Hematologic Abnormalities Research Articles

Acute pancreatitis following asparaginase treatment in pediatric acute lymphoblastic leukemia with a heterozygous SPINK1 c.194 + 2T>C intronic variant: a case report

BackgroundAsparaginase is a critical component of chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but its use is often complicated by asparaginase-associated pancreatitis (AAP). Genetic predispositions, such as variants in the SPINK1 gene, have been linked to an increased risk of pancreatitis. However, the role of genetic factors in relation to asparaginase treatment remains incompletely understood, partly because mutations in pancreatitis-causing genes are rarely found in pediatric ALL.Case descriptionA four-year and three-month-old Chinese girl was admitted to our hospital due to fever for half a day, with no history of significant prior medical history. Initial blood tests revealed hematological abnormalities, including leukopenia, anemia, and thrombocytosis. Bone marrow aspiration identified 81.5% blast cells with B-lymphocyte morphology and immunophenotype, leading to a diagnosis of B-cell acute lymphoblastic leukemia (B-ALL). The patient began treatment under the CCCG-ALL-2015 protocol, which included PEG-asparaginase (PEG-asp). On day 10 of induction, she developed AAP, which was primarily characterized by severe epigastric pain and elevated serum amylase. Despite effective symptom management with analgesics and anti-inflammatory therapy, AAP recurred following administration of L-asparaginase (L-asp). Genetic analysis revealed a heterozygous SPINK1 c.194 + 2T>C variant (rs148954387), a well-known pathogenic variant associated with increased susceptibility to pancreatitis. Sanger sequencing confirmed that the SPINK1 variant was inherited from her asymptomatic mother. The patient's AAP was managed conservatively, and an asparaginase-free regimen ultimately achieved complete remission without recurrence of pancreatitis.ConclusionsThe identification of the SPINK1 c.194 + 2T>C variant, which is recognized as pathogenic, provides valuable information for understanding the heightened risk of AAP in our pediatric ALL patient. Our case underscores the potential role of genetic predisposition in the development of AAP and highlights the importance of considering genetic screening prior to asparaginase therapy in pediatric ALL patients to identify those at increased risk.

Vancomycin-associated DRESS demonstrates delay in AST abnormalities.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse drug eruption characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and organ dysfunction. Identifying causative agents and monitoring disease course in DRESS syndrome is crucial to prevent end-organ damage. The temporal relationship between causative medications including vancomycin and laboratory abnormalities in DRESS has not been studied, limiting the utility of laboratory data in monitoring disease course. Our study aims to investigate associations between medication class and peak serum laboratory values using simple linear regression (absolute eosinophils, creatinine, alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). We found a significant difference between timing of peak AST values among vancomycin-triggered DRESS compared to other trigger groups. These findings draw attention to the increased role of AST as a diagnostic and monitoring tool in DRESS.

Refractory Chylothorax and Ventricular Hypertrophy Treated with Trametinib in a Patient with Noonan Syndrome: 18-Month Follow-Up

RASopathies are a group of genetic syndromes caused by germline mutations in genes involved in the RAS/Mitogen-Activated Protein Kinase signaling pathway, which regulates cellular proliferation, differentiation, and angiogenesis. Despite their involvement at different levels of this pathway, RASopathies share overlapping clinical phenotypes. Noonan syndrome is the most prevalent RASopathy, with an estimated incidence of 1 in 2500 live births, and it is typically inherited in an autosomal dominant manner, with 50% of cases involving gain-of-function mutations in the PTPN11 gene. De novo mutations are common, accounting for 60% of cases. The phenotype of Noonan syndrome includes characteristic facial and physical features, congenital cardiac defects, lymphatic and cerebrovascular anomalies, renal malformations, hematological abnormalities, developmental issues, and an increased risk of cancer. Severe congenital cardiac defects and lymphatic abnormalities significantly impact prognosis, contributing to increased morbidity and mortality. Recent therapeutic advancements have introduced trametinib, an MEK1/2 inhibitor, for treating Noonan syndrome patients with severe cardiac and lymphatic complications. To assess its efficacy, here, we present a case of a newborn with Noonan syndrome who exhibited refractory chylothorax, ventricular hypertrophy, and pulmonary stenosis who was treated with trametinib. The patient demonstrated significant improvement in chylothorax and left ventricular hypertrophy, though pulmonary stenosis persisted. This case further confirms trametinib’s potential as a therapeutic option for severe Noonan syndrome complications, emphasizing the need for further clinical trials to optimize treatment protocols and evaluate long-term outcomes.

Immuno-hematological parameters among adult HIV patients before and after initiation of Dolutegravir based antiretroviral therapy, Addis Ababa, Ethiopia.

