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Copyright (c) 2026 Ali Mohammed Salem Assiri, Fahad M. Aldakheel, Farjah H. AlGahtani

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Red Blood Cell Alloimmunization in Patients with Sickle Cell Disease from Abha, Asir Region, Saudi Arabia
Corresponding Author(s) : Ali Mohammed Salem Assiri
Saudi Journal of Medicine and Public Health, Vol. 3 No. 1 (2026)
Abstract
Background. Red blood cell (RBC) transfusion is a mainstay of treatment for sickle cell disease (SCD), but is associated with alloimmunization, leading to delayed hemolytic transfusion responses and limiting availability of suitable blood. There is little regional data from the south of Saudi Arabia.
Method. This cross-sectional study was performed in Abha, Asir Region, from 2018 to 2020. Two hundred patients aged 14–69 years with SCD were examined for RBC alloantibodies. Blood samples were screened for antibodies and phenotyped (ABO; Rh D, C, c, E, e; K; Fya, Fyb; Jka, Jkb; Lea, Leb; M, N, S, s) using the gel method on an automated platform (Ortho Clinical Diagnostics).
Results. Alloantibodies were detected in 29 of 200 patients (14.5%; 95% CI 10.3 to 20.0%): 16 of 116 males (13.8%) and 13 of 84 females (15.5%). Fifteen of the twenty-nine had multiple antibodies. The most prevalent specificity was anti-E (17 patients, 58.6% of positives) followed by anti-K (11, 37.9%), anti-c (7, 24.1%) and anti-C (4, 13.8%). In 27 of 29 (93.1%) Rh‐ or K‐positive individuals, antibodies to these antigens were detected. Positive individuals had received a median of 12 transfusions (range 5-26).
Conclusions. In Abha, approximately one in seven SCD patients who had transfusion were alloimmunized largely against Rh (E, c, C) and Kell (K) antigens. Further large prospective trials are suggested, along with prophylactic Rh and K matching, preferably prolonged matching, and leukoreduced units.
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- 1. Abbas, M., & Bolad, A. K. (2013). Red blood cell alloimmunization among Sudanese homozygous sickle cell disease patients. American Journal of Medicine and Medical Sciences, 3(4): 61-67 DOI: 10.5923/j.ajmms.20130304.02
- 2. Aggarwal, G., Tiwari, A. K., Dhiman, P., Arora, D., Pabbi, S. M., & Setya, D. (2020). Red blood cell exchange in sickle cell disease patient with multiple alloantibodies. Asian Journal of Transfusion Science, 14(1), 70. https://doi.org/10.4103/ajts.AJTS_36_18
- 3. Al-Asmari, B., Baothman, A., Almohammadi, M., Aljuaid, M., & Jastaniah, W. (2024). Prevalence of red blood cell alloimmunization among pediatric patients with sickle cell disease in Saudi Arabia. Journal of Pediatric Hematology/Oncology, 46(5), e284. https://doi.org/10.1097/MPH.0000000000002889
- 4. Alboog, A. S. T. T., Tayeb, T., Alsager, M., Alnajjar, S., Damanhouri, G., Jarullah, J., & Hindawi, S. I. (2015). Red blood cell alloimmunization in sickle cell disease patients in Jeddah, Saudi Arabia: a pilot study. JKAU Med Sci, 22(3), 35-40. DOI: 10.4197/Med. 22.3.3
- 5. Alkindi, S., AlMahrooqi, S., AlHinai, S., AlMarhoobi, A., Al-Hosni, S., Daar, S., ... & Pathare, A. (2017). Alloimmunization in patients with sickle cell disease and thalassemia: experience of a single centre in Oman. Mediterranean journal of hematology and infectious diseases, 9(1), e2017013. https://doi.org/10.4084/MJHID.2017.013
- 6. Bashawri, L. A. M. (2007). Red cell alloimmunization in sickle-cell anaemia patients. EMHJ-Eastern Mediterranean Health Journal, 13 (5), 1181-1189, 2007. https://iris.who.int/handle/10665/117364
- 7. Boateng, L. A., Ngoma, A. M., Bates, I., & Schonewille, H. (2019). Red blood cell alloimmunization in transfused patients with sickle cell disease in sub-Saharan Africa; a systematic review and meta-analysis. Transfusion medicine reviews, 33(3), 162-169. https://doi.org/10.1016/j.tmrv.2019.06.003
- 8. Campbell-Lee, S. A., & Kittles, R. A. (2014). Red blood cell alloimmunization in sickle cell disease: listen to your ancestors. Transfusion Medicine and Hemotherapy, 41(6), 431-435. https://doi.org/10.1159/000369513
- 9. Fasano, R. M., Meyer, E. K., Branscomb, J., White, M. S., Gibson, R. W., & Eckman, J. R. (2019). Impact of red blood cell antigen matching on alloimmunization and transfusion complications in patients with sickle cell disease: a systematic review. Transfusion medicine reviews, 33(1), 12-23. https://doi.org/10.1016/j.tmrv.2018.07.003
- 10. Gammon, R. R., Blumberg, N., Gilstad, C., Mandal, S., Nair, A. R., & Bocquet, C. (2023). Patient blood management: Myths and facts about red blood cell transfusions. Vox Sanguinis, 118(7), 509-516. https://doi.org/10.1111/vox.13442
- 11. Israelyan, N., Vege, S., Friedman, D. F., Zhang, Z., Uter, S., Fasano, R. M., ... & Chou, S. T. (2024). RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: a multisite study in the USA. Transfusion, 64(3), 526-535. https://doi.org/10.1111/trf.17740
- 12. Kaur, G. (2019). Alloimmunization to Kell blood group system antigen owing to unmatched blood transfusion in a resource-poor setting. Immunohematology.
