Low rate of red blood cell alloimmunization among multi-transfused Beta-thalassemia major patients in Iraq: effective strategies or other reasons?

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Isam Alshihmani, Safaa Abedalelah Faraj, Arezoo Oodi, Zeinab Eftekhar, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6370880/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Thalassemia, a hemoglobin disorder, represents a considerable public health challenge in Iraq. Although blood transfusion is crucial for the survival of β-thalassemia patients, it is associated with health problems, including alloimmunization. This study aimed to investigate the incidence of alloimmunization and identify the types of alloantibodies present in β-thalassemia patients in Wasit province, Iraq. Materials and Methods: This cross-sectional study was conducted on 160 Beta-thalassemia major patients in the Wasit province of Iraq in 2022. Blood samples were collected for alloantibody screening and identification using a commercial kit. The data were analyzed using SPSS-27. Results: 6 patients (3.7%) developed alloantibodies based on immunohematological tests. Of these alloantibodies, 66.6% were against Rh antigens, 33.3% were against Kell antigens, and 16.6% were against Duffy antigens. The most common alloantibodies were anti-D (50%), anti-K (33.3%), anti-C (16.6%), and anti-Fya (16.6%), with one patient developing two types of alloantibodies. Conclusion: The homogeneity between blood donors and patients is the main reason for low rate of alloimmunization. Our study suggests a potential association between the development of alloantibodies and factors such as splenectomy and gender, although the it is not statistically significant (p-value = 0.1); however, no significant association was observed between alloimmunization and the initiation of blood transfusions, ABO blood group, or RhD status (p-value= 0.6). Blood transfusion alloimmunization Beta-thalassemia racial homogeneity 1. INTRODUCTION Thalassemia is a hereditary hemoglobin disorder that affect various regions globally and presents a considerable public health challenge in Iraq. As reported by the Iraqi Ministry of Health, there were 22,000 registered cases of thalassemia in Iraq as of 2022. Thalassemia affects both sexes equally and has an incidence rate of approximately 4.4 per 10,000 live births[ 1 ]. β-thalassemia major is the most common type, accounting for 51% of cases, followed by β-thalassemia intermedia (23.2%) and β-thalassemia minor (7.5%)[ 2 ]. Blood transfusion serves as the principal therapeutic approach for thalassemia; however, it may result in complications including alloimmunization, iron overload, and the risk of infections[ 3 ]. Alloimmunization represents a significant complication associated with blood transfusions, complicating the process of identifying compatible blood units for subsequent transfusions. This issue poses a considerable concern for both patients and healthcare providers[ 4 ]. The rate of alloimmunization is influenced by various factors, including geographic location and the diversity of the population and transfusion of blood from individuals of different ethnic backgrounds may contribute to a higher overall alloimmunization rate[ 5 ]. Alloimmunization primarily pertains to the Rh, Duffy, Kell, and Kidd blood group systems, which are clinically important. The mechanisms underlying alloimmunization are intricate and encompass the antigenic disparities of red blood cells (RBCs) between the donor and recipient, the immune status of the recipient, and the immunomodulatory influences exerted by allogenic blood transfusions on the recipient's immune response[ 6 ]. Considering the critical need to lower the alloimmunization rate in patients with thalassemia, it is imperative to examine both the frequency and underlying causes of alloimmunization, as well as to formulate appropriate corrective and preventive measures[ 7 ]. This research focused on assessing the incidence and determinants of alloimmunization in individuals with β-thalassemia major residing in the Wasit province of Iraq. The findings from this investigation will assist healthcare professionals in employment of strategies aimed at preventing and mitigating the risk of alloimmunization, ultimately enhancing patient outcomes. 2. MATERIAL AND METHOD 2.1. Ethical Considerations The study approved by ethic committee of Tarbiat Modares University approval ID: IR.MODARES.REC.1401.056. Although this study was conducted in Iraq, the study was overseen by institutions affiliated with Iranian researchers and there are no potential concerns about ethical guidelines discrepancies. 2.2. Study design A cross-sectional study was carried out to investigation the prevalence and underlying factors contributing to alloimmunization in patients with β-thalassemia major within the Wasit province of Iraq. This research took place at the transfusion centers and the thalassemia clinic located in Al Kut Women & Children Hospital. The study included 160 samples of β-thalassemia major cases, aged between 3 and 45 years, who regularly attended the Al-Batool hospital thalassemia center in Al Kut for blood transfusions and various medical evaluations and also 100 healthy individuals as control group (age range 2–64) who visited Dr. Fayrouz Hospital in Al-hay city. Blood samples were collected in EDTA-containing tubes as anticoagulants for serological tests. The diagnosis of β-thalassemia was established through clinical assessments, hematological parameters, evaluation of iron overload, hemoglobin levels, and results from electrophoresis. All immunohematological evaluations, including antibody screening and identification, were conducted on fresh samples utilizing standard tube methodologies. The samples were preserved at − 25°C until the commencement of the experimental procedures. 2.3. Inclusion and exclusion criteria All thalassemic patients with a history of at least 10 transfusions, provided that a minimum of 2 weeks has elapsed since their most recent transfusion signed the informed consent for participation in the study were include. If the patients had another non-major thalassemia type or received less than ten transfusions or last blood transfusion occurs in fewer than 2 weeks, they would be excluded from the study. Pregnant women were also excluded from the study. 