Immuno-hematological abnormalities are common among HIV infected individuals as well as patients with highly active antiretroviral therapy (HAART). However, the immuno-hematological outcome of Dolutegravir based antiretroviral therapy (ART) usage is not well investigated. To assess hematological and immunological parameters among adult HIV patients before and after initiation of Dolutegravir based ART regimen at St. Peter Specialized Hospital, Addis Ababa, Ethiopia. A cross-sectional study was conducted from May to July 2021 at St. Peter Specialized Hospital among adult HIV patients. A total of 422 HIV patients on Dolutegravir based ART (combination of Dolutegravir/lamivudine/tenofovir disoproxil fumarate (DTG/3TC/TDF)) for a minimum of 3 months were selected using convenient sampling methods. Socio-demographic as well as clinical data of the participants was obtained using pre-tested structured questionnaires and a review of medical records. Hematological parameters such as CBC was obtained using Beckman coulter automated hematology analyzer and immunological parameters such as CD4 count were determined using BD FACS presto. Statistical analysis of the data was done using SPSS version 21. Paired t-test was used to compare dependent variables before and after initiation of the new HAART and binary logistic regression was used to determine predictors of immuno-hematological abnormalities. P-value < 0.05 was considered as statistically significant. Of 422 adult HIV patients, about 273(64.7%) were females. The mean age of study participants was 42.2 years (±10.4SD). The mean white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), platelet distribution width (PDW), CD4 count, as well as lymphocyte percentage, neutrophil percentage, and platelet counts (PLT) were increased significantly(P<0.05) after 3 months of the Dolutegravir based therapy. While, red cell distribution width (RDW) and mean cell hemoglobin (MCH) were decreased (P<0.05) after the treatment. Other hematological parameters such as mean cell volume (MCV), hematocrit (HCT), mean cell hemoglobin concentration (MCHC), mean platelet volume (MPV) and platelet distribution width (PDW) showed no significant change. On the other hand, the most common hematological abnormalities identified after the new HAART were anemia (12.1%); followed by Leucopenia (11.3%), neutropenia (6%), and thrombocytopenia (4%). Anemia was associated with female sex (AOR = 7.8, 95% CI: 1.9-32.2, P<0.005) and WHO clinical stage III/IV (AOR = 16, 95% CI: 10.63-66.46, P<0.01). There was a significant change in certain immuno-hematological parameters such as WBC count, RBC count, PLT count, Hb, PDW, CD4 count, lymphocyte and neutrophil percentage after initiation of the Dolutegravir based therapy. Anemia was the most common hematological abnormality. Further studies are required to fully comprehend the outcome of the new treatment regimen on immuno-hematological parameters.

Clinical and neuroimaging patterns of perinatal intracranial haemorrhage in fetuses and term-born neonates: a prospective observational cohort study.

To characterise perinatal, clinical and neuroimaging patterns and aetiology of perinatal intracranial haemorrhage (pICH), and to assess potential differences between cases diagnosed antenatally and postnatally. Prospective, observational, single-centre study of 110 consecutive cases of pICH identified in the fetal or neonatal period or diagnosed with presumed pICH between 2014 and 2023. Prematurity-related cases were excluded. Antenatal and postnatal MRI data were analysed for patterns and mechanisms of haemorrhage and their potential aetiology. Potential associations between pICH with perinatal and clinical risk factors were also explored. Fifty-nine of the 110 included cases (53.6%) were diagnosed antenatally (termination of pregnancy, n=22), and postnatal data on 81/88 (92%) children were available. Intraventricular haemorrhage (IVH) was the most common haemorrhage type (83/110 (75.5%)) and was more common prenatally (p=0.004). Subpial haemorrhage was exclusively diagnosed postnatally (p<0.001), and it was more commonly detected in primigravida women (p=0.013). The germinal matrix was the most common origin of IVH (n=56, 50.9%) occuring more frequently prenatally (p<0.001), whereas sinus venous thrombosis-related IVH was more commonly detected postnatally (p=0.002). Subdural haemorrhage was associated with haematological abnormalities (p=0.023). Genetic disorders caused 31.9% of the cases (15 of 47 tested cases). Genetic disorders and associated congenital anomalies were more common in the prenatally diagnosed group (p=0.038 and p=0.04, respectively). The patterns and pathogenesis of pICH appear to be different for prenatally and postnatally diagnosed cases and for types of haemorrhages. Given the important role of genetic factors in prenatal intracranial haemorrhage, next-generation sequencing is indicated in these cases.