- 13. Leal, I., Dos Santos, T. D., Gilli, S., & Castilho, L. (2023). Effects of prophylactic red blood cell (RBC) transfusion with extended antigen matching on alloimmunization in patients with Sickle Cell Disease (SCD). Transfusion and Apheresis Science, 62(6), 103813. https://doi.org/10.1016/j.transci.2023.103813
- 14. Meda, E., Magesa, P. M., Marlow, T., Reid, C., Roberts, D. J., & Makani, J. (2014). Red blood cell alloimmunization in sickle cell disease patients in Tanzania. East African journal of public health, 11(2), 775.
- 15. Natukunda, B., Schonewille, H., Ndugwa, C., & Brand, A. (2010). Red blood cell alloimmunization in sickle cell disease patients in Uganda. Transfusion, 50(1), 20-25. https://doi.org/10.1111/j.1537-2995.2009.02435.x
- 16. O'Suoji, C., Liem, R. I., Mack, A. K., Kingsberry, P., Ramsey, G., & Thompson, A. A. (2013). Alloimmunization in sickle cell anemia in the era of extended red cell typing. Pediatric blood & cancer, 60(9), 1487-1491. https://doi.org/10.1002/pbc.24530
- 17. Rossi, M., Pirenne, F., Le Roux, E., Smaïne, D., Belloy, M., Eyssette‐Guerreau, S., ... & Missud, F. (2023). Delayed haemolytic transfusion reaction in paediatric patients with sickle cell disease: a retrospective study in a French national reference centre. British Journal of Haematology, 201(1), 125-132. https://doi.org/10.1111/bjh.18605
- 18. Setty, B. Y., Betal, S. G., Miller, R. E., Brown, D. S., Meier, M., Cahill, M., ... & Stuart, M. J. (2019). Relationship of Omega-3 fatty acids DHA and EPA with the inflammatory biomarker hs-CRP in children with sickle cell anemia. Prostaglandins, Leukotrienes and Essential Fatty Acids, 146, 11-18. https://doi.org/10.1016/j.plefa.2019.05.004
- 19. Tanhehco, Y. C., Shi, P. A., & Schwartz, J. (2022). Transfusion therapy in sickle cell disease. Annals of Blood, 7. doi: 10.21037/aob-21-67
- 20. Venkateswaran, L., Teruya, J., Bustillos, C., Mahoney Jr, D., & Mueller, B. U. (2011). Red cell exchange does not appear to increase the rate of allo‐and auto‐immunization in chronically transfused children with sickle cell disease. Pediatric Blood & Cancer, 57(2), 294-296. https://doi.org/10.1002/pbc.22985
- 21. Versino, F., Revelli, N., Villa, S., Pettine, L., Zaninoni, A., Prati, D., ... & Fattizzo, B. (2024). Transfusions in autoimmune hemolytic anemias: frequency and clinical significance of alloimmunization. Journal of internal medicine, 295(3), 369-374. https://doi.org/10.1111/joim.13753
- 22. Wahl, S. K., Garcia, A., Hagar, W., Gildengorin, G., Quirolo, K., & Vichinsky, E. (2012). Lower alloimmunization rates in pediatric sickle cell patients on chronic erythrocytapheresis compared to chronic simple transfusions. Transfusion, 52(12), 2671-2676. https://doi.org/10.1111/j.1537-2995.2012.03659.x
- 23. Wihak, T., Burns, M., Miranda, J., Windmueller, G., Oakley, C., & Coakley, R. (2020). Development and feasibility testing of the Comfort Ability Program for sickle cell pain: A patient-informed, video-based pain management intervention for adolescents with sickle cell disease. Clinical Practice in Pediatric Psychology, 8(2), 150-163. https://doi.org/10.1037/cpp0000326
- 24. Wong, K., Lai, W. K., & Jackson, D. E. (2022). HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta‐analysis). Vox Sanguinis, 117(11), 1251-1261. https://doi.org/10.1111/vox.13351
- 25. Yazdanbakhsh, K., Ware, R. E., & Noizat-Pirenne, F. (2012). Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood, The Journal of the American Society of Hematology, 120(3), 528-537. https://doi.org/10.1182/blood-2011-11-327361
- 26. Zanette, A. M. D., de Souza Gonçalves, M., Schettini, L. V., Aguiar, L. M., Bahia, R. C. S., Nogueira, L. A. V., ... & Arruda, S. M. (2010). Alloimmunization and clinical profile of sickle cell disease patients from Salvador-Brazil. Ethnicity & disease, 20(2), 136-141.
