|Year : 2019 | Volume
| Issue : 2 | Page : 214-218
Incidence and frequency of various red blood cell antibodies and the experience of providing antigen-negative transfusion support for patients at a tertiary care super specialty hospital
Ruhi Mehra, Minal Rane, Ujwala D'Mello, Rajesh B Sawant
Department of Transfusion Medicine, Kokilabhen Dhirubhai Ambani Hospital, Mumbai, Maharashtra, India
|Date of Submission||26-Aug-2019|
|Date of Acceptance||07-Oct-2019|
|Date of Web Publication||17-Oct-2019|
Dr. Ruhi Mehra
Department of Transfusion Medicine, Kokilabhen Dhirubhai Ambani Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: The presence of red blood cell (RBC) auto and/or alloantibodies can pose a serious challenge of finding transfusion support for such patients. Aim and Objectives: The aim of this study was to assess the frequency and type of unexpected RBC antibodies in the patient population of a tertiary care super specialty hospital and analyze the transfusion support and its effectiveness in these patients. Methodology: This was a retrospective cross sectional study based on data contained in all blood requests, received over a period of 39 months inclusive of demographic,laboratory and clinical variables. Results: Among the 25,338 patients screened, 122 (0.48%) had alloantibodies and 19 (0.07%) had autoantibodies. Of the 141 patients with atypical antibodies, 109 (77.30%) were female and 32 (22.69%) were male. Antibodies directed against the antigens from various blood group systems were as follows: Rh – 54.5%, MNS – 21.8%, and Lewis – 13.6%. Anti-D (32.8%), Anti-M (16.4%), and Anti-E (10.9%) were the most prevalent. Multiple alloantibodies were seen in 2 (1.41%) cases and autoantibodies coexisting with an alloantibody in 9 (6.38%) cases. Discussion: RBC alloimmunization rate is lower (0.41%) in our hospital in comparison with published reports. Higher alloimmunization in female patients in the age group of 20–40 years mainly associated with a history of pregnancy and comparatively lower rate in males and strongly associated with a history of transfusion in the age group of 40–60 years has been reported in literature. Conclusion: RBC alloimmunization rate (0.55%) in general patients treated in our hospital is lower as compared to other reported rates in our country. The provision of RBC phenotype-matched (Rh and Kell) blood for patients likely to get multiple transfusions right from the beginning may reduce the alloimmunization rates further.
Keywords: Alloimmunization, blood, match, phenotype, transfusion
|How to cite this article:|
Mehra R, Rane M, D'Mello U, Sawant RB. Incidence and frequency of various red blood cell antibodies and the experience of providing antigen-negative transfusion support for patients at a tertiary care super specialty hospital. Glob J Transfus Med 2019;4:214-8
|How to cite this URL:|
Mehra R, Rane M, D'Mello U, Sawant RB. Incidence and frequency of various red blood cell antibodies and the experience of providing antigen-negative transfusion support for patients at a tertiary care super specialty hospital. Glob J Transfus Med [serial online] 2019 [cited 2019 Nov 12];4:214-8. Available from: http://www.gjtmonline.com/text.asp?2019/4/2/214/269396
| Introduction|| |
Transfusion of blood or blood components in many instances is a life-saving measure. However, every transfusion has its own inherent risks. It is always advised to avoid prophylactic transfusions and reserve transfusion for therapeutic purposes only. There are many types of adverse transfusion reactions which can occur, such as allergic, febrile nonhemolytic transfusion reactions, hemolytic transfusion reactions (HTRs), and transfusion transmissible infections being a few of them.
Alloimmunization is an immune-mediated delayed HTR. Multiple transfusions in some recipients can lead to the formation of allo- and/or autoantibodies, which is known as alloimmunization or autoimmunization. This occurs due to disparity between donor and patient red cell antigens. These antibodies can pose a serious challenge for finding transfusion support for such patients. Alloimmunization after exposure to red cell alloantigens depends on genetic and acquired patient-related factors, dose, and immunogenicity of the antigens., Demography of the population being studied influences the incidence of alloimmunization.
