Severe Hyperbilirubinemia Research Articles

Retracted: Establishment and Evaluation of Influencing Factors and Risk Prediction Model of Severe Neonatal Hyperbilirubinemia Complicated with Acute Bilirubin Encephalopathy.

[This retracts the article DOI: 10.1155/2022/1659860.].

Rhesus Negativity Prevalence and Neonatal Outcomes among Pregnant Women Delivered at Bule Hora University Teaching Hospital, West Guji Zone, South Ethiopia.

Rh incompatibility has been an important cause of severe neonatal hyperbilirubinemia, hydrops fetalis, and stillbirth. Among those outcomes, neonatal jaundice is the most common problem. The study is assessed the prevalence of Rhesus (Rh) negativity and neonatal outcomes among pregnant women who delivered at Bule Hora University Teaching Hospital over a 5-year period from January 2017 to December 31, 2022. A retrospective study was conducted on 110 women who delivered at Bule Hora University Teaching Hospital (BHUTH) from January 2017 to December 31, 2021. The complete data of the mother's and neonates' status were extracted from the registration book of the hospital using checklists. The data were double entered using EpiData version 3 and exported to the Statistical Package for Social Sciences (SPSS) version 26 for analysis. Descriptive statistics to determine prevalence and frequencies were used to describe the study population in relation to relevant variables, and the results are presented in tables and charts. The study shows that the prevalence of Rh D-negative among women who delivered was 6.4% [95% CI: 1.83,10.98]. Among Rh-negative women, 1 (25%) of blood group AB, 3 (6.5%) of blood group O, and 2 (6.1%) of blood group A were Rh-D negative. The distributions of O, A, B, and AB blood groups among pregnant women who delivered this hospital were 41.8%, 30%, 24.6%, and 3.6%, respectively. Out of neonates born to Rh-negative women, 1 (14.3%) was born with jaundice. Of women who delivered at BHUT hospital, 61 (55.5%) did not have a previous delivery, 7 (6.4%) had a previous abortion, 5 (4.5%) stillbirth, 1 (0.9) died after birth, 4 (3.6%) had a birth child weight less than 2.6 kg. The study revealed that the prevalence of Rh-negative was comparable with finding of different similar studies. To reduce Rh incompatibility-related HDN, the government should educate mothers and encourage them as they follow ANC facilities and after delivery to health facilities.

Scurvy's Systemic Clinical Picture: A Multiorgan Presentation of a Conspicuous Disease

A man whose diet was limited to consumption of chicken, fish, and bread was admitted for weight loss, dyspnea, and cutaneous lesions. Findings of the physical examination included lower-extremity purpura. Initial work-up demonstrated severe ferropenic anemia, hyperbilirubinemia, vertebral fracture, and dilation of the inferior vena cava and right cardiac chambers. Vitamin C deficiency was documented and, after adequate supplementation, the anemia, hyperbilirubinemia, and bleeding resolved. This case demonstrates the wide, unspecific, and reversible systemic manifestations associated with scurvy, its potential as a great mimicker, and the relevance of nutritional deficiencies even in an apparently nutrient-rich environment.

Effects of Two Different Doses of Ursodeoxycholic Acid on Indirect Hyperbilirubinemia in Neonates with Glucose-6-phosphate Dehydrogenase Deficiency Treated with Phototherapy: A Randomized Controlled Trial

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the causes of severe hyperbilirubinemia, prolonged jaundice, and bilirubin-induced encephalopathy in neonates. In a randomized controlled trial, we evaluated the effect of oral ursodeoxycholic acid (UDCA) on indirect hyperbilirubinemia in G6PD-deficient neonates requiring phototherapy. Intervention group I (N = 45; received phototherapy and 10 mg/kg/day UDCA), Intervention group II (N = 40; received phototherapy and 20 mg/kg/day UDCA), and a control group (N = 49; received phototherapy and placebo). Levels of total serum bilirubin (TSB) in all 3 groups decreased significantly over time (P = .001) but the level of TSB at different hours after admission and the duration of phototherapy did not differ significantly between the 3 groups. After discharge, the 2 intervention groups had a significantly lower rate of readmission than the control group (P = .001). No significant difference was observed between the 10 and 20 mg/kg/day groups. Further evaluation is recommended, especially in terms of the pharmacokinetics of UDCA in neonates. Trial registration number: IRCT20091201002801N4, prospectively registered on 2019-06-1.

