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Background: Haemolytic disease of the foetus and newborn (HDFN) is an immune disorder driven by maternal alloimmunisation against foetal/newborn red blood cell antigens. HDFN can cause significant morbidity and mortality, with symptoms in the foetus ranging from mild anaemia to hydrops fetalis. While in newborns, HDFN can lead to severe forms of neonatal hyperbilirubinaemia and kernicterus. This systematic review (SR) aimed to identify and summarise real-world evidence (RWE) related to the patient burden/experience and economic burden of HDFN. Methods: Electronic database searches supplemented by handsearching of grey literature, were conducted to identify studies that reported the clinical patient burden/experience, and economic burden of HDFN in Europe, the Middle East, and Africa (EMEA). Data from eligible studies were summarised in a narrative synthesis due to heterogeneity between studies. Results: A total of 26 relevant publications were identified for inclusion in the SR, consisting of one study that directly measured Health Related Quality of Life, 9 studies reporting on proxy outcomes for patient burden and 18 studies reporting on economic burden (this includes two double-counted studies reporting more than one outcome type). Neurodevelopment, academic development, behaviour and personality were assessed as proxy outcomes for patient burden given the limited identification of patient-reported outcome data. These studies suggested potential neurodevelopmental impairments in children with HDFN. Despite these indirect insights into patient burden, identified data were limited and results should be interpreted with consideration of the inherent heterogeneity in design and endpoints assessed across RWE studies. Economic burden data were primarily limited to healthcare resource use outcomes, with limited reported data on healthcare costs, it is difficult to draw notable conclusions on the true economic burden of HDFN. Conclusions: The current SR provides a clear summary of the available evidence for the patient experience and economic burden of HDFN. While the limited evidence indicates that HDFN does confer a significant burden on patients, the review identifies the need for further well-powered and representative observational studies using well-defined outcome measures to aid a greater understanding of the burden and experience of HDFN. Trial registration: The protocol for this systematic review was registered in PROSPERO CRD42022328444. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the fetus and newborn (HDFN) is a condition due to maternal blood group antibodies targeting antigens in fetal red blood cells, with significant prenatal/perinatal morbidity and mortality. Severe HDFN cases are often associated with alloimmunization against Rhesus D (RhD) or Kell antigens. Information about HDFN epidemiology and treatment in Latin American countries is limited. This review aims to identify and synthesize the available evidence on the epidemiology and management of HDFN in this region. Methods: In July 2023, EMBASE, PubMed, LILACS, and other databases were searched for articles reporting epidemiology, treatment, prenatal and perinatal outcomes, and patient journey of HDFN cases in Latin American countries. A snowball search of cross-references and gray literature complemented the initial search. Publications in English, Spanish, and Portuguese were reviewed. Data were extracted using a defined template and charted in tables. Results: We reviewed five guidelines and 19 observational studies from Brazil, Chile, Mexico, Argentina, Colombia, Panamá, Paraguay, and Peru. HDFN due to Rh alloimmunization ranged from 0.5 to 5 per 1000 live births, and anti-D remains the most frequent alloantibody type for severe HDFN. The perinatal mortality rate of HDFN is approximately 1.3–1.6 per 100,000 live births, and fetal deaths can reach 30% among patients treated with intrauterine transfusions. Up to 47% of alloimmunized pregnancies were referred to reference centers only during the third trimester. About 60% of eligible pregnancies received anti-D IgG prophylaxis. Conclusions: Although estimates in LATAM countries are scarce and lack standardized measures, we observed that the incidence, morbidity, and mortality of HDFN in this region are problematic. RhD alloimmunization was reported in approximately up to 70% of severe HDFN cases, despite anti D HDFN being largely preventable. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore variations in prenatal care, delivery methods, influencing factors, and neonatal outcomes among Rh-negative pregnant women, so as to improve pregnancy healthcare for this demographic, raise the quality of maternal–fetal management, and safeguard the health of both mother and infant. Methods: This study included 200 women who received routine prenatal care, exhibited no other pregnancy complications, and were admitted for delivery. They were divided into an observation group (100 Rh-negative blood type) and a control group (100 Rh-positive blood type). The study examined differences in pregnancy management, clinical characteristics and pregnancy outcomes between the two groups. Results: The results indicated that singleton pregnancies in Rh-negative mothers are associated with significantly higher rates of postpartum blood loss (305.1 ± 183.8 vs. 246.1 ± 84.9 mL, P = 0.004), neonatal hyperbilirubinemia (39% vs. 23%, P = 0.014), low birth weight (11% vs. 2%, P = 0.01), and NICU admission (30% vs. 18%, P = 0.046) compared to the control group. Among Rh-negative mothers, subgroup analysis by ethnicity revealed a higher incidence of fetal distress in the other ethnic groups compared to the Han and Zhuang groups (16.7%, 0, 6.5%, respectively, P = 0.025). Subgroup analysis based on ABO blood type within Rh-negative mothers did not show any statistical significance in various outcomes (all P > 0.05). Infants with neonatal hyperbilirubinemia born to Rh-negative mothers experienced a quicker resolution of hyperbilirubinemia compared to those whose mothers did not receive intramuscular anti-D immunoglobulin [1.0 (1.0, 1.5) vs. 5.0 (1.5, 10.0), P = 0.002]. Conclusions: The Rh-negative blood type is linked to higher risks of neonatal hyperbilirubinemia, low birth weight, and increased postpartum hemorrhage, resulting in detrimental pregnancy outcomes. Administering anti-D immunoglobulin speeds up the resolution of neonatal hyperbilirubinemia. Thus, prudent and efficient use of anti-D immunoglobulin can mitigate adverse outcomes for both mothers and newborns. [ABSTRACT FROM AUTHOR]

