A cold case of hemolytic disease of the fetus and newborn resolved by genomic sequencing and population studies to define a new antigen in the Rh system.

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.

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

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

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

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

Successful management of severe Kell alloimmunization in pregnancy with intravenous immune globulin.

Hemolytic Disease of the Fetus and Newborn (HDFN) is a condition that affects 1 to 2 out of 1000 patients during pregnancy (1). When an alloantibody is present, it is essential to identify its nature in order to organize appropriate follow-up. Kell-mediated HDFN is rare; it occurs in about 5% of Kell alloimmunized pregnant women. It is important to note that in case of anti-Kell immunization, the severity of HDFN is not correlated with maternal antibody titers, and anemia tends to occur earlier and more severely. Therefore, early diagnosing and management of this condition is crucial. In the management of severe fetal anemia due to Kell immunization, available treatments include in utero transfusion (IUT), immunoglobulin therapy. Other alternative treatments exist, such as plasmapheresis. Intravenous immunoglobulin (IVIG), a noninvasive therapeutic approach, acts through multiple mechanisms. IVIG has been evaluated in cases of RhD immunization with high maternal antibody titers and a history of pregnancies involving early hydrops or intrauterine death. Regarding the potential benefits of intravenous IgG therapy, it may delay the need for early IUT, reduce the overall reliance on IUT, and have a positive impact on obstetric outcomes. This case of IV IgG therapy of anti-Kell immunization offers a thought-provoking avenue for future exploration.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

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.

A single-center, retrospective analysis of 17 cases of hemolytic disease of the fetus and newborn caused by anti-M antibodies.

OBJECTIVE: We aimed to summarize the laboratory findings and clinical features of hemolytic disease of the fetus and newborn (HDFN). METHODS: We retrospectively analyzed the data for 17 infants with anti-M-induced HDFN (anti-M-HDFN) diagnosed between June 2013 and May 2019. Their maternal history, neonatal diagnosis on admission, and laboratory test results were compared with those of 15 infants with HDFN involving the ABO blood group system, 15 infants with HDFN involving the Rh system, and 15 premature infants. RESULTS: In the anti-M-HDFN group, 94.12% (16/17), 35.29% (6/17), and 17.65% (3/17) had free antibodies in plasma, a positive direct antiglobulin test, and a positive elution test, respectively. In 12 infants, free antibody reactions were stronger at 4°C than at 37°C, and the antibody titer at 4°C ranged from 1 to 512. All 17 infants with anti-M-HDFN developed anemia: 14 were treated with blood transfusion and 1 with neonatal exchange transfusion. Sixteen infants improved, and one died. Anti-M-HDFN had a higher rate of maternal stillbirth, lower gestational age, lower birthweight, and higher incidence of respiratory distress than other HDFN types. CONCLUSION: Anti-M may cause HDFN. It may present with varying degrees of anemia, low regenerative anemia, and low bilirubin levels. In addition, infants with anti-M-HDFN may have a negative elution test and direct antiglobulin test. These tests are helpful in examining antibody responses at a low temperature of 4°C.

Incompatible red blood cell transfusion for hemolytic disease of the fetus and newborn secondary to anti-U: A case report.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a challenging condition that may necessitate the need for intrauterine or neonatal transfusion. The ability to provide compatible blood depends on antibody identification and antigen prevalence. We describe the case of a newborn that was affected by HDFN secondary to a high-prevalence antigen of unknown specificity. STUDY DESIGN AND METHODS: A 29-year-old mother underwent emergency cesarean section for fetal distress. The newborn had severe anemia and hyperbilirubinemia. Antibody screening and identification on maternal plasma revealed pan reactivity with negative autocontrol. The cord sample had the same pattern with positive Direct Antiglobulin Test. Incompatible group O red blood cells were transfused to the newborn with no complications. RESULTS: Testing the maternal sample at a reference laboratory revealed the presence of anti-U at a high titer. DISCUSSION: In life-threatening conditions, it may be necessary to transfuse incompatible units. In patients who require transfusion in the presence of an identified antibody against a high-prevalence antigen, sources for rare blood should be explored. These include autologous donations for adults, collecting blood from relatives (including mothers), and fresh or frozen units from rare donors through rare donor registries.