Feline Vector-Borne Diseases and Their Possible Association with Hematological Abnormalities in Cats from Midwestern Brazil

Among the parasitic and infectious diseases affecting cats, those caused by vector-borne pathogens deserve attention due to their ability to cause nonspecific clinical signs and clinicopathological abnormalities. We studied the presence of Cytauxzoon spp., Ehrlichia spp., and Mycoplasma spp. in blood samples from 135 cats referred to the veterinary teaching hospital of the Federal University of Goiás in midwestern Brazil. We also investigated co-infections with Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) as well as the correlation between Mycoplasma spp. infection and cat variables, including age, sex, breed, and complete blood count abnormalities. Upon PCR testing, 20.7% (28/135) of samples were positive for Mycoplasma spp., 1.5% (2/135) for Cytauxzoon spp., and none for Ehrlichia spp. Co-infections with Mycoplasma spp. and Cytauxzoon spp. were detected in the two cats with the latter infection. Mycoplasma spp. infection was statistically associated with the simultaneous presence of thrombocytopenia and leukocytosis. This study confirms a high frequence of Mycoplasma spp. infection, with both M. haemofelis and ‘Candidatus Mycoplasma haemominutum’ circulating in this cat population. The clinical significance of Mycoplasma spp. infection in cats should be further explored and this infection should eventually be included in the differential diagnosis of thrombocytopenia and leukocytosis in otherwise apparently healthy cats.

Clonal haematopoiesis of indeterminate potential predicts recurrence of atrial arrhythmias after surgical ablation for atrial fibrillation

Abstract Background Clonal haematopoiesis of indeterminate potential (CHIP), characterized by the presence of somatic blood cell clone expanding without other haematological abnormalities, was recently shown to be significantly associated with the development and progression of atrial fibrillation (AF). However, the clinical relevance of CHIP in patients underwent surgical atrial ablation remained unexplored. Aims This study investigated the potential role of CHIP in the recurrence of atrial arrhythmias after surgical ablation in patients with AF. Methods Deep-target sequencing of 74 CHIP (a mean depth of coverage = 4051x) was performed in 132 patients with AF (mean age, 60 years; 75.8% male; mean left atrial diameter, 47mm) who underwent surgical ablation without previous atrial ablation between December 2014 and September 2021. Variant allele fraction (VAF) ≥ 2.0% of any targeted genes indicated the presence of CHIP mutations. The primary outcome is the recurrence of any atrial arrhythmias for &amp;gt;30s after a blanking period of 3 months within a year. The clinical significance of CHIP was determined by multivariable Cox proportional hazards regression. Results A total of 17.4% (23 of 132) patients with AF carried CHIP mutations (DNMT3A, 8.3% and TET2, 3.8%). CHIP prevalence varied among AF types, with paroxysmal, persistent, and long-lasting AF counting for 12.5%, 16.5%, and 36.4%, respectively. During one-year follow-up after blanking period, recurrent atrial arrhythmia was documented in 15 (65.2%) and 37 (33.4%) patients in the CHIP and non-CHIP groups, respectively (p = 0.005 for log-rank test). The association of CHIP with atrial arrhythmias recurrence remained significant after fully adjustment (hazard ratio, [95% confidence interval], 1.92 [1.02-3.63]). Conclusions CHIP mutations with a VAF ≥ 2.0% were identified in 17.4% AF patients undertaken surgical ablation and was associated with poor prognosis. CHIP assessment may be useful in the personalized management of patients who planned to perform surgical ablation for AF.

Immunological, Serological and Hematological Changes in COVID 19 Patients of Dhaka City

The analytical test reports of COVID-19 patients admitted in two major hospitals in Dhaka City were analyzed to observe the immunological, serological and hematological abnormalities that can be significant for managing the patients in emergencies. The observed levels of ferritin, procalcitonin, D–Dimer, C-reactive protein (CRP), creatinine and alkaline phosphatase (Alkp) were taken into consideration for this study. Though these parameters were elevated as mentioned for patients from many other countries, in significant cases, the values were normal or even lower than the normal levels. The ferritin level was normal (For men, 24 to 336 micrograms per liter. For women, 11 to 307 micrograms per liter) in only 30% of the patients, whereas, 50% of the patients had higher values and 20% patients had the lower values. Similarly, the procalcitonin (normal value 0.1 to 0.5 ng/mL) level was found to be normal in only 27% of the patients while remaining 73% patients had the high level of this parameter. The D‑Dimer level (less than 0.50) was also found to be normal in only 27% of the patients, whereas 72% of the patients had the higher levels. The C‑reactive protein was within the normal level in only 22% of the patients, whereas, 76% of the patients had the high level of this marker. The creatinine was found to be increased in 60% of the patients. There were 88% patents having increased levels of Alkp with only 12% patients having normal levels. Thus, the elevations of the immunological, serological and hematological parameters were somehow different from those observed from patients in other countries. This information might be useful in managing the hospitalized COVID-19 patients in our country. Jagannath University Journal of Science, Volume 11, Number 1, June 2024, pp. 203−207

Clinical implications of miRNAs in erythropoiesis, anemia, and other hematological disorders.