Plain language summary Haemolytic disease of the fetus and newborn (HDFN) is a rare condition that causes a baby to develop anaemia while growing inside the woman; or after birth. Left untreated, this may lead to stillbirth or neonatal death.HDFN is caused when the pregnant woman's antibodies cross the placenta, enter the baby's circulation, and attach to proteins called antigens (inherited from the father) on the baby's haemoglobin containing red blood cells, and cause them to break apart, causing fetal anaemia.Women routinely have their blood tested at the start of pregnancy to assess their ABO blood group and Rh antigens. There are five main Rhesus antigens: D, C, c, E, e; with anti‐D being responsible for most cases of HDFN. If a woman is found to be Rh D negative; a ‘non‐invasive’ blood test is performed to assess if the fetal blood group is the same as the woman's. If a woman is found to be Rh D negative, and the baby is found to be D positive, the baby is at risk. This is because the baby has inherited the D antigen from the father; so‐called Rhesus incompatibility. Other red blood cell antibodies such as anti‐Kell or anti‐Duffy can also cause fetal anaemia. Women at highest risk of developing HDFN are those who have had at least one previous birth or a sensitising event (such as abdominal trauma) in a current or previous pregnancy, causing the woman and baby's blood to mix.Current treatment for haemolytic disease of the fetus involves giving fetal blood transfusions, with a small risk of early labour or pregnancy loss. If anaemia develops later in pregnancy, early delivery of the baby may be recommended; which could lead to complications of prematurity. In cases of mild HDFN, the baby may only require light therapy for neonatal jaundice. However, if the anaemia occurs earlier in pregnancy and is severe, the baby may need blood transfusions while still in the womb ‐ and after birth may require an exchange transfusion, to remove the woman's antibodies from their circulation and to treat the anaemia.Intravenous immunoglobulin (IVIG) is a potential non‐invasive method to prevent or delay the onset of severe anaemia. It is a blood product given intravenously every week to women who have been deemed at very high risk of early onset HDFN. It can be started at the end of the first trimester until birth, or until anaemia develops. This paper will discuss the evidence behind IVIG and other novel therapies during pregnancy, including the risks and the benefits. The developers of the paper include obstetricians, neonatologists and haematologists to provide different opinions on this topic. [ABSTRACT FROM AUTHOR]

Background Results Discussion Homozygous inheritance of the RN haplotype, characterized by the absence of the high frequency antigen Sec, as well as partial C and e antigens, is rare and is associated with potential for alloimmunization. Anti‐Sec has been reported to be associated with a risk of delayed hemolytic transfusion reaction and hemolytic disease of the fetus and newborn (HDFN).We report the case of a 36‐year‐old pregnant woman with known sickle cell trait (SCT) and homozygous for the RN haplotype with anti‐Sec, anti‐c, and anti‐e. Morphological ultrasound identified dextro‐transposition of the great arteries in the fetus. Neonatal cardiac surgery was planned with cardiopulmonary bypass support. Due to the rarity of this genotype, there were no compatible donors in our registry. For this reason, in addition to two previously glycerolized maternal donations, the mother donated three units during pregnancy and one unit postpartum.This case highlights the many complexities for the blood supplier pertaining to organizing blood donations during pregnancy, the risk of leukoreduction failure and jellification during the deglycerolization process of units from donors with rare blood carrying the SCT, as well as planning the rare‐blood inventory and managing expiry dates to provide transfusion support during delivery, neonatal surgery, and the postoperative period. This case also exemplifies the importance of a strong partnership between blood suppliers and medical teams. [ABSTRACT FROM AUTHOR]

There exists a need to research new diagnostic and therapeutic approaches that consider hemolytic disease of fetus and newborn (HDFN)’s physiopathology and focus not only on the pregnant person’s immune system but also on the fetal immune system. This implies, in the final sense, to view the fetus as our patient. In spite of having found a safe and efficient method of prevention of HDFN more than 50 years ago, HDFN continues to be a relevant cause of perinatal morbidity and mortality, due to lack of access to immunoprophylaxis. In light of the above, we should strive to prevent sensitization and HDFN by ensuring certain health policies across the globe, especially in countries and regions of high morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective: To determine the rate of clinically significant red blood cell (RBC) antibody seroconversion in pregnancy and associated risk factors and neonatal outcomes. Methods: This is a retrospective cohort study of all deliveries within a large multi-hospital system from July 2016 to March 2023. Deliveries with a missing RBC antibody screen on admission for delivery were excluded, as were deliveries with a positive antibody screen on admission for delivery without a record of antecedent type and screen (T&S) in that pregnancy. Deliveries were categorized as 1) not possessing clinically significant antibodies (which includes those with a negative antibody screen, evidence of passive immunity solely due to Rh(D) immune globulin (RhIG), or possessing only non-clinically significant RBC antibodies); 2) previously alloimmunized (i.e. pregnancies that demonstrated clinically significant antibodies on the first T&S, regardless if they accrued additional antibodies throughout the pregnancy); or 3) seroconverted (i.e. no clinically significant antibodies on the first T&S with subsequent development of alloimmunization with clinically significant antibodies). For neonates born to seroconverted patients with clinically significant antibodies, neonatal outcomes such as initial hemoglobin, need for transfusion, and neonatal intensive care unit (NICU) admission were ascertained via chart abstraction. All records were linked with an existing validated database, inclusive of maternal characteristics and pregnancy outcomes, and comparisons were made between three categories based on antibody status with a sub-analysis of two categories. Bivariate analysis was performed with Chi-square for categorical and Wilcoxon rank-sum or Kruskal–Wallis test for continuous variables. Results: There were 58,912 pregnant individuals with 71,384 eligible deliveries during the study period, with 67,570 deliveries remaining after data linkage. Of these, 67,209 (99.5%) deliveries had a negative or non-clinically significant antibody screen at delivery. Of the remaining 361 (0.53%) deliveries, 185 (0.27%) were previously alloimmunized and 176 (0.26%) seroconverted in pregnancy. Among pregnancies demonstrating seroconversion, the most common newly acquired antibodies were anti-E, anti-c, anti-JkA, anti-C, anti-D, anti-M, anti-K, and anti-S. Among the 176 pregnancies complicated by seroconversion, there were four unexplained fetal losses, none of which were attributable to HDFN. Among the 178 liveborn neonates born to the 176 pregnancies demonstrating seroconversion, three (1.7%) infants had initial hemoglobin <13.5 mg/dL, four (2.2%) required postnatal transfusion but all were unrelated to HDFN, and 34 (19.1%) required NICU admission. When comparing deliveries demonstrating seroconversion with those with a negative antibody screen at delivery, advanced maternal age and increasing gravidity and parity were most strongly associated with seroconversion. Conclusion: Development of new clinically significant RBC antibodies in pregnancy occurred at a rate of 0.26% in this large cohort study with no cases of stillbirth or neonatal demise attributable to RBC alloimmunization among pregnancies demonstrating seroconversion. Advanced maternal age and increasing gravidity and parity were most strongly associated with seroconversion in pregnancy. Routine third trimester prenatal assessment of maternal antibody status may not be indicated due to low likelihood for clinically significant seroconversion. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions. Methods: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment. Results: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN. Conclusion: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Objectives: The clinical characteristics and outcomes of hemolytic disease of the newborn (HDN) caused by irregular antibodies remain unclear. Herein, we analyzed the clinical features and prognosis of HDN. Methods: Children admitted to our institution between June 2009 and December 2022 with a definite diagnosis of HDN were evaluated. Patients with irregular antibodies were matched in a 1:3 ratio to those with ABO incompatibility. Children with confirmed Rh-incompatibility hemolytic disease were divided into the RhD subgroup (hemolysis induced by Rh anti-D) and the non-RhD group (hemolysis induced by other Rh antibodies). Results: The irregular antibody and ABO incompatibility group included 32 and 96 patients, respectively. Compared to the ABO incompatibility group, the irregular antibody group showed earlier jaundice; higher incidence of liver and spleen enlargement and anemia; higher direct antiglobulin test (DAT) positivity; earlier and more severe anemia; higher rates of enhanced phototherapy, blood transfusion, and blood exchange; and longer hospital stay (all p < 0.05). Compared to the non-RhD group, the RhD subgroup showed an earlier occurrence of jaundice and a higher incidence of liver and spleen enlargement (both p < 0.05). The multiple irregular antibody subgroup further showed earlier occurrence of jaundice and a higher rate of enhanced phototherapy, blood transfusion, and blood exchange than the single-antibody group (both p < 0.05). Conclusions: HDN caused by irregular red blood cell antibodies is rare, but clinical manifestations are serious. It is important to pay attention to the screening of irregular antibodies during pregnancy, to strengthen monitoring, and to provide intrauterine treatment and early intervention as necessary. [ABSTRACT FROM AUTHOR]