Antibodies reacting at 37°Cin vitro and/or those reactive in the indirect antiglobulin test phase are considered to be clinically significant antibodies, which can lead to HTR or hemolytic disease of fetus and new born (HDFN). These are usually immunoglobulin G (IgG) in nature. The alloantibodies, which frequently develop and are encountered during compatibility testing, are primarily against antigens related to Rh, Kell, Kidd, Duffy, and MNSs blood group systems.
The development of alloantibodies and/or autoantibodies against red blood cell (RBC) antigens complicates RBC cross-matching, shortensin vivo survival of transfused cells, and delays provision of safe transfusions. Finding a compatible unit for patients who have developed alloantibodies becomes a difficult task. Blood units negative for those antigens against which antibodies have been developed should be issued to such alloimmunized patients. Thus, alloimmunization especially in patients who will probably be receiving multiple transfusions throughout their lives complicates and limits transfusion therapy. This contributes to technical complications along with morbidity and mortality. In literature, there are only a few studies that have focused on RBC alloimmunization in general patients.
| Methodology|| |
A retrospective cross-sectional study was conducted at the department of transfusion medicine of a tertiary care super specialty hospital. The data of all patients for whom a blood transfusion was requested during the study of 39 months were analyzed for various variables such as demographic: age and sex; laboratory: alloantibody and autoantibody, units cross-matched and transfused; and clinical: clinical specialty and hemoglobin increment posttransfusion.
Each time a blood requisition was received, the sample was centrifuged at 3000 rpm for 3 min and the plasma obtained was used to perform alloantibody screening using commercially available three-cell panel (Diacell, Bio-rad, Switzerland/Ortho Clinical Diagnostics, New Jersey). Blood samples of patients having a positive screening test were then tested for alloantibody identification using commercially available 11-cell panels (Diacell, Bio-rad, Switzerland/Ortho Clinical Diagnostics, New Jersey) after counseling, discussion, and consent of the clinician and patient. Autoantibodies were detected by incubating patients own plasma with patients own RBCs at 4°C, room temperature, and 37°C for 10 min on Gel card containing polyspecific antihuman globulin (anti IgG + C3d). The corresponding antigen-negative blood was chosen for transfusion. Discrete categorical data were presented as n (%). Continuous data were given as mean.
| Results|| |
Data from 25,388 patients were analyzed. Alloantibodies were found to be present in 141 patients, of which 77% were female whereas 23% were male. Rh group alloantibodies were found to be the most common (46.79%), followed by the MNS group (20.55%). The most common alloantibody identified in females was anti-D (41.28%) (excluding the cases of passively acquired anti-D) while in males was anti-M (34.37%). About 2.83% of patients had multiple antibodies among which one of the antibodies always belonged to the Rh blood group system. In 17.02% of patients, the antibody specificity could not be detected [Table 1].
|Table 1: Frequency of various red blood cell alloantibodies in the studied population|
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The incidence of autoantibody was found to be 0.07%, equal in both males and females. Auto- and alloantibodies were found to be coexistent in six patients, the incidence being more in female patients [Graph 1].
On analyzing the age-wise incidence of these antibodies among the alloimmunized patients, it was found that most antibodies in females occurred in the age group of 20–40 years, i.e., the reproductive age group, while in males, the incidence was common among the age group of 40–60 years [Table 2].
|Table 2: Incidence of red blood cell auto- and allo-antibodies in various age groups of alloimmunized patients|
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Analyzing the patients according to their clinical specialties revealed that most of the antibodies were an incidental finding in the patient who came in for routine health checkup (diagnostic). This was followed by gynecology, cardiac surgery, oncology, and liver transplant patients [Graph 2].
