Red Blood Cell Alloantibodies Research Articles

Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse. Study Design and MethodsRetrospective chart review was conducted at St. Michael’s Hospital (SMH) in Toronto, Canada. All adults with a definite clinical diagnosis of HHT AND inpatient hospital visits between January 1, 2011 and December 31, 2020 AND had undergone transfusion compatibility testing at SMH, were identified. Data were abstracted from electronic medical records. Simple descriptive statistics were used to analyze data. Institutional Research Ethics Board approval was obtained. Results63 HHT patients underwent compatibility testing and were subsequently transfused at SMH. Median patient age at data abstraction was 70 years (Interquartile Range [IQR]: 18) and 35 (56 %) were female. RBC alloantibodies were found in 23 transfused patients (36.5 %) and were predominantly directed against Rh and Kell antigens: Anti-E (65 %), Anti-K (39 %) and Anti-c (22 %) were most common. Excluding an outlier who received 611 RBC units during the study period, the mean number of RBC units transfused per HHT patient at SMH was 22.1 units (Standard Deviation: 40.9, IQR: 17). Six (9.5 %) transfused patients experienced at least one transfusion reaction. ConclusionRBC alloimmunization rate was 36.5 % in our cohort of transfused HHT patients; this is much higher than described in the general population and another transfused HHT cohort. The most commonly observed alloantibodies were Rh and Kell, supporting our policy of prophylactic phenotypic matching for these antigens for all transfused patients with HHT.

Risk factors for red blood cell alloimmunization in patients with hematologic malignancy.

Patients with hematologic malignancy have a higher risk of developing red blood cell (RBC) alloimmunization which can delay blood transfusion. Information on the risk factors for alloimmunization in this group is still limited. This study aimed to determine the prevalence and predictors of RBC alloimmunization among these patients. Electronic medical records of the patients with acute myeloid leukaemia (AML), acute lymphoid leukaemia (ALL), multiple myeloma (MM) and lymphoma from a tertiary care hospital between January 2018 and December 2022 were retrospectively reviewed. Clinical, demographic and transfusion history data of the included patients were analysed. Of the 983 patients with hematologic malignancy, 798 were included in the study. The prevalence of RBC alloantibodies in this population was 4.8% (38 patients). The alloimmunization rate of each subgroup was as followed: AML 9.1%, ALL 2.9%, MM 3.8% and lymphoma 2.5%. The most common alloantibodies were anti-Mia, anti-E and anti-Lea. The majority (29/38, 76.3%) of alloimmunization had a single alloantibody. RBC autoantibody was detected in 10 patients. The detection of autoantibodies and having AML were independently associated with RBC alloimmunization (adjusted odds ratio [aOR] 13.41, 95% confidence interval [CI] 2.00-89.72, p = 0.007 and aOR 11.44, 95% CI 2.02-64.72, p = 0.006, respectively). The prevalence of RBC alloimmunization in the patients with hematologic malignancy was 4.8%. The alloimmunization rate of the AML subgroup was higher than those of other hematologic malignancies. The detection of autoantibodies and the AML diagnosis were identified as potential risk factors for RBC alloimmunization.

Prevalence and specificity of clinically significant red blood cell alloantibodies among hospitalized patients attending a tertiary care center in the southern part of India: A retrospective observational study

