Transfusions in autoimmune hemolytic anemias: Frequency and clinical significance of alloimmunization.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) may be associated with transfusion reactions and risk of alloimmunization. OBJECTIVES: To evaluate the transfusion policy and rate of alloimmunization and its clinical significance in AIHA. METHODS: Data from 305 AIHA patients followed at a reference hematologic Center in Milan, Italy from 1997 to 2022 were retrospectively/prospectively collected (NCT05931718). RESULTS: Overall, 33% patients required transfusions with a response rate of 83% and eight transfusion reactions (7%), none hemolytic. Alloantibodies were detected in 19% of patients, being associated with higher transfusion burden (p = 0.01), lower Hb increase post-transfusion (p = 0.05), and transfusion reactions (p = 0.04). Along decades, the rate of RBC transfusions decreased from 53% to 20% and that of alloimmunization dropped from 30% to 6% likely due to the adoption of prestorage leukoreduction, the use of more restrictive Hb thresholds, and the implementation of molecular typing. CONCLUSIONS: Severe symptomatic AIHA may be safely transfused provided appropriate matching of patients and donors.

Differentiating patient characteristics between platelet refractory patients with and without antibodies to human leukocyte antigens.

BACKGROUND: Predicting whether a patient's platelet refractoriness (PR) is due to immune or nonimmune causes can be challenging. This study compared the demographics and clinical history of PR patients with human leukocyte antigen (HLA) antibodies (HLA-PR) versus PR patients without HLA antibodies. MATERIALS AND METHODS: A retrospective review of all patients with PR consults at a single institution over a 3-year period was performed. Patient charts were reviewed for all patients with confirmed PR, and demographic information (e.g., sex, race and ethnicity, preferred language) and clinical history (e.g., pregnancy, transfusion, primary diagnosis) were collected. Patient characteristics were compared among the HLA and non-HLA cohorts. RESULTS: A total of 295 patients with confirmed PR were identified, of whom approximately 70% did not have HLA antibodies and 30% did. Approximately 84% of the HLA-PR cohort was female. A history of transfusions was not associated with HLA-PR (p = .1). A history of pregnancy was strongly associated with the occurrence of HLA-PR (p < .001). Splenomegaly was associated with PR in the absence of HLA alloimmunization whereas infection, fever, bleeding, and disseminated intravascular coagulation were not. CONCLUSION: In this single-institution retrospective review, a history of pregnancy was strongly associated with HLA-PR, whereas a history of transfusion was not.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Management of a patient with sickle cell disease and multiple red blood cell alloantibodies in preparation for a hematopoietic stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) is currently the only widely available curative option for patients with sickle cell disease (SCD). Alloimmunization in this population is frequent and can complicate transfusion management during the HSCT period. The case of a pediatric patient with severe SCD clinical phenotype, multiple alloantibodies (9), and hyperhemolysis syndrome who underwent haploidentical HSCT is described. STUDY DESIGN AND METHODS: The patient was known for an anti-e, despite RHCE*01.01 allele, which predicts a C- c+ E- weak e+ phenotype. Donors matching the patient's extended phenotype were targeted for RHCE genotyping. RESULTS: Donors homozygotes or heterozygotes for RHCE*01.01 were selected for compatibility analyses and ranked based on strength of reactions. Discordance between zygosity and strength of reactions was observed, as the most compatible donors were heterozygotes for RHCE*01.01. In total, the patient received seven RBC units from two different donors during HSCT process without transfusion reaction or development of new alloantibodies. Six months post-HSCT, his hemoglobin level is stable at around 120 g/L and his chimerism is 100%. DISCUSSION: This case highlights the complexity of transfusion management during HSCT of alloimmunized patients with SCD. Collecting sufficient compatible units requires early involvement of transfusion medicine teams and close communication with the local blood provider. Genotyping of donors self-identifying as Black is useful for identifying compatible blood for those patients but has some limitations. HSCT for heavily alloimmunized patients is feasible and safe with early involvement of transfusion medicine specialists. Further research on the clinical impact of genotypic matching is needed.

