Volume 22, Issue 2 (Summer 2025)
2025, 22(2): 137-149 |
Back to browse issues page
Ethics code: IR.BUMS.REC.1403.233
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Nakhaei Shamahmood M, Nasiri M, Meghdadi M, Mortazi H, Asadifard M, Erfani F, et al . Kell and E Alloantibodies as the Main Causes of Alloimmunization in Transfusion-Dependent Thalassemia Patients: A Cross-Sectional Study. Journal of Iranian Blood Transfusion 2025; 22 (2) :137-149
URL: http://bloodjournal.ir/article-1-1586-en.html
URL: http://bloodjournal.ir/article-1-1586-en.html
Mobina Nakhaei Shamahmood 
, Maziar Nasiri , Mohammadreza Meghdadi , Hasan Mortazi , Masoumeh Asadifard , Farzane Erfani , Omid Hassani Akbarieh , Fateme Mezginejad *
, Maziar Nasiri , Mohammadreza Meghdadi , Hasan Mortazi , Masoumeh Asadifard , Farzane Erfani , Omid Hassani Akbarieh , Fateme Mezginejad *
Abstract: (151 Views)
Background and Objectives
Patients with major thalassemia require regular blood transfusions, and one of the most important complications of repeated transfusions is the development of alloantibodies. This study aimed to assess the frequency and characterize common types of alloantibodies in patient population.
Materials and Methods
This descriptive cross-sectional study was conducted on 45 patients with transfusion-dependent major thalassemia in Birjand, Iran. Antibody screening and subsequent antibody identification tests were performed to detect alloantibodies. Demographic, clinical, and laboratory data including age, gender, and relevant clinical parameters were extracted from the patients’ electronic medical records. Data were analyzed using SPSS version 26, and the chi-square and Fisher’s exact tests were applied to evaluate associations between variables.
Results
A total of 45 patients, comprising 21 males (46.6%) and 24 females (53.3%), with and age ranged from 1 to 36 years, were included in the study. The overall prevalence of alloantibodies was 2.2%-18.1% (95% CI). Four alloantibodies were identified, with anti-K being the most frequent (3 patients, 100%) followed by anti-E (1 patient, 33%). The most common ABO phenotype was type O (42.2%), while Rh antigens c and e, were present in 100% and 93.3% of patients, respectively. Seven patients (15.5%) had undergone splenectomy. No significant association were observed between alloimmunization and age group, gender, blood group, number of transfused blood units, or splenectomy status.
Conclusions
Given the detection of alloantibodies targeting the Kell and Rh (E) blood group systems in the thalassemia population, it is recommended that transfused blood units be matched at a minimum for Kell and Rh antigens.
Patients with major thalassemia require regular blood transfusions, and one of the most important complications of repeated transfusions is the development of alloantibodies. This study aimed to assess the frequency and characterize common types of alloantibodies in patient population.
Materials and Methods
This descriptive cross-sectional study was conducted on 45 patients with transfusion-dependent major thalassemia in Birjand, Iran. Antibody screening and subsequent antibody identification tests were performed to detect alloantibodies. Demographic, clinical, and laboratory data including age, gender, and relevant clinical parameters were extracted from the patients’ electronic medical records. Data were analyzed using SPSS version 26, and the chi-square and Fisher’s exact tests were applied to evaluate associations between variables.
Results
A total of 45 patients, comprising 21 males (46.6%) and 24 females (53.3%), with and age ranged from 1 to 36 years, were included in the study. The overall prevalence of alloantibodies was 2.2%-18.1% (95% CI). Four alloantibodies were identified, with anti-K being the most frequent (3 patients, 100%) followed by anti-E (1 patient, 33%). The most common ABO phenotype was type O (42.2%), while Rh antigens c and e, were present in 100% and 93.3% of patients, respectively. Seven patients (15.5%) had undergone splenectomy. No significant association were observed between alloimmunization and age group, gender, blood group, number of transfused blood units, or splenectomy status.
Conclusions
Given the detection of alloantibodies targeting the Kell and Rh (E) blood group systems in the thalassemia population, it is recommended that transfused blood units be matched at a minimum for Kell and Rh antigens.