Erythropoiesis is regulated by the differential expression of many genes. Besides being transcriptionally regulated, these genes are also with the oath of epigenetic regulation by the microRNAs (miRNAs), in particular. Various miRNAs appear to be very important for the normal process of erythropoiesis and various hematological abnormalities in humans. Therefore, the review aims to summarize the significance of miRNAs in erythropoiesis and different hematological diseases with clinical importance. Our analysis indicates that specific miRNAs regulate erythropoiesis in a stage-specific manner from hematopoietic stem cells to differentiated erythrocytes. Further, many miRNAs have been reported to be linked with various hematological diseases. The importance of miRNAs as biomarkers or therapeutic drug targets for various hematological disorders like anemia, β-thalassemia, and leukemia has been revealed through various clinical studies and clinical trials. The miR-34a mimic and miR-155 inhibitor demonstrate promising therapeutic effects in various hematological malignancies. Additionally, miR-34a, miR-538e, miR-193e, and miR-198 exhibit diagnostic potential in acute myeloid leukemia, while miR-451, miR-151-5p, and miR-1290 show diagnostic potential in B-cell acute lymphoblastic leukemia. Thus, this review encompasses the latest observations and implications of specific miRNAs in erythropoiesis and various hematological disorders. However, challenges persist in developing safe and efficient delivery strategies to target miRNAs specifically, minimizing off-target effects and enhancing therapeutic outcomes. Future mechanistic pre-clinical and clinical research would contribute to overcoming these challenges.

Nanoparticle-Directed Antioxidant Therapy Can Ameliorate Disease Progression in a Novel, Diet-Inducible Model of Coronary Artery Disease.

Oxidative stress plays a crucial role in the pathogenesis of coronary artery disease. In cardiovascular research using murine models, the generation and maintenance of models with robust coronary arterial atherosclerosis has been challenging. We characterized a new mouse model in which the last 3 amino acids of the carboxyl terminus of the HDL (high-density lipoprotein) receptor (SR-B1 [scavenger receptor class B, member 1]) were deleted in a low-density lipoprotein receptor knockout (LDLR-/-) mouse model (SR-B1ΔCT/LDLR-/-) fed an atherogenic diet. We also tested the therapeutic effects of an oxidative stress-targeted nanoparticle in atherogenic diet-fed SR-B1ΔCT/LDLR-/- mice. The SR-B1ΔCT/LDLR-/- mice fed an atherogenic diet had occlusive coronary artery atherosclerosis, impaired cardiac function, and a dramatically lower survival rate, compared with LDLR-/- mice fed the same diet. As SR-B1ΔCT/LDLR-/- mice do not exhibit female infertility or low pup yield, they are far easier and less costly to use than the previously described SR-B1-based models of coronary artery disease. We found that treatment with the targeted nanoparticles improved the cardiac functions and corrected hematologic abnormalities caused by the atherogenic diet in SR-B1ΔCT/LDLR-/- mice but did not alter the distinctive plasma lipid levels. The SR-B1ΔCT/LDLR-/- mice developed diet-inducible, fatal atherosclerotic coronary artery disease, which could be ameliorated by targeted nanoparticle therapy. Our study provides new tools for the development of cardiovascular therapies.

Features of Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic mutation syndrome associated with the c.121A&amp;gt;C, p.(Met41Leu) UBA1 genetic variant: A systematic review

Abstract Introduction/Objective Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic mutation (VEXAS) syndrome was first described in 2020. VEXAS is driven by a mutation in the UBA1 gene on hematopoietic progenitor cells that encodes the E1 ubiquitin-activating protein. Loss of this protein leads to various inflammatory clinical presentations ranging from dermatological, pulmonary, rheumatologic and hematologic. Many UBA1 variants have been identified. We did a systematic review focusing on a particular UBA1 variant gene mutation underlying this disease process. Methods/Case Report Databases were searched for articles discussing VEXAS syndrome until April 2024. Only case reports and case series in the English language were included. Data on patient demographics, clinical presentation, laboratory values, bone marrow findings, dermatologic presentation and skin biopsy findings were extracted. Results (if a Case Study enter NA) 332 articles discussing VEXAS syndrome were retrieved, of which 115 were case reports or case series. These were screened for patients carrying a p.Met41Leu UBA1 gene mutation and only the 25 patients with this genetic variant were ultimately included in our study. The average age was 68 years (59-81 years). 24/25 (96%) patients reported dermatologic symptoms ranging from erythema to urticarial eruptions to erythema multiforme. Fever was the second most common presenting complaint (76%) followed by arthritis (68%), chondritis (36%) and thromboembolic disease (28%). Macrocytic anemia was a common laboratory finding (65%). MDS was seen in 52% of the patients. All patients had hematopoietic progenitor cells with vacuoles. Sweet’s syndrome was the most common initial diagnosis (52%) as skin biopsies in most patients showed dermal edema and neutrophilic dermatoses/infiltration. Conclusion The c.121A&amp;gt;C, p.(Met41Leu) UBA1 variant is frequently related to cutaneous manifestations. In patients with clinical features of an inflammatory disorder with dermatological and hematologic abnormalities, testing for the p.Met41Leu UBA1 mutation might lead to an earlier diagnosis and prompt initiation of effective treatment.