Transfusing children with sickle cell disease using blood group genotyping when the pool of Black donors is limited.

BACKGROUND: Red blood cell transfusion is an effective treatment for patients with sickle cell disease (SCD). Alloimmunization can occur after a single transfusion, limiting further usage of blood transfusion. It is recommended to match for the ABO, D, C, E, and K antigens to reduce risks of alloimmunization. However, availability of compatible blood units can be challenging for blood providers with a limited number of Black donors. STUDY DESIGN AND METHODS: A prospective cohort of 205 pediatric patients with SCD was genotyped for the RH and FY genes. Transfusion and alloimmunization history were collected. Our capacity to find RhCE-matched donors was evaluated using a database of genotyped donors. RESULTS: Nearly 9.8% of patients carried a partial D variant and 5.9% were D-. Only 45.9% of RHCE alleles were normal, with the majority of variants affecting the RH5 (e) antigen. We found an alloimmunization prevalence of 20.7% and a Rh alloimmunization prevalence of 7.1%. Since Black donors represented only 1.40% of all blood donors in our province, D- Caucasian donors were mostly used to provide phenotype matched products. Compatible blood for patients with rare Rh variants was found only in Black donors. A donor with compatible RhCE could be identified for all patients. CONCLUSION: Although Rh-compatible donors were identified, blood units might not be available when needed and/or the extended phenotype or ABO group might not match the patient. A greater effort has to be made for the recruitment of Black donors to accommodate patients with SCD.

A genome-wide association study of alloimmunization in the TOPMed OMG-SCD cohort identifies a locus on chromosome 12.

BACKGROUND: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. STUDY DESIGN AND METHODS: We performed a genome-wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) cohort, which is part of Trans-Omics for Precision Medicine (TOPMed), with whole-genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. RESULTS: We identified one genome-wide significant locus on chr12 (p = 3.1e-9) with no evidence of genomic inflation (lambda = 1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA-Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. DISCUSSION: We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.

Maternal and child life years gained by transfusing low titer group O whole blood in trauma: A computer simulation.

BACKGROUND: Using low titer group O whole blood (LTOWB) is increasingly popular for resuscitating trauma patients. LTOWB is often RhD-positive, which might cause D-alloimmunization and hemolytic disease of the fetus and newborn (HDFN) if transfused to RhD-negative females of childbearing potential (FCP). This simulation determined the number of life years gained by the FCP and her future children if she was resuscitated with LTOWB compared with conventional component therapy (CCT). METHODS: The model simulated 500,000 injured FCPs of each age between 0 and 49 years with LTOWB mortality relative reductions (MRRs) compared with components between 0.1% and 25%. For each surviving FCP, number of life years gained was calculated using her age at injury and average life expectancy for American women. The number of expected future pregnancies for FCPs that did not survive was also based on her age at injury; each future child was assigned the maximum lifespan unless they suffered perinatal mortality or serious neurological events from HDFN. RESULTS: The LTOWB group with an MRR 25% compared with CCT had the largest total life years gained. The point of equivalence for RhD-positive LTOWB compared to CCT, where life years lost due to severe HDFN was equivalent to life years gained due to FCP survival/future childbearing, occurred at an MRR of approximately 0.1%. CONCLUSION: In this model, RhD-positive LTOWB resulted in substantial gains in maternal and child life years compared with CCT. A >0.1% relative mortality reduction from LTOWB offset the life years lost to HDFN mortality and severe neurological events.

RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA.

BACKGROUND: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors. STUDY DESIGN AND METHODS: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays. RESULTS: Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens. DISCUSSION: These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.

Low titer group O whole blood and risk of RhD alloimmunization: Rationale for use in Finland.

