Neonatal Exchange Transfusion Research Articles

Risk factors for exchange transfusion in neonates with unconjugated hyperbilirubinemia: A tertiary care hospital study.

Risk factors for exchange transfusion in neonates with unconjugated hyperbilirubinemia: A tertiary care hospital study.

Effect of Low-volume Exchange Transfusion on Neonatal Hyperbilirubinaemia: A Retrospective Cohort Study

Introduction: A double volume exchange transfusion for hyperbilirubinaemia often requires more than one pack of compatible blood to fulfil the calculated volume. This is often unavailable, necessitating exchange transfusion using less than the calculated double-volume. During practice, the authors found that many patients had a positive therapeutic response even when the exchange blood volume was reduced. Aim: To study the effect of the reduced volume of blood used for exchange transfusion in neonates with hyperbilirubinaemia. Materials and Methods: A retrospective cohort study was conducted in the Neonatal Intensive Care Unit (NICU), Malankara Orthodox Syrian Church Medical College (tertiary level), Kerala, India, between January 2015 and December 2020. Total 116 patients who underwent exchange transfusion for hyperbilirubinaemia, regardless of gestational age, were included. Pre- and postexchange details, blood chemistry and haemogram were collected from the records and analysed. The patients were grouped into group 1 (80-≤120 mL/kg) and group 2 (>120-≤160 mL/kg) based on the volume of blood used for exchange transfusion. The correlation of exchange blood volume with the percentage drop in bilirubin, rebound rise of bilirubin at six hours, duration of phototherapy, and duration of admission was studied using Pearson’s/ Spearman’s correlation. Data were statistically analysed using Independent samples t-test, Paired sample t-test, and Chi-square test to determine, if there was a significant difference between the groups. Results: Out of 116 patients, group 1 had 67 (57.78%) patients, and group 2 had 49 (42.24%) patients. The mean±Standard Deviation (SD) gestational age was 37.6±1.57 weeks, and 59 (50.86%) were males. The mean±SD postexchange bilirubin was 13.12±3.85 mg/ dL in group 1 and 10.26±2.78 mg/dL in group 2, resulting in a bilirubin reduction of 40.74±12.81% and 53.81±11.67%, respectively. The rebound bilirubin at six hours (13.15±4.32 mg/dL vs 11.23±2.30 mg/dL) made no clinical difference in the management of the patient. The median duration of phototherapy was 48 hours, and the median duration of admission was five days in both groups. Conclusion: Exchange transfusion with a lower volume of blood, followed by phototherapy, can lead to a clinically acceptable reduction in serum bilirubin. Non availability of the exact 160 mL/kg of blood for exchange is not an adequate reason to delay exchange transfusion.

Targeted next-generation sequencing identifies eighteen novel mutations expanding the molecular and clinical spectrum of PKLR gene disorders in the Indian population.

Pyruvate kinase deficiency (PKD) is an autosomal recessive condition, caused due to homozygous or compound heterozygous mutation in the PKLR gene resulting in non-spherocytic hereditary hemolytic anemia. Clinical manifestations in PKD patients vary from moderate to severe lifelong hemolytic anemia either requiring neonatal exchange transfusion or blood transfusion support. Measuring PK enzyme activity is the gold standard approach for diagnosis but residual activity must be related to the increased reticulocyte count. The confirmatory diagnosis is provided by PKLR gene sequencing by conventional as well as targeted next-generation sequencing involving genes associated with enzymopathies, membranopathies, hemoglobinopathies, and bone marrow failure disorders. In this study, we report the mutational landscape of 45 unrelated PK deficiency cases from India. The genetic sequencing of PKLR revealed 40 variants comprising 34 Missense Mutations (MM), 2 Nonsense Mutations (NM), 1 Splice site, 1 Intronic, 1 Insertion, and 1 Large Base Deletion. The 17 novel variants identified in this study are A115E, R116P, A423G, K313I, E315G, E318K, L327P, M377L, A423E, R449G, H507Q, E538K, G563S, c.507 + 1 G > C, c.801_802 ins A (p.Asp268ArgfsTer48), IVS9dsA-T + 3, and one large base deletion. In combination with previous reports on PK deficiency, we suggest c.880G > A, c.943G > A, c.994G > A, c.1456C > T, c.1529G > A are the most frequently observed mutations in India. This study expands the phenotypic and molecular spectrum of PKLR gene disorders and also emphasizes the importance of combining both targeted next-generation sequencing with bioinformatics analysis and detailed clinical evaluation to elaborate a more accurate diagnosis and correct diagnosis for transfusion dependant hemolytic anemia in a cohort of the Indian population.