Neonatal Alloimmune Thrombocytopenia with HLA and HPA-3a Antibodies in a Down Syndrome Neonate

Abstract Introduction/Objective Neonatal Alloimmune Thrombocytopenia (NAIT) is a rare cause of thrombocytopenia seen in 1 in 11,000 neonates with lethal risks such as intracranial hemorrhage. This is caused by maternal antibodies against fetal platelets and the most common culprits are antibodies to Human Platelet Antigen-1b (HPA-1b) but rarely to Human Leukocyte Antigen (HLA) antibodies. We describe a rare case of a newborn with Down syndrome with maternal antibodies against HLA and presumed antibodies against HPA-3a. Down syndrome causes hematologic abnormalities with mild thrombocytopenia. Methods/Case Report A preterm male with Down syndrome was born via Cesarean delivery due to non-reassuring fetal heart tracing at a gestational age of 35 weeks. He was admitted for low birth weight and his hospital course was complicated by severe thrombocytopenia of 37 x 10^9/L without bleeding symptoms. Initially attributed to his trisomy 21 but due to his suboptimal response to platelet transfusion, NAIT was suspected. The mother had antibodies against HLA on initial screen and was presumed to have HPA-3a antibodies since she was homozygous for HPA-3b antigen. The neonate was managed with multiple transfusions of platelets and Intravenous Immunoglobulin (IVIG). The platelet count stabilized to 325 x 10^9/L on his 25th day of life. Results (if a Case Study enter NA) n/a Conclusion To our knowledge, this is the only published case of NAIT with both HPA-3a and HLA antibodies in a Down syndrome neonate. It is unclear whether the primary reason for thrombocytopenia is due to NAIT caused by HPA-3a antibodies or HLA antibodies or his existing Down syndrome. This case contributes to understanding the complexity between immune-related diseases such as NAIT and genetic conditions such as Down syndrome. Although NAIT occurs rarely, timely diagnosis and treatment is of utmost importance to prevent lethal complications.

“Synchronous Development of Acute Myeloid Leukemia and Multiple Myeloma: A Rare Case Presentation”

Abstract Introduction/Objective The co-occurrence of acute myeloid leukemia (AML) and multiple myeloma (MM) presents a diagnostic challenge, particularly when it arises without prior chemotherapy exposure. This study aims to elucidate the clinical characteristics, diagnostic approach, and management implications of such synchronous hematologic malignancies through a detailed case report. Methods/Case Report A 64-year-old female with no previous medical history presented with chest pain, shortness of breath, and hematologic abnormalities. Clinical evaluation revealed severe pancytopenia, cystic liver mass, enlarged retroperitoneal lymph nodes, and hypercalcemia. Peripheral blood smear indicated hematologic malignancy, prompting further investigation. Bone marrow aspirate analysis, including flow cytometry and immunohistochemical stains, was performed to confirm the dual cell populations of AML blasts and MM plasma cells. Results (if a Case Study enter NA) Flow cytometric analysis and immunohistochemical stains of the bone marrow aspirate confirmed the presence of distinct cell populations: blasts expressing markers consistent with AML and abundant plasma cells indicative of MM. Monotypism of plasma cells was established, with kappa predominance. Notably, there was no coexpression of markers between the AML blasts and MM plasma cells. Conclusion This case highlights the rare occurrence of synchronous AML and MM in a patient without prior chemotherapy exposure. The diagnostic approach involving flow cytometry and immunohistochemical stains proved essential in confirming the dual hematologic malignancies. Clinicians should be vigilant for such presentations, as timely diagnosis and appropriate management are crucial for optimizing patient outcomes in these complex cases.

Long-term hematopoietic dysfunction in patients with large-scale mitochondrial DNA deletion syndromes.