The document contains abstracts from the Australian and New Zealand Society of Blood Transfusion (ANZSBT) Stream of the BLOOD 2023 Meeting held in Melbourne, Australia. It includes presentations on topics such as monitoring transfusion and patient safety risks, characterizing the Kidd blood group system in a Kenyan population, and applying Massively Parallel Sequencing (MPS) technology for non-invasive prenatal testing to detect red cell and platelet antigens. The research presented aims to improve transfusion practices, understand blood group distribution patterns, and enhance patient outcomes in transfusion. [Extracted from the article]

Alloimmunization to red cell antigens during antenatal period is a serious complication. Antibody titration of maternal blood sample corroborates with severity of disease and helps in planning further management. Conventional Tube Testing (CTT) method is widely accepted for antibody titration in antenatal cases but it can be replaced by Gel Microcolumn Agglutination (GMA) as it offers many advantages. Critical titer levels have been recommended by CTT method, but corresponding levels by GMA are yet to be established due to lack of adequate data. Total of 1020 Rh negative antenatal females were evaluated over a period of four years and those found to be positive on antibody screening were further investigated. Antibody titration by CTT and GMA was carried out and the titers were correlated with the outcome of pregnancy. Out of the 1020 cases screened for antibodies, 112 (10.98%) were detected to be positive by GMA while 40 (3.92%) cases were detected by CTT. Titration was performed by both methods and results were statistically correlated. A moderate correlation was observed where one or more than one antibodies were involved (Pearson's Coefficient 0.756), while a strong correlation (0.893) was observed between the two methods when single antibody (Anti-D) was involved. Titer values obtained by GMA were also higher than CTT. Gel microcolumn agglutination (GMA) was found to be more sensitive and precise method for titration. A titer of 512 by GMA (IgG only) mostly corresponded to the values of 16 by CTT and had good correlation with clinical outcome. [ABSTRACT FROM AUTHOR]

Copyright of Health Bulletin / Zdravstveni Glasnik is the property of Faculty of Health Studies, University of Mostar and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Canadian Medical Association Journal article delves into the diagnosis and management of early pregnancy loss, emphasizing the significance of empathetic communication and supportive follow-up to address the psychological impact on patients. It outlines risk factors, symptoms, diagnosis, and management options, stressing the need for personalized care and informed decision-making. The document also provides resources for patients and underscores the importance of compassionate support during this challenging period, while highlighting the role of Early Pregnancy Assessment Clinics in enhancing patient outcomes and satisfaction. [Extracted from the article]

Objectives: ABO hemolytic disease of the newborn (ABO HDN) is the most common cause of neonatal jaundice due to feto-maternal incompatibility. The objective of this study is to evaluate early predictors of ABO HDN using immuno-hematological and biochemical tests. Materials and method: Newborns with blood group A/B born to group O mothers were prospectively enrolled in the present study. Direct antiglobulin test (DAT) and cord blood bilirubin (CBB) were performed. Total serum bilirubin (TSB) was measured at 72 hours of life. Serum anti-A/B IgG titers of maternal samples were measured. For the statistical analysis, Microsoft Excel 2013 (Microsoft Corporation, NY, USA) and SPSS statistical computer software (version 22) were used. To find the efficacy and cut-off values for various predictors of neonatal jaundice, receiver operating characteristic (ROC) curve analysis was performed. To evaluate the relative importance of predictors for phototherapy (PT), logistic regression was used. Results: A total of 200 ABO incompatible mother-neonate pairs were included in the present study. The incidence of ABO HDN was 10% (n=20). The number of DAT positive cases was 38 (19%). Regression analysis showed a significant influence of antibody titre, CBB and DAT on probability of phototherapy. Antibody titers =512 predicted severe hyperbilirubinemia with 80% sensitivity and 83% specificity; CBB = 2.75 mg/dL had 85% sensitivity and 83% specificity. Conclusion: High risk ABO-incompatible neonates could be identified at birth using maternal antibody titers, DAT and CBB. Early diagnosis with enhanced surveillance will help in optimum utilization of healthcare. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloantibody‐mediated destruction of fetal/neonatal red blood cells (RBCs). While the pathophysiology has been well‐characterized, the clinical and laboratory monitoring practices are inconsistent. Methods: We surveyed 103 US institutions to characterize laboratory testing practices for individuals with fetuses at risk of HDFN. Questions included antibody testing and titration methodologies, the use of critical titers, paternal and cell‐free fetal DNA testing, and result reporting and documentation practices. Results: The response rate was 44% (45/103). Most respondents (96%, 43/45) assess maternal antibody titers, primarily using conventional tube‐based methods only (79%, 34/43). Among respondents, 51% (23/45) rescreen all individuals for antibodies in the third trimester, and 60% (27/45) perform paternal RBC antigen testing. A minority (27%, 12/45) utilize cell‐free fetal DNA (cffDNA) testing to predict fetal antigen status. Maternal antibody titers are performed even when the fetus is not considered to be at risk of HDFN based on cffDNA or paternal RBC antigen testing at 23% (10/43) of sites that assess titers. Discussion: There is heterogeneity across US institutions regarding the testing, monitoring, and reporting practices for pregnant individuals with fetuses at risk of HDFN, including the use of antibody titers in screening and monitoring programs, the use of paternal RBC antigen testing and cffDNA, and documentation of fetal antigen results. Standardization of laboratory testing protocols and closer collaboration between the blood bank and transfusion medicine service and the obstetric/maternal‐fetal medicine service are needed. [ABSTRACT FROM AUTHOR]

The Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee (CTMC) provides evidence-based guidance on safe and effective transfusion practices. Key developments in transfusion medicine in 2023 include findings on red blood cell transfusion strategies for myocardial infarction, updated RBC transfusion guidelines, and the impact of donor sex on transfusion outcomes. Additionally, studies on infectious diseases, blood donor screening, and collections, as well as patient blood management (PBM) metrics and effectiveness, were highlighted. The document also covers advances in hemostasis, hemoglobinopathies, immunohematology, genomics, pediatrics, apheresis, and biotherapies, including the FDA approval of gene therapies for sickle cell disease. Lastly, the text addresses healthcare disparities and diversity, equity, and inclusion (DEI) issues, such as racial disparities in postoperative transfusion outcomes and gender and racial inequity among editorial positions. [Extracted from the article]

Hemolytic disease of the fetus and newborn (HDFN) results from the destruction of the newborn's red blood cells or the fetus by the mother's immune globulin G antibodies. Although HDFN is often caused by RhD and ABO incompatibility, it can also be seen due to minor blood groups such as Kell, Kidd, Duffy, P, MNS, or Rh subgroup (C, c, E, e) alloantibodies. Our study aims to share our experiences regarding a rare cause of HDFN. The files of patients who were followed up with the diagnosis of jaundice in a third-level Neonatology Unit of a university hospital between January 2014 and September 2023 were retrospectively examined. Eleven patients with Kell incompatibility were included in the study. There was no ABO/RhD incompatibility in any case. RhD subgroup incompatibility and Kell incompatibility were present in four cases. Phototherapy was applied to all patients. The patient, whose total bilirubin level was high despite phototherapy, was treated with an exchange transfusion. No complications were observed due to treatment or high total bilirubin. No significant difference was observed between the parameters evaluated according to the gender variable. It should be kept in mind that severe hemolysis and related deaths may occur due to Kell incompatibility. In order to reduce and prevent severe hemolysis due to Kell and other minor blood groups in newborns, transfusing blood products suitable for minor blood groups to women of childbearing age (especially pregnant women) may be a correct approach as a country policy. [ABSTRACT FROM AUTHOR]

Summary: Extension with cE‐matching of the transfusion policy for women under 45 years to prevent alloimmunization and hemolytic disease of the foetus and newborn (HDFN) was evaluated. After implementation of cEK‐matching, anti‐c occurrence decreased from 46.8 to 30.4 per 100 000 pregnancies (RR 0.65, 95% CI 0.54–0.79), while anti‐E occurrence decreased from 122.1 to 89.9 per 100 000 pregnancies (RR 0.74, 95% CI 0.66–0.84). The c‐negative women showed a higher anti‐E occurrence before cEK‐matching and a more pronounced decline with the new policy. This indicates that cEK‐matched transfusion effectively reduces alloimmunization, and that a cK‐matched approach could prevent most transfusion‐related alloimmunization and HDFN. [ABSTRACT FROM AUTHOR]

We experienced a case in which anti-D was detected in an RhD-negative patient who was transfused with RhDnegative red blood cells (RBC). We requested the Japanese Red Cross Tohoku Block Blood Center to perform a genetic analysis of the blood products used, and found a typical DEL gene (c. 1227G＞A) in the donor of the most recently transfused RBC. Since factors other than transfusion were negative for the production of anti-D, it was inferred that transfusion of DEL-type was involved in the production of anti-D. Although the immunogenicity of the DEL-type is considered low, there are scattered reports that transfusion of this type is involved in the production of anti-D. Therefore, it is considered necessary to avoid transfusion of DEL-type RBCs whenever possible to prevent Hemolytic Disease of the Fetus and Newborn (HDFN) in RhD-negative pregnant women and hemolytic transfusion reactions (HTR) in anti-D carriers. Since DEL-type RBCs are also known to carry at least one C antigen, and none have a cc phenotype, the use of D and C antigen negative RBCs for patients described previously is a rational choice in terms of safe transfusion, cost, and supply-demand balance. [ABSTRACT FROM AUTHOR]

The article discusses attitudes towards urgent RhD-positive transfusions in female patients and the risk of hemolytic disease of the fetus and newborn (HDFN). Surveys show a preference for issuing RhD-negative blood products to women and girls, but due to supply constraints, some centers use RhD-positive products in life-threatening situations. Studies indicate that the public values survival in trauma over the risk of future pregnancy complications, supporting the acceptance of RhD-positive transfusions if RhD-negative products are unavailable. Efforts should still be made to provide RhD-negative products to females of childbearing potential, but the surveys demonstrate a willingness to accept lifesaving interventions when necessary. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

The objectives were to evaluate the descriptive features of newborns with a diagnosis of Rhesus (Rh) hemolytic disease, to determine the morbidity and mortality rates, to evaluate the treatment methods and the factors affecting treatment requirements and clinical outcomes during a ten-year period at a tertiary center. Newborn infants who had a positive direct Coombs test and/or had a history of intrauterine transfusion (IUT) due to Rh hemolytic disease were included. The data regarding the prenatal, natal and postnatal periods were collected from hospital records. A total of 260 neonates were included of which 51.2% were female. The mean ± standard deviation gestational age was 36.9 ± 2.7 weeks. The rate of preterm birth was 41.2%. Of 257 mothers whose obstetric medical history could be accessed, 87.2% were multigravida, whereas 76.3% were multiparous. Among mothers who had a reliable history of anti-D immunoglobulin prophylaxis (n=191), 51.3% had not received anti-D immunoglobulin prophylaxis in their previous pregnancies. The antenatal transfusion rate was 31.7% and the frequency of hydrops fetalis was 8.8%. While combined exchange transfusion (ET) and phototherapy (PT) was performed in 15.4% of the babies, the majority either needed phototherapy only (51.1%) or no treatment (33.5%). The mortality rate was 3.8 % (n = 10), and nine babies out of these 10 were those with severe hydrops fetalis. This study showed that Rh hemolytic disease is still a major problem in developing countries. Multiple comorbidities may occur in addition to life threatening complications, including hydrops fetalis, anemia and severe hyperbilirubinemia. High rates of multiparity and low rates of anti-D immunoglobulin prophylaxis are potential barriers for the eradication of the disease. It should be remembered that Rh hemolytic disease is a preventable disease in the presence of appropriate antenatal follow-up and care facilities. [ABSTRACT FROM AUTHOR]