Role of IVIg in Severe Neonatal Jaundice due to Isoimmunization A Retrospective Cohort Study

Aim To see the efficacy of intravenous immunoglobulin (IVIg) in reducing the need for exchange transfusion (ET) in neonates with isoimmune hemolytic disease with serum bilirubin at or above exchange level. Methods Retrospective cohort study conducted in neonatal intensive care unit of a tertiary care center from March 2015 to February 2020 included neonates with gestational age ≥35 weeks with positive Direct Coombs Test with serum bilirubin at or above exchange level according to American Academy of Pediatrics charts with no bilirubin encephalopathy at presentation. Study subjects were followed till discharge. Results ET was prevented in 8/41 (19.5%) cases who received IVIg initially vs. 2/51 cases (3.92%) who didn’t ( P = .02, relative risk: 1.98 with 95% confidence interval [1.32-2.98] with number needed to treat: 2.51). Total duration of phototherapy was significantly lesser in those receiving IVIg ( P < .0001). Conclusion Targeted use of IVIg in isoimmune hemolytic disease of newborn with serum bilirubin rising despite intensive phototherapy or within 2 to 3 mg/dL of the exchange level is more likely to benefit than harm and remain prudent.

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

We aimed to summarize the laboratory findings and clinical features of hemolytic disease of the fetus and newborn (HDFN). 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. 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. 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.

Common Indications of Exchange Transfusion in Neonates with Jaundice Presenting to a Tertiary Care Health Facility

Objective: To determine the frequency of common indications of exchange transfusion in neonates with jaundice presenting to a tertiary care health facility. Study Design: A descriptive cross-sectional study. Place and Duration: Department of Paediatrics, National Institute of Child Health, Karachi Pakistan, from January 2022 to June 2022. Methodology: All neonates up to 28 days of either gender presenting with jaundice were included. Details about gender, ethnicity, blood group, feeding practices and indications of exchange transfusion were noted. Results: The mean age of the patients was 10.71±9.68 days. There were 66 (50.4%) males and 65 (49.6%) females. The Mean weight and gestational age were found to be 3.39±0.37 kg and 39.34±1.07 weeks respectively. Feeding practice among majority (n=78, 59.5%) of the mother was mixed (n=78, 59.5%). ABO incompatibility was observed in 31 (23.7%), Rh incompatibility in 24 (18.3%) and unidentified cause in 11 (8.4%) neonates. Practical Implications: For hyperbilirubinemia in neonates, ABO incompatibility was found to be the most frequent causative factor behind exchange transfusion. Conclusion: ABO incompatibility was found to be the most common indications of exchange transfusion followed by Rh incompatibility in neonates with jaundice presenting to tertiary care facility. Keywords: ABO incompatibility, exchange transfusion, jaundice, Rh incompatibility, neonates.

