title: Investigation of post transfusion red blood cell alloimmunisation in patients with sickle cell disease in Ghana
Creators: name: Boateng, Lilian
Publisher: name: University of Liverpool Repository
Year: 2021

description: Blood transfusion in patients with sickle cell disease (SCD) is associated with the development of antibodies against the foreign transfused red blood cell (RBC) antigens, i.e. RBC alloimmunisation. Very few studies have reported on RBC alloimmunisation in patients with SCD in sub-Saharan Africa (SSA), where antibody testing and RBC matching beyond blood groups ABO and Rh D are not done in most centres. Even when antibody testing is done, it is performed with standard reagent test cells mostly from donors of Caucasian descent that lack antigens that are more prevalent or exclusively present in Africans. This may miss antibodies to the antigens that are predominantly present in Africans, putting patients at risk of haemolytic transfusion reactions upon subsequent transfusions with antigens to which patients have made antibodies. The overall goal of this project was to investigate post transfusion RBC alloimmunisation and adverse transfusion events in patients with SCD in Ghana and to explore ways of optimising transfusion practices to detect alloimmunisation to clinically relevant RBC antigens and, thereby, prevent transfusion reactions. To achieve this: 1. a systematic review of published literature and a meta analysis were performed to determine the estimated frequency of RBC alloimmunisation in SSA. 2. A cross-sectional study was performed and this was in two parts: - first, to determine the prevalence, specificities, and risk factors for RBC alloantibodies against a standard Caucasian antigen panel and eight selected antigens predominantly present in Africans (frequency 0.5% to 32%) and adverse transfusion events assessed by patient recall in multi-transfused patients with SCD. - second, to determine the frequency of 24 clinically relevant RBC antigens- routinely included in commercially available antibody screening panels- among patients with SCD and/or blood donors in Ghanaians of different ethnicity. The systematic literature review and meta-analysis included 15 studies of RBC alloimmunisation in patients with SCD from nine SSA countries. The overall proportion of alloimmunisation in patients with SCD in SSA was 7.4% (95% confidence interval (CI) 5.1-10.0). Antibodies E, D, C and K accounted for almost 50% of the specificities. Antibodies to uncommon and common antigens accounted for 20% and 9% respectively of the antibody specificities. The first part of the cross-sectional study recruited 226 patients with SCD. In these patients antibodies were present in 36 (16%); 25 patients (11.1%) with 26 antibody specificities were positive with the standard Caucasian panel and 11 patients (5.3%) with 11 antibody specificities were positive with the selected African antigens. Receiving the first transfusion after the age of three years (aOR 3.28) and the number of transfusions (aOR 2.00) were positively associated with alloimmunisation. Adverse transfusion reactions were recalled by 68 patients (30%), of which 23 patients had signs suggestive of haemolytic reactions. Adverse transfusion reactions were positively associated with the number of transfusions (aOR 2.06). The second part of the cross-sectional study performed RBC antigen typing for 24 antigens; antigens A, B, D, C, E, c, e, Jka, Jkb, M, N, S, s, Fya, Fyb by serology and low prevalent antigens Cw, K, Kpa, Jsa and Lua and high prevalent antigens k, Kpb, Jsb and Lub by genotyping. The numbers of samples tested per antigen ranged from 117 to 505. Among patients and donors, the antigens and antigen phenotypes frequencies did not differ, except for the C antigen, and the ccddee phenotype. Participants belonged to 26 different ethnic groups and this was categorized into four groups namely Akan, Ga, Ewe and Other. Among the four ethnic groups, frequency variations were observed for some antigens with the Ewe population showing the highest number of antigens (A, B, E, and Lua) and antigen phenotypes (ccDEe, ccDee and Ccddee) differences compared to the other ethnicity groups. The Ga population also differed from the other ethnic groups in the frequency of the Jsa antigen and the Js(a+b+) phenotype. Overall, my research shows that in Ghana patients with SCD do devleop RBC antibodies (16%) following blood transfusions to ‘foreign’ RBC antigens present in the donor blood, and some of these antibodies result in haemolytic transfusion (10%) reactions upon subsequent transfusions. Antibody testing to identify these antibodies and providing appropriate units lacking their corresponding antigens would improve transfusion safety in these patients. Furthermore, since these antibodies are mainly towards the major Rh antigens and some African antigens, standard test cells, which are generally of Caucasian origin, will fail to detect the antibodies to the African antigens, putting the patients at risk for haemolytic transfusion reactions. For effective management of anaemia requiring transfusion in SCD in Ghana, my findings support the routine testing for RBC antibodies using test cells that express the immunogenic African antigens V, VS, Goa, Dantu and Henshaw. Until Africa-specific red cell screening panel are available, in LMICs in sub-Saharan Africa with limited resources, all patients with SCD should be screened for RBC antibodies with the standard Caucasian panel prior to RBC transfusions and indirect antiglobulin crossmatched to select the best suited blood for transfusion.