Erythroblastosis Research Articles

Direct antiglobulin test for the prediction of neonatal hyperbilirubinemia needing an intervention: a systematic review and diagnostic test accuracy meta-analysis

ImportanceThe direct antiglobulin test (DAT) is commonly used as a screening test for predicting significant neonatal hyperbilirubinemia requiring intervention. However, evidence for this approach is limited.ObjectiveThe aim of this study was to evaluate the diagnostic utility of DAT in predicting the need for phototherapy and double volume exchange transfusion (DVET) in neonates with ABO and Rhesus (Rh) incompatibility conditions.MethodsMEDLINE, Embase, CENTRAL, CINAHL, and Web of Science were searched from inception until 1 February 2024. Randomized controlled trials (RCTs) and non-RCTs were eligible for inclusion. Two reviewers screened the titles and abstracts blinded to each other. A Bayesian bivariate random-effects model was employed for the diagnostic test accuracy meta-analyses. Risk of bias was assessed using Quality Assessment for Studies of Diagnostic Accuracy 2 and certainty of evidence (CoE) was adjudged according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines.ResultsIn total, 53 studies were included in the systematic review and 28 were synthesized in the meta-analysis. For the need for phototherapy outcome, the pooled sensitivity [95% credible interval (CrI)] and specificity (95% CrI) of DAT in ABO incompatibility (18 studies, n = 10,110) were 56.1% (44.5%–67.8%) and 83.6% (71.6%–90.8%). For Rh incompatibility (three studies, n = 491), the sensitivity and specificity were 40.4% (12.2%–81.7%) and 89.9% (72.7%–94.6%). The CoE was predominantly low. For the need for DVET outcome, the pooled sensitivity and specificity of DAT in ABO incompatibility (three studies, n = 2,652) were 83.6% (35.8%–99.6%) and 74.5% (40.3%–92.7%). For Rh incompatibility (two studies, n = 240), the sensitivity and specificity were 80.3% (34.2%–97.3%) and 68.0% (25.3%–92.1%). The CoE was predominantly very low.ConclusionIn ABO and Rh incompatibility, DAT probably has moderate specificity and low sensitivity for predicting the need for phototherapy. For DVET, though DAT is possibly a better predictor due to its acceptable sensitivity, the predictive interval was wide. Thus, we do not suggest the routine use of DAT screening to predict the need for phototherapy and DVET. However, it may be used as a second-tier investigation for risk stratification of high-risk neonates.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022297785, PROSPERO (CRD42022297785).

Improving Timely Evaluation of Newborns at Risk for Hemolytic Disease From a Positive Maternal Antibody

Background: Hemolytic disease of the newborn (HDN) is a rare condition with the potential for high morbidity. Local Problem: Practice at a large maternity care center did not align with the American Academy of Pediatrics (AAP) revised hyperbilirubinemia guidelines. Methods: A pre/post-implementation design with Plan-Do-Study-Act cycles was used. Interventions: A clinical pathway was implemented to improve timely evaluation of newborns at risk for HDN due to a positive maternal antibody using cord blood. Results: Cord blood testing increased among the subset of newborns who did not meet collection criteria prior to the practice change (pre: 0% n = 7, post: 39% n = 23). Missed opportunities to test cord blood occurred less frequently post (35 versus 26 days between missed opportunities). Feasibility data identified the need for educational and clinical tools. Conclusions: A clinical pathway and tailored tools support the AAP recommendation. Electronic health record supports could bolster future efforts.