Risk factors for severe hyperbilirubinemia and exchange transfusion in neonates

Background Neonatal jaundice is a common cause of neonatal admission to the hospital. The neonatal jaundice frequency has been increased last decade. 65% of term babies develop jaundice clinically in 1st week (in preterm babies 80%).Methods One hundred and sixty four neonates with severe hyperbilirubinemia, were enrolled in this study. Most important relevant informative data was taken during admission to the hospital. American Academy of Pediatrics (AAP) guidelines were applied in management of the patients, which was been either phototherapy or exchange transfusion with phototherapy ResultsMeanTSB level of 164 cases was 16.6mg/dl. TSB was significantly high in the male, with Rh-ve mothers and Rh+ve babies, more than 37weeks gestational age, admitted after 72 hours of life, were having history of previous siblings affected with jaundice and or received phototherapy and family history of hemolytic diseases. Phototherapy alone was used as treatment modality in most of the patients. On admission to the NCU, the mean age of the infants who needed exchange transfusion 4.97 ±2.24 while the mean TSB level was 20.2±2.84 mg/dL. The most common cause for ET was early discharge from the maternity unit & late admission to the NCU 72.4%. ConclusionsSevere hyperbilirubinemia was been more common in male neonates, > 37weeks of gestational age, with Rh-ve mothers and Rh+ve babies, who admitted after 72hrs of life, . Most of cases treated by phototherapy. The most common cause for ET was early discharge from the maternity unit & late admission to the NCU.

Neonatal Exchange Transfusion: When Should We Think about Hereditary Thrombotic Thrombocytopenic Purpura (hTTP)?

Introduction Neonatal exchange transfusion (NExT) is a procedure to treat severe neonatal hyperbilirubinemia persisting despite phototherapy, to remove red cell allo-antibodies associated with excessive neonatal hemolysis and to correct severe anemia. During the past decades, the number of NExT preformed have steadily decreased, particularly since the introduction of rhesus prophylaxis in rhesus negative women. Hereditary thrombotic thrombocytopenic purpura (hTTP) because of severe congenital ADAMTS13 deficiency is a rare, autosomal recessively inherited disorder with an estimated prevalence of one case per million. Although excessive neonatal hemolysis (often in conjunction with thrombocytopenia) seems to be prevalent in hTTP, patients are seldom diagnosed with hTTP in the neonatal period, possibly because hTTP is not recognized as a differential diagnosis of severe neonatal hyperbilirubinemia and NExT. In this study, we investigated the prevalence of severe neonatal hyperbilirubinemia necessitating NExT among confirmed hTTP patients enrolled in the International Hereditary TTP Registry (www.ttpregistry.net; ClinicalTrials.gov Identifier: NCT01257269), at participating sites and in the literature in the past 20 years. Methods The International Hereditary TTP Registry is a cohort study for patients with confirmed hTTP and their family members, established in 2006. The hTTP Registry collects clinical and treatment information, as well as laboratory parameters retrospectively up to enrollment (including performance of NExT), and then prospectively during annual follow-up visits. Participating study sites and/or national coordinating centers were asked to provide information on the number of and indication for all NExT performed between January 2001 and July 2022. Finally, we performed a literature search to identify reports on NExT / neonatal exchange blood transfusion over the same 20-year period. Results At present, the International Hereditary TTP Registry has enrolled 178 confirmed hTTP patients. Forty-two (24%) of them had required NExT because of severe hyperbilirubinemia in the neonatal period, which led to early diagnosis of hTTP in 7/42 (16%) cases. In the remaining 33 patients treated with NExT, hTTP diagnosis was established in infancy/early childhood (between 3 months - ≤6 years of age) in 20 patients, and in 15 instances after 6 years of age. Of the 136 hTTP patients not requiring NExT, 35 (26%) had a disease onset in the neonatal period although only four of them (11%) were diagnosed at this time, while the majority (20/35 patients, 57%) received their hTTP diagnosis following further acute episodes in late adolescence or adulthood. Twelve of the 20 sites or national coordination centers participating in the International Hereditary TTP Registry answered our survey and reported 70 neonates treated with NExT over a period of 20 years. Indication for NExT were severe hyperbilirubinemia and or severe anemia due to AB0 or Rhesus incompatibility. In none of the cases hTTP was suspected or diagnosed, as immune-hematological findings indicated severe allo-antibody mediated hemolysis. We retrieved from PubMed 887 publications mentioning NExT or neonatal exchange blood transfusion, of which we excluded 229 papers, that did not describe patients treated with exchange transfusions. In the remaining 658 publications, patients were treated with exchange transfusions because of severe hyperbilirubinemia due to AB0-, Rhesus- or minor blood group incompatibilities, glucose-6-phosphate deficiency, sickle cell disease and severe infections. Only three publications mentioned the indication TTP. Conclusions Despite increased awareness and tools to diagnose hTTP, prompt recognition and diagnosis remain a critical impediment and result in delayed diagnosis and treatment. Early and persistent severe hyperbilirubinemia (often in conjunction with thrombocytopenia) necessitating NExT prevalent in newborns later in life diagnosed with hTTP. Differential diagnosis of severe neonatal hyperbilirubinemia should include hTTP and we suggest to determine ADAMTS13 activity together with molecular analysis of the ADAMTS13 gene in case of an ADAMTS13 activity <10% in any newborn requiring NExT for severe hyperbilirubinemia.