Type of Study: Research |
Subject:
Thalasemia
References
1. Vafaei M, Azad M, Shiargar P, Kazemi Haki B. Quality of life in patients with thalassemia major referred to Ardabil Buali Hospital in 2012-13. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch 2015; 25(4): 305-10. [Article in Farsi]
2. Seferi I, Xhetani M, Face M, Burazeri G, Nastas E, Vyshka G. Frequency and specificity of red cell antibodies in thalassemia patients in Albania. Int J Lab Hematol 2015; 37(4): 569-74. [DOI:10.1111/ijlh.12362] [PMID]
3. Tahannejad-Asadi Z, Elahi A, Mohseni A, Talebi M, Khosravi M, Jalalifar MA. Screening and identifying of erythrocyte alloantibodies in patients with Thalassemia major referred to Ahvaz Shafa hospital. Feyz Journals of Kashan University of Medical Sciences 2013; 17(2): 165-72. [Article in Farsi]
4. Davoudi-Kiakalayeh A, Mohammadi R, Pourfathollah AA, Siery Z, Davoudi-Kiakalayeh S. Alloimmunization in thalassemia patients: New insight for healthcare. Int J Prev Med 2017; 8(1): 101. [DOI:10.4103/ijpvm.IJPVM_246_16] [PMID] []
5. De Sanctis V, Kattamis C, Canatan D, Soliman AT, Elsedfy H, Karimi M, et al. β-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis 2017; 9(1): e2017018. [DOI:10.4084/mjhid.2017.018] [PMID] []
6. Mahboudi F, Zeinali S, Merat A, Delmaghani S, Mostafavipour K, Moghadam Z, et al. The molecular basis of beta thalassemia mutations in Fars province, Iran. Iran J Med Sci 1996; 21: 99-104.
7. Najmabad H, Teymourian Sh, Jalilnezhad S, Azad M, Khatibi T, Neyshabouri M, et al. Amplification refractory mutation system (arms) and reverse hybridization in the detection of beta - thalassemia mutations. Archives of Iranian Medicine 2001; 4(4): 165-70.
8. Butler E LM, Coller BS. William's Hematology. 6th ed. USA: McgrowHill; 2001. p. 1290-1292.
9. Orkin SH, Nathan DG, Ginsburg D, Look A, Fisher DE, Lux S. Nathan & Oski's hematology of infancy and childhood. Philadelphia: WB Saunders Company; 2003 p. 1173-1174.
10. Cheng C, Lee C, Lin C. Clinically significant red blood cell antibodies in chronically transfused patients: a survey of Chinese thalassemia major patients and literature review. Transfusion 2012; 52(10): 2220-4. [DOI:10.1111/j.1537-2995.2012.03570.x] [PMID]
11. Azarkeivan A, Ahmadi MH, Zolfaghari S, Shaiegan M, Ferdowsi S, Rezaei N, et al. RBC alloimmunization and double alloantibodies in thalassemic patients. Hematology 2015; 20(4): 223-7. [DOI:10.1179/1607845414Y.0000000189] [PMID]
12. Blaney KD, Howard PR. Basic and applied concepts of immunohematology. Philadelphia: Elsevier; 2001. p. 131-132.
13. Michail-Merianou V, Pamphili-Panousopoulou L, Piperi-Lowes L, Pelegrinis E, Karaklis A. Alloimmunization to red cell antigens in thalassemia: comparative study of usual versus better-match transfusion programmes. Vox Sang 1987; 52(1-2): 95-8. [DOI:10.1111/j.1423-0410.1987.tb02999.x] [PMID]
14. Pineda A, Vamvakas E, Gorden L, Winters J, Moore S. Trends in the incidence of delayed hemolytic and delayed serologic transfusion reactions. Transfusion 1999; 39(10): 1097-103. [DOI:10.1046/j.1537-2995.1999.39101097.x] [PMID]
15. Spanos T, Karageorga M, Ladis V, Peristeri J, Hatziliami A, Kattamis C. Red cell alloantibodies in patients with thalassemia. Vox Sang 1990; 58(1): 50-5.
https://doi.org/10.1111/j.1423-0410.1990.tb02055.x [DOI:10.1159/000461077] [PMID]
16. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells, Molecules, and Diseases 2006; 37(1): 12-20. [DOI:10.1016/j.bcmd.2006.04.005] [PMID]
17. Matteocci A, Pierelli L. Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing. Vox Sang 2014; 106(3): 197-208. [DOI:10.1111/vox.12086] [PMID]
18. 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(2): 95-8. [DOI:10.4103/0973-6247.53884] [PMID] []
19. Singer ST, Wu V, Mignacca R, Kuypers FA, Morel P, Vichinsky EP. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly Asian descent. Blood 2000; 96(10): 3369-73.