Abstract: BACKGROUND: Alloimmunization due to red blood cell (RBC) transfusions may occur due to discrepancy between donor and recipient’s antigenic exposure on RBCs. A thorough literature search shows limited data pertaining to the rate of alloimmunization and specificity of alloantibodies in the general patient population. The main aim of our study is to find the prevalence of alloimmunization rate and specificity of RBC alloantibodies among the patients who were admitted under different clinical departments in a tertiary care hospital. MATERIALS AND METHODS: Our study was a retrospective observational study in which the patient data regarding their blood grouping status, alloimmunization status, and other relevant details were collected from the case records that were recorded between 2021 and 2022. Antibody screening of these patients was carried out using Bio-Rad ID DiaCell I, II, III Asia (Mia+), 3-cell panel with the lot number (45330.13.x). The specificity of these alloantibodies was identified using the 11-cell antibody identification panel Bio-Rad (ID-DiaPanel 11 × 4) which belongs to lot number (06171.47.x–06271.47.x). RESULTS: The overall prevalence of RBC alloimmunization in our study was found to be 1.3% (n = 137). The most prevalent alloantibody in our study was considered to be anti-D (30.65%), followed by anti-c (18.24%) and anti-Jkb (16.05%). Females had a more significant association with the development of alloantibodies than males with P = 0.001. Patients with a history of transfusion also had a significant association with alloantibody formation (P = 0.008). CONCLUSION: Since alloimmunization may result in drastic unforeseen responses in patients during transfusions, prior alloantibody screening may provide an additional safety layer in providing safe transfusions to patients. Hence, this study advocates the provision of antigen-matched RBC units for ABO, Rh, and Kell antigens.

Prevalence of red blood cell alloantibodies in pregnant women with sickle cell disease in Bamako.

Pregnancy in women with sickle cell disease (SCD) is associated with severe complications. Red blood cell (RBC) alloimmunisation is a worrying situation in pregnant women with SCD. This could increase the difficulty in finding a pheno-compatible red blood product. Our study aimed to determine the prevalence of RBC alloantibodies in pregnant women with SCD and to determine the risk factors for alloantibodies formation. We conducted a prospective study at the "Centre National de Transfusion Sanguine de Bamako" from August 2022 to January 2023. For each participant, we collected important information, including obstetrical and transfusion histories. We performed ABO group, Rh and Kell phenotyping, and antibody screening in all study participants. We performed statistical analysis. We recruited 95 pregnant women with SCD. In our study, 62% of our participant had a history of blood transfusion. Only 23% of our pregnant women with SCD had a history of miscarriage. The prevalence of RBC alloantibodies was 14%. The main antibodies detected were anti-E (38%) and pan-agglutinins (23%). Miscarriage history, blood transfusion history, and pregnancy number were the main risk factors for RBC alloimmunisation. The care of pregnant women with SCD is complex and requires collaboration between haematologists, clinicians and gynaecologists. National guidelines should be implemented to make ABO and D typing, Rh and Kell phenotyping and antibody screening routine for all pregnant women. This would facilitate early detection of high-risk situations. Particular attention should be paid to SCD pregnant women with miscarriage and blood transfusion histories.

Characterising the challenges of managing difficult red blood cell alloantibodies in liver transplant recipients

AimsFormation of red blood cell alloantibodies (RBCAs) complicates transfusion support in liver transplantation (LT). Difficult RBCAs (DAs, >3 antibodies or antibodies for which <25% donors are antigen negative) further challenge...

The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population.

Anti-E alloantibody is the most common and important red blood cell(RBC) alloantibody during pregnancy. The study aimed to determine the correlation between RhE alloimmunization and human leukocyte antigen (HLA)allele polymorphism, as well as haplotype diversity, among pregnant individuals in the Chinese Han population. All individuals included in our study were RhE-negative pregnant women of Chinese Han ethnicity, confirmed through serological testing. Pregnancy could be the only potential stimulating factor in RBC alloimmunization. Given the serological testing, the participants were divided into anti-E (responders) and non-anti-E-producing group (non-responders). The class I and II classical HLA genotyping were determined using next-generation sequencing, and the HLA genotype and haplotype frequencies were compared between the responders and non-responders. In total, 76 responders and 94 non-responders were enrolled in this study. Comparison results showed that all HLA class I alleles had no difference between the two groups. For HLA class II phenotypes, responders had higher frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02 and HLA-DQB1*03:03 phenotypes than non-responders, and the differences were statistically significant (pc < 0.05). In addition, the haplotype frequency of HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 in the RhE responders was significantly higher than in the non-responders (31.58% vs. 12.77%; odds ratio, 3.154; 95% confidence interval, 1.823-5.456; pc value, 1.25 × 10-3). Our findings indicated that HLA-DRB1*09:01, HLA-DQA1*03:02 and HLA-DQB1*03:03 might be susceptible alleles for RhE alloimmunization among Chinese Han pregnant females. These three susceptible alleles constituted the unique three-locus haplotype in the RhE responders and collaborated to RhE alloimmunization.

Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.

Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies. Antibodies to biotinylated RBC (B-RBC) occasionally are detected after exposure, which may impact B-RBC survival in subsequent RCS studies. Pediatric patients with SCD receiving monthly chronic transfusions underwent RCS studies, receiving aliquots of allogeneic RBC labeled at distinct densities of biotin (2-18 μg/mL). B-RBC survival was followed for 4 months post-transfusion, and B-RBC antibody screening for 6 months. Patients with warm autoantibodies (WAA) or B-RBC antibodies are reported here. RBC antibodies were detected during RCS in four patients: one with WAA, one with WAA followed by B-RBC-specific antibodies, and two with transient B-RBC antibodies within the first 5 weeks of exposure. B-RBC half-lives (T50) ranged 37.6-61.7 days (mean 47.8 days). There was no evidence of increased hemolysis or accelerated B-RBC clearance in the presence of WAA or B-RBC antibodies. Biotinylation of allogenic RBC can be used to assess the possible effects of RBC antibodies on transfusion survival in individual cases, particularly when it is uncertain if the detected antibodies may result in hemolysis. In the cases presented here, neither WAA nor B-RBC antibodies were associated with significant shortening of B-RBC survival in individuals with SCD.

Distinct RBC alloantibody responses in type 1 interferon-dependent and -independent lupus mouse models.

During transfusion of red blood cells (RBCs), recipients are exposed to both ABO and non-ABO 'minor' antigens. RBC donor units and recipient RBCs are not routinely matched for non-ABO antigens. Thus, recipients are exposed to many RBC alloantigens that can lead to RBC alloantibody production and subsequent clinically significant hemolysis. RBC alloantibodies also significantly limit the provision of compatible RBC units for recipients. Prior studies indicate that the frequency of RBC alloimmunization is increased during inflammatory responses and in patients with autoimmune diseases. Still, mechanisms contributing to alloimmune responses in patients with autoimmunity are not well understood. More than half of adult patients with systemic lupus erythematosus (SLE) produce type 1 interferons (IFNα/β) and express IFNα/β stimulated genes (ISGs). Previously, we reported that IFNα/β promote RBC alloimmune responses in the pristane mouse model, which develops a lupus-like phenotype that is dependent on IFNα/β signaling. However, it is unclear whether IFNα/β or the lupus-like phenotype induces alloimmunization in lupus models. Therefore, we tested the hypothesis that IFNα/β promotes RBC alloimmune responses in lupus by examining alloimmune responses in IFNα/β-independent (MRL-lpr) and IFNα/β-dependent (pristane) lupus models. Whereas pristane treatment significantly induced interferon-stimulated genes (ISGs), MRL-lpr mice produced significantly lower levels that were comparable to levels in untreated WT mice. Transfusion of murine RBCs that express the KEL antigen led to anti-KEL IgG production by pristane-treated WT mice. However, MRL-lpr mice produced minimal levels of anti-KEL IgG. Treatment of MRL-lpr mice with recombinant IFNα significantly enhanced alloimmunization. Collectively, results indicate that a lupus-like phenotype in pre-clinical models is not sufficient to induce RBC alloantibody production, and IFNα/β gene signatures may be responsible for RBC alloimmune responses in lupus mouse models. If these findings are extended to alternate pre-clinical models and clinical studies, patients with SLE who express an IFNα/β gene signature may have an increased risk of developing RBC alloantibodies and may benefit from more personalized transfusion protocols.