2.4. Immunohematological tests In this cross-sectional study, we implemented two distinct approaches: the antibody screening test and the antibody identification test. The Antibody screening test is designed to detect the presence of alloantibodies in patients with β-thalassemia. For this purpose, the pano-screen RBC reagent was utilized to identify any unexpected antibodies in the patient sample. The patient's plasma served as the sample for both methodologies, with results documented on a commercial panel. A positive test result, indicative of antigen-antibody reactivity, occurs when one or more pano-screen reagents exhibit agglutination at any stage of the testing process. Conversely, the absence of antibodies is suggested by a lack of agglutination and hemolysis, which implies that the RBCs didn't express the corresponding antigen or that any produced antibody is in a very low concentration. If antibodies are identified, their specificity is determined using the Panocell method which involved a panel screen, incorporating an antibody identification kit (IBTO 11-cell Kit, IRAN), an anti-human globulin (AHG) kit (Human, Germany), and a low ionic strength solution (LISS) reagent kit (Human, Germany). This process necessitates the use of the patient's plasma (3% suspension) in conjunction with a commercial reagent red cell panel, in equal amounts. The reactions observed with the reagent RBCs are compared to the reactions elicited by the antigens present on the panel. Subsequently, these reactions are analyzed to ascertain the specificity of any antibodies that may be present. All the tests were performed using a standard methods following the manufacturer's instruction. 2.5. Statistical analysis Statistical analysis was performed using SPSS (Statistical Package for the Social Sciences) software version 27. The data were presented using descriptive statistics including mean ± SD, frequencies, and percentages. The Chi-square analysis was employed to compare the alloimmunization rate between our study and other studies. 3. RESULTS Our study comprised 160 individuals, including 70 females (43.8%) and 90 males (56.2%). The age and blood group distribution of participants are detailed in Table 1 . In this investigation, a total of six patients developed alloantibodies, resulting in a prevalence rate of 3.7%. Among these alloantibodies, 66.6% were directed against antigens associated with the Rh system, while 33.3% targeted antigens from the Kell system, and 16.6% were against antigens from the Duffy system. The most frequently observed alloantibodies included anti-D, which was present in three patients (50%), anti-K in two patients (33.3%), anti-C in one patient (16.6%), and anti-Fya in one patient (16.6%). Notably, one patient developed two distinct types of alloantibodies. These results are presented in a categorized format in Table 2 . Among the six patients who developed alloantibodies, the average age was 20 years, with ages ranging from 3 to 34 years. Demographic and other characteristics of these patients are summarized in Table 3 . Table 1 Demographic features of the patients Item No. Frequency Gender Female 70 43.8 Male 90 56.3 Age group in years Equal or less than 15 85 53.1 16–30 67 41.9 more than 30 8 5.0 Blood group O 37 23.1 A 56 35.0 B 60 37.5 AB 7 4.4 Rh antigen Neg 14 8.8 Pos 146 91.3 Table 2 Alloantibodies detected among study participants Blood Group systems Antibodies No. Percentage % Rh-system Anti (D) 3 50 Anti (C) 1 16.6 Kell-system Anti (K) 2 33.3 Duffy Anti (Fy a ) 1 16.6 Total 6* 100 *One patient has two alloantibodies Table 3 Demographic and other characteristics of the patients with alloantibodies No. age Gender BG Rh Disease splenectomy age group 1 18 Female O Neg. combined Yes 16–30 2 3 Female O Pos. No No Equal or less than 15 3 11 Female A Pos. No Yes Equal or less than 15 4 22 Female B Pos. No No 16–30 5 31 Male AB Neg. HCV No more than 30 6 34 Male AB Neg. No No more than 30 Total 6 6 6 6 6 6 6 4. DISCUSSION β-thalassemia major is an inherited lifelong blood disorder. Although bone marrow transplantation represents the most effective treatment option for this condition, the primary therapeutic approach involves blood transfusions. However, continuous blood transfusion is associated with significant complication known as alloimmunization[ 8 ]. This is the first study in central and southern of Iraq to investigate the alloantibodies in Beta-thalassemia patients. The prevalence of alloantibodies among β-thalassemia major patients in our study was 3.7%. Our incidence rate was low and similar to the alloimmunization rate observed in other studies such as the one conducted in North-East of Iran which reported a rate of 2.87%[ 9 ]. Another study in India reported this rate to be 5.6% and the rates obtained in previous studies in Italy, south of Iran, and Iraq were 5.2%, 5.3%, and 5.1%, respectively[ 10 , 11 ]. A separate investigation carried out in 2015 in Yazd, Iran, focused on a cohort of 100 individuals diagnosed with beta-thalassemia to identify the presence of alloantibodies. The findings revealed an alloantibody prevalence rate of 4%[ 12 ].The alloimmunization rate obtained in a study conducted by Chang et al. in Taiwan was reported to be 2.7%[ 13 ]. Ebrahimisadr et al. reported a significantly elevated alloimmunization rate of 63% in their study conducted at the Tehran Regional Blood Transfusion Center in Iran, which involved 184 patients diagnosed with β-thalassemia major. This elevated alloimmunization rate may suggest instances of mismatched blood transfusions between recipients and donors, potentially resulting from the frequent transfusions these patients received.[ 14 ]. In another study conducted by Singer et al., a significant rate of alloimmunization (22%) was identified in thalassemia patients of Asian origin. This was explained by the heterogeneity between the recipients and donors, as 75% of the patients who developed alloimmunization were of Asian descent, whereas 85% of the blood donors were Caucasian[ 15 ]. Higher alloimmunization rates were also reported in Taiwan (37%), Egypt (30%), the arab population in Kuwait (30%), and Greece (22.8%) due to same reason[ 16 – 19 ]. The findings of our research align closely with those of studies conducted in Palestine, Greece, India, Egypt, Pakistan, and Italy, which indicate that alloantibodies associated with the Rh system are the most prevalent, followed by those related to the Kell system.