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 Table of Contents  
Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 61-64

Crossmatch incompatibility, indwelling experience from a single center, Bangladesh

1 Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
2 Department of Transfusion Medicine, Ad-Din Medical College Hospital, Dhaka, Bangladesh
3 Department of Transfusion Medicine, Popular Medical College Hospital, Dhaka, Bangladesh

Date of Submission26-Nov-2020
Date of Decision12-Feb-2021
Date of Acceptance17-Mar-2021
Date of Web Publication29-May-2021

Correspondence Address:
Dr. Sonia Shormin Miah
Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/GJTM.GJTM_110_20

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Background and Objectives: Crossmatch incompatibility among the blood donor and recipient is common. The cause for which may vary in patients despite rational transfusion practices. Provision of appropriate blood components can also be complicated by transfusion, pregnancy, exposure to drug, or various diseases. Therefore, the reasons for assessing the crossmatching incompatibility are important in transfusion safety. The present study was conducted to determine the prevalence of crossmatch incompatibility in this region and the reasons behind it. Methods: In this retrospective observational study, 32,403 crossmatch data were reviewed from crossmatch register between July 2018 and June 2019. Crossmatch was performed with both saline and antihuman globulin method. Incompatible crossmatch was evaluated further. Results: About 0.15% (n = 50) of patients showed crossmatch incompatibility: of this, 66% were female and 34% male. About 80% of crossmatch incompatibility was associated with multiple transfusions; of these, direct antiglobulin test (DAT) was positive in 78% (n = 39) and indirect antiglobulin test (IAT)/antibody screen was positive in 68% (n = 34) of patients. Both DAT and IAT were positive in 46% (n = 23). Further antibody identification was done. Conclusion: This study highlights the need for introducing antibody screening before compatibility testing, especially in multitransfused individuals.

Keywords: Allo- and autoimmunization, incompatible transfusion direct antiglobulin test, indirect antiglobulin test

How to cite this article:
Miah SS, Doha MA, Islam A, Quader MA. Crossmatch incompatibility, indwelling experience from a single center, Bangladesh. Glob J Transfus Med 2021;6:61-4

How to cite this URL:
Miah SS, Doha MA, Islam A, Quader MA. Crossmatch incompatibility, indwelling experience from a single center, Bangladesh. Glob J Transfus Med [serial online] 2021 [cited 2021 Dec 7];6:61-4. Available from: https://www.gjtmonline.com/text.asp?2021/6/1/61/317120

  Introduction Top

Crossmatch in blood transfusion refers to testing donor blood against patients' blood, which is an important pretransfusion testing that has been used since 1907 when Ottenberg first performed it.[1] It is the final step of pretransfusion testing and exerts an essential role in transfusion safety. Most blood banks in resource-rich countries adopted ABO and Rh type and antibody screen or type and screen policy as replacement of traditional crossmatch method. In Bangladesh, saline and antihuman globulin crossmatch by conventional tube technique is still standard procedure for pretransfusion testing.[2]

Although theoretically, transfusion of ABO and RhD group-specific blood carries negligible risk, in practice it has been observed that a donor red blood cell may contain different Rhesus and other minor antigens than that of the recipient which can result in unwanted antigen exposure and production of alloantibody in the recipient. Such a scenario can lead to future crossmatch incompatibility if more transfusion is needed for the same patient, as commonly seen in multiple transfusion patients.[3] Other conditions that can result in crossmatch incompatibilities are previous pregnancy, autoimmune hemolytic anemia (AIHA), failure to identify the subgroup of A and B, and rarely, technical errors. Reviewing the crossmatch incompatibility and its causes helps blood bank specialists and physicians to understand the patient's condition better and can guide proper management.

Aims and objectives

The present study was conducted to determine the prevalence of crossmatch incompatibility in this region and the reasons behind it.

  Materials and Methods Top

This retrospective observational study was performed using crossmatching register. All crossmatch data between July 2018 and June 2019 in the blood bank laboratory were analyzed. Any repetition of patient sample was identified by unique laboratory ID for that particular patient and excluded from the study.

Patient's crossmatch sample (3 ml of plain and ethylenediaminetetraacetic acid each) was received in the laboratory along with blood requisition. The same was crossmatched with donor's sample in pilot tubes.