Frequency of Indirect Hyperbilirubinemia Requiring Exchange Transfusion, Etiology and its Immediate Outcome in Term Neonates in Neonatal ICU of National Institute of Child Health, Karachi

Objectives: The present study assessed the frequency of causes of indirect hyperbilirubinemia (IH) requiring exchange transfusion and its immediate adverse events of exchange transfusion in term neonates. Methods: A prospective, observational study was undertaken at the Neonatal ICU of National Institute of Child Health, Karachi between July 2021 and December 2021. Term neonates arriving at the newborn unit of NICH with indirect hyperbilirubinemia were included in this study. All enrolled neonates were monitored for clinical, biochemical, and hematological adverse events for 7 days following exchange transfusion, and a predesigned performa was used to document observations. Results: Among 730 neonates with indirect hyperbilirubinemia, a total of 63 term neonates underwent exchange transfusion. The most common causes of hyperbilirubinemia were sepsis in 19 (30.2%) patients and ABO incompatibility in 13 (20.6%) patients. The most common adverse events noted were hypokalemia, which occurred in 10 (15.9%) and thrombocytopenia, which occurred in 10 (15.9%) cases. In six patients, sepsis developed. In total, five neonates died while four developed bilirubin encephalopathy. The total serum bilirubin and direct bilirubin among patients were significantly lowered after exchange transfusion (p&lt;0.0001). There were no umbilical catheter-related complications. Bilirubin encephalopathy was present in 4 patients. There were five deaths, but not due to the procedure. Practical implication Conclusion: We highlighted the main causes of indirect hyperbilirubinemia as sepsis and ABO incompatibility in our setting. Furthermore, we also identified the immediate and short-term outcomes of exchange transfusion with a mortality rate of 7.9%. The overall outcome was favorable after the exchange transfusion. Keywords: Hyperbilirubinemia, kernicterus, exchange transfusion, indirect bilirubin, neonates , jaundice

Study on the application value of red blood cell distribution width and platelet distribution width in neonatal exchange transfusion with hyperbilirubinemia

Purpose The study aimed to evaluate the application of Red Blood Cell Distribution Width (RDW) and Platelet Distribution Width (PDW) in the treatment of neonatal exchange transfusion (ET) with hyperbilirubinemia as well as to provide relevant reference materials for clinical diagnosis and treatment. Patients and methods This was a retrospective study in a single center. Between January 2011 and December 2020, a total of 198 neonates, who were admitted to Fujian Maternity and Child Health Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into blood group antibody negative (BGAbN) ET (n = 92) and blood group antibody positive (BGAbP) ET (n = 106) groups. We analyzed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count(PLT) before and after ET; The clinical data of the neonates with hyperbilirubinemia were collected, and RDW and PDW were compared in the two groups before ET.. Results The concentrations of STB, SIB, and platelet count were much higher before ET and decreased significantly after ET; the difference was statistically significant (p<.001); There were significant differences between the two groups in RDW and PDW before ET. Conclusion ET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically; RDW and PDW can help determine neonatal hemolysis caused by blood group antibodies.

