Introduction

Sickle cell disease (SCD) and thalassemia are inherited hemoglobin disorders that predominantly affect individuals of African, Middle Eastern, Mediterranean, and Indian descent and represent a major global health burden [1]. For many patients, particularly those with severe symptoms, regular red blood cell (RBC) transfusions remain a cornerstone of management by correcting chronic anemia and helping to prevent serious complications such as stroke, acute chest syndrome, and progressive organ damage [2]. However, repeated transfusions expose patients to numerous foreign RBC antigens that can stimulate the immune system to produce alloantibodies directed against them. This process, known as RBC alloimmunization, is a well‑recognized complication in patients with transfusion-dependent SCD and thalassemia and can significantly complicate transfusion therapy. RBC alloimmunization can lead to difficulties in finding compatible blood units, delayed hemolytic transfusion reactions, and, in severe cases, life-threatening hyperhemolysis [3].

Current guidelines, including those from the American Society of Hematology (ASH) and the International Collaboration for Transfusion Medicine Guidelines, recommend prophylactic matching for ABO, Rh (C, c, D, E, e), and Kell (K) antigens for all patients with SCD and thalassemia, even in the absence of preexisting alloantibodies [4]. Despite these measures, alloimmunization still occurs. Several factors explain this persistent risk. First, conventional serologic phenotyping may fail to detect variant _Rh _alleles, particularly partial RHD and RHCE alleles, which are common in individuals of African descent, leading to apparent Rh-matched transfusions that are in fact immunologically mismatched [5]. A recent study found clinically significant genotype-phenotype discrepancies in over 20% of patients with SCD, and partial Rh alleles in 17% of cases [5]. Second, standard matching protocols do not extend to other clinically important blood group systems such as Duffy (Fy), Kidd (Jk), and MNS (S/s), leaving patients vulnerable to sensitization against these antigens [6]. Third, in Europe and the USA, recipients of African or Middle Eastern descent are at an increased risk of antigen mismatch because donor pools are predominantly of European origin and red cell antigen profiles differ significantly between these populations [7]. Beyond transfusion-related variables, several patient-related factors have been associated with increased alloimmunization susceptibility. These include older age, female sex, older age at first transfusion, higher cumulative transfusion exposure, history of splenectomy, presence of RBC autoantibodies, and an underlying pro-inflammatory or immunogenetic predisposition [8].

The reported prevalence of alloimmunization varies considerably across populations. A systematic review of 41 cohort studies involving over 9,000 patients with thalassemia reported a pooled prevalence of 11.4%, with antibodies against Rh and Kell antigens accounting for approximately 78% of all alloantibodies identified [9]. In SCD, alloimmunization rates have been reported to range from 8% to 36%, depending on the study population and transfusion practices employed. A recent systematic review focusing specifically on Middle Eastern countries found mean alloimmunization prevalence rates of 13.0% in thalassemia and 14.0% in SCD, with considerable heterogeneity among individual studies [8]. Individual cohort reports range from as low as 2-8% in some African and South Asian centers to over 30% in Omani patients with SCD [10-12]. The aim of this study was to determine the prevalence of RBC alloimmunization among patients with transfusion-dependent thalassemia and SCD in Bahrain and to compare the observed alloimmunization rate with published data from other regional and international studies.