Red Blood Cell Alloimmunization Rates Research Articles

Increased red blood cell alloimmunization rates in transfused aplastic anemia and myelofibrosis patients.

Red blood cell (RBC) alloimmunization (AI) is a well-known complication of RBC transfusions, which results in the formation of alloantibodies to non-self antigens on donor RBCs, putting patients at risk of transfusion-related complications. The rate of AI with RBC transfusions in the general hospitalized population is estimated to be 2%-3%. However, some patients who are deemed "transfusion-dependent" require regular transfusions of blood products due to persistently low cell counts, putting them at even greater risk of RBC AI and increased morbidity. However, few studies currently exist investigating RBC AI in some transfusion-dependent patient populations, e.g., aplastic anemia (AA) and myelofibrosis (MF). We conducted a 5-year retrospective review to investigate the prevalence of RBC AI, alloantibody incidence, and the number of RBC transfusions in AA and MF patients, who received RBC transfusions within our hospital system. During the study period, 64 AA and 93 MF patients received 1301 and 2766 RBC transfusions, respectively. Compared to the RBC AI rate in the generalized hospitalized patient population (1%-2%), patients with AA and MF had an increased rate of RBC AI incidence rate at 14.1% and 12.9%, respectively. Furthermore, patients with primary MF demonstrated an isolated increased RBC AI incidence rate of 13.3%. The most common alloantibodies produced were anti-E and anti-K. Within our institution, patients with AA and MF had increased incidence rates of RBC AI compared to the general hospitalized patient population and may benefit from an antigen-matched protocol to minimize AI-related complications.

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.

SRSF2 or TET2 Mutations in Patients with MDS Predict Increased Red Blood Cell Alloimmunization

INTRODUCTION: Chronic inflammation is associated with increased red blood cell (RBC) alloimmunization. Patients with sickle cell disease (SCD), systemic lupus erythematosus and inflammatory bowel disease, all conditions with increased levels of inflammation, have been shown to be more alloimmunized when compared to the general population. High prevalence rates of RBC alloimmunization have also been observed in patients with myelodysplastic syndrome (MDS). It has recently been shown that an inflammatory microenvironment may be a key driver of MDS pathogenesis. There are a few specific genes recurrently mutated in MDS that have been found to be associated with activation of the innate immune system and formation of the inflammasome, including some involved in epigenetic modification - ASXL1, DNMT3A, EZH2 and TET2 - and spliceosome formation - SF3B1, SRSF2 and U2AF1. The aim of this study was to determine if the genetic mutations driving the inflammatory milieu in MDS could simultaneously be creating an environment that promotes alloimmunization. PATIENTS AND METHODS: We identified patients diagnosed with a myeloid neoplasm, including patients with MDS and acute myeloid leukemia (AML), between 2015 and 2020 on whom a type and screen had been ordered. We recorded the patients’ primary diagnosis, sex, race/ethnicity, age at first sequencing, somatic mutations identified by next generation sequencing (NGS), blood type, antibody screen results, specific alloantibodies and autoantibodies identified, and number of RBC and platelet units transfused. Patients with an autoantibody, a clinically significant alloantibody, or non-specific reactivity with a potential antibody under investigation on their screen were put in the positive antibody screen category, and those with reactivity solely due to Rh immune globulin or monoclonal antibody therapy were put in the negative antibody screen category. Univariate logistic regression was run separately for patients initially diagnosed with AML and those initially diagnosed with a non-AML myeloid neoplasm (MN), using sex, age, race/ethnicity, number of RBC units transfused, and somatic mutation, to determine if any of these variables had a significant association with a positive antibody screen. If quasi-complete separation issues existed, Firth's method for separation was applied to the logistic regression model. All analyses were conducted using a 95% confidence level. RESULTS: Seventy-six patients met inclusion criteria; 44 were male and 32 were female, and ranged in age from 14 to 89 years. The majority of patients were Caucasian (n = 64). Thirty-three patients had an initial diagnosis of AML; 43 were initially diagnosed with a MN, including MDS (n = 36), myeloproliferative neoplasm (n = 2), chronic myelomonocytic leukemia (n = 4) and chronic myeloid leukemia (n = 1). Number of RBC units transfused ranged from 3 - 112 in patients with AML and 0 - 131 in patients with a MN. Thirteen patients with AML had a positive antibody screen (39.4%), compared to 21 patients with a MN (48.8%). Patients with AML most often developed an alloantibody without an accompanying autoantibody (58.3%), while patients with a MN most often developed alloantibodies in addition to autoantibodies (52.4%). Patients with a MN and a SRSF2 mutation had a significantly increased rate of allo- or auto-immunization as compared to patients with AML and a SRSF2 mutation (p-value = 0.035). Similarly, patients with a MN and a TET2 mutation had a significantly increased rate of allo- or auto-immunization as compared to patients with AML and a TET2 mutation (p-value = 0.021). CONCLUSIONS: In patients with a MN, the presence of a SRSF2 or TET2 mutation predicted the presence of at least one allo- or autoantibody. Our data support the hypothesis that genetic mutations involved in formation of the inflammasome may be involved in the increased alloimmunization seen in patients with MDS. Our study of alloimmunization in MDS, and further studies like it, may enable us to predict based on genetic mutations which patients with MDS may be at increased risk for becoming alloimmunized. Similar to prophylactic C, E and K antigen matching that some blood banks employ in patients with SCD to minimize formation of alloantibodies, extended phenotype matching for the most immunogenic antigens could also be considered in patients with MDS and SRSF2 or TET2 mutations to decrease alloimmunization in this patient population.