References
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2. Aggarwal, G., Tiwari, A. K., Dhiman, P., Arora, D., Pabbi, S. M., & Setya, D. (2020). Red blood cell exchange in sickle cell disease patient with multiple alloantibodies. Asian Journal of Transfusion Science, 14(1), 70. https://doi.org/10.4103/ajts.AJTS_36_18
3. Al-Asmari, B., Baothman, A., Almohammadi, M., Aljuaid, M., & Jastaniah, W. (2024). Prevalence of red blood cell alloimmunization among pediatric patients with sickle cell disease in Saudi Arabia. Journal of Pediatric Hematology/Oncology, 46(5), e284. https://doi.org/10.1097/MPH.0000000000002889
4. Alboog, A. S. T. T., Tayeb, T., Alsager, M., Alnajjar, S., Damanhouri, G., Jarullah, J., & Hindawi, S. I. (2015). Red blood cell alloimmunization in sickle cell disease patients in Jeddah, Saudi Arabia: a pilot study. JKAU Med Sci, 22(3), 35-40. DOI: 10.4197/Med. 22.3.3
5. Alkindi, S., AlMahrooqi, S., AlHinai, S., AlMarhoobi, A., Al-Hosni, S., Daar, S., ... & Pathare, A. (2017). Alloimmunization in patients with sickle cell disease and thalassemia: experience of a single centre in Oman. Mediterranean journal of hematology and infectious diseases, 9(1), e2017013. https://doi.org/10.4084/MJHID.2017.013
6. Bashawri, L. A. M. (2007). Red cell alloimmunization in sickle-cell anaemia patients. EMHJ-Eastern Mediterranean Health Journal, 13 (5), 1181-1189, 2007. https://iris.who.int/handle/10665/117364
7. Boateng, L. A., Ngoma, A. M., Bates, I., & Schonewille, H. (2019). Red blood cell alloimmunization in transfused patients with sickle cell disease in sub-Saharan Africa; a systematic review and meta-analysis. Transfusion medicine reviews, 33(3), 162-169. https://doi.org/10.1016/j.tmrv.2019.06.003
8. Campbell-Lee, S. A., & Kittles, R. A. (2014). Red blood cell alloimmunization in sickle cell disease: listen to your ancestors. Transfusion Medicine and Hemotherapy, 41(6), 431-435. https://doi.org/10.1159/000369513
9. Fasano, R. M., Meyer, E. K., Branscomb, J., White, M. S., Gibson, R. W., & Eckman, J. R. (2019). Impact of red blood cell antigen matching on alloimmunization and transfusion complications in patients with sickle cell disease: a systematic review. Transfusion medicine reviews, 33(1), 12-23. https://doi.org/10.1016/j.tmrv.2018.07.003
10. Gammon, R. R., Blumberg, N., Gilstad, C., Mandal, S., Nair, A. R., & Bocquet, C. (2023). Patient blood management: Myths and facts about red blood cell transfusions. Vox Sanguinis, 118(7), 509-516. https://doi.org/10.1111/vox.13442
11. Israelyan, N., Vege, S., Friedman, D. F., Zhang, Z., Uter, S., Fasano, R. M., ... & Chou, S. T. (2024). RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: a multisite study in the USA. Transfusion, 64(3), 526-535. https://doi.org/10.1111/trf.17740
12. Kaur, G. (2019). Alloimmunization to Kell blood group system antigen owing to unmatched blood transfusion in a resource-poor setting. Immunohematology.
