loop of RHCE. Its antithetical antigens include CX (RH9) and the high-incidence MAR (RH51) antigen. Due to the location of Cw on the RHCE gene, almost always coincides with the C antigen. When associated with Cw, the C antigen shows weakened expression, hence an alloanti-C may rarely be made in C+Cw + individuals.[8]

The antigenic frequency of Cw in Latvians is 9%, in Finns - 4%, in Caucasians - 2%, and in the Indian population, its frequency is 1.25%.[9] Unlike many other Rh antigens, in the context of transfusion, the anti-Cw antibody is not typically clinically significant. But maternal Cw alloimmunization is not uncommon, with the reported frequency of 0.1%.[10] Few case reports of mild to severe HDN caused by anti-Cw are found in literature including one case of hydrops fetalis.[9] Anti-CW antibody has the potential to cause mild to severe immediate or delayed hemolytic transfusion reactions. There are case reports in the literature which describe anti-Cw of IgG type. However, Saini et al. reported a rare case of clinically significant IgM Anti-Cw in the obstetric patient from Central India.[10]

Since the antigen prevalence is low, the antibody prevalence against Cw antigen is likely to be very low. In the present study, a total of 18,053 donor samples were tested for antibody screening over the duration of 18 months (January 2019 to June 2021). Of these, 0.06% (n = 11) of total donor samples tested positive on antibody screening. On further testing for Antibody identification, 45.4% (n = 05) found to have weak warm autoantibodies and 54.5% (n = 06) had alloantibodies. Similarly, a total of 12,401 patient samples were tested for antibody screening. Of these, 0.33% (n = 41) of total patient samples tested positive on antibody screening. On further testing for antibody identification, 46.3% (n = 19) patients found to have weak warm autoantibodies and 53.6% (n = 22) patients had alloantibodies. Thus, out of a total of 30,454 samples tested, only two samples (0.006%) were found to be having Anti-Cw antibody, making its prevalence much lower than <0.1%, to fulfill the criteria of rare antibody. It is an IgG type of alloantibody which can cause HTR and HDFN, hence it becomes very important to have Cw cell in the screen panel as well as in the antibody identification panel so that Anti-Cw antibody can be timely picked and identified.

Identification of Anti-Cw antibodies requires the reagent RBCs panel which includes CW Ag-positive RBCs. Due to the low frequency of Cw positive individuals in the populations, some sets of screening cells may not include Cw positive cells and cases with anti-Cw may be missed. In the obstetric patient population, Cw antigen-positive antibody screening cells should be used for antibody screening as these antibodies may not be as infrequent as they are thought to be and can result in clinically significant HDFN. Also if these antibodies are identified, titer in maternal serum and assessment of fetal wellbeing should be done aggressively. When anti-Cw is detected in a patient's pre-transfusion sample, there is usually no requirement for the selection of Cw-negative donor RBCs. In fact, more than 98% of donor units are Cw-negative. For patients with Anti-Cw antibody, RBC units that are cross-match compatible at 37°C in the IAT phase should be selected for transfusion.


  Conclusion Top


Antibody screening and identification are recommended in pretransfusion testing, especially in multi-transfused patients and patients belonging to the reproductive age group, so that antibody to low-frequency antigen can be detected and its potential to cause HTR and HDN can be assessed.

Patient consent

This is a retrospective data analysis study. Patients have given their consent during their hospitalization and treatment. All ethical norms as per Declaration of Helsinki on Ethical Principles for Medical Research are followed.Identity of patient is not disclosed anywhere.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Callender ST, Race RR. A serological and genetical study of multiple antibodies formed in response to blood transfusion by a patient with lupus erythematous diffuses. Ann Eugen 1946;13:102.  Back to cited text no. 1
    
2.
Mennier D, Peng S, Clarke G. Rh System: Anti-Cw. Ottawa: Canadian Blood Services; 2019. Available from: https:// professionaleducation.blood.ca/en/transfusion/best-practices/ serological-best-practices. [Last accessed on 2021 Jun 08].  Back to cited text no. 2
    
3.
Klein H, Anstee D. The Rh blood group system (including LW and RHAG). In: Mollison's Blood Transfusion in Clinical Medicine. 12th ed. West Sussex, UK; Wiley Blackwell; 2013. p. 180.  Back to cited text no. 3
    
4.
Solanki A, Chandra T, Singh A. Prevalence of red blood cell antibodies in whole blood donors: A single-centre experience in north India. Indian J Med Res 2020;152:280-4.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Mangwana S, Kacker A, Simon N. Red cell alloimmunization in multi-transfused, oncology patients: Risks and management. Glob J Transfus Med 2019;4:74-8.  Back to cited text no. 5
  [Full text]  
6.
Avent ND, Reid ME. The Rh blood group system: A review. Blood 2000;95:375-87.  Back to cited text no. 6
    
7.
Westhoff CM. The Rh blood group system in review: A new face for the next decade. Transfusion 2004;44:1663-73.  Back to cited text no. 7
    
8.
Westhoff CM, Seigel DL. Rh and LW blood group antigens. In: Simon TL, McCullough J, Synder EL, Solheim BG, Trauss RG, editors. Rossi's Principles of Transfusion Medicine. 5th ed. West Sussex, UK; Wiley Blackwell; 2016.  Back to cited text no. 8
    
9.
Jain A, Elhence P, Tripathi A, Pandey H, Agarwal P. Anti- c (w): In a young female patient. A case report with review of literature and frequency of low incidence c (w) (rh8) antigen in north India. Indian J Hematol Blood Transfus 2014;30:440-4.  Back to cited text no. 9
    
10.
Saini N, Sood T, Kaur R, Mittal K, Kumar R, Kaur P. Clinically significant IgM Anti-Cw: A rare report. Indian J Hematol Blood Transfus 2017;33:298-9.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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