Early Predictors of Hyperbilirubinemia in Full Term Newborn

Abstract Introduction: Predictive markers enabling Pediatricians to identify which neonates will develop jaundice have mandatory for prevention of severe hyperbilirubinemia. We aim to determine the critical cord bilirubin and albumin levels and bilirubin/albumin ratio. Design: This prospective study included131full-termnewborns. Hyperbilirubinemia can be predicted by Measuring cord bilirubin , albumin and bilirubin/albumin ratio. Results: Neonatal hyperbilirubinemia (67.8%) had cord albumin level less than or equal to 2.7gm/dl. CordBilirubin/albumin ratio cutoff value greater than 0.62 had a good predictive value with a sensitivity of 100% and specificity of 88.36%, Conclusion: neonatal hyperbilirubinemia predictors are Cord BILIRUBIN/ALBUMIN ratio , serum bilirubin and albumin.

Universal screening for hyperbilirubinemia in term healthy newborns at discharge: A systematic review and meta-analysis.

All term healthy neonates are screened for jaundice before hospital discharge as a standard clinical practice, but methods vary from clinical screening (visual inspection and/or risk factor assessment) to transcutaneous bilirubin (TcB) or total serum bilirubin (TSB) testing, depending on the setting. This systematic review of randomized and non-randomized studies evaluated the effectiveness of universal TcB and universal TSB screening at discharge compared to clinical screening alone for term healthy neonates. The outcomes were neonatal mortality, readmission for jaundice, severe hyperbilirubinemia (>20 mg/dL), jaundice requiring exchange transfusion, and bilirubin-induced neurological dysfunction (BIND). We searched MEDLINE via Ovid, EBM reviews, Embase, CINAHL, clinical trials databases, and reference lists of retrieved articles. Two authors separately evaluated the risk of bias, extracted data, and synthesized effect estimates using relative risk (RR) for randomized and odds ratio (OR) for non-randomized studies. For universal TcB at discharge, we included one randomized trial enrolling 1858 participants and four non-randomized studies enrolling 375 956 participants. No study reported neonatal mortality. The randomized trial suggested that universal TcB at discharge may decrease readmission for jaundice (risk ratio (RR) = 0.24, 95% confidence interval (CI) = 0.13 to 0.46; low certainty evidence) and severe hyperbilirubinemia (RR = 0.27, 95% CI = 0.08 to 0.97; low certainty evidence), but the effect on jaundice requiring exchange transfusion (RR = 0.20, 95% CI = 0.01 to 41.6) and BIND (RR = 0.33, 95% CI = 0.01 to 8.17) was uncertain. Meta-analysis of non-randomized studies suggested that TcB may decrease severe hyperbilirubinemia (odds ratio (OR) = 0.25, 95% = CI 0.12 to 0.52; low certainty evidence) and jaundice requiring exchange transfusion (OR = 0.28, 95% CI = 0.19 to 0.42; low certainty evidence), but the effect on readmission for jaundice was uncertain (OR = 1.01, 95% CI = 0.38 to 2.7; very low certainty evidence). For universal TSB, we included three studies from the United States enrolling 490 426 participants. The effect on severe hyperbilirubinemia (OR = 0.37, 95% CI = 0.15 to 0.88), jaundice requiring exchange transfusion (OR = 0.53, 95% CI = 0.13 to 2.25) and readmission for jaundice (OR = 1.01, 95% CI = 0.62 to 1.67) was uncertain. Universal TcB at discharge may improve clinical outcomes for term healthy neonates. Evidence for universal TSB is uncertain. PROSPERO 2020 CRD42020187279.

Phototherapy services for newborns with jaundice: Availability and practices in Southeast Nigeria

Severe neonatal hyperbilirubinemia remains a cause of neurologic damage in children in low-income countries. Phototherapy, which is the standard of care for neonatal hyperbilirubinemia is not only necessary but an essential neonatal service that should be readily available in all health facilities with maternal and newborn services. The study describes the availability and distribution of phototherapy service in secondary health facilities in Southeast Nigeria. This was a cross-sectional descriptive study carried out in four of the largest cities in Southeast Nigeria using purposive and convenient sampling methods. A questionnaire was administered and information regarding the availability of phototherapy machines, its use and availability of personnel was obtained. A total of 77 facilities were surveyed. Fifty-five (71.4%) of the studied facilities manage jaundice in their facility. Of these, 45/55 (81.8%) use phototherapy in the management of jaundice in newborns. The most used phototherapy is Light-Emitting Diode (LED) (42.2%). Others were fluorescent (26.6%), fabricated LED (11.1%) and fabricated fluorescent (20%). Routine serum bilirubin assay was done in 60 (77.9%) facilities even though majority was done in laboratories outside the facility. Non-invasive serum bilirubin monitoring was available in only two facilities. Only 21 (47.7%) had a servicing protocol for their phototherapy machines, and just 12 (27.7%) of these services were offered by a biomedical engineer. Phototherapy use in secondary health facilities is suboptimal. There is urgent need for states health authorities to collaborate with private health facilities especially those offering maternal and child services in provision of phototherapy machines and help in the training health workers for optimal management of neonatal hyperbilirubinemia.