Determination of ABO antibody titre and haemolysin test of group O whole blood used for exchanged transfusion in a teaching hospital

Background: Group O blood donor is more readily available and is frequently used as a universal red cell donor and emergency O whole blood (EM O) for exchange transfusion in neonates. Sera from group O donors contains two separable haemolysin antibodies, anti-A and anti-B, and a cross-reacting antibody called anti-A, B (mostly IgG). The presence of haemolysins in the donors may lead to haemolysis in the recipients. Objectives: This study aims to determine the prevalence of anti-A and anti B haemolysins and titer among group O donors that we screened for emergency group O (EM O) whole blood Methodology: A cross sectional study was done to determine the prevalence of anti-A and anti B haemolysin and titer among group O blood donors screened for EM O whole blood for exchange transfusion in neonates at a teaching hospital from January to December 2018. Samples of 350 voluntary group O regular donors were selected for ABO antibodies titration and haemolysin test using the conventional tube technique at room temperature. Donors were screened for titer of 1:50 and 1:100 only. ABO antibody titer of ≥1:100 was considered as a high titer and not suitable for exchange transfusion. Titer of ≤1:50 were labeled as EM O whole blood and will be suitable for exchange transfusion. Results: A total of 350 group O blood donors were screened for the anti A and anti B haemolysin and titer. The majority of blood group O donors were male (n=215, 61%) and were age from 18-30 years old (51%). Malay was the predominant group (83%). About 52.9% of the donors were low titer (≤1:50), and 47.1% were high titer (≥1:100). Low titer was seen predominantly among male donors (61.8%). The prevalence of haemolysins in group O donors was 5.4% (n=19). Anti A and anti B haemolysins were seen in 0.57% and 2.28% of the donors, respectively, while donors having both A and B haemolysins in their sera was 2.57%. Conclusion: Prevalence of anti-A and anti-B haemolysins were low among group O blood donors. However, a significant percentage of group O donors have high titer of anti-A or anti-B. Therefore, despite the labour intensiveness of haemolysis titration technique and the frequent transfusion of group O blood for exchange transfusion, there is the need to routinely screen our donors for haemolysins in order to identify those posing the greatest risk to recipients. Bangladesh Journal of Medical Science Vol. 21 No. 02 April’22 Page : 368-372

Efficacy of Double Volume Exchange Transfusion in Term Neonates with Hyperbilirubinemia Due to Abo Incompatibility

Objectives: To determine the efficacy of double volume exchange transfusion in term neonates with hyperbilirubinemia due to ABO incompatibility. Materials and Methods: This was a descriptive case series study conducted in the Neonatal Unit, Department of Pediatrics, Sheikh Zayed Hospital, Rahim Yar Khan from 30-09-2016 to 29-12-2017. Results: Total cases were 87, out of which 47 (54.02%) were males with a mean age of 4.32±1.51 days. The efficacy of double exchange transfusion was seen in 28 (32.18%) cases. Conclusion: The efficacy of double volume exchange is seen in 28 (32.18%) out of 87 cases and it is significantly high in cases when the exchange is done within the first 3 days of birth (p= 0.01). Keywords: ABO incompatibility, hyperbilirubinemia, double volume exchange transfusion.