Prenatal, perinatal, and environmental risk factors contribute to the high prevalence of autism spectrum disorder in northeastern Bangladesh

Objectives Autism spectrum disorder (ASD) is a neurodevelopmental condition with increasing prevalence worldwide, including in Bangladesh. This study investigated prenatal, perinatal, and environmental risk factors associated with ASD in northeastern Bangladesh, where data on the disorder is scarce. Methods A cross-sectional study was conducted with 168 children diagnosed with ASD (CWA), 167 typically developing children (TDC), and 185 unaffected siblings (Sib), recruited from five government-approved specialized schools in Sylhet, northeastern Bangladesh. Diagnoses were confirmed using a modified ADI-R/ADOS, and logistic regression was used to analyze associated risk factors. Results Advanced maternal age, firstborn status, and a history of consanguinity were significant prevalence of prenatal/perinatal complications, including birth asphyxia and blood Rh incompatibility, compared to TDC and Sib. A considerable gap in scientific awareness was noted, with many parents attributing their child’s condition to associated with ASD. Parental exposure to mercury-based dental amalgam was also strongly linked to ASD. CWA had a higher generational or religious belief. Conclusions We identified critical risk factors contributing to the high prevalence of ASD in northeastern Bangladesh, underscoring the need for enhanced diagnostic, educational, and healthcare strategies to ensure good health and well-being and to provide quality education for individuals with ASD.

Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn

Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist. To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care. In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024. Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes. The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes. In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.

Hyperbilirubinemia in neonates with blood group incompatibilities - A bane or a boon for the management.

Neonatal hyperbilirubinemia, or newborn jaundice, is a common condition caused by high bilirubin levels. Blood group incompatibility between mother and baby is a major cause. This study examined the link between different blood group incompatibilities and their management in newborns with jaundice. This prospective observational study included 190 neonates with hyperbilirubinemia requiring phototherapy. They were divided into two groups: control (blood group compatible) and case (blood group incompatible). Data on demographics, investigations, and management were collected. Blood group incompatibility was present in 36.3% of cases, primarily ABO (28.9%). Rh incompatibility and ABO+Rh incompatibility accounted for 5.3% and 1.6%, respectively. DAT was positive in 32.7% of ABO incompatible cases, with anti-B more prevalent. Neonates with ABO incompatibility had the highest mean total serum bilirubin (TSB) level (13.04mg/dL) and the largest overall decrease in TSB (-33.77%).The mean phototherapy duration was significantly longer in cases (44.1h) compared to controls (35.5h). ABO incompatible neonates had a longer average phototherapy duration (42.32h) compared to controls. However, ABO+Rh and pure Rh incompatible cases had highest phototherapy duration among cases. Moreover, within ABO cases, the mean phototherapy duration was higher in DAT-positive cases (46h) compared to DAT-negative cases (40.2h). Delivery mode, parity, and gender did not significantly influence phototherapy duration, but gestational age might play a role. Various blood group incompatibilities, beyond RhD, are significantly associated with hyperbilirubinemia requiring phototherapy. ABO incompatibility was the most common cause. Neonatal jaundice is linked to blood group mismatch, with ABO+Rh and pure Rh incompatibility requiring longer phototherapy. However, ABO incompatible cases had longer phototherapy in comparison to controls. Gestational age might influence phototherapy duration.

How I use noninvasive prenatal testing for red blood cell and platelet antigens.

Alloimmunization during pregnancy occurs when a mother produces antibodies against fetal antigens, leading to complications like hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). HDFN involves destruction of fetal red blood cells, potentially causing severe anemia, hydrops fetalis, and fetal death. FNAIT affects fetal platelets and possibly endothelial cells, resulting in risk of intracranial hemorrhage and brain damage. Traditional invasive methods for fetal antigen genotyping, like amniocentesis, carried miscarriage risks. The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma enabled safe, non-invasive prenatal testing (NIPT). Initially used for RhD blood group typing, NIPT now covers various blood group antigens. Advances in technology have further enhanced NIPT's accuracy. Despite challenges such as low cff-DNA fractions and complex genetic variations, NIPT has become essential in managing alloimmunized pregnancies. In NIPT it is important to prevent both false positive results and false negative results. Particularly in the coming decades, more possibilities for personalized antenatal treatment for HDFN and FNAIT cases will become apparent and accurate NIPT blood group antigen typing results are crucial for guiding clinical decisions. In this paper we describe this journey and provide practical tools for the clinic.

Rho(D) immune globulin shortage and fetal Rh(D) screening with cell-free DNA.