After collection of sample, it was centrifuged at 3000 rpm for 3 min to separate the plasma from the red cells. Forward (cell) grouping (ABO and Rh typing) was done using commercially available monoclonal reagents (Tulip) and reverse grouping using freshly made reagent “A,” “B,” and “O” cell. Crossmatch was performed in tubes by indirect antihuman globulin method using polyspecific antihuman globulin reagent (Immucor), and the results were recorded in crossmatch register.

If any incompatibility in crossmatch was encountered, regrouping and crossmatching of patient and donor samples was performed to exclude any blood group discrepancy or technical error.

A detailed history of the patient was obtained consisting of current illness, historical blood group, transfusion history, drug history, and if female, obstetric history. If the problem still persisted despite group confirmation, then patient's sample was subjected to antibody screening in indirect antihuman globulin method using freshly prepared pooled “O” cell and polyspecific (immunoglobulin G and C3d) antihuman globulin (Tulip). Before antibody screening, the prepared “O” cell was checked to ensure the presence of D, C, c, E, and e antigens using commercial antisera (Tulip and Immucor). In case of positive antibody screen, antibody identification was done using identification panels. Direct antihuman globulin test was also performed in each case to see whether autoantibody was the cause of crossmatching error. Elution was also done to detect the autoantibody.

Identification of detected antibody

For this study to detect the specific alloantibody, we used freshly prepared in house red cell panels – R1R1, R1r, R2r, R1R2, R0R0, rr, r//r, r/r covering K+k+, Fya + b+, Jka+b+, M+N+ antigens. In all cases, positive and negative controls were used along with ICT to validate the test results.

Ethical consideration

This study has obtained approval from the institutional ethical review board.

Statistical method

All the data of crossmatch register from July 2018 to June 2019 were analyzed by Microsoft Excel 2016 and presented in tabular and graphical form.

  Results Top

A total of 32,403 patient samples were received from different departments [Table 1] during the study period from July 2018 to June 2019 in the blood bank. Among them, 50 (0.15%) patient samples were found incompatible against 163 donor units. The crossmatch incompatibility was higher in females 66% (n = 33) than in males 34% (n = 17). The age distribution of patients subjected to crossmatch incompatibility ranged from 5 to 80 years and the mean age was 26.3 ± 19.32 with maximum patients under 20 years of age and incompatible crossmatches were lesser as age advanced.
Table 1: Distribution of total patients for crossmatching

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History revealed that 40 out of these 50 patients received multiple transfusions, which means that in our setting, 80% crossmatch incompatibility was associated with multiple transfusions. Overall 70% of total crossmatch incompatibility was associated with thalassemia, hematological malignancy, and AIHA [Figure 1].
Figure 1: Conditions associated with incompatible crossmatch

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Among the patients' blood that was found incompatible with several donor units, direct antiglobulin test (DAT) was positive in 78% (n = 39) and DAT/antibody screen was positive in 68% (n = 34) of patients. Both DAT and indirect antiglobulin test (IAT) was positive in 46% (n = 23) of patients.

Out of 24 IAT-positive patients, causative alloantibody was identified in 95% (n = 22) of patients. Among the 22 patients, 23% (n = 5) of cases were due to multiple alloantibodies and 77% (n = 17) were due to single alloantibody.

Among the DAT-positive cases (n = 39), thalassemia was identified in 15 (38.46%), AIHA 19 (48.71%), and malignancy 3 (7.69%).

Both the DCT and ICT were positive in 23 cases. The breakup of these was as follows: thalassemia 15 (65.21%), AIHA 6 (26.08%), and malignancy 2 (8.69%).

Moreover, most of the alloantibodies that could be identified in patient's sera belonged to Rh system (92%). Anti-Fyb was detected in one patient (4%). The most common alloantibody identified was anti-E (46%, n = 11) followed by anti-C (25%, n = 6). Both anti-C and anti-E antibodies were found in five patients. Causative antibody could not be identified in one patient [Table 2].
Table 2: Causative antibodies in Incompatible crossmatch among 24 indirect antiglobulin test-positive patients

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  Discussion Top

Crossmatching incompatibility during pretransfusion testing is a common entity. In this study, we found that crossmatching incompatibility was 0.15%, whereas in a study from eastern India, Kolkata, it was about 0.69%,[4] and another study by Bhatt et al.[5] in western India showed that the overall incidence is about 0.21%.