BACKGROUND: Prehospital low-titer group O whole blood (LTOWB) used for patients with life-threatening hemorrhage is often RhD positive. The most important complication following RhD alloimmunization is hemolytic disease of the fetus and newborn (HDFN). Preceding clinical use of RhD positive LTOWB, we estimated the risk of HDFN due to LTOWB prehospital transfusion in the Finnish population. STUDY DESIGN AND METHODS: We collected data on prehospital transfusions in Tampere and Helsinki University Hospital areas. Using the mean of reported alloimmunization rates in trauma studies (24%) and a higher reported rate representing trauma patients of 13-50 years old (42.7%), we estimated the risk of HDFN and extrapolated it to the whole of Finland. RESULTS: We estimated that in Finland, with the current prehospital transfusion rate we would see 1-3 cases of severe HDFN due to prehospital LTOWB transfusions every 10 years, and fetal death due to HDFN caused by LTOWB transfusion less than once in 100 years. DISCUSSION: The estimated risk of serious HDFN due to prehospital LTOWB transfusion in the Finnish population is similar to previous estimates. As Finland routinely screens expectant mothers for red blood cell antibodies and as the contemporary treatment of HDFN is very effective, we support the prehospital use of RhD positive LTOWB in all patient groups.

Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

BACKGROUND: Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child. STUDY DESIGN AND METHODS: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. RESULTS: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively). CONCLUSION: Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

Society for Maternal-Fetal Medicine Statement: RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation.

Guidelines for the management of first-trimester spontaneous and induced abortion vary in terms of rhesus factor D (RhD) testing and RhD immune globulin (RhIg) administration. These existing guidelines are based on limited data that do not convincingly demonstrate the safety of withholding RhIg for first-trimester abortions or pregnancy losses. Given the adverse fetal and neonatal outcomes associated with RhD alloimmunization, prevention of maternal sensitization is essential in RhD-negative patients who may experience subsequent pregnancies. In care settings in which RhD testing and RhIg administration are logistically and financially feasible and do not hinder access to abortion care, we recommend offering both RhD testing and RhIg administration for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals. Guidelines for RhD testing and RhIg administration in the first trimester must balance the prevention of alloimmunization with the individual- and population-level harms of restricted access to abortion.

The use of free DNA for fetal RHD genotyping in the Rh negative pregnant patient-the time has come.

Cell-free DNA to determine the fetal RHD genotype from the maternal circulation was first described in 1993. High throughput assays using polymerase chain reaction technology were introduced in Europe and gained widespread acceptance in the management of the Rhesus alloimmunized pregnancy. The specificity and sensitivity of these assays approached 99%. As confidence was gained with these results, Scandinavian countries began to employ cell-free DNA for fetal RHD typing as an integral component of their introduction of antenatal Rhesus immune globulin in non-alloimmunized pregnancies. Since 40% of RhD-negative pregnant women will carry an RhD-negative fetus, doses of Rhesus immune globulin were conserved. Recently 2 U.S. companies have introduced cell-free DNA assays for RHD as part of their noninvasive prenatal testing assays. Both utilize next generation sequencing and have developed methodologies to detect the aberrant RHD pseudogene and the hybrid RHD-CE-Ds genotype. In addition, excellent correlation studies with either neonatal genotyping or serology have been reported. The manufacturer of RhoGAM has recently announced a national shortage. Given the current availability of reliable cell-free DNA assays for determining the RHD status of the fetus, the time has come to implement this strategy to triage the antenatal use of Rhesus immune globulin in the U.S.

Prediction of the antigenic regions in eight RhD variants identified by computational biology.

BACKGROUND AND OBJECTIVES: Changes in RHD generate variations in protein structure that lead to antigenic variants. The classical model divides them into quantitative (weak and Del) and qualitative (partial D). There are two types of protein antigens: linear and conformational. Computational biology analyses the theoretical assembly of tertiary protein structures and allows us to identify the 'topological' differences between isoforms. Our aim was to determine the theoretical antigenic differences between weak RhD variants compared with normal RhD based on structural analysis using bioinformatic techniques. MATERIALS AND METHODS: We analysed the variations in secondary structures and hydrophobicity of RHD*01, RHD*01W.1, W2, W3, RHD*09.03.01, RHD*09.04, RHD*11, RHD*15 and RHD*21. We then modelled the tertiary structure and calculated their probable antigenic regions, intra-protein interactions, displacement and membrane width and compared them with Rhce. RESULTS: The 10 proteins are similar in their secondary structure and hydrophobicity, with the main differences observed in the exofacial coils. We identified six potential antigenic regions: one that is unique to RhD (R3), one that is common to all D (R6), three that are highly variable among RhD isoforms (R1, R2 and R4), one that they share with Rhce (R5) and two that are unique to Rhce (Ra and Rbc). CONCLUSION: The alloimmunization capacity of these subjects could be explained by the variability of the antigen pattern, which is not necessarily recognized or recognized with lower intensity by the commercially available antibodies, and not because they have a lower protein concentration in the membrane.