Despite the availability of Rh(D) immune globulin (RhIg) to prevent alloimmunization in Rh(D)-negative pregnant patients, anti-Rh(D) alloimmunization remains a prevalent cause of hemolytic disease of the fetus and newborn (HDFN). Recent RhIg shortages have caused clinicians and professional societies to identify methods to prioritize RhIg administration. New cell-free DNA (cfDNA) tests to predict fetal red blood cell antigen genotypes have been proposed as an option to prioritize the administration of RhIg to Rh(D)-negative pregnant people. Commercial laboratories offer fetal Rh(D) genotype testing as part of cfDNA screening for fetal aneuploidy. Studies indicate that these tests have a high sensitivity and specificity for the detection of fetal Rh(D) status. Considering the current RhIg shortage, the American College of Obstetricians & Gynecologists (ACOG) suggests that utilizing cfDNA tests to determine fetal Rh(D) status is a reasonable approach to prioritize RhIg administration when supply is limited. cfDNA screening for fetal Rh(D) status is a reasonable approach to triage the administration of RhIg in the setting of the current RhIg shortage. Utilization of cfDNA screening for fetal Rh(D) and other red blood cell antigen status is likely to increase in routine care. Research, professional society guidance, and education are necessary to ensure well tolerated and equitable utilization.

CHARACTERISTICS OF RELATIONSHIPS BETWEEN BIOCHEMICAL INDICATORS OF CORD BLOOD OF NEWBORNS FROM MOTHERS IN THE RISK GROUP FOR THE DEVELOPMENT OF HEMOLYTIC DISEASE OF NEWBORNS

A hemolytic disease of the newborn may occur when the mother and fetus are incompatible according to the AB0 system or the Rh factor. Hemolytic disease is primarily observed in instances where the mother has blood group 0(I) according to the AB0 system, and in the fetus or newborn, according to the degree and frequency of inheritance, it is A(II), B(III). It is the most prevalent manifestation of the newborn nosology, with the initial stage being growth itself, and the level of total bilirubin (its indirect fraction). It is probable that other clinical and biochemical indicators undergo direct metabolic changes in response not only to the state of progressive hyperbilirubinemia, but also as an adaptive mechanism even in the absence of hemolytic disease in children of this group. The aim of the study. To conduct an analysis of the relationships between the biochemical indicators of umbilical cord blood from mothers with 0(I) blood group and with a negative Rh(D) factor, regardless of the blood group, without signs of hemolytic disease (HDN). Research materials and methods. This work involved the analysis of 30 umbilical cord blood samples, as well as the determination of the infant group (according to the AB0 system) and rhesus blood affiliation. The objective was to assess the main biochemical indicators of the newborn's functional state. The analysis included total and direct bilirubin, total protein, albumin, the calculation of the albumin-globulin coefficient, glucose, urea, creatinine, and the activity of a group of enzymes (ALT, AST, γ-GT, AF, total LDH (LDHtotal)). The statistical calculation of the obtained results was carried out using the Pearson correlation test (rxy). Group comparisons were carried out using the Wilcoxon-Mann-Whitney-Test (for the coincidence of the Rhesus characteristics of maternal and cord blood) and the The Kruskal–Wallis test for comparing the average values ​​of three or more samples (for the coincidence of maternal and cord blood groups when inheriting this characteristic). The ratio of groups and rhesus was evaluated according to Fisher's comparative test (F-distribution). Research results and their discussion. In the correlation analysis of the obtained data, a positive correlation was noted according to the Pearson test between the level of albumin and total protein (rxy=0.867, p=0.000). In the format of nitrogenous exchange, probable changes are also observed between the concentration of urea and total protein (p=0.023), between urea and albumin (p=0.033), and between creatinine and urea (p=0.025). Our studies show positive correlations between the activity of AF and AST (rхy=0.914, р=0.000), between LDHtotal and AST (rхy=0.637, р=0.000), as well as between LDHtotal and AF (rхy=0.517, p=0.004). All these indicators are important for a comprehensive assessment of biochemical homeostasis. It was found that the inheritance from mother to child of the rhesus and group traits also affects the value of ALT, AST, creatinine. Concusions. The analysis of umbilical cord blood indicators in a small group of samples (30) indicates probable changes and correlational relationships between them. To enhance the reliability and significance of the data, we intend to expand the number of samples under study. This will enable us to either substantiate or invalidate the current findings and, in due course, establish reference values for the Bukovyna region.