In our study, we observed that the majority of incompatible crossmatches were found in females (56.44%), which is also comparable to the study by Bhattacharya et al. in eastern India (59%). Like in other studies, we observed that females are more likely to develop alloimmunization than males.[6]

Incompatibility was more common in the age group under 20 years. Majority of these were multiple transfused thalassemic patients. In Bangladesh, Rh phenotyping and determination of minor blood group antigens before first blood transfusion in patients with major thalassemia is still not a routine practice. Further, most blood centers in the country do not have the necessary logistics for antibody screening. Another important fact is that antibody screening of patient's and donor's blood before blood transfusion is not performed routinely.[7]

Other diseases associated with crossmatch incompatibilities were AIHA (8%) and hematological and nonhematological malignancy (6%). No specific association was found in 5% of patients. These findings are comparable to Bhattacharya et al. but are in contrast to the findings by Bhatt et al. where most incompatibilities were found in AIHA patients (40%).

Most of the alloantibodies that could be identified in patient's sera belonged to Rh system (92%). Several studies conducted in South Asia regions also found that antibody to Rh antigens was the most common alloantibody developed in thalassemia major patients due to multiple transfusions.[8]

In our study, we also found that 30 patients (60%) among 50 incompatible crossmatches were DAT positive. Dhawan et al.[5] reported that 28.2% of their patients developed autoantibodies. It may be because chronically transfused thalassemia patients are prone to develop red cell autoantibodies along with alloantibodies.[9]

Limitations of this study

Due to resource limitations, commercial cell panels were not used.

  Conclusion Top

The study showed that multiple transfusions were associated with majority of the crossmatch incompatibility encountered in our setting. Antibodies developed against Rh antigens were the major contributors.

This study highlights the need for introducing antibody screening before compatibility testing, especially in multitransfused individuals like thalassemics.


The authors thank the Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, for concluding this study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Mollison PL, Engelfriet CP, Contrearas M. Red cell grouping Technique. In: Blood Transfusion in Clinical Medicine. 10th ed. New Jersey. USA. Black Well Science Publication. 1997. p. 267-77.  Back to cited text no. 1
WHO. Situation Assessment of Public & Private Blood bank Centers in Bangladesh. WHO Report; 2012.  Back to cited text no. 2
Vidushi, Sidhu M, Shah SN. Evaluation of incompatible crossmatch. Global J Trans Med 2020;5:68-72.  Back to cited text no. 3
Bhattacharya P, Samanta E, Afroza N, Naik A, Biswas R. An approach to incompatible cross-matched red cells: Our experience in a major regional blood transfusion center at Kolkata, Eastern India. Asian J Transfus Sci 2018;12:51-6.  Back to cited text no. 4
[PUBMED]  [Full text]  
Bhatt JK, Patel TR, Gajjar MD, Solanki MV, Bhatnagar NM, Shah SD. Evaluation of incompatible crossmatch at blood bank of a tertiary care teaching hospital in Western India. Pathol Lab Med 2016;7. Available from: http://www.openventio.org. [Last accessed 15/5/2021].  Back to cited text no. 5
Klapper E, Zhang Y, Figueroa P, Ness P, Stubbs J, Abumuhor I, et al. Toward extended phenotype matching: A new operational paradigm for the transfusion service. Transfusion 2010;50:536-46.  Back to cited text no. 6
Sood R, Makroo RN, Riana V, Rosamma NL. Detection of alloimmunization to ensure safer transfusion practice. Asian J Transfus Sci 2013;7:135-9.  Back to cited text no. 7
[PUBMED]  [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.  Back to cited text no. 8
[PUBMED]  [Full text]  
Pandey H, Das SS, Chaudhary R. Red cell alloimmunization in transfused patients: A silent epidemic revisited. Asian J Transfus Sci 2014;8:75-7.  Back to cited text no. 9
[PUBMED]  [Full text]  


  [Figure 1]

  [Table 1], [Table 2]


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