Red Blood Cell Alloimmunization Rates and Related Factors of Patients with Thalassemia in Shiraz, Iran.

The development of antibodies against red blood cell (RBC) antigens is one of the most significant adverse effects of chronic blood transfusions. This study aimed to estimate the frequency and causes of RBC immunization in patients with major thalassemia. The findings could help determine the limitation of current practices and help future developments in the selection of suitable blood units for the transfusion support of patients with thalassemia. The alloimmunization rate was detected in 52 of 650 patients with major thalassemia (8%). The most frequent antibodies were against K (50%), D (26%), and E (15.4%). Sex, age, and splenectomy did not have any impact on the immunization rate. Immunization was lower in patients who had received only leuko-reduced blood units. It is recommended that antibody screening before the first transfusion and extended RBC matching particularly for the most frequent antigens (ABO/Rh/Kell) should be performed for patients with thalassemia.

Alloimmunization and autoimmunization in adult transfusion-dependent thalassemia patients: a report from a comprehensive center in Israel.

Patients with beta thalassemia major (TM) are transfusion-dependent (TD) since early childhood and for life. Development of alloantibodies and autoantibodies against red blood cell (RBC) antigens is increasingly recognized as a significant transfusion hazard, especially among heavily transfused patients. The aim of this study is to assess RBC alloimmunization and autoimmunization rates in TD TM patients treated in our Comprehensive Center of Adult Thalassemia, Hemoglobinopathies and Rare Anemias. TD TM patients, regularly transfused every 2-3 weeks, were included in the study. Clinical and RBC transfusion records, including RBC antibodies, since diagnosis in early childhood, were retrieved from patients' files and from the blood bank database. Forty TD TM patients, > 18 years of age, were included in the study. Alloimmunization was demonstrated in 17 (42.5%) patients. Thirty-four alloantibodies were detected, with the most frequent being RH related (12 of 34, 35.3%) followed by those of the Kell system (8 of 34, 23.5%). Age at first transfusion was positively related to the probability of developing alloantibodies (p = 0.02). Splenectomy was found to be correlated with developing alloantibodies (p = 0.016). Logistic regression analysis of the lifelong probability of developing alloantibodies on the age at first transfusion and splenectomy demonstrates a strong positive relationship (p = 0.002). A substantially high rate of alloimmunization was found among adult TD TM patients. Early initiation of RBC transfusions, avoidance of splenectomy and extended Rh and K antigen matching, can reduce the incidence of alloimmunization in TD TM patients.

Red cell alloimmunization among haemato-oncologic patients in a teaching hospital in Malaysia

Background: The aim of the study is to estimate the prevalence and specificity of red blood cell alloantibody among haemato-oncologic patients and to correlate the association of antibody development with other factors such as age, gender, race, number of packed red blood cell (RBCs) transfused and diagnosis. Materials and Methods: This prospective cross-sectional study was conducted in Transfusion Medicine Unit, HUSM. Clinical and serological data of 216 haemato-oncologic patients who who received blood transfusions were collected and analysed. The blood samples were subjected to the standard immunohematological procedure for RBC antibody screening and identification using reagents of Diamed-ID Gel microtyping system Results: RBC alloimmunization rate among haemato-oncologic patients was 3.2%. Red cell antibodies were detected in seven patients. Four patients developed single antibody, while three develop multiple antibodies. However, we noted all seven patients were Malay with lymphoproliferative disease and majorities were adult male (71.4%) patients. Conclusions: The prevalence of RBC alloimmunization in post transfusion haemato-oncology patients was low despite of multiple transfusions and it is comparable with other diseases, which required multiple transfusions. Therefore, it is important to prioritize the extended antigen matching to patients that will be most benefit.