The combined effect of anti-D and non-D Rh antibodies in maternal alloimmunization

Objective:This study aims to investigate the distribution of antibodies that cause hemolytic disease of the fetus and newborn (HDFN) and compare the clinical outcomes of pregnancies affected by anti-D and anti-D combined with non-D Rh alloimmunization.Materials and Methods:We retrospectively searched and obtained the perinatal and neonatal data of patients with anti-D antibodies and anti-D combined with non-D Rh antibodies (anti-c, -C, -e, -E, and -Kell) from October 2015 to December 2018 at the University of Health Sciences Turkey, Kanuni Sultan Süleyman Training and Research Hospital. Univariate and multiple logistic regression analyses and adjusted odds ratios with their confidence intervals were used to define independent risk factors for non-D antibody positive.Results:The severe fetal hydrops rate was significantly higher in the anti-D combined non-D group (3/25, 12%) than in the anti-D group (1/128, 0.08%, p<0.001). The intrauterine transfusion (IUT) requirement in the anti-D combined non-D group (16/25, 64%) tended to be significantly higher than that in the anti-D group (5/128, 7.46%, p<0.001). The incidence of neonatal exchange transfusion, top-up transfusion, and postnatal phototherapy frequency in the anti-D combined non-D group was significantly higher than in the anti-D group.Conclusion:Anti-D combined with another non-D Rh alloantibody resulted in significantly higher HDFN rates than the anti-D alloimmunized pregnancies. Also, anti-D in association with non-D Rh antibodies resulted in more severe HDFN requiring more invasive treatment procedures, including IUT, neonatal exchange transfusion, or top-up transfusion.

A window of opportunity: systems thinking for prevention of haemolytic disease of the fetus and newborn with transfusion policy.

A window of opportunity: systems thinking for prevention of haemolytic disease of the fetus and newborn with transfusion policy.

A comparison of the effect of X and gamma irradiation on red cell storage quality.

Irradiation of red cell components is indicated for recipients at risk of transfusion-associated graft vs. host disease. Current technologies available comprise of a gamma (γ) or an x source of radiation. The benefits of x vs. γ include non-radioactivity and hence no decay of the source. We aimed to compare the effect of the two technologies on red cell component storage quality post-irradiation. Paired units of red cell concentrates (RCC), neonatal red cell splits (RCS), red cells for intra-uterine transfusion (IUT) or neonatal exchange transfusion (ExTx) were either γ- or x-irradiated. Units were sampled and tested for five storage parameters until the end of shelf life. Equivalence analysis of storage quality parameters was performed for pairs of the same components (RCC, RCS, IUT or ExTx) that were either γ- or x-irradiated. Nearly all component comparisons studied showed equivalence between γ and x irradiation for haemolysis, ATP, 2,3-DPG, potassium release and lactate production. The exceptions found that were deemed non-equivalent were higher haemolysis with x irradiation for ExTx, lower 2,3-DPG with x irradiation for RCS irradiated early and higher ATP with x irradiation for IUT. However, these differences were considered not clinically significant. This study has demonstrated that a range of red cell components for use in different age groups are of acceptable quality following x irradiation, with only small differences deemed clinically insignificant in a few of the measured parameters.

Are fetal bilirubin levels associated with the need for neonatal exchange transfusions in hemolytic disease of the fetus and newborn?

Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the clinical value of fetal bilirubin assessment is not well known, and the information is rarely used. We speculated that there could be a role for this measurement in predicting the need for neonatal exchange transfusion. This study aimed to evaluate the predictive value of fetal bilirubin for exchange transfusions in severe hemolytic disease of the fetus and newborn. A total of 186 infants with Rh alloantibody-mediated hemolytic disease of the fetus and newborn treated with one or more intrauterine transfusions at the Leiden University Medical Center between January 2006 and June 2020 were included in this observational study. Antenatal and postnatal factors were compared between infants with and without exchange transfusion treatments. The primary outcome was the fetal bilirubin levels before the last intrauterine transfusion in relation to the need for exchange transfusion. In a multivariate logistic regression analysis, the fetal bilirubin level before the last intrauterine transfusions (odds ratio, 1.32; 95% confidence interval, 1.09-1.61 per 1 mg/dL) and the total number of intrauterine transfusions (odds ratio, 0.63; 95% confidence interval, 0.44-0.91 per intrauterine transfusion) were independently associated with the need for exchange transfusion. The area under the curve was determined at 0.71. A Youden index was calculated at 0.43. The corresponding fetal bilirubin level was 5 mg/dL and had a sensitivity of 79% and a specificity of 64%. A high fetal bilirubin level before the last intrauterine transfusion was associated with a high likelihood of neonatal exchange transfusion.