https://doi.org/10.1182/blood.V96.10.3369 [DOI:10.1182/blood.V96.10.3369.h8003369_3369_3373]
20. Kiani A, Abdi J, Shirkhani Y, Kashi M. Prevalence of alloimmunization against RBC antigens in thalassemia major patients of Lorestan province in 1383. Sci J Iran Blood Transfus Organ 2006; 3(3): 265-71. [Article in Farsi]
21. Al‐Riyami AZ, Al‐Muqbali A, Al‐Sudiri S, Murthi Panchatcharam S, Zacharia M, Al‐Mahrooqi S, et al. Risks of red blood cell alloimmunization in transfusion‐dependent β‐thalassemia in Oman: a 25‐year experience of a university tertiary care reference center and a literature review. Transfusion 2018; 58(4): 871-8. [DOI:10.1111/trf.14508] [PMID]
22. Chao YH, Wu KH, Lu JJ, Shih MC, Peng CT, Chang CW. Red blood cell alloimmunisation among Chinese patients with β-thalassaemia major in Taiwan. Blood Transfus 2013; 11(1): 71-4.
23. Ahmed AM, Hasan NS, Ragab SH, Habib SA, Emara NA, Aly AA. Red cell alloimmunization and autoantibodies in Egyptian transfusion-dependent thalassaemia patients. Arch Med Sci 2010; 6(4): 592-8. [DOI:10.5114/aoms.2010.14473] [PMID] []
24. Obeidi N, Mankhian AR, Hatami G, Emami H. Antibody screening in patients with thalassemia major. Lab Med 2011; 42(10): 618-21. [DOI:10.1309/LMBF1AT2HEVYUS7D]
25. Ahmadi D. Frequency of minor blood group alloantibodies in beta-thalassemia major blood recipients in Kermanashah (1999). 2001. p:23.
26. Rostamian H, Javandoost E, Mohammadian M, Alipour A. Prevalence and specificity of red blood cell alloantibodies and autoantibodies in transfused Iranian β-thalassemia patients: A systematic review and meta-analysis. Asian J Transfus Sci 2022; 16(1): 111-20. [DOI:10.4103/ajts.AJTS_39_20] [PMID] []
27. Shamsian B, Arzanian MT, Shamshiri AR, Alavi S, Khojasteh O. Frequency of red cell alloimmunization in patients with beta-major thalassemia in an Iranian referral hospital. 2008; 2(1): 13-17.
28. Karimi M, Nikrooz P, Kashef S, Jamalian N, Davatolhagh Z. RBC alloimmunization in blood transfusion‐dependent β‐thalassemia patients in southern Iran. Int J Lab Hematol 2007; 29(5): 321-6. [DOI:10.1111/j.1365-2257.2006.00856.x] [PMID]
29. 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. Iranian Journal of Blood and Cancer 2013; 6(1): 41-6.
30. Ameen 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): 1604-10. [DOI:10.1046/j.1537-2995.2003.00549.x] [PMID]
31. El Danasoury AS, Eissa DG, Abdo RM, Elalfy MS. Red blood cell alloimmunization in transfusion‐dependent Egyptian patients with thalassemia in a limited donor exposure program. Transfusion 2012; 52(1): 43-7. [DOI:10.1111/j.1537-2995.2011.03234.x] [PMID]
32. Ho HK, Ha SY, Lam CK, Chan GC, Lee TL, Chiang AK, et al. Alloimmunization in Hong Kong southern Chinese transfusion-dependent thalassemia patients. Blood 2001; 97(12): 3999-4000. [DOI:10.1182/blood.V97.12.3999] [PMID]
33. Patel AS, Gamit S, Gohil M. Role of RBC's alloimmunization in multiple transfused thalassaemia patients. Int J Res Med Sci 2016; 4(3): 822-8. [DOI:10.18203/2320-6012.ijrms20160526]
34. Gupta R, Singh DK, Singh B, Rusia U. Alloimmunization to red cells in thalassemics: emerging problem and future strategies. Transfus Apher Sci 2011; 45(2): 167-70. [DOI:10.1016/j.transci.2011.07.014] [PMID]
35. Bilwani F, Nabi G, Adil S, Usman M, Hassan F, Khurshid M. Frequency of irregular red cell alloantibodies in patients with thalassemia major: a bicenter study. J Pak Med Assoc 2005; 55(12): 563-5.