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

BACKGROUND AND OBJECTIVES: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Incidence of formation of anti-D between patients with and without a history of solid organ transplant.

BACKGROUND AND OBJECTIVES: Solid organ transplant surgeries including liver transplants constitute a substantial risk of bleeding complications and given frequent national blood shortages, supporting D-negative transplant recipients with D-negative red blood cell products perioperatively can be difficult for the transfusion services. This study was designed to compare the incidence of alloimmunization after D-mismatched red cell transfusions between patients with and without a history of solid organ transplant at a single tertiary care hospital. The patients undergoing solid organ transplants are on strong immunosuppressive regimens perioperatively to help reduce the risk of rejection. We hypothesized that the use of these immunosuppressive agents makes these patients very less likely to mount an immune response and form anti-D antibodies when exposed to the D-positive red blood cell products perioperatively. STUDY DESIGN AND METHODS: At our center, D-negative patients who received ≥1 unit of D-positive red blood cell products were identified using historical transfusion records. Antibody testing results were examined to determine the incidence of the formation of anti-D and any other red cell alloantibodies after transfusion and these results were compared between patients with and without a history of solid organ transplant. RESULTS: We were able to identify a total of 22 patients over 10 years with D-negative phenotype who had undergone a solid organ transplant and had received D-positive red blood cell products during the transplant surgeries. We also identified a second group of 54 patients with D-negative phenotype who had received D-positive red blood cell products for other indications including medical and surgical. A comparison of the data showed no new anti-D formation among patients with a history of D mismatched transfusion during solid organ transplant surgeries. CONCLUSION: Among our limited study population, we observed a very low likelihood of D alloimmunization among solid organ transplant recipients. A larger, prospective study could help further evaluate the need for prophylactic D matching for red cell transfusions during solid organ transplant surgeries.

RhD mismatch does not affect haematopoietic recovery, graft-versus-host disease and survival in allogeneic haematopoietic cell transplantation: A Japanese registry-based study.

BACKGROUND AND OBJECTIVES: ABO blood group mismatch between the donor and the recipient can affect the success of the transplant as well as problems with the red blood cells during allogeneic haematopoietic cell transplantation (HCT). However, the impact of the Rhesus (Rh) D mismatch on transplant outcomes in allogeneic HCT has been poorly elucidated. MATERIALS AND METHODS: We retrospectively evaluated the impact of the RhD mismatch on post-transplant outcomes in 64,923 patients who underwent allogeneic HCT between 2000 and 2021 using a Japanese registry database. RESULTS: Out of the whole group, 64,293, 322, 270 and 38 HCTs were done when the recipient or donor was RhD-mismatched with (+/+), (-/+), (+/-) or (-/-) combinations. The difference in RhD between recipient/donor (-/+), (+/-) and (-/-) did not affect haematopoietic recovery, acute and chronic graft-versus-host disease (GVHD), overall survival (OS), non-relapse mortality (NRM) or relapse when RhD (+/+) was used as the reference group in multivariate analysis. CONCLUSION: Our registry-based study demonstrated that RhD mismatch between recipient and donor did not significantly impact haematopoietic recovery, GVHD, OS, NRM or relapse after allogeneic HCT. These data suggest that RhD mismatches may not need to be avoided for recipient and donor combinations in allogeneic HCT.

The selection and preparation of red cell components for intrauterine transfusion: A national survey.