Pearson syndrome (PS) and Kearns-Sayre syndrome (KSS) are single large-scale mitochondrial DNA deletion (SLSMD) syndromes. PS is characterized by severe, transient childhood cytopenia, whereas KSS typically manifests later in life without hematologic abnormalities. Despite distinct clinical presentations, both share a common mitochondrial DNA deletion. Recent observations suggest a potential link between PS progression and myeloid malignancy development, indicating that bone marrow failure (BMF) may be a key aspect of PS pathology and potentially universal across SLSMDs. This study explores longitudinal hematological manifestations of SLSMD syndromes, focusing on bone marrow (BM) dysfunction. Sixteen patients with SLSMDs (13 PS and 3 KSS) were followed, of whom 75% experienced cytopenia, necessitating blood transfusions in 56%. Despite achieving transfusion independence at a median age of 24 months, persistent hematological abnormalities were noted. Comprehensive longitudinal BM studies were conducted in 62% of subjects and consistently revealed signs of marrow dysfunction, even without concurrent cytopenia. Median BM cellularity at a median age of four years and eight months was 50%, with histological signs of dyserythropoiesis, abnormal megakaryocytes, and signs suggesting myelodysplasia. Reduced CD34+ counts and BM colony-forming unit capacity were noted, alongside chromosome 7 aberrations in 16% of patients on cytogenetic studies. Our findings establish BM dysfunction as a persistent hallmark of SLSMD syndromes, posing a risk of clonal evolution and acquisition of chromosome 7 aberrations. This aligns with recent literature, emphasizing enduring BMF in SLSMD syndromes and advocating for tailored hematological monitoring guidelines for this unique patient cohort.

Maternal Immune Thrombocytopenic Purpura Leading to Severe Neonatal Autoimmune Thrombocytopenia: Report of Two Cases

Introduction: In neonatal intensive care units, neonatal thrombocytopenia is one of the common hematological abnormality seen. Neonatal autoimmune thrombocytopenia should be considered in any neonate who is born to a known case of immune thrombocytopenia purpura (ITP) mother, with early onset thrombocytopenia without any signs of sepsis. Neonatal ITP is a condition of autoantibody mediated platelet destruction. Case details: Two neonates with thrombocytopenia, born to mothers with ITP are described in this report. Lowest platelet count noted was 7000 cells/cmm in one of the neonate. Both neonates received intra venous immunoglobulin (IVIG) while one neonate had persistent and severe thrombocytopenia requiring multiple random donor platelet (RDP) transfusions followed by oral steroid as well. Conclusion: Neonatal thrombocytopenia associated with maternal ITP need close monitoring, early sampling and diagnosis to prevent any possible complications and warrant early initiation of treatment.

7563 Investigation of the safety of GH treatment for Noonan syndrome -single center experience

Abstract Disclosure: M. Ishimaru: None. S. Fukui: None. E. Tanimoto: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. H. Doi: None. M. Igarashi: None. T. Kashima: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. [Background] Growth hormone (GH) treatment for Noonan syndrome (NS) was approved in Japan in 2017. Although there have been no reports of serious adverse reactions associated with GH treatment for NS, there have been reports of myocardial thickening and warnings about malignant tumours which might be related to GH treatment. [Objective] To investigate the short- and long-term safety of GH treatment in patients with NS treated with GH at our hospital. [Methods and results] Medical records of 21 patients with NS (12 males and 9 females) treated with GH at our hospital from August 2006 to April 2023 were investigated retrospectively. Genetic diagnosis was performed in 13 patients, the others were clinically diagnosed. The patients ranged in age from 3 y 1 m to 11 y 6 m at the start of treatment, and the duration of treatment ranged from 11 m to 9 y 5 m. 2 patients had existing hypertrophic cardiomyopathy (HCM), and no patients experienced malignant neoplasmas or other hematologic abnormalities before treatment. The height was on average -3.60 SD at the start of treatment and had improved to an average of -2.10 SD at the most recent measurement. GH treatment was well-tolerated and no new severe adverse events were observed except for two who developed HCM after initiation of GH treatment. One patient developed HCM at the age of 17y and 0 m, 7 y 4 m after starting treatment. The treatment was continued in consultation with a cardiologist and completed at the age of 17 y and 4 m. Another patient was diagnosed as HCM 2 years and 3 months after the start of treatment. At the age of 7 y 2 m, 3 y 5 m after starting treatment, GH treatment was temporarily stopped by the cardiologist's decision. [Discussion] More than half of the children with Noonan syndrome have been reported to have short stature, indicating the effectiveness of GH treatment. Improvement of short stature has also been observed in our GH-treated cases. On the other hand, malignant tumours occur more frequently in NS and 50% of patients, with or without cardiomyopathy, are reported to have abnormal electrocardiograms. Long-term effect of GH and long-acting GH treatment on neoplasm formation and/or cardiac diseases should be carefully monitored. [Conclusion] The safety issues of GH treatment in Noonan syndrome should be monitored carefully. Presentation: 6/3/2024

