RED Blood Cell Alloimmunization in Sickle Cell Anaemia Patients in Kilifi, Kenya

Background: Sickle cell anaemia (SCA) patients rely on transfusions as an intervention for management of their disease. In Kenya, matching of blood between donors and recipients is only performed for major ABO and Rhesus D antigens, without extended matching for clinically significant minor blood groups. Similarly, although cross matching is done before blood is issued, routine screening for red blood cell (RBC) alloantibodies, which increase the risk of haemolytic transfusion reactions, is not performed. Both the WHO and the American Society of Hematology recommend that RBC antigen profiling and matching for clinically significant antigens is necessary to reduce the risks of alloimmunization. The diversity of these antigens among patient cohorts has not been established. Our study aimed to establish the RBC antigen diversity and the burden of alloimmunization among SCA patients with a history of transfusion in Kilifi, Kenya.

Methods: The study was conducted at Kilifi County Referral Hospital, where transfused individuals with SCA were identified retrospectively from hospital admission records (N=98, 2002-2023) and cross-sectionally at the SCA clinic (N=167, 2023-2024). Corresponding plasma samples were screened for alloantibodies, and alloantibodies identified in positive samples using proprietary methods (Bio-Rad ID-Diacell and ID-diapanel cells). Phenotyping for ABO, RhCDE, Kell, Duffy, Kidd, Lewis, Lutheran, P1 and MNS blood groups was done on RBCs collected from the cross-sectional survey participants using Bio-Rad phenotyping gel-cards.

Results: The median age for the paediatric retrospective admissions was 4.9 (IQR, 2.3-7.9) years and 54% were female. The number of transfusions received ranged from 1 to 13, the median age at first transfusion being 2.3 (IQR, 1.0-4.8) years. Alloantibodies were identified in fourteen (14.3%) participants and one (1.0%) had an autoantibody. Eight alloantibodies were identified; two anti-e, plus one each of anti-E, anti-M, anti-S, anti-s, anti-Lu^a & anti-Le^b. Five others had pan reactive alloantibodies and three had antibodies of unidentified specificity.

The median age of children in the cross-sectional survey was 10.7 years (IQR 5.9-15.1, age range 1-46 years) 46.5% of the participants were female The prevalence of blood groups O, A, B and AB was 54.9%, 18.3%, 23.7% and 3.1% respectively while 96.5% were RhD positive. Highly expressed antigens were D, c, e, Kp^b, k and Jk^a while Fy^a, Fy^b and K were rarer antigens. Phenotypes with low expression (<1%) were CCD.ee, CcD.Ee, CCD.EE, M+N+S+s-, M-N-S-s+, K+k+, Le(a+b+) and Fy(a+b+) respectively. Ten (6%) participants were positive for alloantibodies and two (1.0%) had an autoantibody (1.2%). Seven alloantibodies were identified: anti-D (N=2), -C, -C^W, -e, -E and -Le^a. Two had antibodies of unidentified specificity and one a pan reactive alloantibody.

Increase in age among retrospective admissions and the cross-sectional survey participants was significantly associated with the development of antibodies, p=0.028 and p=0.040 respectively.

Conclusion: The rates of alloimmunization in the cross-sectional survey were similar to those previously reported in the East Africa region (2.9-8%) while that among the hospital admission cohort was higher (14.3%). Most antibodies were to Rh and MNS blood groups and increasing age was significantly associated with alloantibody development. There is need for transfusion services in sub-Saharan African countries to consider alloantibody screening, especially in SCA children, to reduce the risk of alloimmunization and ensure transfusion safety.

Ware:Merck Pharmaceuticals: Other: Medical Advisory Board; Nova Laboratories: Other: Medical Advisory Board; Theravia: Other: Medical Advisory Board; Novo Nordisk: Other: Health Equity Advisory Board.