13. Leal, I., Dos Santos, T. D., Gilli, S., & Castilho, L. (2023). Effects of prophylactic red blood cell (RBC) transfusion with extended antigen matching on alloimmunization in patients with Sickle Cell Disease (SCD). Transfusion and Apheresis Science, 62(6), 103813. https://doi.org/10.1016/j.transci.2023.103813
14. Meda, E., Magesa, P. M., Marlow, T., Reid, C., Roberts, D. J., & Makani, J. (2014). Red blood cell alloimmunization in sickle cell disease patients in Tanzania. East African journal of public health, 11(2), 775.
15. Natukunda, B., Schonewille, H., Ndugwa, C., & Brand, A. (2010). Red blood cell alloimmunization in sickle cell disease patients in Uganda. Transfusion, 50(1), 20-25. https://doi.org/10.1111/j.1537-2995.2009.02435.x
16. O'Suoji, C., Liem, R. I., Mack, A. K., Kingsberry, P., Ramsey, G., & Thompson, A. A. (2013). Alloimmunization in sickle cell anemia in the era of extended red cell typing. Pediatric blood & cancer, 60(9), 1487-1491. https://doi.org/10.1002/pbc.24530
17. Rossi, M., Pirenne, F., Le Roux, E., Smaïne, D., Belloy, M., Eyssette‐Guerreau, S., ... & Missud, F. (2023). Delayed haemolytic transfusion reaction in paediatric patients with sickle cell disease: a retrospective study in a French national reference centre. British Journal of Haematology, 201(1), 125-132. https://doi.org/10.1111/bjh.18605
18. Setty, B. Y., Betal, S. G., Miller, R. E., Brown, D. S., Meier, M., Cahill, M., ... & Stuart, M. J. (2019). Relationship of Omega-3 fatty acids DHA and EPA with the inflammatory biomarker hs-CRP in children with sickle cell anemia. Prostaglandins, Leukotrienes and Essential Fatty Acids, 146, 11-18. https://doi.org/10.1016/j.plefa.2019.05.004
19. Tanhehco, Y. C., Shi, P. A., & Schwartz, J. (2022). Transfusion therapy in sickle cell disease. Annals of Blood, 7. doi: 10.21037/aob-21-67
20. Venkateswaran, L., Teruya, J., Bustillos, C., Mahoney Jr, D., & Mueller, B. U. (2011). Red cell exchange does not appear to increase the rate of allo‐and auto‐immunization in chronically transfused children with sickle cell disease. Pediatric Blood & Cancer, 57(2), 294-296. https://doi.org/10.1002/pbc.22985
21. Versino, F., Revelli, N., Villa, S., Pettine, L., Zaninoni, A., Prati, D., ... & Fattizzo, B. (2024). Transfusions in autoimmune hemolytic anemias: frequency and clinical significance of alloimmunization. Journal of internal medicine, 295(3), 369-374. https://doi.org/10.1111/joim.13753
22. Wahl, S. K., Garcia, A., Hagar, W., Gildengorin, G., Quirolo, K., & Vichinsky, E. (2012). Lower alloimmunization rates in pediatric sickle cell patients on chronic erythrocytapheresis compared to chronic simple transfusions. Transfusion, 52(12), 2671-2676. https://doi.org/10.1111/j.1537-2995.2012.03659.x
23. Wihak, T., Burns, M., Miranda, J., Windmueller, G., Oakley, C., & Coakley, R. (2020). Development and feasibility testing of the Comfort Ability Program for sickle cell pain: A patient-informed, video-based pain management intervention for adolescents with sickle cell disease. Clinical Practice in Pediatric Psychology, 8(2), 150-163. https://doi.org/10.1037/cpp0000326
24. Wong, K., Lai, W. K., & Jackson, D. E. (2022). HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta‐analysis). Vox Sanguinis, 117(11), 1251-1261. https://doi.org/10.1111/vox.13351
25. Yazdanbakhsh, K., Ware, R. E., & Noizat-Pirenne, F. (2012). Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood, The Journal of the American Society of Hematology, 120(3), 528-537. https://doi.org/10.1182/blood-2011-11-327361
26. Zanette, A. M. D., de Souza Gonçalves, M., Schettini, L. V., Aguiar, L. M., Bahia, R. C. S., Nogueira, L. A. V., ... & Arruda, S. M. (2010). Alloimmunization and clinical profile of sickle cell disease patients from Salvador-Brazil. Ethnicity & disease, 20(2), 136-141.