Fc mutagenesis enhances the functionality of anti-RhD monoclonal antibodies.

Haemolytic disease of the foetus and newborn (HDFN) due to Rhesus D (RhD) antigen mismatch between the mother and foetus has been a significant cause of neonatal jaundice, recurrent miscarriage and stillbirth throughout history. Anti-RhD prophylaxis using polyclonal immunoglobulin G (RhD-pIgG) derived from the plasma of RhD-negative donors immunised with RhD-positive red blood cells (RBCs), has reduced the incidence of HDFN, but this approach is currently restricted to developed countries. Monoclonal antibodies (mAbs) offer a promising alternative to address this pressing need, but prior attempts to develop effective anti-RhD mAbs have failed, in some cases due to differences in fucosylation patterns between mAbs produced in cell lines and RhD-pIgG. CHO cell lines, commonly used for pharmaceutical protein production, induce high levels of fucosylation, reducing the antibody-dependent cellular cytotoxicity (ADCC) activity crucial for clearing RhD-positive RBCs. In contrast,RhD-pIgG has lower fucosylation levels, which enhances ADCC activity. Regulating the glycan levels of mAbs during production requires specialized cell lines and culture conditions. In this study, we took an alternative approach through antibody engineering. The Fc regions of two existing anti-RhD mAbs (Brad3 and Fog1) were subjected to mutagenesis to introduce ADCC enhancing mutations and then expressed in CHO cells under standard conditions. We demonstrate that targeted Fc mutagenesis significantly enhanced ADCC compared to the wild-type mAbs, while preserving RhD binding and efficient production in CHO cells. Furthermore, these Fc variants achieved comparable efficacy to RhD-pIgG, suggesting a new strategy for producing anti-RhD mAbs with improved functionality, without the need for glycoengineering.

The Use of Novel Therapies in the Management of Haemolytic Disease of the Fetus and Newborn (HDFN): Scientific Impact Paper No. 75.

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.

Onasemnogene Abeparvovec is Safe in Hemolytic Disease of the Newborn: A Case Report.

Spinal muscular atrophy (SMA) is a rare autosomal recessive genetic disease caused by Survival Motor Protein 1 (SMN1) gene mutations. Classically divided into three types, SMA is characterized by hypotonia, weakness, and tongue fasciculation in the first 6 months of life in type 1, inability to walk and limb weakness in type 2, and failure to run with proximal weakness in type 3 SMA. With the advent of newborn screening, treating presymptomatic patients with Onasemnogene abeparvovec (OA) is the treatment of choice in some centers worldwide. The incidence of jaundice is high in this age group, with no recommendation to guide the use of OA in newborns with jaundice. To our knowledge, treating an SMA patient with alloimmune hemolytic disease of the newborn (HDN), a relatively common disease in the newborn period, has never been reported in the past. We report our experience with dosing a presymptomatic child with SMA who had neonatal jaundice and hemolytic anemia due to hemolytic disease of the newborn who tolerated the treatment well. To our knowledge, this is the first case to report the safety of this novel treatment for an SMA patient with alloimmune HDN.

A Comparative Analysis of the Efficacy of Blood Exchange Therapy in Neonatal Hyperbilirubinemia Induced by ABO and Rh Incompatibility.