Parent perceptions of emergent blood transfusion in children.

BACKGROUND: RhD-negative blood products are in chronic short supply leading to renewed interest in utilizing RhD-positive blood products for emergency transfusions. This study assessed parental perceptions of emergency RhD-positive blood use in children. METHODS: A survey of parents/guardians was conducted on their tolerance of transfusing RhD-positive blood to RhD-negative female children ≤17 years old at four level 1 pediatric hospitals. RESULTS: In total, 621 parents/guardians were approached of whom 378/621 (61%) completed the survey in its entirety and were included in the analysis. Respondents were mostly females [295/378 (78%)], White [242/378 (64%)], had some college education [217/378 (57%)] and less than $60,000 annual income [193/378 (51%)]. Respondents had a total of 547 female children. Most children's ABO [320/547 (59%)] and RhD type [348/547 (64%)] were not known by their parents; of children with known RhD type, 58/186 (31%) were RhD-negative. When the risk of harm to a future fetus was given as 0-6%, more than 80% of respondents indicated that they were likely to accept RhD-positive blood transfusions on behalf of RhD-negative female children in a life-threatening situation. The rate of willingness to accept emergent RhD-incompatible blood transfusions significantly increased as the potential survival benefit of the transfusion increased. CONCLUSION: Most parents were willing to accept RhD-positive blood products on behalf of RhD-negative female children in an emergency situation. Further discussions and evidence-based guidelines on transfusing RhD-positive blood products to RhD-unknown females in emergency settings are needed.

Passive transfer of alloantibodies through breast milk as a mediator of hemolytic anemia.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is characterized by destruction of fetal/neonatal red blood cells (RBCs) secondary to maternally derived antibodies, which are typically thought to be passively acquired via placental transfer. Few cases have examined the possibility of HDFN mediated by maternal antibodies passively transferred via breast milk. METHODS: We describe two cases of persistent HDFN in infants potentially mediated by passively acquired antibodies via maternal breast milk. We discuss supporting and refuting evidence that may account for this possibility and describe testing methodology illustrating how maternal alloantibodies can be detected in breast milk. RESULTS: In both cases, anti-D antibodies were detected in maternal breast milk. One patient experienced a significant decrease in anti-D plasma titer from 64 to 4 dilutions following 2 weeks of breastfeeding cessation. The other patient experienced a resolution of anemia without breastfeeding cessation. CONCLUSION: There is a paucity of data regarding the lifespan of passively acquired RBC antibodies in neonatal circulation, with significant variation noted between passively acquired IgG based on studies utilizing intravenous immunoglobulin compared to studies of maternally-acquired antiviral IgG antibodies. While our data do not definitively implicate passive transfer of alloantibodies in breast milk as a mediator of HDFN, they do illustrate the need for further investigation into the mechanisms and kinetics of passively acquired antibodies in neonatal circulation.

Comparison of automated solid phase versus manual saline indirect antiglobulin test methodology for non-ABO antibody titration: Implications for perinatal antibody monitoring.

BACKGROUND: Accurate antibody titration is crucial in prenatal evaluations to identify patients who need clinical monitoring for hemolytic disease of the fetus and newborn (HDFN) causing fetal anemia. This study compares the established gold standard method of manual tube saline indirect antiglobulin testing (SIAT) with the newer automated solid phase (ASP) method of antibody titration and aims to establish the critical titer threshold for ASP that corresponds to the previously established SIAT critical threshold of ≥16 used in our laboratory. STUDY DESIGN AND METHODS: One hundred fifty-seven prenatal and donor plasma samples with known antibodies were tested using both SIAT and ASP methodologies and results were compared. RESULTS: The study found that ASP titers were, on average, 1.33 dilutions higher than SIAT titers. The critical titer cutoff for ASP was determined to be ≥32, which is one tube higher than the SIAT cutoff of ≥16. DISCUSSION: The ASP method for antibody titration offers greater reproducibility and efficiency compared with manual SIAT titration. This study suggests that a titer cutoff of ≥32 is appropriate for most clinically significant antibodies using ASP. However, further research is needed to determine the comparability of ASP with SIAT in samples with multiple antibodies, anti-M antibodies, and other less common antibodies. Validation of the ASP titer cutoff against HDFN clinical outcomes is required before implementing this test for routine use in perinatal antibody titration.

