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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 1  |  Issue : 1  |  Page : 12-15

Red Blood Cell Alloimmunization in Multi - transfused Patients: A Bicentric Study in India


1 From the Department of Blood Bank, Fortis Escorts Hospital, New Delhi, India
2 From the Department of Immunohaematology, Rotary Bangalore TTK Blood Bank, Bangalore Medical Services Trust, Bengaluru, Karnataka, India

Date of Web Publication3-Mar-2016

Correspondence Address:
Amit Agrawal
From the Department of Blood Bank, Fortis Escorts Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2455-8893.178005

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  Abstract 

Background: It is well-known that alloimmunization to red blood cell antigens resulting from the genetic disparities between donor and recipient is one of the risks of blood transfusion. The antibody screening cells are used to detect unexpected antibodies. The risk of alloimmunization is higher in patients who have received multiple blood transfusions such as thalassemia, other hematological disorders, renal failure patients on dialysis who receive blood transfusions, and females with bad obstetric history. Antibody screening test using 2–3 cells panel is not a mandatory pretransfusion testing in India and is performed routinely in limited blood centers.
Materials and Methods: This bicentric study has been carried out to look at prevalence of antibodies in multi-transfused patients who have higher risks of alloimmunization such as patients who have received multiple blood transfusions such as thalassemia, other hematological disorders, renal failure patients on dialysis who receive blood transfusions, and females with bad obstetric history in the North as well as South India. The study was conducted at two blood centers, one regional blood transfusion of North India and one at South India. Totally, 4569 cases were analyzed and 258 patients were selected for antibody screening and identification.
Results: Of total 4569 patients, 258 multi-transfused patients were studied. Among these, seven patients (2.71%) were found alloimmunized. The risk of alloimmunization was 2.90% in thalassemia, 0% in chronic renal failure patients, 3.77% in pregnant females with bad obstetric history, and 2.78% in other multi-transfused patients like cancer.
Discussion: Regular monitoring through antibody screening and transfusion of blood matched for minor erythrocyte antigens are recommended in these patients.

Keywords: Alloimmunization, blood transfusion, red blood cells


How to cite this article:
Agrawal A, Mathur A, Dontula S, Jagannathan L. Red Blood Cell Alloimmunization in Multi - transfused Patients: A Bicentric Study in India. Glob J Transfus Med 2016;1:12-5

How to cite this URL:
Agrawal A, Mathur A, Dontula S, Jagannathan L. Red Blood Cell Alloimmunization in Multi - transfused Patients: A Bicentric Study in India. Glob J Transfus Med [serial online] 2016 [cited 2019 Aug 18];1:12-5. Available from: http://www.gjtmonline.com/text.asp?2016/1/1/12/178005


  Introduction Top


The transfusion of blood and components has become an integral part of patient management in modern medicine. As a result, the blood transfusion services play an important role and are responsible for ensuring sufficient quality and safe blood supply. Blood transfusion support is vital to the management of patients with hematologic disorders and malignancies. Many such patients require blood transfusion during their illness or may be lifetime.[1]

The discovery of the ABO blood group system by Karl Landsteiner greatly reduced the fatalities associated with blood transfusion. Introduction of the indirect antiglobulin test (IAT) by Coombs added a new dimension to the safety of blood transfusion with the identification of alloantibodies causing hemolytic disease of the newborn or transfusion reactions. This led to the discovery of about 300 blood group antigens as per International Society of Blood Transfusion.[2]

Blood groups are antigens and alloimmunization occurs when an incompatible antigen introduced in an immunocompetent host evokes an immune response. Clinically significant red blood cell (RBC) alloantibodies develop in 6–36% of multi-transfused patients and can pose major problems in long-term transfusion therapy.[3]

It is well-known that alloimmunization to RBC antigens resulting from the genetic disparities between donor and recipient is one of the risks of blood transfusion. The risk depends on the recipient's exposure to the foreign antigen and its immunogenicity. Immunization may also be influenced by the number and frequency of the transfusions as well as the recipient's sex, age, and underlying disease.[1]

The most important irregular RBC alloantibodies in daily transfusion practice, in terms of frequency of occurrence, are directed toward RH (anti- D, -C, -E, -c, and -e), Kell (anti-K), FY (anti-Fya and -Fyb), JK (anti-Jka and -Jkb), and MNS (anti-M, -S, and -s) blood group systems. Of these, the D-antigen is the most immunogenic, resulting in more than 80% of immunocompetent D-negative persons becoming alloimmunized after a transfusion of D-positive erythrocytes. Clinically significant antibodies are known to cause transfusion reactions and hemolytic disease of the newborn. The antibody screening cells are used to detect unexpected antibodies:

  1. Patient serum before transfusion to make sure a patient has no unexpected antibodies to react with donor cells
  2. Maternal serum to make sure a pregnant mother has no antibodies to react with fetal cells (hemolytic disease of the newborn).


