Hematology Commons^™

Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry

Research Days

Background: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome caused by ribosomal protein gene mutations leading to apoptosis of erythroid progenitors. We identified a novel heterozygous variant (c.167+769C>T) in the noncoding region of RPL30 in a patient diagnosed with DBA.

Objectives/Goal: We hypothesized that this variant stunts erythroid differentiation at the proerythroblast stage and is pathogenic for DBA.

Methods/Design: We developed an induced pluripotent stem cell (iPSC) model with a wild type (WT) and three CRISPR-Cas9 edited RPL30 mutant clones. iPSCs were differentiated into hematopoietic stem cells, which were assessed by flow cytometry and single cell …

Effect Of Social Determinants Of Health On Clinic Visit Attendance In Patients With Hemophilia, Shailly Gaur Md, Brian Lee Phd, Mph, James Anderst Md, Msci, Katie Foote Lscsw, Lcsw, Osw-C, Andrea Bradley-Ewing Mpa, Ma, Shannon Carpenter Md

Research Days

Background

Social determinants of health (SDOH) create barriers to seeking care regularly, especially for patients with chronic disease. Patients with moderate-severe hemophilia A and B (factor 8 and 9 deficiencies respectively) have a life-long higher risk of bleeding and require chronic therapies. Specialized care is offered through hemophilia treatment centers (HTCs); however, these can be difficult to access for some individuals. Previous SDOH research in this patient population has been limited; therefore, it can be difficult to identify the barriers to care that exist. There is a need to examine SDOH more thoroughly to create patient-directed interventions to improve access …

Respiratory Failure In Pediatric Hematology And Oncology Patients On Extracorporeal Membrane Oxygenation: A Comparative Analysis, Michelle Brown Do, Jenna Miller, Asdis Finnsdottir Wagner, Erin Hall, Maya Dewan Md, Christopher Dandoy Md, Kalee Grassia Md, Bin Zhang Phd

Research Days

This project was a retrospective comparative analysis between two tertiary care pediatric institutions. The primary objective entailed examining survival outcomes in the oncologic and hematopoetic stem cell transplant patient populations with respiratory failure in the presence and absence of ECMO support.

Early Cholestasis And Vitamin K Deficiency Secondary To Biliary Atresia Presenting As Coagulopathy And Thymic Hemorrhage, Abbey Elsbernd, Lauren Amos Md

Research Days

Background

Bleeding and progressive coagulopathy are established symptoms of early cholestasis, including extrahepatic biliary atresia. We present a patient with bleeding secondary to vitamin K deficiency and cholestasis-induced fat malabsorption with unusual presentation of mediastinal mass.

Objective

Describe a case of late-onset vitamin K deficiency and cholestasis presenting as jaundice and coagulopathy with associated bleeding into thymic structures Design/Method

Case report

Results

A 4-week-old term male infant was brought to the ED with fussiness and bruising. Prior to presentation, he was afebrile and followed regularly with his primary care provider for jaundice below phototherapy thresholds. Infant received vitamin K at …

Testing For Bleeding Disorders In Child Abuse: Adherence To Aap Recommendations And Results Of Testing., Lyndsey Hultman, James Anderst, Henry T. Puls, Shannon L. Carpenter, Angela Doswell, Angela N. Bachim, Joanne Wood, Kristine Campbell, Daniel M. Lindberg

Research Days

This was a retrospective, descriptive study of bleeding disorder testing practices among subjects in CAPNET, a multicenter research network of children evaluated by Child Abuse Pediatricians for concern of child physical abuse.

Functional Evaluation Of A Novel Rpl30 Mutation And Its Role In Diamond Blackfan Anemia (Dba), Alexandra Prosser, Alexandria Cockrell, Danny Miller, Chris Seidel, Tamara Potapova, John M. Perry, Midhat Farooqi, Erin M. Guest, Jennifer Gerton

Research Days

Background: Bone marrow failure is life-threatening and requires prompt, intensive treatment, which is dependent upon identification of genetic drivers. Although there has been investigation into associated genetic mutations, especially in Diamond Blackfan anemia (DBA), the relationship between genotype and phenotype remains unclear.DBA has been identified as a ribosomopathy, also known as a disease associated with defects in ribosome biogenesis. We identified a novel heterozygous variant (c.167+769C >T) in the noncoding region of RPL30 in a patient with clinical diagnosis of DBA. Clinical RNA sequencing (RNA-seq) suggests the variant generates a novel splice acceptor site resulting in truncated RPL30 transcripts. Elucidation …

Increasing Incentive Spirometry Use In Patients With Sickle Cell Disease: Longer Follow-Up Of Pdsa Cycle 1, Alexandra Prosser, Thomas Cochran