Antibody Screening, Identification and Red Cell Alloimmunisation Analysis in Multi-Transfused Patients at a Tertiary Care Hospital, Amritsar, India

Introduction: Alloimmunisation to red blood cell antigens, resulting from genetic disparities between donors and recipients, is one of the risks associated with blood transfusions. Antibody screening cells are used to detect unexpected antibodies. The risk of alloimmunisation is higher in patients who have undergone multiple blood transfusions. Aim: To estimate the frequency of various Red Blood Cell (RBC) alloantibodies and to determine the types of antibodies present in repeatedly transfused patients. Materials and Methods: This cross-sectional study was conducted on 200 patients with a history of multiple blood transfusions from October 1, 2019, to April 30, 2021, at the blood centre of Sri Guru Ram Das Institute of Medical Sciences and Research (SGRDIMSR), Amritsar, Punjab, India. Antibody detection and identification were performed, and the results were recorded. The data was statistically analysed using the Statistical Package for Social Sciences (SPSS) version 26.0 to draw relevant conclusions. The observations were tabulated in the form of numbers and percentages. Categorical data was analysed using the Chi-square test. The level of significance was determined as p≤0.05. Results: The study included 200 patients who were on multiple transfusions. The most common blood group among the patients was B positive (39%), followed by O positive (26%). The majority of patients (73.50%) had solid malignancies, followed by 28 (14%) thalassemia patients and 25 (12.50%) patients with chronic kidney disease. Solid malignancies included patients with breast cancer, cervical cancer, ovarian cancer, prostate cancer, and liver cancer. Alloantibodies were found in 15 patients (7.50%), of which 11 had solid malignancies and 4 had thalassemia. The most frequent antibody detected was the anti-K antibody (40%). Alloantibody formation was observed in both males and females. However, no statistical significance was found between gender and alloimmunisation (p=0.940). Conclusion: The effect of alloimmunisation can be avoided by routine RBC antibody screening before blood transfusion, especially in patients with a history of multiple blood transfusions. These measures decrease the incidence of red blood cell alloimmunisation and delayed hemolytic transfusion reactions in multi-transfused patients.

Development of Non-ABO Red Blood Cell Alloantibodies in Patient Undergoing Allogeneic Haematopoietic Stem Cell Transplant

Development of Non-ABO Red Blood Cell Alloantibodies in Patient Undergoing Allogeneic Haematopoietic Stem Cell Transplant

Frequency of red blood cell allo-immunization in patients undergoing blood transfusion at the Uganda Cancer Institute.

There is limited data on red blood cell (RBC) alloimmunization in patients with cancer in sub-Saharan Africa (SSA). We examined the frequency of RBC alloimmunization in transfused patients with cancers in Uganda. A randomized control trial was conducted on participants at the Uganda Cancer Institute. Eligible participants were age ≥15 years and required blood transfusion. Participants were randomized to receive either leucoreduced or non-leucoreduced blood transfusion. Participants' plasma samples were screened for RBC alloantibodies at enrolment and 3-4 weeks after blood transfusion using a 2-cell panel of reagent group O RBCs using the tube method. Antibody identification was performed using a 10-cell panels of reagent RBCs. Participants were considered alloimmunized if antibodies to RBC antigens were identified. A total of 277 participants were randomized (leucoreduced blood, n=137; non-leucoreduced blood, n=140). Overall, the most represented diagnoses were gynaecological cancers (n=88, 31.8%), acute leukaemia (n=35, 12.6%), and gastrointestinal cancers (n=25, 9.0%). Concomitant HIV infection was present in 26 (9.4%) participants. Most participants received <5 units of blood during the study. No study participant developed allo-antibodies. There was no RBC alloimmunization in participants with cancers. Routine RBC allo-antibody screening in all patients with cancer in SSA requires further research.

Prevalence of red blood cell alloantibodies among blood donors in the French Military Blood Institute: A 10-year retrospective study.