[ 10 , 16 , 19 – 21 ]. However, in a study conducted by Ameen et al. on Arab thalassemia patients in Kuwait, the alloantibodies against antigens from the Kell-system (anti-K) found to be the most common alloantibodies followed by those against the Rh-system(anti-E)[ 18 ]. And also, in a study conducted by Karimi et al in Iran, the Kell system antibodies are recognized as the most prevalent ones[ 22 ]. The elevated prevalence of anti-D alloantibodies among D-negative individuals in our study was attributed to procedural inaccuracies within the blood transfusion system or the blood bank. This situation necessitates the implementation of corrective measures to ensure accurate identification of the D antigen. So, accurate and highly reliable methods for the detection of D-negative and D-weak, as well as establishing an electronic system that includes all blood transfusion centers in Iraq to create a database containing the donors' previous health status, are recommended. Various factors influence the variability in alloimmunization rates. Keys among these are the immunological status of the patients, the disparities in antigenicity between the recipients and the donors, as well as the alterations in the host's immune response (immunomodulatory effects) resulting from blood transfusions[ 15 , 23 ]. So, the homogeneity of populations, could explain the low rate of alloimmunization in our study same as mentioned studies conducted in India, Iran and Iraq and the high rate of alloimmunizations in Kuwait and Asia. In our investigation, a total of 20 patients underwent splenectomy, with 2 individuals subsequently developing alloantibodies. This observation suggests a potential association between splenectomy and the emergence of alloantibodies, although the relationship is not statistically significant (p-value = 0.1). Research conducted by Sirchia et al. in Italy, Hammam A. H. Ali in Palestine, Karimi et al. in Southern Iran, Al-Mousawi et al. in Iraq, and Pahuja et al. in India has indicated no significant correlation between alloantibody production and splenectomy[ 10 , 20 , 22 , 24 ]. This finding contrasts with the conclusions drawn by Singer and Hussein, who posited that splenectomy might activate the immune system to generate alloantibodies due to the altered deformability of RBCs[ 15 , 16 ]. Additionally, Davoudi-Kiakalayeh identified splenectomy as a potential risk factor for alloimmunization in patients with thalassemia[ 25 ]. Although it has been said that the absence of the filtration process, a critical function of the spleen, in patients who have undergone splenectomy may contribute to the elevated rate of alloimmunization observed in individuals with thalassemia who have had their spleens removed, but the relation between splenectomy and the production of alloantibodies remains a contentious issue, with no consensus currently established. Further research in this area is necessary to gain a clearer understanding.[ 26 ] There are also different opinions regarding the impact of patient age on the alloimmunization. For instance, in our study, we found a relationship between the start of blood transfusion and alloimmunization but this relationship wasn’t significant (p-value = 0.6). So that, among the 39 patients who commenced blood transfusions after the age of 3 years old, 4 individuals exhibited alloantibodies. In contrast, among those 121 patients who received their first transfusion between the ages of 1–3, only 2 individuals were found to have alloantibodies. That is, out of the 39 patients starting blood transfusion at ages above 3 years, 4 developed alloantibodies. However, out of the 121 patients starting blood transfusion at ages between 1–3, only two developed alloantibodies. Singer and Al-Mousavi et al. also contend that the age of a patient during their initial blood transfusion may influence the likelihood of alloimmunization. They suggest that receiving a transfusion at a young age, specifically between 1 and 3 years, may foster tolerance and offer protective benefits to the immune system in relation to alloimmunization.[ 16 , 24 ]. However, Ameen, and Karimi et al. believe that there is no substantial correlation between the initiation of blood transfusion and the occurrence of alloimmunization[ 18 , 22 ]. In our study, we reported that there is no relationship between alloimmunization and gender. Our findings, which revealed 4 alloimmunized females compared to only 2 males, suggest a potential relationship between gender and alloimmunization. In a study by Bauer the female gender identified as a contributing risk factor for alloimmunization, whereas Hussein et al recommended the male gender as a risk for the same condition. Conversely, Dogra reported no significant correlation between gender and alloimmunization[ 16 , 27 ]. 5. CONCLUSION In summary, it seems the homogeneity between blood donors and patients is the main reason for low rate of alloimmunization. Our study suggests a potential association between the development of alloantibodies and factors such as splenectomy and gender, although the it is not statistically significant; however, no significant association was observed between alloimmunization and the initiation of blood transfusions, ABO blood group, or RhD status. As previously mentioned, there is considerable disagreement regarding the impact of some factors on the rate of alloimmunization. Therefore, further investigations on alloimmunization and its associated factors in larger populations are recommended. Declarations Acknowledgments I express my special gratitude to the staff of Immunohematology Lab of Iranian Blood Transfusion Organization and as well as all the workers in the Thalassemia Center in Wasite province. Conflicts of Interest The authors declare no conflicts of interest. Author Contributions Contributions to the current study includes MA.JF. and S.AF. and AA.PF. and I.A. in study idea and design and in the literature review, and drafting and revising the manuscript critically for importance intellectual content. I.A. and A.O. in conducting the trial, data gathering, drafting the proposal, following up with ethical committee for approval, and revising the manuscript critically for importance intellectual content. Z.E. in drafting the revised manuscript and literature review, and analysis and interpretation of revised version and drafting the manuscript. AA.PF. in the proposal preparation and statistics and analysis and drafting the revised manuscript. All authors have read and approved the final version of the manuscript. The corresponding author, Ali Akbar Pourfathollah, had full access to all the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. Declaration of Interest This paper was not funded. Ethics approval statement This study was approved by ethic committee Tarbiat Modares University with Ethics code: IR.MODARES.REC.1401.056. Transparency Statement The lead author Ali Akbar Pourfathollah affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. data availability statement The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Muncie HL, Jr., Campbell J. 