Maternal Red Blood Cell Alloimmunization Managed with Intrauterine Blood Transfusion: Predictors of Poor Outcome

Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different antigens capable of causing maternal red blood cell (RBC) alloimmunization and severe fetal hemolytic disease. Anti-K and anti-D are responsible for a significant proportion of fetal anemia requiring intrauterine transfusion (IUT). Whilst IUT of packed RBCs improves neonatal survival and morbidity, clinical prognostic indicators are lacking. Our primary objective was to identify predictors of adverse outcome. Methods: We conducted a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada. All pregnant patients alloimmunized with anti-K and anti-D as a single antibody, between 1991 and 2018 were included. Data were obtained from patient medical records, ultrasound reports and information from the transfusion medicine laboratory. Data included maternal demographics, antibody titers, pregnancy history, number of IUTs, hemoglobin (HB) concentration at the beginning and end of all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age at delivery, birth weight, HB at birth and need for neonatal transfusion, phototherapy or intravenous immunoglobulins (IVIG). Our primary outcome was the composite outcome of stillbirth or neonatal death (SB/NND). We also constructed a secondary outcome consisting of top-up neonatal transfusion, exchange transfusion, phototherapy, or use of IVIG. Medians and interquartile ranges (IQR) or mean±SD were used as summary statistics and compared by Mann-Whitney or t-test; p&amp;lt;0.05 was statistically significant. Outcome predictors were identified using multivariable logistic or linear regression analysis; accounting for patient level clustering by marginal Generalized Estimating Equation did not significantly affect variables. Data were analyzed using SPSS. Results: 116 women with 128 pregnancies and 425 IUTs with anti-K or anti-D as a single antibody were identified. Median maternal age was 31 years (27.0-35.0) for anti-K and 32 years (23.6-40.6) for anti-D. The gestational age at 1st IUT differed significantly between anti-K and anti-D (24.3 vs 28.7 weeks respectively, p=0.004). Women with anti-K antibodies required more IUTs than women with anti-D (3.84 vs 3.12 IUTs, p=0.036) and HB at 1st IUT was significantly lower in the anti-K group (5.10 vs 7.05 g/dL, p=0.001) (Table 1). Following initiation of IUT, the time from 1st IUT to delivery was 69.6 days in the anti-K group and 54.6 in the anti-D group (p=0.06). The daily decrease of HB between 1st and 2nd IUT (as a marker of disease severity), development of fetal hydrops and severe preterm birth did not differ significantly between the two groups. Mean gestation age at delivery was 35.0 weeks in the anti-K and 36.0 weeks in the anti-D group (p=0.28), with 87.1% and 93.9% survival (p=0.37), respectively. The proportion of neonates requiring phototherapy, IVIG and exchange/top-up transfusion was comparable across the two antibody groups (Table 1). Regression analysis showed that delivery occurred sooner if HB dropped more rapidly between the first two IUTs (p=0.01). Each additional transfusion gained on average 22.5 days in utero (Table 2). In multivariable analysis, gestational age at 1st IUT was the only predictor of a SB/NND outcome (adjusted OR 0.79 [95%CI 0.67-0.93]; p=0.006). With 1st IUT at 23 weeks, the risk of SB/NND was 8%, but only 2.5% at 28 weeks and &amp;lt;0.01% at 36 weeks (Table 3). Gestational age at delivery (adjusted OR 1.11 [95%CI 1.00 to 1.23]; p=0.046) and HB at 1st IUT (adjusted OR 0.84 [95%CI 0.72 to 0.99]; p=0.038) were the only predictors of a composite adverse blood product requirement/intervention outcome (Table 4). The odds of blood product requirement/intervention postnatally at 1st IUT (median HB at 1st IUT of 6.6g/dL) at 28 weeks were 43% and increased by a further 38% for delivery at 34 weeks. Conclusion: The earlier in gestation that IUTs are implemented, the higher the odds of a SB/NND; however the later the gestation at delivery, the greater the odds of the neonate requiring blood products post-partum. The greater the HB drop between the 1st and 2nd IUT, the shorter the 'time between the first IUT and delivery', which increases the odds of a SB/NND outcome. Disclosures Garbowski: Vifor Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imara: Consultancy. Shehata:Ferring: Honoraria.