Screening for red blood cell alloantibodies (RBC-Ab) is a critical step in ensuring blood transfusion safety performed by blood donation screening laboratories. We aim to evaluate the prevalence of the RBC-Ab among healthy blood donors. Antibody screening of serum of all voluntary blood donors was performed as a routine immune-haematological procedure by a solid-phase method on a fully automated immunohaematology analyser. Positive sera were further investigated to identify the specificity of RBC-Ab by a commercially available red cell panel. Between January 2012 and December 2021, a total of 212,218 donations were screened for the presence of RBC-Ab, 74% from male donors (n = 157,898) and 26% from female donors (n = 54,320). Mean age at donation time was 32 ± 12 years. A total of 1007 donations were screened positive (0.47%), and 131 were confirmed positive for alloantibodies in their serum, yielding a prevalence of 0.06% (95% confidence interval: 0.05-0.07). Most frequent alloantibodies identified were of RH blood group system (64%), followed by anti-MNS (19%), anti-Kidd and Lewis (6% each) and anti-KEL (4%). The results showed a statistically higher prevalence of alloantibodies in women than men. Our results showed a lower prevalence as compared to the available data, which might be related to our study population. The prevalence of positive antibody screening in healthy donors in this study was found to be 0.47%, while the prevalence of alloantibodies was 0.06%. The most common alloantibodies were anti-RH1 (25%) and anti-RH3 (24%).

Prevalence of alloantibodies associated with haemolytic disease of the fetus and newborn in pregnant women at the Ekiti State University Teaching Hospital, Ado-Ekiti, Southwest Nigeria.

Haemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens, which could result in fetal anaemia, hyperbilirubinaemia, kernicterus, and death. This study was designed to determine the prevalence of alloantibodies against erythrocyte antigens in blood samples of pregnant women during the first trimester which may cause HDFN. A total of 123 consenting pregnant women attending the antenatal clinic of Ekiti state University Teaching Hospital, Ado Ekiti participated in the study which lasted three months. The participants were within the ages of 16 to 45 years old across the major ethnic group in Nigeria. ABO/Rh typing, screening and identification of red blood cell alloantibodies were carried out using standard protocols. 15 (12.2%) subjects had detectable antibodies known to cause haemolytic disease of the fetus and newborn (HDFN). The specificity of the antibodies was as follows: anti-K (5, 33%), anti-k (3, 20%), anti- Jsa (2, 13%), anti-C. (3, 20%), and anti-E (2, 13 %). Based on ethnicity, the prevalence of Kell antibodies was highly significant among the Yorubas as well as anti-C and anti-E. The observation was similar in the Igbo and Hausa groups. There is a need to determine these antibodies and monitor their titre in pregnant women to manage or prevent the morbidity and mortality associated with HDFN during routine antenatal care.

Comparison of the conventional tube and erythrocyte-magnetized technology in titration of red blood cell alloantibodies

Erythrocyte alloantibodies are mainly produced after immune stimulation, such as blood transfusion, pregnancy, and transplantation, and are the leading causes of severe hemolytic transfusion reactions and difficulty in blood grouping and matching. Therefore, antibody screening is critical to prevent and improve red cell alloantibodies. Routine tube assay is the primary detection method of antibody screening. Recently, erythrocyte-magnetized technology (EMT) has been increasingly used in clinical practice. This study intends to probe the application and efficacy of the conventional tube and EMT in red blood cell alloantibody titration to provide a reference for clinical blood transfusion. To investigate the application value of conventional tube and EMT in red blood cell alloantibody titration and enhance the safety of blood transfusion practice. A total of 1298 blood samples were harvested from blood donors at the Department of Blood Transfusion of our hospital from March 2021 to December 2022. A 5 mL blood sample was collected in tubing, which was then cut, and the whole blood was put into a test tube for centrifugation to separate the serum. Different red blood cell blood group antibody titers were simultaneously detected using the tube polybrene test, tube antiglobulin test (AGT), and EMT screening irregular antibody methods to determine the best test method. Simultaneous detection was performed through the tube polybrene test, tube AGT and EMT screening irregular antibodies. It was discovered that the EMT screening irregular antibody method could detect all immunoglobulin G (IgG) and immunoglobulin M (IgM) irregular antibodies, and the results of manual tube AGT were satisfactory, but the operation time was lengthy, and the equipment had a large footprint. The EMT screening irregular antibody assay was also conducted to determine its activity against type O Rh (D) red blood cells, and the outcomes were satisfactory. Furthermore, compared to the conventional tube method, the EMT screening irregular antibody method was more cost-effective and had significantly higher detection efficiency. With a higher detection rate, the EMT screening irregular antibody method can detect both IgG and IgM irregular antibodies faster and more effectively than the conventional tube method.

