Erythroblastosis Research Articles

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>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.

DIAGNÓSTICO E MONITORAMENTO DA ERITROBLASTOSE FETAL: UMA REVISÃO DA LITERATURA

The text addresses fetal erythroblastosis, a serious condition resulting from blood incompatibility between mother and fetus, generally due to the Rh factor. Initially, the discovery of the ABO and Rh blood systems is discussed, highlighting the importance of the latter for understanding the disease. Objective: to understand the pathophysiological mechanisms of fetal erythroblastosis, focusing on Rh incompatibility, thereby analyzing the impacts of fetal erythroblastosis on health of the fetus and newborn.Methods: The work is a bibliographical review where topics such as pathophysiology, diagnosis and prevention of the disease studied were researched.Conclusion: Diagnosis is essential, being done through prenatal exams, such as the Coombs test, which detects the presence of maternal antibodies against fetal antigens. Treatment includes administration of anti-Rh immunoglobulin to prevent the mother’s sensitization to the baby’s Rh factor. Prevention also involves the administration of this immunoglobulin during pregnancy and after birth, if necessary, to avoid future complications and ensure the baby’s safety.

Neonatal Jaundice Risk Factors and Multidirectional Intensive Phototherapy Management at Azadi Teaching Hospital in Kirkuk City

Background: A common illness in infants, neonatal jaundice is caused by high bilirubin levels in the first few days of life, which results in yellowing of the skin and eyes. Aim: This study aims to explore neonatal jaundice risk factors and assess the efficacy of multidirectional intensive phototherapy management at Azadi Teaching Hospital in Kirkuk City. Patients and Methods: In this retrospective cross-sectional study spanning from April 1st, 2021, to October 1st, 2021, a total of 497 newborns were examined. Jaundiced neonates underwent intensive phototherapy utilizing the Bilisphere 360 system, which featured a chamber with 16 cylindrical, blue TL 20W/52 fluorescent tubes. The newborns were positioned on a gauze hammock suspended at the chamber's center, illuminated on all sides. Results: A study found that neonatal jaundice affects 50.70% of studied neonates, primarily in the 16-21-day age group, with males accounting for 57.95% of the sample. 94.84% of neonates experience jaundice due to ABO blood group incompatibility and 88.10% due to Rh incompatibility. Additionally, 77.78% of term deliveries are associated with jaundice. Infants with jaundice have higher Thyroid Stimulating Hormone (TSB) and Thyroid Stimulating Hormone (TSH) levels and a younger mean age compared to non-jaundiced infants. Bilisphere 360 proves significantly more effective in the critical 12 to 48 hours after admission, with a mean total bilirubin of 10.71 ± 1.01 mg/dl compared to 14.65 ± 1.71 mg/dl for Neonatal Exchange Transfusions (P-Value: 0.001). Factors like blood group incompatibility, labor duration, and birth weight influence TSB levels in jaundiced neonates. The Bilisphere 360 method is found to be more effective in managing neonatal jaundice than Neonatal Exchange Transfusions in reducing total bilirubin levels.