36. Ghasemi A, Abbasian S, Ghaffari K, Salmanpour Z. Prevalence of alloantibodies and autoantibodies in transfusion dependent thalassemia patients. Iranian Journal of Blood and Cancer 2016; 8(3): 80-5.
37. Mirzaeian A, Tamaddon G, Naderi M, Hosseinpour M, Sargolzaie N. Prevalence of alloimmunization against RBC antigens in thalassemia major patients. Zahedan Journal of Research in Medical Sciences 2013; 15(7): 55-8.
38. Mohamadimaram M, Gharehbaghian A, Abdollahi A, Khansari M. The prevalence of undesired blood group antibodies in thalassemia patients. Sci J Iran Blood Transfus Organ 2020; 17(2): 91-9. [Article in Farsi]
39. Darvishi P, Azami M, Sayehmiri K, Sayehmiri F, Goodarzi A, Azarkeivan A, et al. Red blood cell alloimmunization in Iranian beta‐thalassemia patients: a systematic review and meta‐analysis. ISBT Science Series 2016; 11(3): 163-73. [DOI:10.1111/voxs.12299]
40. Hussein E, Desooky N, Rihan A, Kamal A. Predictors of red cell alloimmunization in multitransfused Egyptian patients with β-thalassemia. Arch Pathol Lab Med 2014; 138(5): 684-8. [DOI:10.5858/arpa.2013-0016-OA] [PMID]
41. El-Beshlawy A, Salama AA, El-Masry MR, El Husseiny NM, Abdelhameed AM. A study of red blood cell alloimmunization and autoimmunization among 200 multitransfused Egyptian β thalassemia patients. Sci Rep 2020; 10(1): 21079. [DOI:10.1038/s41598-020-78333-y] [PMID] []
42. 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. [DOI:10.3109/03630269.2015.1077460] [PMID]
43. Azarkeivan A, Ansari S, Ahmadi MH, Hajibeigy B, Maghsudlu M, Nasizadeh S, et al. Blood transfusion and alloimmunization in patients with thalassemia: multicenter study. Pediatr Hematol Oncol 2011; 28(6): 479-85. [DOI:10.3109/08880018.2011.568595] [PMID]
44. Ebrahimisadr P, Bakhshandeh Z, Majidiani H. Red cell alloantibodies in beta-thalassaemia major patients' blood referring to the regional blood transfusion center of Tehran, Iran. Bioimpacts 2020; 11(2): 129-33. [DOI:10.34172/bi.2021.20] [PMID] []
45. Keramati MR, Sadeghian MH, Zarmehri AM. Red blood cells alloimmunization and autoimmunization in multi-transfused thalassemia patients in south of Iran. Iran J Pediatr Hematol Oncol 2019; 9(1): 40-7.
46. Afshari M, Amiri F, Seyedi M, Biglari M, Jambozorg H. Evaluation of alloantibodies in thalassemia patients referred to Hamadan Besat hospital in 2019. Sc J Iran Blood Transfus Organ 2021; 18(3): 187-95. [Article in Farsi]
47. Davari K, Soltanpour MS. Study of alloimmunization and autoimmunization in Iranian β-thalassemia major patients. Asian J Transfus Sci 2016; 10(1): 88-92. [DOI:10.4103/0973-6247.172179] [PMID] []
48. Vaziri M, Javadzadeh Shahshahani H, Moghaddam M, Taghvaee N. Prevalence and specificities of red cell alloantibodies in transfusion-dependent beta thalassemia patients in Yazd. Iran J Ped Hematol Oncol 2015; 5(2): 93-9.
49. Hassan K, Younus M, Ikram N, Naseem L, Zaheer HA. Red cell alloimmunization in repeatedly transfused thalassemia major patients. Int J Pathol 2018; 16-9.