Recipient factors influencing red blood cell alloimmunization

Red blood cell (RBC) alloantibodies develop in a subset of individuals following exposure to non‐self RBCs through transfusion, pregnancy or other activities; these antibodies can lead to difficulty locating compatible RBCs, acute or delayed haemolytic transfusion reactions, or haemolytic disease of the newborn. Alloimmunization is underestimated due in part to antibody evanescence, the random nature of post‐transfusion antibody screens, fragmented medical care and the lack of widespread antibody registries. Factors that influence who will develop detectable alloantibodies are not well understood. Transfusion burden is one risk factor for alloimmunization, though many highly transfused individuals never form alloantibodies despite exposure to many RBC units (and many non‐self blood group antigens). Individuals with sickle‐cell disease (SCD) and myelodysplastic syndrome (MDS) are more likely to form RBC alloantibodies than most other patient populations. Individuals with rheumatologic and other forms of autoimmunity, though not chronically transfused, are also at higher‐than‐average risk of forming RBC alloantibodies. Inflammation, in a broad sense, is one common thread amongst these diagnoses associated with high prevalence rates of RBC alloimmunization. Reductionist murine models support some types of inflammation (including viral‐like stimuli) around the time of RBC exposure as being associated with an increased likelihood of alloantibody formation. Strategies other than transfusion avoidance or extended antigen matching beyond ABO/Rh would be beneficial to prevent new RBC alloantibody formation, especially in patients at highest risk.

Incidence and frequency of various red blood cell antibodies and the experience of providing antigen-negative transfusion support for patients at a tertiary care super specialty hospital

Introduction: The presence of red blood cell (RBC) auto and/or alloantibodies can pose a serious challenge of finding transfusion support for such patients. Aim and Objectives: The aim of this study was to assess the frequency and type of unexpected RBC antibodies in the patient population of a tertiary care super specialty hospital and analyze the transfusion support and its effectiveness in these patients. Methodology: This was a retrospective cross sectional study based on data contained in all blood requests, received over a period of 39 months inclusive of demographic,laboratory and clinical variables. Results: Among the 25,338 patients screened, 122 (0.48%) had alloantibodies and 19 (0.07%) had autoantibodies. Of the 141 patients with atypical antibodies, 109 (77.30%) were female and 32 (22.69%) were male. Antibodies directed against the antigens from various blood group systems were as follows: Rh – 54.5%, MNS – 21.8%, and Lewis – 13.6%. Anti-D (32.8%), Anti-M (16.4%), and Anti-E (10.9%) were the most prevalent. Multiple alloantibodies were seen in 2 (1.41%) cases and autoantibodies coexisting with an alloantibody in 9 (6.38%) cases. Discussion: RBC alloimmunization rate is lower (0.41%) in our hospital in comparison with published reports. Higher alloimmunization in female patients in the age group of 20–40 years mainly associated with a history of pregnancy and comparatively lower rate in males and strongly associated with a history of transfusion in the age group of 40–60 years has been reported in literature. Conclusion: RBC alloimmunization rate (0.55%) in general patients treated in our hospital is lower as compared to other reported rates in our country. The provision of RBC phenotype-matched (Rh and Kell) blood for patients likely to get multiple transfusions right from the beginning may reduce the alloimmunization rates further.

The Role of the Immunological Synapse in Differential Effects of APC Subsets in Alloimmunization to Fresh, Non-stored RBCs.

Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantibodies can be a problem as they may mediate hemolysis or pose barriers to future transfusion support. While there is currently no reliable way to predict which RBC recipients will make an alloantibody response, risk factors such as inflammation have been shown to correlate with increased rates of RBC alloimmunization. The underlying mechanisms behind how inflammation mediates alloantibody production are incompletely defined.Methods: To assess erythrophagocytosis, mice were treated with PBS or inflammatory stimuli followed by a transfusion of allogeneic RBCs labeled with a lipophilic dye. At multiple time points, RBC consumption and expression of activation makers by leukocytes was evaluated. To determine which antigen presenting cell (APC) subset(s) were capable of promoting allogeneic T cell activation, sorted leukocyte populations (which had participated in erythrophagocytosis) were co-cultured in vitro with allogeneic CD4+ T cells; T cell proliferation and ability to form immunological synapses with APCs were determined.Results: Upon transfusion of fresh allogeneic RBCs, multiple APCs consumed transfused RBCs. However, only CD8+ and CD11b+ dendritic cells formed productive immunological synapses with allogeneic T cells and stimulated proliferation. Importantly, allogeneic T cell activation and RBC alloantibody production occurred in response to RBC transfusion alone, and transfusion in the context of inflammation enhanced RBC consumption, the number of immune synapses, allogeneic T cell proliferation, and the rate and magnitude of alloantibody production.Conclusions: These data demonstrate that regardless of the ability to participate in RBC consumption, only a subset of APCs are capable of forming an immune synapse with T cells thereby initiating an alloantibody response. Additionally, these data provide mechanistic insight into RBC alloantibody generation.

6 A Novel Association Between High Red Blood Cell Alloimmunization Rates and Hereditary Hemorrhagic Telangiectasia (HHT)

6 A Novel Association Between High Red Blood Cell Alloimmunization Rates and Hereditary Hemorrhagic Telangiectasia (HHT)

A novel association between high red blood cell alloimmunization rates and hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder associated with multiple arteriovenous malformations. HHT patients may require red blood cell (RBC) transfusion due to spontaneous hemorrhage or surgical bleeding. Because HHT-associated hemorrhage often occurs in submucosa we hypothesized that RBC alloimmunization rates in HHT patients may be higher than those observed in other transfused patients and investigated this in a retrospective study. Eighty-five patients with HHT who were transfused at our tertiary care facility were identified. A group of randomly selected, chronically transfused patients without HHT were used as controls (n = 207). RBC transfusion and alloantibody data were extracted from medical records. Alloimmunization rates among patients with HHT were significantly higher than those of controls (15.29% vs. 2.42%; p < 0.001), while HHT patients received fewer RBC transfusions at our institution compared to controls (4.27 units vs. 8.84 units; p < 0.0001). Anti-E, -K, and -c were the three most common alloantibodies identified in HHT patients. There was a trend for HHT patients to make more antibodies per alloimmunized patient than controls (2.38 alloantibodies vs. 1.60 alloantibodies), although this difference was not significant (p = 0.37). To our knowledge, this is the first study to evaluate RBC alloimmunization rates in patients with HHT. It is unclear whether the high alloimmunization rates observed are due to lifetime transfusion burden, underlying disease pathophysiology, or other variables. Additional studies are needed to evaluate the generalizability of our findings to other HHT populations and to consider the utility of prophylactic antigen matching for C/E/K.

Frequency of red blood cell alloimmunization in sickle cell patients and healthy donors: the influence of racial and antigenic pattern differences

Background: Red blood cell (RBC) transfusions are frequently used in patients with sickle cell disease (SCD) to treat and prevent of their disease complications. However repeated blood transfusions are often complicated by RBC alloimmunization. Race and antigenic pattern differences are the common risk factor to develop alloimmunization. This study was performed to determine the frequency of RBC alloimmunzation in sickle cell patients and healthy blood donors.Methods: This is a cross sectional study that has been done on 140 patients with SCD and 140 healthy blood donors from April 2015 to April 2016. The RBC phenotype of all patients and donors investigated by Tub method and all panel test phases were done at immunohematology laboratory of Iranian Blood Transfusion Organization of Ahwaz.Results: Of all SCD patients 61 (43.6%) were male and 79 (56.4%) were female. 68 (48.5%) were HbSS and 72 (51.4%) were S/B thalassemia. The mean age of patients was 19.69 (range: 2-60) years. Of all patients, 114 (81.25%) had received transfusion. The RBC alloimmunization rate among SCD patients was 7.1% and 50% of the RBC alloimmunization had anti-Kell and 30% had anti-Rh. The comparison of the RBC phenotypes between the group of patients with SCD and the group of blood donors (non-Arab) revealed a statistically significant difference in the frequency of S (54% vs. 67%, p=0.024), M (82.7% vs. 90.7%, p=0.049), and FYb (73.4% vs. 55.7%, p=0.002).Conclusions: Althoguh alloimmunization rate in SCD patients in this study was lower than reported by other studies but cross matchining at least for the Rh and Kell systems from the time of initial transfusion may decrease the incidence of alloimmunization.