Investigation of EEG changes before and after phototherapy in infants with severe hyperbilirubinemia.

Despite the known effect of hyperbilirubinemia in neonates, the effect of phototherapy on electroencephalography (EEG) remains unknown. Therefore, we aimed to determine the alteration of electroencephalography in infants with hyperbilirubinemia before and after phototherapy. This cross-sectional study was performed on infants of≥35 weeks of gestation with hyperbilirubinemia. Information including age, sex, birth weight, hemoglobin levels, and treatment measures was recorded. In all studied infants, an EEG was performed before (in the first eight hours of hospitalization) and after treatment (after phototherapy or blood transfusion). The required duration of phototherapy, hospitalization and adverse effects were assessed then EEG of the neonates was compared before and after treatment. A total of 52 infants (44% female and 56% male) were included in this study. Mean gestational age, weight, and bilirubin were 38.6±1.53 weeks, 3150±625 g, and 23.87±4.36 mg/dl, respectively. The most common findings before phototherapy were Frontal Theta (21 patients, 40.4 percent) and Delta Brush (14 patients, 26.9%), while the most common findings after phototherapy were Frontal Theta (20 patients, 38.5%) and Delta Brush (19 patients, 36.5%). Mean±SD of bilirubin in infants with and without Delta Brush was 21.30±1.67 mg/dl and 19.95±0.94 mg/dl, respectively. Hyperbilirubinemia in newborns may be linked to altered EEG findings. After phototherapy, the Frontal theta was reduced, but the Delta brush was intensified. Bilirubin levels were higher in infants with Delta Brush in their EEG compared to infants without this finding.

Exchange blood transfusion for hyperbilirubinaemia: Neonatal characteristics and short-term outcomes

Background. Factors that have been associated with severe hyperbilirubinaemia requiring exchange blood transfusion (EBT) are early discharge, late preterm birth and haemolytic disease. Early discharge is a common practice in neonatal care, so it is important to identify and audit neonates who received EBT, in order to identify modifiable factors. 
 Objectives. To describe the characteristics and outcomes of infants requiring EBT. 
 Methods. We reviewed records of infants admitted with severe jaundice requiring EBT from January 2009 to December 2013. Descriptive analysis of characteristics, clinical presentation, laboratory findings and outcome at discharge was performed. 
 Results. A total of 150 neonates received EBT (30 per year), and 101 were reviewed. Of these, 34 (33.7%) were inpatients and 67 (66.3%) were new admissions (2.34/1 000 new admissions). The majority of neonates requiring EBT were born vaginally (86.1%), were late preterm births (20.8%) and were exclusively breastfed (82.2%). The median postnatal age at presentation was 5 days. Clinical signs suggestive of acute bilirubin encephalopathy were present in 24.8% of cases. Among mother-infant pairs with known blood groups, 9.3% and 70.4% had rhesus (Rh) and ABO incompatibility, respectively. A Coombs test was positive in 62.5% of those with Rh incompatibility compared with 31.7% of those with ABO incompatibility. A total of 6 patients (5.9%) died, all within 7 days of EBT, but none during EBT. 
 Conclusion. The majority of neonates requiring EBT presented post discharge after birth and had been born vaginally at term, suggesting early discharge after delivery. More than two-thirds of cases were related to ABO incompatibility. Screening for jaundice before discharge must be prioritised, especially for infants born to mothers who are Rh negative or ABO blood group O.