History and current standard of postnatal management in hemolytic disease of the fetus and newborn.

Since the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and clinicians came to the current understanding that fetal and neonatal red blood cells (RBC) are hemolyzed by maternal alloantibodies directed against RBC antigens potentially leading to severe disease. Preventative measures, such as Rhesus(D) immunoprophylaxis (RhIG), have greatly decreased the prevalence of Rh(D)-mediated HDFN, although a gap between high-income countries and middle- to low-income countries was created largely due to a lack in availability and high costs of RhIG. Other important developments in the past decades have improved the identification, monitoring, and care of pregnancies, fetuses, and neonates with HDFN. Prenatally, fetal anemia may occur and intrauterine transfusions may be needed. Postnatally, pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for anemia in the late phase of the disease. Through this review, we aim to provide an overview of important historic events and to provide hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Secondarily, we aim to describe recent scientific findings and evidence gaps. CONCLUSION:  Multiple developments have improved the identification, monitoring, and care of pregnancies and neonates with HDFN throughout the centuries. Pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for late anemia in the late phase of the disease. Future studies should be set in an international setting and ultimately aim to eradicate HDFN on a global scale. WHAT IS KNOWN: • Developments have led to a greater understanding of the pathophysiology, an improved serological identification and monitoring of at-risk cases and the current pre- and postnatal treatment. WHAT IS NEW: • This review provides the pediatrician with hands-on guidelines for the delivery and postnatal management of neonates with HDFN. • Future studies should be set in an international setting with the ultimate aim of eradicating HDFN.

Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.

BACKGROUND: Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research. METHODS: We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality. RESULTS: We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks. CONCLUSION: These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.

Hemolytic disease of the fetus and newborn: rapid review of postnatal care and outcomes.

BACKGROUND: Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research. METHODS: We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies. RESULTS: Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0-20.0] in K-mediated HDFN and 26.5% [IQR: 18.0-42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0-56.0] and 60.0% [IQR: 20.0-72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0-4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies. CONCLUSION: Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2021 CRD42021234940. Available from:  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940 .

Significance of immunohematologic testing in mother and newborn ABO incompatibility.

The aim of this study was to define risk factors for jaundice and anemia in newborns with a positive direct antiglobulin test (DAT) and/or with an incompatible crossmatch due to ABO incompatibility between mother and newborn. ABO incompatibility has become a more significant cause of hemolytic disease of the fetus and newborn since the introduction of effective anti-D prophylaxis. The condition is common and, if clinically significant at all, causes only mild jaundice, which can be treated with phototherapy (PT). However, rare and serious presentations, requiring transfusion therapy, have been noted. Clinical, laboratory, and immunohematologic data were collected retrospectively from medical records of ABO-incompatible newborns and their mothers over a 5-year period (2016-2020) from University Hospital Centre Zagreb. Two groups of newborns were compared: those who needed medical intervention because of hyperbilirubinemia or anemia and those who did not. Within the group of newborns requiring intervention, we also compared those with A and B blood groups. Over the 5-year period, 72 of 184 (39%) newborns required treatment. The treatment was PT in 71 (38%) newborns and erythrocyte transfusion in 2 (1%). In 112 (61%) newborns, ABO incompatibility was an accidental finding while performing blood group typing; these newborns did not require any therapy. In conclusion, we found a statistical, but not clinically significant, difference between the groups of treated and untreated newborns, related to the mode of delivery and DAT positivity within hours of delivery. There were no statistically significant differences in characteristics between the groups of treated newborns, except for two newborns with blood group A who received erythrocyte transfusions.