If antibody screening is positive, additional tests are carried out to specifically identify antibody using the antibody identification panel and RBC antigen typing.

Screening cells are prepared from cells from two or three individual donors. These cells are procured from Group O blood donor and to be licensed by the Food and Drug Administration and must contain the following antigens: D, C, E, c, e, M, N, S, s, P1, Le a, Le b, K, k, Fy a, Fy b, Jk a, and Jk b. The most common clinically significant antigens must be present to detect the clinically significant antibodies. The presence of homozygous antigens on the RBCs is preferred to have a double dose of the antigen resulting in stronger reactions and ability to detect weaker antibodies.

Antibody screening test using 2–3 cells panel is not a mandatory pretransfusion testing in India and is performed routinely in limited blood centers. Very few studies have been carried out in India to look at prevalence of antibodies in multi-transfused patients. Therefore, there are limited data available to show the RBC alloantibody prevalence in a population which represents 17% of earth's population.

This bicentric study (one regional blood transfusion center of North India and South India) has been carried out to look at prevalence of antibodies in multi-transfused patients who have higher risks of alloimmunization such as thalassemia, other hematological disorders, renal failure patients on dialysis, and females with bad obstetrics history.


  Materials and Methods Top


The study was conducted at two stand-alone blood banks and regional blood transfusion centers in India. One in North India (referred as Center-I) which collects 25,000 units in a year and other from South India (referred as Center-II) which collects 35,000 units in a year. Both the blood centers have 100% voluntary blood donation and 100% blood component separation facility.

This study was conducted during February 1, 2012,–March 31, 2012, at both the centers in parallel. The pretransfusion testing protocol followed at both the centers was blood typing, IAT, and cross match. The antibody screening using 3 cells is not a routine practice at both the centers.

The patients included in the study were thalassemia, other hematological disorders, renal failure patients on dialysis who receive blood transfusions, and females with bad obstetrics history. These samples underwent initial antibody screening using commercial 3-cell panel. The samples with positive antibody screening were tested for antibody identification using 11-cell panel. The antibody screening cells and antibody identification cell panel used were procured from Diagast (DIAGAST251-Avennue Eugene Avinee-BP 9-59374 LOOS, FRANCE), and test was performed on Qwalys3, fully automatic machine working on erythrocyte magnetization technology and software to interpret the results.


  Results Top


In the study, totally, pretransfusion testing done at Center-I was 2315, total crossmatch tests done were 3760. One hundred fifty-four patients were selected for antibody screening tests at Center-I categorized as 24 thalassemic, 91 pregnant females with bad obstetric history, 8 chronic renal failure patient, 31 cancer patient, and other multi-transfused patients. Antibody screening was found positive in two patients, one thalassemic and other was pregnant female with bad obstetric history. On antibody identification, anti-C was found in thalassemic and anti-D and anti-K were found in the second patient.

At Center-II, totally, 2254 pretransfusion testing and 3667 crossmatch tests were done. A total of 104 cases were selected for the study categorized as 45 thalassemic, 15 pregnant females with bad obstetric history, 39 chronic renal failure, and 5 cancer patients. The antibody screening was found positive in total five patients, three were pregnant females, one was thalassemic, and other one was cancer patient. On antibody identification, two out of three pregnant females had anti-D and anti-D with anti-E in the third patient. In thalassemic patient, anti-K was found, and anti-Jkb was detected in acute myeloid leukemia patient [Table 1] and [Table 2].
Table 1: Rate of RBC alloimmunization and antibodies

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Table 2: Details of patient with positive antibody screen

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Including both the centers, of total 4569 patients, 258 multi-transfused patients were studied. Among these, seven patients (2.71%) were found alloimmunized. The risk of alloimmunization was 2.90% in thalassemia, 0% in chronic renal failure patients, 3.77% in pregnant females with bad obstetric history, and 2.78% in other multi-transfused patients like cancer [Table 3].
Table 3: RBC alloimmunization in different patient categories

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RBC alloantibody Rh and Kell were found prevalent in both geographical zones of India-North and South. The rate of alloimmunization in multi-transfused patients at South India blood center was 4.8% and 1.2% at North India blood center.