The transfusion of compatible and specific antigen-negative units is required for these patients. On analyses, it was found that 764 units had to be crossmatched for these patients, of which only 407 were found to be compatible. Of these 56 units were transfused which were well tolerated by these patients and the mean hemoglobin (Hb) increase per unit RBC transfused was found to be 0.9 g/dl [Table 3].
|Table 3: Our experience of finding compatible units for alloimmunized patients|
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| Discussion|| |
Few articles are available in literature on the frequency of minor blood group antigens in the Indian population. These antigens come into play in patients who receive repeated blood transfusions. The RBC antigenic difference between the donor and the recipient is an important factor which contributes to the development of alloantibodies in the recipient, the recipient's immune status, and the immunomodulatory effect of transfusion being the other contributory factors. Antigen typing of all donor units especially for the minor blood group antigens is not routinely performed in all the blood banks. Each transfusion episode exposes the recipient to the minor blood group antigens which are absent on their RBCs; this leads to their sensitization and the development of alloantibodies begins. Once a patient develops alloantibodies, a lot of time and resources are utilized in finding the fully compatible, which is also negative for the corresponding antigen. The transfusion of any other blood unit to such a patient poses the risk of developing a transfusion reaction in the recipient. Even if the reaction is not a florid one due to low titers of the alloantibody in the recipient, the desired Hb increment will not be observed in such cases. Therefore, it is very essential to provide a blood unit which is negative for the implicated minor blood group antigen and is compatible at all the respective thermal range of action of the alloantibody identified.
The rate of alloimmunization in our patient population was found to be 0.55%. On comparing with the other available literature reports from India, it was noted that our rate was a lower side. In the study conducted by Thakral et al., the alloimmunization rate was reported to be 3.4% and Pujani et al. reported the alloimmunization rate of 3.79% among the thalassemic patients [Table 4]. The rate was found to be 9.8% by Shukla and Chaudhary among the patients of chronic renal failure. On further analyses, it was found that the low immunization rate could be attributed to the fact that our patients were transfused with Rh-Kell antigen-matched blood units. Matching for the most immunizing antigens helped in preventing the sensitization of this recipients and thus prevented the formation of alloantibodies in them.
|Table 4: Incidence of red blood cell alloimmunization: Various published reports in India|
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Among the alloimmunized antibodies, the Rh blood group system was found to be the most common in our study. Similar results were obtained in studies conducted by Dhawan et al. (52.17%), Al-Joudi et al., (37.4%) and Sadeghian et al.(88.88%, Anti-D). Almost 48% of the RBC alloantibodies belong to Rh–Kell group system as also reported in our country.,, Higher alloimmunization rate in female patients in the age group of 20–40 years is mainly associated with a history of pregnancy. Literature reports comparatively lower rate in males that is strongly associated with a history of transfusion in the age group of 40–60 years. Patients with autoantibodies may have a higher transfusion rate and often require immunosuppressive drugs, splenectomy, or alternative treatments.,
Once a patient develops alloantibodies searching a compatible unit involves finding a unit that is negative for the corresponding antigen. Specific antisera are available which help in screening the PRBC units for the presence/absence of specific antigens. The number of units to be screened depends on the prevalence of that specific antigen in the population. When such compatible antigen-negative units were transfused to these alloimmunized patients, the mean Hb increment observed was 0.9 g/dl, which is similar to the expected Hb increment of 1 g/dl. The blood banks which do not have the resources of identifying the alloantibodies rely on the multiple random units crossmatch methodology for finding the compatible unit for the patient.