6928 Vitamin D excess in a patient with hypoparathyroidism after parathyroidectomy

Abstract Disclosure: Z. Zavgorodneva: None. A. Barsegian: None. F. Zhang: None. Introduction. We describe a case of a patient with mild persistent hypoparathyroidism after parathyroidectomy with autotransplantation, which was indicated for ESRD-related secondary hyperparathyroidism. The patient presented with nonspecific complaints and was found to have a high Vitamin D level after long-term moderate-dose Vitamin D supplementation. Case report. A 71-year-old male with a past medical history of end-stage renal disease (ESRD) undergoing hemodialysis for the past 18 years, as well as a history of parathyroidectomy with autoimplantation of parathyroid glands in the forearm in 2010 due to severe secondary hyperparathyroidism, presented to the hospital complaining of generalized weakness and lower extremity cramps that had been ongoing for a few weeks. Further investigations did not reveal evidence of infectious processes. A review of medications indicated the absence of statins among his outpatient medications. No focal neurological deficits or objective signs of muscle weakness were identified. Laboratory findings showed no significant metabolic derangements or haematological abnormalities. Inflammatory markers and creatine phosphokinase were within normal ranges. As part of the workup for generalized subjective weakness and ESRD, Vitamin D levels were checked, revealing a result of of120 ng/mL. The patient reported taking over-the-counter 2000 IU of Vitamin D twice daily for the past six years despite having a normal level of Vitamin D checked five years prior to admission. Calcium supplements were initiated in the postoperative period and continue to be administered at a dose of 600 mg daily. Analysis of the PTH-calcium axis demonstrated persistent mild hypoparathyroidism with hypocalcemia since the time of the surgery. However, there was an observed tendency for calcium levels to improve, especially in the last six years. Vitamin D supplement was discontinued, and the patient was subsequently discharged home with the continuation of physical therapy. Discussion. Explaining the origin of the high level of Vitamin D in this patient poses a challenge. There is limited data in the literature regarding the long-term effects of vitamin D use when the initial Vitamin D levels are normal. Additionally, there are numerous abstracts suggesting significantly higher doses of Vitamin D received for up to 6 years without any evident biochemical or clinical consequences. Moreover, the typical consequences of Vitamin D toxicity, such as hypercalcemia, can not be present in patients who underwent parathyroidectomy. Therefore, it is possible to consider that the severe generalized subjective weakness may be a sign of Vitamin D toxicity itself. Presentation: 6/1/2024

7876 Complex Complications of Thionamide Therapy in One Patient: Methimazole-Induced Agranulocytosis and PTU-Induced ANCA-Vasculitis

Abstract Disclosure: E. Zweibach: None. A. Chang: None. Introduction: Thionamides, including methimazole and propylthiouracil (PTU), are essential for treating Graves' disease but can cause serious side effects such as agranulocytosis and ANCA-vasculitis. Although agranulocytosis itself is quite uncommon, the incidence of ANCA vasculitis is even more infrequent, making combination of conditions particularly exceptional. We present a unique case of a Graves' disease patient who suffered both complications: agranulocytosis due to methimazole and ANCA vasculitis from PTU, with successful resolution of both the clinical signs and laboratory findings following drug discontinuation. Case: 61-year-old female with a history of Graves' disease previously managed with methimazole but discontinued due to agranulocytosis, presented with lower extremity swelling, atrial fibrillation with RVR, and high output cardiac failure. Laboratory tests showed hyperthyroidism (TSH 0.008, Free T4 3.07), leading to a diagnosis of thyroid storm. Patient was started on PTU inpatient and discharged with this medication to home. Eight months later, the patient developed alarming signs including gross hematuria, oral ulcers, widespread muscle pain, found to have AKI with Cr of 2.79 and hospitalized for further eval. While hospitalized, the patient was found to have a range of complications including leukopenia with normal granulocyte count, anemia, AKI, proteinuria, and microscopic hematuria. Rheumatological evaluation showed +ANA and a high ANCA titer &amp;gt;1:1280, along with elevated levels of MPO and PR-3, and reduced complement levels. These symptoms and laboratory findings led to a diagnosis of ANCA vasculitis induced by PTU, resulting in the cessation of this medication. Following the discontinuation of PTU there was a notable improvement with normalization of serum Cr and resolution of proteinuria within 1.5 months. Concurrently, MPO and PR-3 levels began to decrease, and her hematological abnormalities resolved. During this period, her Free T4 levels gradually increased, leading to the administration of radioactive iodine for the treatment of her Graves' disease. Discussion: This case underscores the complexities in treating a patient with Graves' disease highlighting the unpredictable and severe side effects of antithyroid drugs like agranulocytosis and ANCA vasculitis. We report the first documented case of sequential thionamide-induced complications: agranulocytosis with methimazole, followed by ANCA vasculitis with propylthiouracil. Although both can arise from immune responses to these medications, they are distinct in their pathophysiology and are not associated with one another. The unpredictable nature of these side effects complicates prevention. Educating patients to promptly report any unusual symptoms and immediate medical intervention with drug discontinuation are key to managing these adverse reactions effectively. Presentation: 6/1/2024

Clinician-Ordered Peripheral Smear Review by a Pathologist Has Low Clinical Utility-A Reference Laboratory Perspective.