Irradiation of Red Blood Cells and Alloimmunization.

Animal models suggest that red blood cell (RBC) damage incurred during storage can increase immunogenicity to some RBC antigens. We hypothesized that RBC irradiation, a source of oxidative damage, may result in higher RBC alloimmunization rates among transfusion recipients. Individuals receiving 1 or more gamma-irradiated RBC units, with follow-up antibody screening, were studied. We recorded diagnosis at the time of first irradiated RBC-unit transfusion, total irradiated RBCs received, and alloantibodies detected before and after irradiated RBC transfusion. The alloimmunization rate for patients receiving irradiated RBCs was 1.9% (3/154); this rate was not significantly different from the rate of 2.5% (5/200) derived from a control group that had undergone transfusion with nonirradiated RBCs ( P > .99). Most of the study subjects (83/154 [53.9%]) did not harbor an immunosuppressive disorder at the time of transfusion of irradiated RBCs, with postoperative bleeding (36/83 [43.4%]) being the most common diagnosis. This analysis provides reassurance that irradiated RBCs are not more immunogenic in patients with immunosuppression than in patients with immunocompetence.

Determination of Red Blood Cell Alloimmunization Rates in Transfused Patients with Hematologic and Oncologic Malignancies

▪Introduction: Patients with hematological and oncological malignancies are among the most frequent recipients of chronic red blood cell (RBC) transfusion therapy. One of the risks associated with chronic RBC exposure is the development of blood group antibodies. However, there are few extensive studies of alloimmunization rates associated with hematological or oncological malignancies in adult patients despite the frequency with which they are transfused. As such, the aims of this study were: 1) to determine the alloimmunization rate associated with malignant conditions in general, 2) to establish and compare alloimmunization rates for individuals with different forms of hematological and oncological neoplasia, and 3) to determine if any oncological disorder(s) appeared to predispose individuals to alloimmunization such that antibody mitigation measures could be employed for these diagnoses.Methods: Patients included were those undergoing type and screen testing at the study site (n=18,750 unique, active subjects in our facility’s transfusion record database). For each of these subjects, the electronic medical record was retrospectively reviewed to determine if a history of a hematologic or oncologic malignancy was present. Disorders grouped as ’hematologic malignancies’ in this study included: acute leukemia (myeloid or lymphoid), mast cell diseases, multiple myeloma, myelodysplastic syndromes, myeloproliferative disorders, and non-Hodgkin lymphoma (T- or B-cell). ’Non-hematologic’ cancers in this study were broadly grouped as follows: bladder, colon, head/neck, lung, prostate, skin, soft tissue/sarcoma. If a patient had a history of any of the above neoplastic diseases, further inclusion in the study required: 1) that the patient undergo at least one RBC unit transfusion after their diagnosis was established and 2) that at least one follow-up antibody screen test be performed after their first RBC transfusion post-diagnosis. When these additional inclusion criteria were met, the following data were collected for each subject: malignancy type, race/ethnicity, gender, and the number and specificity of antibodies detected. Ratio data were compared using the chi-square test with Yates’ correction for continuity; P values <0.05 were considered significant.Results: A total of 69 patients became alloimmunized after their diagnosis of a malignancy; these patients were overwhelmingly male (66/69; 95.7%) and most identified as white, non-Hispanic (50/69; 72.5%). The alloimmunization rate among patients with any malignancy diagnosis was 1.5% (69/4687), which was significantly lower than the general, historical alloimmunization rate at our facility (443/18750; 2.4%; P=0.0019). Of total transfused patients with a malignancy, most were diagnosed with a non-hematological disorder(4371/4687; 93.3%) and such malignancies were associated with an alloimmunization rate of 1.3% (55/4371) following transfusion. By comparison, the alloimmunization rate for transfused patients with hematological malignancies was 2.8% (14/501), which was significantly higher (P=0.011). When alloantibody development was analyzed on a disorder-by-disorder basis, the five highest alloimmunization rates were seen in: myelodysplastic syndromes (8/71; 11.2%), soft tissue cancers (3/50; 6.0%), acute leukemia (1/34; 2.9%), renal cancer (3/113; 2.7%), and myeloproliferative disorders (2/75; 2.7%). Alloimmunization rates under 2% were observed for all other hematological and non-hematological malignancies encountered in our patient population.Conclusions: RBC alloimmunization rates in transfused patients with malignancy were significantly lower than historical controls, suggesting that the immunosuppressive nature of these disorders and/or their associated therapies may play a role in limiting blood group antibody development. Hematologic disorders were associated with higher alloimmunization rates than non-hematologic malignancies, which may reflect a larger transfusion burden in these illnesses (a factor to be evaluated in future analyses). Overall, only myelodysplastic syndromes and soft tissue malignancies were associated with antibody formation rates substantially higher than historical controls. Therefore, consideration for prophylactic antigen matching to prevent alloimmunization may be warranted for these conditions. DisclosuresNo relevant conflicts of interest to declare.

