Childhood autoimmune hemolytic anemia: A scoping review.

BACKGROUND AND OBJECTIVE: Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. METHODS: This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. RESULTS: Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. CONCLUSIONS: We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies.

Hypoglycemia Associated With PEG-asparaginase and 6-MP Therapy During Treatment of Acute Lymphoblastic Leukemia in Pediatric Patients: A Case Series.

BACKGROUND: Asparaginases are a mainstay treatment for pediatric acute lymphoblastic leukemia (ALL). Recent reports identified hypoglycemia associated with asparaginases. Other reports describe hypoglycemia associated with 6-mercaptopurine (6-MP), another fundamental ALL therapy. Little is known about the risk of hypoglycemia associated with ALL therapy, an adverse event that puts children at risk of decreased level of consciousness, seizures, and possibly negative neurocognitive sequelae. METHODS: We performed a retrospective chart review of 6 children with hypoglycemia during ALL treatment in our institution from May 2016 to August 2019. Timing and duration of hypoglycemia relative to polyethylene glycol (PEG)-asparaginase, 6-MP, and corticosteroids were determined. Laboratory values of the critical sample were collected. RESULTS: The median age was 2.75 (interquartile range: 1.88 to 3.63) years. Three patients had trisomy 21. The onset of hypoglycemia was 5 to 19 days after the most recent PEG-asparaginase administration or 6 to 7 months after initiating daily 6-MP. Sixteen hypoglycemic events were documented, and 9/16 had a critical sample drawn. Six events were hypoketotic, associated with PEG-asparaginase. Three were ketotic, associated with 6-MP. Two patients required treatment with diazoxide and cornstarch. CONCLUSIONS: Hypoglycemia associated with PEG-asparaginase occurred later and lasted longer than previous reports with l-asparaginase, with the likely mechanism being hyperinsulinism. 6-MP was associated with ketotic hypoglycemia.

Severe iron deficiency anemia in the paediatric emergency department: A retrospective study.

Background: Transfusion is discouraged in hemodynamically stable children with severe iron deficiency anemia (IDA). Intravenous (IV) iron sucrose (IS) could be an alternative for some patients; however, there is a paucity of data on its use in the paediatric emergency department (ED). Methods: We analyzed patients presenting with severe IDA at the Children's Hospital of Eastern Ontario (CHEO) ED between September 1, 2017, and June 1, 2021. We defined severe IDA as microcytic anemia <70 g/L and either a ferritin <12 ng/mL or a documented clinical diagnosis. Results: Of 57 patients, 34 (59%) presented with nutritional IDA and 16 (28%) presented with IDA secondary to menstrual bleeding. Fifty-five (95%) patients received oral iron. Thirteen (23%) patients additionally received IS and after 2 weeks, the average Hgb was similar to transfused patients. The median time for patients receiving IS without PRBC transfusion to increase their Hgb by at least 20 g/L was 7 days (95%CI 0.7 to 10.5 days). Of 16 (28%) children who were transfused with PRBC, there were three mild reactions, and one patient who developed transfusion associated circulatory overload (TACO). There were two mild and no severe reactions to IV iron. There were no return visits to the ED due to anemia in the following 30 days. Conclusions: Management of severe IDA with IS was associated with a rapid rise in Hgb without severe reactions or returns to ED. This study highlights a strategy for management of severe IDA in hemodynamically stable children that spares them the risks associated with PRBC transfusion. Paediatric specific guidelines and prospective studies are needed to guide the use of IV iron in this population.

Successful Transjugular Portosystemic Shunt Treatment of Pediatric Sinusoidal Obstruction: Case Report and Review of Literature.