Design of a Phase 3, Global, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab is a neonatal fragment crystallizable (Fc) receptor (FcRn)-blocking monoclonal antibody that inhibits placental immunoglobulin G (IgG) transfer and lowers circulating maternal IgG levels. In an open-label, single-arm, phase 2 study, nipocalimab demonstrated evidence of safety and efficacy that support further investigation in a pivotal phase 3 trial of recurrent hemolytic disease of the fetus and newborn (HDFN). The phase 3 AZALEA study aims to evaluate the efficacy and safety of nipocalimab in a larger population at risk for severe HDFN, defined as HDFN associated with poor fetal outcomes or neonatal death. AZALEA is a multicenter, randomized, placebo-controlled, double-blind, phase 3 study enrolling alloimmunized pregnant individuals (N ≈ 120) at risk for severe HDFN based on obstetric history. Participants are randomized 2:1 to receive intravenous 45 mg/kg nipocalimab or placebo weekly from 13-16 to 35 weeks gestational age (GA). During the double-blind treatment period, participants receive standard-of-care weekly monitoring for fetal anemia until planned delivery at 37 to 38 weeks of GA. Postnatal follow-up periods are 24 weeks for maternal participants and 104 weeks for neonates/infants. The primary endpoint is the proportion of pregnancies that do not result in intrauterine transfusion (IUT), hydrops fetalis, or fetal loss/neonatal death from all causes. Key secondary endpoints include the severity of HDFN as measured by a composite HDFN severity index, the earliest time to occurrence of IUT or hydrops fetalis, the modified neonatal mortality and morbidity index in liveborn neonates, and the number of IUTs received. Other endpoints are safety, patient- and caregiver-reported outcomes, pharmacokinetics, pharmacodynamics (e.g., IgG, FcRn receptor occupancy), and immunogenicity of nipocalimab. AZALEA, the first placebo-controlled, randomized, multicenter, prospective trial in severe HDFN, is designed to evaluate the safety and efficacy of nipocalimab, a potential preventive and noninvasive intervention, in at-risk HDFN pregnancies. · Severe HDFN leads to poor fetal/neonatal outcomes.. · IUTs are associated with complications and fetal loss.. · Nipocalimab blocks IgG recycling and placental transfer.. · Nipocalimab reduces fetal anemia and IUTs in early-onset severe HDFN.. · The phase 3 AZALEA study evaluates nipocalimab in severe HDFN..

Characterization of blood bank and transfusion medicine practices for pregnant individuals with fetuses at risk of hemolytic disease in the United States.

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. 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. 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. 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.

Karl Landsteiner (1868-1943): A Versatile Blood Scientist.

Karl Landsteiner (1868-1943) was an Austrian-American biologist, physician, and immunologist whose groundbreaking discoveries revolutionized the fields of transfusion medicine, immunology, and virology. His most famous work was the identification of the ABO blood group system in 1901, which explained the causes of transfusion reactions and laid the foundation for safe blood transfusions. This discovery earned him the Nobel Prize in Physiology or Medicine in 1930. Landsteiner continued his research, identifying the MN and P blood group system in 1927 and the Rh blood group system in 1940, which addressed the complexities of the Hemolytic Disease of the Fetus and Newborn (HDFN). His work on the poliovirus in 1908, in collaboration with Erwin Popper, established the infectious nature of the disease and laid the groundwork for future vaccine development. Landsteiner's versatility as a scientist is evident in the breadth of his work, spanning hematology, immunology, and virology. His ability to navigate diverse fields and see connections between them allowed him to make pioneering discoveries that have had a lasting impact on medical practice, particularly in blood transfusion, organ transplantation, and immunotherapy. Landsteiner's legacy as the "Father of Transfusion Medicine" is reinforced by the standardization of blood typing procedures, which have saved millions of lives worldwide.

Incidence and risk factors of neutropenia in neonates with hemolytic disease of the newborn

Background Hemolytic disease of the newborn (HDN) is a less recognized cause of neonatal neutropenia. Therefore, this study aims to estimate the incidence of neutropenia and identify associated factors in infants with HDN at a tertiary care center. Methods This retrospective cohort study included infants with HDN who presented at a tertiary care center in Saudi Arabia between March 2008 and September 2023. Neutropenia was defined as an absolute neutrophil count of less than 1.5 μL. Results Among 339 neonates with HDN, 50.1% were male, and 49.9% were female. Rh isoimmunization was the most common antibody type, observed in 58.7% of cases. The severity of HDN was classified as mild in 62.6% of neonates, moderate in 33.3%, and severe in 4.1%. Neutropenia was more prevalent in moderate-to-severe HDN cases (P = 0.047). The incidence rate of neutropenia was 4.1 per 1,000 person-days, with 7.4% of neonates (25/339) being neutropenic at birth. Among these, 17 out of 25 neonates showed resolution within 2 days. Multivariate analysis identified male gender (P = 0.022), low gestational age (P = 0.008), low birth weight (P = 0.039), and the need for exchange transfusion (P = 0.036) as significant risk factors for neutropenia. Conclusion Neutropenia in infants with HDN, irrespective of antibody type, is generally a benign, self-limiting condition. This condition predominantly affects male neonates with moderate-to-severe HDN and prematurity and can be managed conservatively.

Management and Treatment Outcomes of Hemolytic Disease of the Fetus and Newborn (HDFN)-A Retrospective Cohort Study.