Red Cell Alloimmunization Rates in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Introduction: Donor selection for allogeneic hematopoietic stem cell transplant (allo-HSCT) is dependent on matching with the intended recipient HLA allele profile, but not blood group compatibility. Red blood cell (RBC) phenotype matching is not considered, even if recipient alloantibodies are present pre-HSCT. Historically, up to 3.7% of allo-HSCT recipients have been found to develop new RBC alloantibodies following allo-HSCT. We completed an audit of all adult and pediatric allo-HSCT recipients of the Alberta Bone Marrow and Blood Cell Transplant Program to define the rate of RBC alloimmunization, and evaluate the impact of this RBC alloantibody presence on donor marrow engraftment in our allo-HSCT recipient population.Methods:A retrospective review was completed including all allogeneic pediatric and adult HSCT recipients between January 1, 2007 and January 1, 2015. Data was obtained from review of cellular therapy laboratory electronic records with red cell alloantibody information extracted manually from the transfusion medicine laboratory information system.Results: A total of 674 patients, including 104 pediatric recipients (<18 years old), underwent 697 allo-HSCT procedures (591 peripheral blood, 45 marrow, 61 cord blood). The mean HSCT recipient age was 40 (range 0-66) and most common HSCT indication was acute myeloid leukemia. Myeloablative conditioning was given to all adults and 86% of pediatric recipients. Fully HLA matched grafts were provided to 77% of recipients. ABO compatibility status of allo-HSCT procedures included the following: 362 (52%) ABO identical grafts, 154 (22%) grafts with a minor incompatibility, 143 (21%) grafts with a major incompatibility, and 38 (5.0%) grafts with bidirectional incompatibility. Rh mismatches were present in 165 (24%) of donor-recipient pairs.A total of 47 allo-HSCT recipients, including 3 pediatric and 44 adult patients, were found to have RBC alloantibodies before or after allo-HSCT. A total of 45 (6.4%) of allo-HSCT recipients had detectable RBC alloantibodies pre-HSCT, with 69 individual alloantibodies identified. The most common RBC alloantibody was anti-E (30%). Antibody screen results available on the day of or following HSCT in 43 allo-HSCT recipients found: 12 (28%) with antibody disappearance pre-HSCT and a negative screen on the date of allo-HSCT, 15 (35%) with antibody waning to disappearance after allo-HSCT, and 11 (26%) with persistence of pre-HSCT antibodies following allo-HSCT. New post-HSCT RBC alloantibodies were detected in 3 adult recipients of peripheral blood collected stem cell grafts (anti-D; anti-Kpa; anti-K plus anti-E), with an overall rate of 0.4%. These patients all received myeloablative conditioning and grafts which were ABO identical or had a minor ABO incompatibility. The anti-D antibody developed post-transplant in an Rh positive recipient of an Rh negative graft. Thus, the calculated overall rate of anti-D development in Rh mismatched HSCT recipients was 0.6%. There was no observed impact on neutrophil and platelet engraftment comparing adult allo-HSCT recipients who did and did not have pre-HSCT RBC alloantibodies.Conclusion: The risk of post-HSCT RBC alloantibody development is very low, even in Rh mismatched donor-recipient pairs. ABO incompatibility does not affect the risk of post-HSCT alloantibody development. Allo-HSCT recipients infrequently have pre-HSCT RBC alloantibodies, which may disappear after myeloablative conditioning. The presence of RBC alloantibodies pre-HSCT does not appear to impact donor marrow engraftment. The results of our retrospective study are limited by the availability, timing and frequency of post-HSCT antibody screen investigations. The decision to perform an antibody screen post-HSCT is a clinical one, typically dependent on recipient transfusion needs. Further prospective research is required to more accurately determine the rate of new post-HSCT alloantibody development and duration of alloantibody persistence or disappearance in allo-HSCT recipients. Results of these studies may also help guide RBC transfusion decisions in HSCT recipients known to have pre-HSCT RBC alloantibodies with proven engraftment and a negative post-HSCT antibody screen. DisclosuresNo relevant conflicts of interest to declare.