  Discussion Top


This bicentric study was an effort to characterize blood group alloantibody prevalence in 2 different zones of India-North and South.

Our results revealed that antibody prevalence in thalassemia patient was 2.90% with antibody specificity C (1.44%), K (1.44%). Few studies reported comparison of prevalence and antibody specificity. There are also studies that found higher and lower immunization rates.

A similar study was conducted by Pahuja et al. on 211 thalassemics of Indian origin revealed frequency of alloimmunization 3.79% and antibodies identified were anti-E, anti-K, anti-D, anti-Kp (a), anti-c (w), anti-c, and anti-Jk (a).[4]

In a study conducted by Bhatti et al. in 2004 on 161 patients in India, antibody prevalence was 4.97% with antibody specificity belonged mainly to Rh system, with one antibody each of anti-K, anti-Jsb, and anti-Jka. Study conducted by Hassab et al. in 2008 on 200 thalassemic patients in Egypt showed antibody prevalence was 10.5% with antibody specificity, anti-E (23.8%), anti-D (19%), anti-K (19%), anti-E (14.3%) and each of anti-Fy (a), anti-Js (a), anti-Lu (a), anti-N, and anti-S in one patient (4.8%). Similarly, in a study conducted by Gupta et al. on 116 thalassemics in India, RBC alloantibodies were found in 11 patients (9.48%). The most common antibody was anti-E found in 4 (36.4%) patients, followed by anti-K (three patients, 27.2%), anti-Kp (a) (two patients, 18.2%), and anti-c (w) (two patients, 18.2%). In all these studies, no relation was observed for a number of transfusions, blood group.[5],[6],[7]

In a multicentric study conducted on 835 patients by Azarkeivan et al., antibody screening showed positive results in 22 pediatric cases (7.7%) and 79 adults (14.4%). Anti-Kell antibody was seen in 34 (33.7%) cases, anti-D was seen in 11 (10.9%) cases, and anti-E in was seen in 10 (9.9%) cases. The authors observed 8 anti-D+C (7.9%) cases, 1 anti-D+E (1%), 3 anti-Kell+E, 3 anti-Kell+Kpa (3%), and 1 anti-Kell+D double antibodies.[8]

In our study, antibody prevalence in pregnant female was 3.77% with antibody specificity of D (1.89%), D and E (0.94%), D and K (0.94%), K (0.94%); while in a study conducted by Lee et al. on 28303 Chinese women during pregnancy, 213 (0.79%) women were found to have a total of 230 irregular antibodies. About 137 (0.64%) were ethnic Chinese, and a total of 160 irregular antibodies were identified in their blood samples. About 58 of these Chinese women (0.27%) were found to have 66 clinically significant antibodies, the most common antibodies encountered; these were anti-Mi (57.6%), anti-E (19.7%), anti-S (10.6%), and anti-c (7.6%).[9]

The patients of chronic renal failure who have received blood transfusions are also at risk of alloimmunization. In a study carried by Habibi and Lecolier, 7 (1.27%) out of 405 patients developed RBC alloantibodies. According to the study from India Shukla and Chaudhary, there is 1.3% risk of alloimmunization in chronic renal failure patients. We included 47 chronic renal failure patients in the study, none of the patient was found alloimmunized.[10],[11]

In our study on 258 multi-transfused patients, antibody prevalence was 2.71% with antibody specificity anti-D (0.78%), anti-C, anti-K, anti-Jk (b), anti-D and –K, and anti-D and -E (0.39%). Similarly in a study carried out by Thakral et al. on 531 multi-transfused patients of North India, alloimmunization in transfused patients was 3.4% (18/531), with anti-c was the most common specificity (38.8%), followed by anti-E (22.2%), anti-M (11.1%), anti-Le (a) (11.1%), anti-D (5.6%), anti-Jk (a) (5.6%), and anti-Le (b) (5.6%). In a study conducted by Yousuf et al. in Malaysia on 24,263 patients, antibody screening tests were positive in 184 patients with the incidence of 0.76%, 161 alloantibodies were identified. The suspected anti-Mia alloantibody was observed most frequently (49/161, 30.4%) followed by anti-E (30/161, 18.6%) and anti-D (22/161, 13.7%). Anti-E and anti-c were the most common multiple alloantibodies in combination.[12],[13]


