Red Blood Cell Alloimmunization in Transfused Patients With Sickle Cell Disease in Sub-Saharan Africa; a Systematic Review and Meta-Analysis

Abstract

Sickle cell disease (SCD) is the most common monogenic disorder in sub-Saharan Africa (SSA). Blood transfusion to increase the oxygen carrying capacity of blood is vital in the management of many patients with SCD. However, red blood cell (RBC) alloimmunization is a major challenge to transfusions in these patients. Commonly in SSA, pre-transfusion tests only involve ABO D grouping and compatibility without RBC antibody testing. Data on the frequency of RBC alloimmunization in patients with SCD in SSA is limited. We performed a systematic review and meta-analysis on available data on alloimmunization in transfused patients with SCD to determine the published prevalence of RBC alloimmunization in SCD patients in SSA. Six databases were systematically searched to identify relevant studies, without year or language restrictions. In all, 249 articles were identified and 15 met our selection criteria. The overall proportion of alloimmunization was 7.4 (95% CI: 5.1-10.0), per 100 transfused patients. Antibodies against E, D, C and K antigens accounted for almost half of antibody specificities and antibodies to low and high frequency antigens were also common and represented almost 30% (20% to low frequency antigens and 9% to high frequency antigens) of specificities. Heterogeneity between studies was moderate and meta-analysis found region of Africa as the major contributor to the heterogeneity. We also observed inconsistencies across studies in reporting of factors that may influence alloimmunization. This review provides an overview of the extent of the alloimmunization problem in SSA and provides a baseline against which to compare the effect of any interventions to reduce the alloimmunization risk.

Red blood cell alloimmunization among recipients of blood transfusion in India: A systematic review and meta‐analysis

“…Ngoma et al in a systematic review on the recipients of RBC transfusion of sub‐Saharan Africans noted an alloimmunization rate of 6.7%, and anti‐E was the commonest antibody in the study population [52]. A systematic review and meta‐analysis of alloimmunization of patients with sickle cell disease of sub‐Saharan Africa showed an overall proportion of alloimmunization of 7.4 (95% confidence interval: 5.1–10.0) per 100 transfused patients [53]. Antibodies against E, D, C and K antigens accounted for almost half of antibody specificities in their population.…”

“…Literature review on rate of alloimmunization in transfusion recipients , a anti-K, anti-C and anti-D Sub-Saharan Africa,Boateng et al (2019) [53] Sickle cell disease 7.40% Anti-E, a anti-D, anti-C and anti-KIran, Darvishi et al (2016) [54] Thalassemia 10% Anti-K, a anti-D and anti-E Iran, Hosseini et al (2020) [55] Patients on regular transfusion 0-55% Anti-K, a anti-E, anti-D, anti-C and anti-c China, Chen et al (2016) [56] Prevalence of unexpected antibodies among Chinese population 0.23% Anti-E, a anti-D, anti-C and anti-c World, Franchini et al (2019) [57] Patients with transfusion dependent thalassemia 11.40% Anti-K, a anti-E, anti-D, anti-c and anti-C Brazil, Gomes et al (2019) [58] Patients with sickle cell disease 28.39% (mean incidence) Rh followed by Kell system Present study (2021) Recipients of RBC transfusion (hospital-based studies) 0.5% Anti-D, a anti-E, anti-c and anti-K Multiply-transfused patients 4.8% Anti-E, a anti-c and anti-K a Most common. on.…”

Transfusion Practice, Post-Transfusion Complications and Risk Factors in Sickle Cell Disease in Senegal, West Africa.

“…Anti-Rhesus and anti-Kell specificities were reported by most studies in Africa or developed countries. 21,29 The high immunogenicity of these two systems other than the ABO system could partially explain the high incidence.…”

Global perspectives on cellular therapy for children with sickle cell disease

“…In a recent review of transfusion practices in Senegal, 16% of patients were found to have alloantibodies to red blood cells (RBC) and 7.8% had elevated ferritin suggestive of iron overload [23]. A meta-analysis of studies reviewing alloimmunization in Africa identified prevalence rates ranging from 4 to 26% [24]. High rates of either iron overload or alloimmunization would contribute to worse posttransplant outcomes [25].…”