Background: The Jra antigen is a high-prevalence red blood cell (RBC) antigen. Reports on cases of fatal hemolytic disease of the fetus and newborn and acute hemolytic transfusion reactions suggest that antibodies against Jra (anti-Jra) have potential clinical significance. Identifying anti-Jra is challenging owing to a lack of commercially available antisera. We developed an alternative approach to rapidly predict the presence of anti-Jra using the Taq-Man single-nucleotide polymorphism (SNP)-genotyping method. Methods: Residual peripheral blood samples from 10 patients suspected of having the anti-Jra were collected. Two samples with confirmed Jr(a-) RBCs and anti-Jra were used to validate the TaqMan genotyping assay by comparing the genotyping results with direct sequencing. The accuracy of the assay in predicting the presence of anti-Jra was verified through crossmatching with in-house Jr(a-) O+ RBCs. Results: The TaqMan-genotyping method was validated with two Jr(a-) RBC- and anti-Jraconfirmed samples that showed concordant Jra genotyping and direct sequencing results. Jra genotyping for the remaining samples and crossmatching the serum samples with inhouse Jr(a-) O+ RBCs showed consistent results. Conclusions: We validated a rapid, simple, accurate, and cost-effective method for predicting the presence of anti-Jra using a TaqMan-based SNP-genotyping assay. Implementing this method in routine practice in clinical laboratories will assist in solving difficult problems regarding alloantibodies to high-prevalence RBC antigens and ultimately aid in providing safe and timely transfusions and proper patient care. [ABSTRACT FROM AUTHOR]

The article discusses a case of a baby born with both hemolytic disease of the fetus and newborn (HDFN) and neonatal alloimmune thrombocytopenia. The baby, born prematurely, required treatment including RBC transfusion, IVIg, and phototherapy for HDFN and platelet transfusion for thrombocytopenia. Maternal testing revealed HLA antibodies and anti-HPA-1a, contributing to the baby's condition. This case is the first reported instance of concurrent HDFN and FNAIT in scientific literature. [Extracted from the article]

The article in the journal "Transfusion" discusses the identification of a novel RHD allele with a c.336T>G missense variant in a Chinese individual, resulting in a weakened D phenotype. Serological tests and DNA sequencing were used to identify this rare allele, which was not found in existing genetic databases. The study suggests that the amino acid change at residue 112 may impair membrane integration and D protein expression, leading to the weak D antigen phenotype. This research contributes new insights into the understanding of weak D antigen expression caused by RHD alleles. [Extracted from the article]

The article discusses the prevention of anti-D alloimmunisation in D-negative recipients receiving solid organ transplants from D-positive donors. It highlights the importance of estimating residual D-positive RBCs in recipients post-transplant and administering prophylactic anti-D (PAD) to prevent sensitisation. The study recommends routine administration of 1500 IU PAD for D-negative adult patients following a D-positive SOT to mitigate sensitisation risks. The findings underscore the critical role of PAD administration in safeguarding patients' long-term health outcomes and minimizing complications associated with alloimmunisation events. [Extracted from the article]

Anti‐D antibody is the most common cause of hemolytic disease of the newborn (HDN). Other antigens have emerged, causing significant damage to the newborn. We report a case of a 31‐week dichorionic diamniotic twin born emergently to a mother with anti‐C and anti‐D antibodies who required multiple percutaneous umbilical cord blood sampling (PUBS) and transfusions. Extensive resuscitation at birth was required due to severe anemia, hypovolemia, and prematurity. Ensuing liver damage occurred with subsequent profound coagulopathy, transaminitis, and direct hyperbilirubinemia that required significant support. This patient developed several unique findings including the inability to monitor oxygen saturations due to dermal bilirubin deposits and staining of baby teeth. This case report highlights the importance of early identification of additional Rh antibodies due to concern for development of more severe forms of HDN. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies attacking fetal blood cell antigens. Despite routine antenatal anti-D prophylaxis, intrauterine transfusions (IUTs) are still needed in some HDFN cases. Methods: We conducted a retrospective cohort study on newborns with HDFN born in the 1st Department of Obstetrics and Gynecology of the Medical University of Warsaw. We analyzed 274 neonates with HDFN, identifying 46 who required IUT due to fetal anemia and 228 who did not. The laboratory results, management, and outcomes were compared between these groups. Results: Comparative analysis showed that newborns treated with IUT were more likely to have significant anemia, hyperbilirubinemia, and iron overload, indicated by a high ferritin concentration. These neonates more often required top-up transfusions, phototherapy, intravenous immunoglobulin infusions, and exchange transfusions. The length of stay was longer for newborns who received IUT. Conclusions: HDFN requiring IUT is associated with a greater number of complications in the neonatal period and more often requires additional treatment compared to HDFN not requiring IUT. [ABSTRACT FROM AUTHOR]

The article offers information on the role of inhibiting immunoglobulin G (IgG) to prevent hemolytic disease of the fetus and newborn (HDFN). Topics discussed include the mechanism of action of the monoclonal antibody nipocalimab; the potential benefits of delaying intrauterine transfusion; and the need for further clinical trials to determine its efficacy and safety.