  Conclusion Top


Multi-transfused patients are always at higher risk of alloimmunization and this creates difficulty in their pretransfusion testing. Our data show that alloimmunization to minor erythrocyte antigens and erythrocyte alloimmunization, of variable clinical significance, are frequent findings in Indian patients. We recommend including antibody screening test in routine pretransfusion testing protocol at least for the patients who are at higher risk of alloimmunization and require long-term transfusion dependence. This test may not be cost-effective for all the patients currently in our country. However, it will definitely add significant value in blood safety.

We also recommend obtaining an RBC antigen phenotype on all thalassemia patients and other patients at high risk of alloimmunization before the start of transfusion support and if feasible, providing leukodepleted blood.

Extensive antigen matching before transfusion of patients should be a routine practice for such patients. Being costly exercise, reference centers facility should be created to provide antigen negative blood to such patients and pool of regular voluntary donors should be screened and developed to provide antigen negative blood to such patients. Considering the different ethnicity and huge population in India, we need regular monitoring of alloimminization in our patients.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Schonewille H, Haak HL, van Zijl AM. Alloimmunization after blood transfusion in patients with hematologic and oncologic diseases. Transfusion 1999;39:763-71.  Back to cited text no. 1
    
2.
Pathak S, Chandrashekhar M, Wankhede GR. Type and screen policy in the blood bank: Is AHG cross-match still required? A study at a multispecialty corporate hospital in India. Asian J Transfus Sci 2011;5:153-6.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
Brantley SG, Ramsey G. Red cell alloimmunization in multitransfused HLA-typed patients. Transfusion 1988;28:463-6.  Back to cited text no. 3
    
4.
Pahuja S, Pujani M, Gupta SK, Chandra J, Jain M. Alloimmunization and red cell autoimmunization in multitransfused thalassemics of Indian origin. Hematology 2010;15:174-7.  Back to cited text no. 4
    
5.
Bhatti FA, Salamat N, Nadeem A, Shabbir N. Red cell immunization in beta thalassaemia major. J Coll Physicians Surg Pak 2004;14:657-60.  Back to cited text no. 5
    
6.
Hassab AH, Sorour AF, Ahmed MI, Salama MA, Aly AK. Antibody screening in repeatedly transfused patients. Egypt J Immunol 2008;15:1-14.  Back to cited text no. 6
    
7.
Gupta R, Singh DK, Singh B, Rusia U. Alloimmunization to red cells in thalassemics: Emerging problem and future strategies. Transfus Apher Sci 2011;45:167-70.  Back to cited text no. 7
    
8.
Azarkeivan A, Ansari S, Ahmadi MH, Hajibeigy B, Maghsudlu M, Nasizadeh S, et al. Blood transfusion and alloimmunization in patients with thalassemia: Multicenter study. Pediatr Hematol Oncol 2011;28:479-85.  Back to cited text no. 8
    
9.
Lee CK, Ma ES, Tang M, Lam CC, Lin CK, Chan LC. Prevalence and specificity of clinically significant red cell alloantibodies in Chinese women during pregnancy – A review of cases from 1997 to 2001. Transfus Med 2003;13:227-31.  Back to cited text no. 9
    
10.
Shukla JS, Chaudhary RK. Red cell alloimmunization in multi-transfused chronic renal failure patients undergoing hemodialysis. Indian J Pathol Microbiol 1999;42:299-302.  Back to cited text no. 10
[PUBMED]  Medknow Journal  
11.
Habibi B, Lecolier B. Limited indications for phenotyped blood in the prevention of transfusion-induced anti-red blood cell alloimmunization in chronic kidney failure. Nephrologie 1983;4:279-82.  Back to cited text no. 11
    
12.
Thakral B, Saluja K, Sharma RR, Marwaha N. Red cell alloimmunization in a transfused patient population: A study from a tertiary care hospital in north India. Hematology 2008;13:313-8.  Back to cited text no. 12
    
13.
Yousuf R, Abdul Aziz S, Yusof N, Leong CF. Incidence of red cell alloantibody among the transfusion recipients of Universiti Kebangsaan Malaysia Medical Centre. Indian J Hematol Blood Transfus 2013;29:65-70.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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