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.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn

BackgroundIn 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.MethodsIn 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%).ResultsLive 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.ConclusionsNipocalimab 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.)

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

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. 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). 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%). 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.

Feto-maternal outcome of Rh-Negative pregnancy presenting in a tertiary healthcare centre

Background: The term "Rhesus incompatibility" describes the mismatched Rh types of the mother and the fetus. It is linked to the onset of hemolytic disease of the newborn (HDN) ranging from haemolytic anemia to hydrops fetalis and also related to maternal Rh sensitization. The disease incidence is currently declining globally, having dropped from 1.3%–1.7% in the 1980s to 0.17% in the 1990s1. Erythroblastosis foetalis is one of the most terrible consequences of an ABO incompatible or Rh incompatible pregnancy. About 10% of all Rh-negative pregnancies result in Rh incompatibility in the Rh-negative mother carrying a Rh-positive fetus. Methods: This observational study was carried out among 60 Rh negative pregnant women attending our antenatal clinic and delivered in our institution from October 2022 to March 2024.The Rh negative women were followed up with a series of investigations such as Indirect Coombs Test (ICT), MCA-PSV and with regular antenatal care (ANC). After birth neonates were followed up with blood grouping and Rh typing, direct coombs test (DCT), duration of phototherapy, duration of NICU stay , need for immunoglobulin and exchange transfusion were recorded to evaluate the maternal and neonatal outcomes.The data was collected and tabulated in Microsoft excel sheet and the percentages were calculated. Results: This study included a total of 60 Rh negative mothers ,where 48 (80%) of them were aged less than 30 years and 12 of them (20%) were more than 30 years of age. Antenatally, 51 (85%) women were ICT negative and received RAADP, 9(15%) women were ICT positive and anti D titres were less than 1:16 followed up with MCA-PSV which was normal/less than 1.5MoM. The total preterm births were 6(10%).The total admissions to NICU were 12(20%) in our study. All the 9 babies born to ICT positive mothers turned out to be Direct Coombs test (DCT) positive and were managed with double surface phototherapy. For 2(3.3%) babies, human immunoglobulin was given. Only 1(1.6%) baby required exchange transfusion. Conclusion: We conclude that, severe hyperbilirubinemia and hydrops foetalis, which were observed previously are drastically reduced with recent advances and the use of Routine antenatal Anti D prophylaxis (RAADP). Neonatal morbidity and mortality reduced drastically with newer advances like immunoglobulin reducing the need for exchange transfusion and better NICU care. ICT positivity of 15% despite of postnatal immunisation suggest that there is chances of silent fetomaternal haemorrhage during antenatal period, health care professionals should be more knowledgeble with prenatal screening, the value of blood grouping and Rh typing, anti-D immunisation following sensitising events like MTP, abortion, ectopic pregnancy, ECV and regular implementation of RAADP in clinical practice.

Screening and Identification of Erythrocyte Antibodies: A Narrative Literature Review

Red blood cell (RBC) alloimmunization, the development of antibodies against foreign red blood cell antigens, is a critical concern in transfusion medicine. Alloantibodies can lead to adverse transfusion reactions, including hemolytic disease of the fetus and newborn (HDFN) and delayed hemolytic transfusion reactions (DHTR). This comprehensive literature review explores the intricacies of RBC alloimmunization, focusing on the screening and identification of erythrocyte antibodies. We delve into the prevalence and clinical significance of various alloantibodies, the underlying immunological mechanisms, and the evolution of laboratory techniques for their detection. Additionally, we discuss the challenges and future directions in managing alloimmunization, emphasizing the importance of personalized medicine and innovative approaches to ensure safe and effective blood transfusions.

Maternal IgG in hemolytic disease of the fetus and newborn-ABO incompatibility

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 enzyme-linked 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.

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

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. 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. 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). 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.

Metabolomics-based study on the significance of differential metabolite binding IgG isoforms in Hemolytic disease of newborn

ABSTRACT 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.

Exchange Transfusion Trends and Risk Factors for Extreme Neonatal Hyperbilirubinemia over 10 Years in Shiraz, Iran.

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. 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. 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. 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.

Incidence and Risk Factors of Cholestasis in Newborns with Hemolytic Disease-A Case-Control Study.

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.