Reticulocytes in donor blood units enhance red blood cell alloimmunization.

Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increased RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.

Prevalence and specificity of red blood cell antibodies in patients transfused in tertiary hospitals in Burkina Faso.

Sub-Saharan African countries face the challenge of immunological transfusion safety that puts many patients at risk of post-transfusion hemolytic reactions. This is because pre-transfusion testing for irregular/unexpected antibodies that helps to prevent these risks are neither universally available nor accessible. The aim of our study was to determine the prevalence of red blood cell alloantibodies and their specificity in patients transfused in Burkina Faso. This was a cross-sectional study including patients who had received at least one blood transfusion. Indirect antiglobulin testing using LISS-enhanced medium gel column agglutination technique was used for antibodies screening and identification. Enzymatic technique with papain-treated red cell reagent was performed in attempt to solve some difficulties if necessary as well as auto-control test and RH-KEL phenotyping when possible to help antibodies identification. A total of 832 patients were included, 51.6% of whom were female, and the median (IQR) age was 34 (20-49) years. Of these, 43.7% had chronic kidney disease and 20.4% were sickle cell patients. The median (IQR) number of immunisation episodes (blood transfusion and pregnancies) was 3 (2-6) with the median (IQR) number of blood units received per patient of 2 (1-5). The proportion of patients with RBCs antibodies was 6.4% (53/832), with mainly anti-Rh antibodies. A combination of 2 antibodies was found in 7 patients and a combination of 3 antibodies in one patient. Antibodies of unknown specificity (AUS) were encountered in 29%. Independent factors associated with antibody positivity were age (OR=1.02; p=0.026), sickle cell disease (OR=3.23; p=0.017) and receiving more than 10 blood units (OR=7.33; p=0.01). In this study, the proportion of patients with RBC antibodies was quite similar to that observed in Sub-Saharan African countries. However, the availability and accessibility of pre-transfusion compatibility tests as well as the quality of methods used should be improved to ensure the safety of blood transfusions.

Red Blood Cell Alloimmunization and Its Associated Factors among Chronic Liver Disease Patients in a Teaching Hospital in Northeastern Malaysia

Red blood cell (RBC) alloimmunization is an important complication of blood transfusion. Variations in the frequency of alloimmunization have been noted among different patient populations. We aimed to determine the prevalence of RBC alloimmunization and associated factors among chronic liver disease (CLD) patients in our center. This is a case-control study involving 441 patients with CLD who were being treated at Hospital Universiti Sains Malaysia and subjected to pre-transfusion testing from April 2012 until April 2022. Clinical and laboratory data were retrieved and statistically analyzed. A total of 441 CLD patients were included in our study, with the majority being elderly, with the mean age of patients 57.9 (SD ± 12.1) years old, male (65.1%) and Malays (92.1%). The most common causes of CLD in our center are viral hepatitis (62.1%) and metabolic liver disease (25.4%). Twenty-four patients were reported to have RBC alloimmunization, resulting in an overall prevalence of 5.4%. Higher rates of alloimmunization were seen in females (7.1%) and patients with autoimmune hepatitis (11.1%). Most patients developed a single alloantibody (83.3%). The most common alloantibody identified belonged to the Rh blood group, anti-E (35.7%) and anti-c (14.3%), followed by the MNS blood group, anti-Mia (17.9%). There was no significant factor association of RBC alloimmunization among CLD patients identified. Our center has a low prevalence of RBC alloimmunization among CLD patients. However, the majority of them developed clinically significant RBC alloantibodies, mostly from the Rh blood group. Therefore, phenotype matching for Rh blood groups should be provided for CLD patients requiring blood transfusions in our center to prevent RBC alloimmunization.