Effect of neonatal reticulocytosis on glucose 6-phosphate dehydrogenase (G6PD) activity and G6PD deficiency detection: a cross-sectional study

BackgroundScreening for G6PD deficiency in newborns can help prevent severe hemolysis, hyperbilirubinemia, and bilirubin encephalopathy, as recommended by the World Health Organization (WHO). It has been speculated that the presence of a high number of reticulocytes in newborns interferes with the diagnosis of G6PD deficiency since reticulocytes contain higher amounts of G6PD enzyme than mature erythrocytes. Therefore, the purposes of this study were to assess the effect of reticulocytosis in the determination of blood G6PD activity in Thai newborns by using a novel automated UV-based enzymatic assay and to validate the performance of this assay for the detection of G6PD deficiency in newborn samples.MethodsThe levels of reticulocytes and G6PD activity were measured in blood samples collected from 1,015 newborns. G6PD mutations were identified using TaqMan® SNP genotyping assay, PCR–restriction fragment length polymorphism (PCR–RFLP), and direct sequencing. The correlation between the levels of reticulocytes and G6PD activity was examined. The performance of the automated method was compared with that of the fluorescent spot test (FST) and the standard quantitative assay.ResultsThe automated assay detected G6PD deficiency in 6.5% of the total newborn subjects compared to 5.3% and 6.1% by the FST and the standard method, respectively. The minor allele frequencies (MAFs) of G6PD ViangchanG871A, G6PD MahidolG487A, and G6PD UnionC1360T were 0.066, 0.005, and 0.005, respectively. The reticulocyte counts in newborns with G6PD deficiency were significantly higher than those in normal male newborns (p < 0.001). Compared with normal newborns after controlling for thalassemias and hemoglobinopathies, G6PD-deficient patients with the G6PD ViangchanG871A mutation exhibited elevated reticulocyte counts (5.82 ± 1.73%, p < 0.001). In a group of G6PD normal newborns, the percentage of reticulocytes was positively correlated with G6PD activity (r = 0.327, p < 0.001). However, there was no correlation between G6PD activity and the levels of reticulocytes in subjects with G6PD deficiency (r = -0.019, p = 0.881). The level of agreement in the detection of G6PD deficiency was 0.999, while the area under the receiver operating characteristic (AUC) curve demonstrated that the automated method had 98.4% sensitivity, 99.5% specificity, 92.4% positive predictive value (PPV), 99.9% negative predictive value (NPV), and 99.4% accuracy.ConclusionsWe report that reticulocytosis does not have a statistically significant effect on the detection of G6PD deficiency in newborns by both qualitative and quantitative methods.

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.

Long-Awaited AAP Hyperbilirubinemia Guidelines Have Arrived.

Long-Awaited AAP Hyperbilirubinemia Guidelines Have Arrived.

A step closer to bedside detection of hemolysis in newborns

Hemolysis is a well-known risk factor for severe hyperbilirubinemia in newborns. However, as standard laboratory tests for hemolysis (reticulocyte count, blood type, Coomb’s test) have relatively low specificity and sensitivity, determining the degree of hemolysis remains a clinical challenge in this population. The catabolism of heme produces bilirubin and equimolar amounts of carbon monoxide, which is easily measurable in exhaled breath (corrected for ambient carbon monoxide, ETCOc). Even though the American Academy of Pediatrics suggested in 2004 that bedside measurement of ETCOc would be useful to detect high-risk infants prior to discharge;1 there has been little adoption of the technique, partly because of a lack of reference values based on large populations.

Unlikely debris in the biliary tree: Metastatic prostate cancer masquerading as a Klatskin tumor

Introduction: Prostate cancer is a common malignancy in the United States and worldwide. Most often patients present with localized disease and are asymptomatic at the time of diagnosis. Rarely, advanced disease is present at the time of initial diagnosis, usually heralded by bone pain, fatigue, or weight loss, but jaundice is typically not a presenting symptom among patients newly diagnosed with metastatic prostate cancer. Case Report: A 74-year-old male presented with painless jaundice. He had severe hyperbilirubinemia and imaging demonstrated mediastinal and abdominal lymphadenopathy in addition to biliary ductal dilation with an enhancing mass at the confluence of the left and right hepatic ducts. While the presentation and imaging were classic for a newly diagnosed Klatskin tumor, or perihilar cholangiocarcinoma, tissue biopsies from the biliary lesion and mediastinal and gastrohepatic lymph nodes were all consistent with metastatic adenocarcinoma of prostatic origin. Prostate specific antigen was elevated to 205 ng/mL. The patient underwent biliary stenting and subsequently began treatment with androgen-deprivation therapy with marked improvement in serum prostate specific antigen and resolution of hyperbilirubinemia. Conclusion: We describe a unique case of a patient who presented with painless jaundice and imaging suspicious for a Klatskin-type cholangiocarcinoma. Multiple imaging modalities and repeated biopsies were required to prove this patient actually had metastatic prostate cancer. This case highlights the importance of finalizing an accurate tissue diagnosis prior to initiating management with systemic therapies specific to disease site and biology.