This study challenges the prevailing view that hemolytic diseases of the newborn (HDN) associated with the Rh blood group system are more severe than those caused by the ABO system. The objective was to assess the effectiveness of exchange transfusion (ET) in managing HDN, with a focus on comparing treatment outcomes between ABO and Rh incompatibility cases. A study enrolled 125 neonates diagnosed with hyperbilirubinemia, comprising 66 males and 59 females. The gestational age of the neonates ranged from 33 to 41weeks, and their birth weights varied between 2.11 to 4.3 kilograms. Based on the etiology of hemolysis, the study categorized 73 cases as ABO group and 52 as Rh group. Post- ET, there was a significant reduction in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet (PLT) counts (P<0.001). Pre- ET, differences in SIB and PLT were noted between neonates with ABO and Rh incompatibilities (P<0.05). There was no statistically significant disparities in the therapeutic effects of ET on STB, SIB, and PLT levels when comparing male and female neonates across both the ABO and Rh incompatibility groups. Our study demonstrated that ET is efficacious in reducing bilirubin levels and platelet counts in neonates presenting with ABO and Rh blood group incompatibilities. Notably, the effectiveness of ET was found to be independent of the neonates' gender, a finding that underscores the universal applicability of this treatment approach. Our study observation contradicts the prevalent belief that HDN associated with the Rh system is inherently more severe than that linked to the ABO system. This revelation underscores the imperative for the swift implementation of ET in managing cases of severe hyperbilirubinemia.

Clinical Characteristics and Prognosis of Hemolytic Disease of the Newborn Caused by Irregular Antibodies: A 13-Year Retrospective Analysis.

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. 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). 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). 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.

Retrospective analysis of neonatal hyperbilirubinemia at Hiwot Fana Comprehensive Specialized Hospital, Ethiopia: prevalence, associated factors, and treatment outcome

BackgroundNeonatal hyperbilirubinemia, a condition marked by yellow discoloration of the skin and eyes due to elevated bilirubin levels, poses significant risks including kernicterus, a severe form of bilirubin encephalopathy. Understanding its prevalence, associated factors, and outcomes is crucial for effective management.ObjectivesThis study aimed to assess the prevalence, associated factors, and treatment outcomes of neonatal hyperbilirubinemia at Hiwot Fana Comprehensive Specialized Hospital, Eastern Ethiopia.MethodologyA hospital-based, cross-sectional study was conducted. We reviewed the medical charts of 328 neonates admitted to the Neonatal Intensive Care Unit of Hiwot Fana Comprehensive Specialized Hospital between January 1, 2019, and December 30, 2020. Data were collected using a checklist and analyzed with SPSS version 22, employing descriptive statistics and logistic regression.ResultThe prevalence of neonatal hyperbilirubinemia was 44.2% (95% CI 38.9, 49.6). Sepsis (66.9%) and Rh incompatibility (4.8%) were prevalent among neonates with neonatal hyperbilirubinemia. Prematurity and age at admission were significantly associated with neonatal hyperbilirubinemia. Most neonates with neonatal hyperbilirubinemia (94%) were treated with phototherapy alone, while a smaller proportion (6%) required a combination of phototherapy and exchange transfusion. The overall improvement rate was 93.8%, with a mortality rate of 1.4% due to bilirubin encephalopathy.ConclusionNeonatal hyperbilirubinemia was prevalent among neonates admitted to Hiwot Fana Comprehensive Specialized Hospital, with significant associations to age at admission, prematurity, and sepsis. Effective management, including timely phototherapy and addressing resource shortages, is crucial to improving neonatal outcomes.

Identifying Hemolytic Disease of the Fetus and Newborn within a Large Integrated Health Care System.