Hemolytic disease of the fetus and newborn mediated by anti-Dia in a U.S. hospital.

Dia is one of the most clinically significant low-prevalence antigens in the Diego blood group system, since antibodies to Dia have, albeit rarely, been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). Given the geographical association, most anti-Dia HDFN cases have been reported in Japan, China, and Poland. We describe a case of HDFN in a neonate born to a 36-year-old G4P2012 woman of self-identified Hispanic ethnicity and of South American descent with multiple negative antibody detection tests in a U.S. hospital. Upon delivery, a cord blood direct antiglobulin test was positive (3+ reactivity), and neonatal bilirubin levels were moderately elevated, but phototherapy and transfusion were not required. This case highlights a rare, unexpected cause of HDFN in the United States secondary to anti-Dia, given the near-universal absence of this antigen and antibody in most U.S. patient populations. The case also demonstrates the need for awareness of antibodies to antigens that are considered "low-prevalence" in most populations but that might be encountered more frequently in specific racial or ethnic groups and may require more extensive testing.

Navigating the challenges of Bombay phenotype (Oh ) and twin pregnancy; a case report and literature review.

BACKGROUND: Bombay phenotype (Oh ) is a rare blood group and poses unique challenges during pregnancy, including an adequate supply of blood products in case of postpartum hemorrhage (PPH) and the risk of hemolytic disease of the fetus and newborn (HDFN). Case reports of antenatal care in this cohort are scarce. Herein, we present a case of twin pregnancy in an Oh woman and outline her multidisciplinary management. We summarize the literature to better inform decision-making and patient blood management in the antenatal care of Oh women. CASE DESCRIPTION: A 22-year-old G1P0 presented at 15 weeks gestation with dichorionic diamniotic twins and known Oh phenotype. Hematinics were optimized to minimize anemia. Anti-H titers were tracked and were 1:256 at both 28 and 36 weeks gestation. Regular middle cerebral artery dopplers were performed to assess for fetal anemia. There was constant communication with obstetrics and anesthetics teams. Both autologous frozen and directly donated fresh red cells were available as part of a clear, detailed transfusion plan. Transfusion was not required and neither child was affected by HDFN. The neonates were group O, DAT negative, and group A, DAT positive. Maternal anti-A was detected in the neonatal eluate. CONCLUSION: To our knowledge, this is only the second report of twin pregnancy in an Oh female and the first time a detailed transfusion plan has been published. Through employing patient blood management strategies, engaging a collaborative multidisciplinary approach, and establishing a clear delivery plan, the antenatal challenges of Bombay phenotype are surmountable.

Attitudes of American adult women toward accepting RhD-mismatched transfusions in bleeding emergencies.

BACKGROUND: There is an increasing literature demonstrating the benefits of prehospital and early in-hospital transfusions. RhD-positive products might only be available during these phases, which could pose consequences for future pregnancies if D-alloimmunization occurs. This survey measured the willingness of females to accept urgent but incompatible transfusions in light of the potential for future pregnancy complications. METHODS: A survey was designed to assess the willingness of females ≥18 years of age to accept urgent incompatible transfusions when different absolute risk reductions in maternal mortality were presented along with a static rate of 0.3%-4.0% risk of harm to future pregnancies. The survey was sent electronically to women who are part of the Washington University Research Enhancement Core database. RESULTS: A total of 4896 delivered survey email invitations were distributed and 325 (6.6%) responses were received; 16 responses were excluded leaving 309 responses for analysis. Most of the responding women were White, college-educated, and lived in Missouri. At least 90% of the respondents would accept an urgent incompatible transfusion when the absolute risk reduction in maternal mortality was ≥4%. Women without a college degree, who lived in Illinois, who were not able to have children appeared to be less willing than their counterparts to receive an incompatible transfusion when the absolute risk reduction in maternal mortality was low. CONCLUSION: This survey demonstrated that adult women are highly likely to be open to accept urgent incompatible blood transfusions during a bleeding emergency when the absolute risk reduction in maternal mortality was ≥4%.