Red blood cell alloimmunization in transfused patients with bone marrow failure syndromes.

Red blood cell (RBC) alloimmunization is a concern for patients who receive multiple or chronic transfusions. Alloimmunization prevalence in transfused patients with bone marrow failure syndrome (BMFS) is unknown. This study aimed to determine physician practice for RBC antigen matching, immunization rates, and antibody specificities in patients with BMFS. The clinical records of all patients with BMFS seen at the Children's Hospital of Philadelphia between 2001 and 2015 were reviewed. Immunization rate was determined per 100 units transfused. ABO/D, C, E, and K (CEK) RBC matching was requested for 21.8% of patients. A total of 3782 RBC units were transfused to 87 patients, of which 2551 (67.5%) were CEK matched and 1231 (32.5%) were ABO/D only matched. The majority of units transfused to patients on a chronic transfusion regimen were CEK matched (89.6% of 2728 units). No anti-C, -E, or -K antibodies formed in any patient during the 14-year study period. Two alloantibodies and two autoantibodies formed, resulting in a rate of 0.05 alloantibodies and 0.05 autoantibodies per 100 units transfused. The prevalence of alloimmunization was 2.3%. The rate and prevalence of RBC alloimmunization were low in patients with BMFS. CEK matching avoided alloimmunization to these antigens in chronically transfused patients.

Female sex of older patients is an independent risk factor for red blood cell alloimmunization after transfusion.

More women than men are encountered with red blood cell (RBC) antibodies. It is not clear whether this difference is explained by more immunizing events in women or by a different acting immune system. To assess whether there is a difference in the posttransfusion RBC alloimmunization rate between women and men, a study on RBC alloimmunization during a 5-year period was conducted in patients with at least one antibody follow-up more than 14 days after transfusion. Data on transfusion and antibody follow-up characteristics in female and male transfusion recipients from the Leiden University Medical Center laboratory database were collected. Hazard ratios of alloimmunization, according to sex of the transfusion recipient, were estimated using Cox proportional hazards regression models taking possible confounders into account. From a total of 1699 women and 1969 men who were eligible, 4.2% of women and 3.4% of men (relative risk, 1.3; 95% confidence interval [CI], 0.9-1.8) developed posttransfusion antibodies. Adjustment for confounders resulted in a relative 80% higher risk in women older than 45 years of age. Elder women beyond childbearing age have a higher risk of posttransfusion antibody formation compared to men.

Blood donation by African migrants and refugees in Australia

Changing population demographics have important implications for the ability of transfusion services to meet the transfusion requirements of minority groups. In Western countries, differences in red‐blood‐cell (RBC) antigens between predominantly Caucasian blood donors and recipients from different demographic backgrounds may result in higher RBC alloimmunization rates, particularly in those who are chronically transfused, and can make it more difficult to source compatible blood. Ensuring blood donors are representative of the general population is particularly relevant for patients of African descent, who have a number of important blood group differences from Caucasians. However, there are challenges in ensuring a representative donor population, especially when the national population is very multicultural. Research in African migrants and refugees living in Australia has identified blood donation knowledge, misconceptions about blood donation from experiences prior to migration, and perceptions or experiences of discrimination within the host country as important determinants of blood donation. Therefore, promotion of knowledge and awareness of blood donation and blood and health service processes should be considered to assist with the recruitment of migrant donors.

Designated Donor Program Enrollment Does Not Affect Red Blood Cell Alloimmunization Rates in Children with Sickle Cell Disease on Chronic Transfusion Therapy