Outcome of neonatal jaundice in term neonates with ABO incompatibility at tertiary level center

Background: Neonatal jaundice is extremely common as almost every new-born develops an unconjugated serum bilirubin level of more than 1.8 mg/dl during the first seven days of life. ABO incompatibility is associated in about 20% of all pregnancies but manifestations of ABO haemolytic disease of new-born occurs in &lt;10% of these cases. True incidence of ABO incompatibility, particularly in developing countries like Nepal, is not understood sufficiently. Furthermore, the confirmation of severe ABO incompatibility cannot be made accurately using only a single test. Hence, this study was done to know the outcome of jaundice in ABO incompatibility patients.Methods: This was a descriptive cross-sectional study done at Department of Paediatrics, between August 2018 to July 2019. All term neonates born to ‘O’ positive mother, with blood group A or B positive, and fulfilling the selection criteria were included in the study. Sample size was calculated to be 114 with confidence level at 95% and prevalence of ABO haemolytic disease as 11.4% with margin of error 5%.Results: Severe ABO incompatibility as evident by presence of jaundice within 24 hours of life, a positive result on direct coomb’s test and haemolytic picture on peripheral blood smear was observed in 12% of the total enrolled 200 neonates. Modalities of treatment showed significant relation with severe ABO incompatibility indicating increased need for double volume exchange transfusion in neonates with severe ABO incompatibility.Conclusions: Phototherapy was found to be effective in the management of most of the cases of neonatal jaundice in term ABO incompatible neonates but some cases, requiring exchange transfusion can occur, mostly in presence of positive result on direct Coomb’s test.

The role of Albumin infusion before exchange transfusion in term neonates with hyperbilirubinemia

The role of Albumin infusion before exchange transfusion in term neonates with hyperbilirubinemia

Molecular heterogeneity of pyruvate kinase deficiency.

Red cell pyruvate kinase (PK) deficiency is the most common glycolytic defect associated with congenital non-spherocytic hemolytic anemia. The disease, transmitted as an autosomal recessive trait, is caused by mutations in the PKLR gene and is characterized by molecular and clinical heterogeneity; anemia ranges from mild or fully compensated hemolysis to life-threatening forms necessitating neonatal exchange transfusions and/or subsequent regular transfusion support; complications include gallstones, pulmonary hypertension, extramedullary hematopoiesis and iron overload. Since identification of the first pathogenic variants responsible for PK deficiency in 1991, more than 300 different variants have been reported, and the study of molecular mechanisms and the existence of genotype-phenotype correlations have been investigated in-depth. In recent years, during which progress in genetic analysis, next-generation sequencing technologies and personalized medicine have opened up important landscapes for diagnosis and study of molecular mechanisms of congenital hemolytic anemias, genotyping has become a prerequisite for accessing new treatments and for evaluating disease state and progression. This review examines the extensive molecular heterogeneity of PK deficiency, focusing on the diagnostic impact of genotypes and new acquisitions on pathogenic non-canonical variants. The recent progress and the weakness in understanding the genotype-phenotype correlation, and its practical usefulness in light of new therapeutic opportunities for PK deficiency are also discussed.