BACKGROUND In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti--neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.) [ABSTRACT FROM AUTHOR]

Background: Antibodies against blood group antigens play a key role in the pathophysiology of haemolytic transfusion reactions (HTRs) and haemolytic disease of the fetus and newborn (HDFN). This study aimed to determine the frequencies of alleles, genotypes, and risk of alloimmunisation of clinically significant blood group systems in ethnic northeastern Thais. Methods: In total, 345 unrelated, healthy, ethnic northeastern Thais were tested using the in‐house PCR‐sequence specific primers (PCR‐SSP) method for simultaneously genotyping of RHCE, Kell, Duffy, Kidd, Diego and MNS glycophorin hybrids and results confirmed by Sanger sequencing. Results: In this cohort, the alleles RHCE*C (81.0%) and RHCE*e (84.8%) were more prevalent than RHCE*c (19.0%) and RHCE*E (15.2%). The most common predicted haplotype combinations of the RHCE alleles were C+c‐E−e+(R1R1) (59.4%) followed by the C+c+E+e+ (R1R2) (20.6%) and C+c+E−e+ (R1r) (11.3%). The KEL*01 allele was not found in this study. The frequencies of FY*01 and FY*02 were 88.3% and 11.7%, respectively. The genotype FY*02/02 was found in four samples (1.2%). The frequencies of JK*01 and JK*02 were 52.5% and 47.5%, respectively. Homozygous JK*02/02 was found in 81 samples (23.5%). The frequencies of DI*01 and DI*02 were 0.6% and 99.4%, respectively. In total, 64 samples (18.6%) were found to carry the MNS glycophorin hybrids. Conclusions: Our results indicated a possible high risk of c, E, Fyb, Jka, Jkb and Mia alloimmunisation in these populations. Moreover, methods established for genotyping clinically significant blood groups in this study can now be utilised in routine clinical application. [ABSTRACT FROM AUTHOR]

Introduction: Anti‐D detection and titration plays a major role in RhD negative antenatal cases both, for monitoring maternal as well as fetal status as well as initiation of early therapeutic interventions, such as intra‐uterine transfusions (IUT) to improve maternal as well as fetal morbidity and mortality and reduce the adverse effects of haemolytic disease of fetus and newborn (HDFN). We conducted a survey focusing on the policies and procedures of anti‐D detection and titration among major tertiary care centres across India. Methodology: The survey was drafted by a working group of transfusion medicine and immunohematology specialists from six different centres in India. Data were obtained via the use of an online questionnaire. Results: Results were categorised into four categories, Hospital information, immuno‐haematological testing methodology, clinical significance of anti‐D testing and the role of transfusion medicine specialists. The survey highlighted the modalities as well as the methodologies of anti‐D detection and titration in antenatal women across different major tertiary care centres in India. Conclusion: This survey provided a unique snapshot of the prevalent methodologies being employed by major tertiary care centres across the country for detection and titration of anti‐D levels as well as the important role it plays in the therapy of affected antenatal women to minimise adverse effects on the fetus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hemolytic disease of the fetus and newborn (HDFN) is the development of anemia, hyperbilirubinemia, and finally hydrops fetalis in the fetus when antibodies to antigens on the surface of erythrocytes are transferred from the placenta to the fetus. The most common cause is D‐HDFN. K (KEL1) from the Kell blood group system is the most potent immunogenic antigen after D among all blood group antigens. K‐HDFN occurs in 0.1–0.3% of pregnant women. It accounts for 10% of cases of antibody‐mediated severe fetal anemia. We present a successful management of Kell alloimmunization in a pregnant woman who had 3 times pregnancy loss with hydrops fetalis due to K‐HDFN and who was proven to have K‐HDFN in the postnatal period in her last pregnancy. [ABSTRACT FROM AUTHOR]

We experienced a case of hemolytic anemia in a baby at late onset from a pregnant woman with anti-E titer, 128 times. Red blood cell (RBC) transfusion performed on day 11 after birth resulted in an improvement in hemoglobin, but anemia recurred 51 days later. We measured the IgG subclass and conducted a Monocyte Monolayer Assay (MMA) over time, and then analyzed the association of the condition of the mother and the child's RBC ratio post-transfusion. Anti-E of the mother and the baby were of the IgG1 type, and MMA rates were low in both. The delayed progression and recurrence of hemolysis in this case were due to the low MMA, resulting from the anti-E derived from IgG1 type, and because the remaining anti-E reacted with the baby's RBCs that were regenerated after transfusion. Neonatal hemolytic disease caused by anti-E, high-titer IgG1 requires long-term follow-up. Analysis of IgG subclasses of irregular antibodies in pregnant women may help predict the pathology of Hemolytic Disease of the Fetus and Newborn (HDFN). [ABSTRACT FROM AUTHOR]

With the use of Anti-D prophylaxis for rhesus D-negative pregnant women, other Rh and non-Rh allo-antibodies have become relatively more important. The index case reports severe hemolytic disease of the newborn due to anti-E antibody in a full-term baby boy born to a COVID-19-positive mother. The antibody screening of the mother performed during Booking of pregnancy at 9th week of gestation was negative. Subsequently the mother was lost to follow-up till delivery due to COVID pandemicity. At birth, the baby was icteric but non-hydropic, his direct antiglobulin test (DAT) was strong positive (4+ by column agglutination technology) and required top-up transfusion and phototherapy at Neonatal Intensive Care Unit. Elution of DAT-positive red cells rendered anti-E which could have formed as "late developing" red cell allo-anti-E in the pregnancy. A repeat antibody screening around 28th week gestation is of prime importance to detect any underlying allo-antibody in a multigravida and thus enabling close monitoring of fetus and initiation of early management as desired. [ABSTRACT FROM AUTHOR]

BACKGROUND: High titers of anti-A and anti-B are considered to be one reason for hemolytic transfusion reactions and ABO hemolytic disease in fetus and neonates. There is no consensus for critical ABO antibody titers to guide transfusion or transplant decisions. Implementation of ABO titer measurement can favor reduction in transfusion reactions in nongroup "O" recipients. AIMS: This study aimed to understand the trend and quantification of anti-A and anti-B antibody titers in Group "O" donors in this geography. SUBJECTS AND METHODS: A prospective study was conducted in 218, Group "O" blood donors in the year 2021, during the COVID-19 pandemic. Immunoglobulin (Ig) M antibody titers were measured by hemagglutination and IgG titers by solid-phase red cell adherence. Antibody titers ≥128 for IgG and ≥64 for IgM were considered "high titers." Epi Info 7.1 software was used for statistical analysis, with P < 0.05 significant. RESULTS: About 96.75% of blood donors were male with a median age of 33.16 ± 8.8 years. ABO antibody titers ranged from 0 to 1024. The prevalence of titers of <128 for IgG anti-A and anti-B was 79.36% and 86.24%, respectively, and 88.53% for both anti-A and anti-B IgM (<64). High IgG anti-A antibody titers were exhibited in 20.64% and anti-B titers in 13.76% of donors. None of the recipients showed any hemolytic reactions. CONCLUSIONS: The donor population showed predominance of low isoagglutinin titers. Defining critical titers will help formulate institutional guidelines on ABO-incompatible platelet transfusions and transplants. The use of automation in ABO titer assays removes interobserver variations and offers precise, reproducible, and less labor-intensive assays in resource-constrained settings. [ABSTRACT FROM AUTHOR]