Approaches for the prevention of alloimmunization are under debate. They range from the provision of RBCs matched for all the major antigens associated with clinically significant antibodies to blood matched only for antibodies that have already been made. There are limited data on the RBC phenotypes and the extent of alloimmunization among Asians. The provision of phenotype matched and antigen-negative blood can be made if phenotyped blood donor registry is available.
| Conclusion|| |
RBC alloimmunization rate (0.55%) in our hospital is lower compared to other reported rates in our country. The blood group systems which were found to be the most common among the alloimmunized patients were Rh, MNS, and Kell. The high frequency of Anti-D alloantibody implies that quality programs for the determination of weak D-positive RBCs should be improved and updated so that the rate of alloantibody synthesis can be reduced. RBC antigen typing before the first transfusion and issue of antigen-matched blood should be tried wherever possible. The provision of RBC phenotype-matched (Rh and Kell) blood for patients likely to get multiple transfusions right from the beginning may reduce alloimmunization rates further. The mean increase in Hb per unit RBC transfused was 0.9 g/dl, which shows the good survival rate of Rh-Kell-matched RBC units transfused. Developing a phenotyped donor registry has become a need of the hour.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Cartron JP, Colin Y. Structural and functional diversity of blood group antigens. Transfus Clin Biol 2001;8:163-99.
Siegel DL. The human immune response to red blood cell antigens as revealed by repertoire cloning. Immunol Res 1998;17:239-51.
Makroo RN, Bhatia A, Gupta R, Phillip J. Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population. Indian J Med Res 2013;137:521-6.
] [Full text]
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.
Pujani M, Pahuja S, Dhingra B, Chandra J, Jain M. Alloimmunisation in thalassaemics: A comparison between recipients of usual matched and partial better matched blood. An evaluation at a tertiary care centre in India. Blood Transfus 2014;12 Suppl 1:s100-4.
Shukla JS, Chaudhary RK. Red cell alloimmunization in multi-transfused chronic renal failure patients undergoing hemodialysis. Indian J Pathol Microbiol 1999;42:299-302.
] [Full text]
Dhawan HK, Kumawat V, Marwaha N, Sharma RR, Sachdev S, Bansal D, et al.
Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients. Asian J Transfus Sci 2014;8:84-8.
] [Full text]
Al-Joudi F, Ali AB, Ramli MB, Ahmed S, Ismail M. Prevalence and specificities of red cell alloantibodies among blood recipients in the Malaysian state of Kelantan. Asian J Transfus Sci 2011;5:42-5.
] [Full text]
Sadeghian MH, Keramati MR, Badiei Z, Ravarian M, Ayatollahi H, Rafatpanah H, et al.
Alloimmunization among transfusion-dependent thalassemia patients. Asian J Transfus Sci 2009;3:95-8.
] [Full text]
Reyhaneh K, Ahmad G, Gharib K, Vida V, Raheleh K, Mehdi TN. Frequency & specificity of RBC alloantibodies in patients due for surgery in Iran. Indian J Med Res 2013;138:252-6.
] [Full text]
Makroo RN, Bhatia A, Hegde V, Chowdhry M, Thakur UK, Rosamma NL. Antibody screening & identification in the general patient population at a tertiary care hospital in New Delhi, India. Indian J Med Res 2014;140:401-5.
] [Full text]
Zaman S, Chaurasia R, Chatterjee K, Thapliyal RM. Prevalence and specificity of RBC alloantibodies in Indian patients attending a tertiary care hospital. Adv Hematol 2014;2014. Available from: http://dx.doi.org/10.1155/2014/749218
. [Last accessed on 2019 Sep 14].
Kruatrachue M, Sirisinha S, Pacharee P, Chandarayingyong D, Wasi P. An association between thalassaemia and autoimmune haemolytic anaemia (AIHA). Scand J Haematol 1980;25:259-63.
Argiolu F, Diana G, Arnone M, Batzella MG, Piras P, Cao A. High-dose intravenous immunoglobulin in the management of autoimmune hemolytic anemia complicating thalassemia major. Acta Haematol 1990;83:65-8.
Lau FY, Wong R, Chan NP, Chui CH, Ng E, Ng MH, et al.
Provision of phenotype-matched blood units: No need for pre-transfusion antibody screening. Haematologica 2001;86:742-8.
[Table 1], [Table 2], [Table 3], [Table 4]