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Alloimmunization and red cell autoimmunization in multitransfused thalassemics of Indian origin. Hematology (Amsterdam, Netherlands). 2010;15(3):174–7. Zaidi U, Borhany M, Ansari S, Parveen S, Boota S, Shamim I, et al. Red cell alloimmunisation in regularly transfused beta thalassemia patients in Pakistan. Transfusion medicine (Oxford, England). 2015;25(2):106–10. Karimi M, Nikrooz P, Kashef S, Jamalian N, Davatolhagh Z. RBC alloimmunization in blood transfusion-dependent beta-thalassemia patients in southern Iran. International journal of laboratory hematology. 2007;29(5):321–6. Keikhaei B, Far AH, Abolghasemi H, Mousakhani H, Ghanavat M, Moghadam M. Red blood cell alloimmunization in patients with thalassemia major and intermediate in southwest Iran. Iran J Blood Cancer. 2013;6(1):41–6. Al-Mousawi MM, Al-Allawi NA, Alnaqshabandi R. Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq. Hemoglobin. 2015;39(6):423–6. Davoudi-Kiakalayeh A, Mohammadi R, Pourfathollah AA, Siery Z, Davoudi-Kiakalayeh S. Alloimmunization in Thalassemia Patients: New Insight for Healthcare. International journal of preventive medicine. 2017;8:101. Azarkeivan A, Ahmadi MH, Gharehbaghian A, Zolfaghari S, Nasizadeh S, Maghsudlu M, et al. Antibody screening and identification by gel method in thalassemic patients. Scientific Journal of Iran Blood Transfus Organ. 2008;5(2):99–108. Dogra A, Sidhu M, Kapoor R, Kumar D. Study of red blood cell alloimmunization in multitransfused thalassemic children of Jammu region. Asian journal of transfusion science. 2015;9(1):78–81. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6370880","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":439492503,"identity":"d356fdc6-38fc-49b7-b00e-77a856957060","order_by":0,"name":"Isam Alshihmani","email":"","orcid":"","institution":"Tarbiat Modares University","correspondingAuthor":false,"prefix":"","firstName":"Isam","middleName":"","lastName":"Alshihmani","suffix":""},{"id":439492506,"identity":"8c2a0da9-e909-4469-9d95-ed02754aee2d","order_by":1,"name":"Safaa Abedalelah Faraj","email":"","orcid":"","institution":"Wasit University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Safaa","middleName":"Abedalelah","lastName":"Faraj","suffix":""},{"id":439492518,"identity":"1f3937a7-8db4-44cc-81f2-cacc2c0a5b22","order_by":2,"name":"Arezoo Oodi","email":"","orcid":"","institution":"High Institute for Research and Education in Transfusion Medicine","correspondingAuthor":false,"prefix":"","firstName":"Arezoo","middleName":"","lastName":"Oodi","suffix":""},{"id":439492520,"identity":"8be160c6-1b29-423a-bf28-1ebf1702c4b4","order_by":3,"name":"Zeinab Eftekhar","email":"","orcid":"","institution":"Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zeinab","middleName":"","lastName":"Eftekhar","suffix":""},{"id":439492523,"identity":"bb76f759-29d0-4172-a1e8-44216a11fae4","order_by":4,"name":"Mohammad Ali Jalali Far","email":"","orcid":"","institution":"Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Ali Jalali","lastName":"Far","suffix":""},{"id":439492524,"identity":"1db3e94d-52a2-4bd9-b351-4529acd49837","order_by":5,"name":"Ali Akbar Pourfathollah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArUlEQVRIiWNgGAWjYLCCCgYbBgYJkrScYUgjXcthErSYs/eYfThQcz6xf3bzwQcMNTbRBLVY9pwxnnHg2O3EGXeOJRswHEvLbSCkxeBGjjHzB7bbiQ03cswkGBsOE6eF4cC/c4nzSdNysO1A4gaitVj2HCtmONiXbLzxRlqyQQIxfjFnb97McOCbney8G8kHH3yosSHCYVDaEawygZByZC32xCgeBaNgFIyCEQoA3j9ESJ9vZy8AAAAASUVORK5CYII=","orcid":"","institution":"Tarbiat Modares University","correspondingAuthor":true,"prefix":"","firstName":"Ali","middleName":"Akbar","lastName":"Pourfathollah","suffix":""}],"badges":[],"createdAt":"2025-04-03 16:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6370880/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6370880/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81225678,"identity":"d59cbfcf-503c-45e5-a2f6-5eae54b5afbb","added_by":"auto","created_at":"2025-04-23 16:08:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":624976,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6370880/v1/7aafc867-7933-4dd8-8804-a1995081ef64.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Low rate of red blood cell alloimmunization among multi-transfused Beta-thalassemia major patients in Iraq: effective strategies or other reasons?","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eThalassemia is a hereditary hemoglobin disorder that affect various regions globally and presents a considerable public health challenge in Iraq. As reported by the Iraqi Ministry of Health, there were 22,000 registered cases of thalassemia in Iraq as of 2022. Thalassemia affects both sexes equally and has an incidence rate of approximately 4.4 per 10,000 live births[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. β-thalassemia major is the most common type, accounting for 51% of cases, followed by β-thalassemia intermedia (23.2%) and β-thalassemia minor (7.5%)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBlood transfusion serves as the principal therapeutic approach for thalassemia; however, it may result in complications including alloimmunization, iron overload, and the risk of infections[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Alloimmunization represents a significant complication associated with blood transfusions, complicating the process of identifying compatible blood units for subsequent transfusions. This issue poses a considerable concern for both patients and healthcare providers[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The rate of alloimmunization is influenced by various factors, including geographic location and the diversity of the population and transfusion of blood from individuals of different ethnic backgrounds may