ABSTRACT: For identification (ID) of irregular antibodies, a standard antibody identification (AI) panel consisting of 18 mandatory antigens expressed on reagent red blood cells is used. The phenotype for each antigen is listed on a red cell antigram provided with each lot of the ID panel. In addition, special type of low-incidence antigens that are clinically significant are separately mentioned on the left- or right-hand column or on the reverse of the antigram. These cases highlight the importance of diligent AI to ensure safe transfusions and prevent adverse transfusion reactions in patients. The ID of rare and low-incidence red cell alloantibodies is important in ensuring safe transfusions and preventing hemolytic disease of fetus and newborn. In routine practice, these types of antibodies are often categorized as having an undetermined specificity due to their rarity and low prevalence in the population. We describe two cases of successful ID of rare and low-incidence red cell alloantibodies, Anti-Colton-b (Co(b)) and Anti-Kpa. Type and screen and irregular AI were performed on Immucor NEO Iris® (SPRCA), for both the female patients. Autocontrol and direct agglutination test were performed by column agglutination technique method (BIO-RAD, Coombs Anti-Ig G cards) and were negative for both the patients. Analysis of respective antigrams was done to rule out or rule in irregular antibodies. Initially, the reaction pattern indicated the presence of anti-Co(b) and anti-Kpa. However, the reaction only occurred in one cell out of the 14 cells tested for both patients. To ensure accuracy, the samples were rerun using different lots using the SPRCA methodology. To confirm the presence of anti-Co(b) antibodies, a selected panel cell was treated with an enzyme to enhance the expression of the Co(b+) antigen. Anti-Co(b) and anti-Kpa alloantibodies were successfully identified and AHG crossmatched; compatible and phenotype-matched blood units were reserved for the patients. Low prevalence antibodies are often missed during antibody screening due to lack of corresponding antigen-positive cells in cell panels or due to their weak reaction pattern and considering it for nonspecific reaction. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and Objectives: "Block D" in hemolytic disease of the fetus and newborn (HDFN) is quite rare and should be evaluated meticulously. We analyzed "Block D" phenomenon in neonates with HDFN due to rhesus (Rh) incompatibilities. The objective of this study was to identify the blocking phenomenon in HDFN by simple, sensitive methods so that they can be implemented in routine practices. Methods: The study was conducted over 10 years, and written informed consent was taken from each participating parent/guardian. Detailed immunohematological workup for "Block D" was done on 11 samples. Complete patient details were obtained from the hospital information system. All laboratory parameters of neonates were observed till discharge from the hospital. Results: All mothers were Rh-D negative with a median age of 28 years. All of them revealed anti-Rh-D antibodies in their serum with titer ranging from 256 to 1024. All neonatal red cells were direct antiglobulin test (DAT) positive and initially Rh-D negative. Rh-D typing on eluted red cells confirmed the presence of D antigen. Strong positive and negative correlations were observed between newborn anti-D immunoglobulin G titer and newborn DAT (r = +0.71, P = 0.031) and newborn DAT and newborn hemoglobin (Hb) (r = −0.78, P = 0.032), respectively. While all neonates received phototherapy, four of them also received exchange transfusion. Gradual increase in mean Hb and decrease in both total serum bilirubin and DAT were observed from day 0 to day 7 (P < 0.05). Conclusion: "Block D" though uncommon signifies the severity of HDFN. Often this phenomenon is missed due to a lack of standard protocol. Through detailed immunohematological characterizations, we could develop a diagnostic pathway to confirm "Block D" in HDFN which can be easily established in the resource-constrained laboratories. [ABSTRACT FROM AUTHOR]

Rh hemolytic disease of the fetus and newborn is a potential risk for D-negative mothers who produce anti-D during pregnancy, which can lead to morbidity and mortality in subsequent pregnancies. To prevent this hemolytic disease, Rho(D) immune globulin (RhIG) is generally administered to D-negative mothers without anti-D at 28 weeks of gestation and shortly after delivery. However, current guidelines suggest that pregnant mothers with molecularly defined weak D types 1, 2, 3, 4.0, and 4.1 do not need RhIG as they are unlikely to produce alloanti-D when exposed to fetuses with D-positive red cells. This issue and the necessity of RHD genotyping have been extensively discussed in Western countries, where these variants are relatively common. Recent evidence indicates that women with Asiantype DEL (c.1227G>A) also do not form alloanti-D when exposed to D-positive red cells. We report that mothers with molecularly defined Asian-type DEL, similar to those with weak D types 1, 2, 3, 4.0, and 4.1, do not require RhIG before and after delivery. Collectively, this review could pave the way for the revision of international guidelines to include the selective use of RhIG based on specific genotypes, particularly in women with the Asian-type DEL. [ABSTRACT FROM AUTHOR]

Background/Objectives: One of the rare causes of cholestasis may be hemolytic disease of the fetus and newborn (HDFN). Methods: We retrospectively analyzed 88 medical records of HDFN newborns with cholestasis and 186 records of children with HDFN without cholestasis and conducted an observational, case-control, retrospective study. Results: Factors influencing the risk of cholestasis were lower gestational age at birth (36.83 ± 1.9 vs. 37.57 ± 1.8, p = 0.002), Rh or Kidd HDFN (80.7% vs. 53.2%), and the need for intrauterine transfusion (27.3 vs. 11.8%). The subjects had lower hemoglobin concentrations at birth (14.01 ± 3.8 vs. 16.39 ± 2.8 g/dL) and during whole hospital stay, higher cord blood total bilirubin concentration (4.26 ± 1.8 vs. 2.39 ± 1.4 mg/dL), higher maximum bilirubin concentration (15.27 ± 5.8 vs. 10.24 ± 3.4 mg/dL), and more frequent liver ultrasound abnormalities (19.9 vs. 6.3%). They also required more extended hospitalization due to higher rates of postnatal blood transfusion (33 vs. 3.8%), more frequent need for exchange transfusion (8.8% vs. 2.2%), more extended time and higher risk of phototherapy (94.3 vs. 59.1%), and higher usage of immunoglobulins (55.7 vs. 8.1%), parenteral nutrition (45.5 vs. 12.9%), and antibiotics (14.8 vs. 4.8%). Conclusions: The risk factors for cholestasis in children with HDFN are lower gestational age at delivery, Rh and Kidd serological type of HDFN, and the need for intrauterine transfusions. [ABSTRACT FROM AUTHOR]