Review on Pathology

While red blood cell (RBC) transfusion is the most common medical intervention in hospitalized patients, as with any therapeutic, it is not without risk. Allogeneic RBC exposure can result in recipient alloimmunization, which can limit the availability of compatible RBCs for future transfusions and increase the risk of transfusion complications. Despite these challenges and the discovery of RBC alloantigens more than a century ago, relatively little has historically been known regarding the immune factors that regulate RBC alloantibody formation. Through recent epidemiological approaches, in vitro–based translational studies, and newly developed preclinical models, the processes that govern RBC alloimmunization have emerged as more complex and intriguing than previously appreciated. Although common alloimmunization mechanisms exist, distinct immune pathways can be engaged, depending on the target alloantigen involved. Despite this complexity, key themes are beginning to emerge that may provide promising approaches to not only actively prevent but also possibly alleviate the most severe complications of RBC alloimmunization

Red blood cell alloantibodies in paediatric transfusion in sub-Saharan Africa: A new cohort and literature review.

Blood transfusion support predisposes transfused children to the risk of erythrocyte alloimmunization in Sub-Saharan Africa. A cohort of 100 children receiving one to five blood transfusions were recruited for screening and identification of irregular antibodies using gel filtration technique. The mean age was 8 years and the sex-ratio at 1.2. The retrieved pathologies were: major sickle cell anaemia (46%), severe malaria (20%), haemolytic anaemia (4%), severe acute malnutrition (6%), acute gastroenteritis (5%), chronic infectious syndrome (12%) and congenital heart disease (7%). The children presented with haemoglobin levels≤6g/dl, and 16% of them presented positive irregular antibodies directed against the Rhesus (30.76%) and Kell (69.24%) blood group systems. A literature review shows that irregular antibody screenings vary from 17% to 30% of transfused paediatric patients in Sub-Saharan Africa. These alloantibodies are in particular directed against the Rhesus, Kell, Duffy, Kidd and MNS blood group and generally found in sickle cell disease and malaria. This study highlights the urgent need of extended red blood cell phenotyping including typing for C/c, E/e, K/k, and Fya/Fyb, and if possible Jka/Jkb, M/N, and S/s for children before transfusion in Sub-Saharan Africa.

Commentary: Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia.

Pereda et al. recently reported three cases in which daratumumab was utilized to reduce the 36 burden of red blood cell (RBC) and human leukocyte antigen (HLA) alloantibodies (1). These 37 cases support the need for further investigation into the potential use of daratumumab and related 38 plasma cell depletion therapies for patients with significant alloimmunization. However, the 39 authors' cases, particularly cases 1 and 2 in which the authors describe patients with sickle cell 40 disease (SCD) and multiple RBC antibodies, lack sufficient immunohematology and transfusion 41 details to reliably conclude the effectiveness and safety of daratumumab to reduce and existing alloantibodies can persist despite daratumumab treatment (3-6). Secondly, the 80 authors fail to acknowledge the possibility that the alloantibodies may have disappeared naturally 81 through the phenomenon of evanescence. Numerous studies have shown that many patients' 82 RBC alloantibodies will decline in titer to levels below a detectable threshold without further 83 exposure (7-9). Though the loss of all antibodies due to evanescence may be less likely, not 84 accounting for this potential mechanism of a waning antibody is concerning. 85 86 Furthermore, literature demonstrates that even if these antibodies have become undetectable, 87 these patients may still be at risk for DHTRs (10-13).