contribute to a higher overall alloimmunization rate[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Alloimmunization primarily pertains to the Rh, Duffy, Kell, and Kidd blood group systems, which are clinically important. The mechanisms underlying alloimmunization are intricate and encompass the antigenic disparities of red blood cells (RBCs) between the donor and recipient, the immune status of the recipient, and the immunomodulatory influences exerted by allogenic blood transfusions on the recipient's immune response[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Considering the critical need to lower the alloimmunization rate in patients with thalassemia, it is imperative to examine both the frequency and underlying causes of alloimmunization, as well as to formulate appropriate corrective and preventive measures[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This research focused on assessing the incidence and determinants of alloimmunization in individuals with β-thalassemia major residing in the Wasit province of Iraq. The findings from this investigation will assist healthcare professionals in employment of strategies aimed at preventing and mitigating the risk of alloimmunization, ultimately enhancing patient outcomes.\u003c/p\u003e"},{"header":"2. MATERIAL AND METHOD","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Ethical Considerations\u003c/h2\u003e \u003cp\u003eThe study approved by ethic committee of Tarbiat Modares University approval ID: IR.MODARES.REC.1401.056. Although this study was conducted in Iraq, the study was overseen by institutions affiliated with Iranian researchers and there are no potential concerns about ethical guidelines discrepancies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Study design\u003c/h2\u003e \u003cp\u003eA cross-sectional study was carried out to investigation the prevalence and underlying factors contributing to alloimmunization in patients with β-thalassemia major within the Wasit province of Iraq. This research took place at the transfusion centers and the thalassemia clinic located in Al Kut Women \u0026amp; Children Hospital. The study included 160 samples of β-thalassemia major cases, aged between 3 and 45 years, who regularly attended the Al-Batool hospital thalassemia center in Al Kut for blood transfusions and various medical evaluations and also 100 healthy individuals as control group (age range 2\u0026ndash;64) who visited Dr. Fayrouz Hospital in Al-hay city. Blood samples were collected in EDTA-containing tubes as anticoagulants for serological tests. The diagnosis of β-thalassemia was established through clinical assessments, hematological parameters, evaluation of iron overload, hemoglobin levels, and results from electrophoresis. All immunohematological evaluations, including antibody screening and identification, were conducted on fresh samples utilizing standard tube methodologies. The samples were preserved at \u0026minus;\u0026thinsp;25\u0026deg;C until the commencement of the experimental procedures.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Inclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eAll thalassemic patients with a history of at least 10 transfusions, provided that a minimum of 2 weeks has elapsed since their most recent transfusion signed the informed consent for participation in the study were include. If the patients had another non-major thalassemia type or received less than ten transfusions or last blood transfusion occurs in fewer than 2 weeks, they would be excluded from the study. Pregnant women were also excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Immunohematological tests\u003c/h2\u003e \u003cp\u003eIn this cross-sectional study, we implemented two distinct approaches: the antibody screening test and the antibody identification test. The Antibody screening test is designed to detect the presence of alloantibodies in patients with β-thalassemia. For this purpose, the pano-screen RBC reagent was utilized to identify any unexpected antibodies in the patient sample. The patient's plasma served as the sample for both methodologies, with results documented on a commercial panel. A positive test result, indicative of antigen-antibody reactivity, occurs when one or more pano-screen reagents exhibit agglutination at any stage of the testing process. Conversely, the absence of antibodies is suggested by a lack of agglutination and hemolysis, which implies that the RBCs didn't express the corresponding antigen or that any produced antibody is in a very low concentration. If antibodies are identified, their specificity is determined using the Panocell method which involved a panel screen, incorporating an antibody identification kit (IBTO 11-cell Kit, IRAN), an anti-human globulin (AHG) kit (Human, Germany), and a low ionic strength solution (LISS) reagent kit (Human, Germany). This process necessitates the use of the patient's plasma (3% suspension) in conjunction with a commercial reagent red cell panel, in equal amounts. The reactions observed with the reagent RBCs are compared to the reactions elicited by the antigens present on the panel. Subsequently, these reactions are analyzed to ascertain the specificity of any antibodies that may be present. All the tests were performed using a standard methods following the manufacturer's instruction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS (Statistical Package for the Social Sciences) software version 27. The data were presented using descriptive statistics including mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, frequencies, and percentages. The Chi-square analysis was employed to compare the alloimmunization rate between our study and other studies.