BACKGROUND Hemolytic disease of the fetus and newborn (HDFN) is a type of anemia in the fetus or newborn, characterized by anemia, jaundice, hyperbilirubinemia, and brain damage. IgG is the only antibody that can cross the placenta. The IgG subtypes have a different ability to destroy red blood cells (RBCs). IgG1 and IgG3 can bind to Fc-phagocyte cell receptors and cause hemolysis, while IgG3 has more ability than IgG1. This study aimed to identify the antibody IgG subtype contributing to clinical manifestation differences in HDFN. METHODS This study used blood and umbilical cord blood samples from 30 pairs of mother-baby. The samples were grouped into control (not jaundice/normal bilirubin levels) and jaundice/hyperbilirubinemia groups. A self-developed IgG subtype enzymelinked immunosorbent assay protocol was performed on maternal samples, resulting in optical density. Statistical analysis was performed using SPSS software version 23. RESULTS Blood type was associated with total bilirubin expression (p = 0.005). IgG1 anti-A, IgG3 anti-A, IgG4 anti-A, IgG1 anti-B, IgG3 anti-B, and IgG4 anti-B significantly affected hyperbilirubinemia in newborns (p = 0.041, 0.013, 0.017, 0.028, 0.001, and 0.007, respectively). CONCLUSIONS IgG1 and IgG3 were more significant in causing clinical problems. IgG4 suppressed IgG activation, resulting in no destruction of the infant's RBCs. [ABSTRACT FROM AUTHOR]

Background: A 54‐year‐old Hispanic OPos female with known history of anti‐Rh17 antibodies was diagnosed with Philadelphia‐Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr0, is a high‐frequency antigen composed of several epitopes on the RhCE protein. Anti‐Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens. Anti‐Rh17 antibodies are clinically significant given multiple case reports of hemolytic disease of the fetus and newborn (HDFN). Finding compatible units for patients with anti‐Rh17 can be particularly difficult given that only 1 in 100,000 people are Rh17 negative. Study Design and Methods: Search for compatible units was conducted by the American Rare Donor Program (ARDP) with no leads. After chemotherapy induction and despite erythropoiesis stimulating agent administration, the patient's hemoglobin continued to trend down to a nadir of 2.8 g/dL. Here we report transfusion of incompatible pRBC to this patient with critically symptomatic anemia. HBOC‐201 (Hemopure) was obtained and administered under an emergency compassionate/expanded access designation from the Food and Drug Administration (FDA) under an emergency Investigational New Drug (IND) application. Results and Discussion: Overall difficulties in this case included the challenge of finding compatible units, dilemma of transfusing incompatible units in a patient with severe anemia and obtaining alternatives to blood products. This case report demonstrates the successful use of HBOC‐21 in treating life‐threatening anemia. [ABSTRACT FROM AUTHOR]

Background: We report an obstetric case involving an RhD‐positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low‐prevalence antigen on the paternal and newborn RBCs. Results: Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c.486C>G (GenBank MZ326705) on the RHCE*Ce allele, for both the father and newborn. A subsequent genomic‐based study to profile blood groups in an Indigenous Australian population revealed the same SNV in 2 of 247 individuals. Serology testing showed that the maternal antibody reacted specifically with RBCs from these two individuals. Discussion: The maternal antibody was directed against a novel antigen in the Rh blood group system arising from an RHCE c.486C>G variant on the RHCE*Ce allele linked to RHD*01. The variant predicts a p.Asn162Lys change on the RhCE protein and has been registered as the 56th antigen in the Rh system, ISBT RH 004063. Conclusion: This antibody was of clinical significance, resulting in a mild to moderate hemolytic disease of the fetus and newborn (HDFN). In the past, the cause of such HDFN cases may have remained unresolved. Genomic sequencing combined with population studies now assists in resolving such cases. Further population studies have potential to inform the need to design population‐specific red cell antibody typing panels for antibody screening in the Australian population. [ABSTRACT FROM AUTHOR]

Background: Exchange transfusion (ET) is an effective treatment for acute bilirubin encephalopathy and extreme neonatal hyperbilirubinemia (ENH). It can reduce mortality and morbidity. This study aimed to investigate the trends and risk factors of ENH requiring ET in hospitalized neonates in Iran. Methods: A retrospective analysis of medical records of neonates who underwent ET due to ENH was conducted from 2011 to 2021, in Shiraz, Iran. Clinical records were used to gather demographic and laboratory data. The quantitative data were expressed as mean±SD, and qualitative data was presented as frequency and percentage. P<0.05 was considered statistically significant. Results: During the study, 377 ETs were performed for 329 patients. The annual rate of ET decreased by 71.2% during the study period. The most common risk factor of ENH was glucose-6-phosphate dehydrogenase (G6PD) deficiency (35%), followed by prematurity (13.06%), ABO hemolytic disease (7.6%), sepsis (6.4%), Rh hemolytic disease (6.08%), and minor blood group incompatibility (3.34%). In 28.52% of the cases, the cause of ENH was not identified. 17 (5.1%) neonates had acute bilirubin encephalopathy, of whom 6 (35.29%) had G6PD deficiency, 6 (35.29%) had ABO incompatibility, and 2 (11.76%) had Rh incompatibility. Conclusion: Although the rate of ET occurrence has decreased, it seems necessary to consider different risk factors and appropriate guidelines for early identification and management of neonates at risk of ENH should be developed. The findings of the study highlighted the important risk factors of ENH in southern Iran, allowing for the development of appropriate prevention strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in _4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Anti‐PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti‐PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti‐PP1PK alloimmunization in a 23‐year‐old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti‐PP1Pk titers. Twice‐weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery‐peak systolic velocities (MCA‐PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen‐negative, ABO‐compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA‐PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice‐weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti‐PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti‐PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan. [ABSTRACT FROM AUTHOR]