BACKGROUND AND OBJECTIVES: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT. MATERIALS AND METHODS: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed. RESULTS: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites. CONCLUSION: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting.

Does high body mass index (>25 kg/m2) or weight (>80 kg) reduce the effectiveness of anti-D prophylaxis in Rh(D)-negative pregnant women? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal antibodies, often triggered by foetal antigens, destroy foetal and neonatal red blood cells. Factors like antibody strength, quantity and gestational age influence HDFN severity. Routine antenatal anti-D prophylaxis (RAADP) has significantly reduced HDFN cases. However, the effect of overweight/obesity (body mass index [BMI] > 25/30 kg/m2) on anti-D prophylaxis efficacy remains unclear. This systematic review will examine the impact of BMI on anti D prophylaxis effectiveness in Rh(D) negative pregnant women. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. We searched databases from 1996 to 2023, focusing on studies exploring the link between high BMI/weight and anti-D serum levels in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. Ten eligible studies were included, three suitable for meta-analysis. Study quality was assessed using the Strengthening the Reporting Observation Studies in Epidemiology (STROBE) checklist. Statistical analyses included Pearson correlation coefficients and risk differences. RESULTS: Our meta-analysis revealed a significant negative correlation (r = -0.59, 95% confidence interval [CI]: -0.83 to -0.35, p = 0.007) between high BMI/weight and serial anti-D levels in in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. High BMI/weight had lower odds of serial anti-D level exceeding 30 ng/mL (arcsine risk difference [ARD] = 0.376, 95% CI: 0.143-0.610, p = 0.002). Heterogeneity among studies was low (I2 = 0). CONCLUSION: While our analysis suggests a potential linkage between high BMI/weight and reduced efficacy of anti-D prophylaxis, caution is warranted due to study limitations. Variability in study design and confounding factors necessitate careful interpretation. Further research is needed to confirm these findings and refine clinical recommendations.

Disease severity in subsequent pregnancies with RhD immunization: A nationwide cohort.

BACKGROUND AND OBJECTIVES: To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. MATERIALS AND METHODS: Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD-positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD-positive child and thus after receiving anti-D at least twice (group A) or during the first pregnancy at risk for immunization (group B). RESULTS: Sixty-two RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD-positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non-intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody-dependent cell-mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD-positive child (group B), often before they had ever received anti-D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION: RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD-positive child are at highest risk of severe disease in the next pregnancy.

Risk of new alloimmunization in patients on anti-CD38 treatment using tube LISS-IAT method.

BACKGROUND: Daratumumab is a monoclonal antibody that targets CD38, a transmembrane protein expressed on many cells including RBCs and to a greater extent on myeloma cells. It has been used for treatment of multiple myeloma and autoimmune diseases. Transfusion management of patients on such therapy can be challenging as these drugs cross-react with RBC surface antigens and cause panreactivity. MATERIAL AND METHODS: A retrospective study of the 68 patients treated with anti-CD38 from 2018-2023 was carried out. Data regarding transfusion history and antibody screens were analyzed. Depending whether they had immunohematological work-up before or during the treatment- DAT, antibody screen (CAT and tube), RBC pheno/genotyping and serologic cross-matches (CAT and tube) were performed for each patient. All cases with positive CAT IAT were retested in LISS-tube and cross-matches were performed with phenotypically matched units in LISS-tube. RESULTS: Antibody screen has shown panagglutination with all panel cells with low and variable agglutination intensity (weak to 2 +). Panagglutination remained positive for 1 - 6 months after drug cessation. Positive DAT was seen in 60,6% patients, while autocontrol was negative. Ficin treated panel-cells eliminated nonspecific reactivity. LISS-tube antibody screen and cross-matches were negative for all patients, apart from 3 patients who had preexisting antibodies. No new antibodies were detected during the course of the study. CONCLUSION: Among study group there were no newly identified alloantibodies, meaning that the policy of transfusing them with matched RBCs and performing IAT/cross-matches in tube is a safe and effective policy according to the findings of this study.