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eOur study comprised 160 individuals, including 70 females (43.8%) and 90 males (56.2%). The age and blood group distribution of participants are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In this investigation, a total of six patients developed alloantibodies, resulting in a prevalence rate of 3.7%. Among these alloantibodies, 66.6% were directed against antigens associated with the Rh system, while 33.3% targeted antigens from the Kell system, and 16.6% were against antigens from the Duffy system. The most frequently observed alloantibodies included anti-D, which was present in three patients (50%), anti-K in two patients (33.3%), anti-C in one patient (16.6%), and anti-Fya in one patient (16.6%). Notably, one patient developed two distinct types of alloantibodies. These results are presented in a categorized format in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eAmong the six patients who developed alloantibodies, the average age was 20 years, with ages ranging from 3 to 34 years. Demographic and other characteristics of these patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic features of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItem\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAge group in years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEqual or less than 15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emore than 30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBlood group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eRh antigen\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAlloantibodies detected among study participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood Group systems\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAntibodies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRh-system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAnti (D)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAnti (C)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e16.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKell-system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAnti (K)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e33.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuffy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAnti (Fy\u003c/b\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e16.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e6*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*One patient has two alloantibodies\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and other characteristics of the patients with alloantibodies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRh\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDisease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003esplenectomy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eage group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNeg.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ecombined\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePos.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEqual or less than 15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePos.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eEqual or less than 15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePos.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNeg.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003emore than 30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNeg.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003emore than 30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eβ-thalassemia major is an inherited lifelong blood disorder. Although bone marrow transplantation represents the most effective treatment option for this condition, the primary therapeutic approach involves blood transfusions. However, continuous blood transfusion is associated with significant complication known as alloimmunization[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis is the first study in central and southern of Iraq to investigate the alloantibodies in Beta-thalassemia patients. The prevalence of alloantibodies among β-thalassemia major patients in our study was 3.7%. Our incidence rate was low and similar to the alloimmunization rate observed in other studies such as the one conducted in North-East of Iran which reported a rate of 2.87%[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnother study in India reported this rate to be 5.6% and the rates obtained in previous studies in Italy, south of Iran, and Iraq were 5.2%, 5.3%, and 5.1%, respectively[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA separate investigation carried out in 2015 in Yazd, Iran, focused on a cohort of 100 individuals diagnosed with beta-thalassemia to identify the presence of alloantibodies. The findings revealed an alloantibody prevalence rate of 4%[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].The alloimmunization rate obtained in a study conducted by Chang et al. in Taiwan was reported to be 2.7%[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEbrahimisadr et al. reported a significantly elevated alloimmunization rate of 63% in their study conducted at the Tehran Regional Blood Transfusion Center in Iran, which involved 184 patients diagnosed with β-thalassemia major. This elevated alloimmunization rate may suggest instances of mismatched blood transfusions between recipients and donors, potentially resulting from the frequent transfusions these patients received.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn another study conducted by Singer et al., a significant rate of alloimmunization (22%) was identified in thalassemia patients of Asian origin. This was explained by the heterogeneity between the recipients and donors, as 75% of the patients who developed alloimmunization were of Asian descent, whereas 85% of the blood donors were Caucasian[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Higher alloimmunization rates were also reported in Taiwan (37%), Egypt (30%), the arab population in Kuwait (30%), and Greece (22.8%) due to same reason[\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e The findings of our research align closely with those of studies conducted in Palestine, Greece, India, Egypt, Pakistan, and Italy, which indicate that alloantibodies associated with the Rh system are the most prevalent, followed by those related to the Kell system.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, in a study conducted by Ameen et al. on Arab thalassemia patients in Kuwait, the alloantibodies against antigens from the Kell-system (anti-K) found to be the most common alloantibodies followed by those against the Rh-system(anti-E)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. And also, in a study conducted by Karimi et al in Iran, the Kell system antibodies are recognized as the most prevalent ones[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The elevated prevalence of anti-D alloantibodies among D-negative individuals in our study was attributed to procedural inaccuracies within the blood transfusion system or the blood bank. This situation necessitates the implementation of corrective measures to ensure accurate identification of the D antigen. So, accurate and highly reliable methods for the detection of D-negative and D-weak, as well as establishing an electronic system that includes all blood transfusion centers in Iraq to create a database containing the donors' previous health status, are recommended.