Background:Chronic red blood cell (RBC) transfusion therapy is the predominant treatment modality in children with sickle cell disease (SCD) at high risk of first or recurrent strokes. RBC alloimmunization develops in some patients receiving chronic transfusion therapy, due in part to genetic differences in the prevalence of blood group antigens between the patient population and the blood donor pool. Many children’s hospitals have developed designated donor or “buddy” programs to recruit African-American blood donors and assign them to specific SCD patients with matched phenotypes, particularly in the Rh and Kell antigen groups, to reduce the likelihood of RBC alloimmunization. However, the practical constraints of such programs may make it difficult to ensure that patients’ transfusions always come from designated donors. Moreover, it is unclear whether such programs result in a lower risk of RBC alloimmunization when compared to the use of non-designated-donor but phenotype-matched RBC units. We aimed to determine the proportion of transfusions from designated donors at our institution, hypothesizing that the development of new RBC alloantibodies is associated with a lower proportion of transfused units from designated donors.Methods:This is a single-institution retrospective cohort study of 38 patients with SCD who received chronic transfusion therapy (manual exchange or erythrocytapheresis) for primary or secondary stroke prevention from 1/1/2008 through 12/31/2012. Patients on transfusion therapy for 6 or more months were included. Subjects were censored at last date of follow-up or date of hematopoietic stem cell transplant. The local designated donor program was started in 1999. Designated donors are selected to be ABO/RhD compatible and phenotype-matched to patients for the C, E, and K antigens. When units from designated donors are not available, compatible units phenotype-matched for C, E, and K are issued from general inventory. The number and percentage of units transfused from either designated or non-designated donors, and the identification of new RBC alloantibodies during the study period, were evaluated. The rates of alloimmunization were compared between patients who received a “high” (above the median) or “low” (below the median) proportion of designated donor units. Categorical variables were compared with Fisher’s exact test and medians with the Mann-Whitney U-test in SPSS version 21 (IBM, Armonk, NY). A p-value below 0.05 was statistically significant.Results:During the study period, 38 subjects (42% male) met all inclusion criteria. A median of 120 units (IQR 60-186) was transfused to each subject, and each subject received a median of 63% (IQR 45%-77%) of units from designated donors. Of the 38 subjects, 18 (47%) produced at least one newly identified RBC alloantibody during the study period. Among these 18 antibody producers, a total of 29 new alloantibodies were detected, with a range of 1-3 per subject. Ten of the newly identified alloantibodies were directed against C, D, E, or K. No statistically significant difference between antibody producers and non-producers was identified for total number of RBC units transfused (median 161 vs. 96, p = 0.067), number of units transfused from designated donors (median 107 vs. 49, p = 0.099), number of non-designated-donor, phenotype-matched units transfused from general inventory (median 38 vs. 26, p = 0.059), or proportion of units transfused from designated donors (median 68% vs. 49%, p = 0.28). Although there was a trend toward a higher incidence of alloimmunization in patients who received a high proportion of designated donor units (OR 2.4, CI 0.6-8.7), it was not statistically significant (p= 0.33).Conclusions:Despite receiving phenotypically matched RBC units, almost half of the children with SCD on chronic transfusion therapy in this cohort developed new RBC alloantibodies during a five-year period. The number of units transfused from a designated donor did not significantly affect alloimmunization rate. One-third of the new alloantibodies were directed against antigens specifically matched for in the designated donor program. Patient-specific factors, such as genetic variation in the Rh locus, may be responsible for the risk of alloimmunization. Alternative matching strategies, such as genotypic matching of RBC donors and recipients, should be explored in prospective studies. DisclosuresJackups:Immucor: Consultancy.

Red Blood Cell Alloimmunization Mitigation Strategies

Hemolytic transfusion reactions due to red blood cell (RBC) alloantibodies are a leading cause of transfusion-associated death. In addition to reported deaths, RBC alloantibodies also cause significant morbidity in the form of delayed hemolytic transfusion reactions. These alloantibodies may also cause morbidity in the form of anemia, with compatible RBC units at times being unable to be located for highly alloimmunized patients, or in the form of hemolytic disease of the newborn. Thus, preventing RBC alloantibodies from developing in the first place, or mitigating the dangers of existing RBC alloantibodies, would decrease transfusion-associated morbidity and mortality. A number of human studies have evaluated the impact on RBC alloimmunization rates of providing partially phenotypically or genotypically matched RBCs for transfusion, and a number of animal studies have evaluated the impact of single variables on RBC alloimmunization. The goal of this review is to take a comprehensive look at existing human and animal data on RBC alloimmunization, focusing on strategies that may mitigate this serious hazard of transfusion. Potential factors that impact initial RBC alloimmunization, on both the donor and recipient sides, will be discussed. These factors include, but are not limited to, exposure to the antigen and an ability of the recipient's immune system to present that antigen. Beyond these basic factors, coexisting "danger signals," which may come from the donor unit itself or which may be present in the recipient, also likely play a role in determining which transfusion recipients may become alloimmunized after RBC antigen exposure. In addition, to better understanding factors that influence the development of RBC alloantibodies, this review will also briefly discuss strategies to decrease the dangers of existing RBC alloantibodies.