Retrospective analysis of direct antiglobulin test positivity at tertiary academic hospital over 10 years.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a clinically significant problem that may potentially affect any pregnancy. Direct antiglobulin test (DAT) is considered to be an important test in identifying newborns who are suspected to have HDN. This study aims in reviewing data regarding a positive DAT result concerning etiology and the development of HDN over a period of 10 years. STUDY DESIGN AND METHODS: A retrospective study of all neonates with a positive DAT result between January 2011 and December 2020 was performed. Data were obtained from patients' electronic hospital files, transfusion medicine databases, and medical birth records. Laboratory parameters along with clinical interventions in neonates with a DAT-positive result and a comparison group of DAT-negative neonates were performed. RESULTS: 36,000 deliveries were registered in this period. 176 (2.65 %) neonates had a positive DAT result. ABO-incompatibility was the most common cause with 59.1 %; Rh incompatibility 13.8 %, minor blood group incompatibility, and other RBC-related antibodies 10.1 %, and unspecified etiology in 17 % of cases. Among DAT-positive cases, 32.7 % of neonates were diagnosed with HDN. ABO-incompatibility was the major reason as well. Initial mean total bilirubin levels were higher in the DAT-positive group than the control group (p < 0.001), and these neonates also had a lower initial hemoglobin level (p < 0.001). The need for therapeutic interventions was significantly higher in DAT-positive neonates (p < 0.001) as 86.8 % underwent phototherapy, with 32.7 %, and 17.6 % receiving exchange transfusion (ET) and intravenous immunoglobulin (IVIG), respectively. CONCLUSION: In conclusion, ABO incompatibility was the most common cause for neonatal DAT positivity. Besides the common causes of DAT positivity, there would be rare but important conditions that may lead to a positive result, such as antibodies passively acquired from mothers in the context of alloimmunizations or using drugs. In addition, as a high rate of therapeutic intervention was identified among neonates with a DAT-positive result, there is a crucial need for increasing awareness regarding early diagnosis of the condition, careful monitoring, and the employment of prenatal alloimmunization screening tests.

Non-Invasive Fetal K Status Prediction: 7 Years of Experience.

Introduction: In the Kell blood group system, the K and k antigens are the clinically most important ones. Maternal anti-K IgG antibodies can lead to the demise of a K-positive fetus in early pregnancy. Intervention can save the fetus. Prenatal K status prediction of the fetus in early pregnancy is desirable and gives a good basis for pregnancy risk management. We present the results from 7 years of clinical experience in predicting fetal K status as well as some theoretical considerations relevant for design of the assay and evaluation of results. Methods: Blood was collected from 43 women, all immunized against K, at a mean gestational age of 18 weeks (range 10-38). A total of 56 consecutive samples were tested. The KEL *01.01 /KEL *02 single nucleotide variant that determines K status was amplified from maternal plasma DNA by PCR without allele specificity. The PCR product was sequenced by NGS technology, and the number of sequenced KEL *01.01 and KEL *02 reads were counted. Prediction of the fetal K status was based on this count and was compared with the serologically determined K status of the newborns. Results: All fetal K predictions were in accordance with postnatal serology where available (n = 34), using our current data analysis. Conclusion: We have developed an NGS-based method for the non-invasive prediction of fetal K status. This approach requires special considerations in terms of primer design, stringent preanalytical sample handling, and careful analytical procedures. We analyzed samples starting at GA 10 weeks and demonstrated the correct prediction of fetal K status. This assay enables timely clinical intervention in pregnancies at risk of hemolytic disease of the fetus and newborn caused by maternal anti-K IgG antibodies.

Survey of newborn direct antiglobulin testing practice in United States and Canadian transfusion services.

BACKGROUND: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. STUDY DESIGN AND METHODS: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. RESULTS: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). CONCLUSION: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.