This study aims to identify hemolytic disease of the fetus and newborn (HDFN) pregnancies using electronic health records (EHRs) from a large integrated health care system. A retrospective cohort study was performed among pregnant patients receiving obstetrical care at Kaiser Permanente Southern California health care system between January 1, 2008, and June 30, 2022. Using structured (diagnostic/procedural codes, medication, and laboratory records) and unstructured (clinical notes analyzed via natural language processing) data abstracted from EHRs, we extracted HDFN-specific "indicators" (maternal positive antibody test and abnormal antibody titer, maternal/infant HDFN diagnosis and blood transfusion, hydrops fetalis, infant intravenous immunoglobulin [IVIG] treatment, jaundice/phototherapy, and first administrated Rho[D] Immune Globulin) to identify potential HDFN pregnancies. Chart reviews and adjudication were then performed on select combinations of indicators for case ascertainment. HDFN due to ABO alloimmunization alone was excluded. The HDFN frequency and proportion of each combination were fully analyzed. Among the 464,711 eligible pregnancies, a total of 136 pregnancies were confirmed as HDFN pregnancies. The percentage of the HDFN-specific indicators ranged from 0.02% (infant IVIG treatment) to 34.53% (infant jaundice/phototherapy) among the eligible pregnancies, and 32.35% (infant IVIG treatment) to 100% (maternal positive antibody test) among the 136 confirmed HDFN pregnancies. Four combination groups of four indicators, four combination groups of five indicators, and the unique combination of six indicators showed 100% of HDFN pregnancies, while 80.88% of confirmed HDFN pregnancies had the indicator combination of maternal positive antibody test, maternal/infant HDFN diagnosis, and infant jaundice/phototherapy. We successfully identified HDFN pregnancies by leveraging a combination of medical indicators extracted from structured and unstructured data that may be used in future pharmacoepidemiologic studies. Traditional indicators (positive antibody test results, high titers, and clinical diagnosis codes) alone did not accurately identify HDFN pregnancies, highlighting an unmet need for improved practices in HDFN coding. · A case ascertainment method was developed to identify HDFN from structured and unstructured data.. · The method used in this study may be used in future pharmacoepidemiologic studies.. · The study highlighted an unmet need for improved practices in HDFN coding..

Clinical profile of neonatal jaundice patients admitted in a tertiary care hospital in Khulna, Bangladesh

Background: A significant proportion of term and preterm infants develop neonatal jaundice. Jaundice in an otherwise healthy term infant is the most common reason for readmission to the hospital. Therefore, it is necessary to evaluate different aspects of neonatal jaundice in our clinical setup. Objective: The objective of this research was to find out different associated causes, clinical features, and treatment options for neonatal jaundice. Methods: A cross-sectional study was conducted in Gazi Medical College Hospital (GMCH), Khulna, Bangladesh with a total number of 140 neonates with jaundice from January 2018 to January 2021. All data were collected and analyzed prospectively. Convenient purposive sampling was the sampling method. Results: In this study, 79.2% of neonates were full-term and 20.8% were preterm neonates. Physiological jaundice (33.5%) was found as the commonest type. Jaundice with infection was associated with 32.8% of cases. Jaundice with umbilical redness, discharge, and/or foul-smelling (17.9%), and reluctance to feed were commonly associated symptoms. Hepatomegaly and splenomegaly were detected in 7.1% and 3.6% neonates respectively. Phototherapy was given in 61% of cases and 17.8% (25) cases exchange therapy was required. In neonates with physiological jaundice, phototherapy was recommended for most of the cases. In the case of ABO and Rh incompatibility, exchange therapy was required most often along with phototherapy. Conclusion: Physiological jaundice is the most common pattern of neonatal jaundice. Most often, neonatal jaundice may co-exist with neonatal infections. In most cases, phototherapy is required along with or without exchange therapy, depending upon the associated causes and conditions. Mediscope 2024;11(2): 58-61