The development and validation of a predictive model for neonatal phototherapy outcome using admission indicators.

Delayed exchange transfusion therapy (ETT) after phototherapy failure for newborns with severe hyperbilirubinemia could lead to serious complications such as bilirubin encephalopathy (BE). In this current manuscript we developed and validated a model using admission data for early prediction of phototherapy failure. We retrospectively examined the medical records of 292 newborns with severe hyperbilirubinemia as the training cohort and another 52 neonates as the validation cohort. Logistic regression modeling was employed to create a predictive model with seven significant admission indicators, i.e., age, past medical history, presence of hemolysis, hemoglobin, neutrophil proportion, albumin (ALB), and total serum bilirubin (TSB). To validate the model, two other models with conventional indicators were created, one incorporating the admission indicators and phototherapy failure outcome and the other using TSB decrease after phototherapy failure as a variable and phototherapy outcome as an outcome indicator. The area under the curve (AUC) of the predictive model was 0.958 [95% confidence interval (CI): 0.924–0.993] and 0.961 (95% CI: 0.914–1.000) in the training and validation cohorts, respectively. Compared with the conventional models, the new model had better predictive power and greater value for clinical decision-making by providing a possibly earlier and more accurate prediction of phototherapy failure. More rapid clinical decision-making and interventions may potentially minimize occurrence of serious complications of severe neonatal hyperbilirubinemia.

Impact of National Clinical Practice Guidelines on Exchange Transfusion for Severe Neonatal Hyperbilirubinemia in Singapore

Aims: To review the incidence of double volume exchange transfusion for severe neonatal hyperbilirubinemia in infants ≥35 weeks’ gestational age before and after implementation of National Clinical Practice Guidelines (NCPGNJ), analyze etiologies for severe hyperbilirubinemia, readmission rates for phototherapy and neurodevelopmental outcomes up to 2 years.&#x0D; Study Design: Retrospective study&#x0D; Place and Duration of Study: KK Women’s and Children’s Hospital, Singapore, between January 2016 and December 2021.&#x0D; Methodology: National Clinical Practice Guidelines on Evaluation and Management of Neonatal Jaundice (NCPGNJ) was implemented in January 2019. We retrospectively reviewed the medical records of neonates in our center who underwent double volume exchange transfusion for severe neonatal hyperbilirubinemia before and after implementation of the national clinical practice guidelines.&#x0D; Results: Overall, 56 infants underwent double volume exchange transfusion for severe hyperbilirubinemia during the study period. There was a decline in the incidence of exchange transfusion from 107 per 100 000 live births in epoch 1 (2016-2018) to 61 per 100 000 live births in epoch 2 (2019-2021). There was a steady decline in overall phototherapy rates (p=0.06), readmission rates for phototherapy (p=0.04) and number of neonates needing exchange transfusion (p=0.25). ABO-hemolytic disease of the newborn was the most common etiology. One infant had delayed presentation of severe hyperbilirubinemia and eventually developed cerebral palsy. The rest of the infants had normal neurodevelopmental and audiological assessments at follow-up.&#x0D; Conclusion: The evidence-based National Clinical Practice Guidelines (NCPGNJ) has reduced the incidence of exchange transfusion. It provides a unified framework for all healthcare professionals who manage neonates with hyperbilirubinemia in different healthcare settings.

Early indicators of neonatal‐onset hereditary thrombotic thrombocytopenia purpura

BackgroundNeonatal‐onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO incompatibility. ObjectiveTo explore early indicators of neonatal‐onset hTTP. Methodsstudy was a retrospective case series of newborns with hTTP and ABO incompatibility. We compared the clinical characteristics and laboratory test results in these two groups. Resultsstudy included four hTTP patients and 20 ABO‐incompatible newborns. All patients manifested disease during the neonatal period. There were equal numbers of males and females in each group. hTTP newborns showed earlier (median difference, 57.0 h; 95% confidence interval [CI], 24.0–65.0) and more severe hyperbilirubinemia (mean difference, 8.0 mg/dl; 95% CI, 3.8–12.1) than ABO‐incompatible newborns. In hTTP newborns, anemia was more common within 7 days after birth than in ABO‐incompatible newborns (odds ratio, 25.4; 95% CI, 1.2–551.6), and platelet counts were lower than in ABO‐incompatible newborns (17 ± 12 × 109/L vs. 291 ± 76 × 109/L). The levels of serum creatinine (median difference, 51.8 μmol/L; 95% CI, 16.0–109.4) and blood urea nitrogen (median difference, 5.7 mmol/L; 95% CI, 2.8–38.7) were higher in hTTP newborns than in ABO‐incompatible newborns. There were no significant differences in white blood cell counts, C‐reactive protein, alanine aminotransferase, or albumin levels. ConclusionsSevere jaundice soon after birth, early anemia, and severe thrombocytopenia were more common in newborns with hTTP than ABO incompatibility. These are distinguishing early features of hTTP.