\u003c/p\u003e \u003cp\u003eVarious factors influence the variability in alloimmunization rates. Keys among these are the immunological status of the patients, the disparities in antigenicity between the recipients and the donors, as well as the alterations in the host's immune response (immunomodulatory effects) resulting from blood transfusions[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. So, the homogeneity of populations, could explain the low rate of alloimmunization in our study same as mentioned studies conducted in India, Iran and Iraq and the high rate of alloimmunizations in Kuwait and Asia.\u003c/p\u003e \u003cp\u003eIn our investigation, a total of 20 patients underwent splenectomy, with 2 individuals subsequently developing alloantibodies. This observation suggests a potential association between splenectomy and the emergence of alloantibodies, although the relationship is not statistically significant (p-value\u0026thinsp;=\u0026thinsp;0.1). Research conducted by Sirchia et al. in Italy, Hammam A. H. Ali in Palestine, Karimi et al. in Southern Iran, Al-Mousawi et al. in Iraq, and Pahuja et al. in India has indicated no significant correlation between alloantibody production and splenectomy[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This finding contrasts with the conclusions drawn by Singer and Hussein, who posited that splenectomy might activate the immune system to generate alloantibodies due to the altered deformability of RBCs[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additionally, Davoudi-Kiakalayeh identified splenectomy as a potential risk factor for alloimmunization in patients with thalassemia[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Although it has been said that the absence of the filtration process, a critical function of the spleen, in patients who have undergone splenectomy may contribute to the elevated rate of alloimmunization observed in individuals with thalassemia who have had their spleens removed, but the relation between splenectomy and the production of alloantibodies remains a contentious issue, with no consensus currently established. Further research in this area is necessary to gain a clearer understanding.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThere are also different opinions regarding the impact of patient age on the alloimmunization. For instance, in our study, we found a relationship between the start of blood transfusion and alloimmunization but this relationship wasn\u0026rsquo;t significant (p-value\u0026thinsp;=\u0026thinsp;0.6). So that, among the 39 patients who commenced blood transfusions after the age of 3 years old, 4 individuals exhibited alloantibodies. In contrast, among those 121 patients who received their first transfusion between the ages of 1\u0026ndash;3, only 2 individuals were found to have alloantibodies. That is, out of the 39 patients starting blood transfusion at ages above 3 years, 4 developed alloantibodies. However, out of the 121 patients starting blood transfusion at ages between 1\u0026ndash;3, only two developed alloantibodies. Singer and Al-Mousavi et al. also contend that the age of a patient during their initial blood transfusion may influence the likelihood of alloimmunization. They suggest that receiving a transfusion at a young age, specifically between 1 and 3 years, may foster tolerance and offer protective benefits to the immune system in relation to alloimmunization.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, Ameen, and Karimi et al. believe that there is no substantial correlation between the initiation of blood transfusion and the occurrence of alloimmunization[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, we reported that there is no relationship between alloimmunization and gender.\u003c/p\u003e \u003cp\u003eOur findings, which revealed 4 alloimmunized females compared to only 2 males, suggest a potential relationship between gender and alloimmunization. In a study by Bauer the female gender identified as a contributing risk factor for alloimmunization, whereas Hussein et al recommended the male gender as a risk for the same condition. Conversely, Dogra reported no significant correlation between gender and alloimmunization[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eIn summary, it seems the homogeneity between blood donors and patients is the main reason for low rate of alloimmunization. Our study suggests a potential association between the development of alloantibodies and factors such as splenectomy and gender, although the it is not statistically significant; however, no significant association was observed between alloimmunization and the initiation of blood transfusions, ABO blood group, or RhD status. As previously mentioned, there is considerable disagreement regarding the impact of some factors on the rate of alloimmunization. Therefore, further investigations on alloimmunization and its associated factors in larger populations are recommended.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI express my special gratitude to the staff of Immunohematology Lab of Iranian Blood Transfusion Organization and as well as all the workers in the Thalassemia Center in Wasite province.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContributions to the current study includes MA.JF. and S.AF. and AA.PF. and I.A. in study idea and design and in the literature review, and drafting and revising the manuscript critically for importance intellectual content. I.A. and A.O. in conducting the trial, data gathering, drafting the proposal, following up with ethical committee for approval, and revising the manuscript critically for importance intellectual content. Z.E. in drafting the revised manuscript and literature review, and analysis and interpretation of revised version and drafting the manuscript. AA.PF. in the proposal preparation and statistics and analysis and drafting the revised manuscript. All authors have read and approved the final version of the manuscript. The corresponding author, Ali Akbar Pourfathollah, had full access to all the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis paper was not funded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by ethic committee Tarbiat Modares University with Ethics code: IR.MODARES.REC.1401.056.