Evaluation of Anti-k Antibody in a Patient Undergoing Redo Sternotomy

Abstract Introduction/Objective Introduction: The Kell blood group system, discovered in 1946, holds paramount significance in transfusion medicine and hemolytic disease of the newborn (HDN). Named after Mrs. Kelleher, who exhibited anti-Kell antibodies resulting in HDN, this system comprises 25 antigens, with the original K antigen retaining primary importance. Additionally, Levine et al. identified anti-Cellano, now known as anti-k, presenting an antibody antithetical to anti-K. Methods/Case Report Case Presentation: A 60-year-old male with a history of bioprosthetic aortic valve insufficiency, pulmonary homograft stenosis, and recurrent aortic insufficiency presents for a fourth redo sternotomy for root and ascending aorta replacement. Preoperative assessment revealed a positive antibody screen for anti-k, a clinically significant antibody associated with decreased survival of transfused red blood cells (RBCs). Given limited compatible blood units available, efforts are underway to secure additional donations before the scheduled surgery on 2/22/24. The patient’s medical history indicates no recent blood transfusions or iron therapy, with the last transfusion in 1996. He is anticoagulated with warfarin for mechanical valve and atrial fibrillation, necessitating preoperative bridging with Lovenox injections. Methods The patient’s antibody screen and initial panel demonstrated pan-reactivity with 3+ reactivity, suggesting an antibody targeting a high-frequency antigen. Further testing using polyethylene glycol (PEG) confirmed the presence of anti-k, supported by negative reactions to additional K-negative cells. The absence of other clinically significant antibodies was verified using 0.2 M Dithiothreitol (DTT) modified cells. Results (if a Case Study enter NA) NA Conclusion Conclusion: The identification of anti-k antibody underscores the critical role of preoperative antibody screening in mitigating transfusion-related complications, particularly in patients requiring complex surgical interventions. Collaborative efforts between clinical teams and transfusion medicine specialists are imperative to ensure adequate blood product availability and optimize patient outcomes.To prevent further exposure, it is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they possess.k antigen blood donors are underrepresented in the general donor pool. It is recommended to develop a systematic recruitment for k antigen donors.

Genotyping for Weak and Partial D Rh Status to Optimize Usage of Limited Blood Supplies

Abstract Introduction The Rh antigen group, expressed on erythrocytes and encoded by highly polymorphic RHD and RHCE genes on chromosome 1 (1p36-p34), is notable in transfusion medicine due to its high polymorphism, strong immunogenicity and ability to cause hemolytic transfusion reactions in patients and hemolytic disease of the fetus and newborn (HDFN). The D antigen specifically contains multiple epitopes with variations that include decreased expression (weak D) or loss of certain epitopes (partial D) which expose patients to risk of alloimmunization depending on the subtype of the Rh(D) antigen. Hence, serologic weak D testing followed by molecular testing is not performed except for donors testing negative for Rh(D) antigen and newborns typing negative for Rh(D) and born to Rh(D) negative mothers. Given the current shortages of blood supplies, understanding patients’ genotypes in the context of weak or partial D-typing and risk of alloimmunization can be essential in the management of increasingly limited supplies of red blood cell (RBC) units. Objective To further characterize patients that initially type negative for Rh(D) but positive for weak D with molecular testing to investigate risk of alloimmunization, retype the Rh(D) and avoid unnecessary use of Rh(D) negative RBC units during critical shortages of RBC units. Methods We collected the results of ABO/Rh(D) typing for patients with negative Rh(D) testing but positive weak D test over a period of four weeks in December 2023 and had D-variant molecular testing performed by a reference laboratory. Initial serologic ABO/Rh(D) was performed in tube followed by weak D testing by indirect Coombs test in tube. Results The total number of patients who initially tested negative for Rh(D) but positive (weak to +4) for weak-D was three patients. Two patients showed a probable genotype of RHD*01W.1 (RHD* weak type 1, 809T&amp;gt;G (V270G)) homozygous which indicated the presence of weak D+ type 1. Patients with weak D+ type 1 can receive Rh(D) positive red cell units, and they are not at risk of alloimmunization and developing anti-D. The third patient showed a probable genotype RHD*DVI type 2 homozygous (lack of Rh(D) exons 4 through 6) and indicated the presence of partial D antigen. Patients with partial D antigen should receive RH(D) negative red cell units as they are at risk of alloimmunization and developing anti-D. Conclusions Although the vast majority of Transfusion Medicine services do not perform the serologic weak D test with reflex to molecular testing, characterizing patients who test negative with initial serologic Rh(D) testing with serologic and molecular D-tests may aid in retyping the Rh(D) of patients during critical shortages, particularly for patients with ABO blood group O.