Background: In adults with medically refractory sinusoidal obstruction syndrome (SOS), a transjugular intrahepatic portosystemic shunt (TIPS) has been used successfully to improve portal hypertension and symptoms such as ascites. There is limited data on the use of TIPS for SOS in pediatric patients. Methods: The index case was reviewed retrospectively. PubMed and Medline databases were searched to identify other cases. Results: A 4-year-old male with high-risk neuroblastoma, developed SOS after tandem autologous stem cell transplant. He was medically managed with defibrotide, diuretics, and peritoneal drainage, but, due to refractoriness, he underwent TIPS day +54 following bone marrow transplant. Hepatic venous pressure gradient improved from 17 to 8 mm Hg following TIPS placement with significant improvement in the patient's clinical status and ascites. However, 15 months later, his shunt remained patent, and he remains clinically well with stable liver enzymes. A literature review identified 13 pediatric cases of TIPS for SOS due to varied causes. TIPS caused a median hepatic venous pressure gradient of 9 mmHg (range, 2-38 mm Hg). The mortality following the procedure was 15%, with 2 cases who died at 2- and 11-days post-TIPS. At the time of the last follow-up (range 8-25 months), 5 patients were alive, and 8 were lost to follow-up. Conclusion: We present here a pediatric case of SOS due to stem cell transplant treated successfully with TIPS with a review of the literature. A timely, individualized application of TIPS can be effective in treating children with medication-refractory SOS.

Acute myeloid leukaemia presenting as proptosis in an infant.

Paediatric patients with acute myeloid leukaemia (AML) often present with symptoms associated with the disruption of normal haematopoiesis and subsequent cellular deficiencies. Periosteal reactions are common in paediatric leukaemia, but typically manifest as a thin, laminated pattern along long bones. Aggressive periosteal reactions are much less frequently seen. Here, we report a case of paediatric AML initially presenting with proptosis and periorbital swelling caused by aggressive, sunburst periosteal reactions surrounding the sphenoid and zygomatic bones. This unique presentation emphasises the importance of considering leukaemic infiltration in the differential for sunburst periosteal reaction in paediatric patients.

Effect of Eye Masks on Neonatal Stress Following Dilated Retinal Examination: The MASK-ROP Randomized Clinical Trial.

IMPORTANCE: Although screening examinations for retinopathy of prematurity (ROP) prevent blindness, they are physiologically stressful for infants. Photosensitivity during mydriasis may contribute to postexamination stress, and reducing light stimulation may make infants more comfortable. OBJECTIVE: To determine the effect of a phototherapy mask worn during mydriasis on infant stress in the 12-hour period following ROP screening. DESIGN, SETTING, AND PARTICIPANTS: The Effect of Eyemasks on Neonatal Stress Following Dilated Retinal Examination (MASK-ROP) randomized clinical trial with patient recruitment from April 2016 to June 2017 at neonatal intensive care units at St Michael's Hospital and Sunnybrook Health Sciences Center in Toronto, Ontario, Canada. A consecutive series of infants with birth weight of less than 1500 g and/or gestational age of less than 32 weeks undergoing their first ROP screening were analyzed beginning in July 2017. Analysis was intention to treat. INTERVENTIONS: Patients were randomized to wear a phototherapy mask for a minimum of 4 hours after dilating drop instillation in addition to standard comfort measures. MAIN OUTCOMES AND MEASURES: Number of desaturation, bradycardic, or apneic events during the 12-hour postexamination period. RESULTS: Of 51 infants who were examined, 28 (54.9%) were randomized to the treatment group (ie, used a mask) and 23 (45.1%) to the control group. Overall, 10 (35.7%) and 13 infants (56.5%) received ventilator support at the time of examination in the treatment and control groups, respectively. The mean (SD) gestational age was 27.9 (2.4) weeks, 32 (63%) were boys, and the mean (SD) birth weight was 1058.6 (312.0) g. The number of all stressful events were lower in the treatment group compared with controls in the 12-hour postexamination period, adjusted for events prior to examination and ventilation status (mean [95% CI] events, 1.0 [0.6-1.8] vs 1.7 [1.0-1.7]; rate ratio [RR], 0.57; 95% CI, 0.3-1.2; P = .12). Risk factors associated with increased stress included younger gestational age (RR, 1.32; 95% CI, 1.2-1.5 per week), lower birth weight (RR, 1.39; 95% CI, 1.2-1.5 per 100 g), ventilator support around the time of examination (RR, 2.67; 95% CI, 1.3-5.6), intraventricular hemorrhage (RR, 3.78; 95% CI, 1.9-7.3), and hyponatremia (RR, 3.42; 95% CI, 1.8-6.6). No adverse events occurred while using eye masks. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that light sensitivity may play a role in stress observed in the late postexamination period. However, unequal distribution of infants receiving ventilator support placed certain neonates at higher risk of stress, and the clinical significance of this intervention's benefit could not be concluded with confidence. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03824782.