50. Reisner E, Kostyu D, Phillips G, Walker C, Dawson D. Alloantibody responses in multiply transfused sickle cell patients. Tissue Antigens 1987; 30(4): 161-6. [DOI:10.1111/j.1399-0039.1987.tb01615.x] [PMID]
51. Saied DA, Kaddah AM, Eldin RMB, Mohaseb SS. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent Egyptian thalassemic patients. J Pediatr Hematol Oncol 2011; 33(6): 409-14. [DOI:10.1097/MPH.0b013e3182208154] [PMID]
52. Koochakzadeh L, Kajiyazdi M, Khoshhal F, Hashemi A, Khabazkhoob M. Prevalence of alloantibodies in thalassemia patients and its relationship with age, gender and blood group. Acta Med Iran 2023; 61(1): 52-6. [DOI:10.18502/acta.v61i1.12126]
53. Eghbali A, Rahimi-Afzal R, Mehrabi S, Sanatkar SA, Mousavi-Hasanzadeh M. Frequency and risk factors of red blood cell alloimmunization in thalassemia major patients in Markazi province. Iran J Pediatr Hematol Oncol 2019; 9(1): 25-31.
54. Abdulqader AMR, Mohammed AI, Mohammed NI. Red cell alloimmunization and autoimmunization in multi-transfused thalassemia patients in Sulaymaniyah Province-Iraq. Korean J Clin Lab Sci 2020; 52(2): 98-104. [DOI:10.15324/kjcls.2020.52.2.98]
55. Paramore C, Vlahiotis A, Moynihan M, Cappell K, Ramirez-Santiago A. Treatment patterns and costs of transfusion and chelation in commercially-insured and medicaid patients with transfusion-dependent β-thalassemia. Blood 2017; 130: 5635. [DOI:10.1016/j.jval.2018.04.1750]
56. Sharma A, Mathew ME, Puri L. Splenectomy for people with thalassaemia major or intermedia. Cochrane Database Syst Rev 2019; 9(9): CD010517. [DOI:10.1002/14651858.CD010517.pub3] [PMID]
57. Azarkeivan A, Ahmadi MH, Gharehbaghian A, Zolfaghari S, Nasizadeh S, Maghsudlu M, et al. Antibody screening and identification by gel method in thalassemic patients. Sci J Iran Blood Transfus Organ 2008; 5(2): 99-108. [Article in Farsi]
58. Thompson AA, Cunningham MJ, Singer ST, Neufeld EJ, Vichinsky E, Yamashita R, et al. Red cell alloimmunization in a diverse population of transfused patients with thalassaemia. Br J Haematol 2011; 153(1): 121-8. [DOI:10.1111/j.1365-2141.2011.08576.x] [PMID] []
59. Pazgal I, Yahalom V, Shalev B, Raanani P, Stark P. Alloimmunization and autoimmunization in adult transfusion-dependent thalassemia patients: a report from a comprehensive center in Israel. Ann Hematol 2020; 99(12): 2731-6. [DOI:10.1007/s00277-020-04104-4] [PMID]
60. Ansari S, Voosogh P, Moshtaghian S. Assessment of frequency of alloimmunization and erythrocyte autoimmunization in transfusion dependent thalassemia patients. Acta Med Iran 2008; 46(2): 137-40.
61. Mincheff M. Changes in donor leukocytes during blood storage. Implications on post‐transfusion immunomodulation and transfusion‐associated GVHD. Vox Sang 1998; 74(S2): 189-200. [DOI:10.1111/j.1423-0410.1998.tb05420.x] [PMID]
62. Fluit C, Kunst V, Drenthe‐Schonk A. Incidence of red cell antibodies after multiple blood transfusion. Transfusion 1990; 30(6): 532-5. [DOI:10.1046/j.1537-2995.1990.30690333485.x] [PMID]
63. Rosse WF, Gallagher D, Kinney TR, Castro O, Dosik H, Moohr J, et al. Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease. Blood 1990; 76(7): 1431-7.
https://doi.org/10.1182/blood.V76.7.1431.1431 [DOI:10.1182/blood.V76.7.1431.bloodjournal7671431]
64. Schonewille H, Van De Watering LM, Loomans DS, Brand A. Red blood cell alloantibodies after transfusion: factors influencing incidence and specificity. Transfusion 2006; 46(2): 250-6. [DOI:10.1111/j.1537-2995.2006.00708.x] [PMID]
65. 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(2): 84-8. [DOI:10.4103/0973-6247.137438] [PMID] []
66. Arianezhad A, Eslamizadeh R, Momeni A, Yazdanpanah P, Behzadifard M. Investigation of alloimmunization in beta-thalassemia major patients: a cross-sectional study. Ann Med Surg 2025; 87(4): 1893-6. [DOI:10.1097/MS9.0000000000003092] [PMID] []
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