S3168 Sinusoidal Obstruction Syndrome: A Known and Often Missed Complication of Oxaliplatin Therapy

Introduction: Sinusoidal obstruction syndrome (SOS) is caused by sinusoidal endothelial injury due to hematopoietic cell transplantation, liver irradiation or exposure to chemotherapy such as oxaliplatin and may occur days to weeks following exposure. SOS can be a life-threatening complication and its presentation may include jaundice, volume overload or hepatic failure. We present the case of a 32-year-old male with gastroesophageal adenocarcinoma who underwent oxaliplatin-based chemotherapy and developed SOS. Case Description/Methods: A 32-year-old male with no significant medical history presented with dysphagia and weight loss. Esophagogastroduodenoscopy showed a mass at the gastroesophageal junction. He underwent diagnostic laparoscopy which showed peritoneal metastasis. Tissue biopsy was consistent with stage 4 gastroesophageal junction adenocarcinoma. He was started on 5-fluorouracil (5-FU), oxaliplatin and nivolumab. The patient developed thrombocytopenia and moderate aminotransferase elevation after 6 cycles of chemotherapy. An abdominal ultrasound obtained after 10 of 12 cycles of chemotherapy showed portal hypertension. Subsequent abdominal imaging showed worsening ascites (serum ascites to albumin gradient > 1.1), anasarca and splenomegaly. Transjugular liver biopsy showed elevated portal hepatic venous pressure gradient, focal sinusoidal dilatation and centrizonal ischemic changes suggesting drug induced hepatopathy, and a diagnosis of oxaliplatin induced SOS was made. The patient was not a candidate for defibrotide and was treated conservatively. He continued to have worsening ascites with severe direct hyperbilirubinemia and moderately elevated aminotransferases without biliary obstruction (Figure). Discussion: Oxaliplatin-based chemotherapies are known to cause the potentially life-threatening complication of SOS which is oftentimes missed. Our patient developed signs and symptoms suggestive of SOS by cycle 10 of oxaliplatin therapy. These changes included thrombocytopenia, elevated liver associated enzymes, volume overload and portal hypertension. He went on to complete 12 cycles of oxaliplatin with eventual worsening of his portal hypertension related symptoms and worsening of his hepatic function. This case highlights the importance of having a high index of suspicion for the development of SOS with plans to pursue patient-centered discussions regarding alternative chemotherapeutic regimens, instituting prophylactic therapies and timely SOS screening protocols.Figure 1.: Timeline of events leading up to SOS diagnosis.

Intensive phototherapy as the initial management of severe hyperbilirubinemia in neonates

Hyperbilirubinemia is one of the most common clinical phenomena found in newborns, which is about 60% of term infants and 80% of preterm infants in the first week of life. Severe hyperbilirubinemia can cause encephalopathy and permanent neurodevelopmental damage with an incidence that varies between 4% - 60.3% and mortality rate of 13% to 56.8% worldwide. Phototherapy and exchange transfusion are therapeutic modalities for infants with severe hyperbilirubinemia. Intensive phototherapy has fewer side effects and can reduce the need for exchange transfusion. This treatment is rarely needed if intensive phototherapy is effective, current guidelines for the management of hyperbilirubinemia focus on the use of intensive phototherapy as initial treatment. This literature review aims to discuss intensive phototherapy as the initial management of severe hyperbilirubinemia in neonates.

Complex Sources of Hyperbilirubinemia

The authors present a case of a patient with severe hyperbilirubinemia due to acute hepatitis B infection which resolved without intervention with subsequent normalization of synthetic and excretory liver function. Despite this, the patient remained jaundiced due to unconjugated hyperbilirubinemia in the context of a recent diagnosis and flare of hereditary spherocytosis. Due to the complex clinical presentation, the patient underwent a liver biopsy with the additional genetic diagnosis of Gilbert’s Syndrome being established. This illustrates an unusual case of both Hepatitis B and hereditary spherocytosis being a potential cause for a flare of Gilbert Syndrome.