Anti-LAN Antibodies: Clinical Implications and Case Presentation

Abstract Introduction/Objective The LAN system, originating from the 901 Series of High Incidence antigens, transitioned to a recognized System in 2012. The LAN antigen, situated on ABCB6, a multipass membrane protein associated with porphyrin transport, plays a crucial role in heme synthesis. Functionally, LAN acts as an ATP-binding cassette transporter on the red blood cell membrane. Comprising a single antigen, LAN exhibits elevated expression in various tissues including the heart, skeletal muscles, fetal liver, mitochondrial membrane, eye, and Golgi apparatus. Notably, LAN shows no specific association with any particular geographic or ethnic group. Resistant to Ficin/Papain, Trypsin, α-Chymotrypsin, and 0.2M DTT, LAN antibodies primarily consist of IgG and necessitate IAT for detection. While Anti-LAN has been implicated in Hemolytic Transfusion Reactions (HTRs), its involvement in Hemolytic Disease of the Fetus and Newborn (HDFN) remains infrequent. LAN-negative blood is exceedingly rare, often requiring Monocyte Monolayer Assay Testing (MMA) for clinical assessment. Methods/Case Report Case Presentation: An 81-year-old female with a medical history including seizure disorder, hypertension (HTN), hyperlipidemia (HLD), gastroesophageal reflux disease (GERD), small bowel obstruction, and high-grade de-differentiated metastatic retroperitoneal liposarcoma presented for preoperative evaluation. A type and screen ordered as part of outpatient preoperative assessments revealed a positive antibody screen. Further investigation traced the origin of the anti-LAN antibody to an external facility since 2017. Antibody identification indicated the reactivity of the patient’s plasma with all cells (1+ AHG in PEG), excluding the auto control. Utilizing rare frozen antisera anti-LAN, the patient was phenotyped for LAN, yielding a LAN-negative status. Subsequent testing with three rare frozen LAN-negative group O cells aimed to exclude clinically significant antibodies. Differential adsorption, employing a comprehensive baseline RBC phenotype record obtained from the external facility, ruled out anti-E, anti-K, and anti-Fyb, thereby confirming Anti-LAN specificity. Results (if a Case Study enter NA) NA Conclusion The exceptional rarity of LAN-negative blood underscores the high prevalence of reactivity to Anti-LAN antibodies, exceeding 99% in most populations. In select cases, autologous transfusion may emerge as a viable management strategy. Consequently, the patient’s surgical procedure has been deferred, with no immediate requirement for blood products.

Red Blood Cell (RBC) Antigen Confirmation Workflow – A Positive Impact at an Academic Medical Center

Abstract Introduction/Objective Introduction: Blood group antigens, present on the surface of red blood cells (RBCs), play a crucial role in transfusion medicine. These antigens are recognized serologically and form the basis of RBC phenotyping. Understanding the significance of antigen-negative RBCs is essential for mitigating the risk of hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). This study aims to assess the impact of implementing a new RBC antigen confirmation workflow on transfusion service efficiency and patient outcomes. Methods/Case Report Method: The study involved collaboration between our Transfusion Services Department (TS), the Blood Center supplier, and the Apheresis department. A comprehensive review of historical practices and FDA recommendations regarding RBC antigen labeling was conducted. Changes were implemented to streamline antigen confirmation testing and labeling processes. The impact on TS workload, turnaround time, and patient care metrics was evaluated. Results (if a Case Study enter NA) Results: Implementation of the new RBC antigen confirmation workflow led to a significant reduction in antigen confirmation tests performed by TS, with a 607% decrease observed from 2020 to 2023. Concurrently, the workload for reference lab workups increased by 337% over the same period. This shift in workload distribution allowed TS staff to focus more on patient reference workup cases and case review. The improved workflow efficiency resulted in enhanced turnaround times for providing patients with antigen-negative RBCs, ultimately improving the patient experience. Conclusion Conclusion: The adoption of the new RBC antigen confirmation workflow has resulted in compliance with FDA labeling requirements, efficient utilization of TS staff resources, and decreased turnaround times for blood delivery. These improvements have positively impacted patient care by ensuring timely access to compatible blood products. Future steps include developing reports to track turnaround time for patients with special blood product needs and continuing collaboration with the blood supplier and the Apheresis department to optimize inventory management and transfusion processes.