Research Days

Problem Statement/Question: Acute chest syndrome (ACS) is one of the leading causes of morbidity and mortality in patients with sickle cell disease. Patients are at higher risk for this complication during hospital admission due to limited mobility leading to decreased lung inflation. The National Heart, Lung, and Blood Institute (NHLBI) recommends providing ten breaths of incentive spirometry (IS) every two hours while awake for patients admitted to the hospital with sickle cell disease to help prevent development of acute chest syndrome. Without this intervention, patients are more likely to develop ACS requiring increased level of care, prolonged hospital stays, and …

Case Series: Bone Marrow Failure In Teen Siblings With Unique Rps19 Variant, Alexandra Prosser

Research Days

Background: Upon diagnosis of aplastic anemia, inherited bone marrow failure syndromes and acquired etiologies must be considered. Investigating causality is particularly important when multiple family members are affected. It is also essential to identify novel causative genetic variants of bone marrow failure to direct treatment in these patients.

Objectives: To describe the diagnosis and management of siblings who presented two weeks apart with severe pancytopenia and were diagnosed with severe aplastic anemia.

Methods: The first patient is a 13-year-old non-binary female who presented with severe pancytopenia on routine labs. Bone marrow biopsy revealed marked hypocellularity (0-10%) with hypoplasia. The second …

A Novel Approach To Triosephosphate Isomerase Deficiency, Kyra Mccarty

Research Days

Background: Triosephosphate isomerase deficiency (TPID) is a glycolytic pathway enzymopathy causing hemolytic anemia and neurologic dysfunction. TPID is caused by mutations in the TPI1 gene. These patients experience severe hemolytic anemia in infancy followed by progressive neurodegeneration. Diagnosis of TPID is made by measuring decreased TPI enzyme activity elevated dihydroxyacetone phosphate (DHAP) levels in the blood. The diagnosis is confirmed by molecular genetic testing. Neurological involvement typically manifests between 6 and 24 months of age, causing progressive motor dysfunction. Chronic axonal neuropathy is often present on nerve biopsy, and peripheral neuropathy is evident on electrophysiologic studies. Splenectomy and blood transfusions …

Primary Venous Thromboprophylaxis In Pediatric Oncology Patients, Kyra Mccarty

Research Days

Background: The Virchow’s Triad principles of venous stasis, endothelial damage, and hypercoagulability are all features of malignancy and contribute to the increased risk venous thromboembolism (VTE) seen in oncology patients. Additionally, certain chemotherapy treatments, presence of a central venous catheter and immobility are also intrinsically associated with malignancy diagnoses and exacerbate this risk. However, much debate exists over the use of thromboprophylaxis in the pediatric population, primarily due to lack of evidence regarding safety and efficacy, primarily the risk of major bleeding. Multiple retrospective studies have attempted to identify the primary risk factors for VTE in this pediatric oncology patient …

A Study Examining The Safety And Efficacy Of Ferric Carboxymaltose In A Large Pediatric Cohort, Chandni Dargan Md, David Simon Do

Research Days

Background: Iron deficiency anemia (IDA) is common in the pediatric population with varying high-risk factors. Intravenous (IV) iron supplementation has become more desirable in patients with moderate to severe anemia and in patients who are either unresponsive to or have adverse side-effects secondary to oral iron. Iron sucrose and Iron dextran have been traditionally used in pediatrics while ferric carboxymaltose (FCM) has only been FDA approved in adults. One of the major advantages of FCM is the ease of dosing and efficacy. Though FCM was approved for adults in 2013 and there have been no safety concerns, it is not …

A New Paradigm: Ecmo Therapy In Pediatric Hematology/Oncology Patients, Igor Areinamo

Research Days

Background: The use of extracorporeal membrane oxygenation (ECMO) for support of pediatric patients has significantly increased in the past years. Patients with known oncologic diseases, immunodeficiencies, or bone marrow transplants (BMT) have traditionally not been considered candidates for Extracorporeal membrane oxygenation (ECMO) due to perceived high risk for mortality. Ongoing advances have continued to push the boundaries of ECMO use and we report our recent experience with this patient population

Objectives/Goal: To evaluate survival to discharge of pediatric patients who require ECMO support and who also have an underlying hematologic or oncologic disease process. To determine specific patient characteristics that …

Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson

Research Days

Background: Our center receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurately interpreting lab results. Bhasin et al showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little published about the referral patterns to pediatric hematology and the outcomes of these referrals.

Objectives/Goal: To characterize our hematology referrals for bleeding disorder …

Right Arm Pain, Color Change And Swelling In A 17-Year-Old Male Baseball Pitcher, Alvin Chi

Research Days

No abstract provided.