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTransparency Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe lead author Ali Akbar Pourfathollah affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003edata availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMuncie HL, Jr., Campbell J. 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Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly asian descent. Blood. 2000;96(10):3369\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussein E, Ahmed Eldesoukey N, Rihan A, Kamal A. Predictors of red cell alloimmunization in multitransfused Egyptian patients with β-thalassemia. Archives of pathology \u0026amp; laboratory medicine. 2014;138(5):684\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang LY, Liang DC, Liu HC, Chang FC, Wang CL, Chan YS, et al. Alloimmunization among patients with transfusion-dependent thalassemia in Taiwan. Transfusion medicine (Oxford, England). 2006;16(3):200\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmeen R, Al-Shemmari S, Al-Humood S, Chowdhury RI, Al-Eyaadi O, Al-Bashir A. RBC alloimmunization and autoimmunization among transfusion-dependent Arab thalassemia patients. Transfusion. 2003;43(11):1604\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpanos T, Karageorga M, Ladis V, Peristeri J, Hatziliami A, Kattamis C. Red cell alloantibodies in patients with thalassemia. Vox sanguinis. 1990;58(1):50\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePahuja S, Pujani M, Gupta SK, Chandra J, Jain M. Alloimmunization and red cell autoimmunization in multitransfused thalassemics of Indian origin. Hematology (Amsterdam, Netherlands). 2010;15(3):174\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaidi U, Borhany M, Ansari S, Parveen S, Boota S, Shamim I, et al. Red cell alloimmunisation in regularly transfused beta thalassemia patients in Pakistan. Transfusion medicine (Oxford, England). 2015;25(2):106\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarimi M, Nikrooz P, Kashef S, Jamalian N, Davatolhagh Z. RBC alloimmunization in blood transfusion-dependent beta-thalassemia patients in southern Iran. International journal of laboratory hematology. 2007;29(5):321\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeikhaei B, Far AH, Abolghasemi H, Mousakhani H, Ghanavat M, Moghadam M. Red blood cell alloimmunization in patients with thalassemia major and intermediate in southwest Iran. Iran J Blood Cancer. 2013;6(1):41\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Mousawi MM, Al-Allawi NA, Alnaqshabandi R. Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq. Hemoglobin. 2015;39(6):423\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavoudi-Kiakalayeh A, Mohammadi R, Pourfathollah AA, Siery Z, Davoudi-Kiakalayeh S. Alloimmunization in Thalassemia Patients: New Insight for Healthcare. International journal of preventive medicine. 2017;8:101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzarkeivan A, Ahmadi MH, Gharehbaghian A, Zolfaghari S, Nasizadeh S, Maghsudlu M, et al. Antibody screening and identification by gel method in thalassemic patients. Scientific Journal of Iran Blood Transfus Organ. 2008;5(2):99\u0026ndash;108.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDogra A, Sidhu M, Kapoor R, Kumar D. Study of red blood cell alloimmunization in multitransfused thalassemic children of Jammu region. Asian journal of transfusion science. 2015;9(1):78\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Blood transfusion, alloimmunization, Beta-thalassemia, racial homogeneity","lastPublishedDoi":"10.21203/rs.3.rs-6370880/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6370880/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eThalassemia, a hemoglobin disorder, represents a considerable public health challenge in Iraq. Although blood transfusion is crucial for the survival of β-thalassemia patients, it is associated with health problems, including alloimmunization. This study aimed to investigate the incidence of alloimmunization and identify the types of alloantibodies present in β-thalassemia patients in Wasit province, Iraq.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods: \u003c/strong\u003eThis cross-sectional study was conducted on 160 Beta-thalassemia major patients in the Wasit province of Iraq in 2022. Blood samples were collected for alloantibody screening and identification using a commercial kit. The data were analyzed using SPSS-27.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e6 patients (3.7%) developed alloantibodies based on immunohematological tests. Of these alloantibodies, 66.6% were against Rh antigens, 33.3% were against Kell antigens, and 16.6% were against Duffy antigens. The most common alloantibodies were anti-D (50%), anti-K (33.3%), anti-C (16.6%), and anti-Fya (16.6%), with one patient developing two types of alloantibodies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe homogeneity between blood donors and patients is the main reason for low rate of alloimmunization. Our study suggests a potential association between the development of alloantibodies and factors such as splenectomy and gender, although the it is not statistically significant (p-value = 0.1); however, no significant association was observed between alloimmunization and the initiation of blood transfusions, ABO blood group, or RhD status (p-value= 0.6).\u003c/p\u003e","manuscriptTitle":"Low rate of red blood cell alloimmunization among multi-transfused Beta-thalassemia major patients in Iraq: effective strategies or other reasons?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-08 11:42:47","doi":"10.21203/rs.3.rs-6370880/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3b459e2b-aef2-4fd1-ab8b-ed5e87b5f045","owner":[],"postedDate":"April 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-23T16:08:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-08 11:42:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6370880","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6370880","identity":"rs-6370880","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}