Clinician-ordered peripheral smear review by pathologist (CPSR) is commonly ordered and has been recommended for decades. However, the clinical utility of this labor-intensive test in the reference laboratory has not been examined. The objective of this study is to assess hematologic abnormalities identified in CPSR orders and to correlate them with complete blood count (CBC) and laboratory-derived smear review (LDSR) in the reference laboratory. Two hundred consecutive CPSRs with corresponding CBCs from April 2023 were run by Sysmex® XN-11 analyzers, and their peripheral smears were examined by a board-certified hematopathologist. Hematologic abnormalities of CPSRs were assessed, and the correlation between CPSR and CBC/LDSR was reviewed. Nearly one-third of CPSRs (29%) had normal peripheral smears and CBCs. The majority of CPSRs showed nonspecific quantitative abnormalities. When compared against CPSR results, LDSR criteria identified 100% of hematologic abnormalities appropriately. Samples that were not flagged for review by LDSR rules were also reviewed (n = 174) to rule out clinically meaningful false negatives. One minor discrepancy (0.6% of cases) of small platelet aggregates was observed in a patient with a reported platelet count of 139 K/uL that was missed by the LDSR process. In the reference laboratory setting, our findings demonstrate that LDSR adequately detects significant hematologic abnormalities and, therefore, CPSR should be discontinued.

Methanolic stem-bark extracts of Adansonia digitata modulates haematological and antioxidant parameters in streptozotocin-induced diabetic rats

Background and AimDiabetes mellitus is associated with haematological abnormalities and oxidative stress, contributing to disease progression and complications. Adansonia digitata, is a traditional medicinal plant well known for its potential therapeutic properties. This study investigates the effects of methanolic stem-bark extracts of Adansonia digitata on haematological and antioxidant status in streptozotocin-induced diabetic rats. Experimental ProcedureFourty-two wistar rats were distributed into 6 groups of 7 each. Group 1 served as normal control, group 2 to 6 animals were made diabetic by intraperitoneal administration of single dose of 50 mg kg-1 streptozotocin. Group 2 served as the negative control and did not receive treatment, group 3 served as the positive control and received 150 mg kg-1 metformin (Glucophage) (standard drug), while group 4, 5 and 6 received oral treatment of 100 mg kg-1, 200 mg kg-1 and 300 mg kg-1 of Adansonia digitata stem-bark methanolic extract respectively for 21days, after which the animals were sacrificed, and blood and liver were collected for haematological analysis including White Blood cell (WBC), red blood cell (RBC), haemoglobin (HGB), hematocrit (H CT), platelet (PLT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentration and antioxidant parameters including antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD) activities] and oxidative stress marker [thiobarbituric acid reactive substance (TBARS)]. ResultsSTZ administration evoked a marked (p < 0.05) decline in the level of WBC, RBC, HGB, PLT, LYM and MCV in the diabetic rats when compared with the normal control. Howbeit, treatment with methanolic extracts of adansonia digitata stem-bark led to a profound (p < 0.05) increase in concentrations of these parameters close to the normal. In addition, STZ caused a non-significant (p > 0.05) decrease in MCH and MCHC. On the contrary, STZ caused an insignificant (p > 0.05) increase in the levels of TB and DB, but a significant (p > 0.05) increase IDB level in the diabetic control group when compared with the normal control group, while treatment with stem-bark extracts resulted in a marked (p > 0.05) fall in IDB level. Furthermore, there was a marked (P < 0.05) reduction in the activity of hepatic CAT and SOD and a considerable (P < 0.05) elevation in Malondialdehyde (MDA) level in the hepatic tissue of the diabetic control. Nonetheless, Adansonia digitata stem-bark extracts profoundly (P < 0.05) raised the activities of the enzymes and concomitantly counteracted MDA level. The extract elicited strong potency at 300 mg kg-1 which is comparable to metformin (Glucophage). ConclusionConsequently, this study advocates for the utility of Adansonia digitata extracts for the development of novel drugs for combating diabetes mellitus, associated hematological and oxidative stress complications and other ailments. Further research is needed to evaluate the clinical relevance of these effects in human subjects and to provide information on the sustained efficacy of the extracts in chronic models. Significant statementOxidative stress and hematological abnormalities are two of the consequences linked to diabetes mellitus. Anaemia and poor blood coagulation are two haematological changes that increase the risk of diabetes-related illness and death. Furthermore, oxidative stress is essential to the pathophysiology of diabetic complications such as nephropathy and cardiovascular disease. In addition, there are reports on hematological and biochemical alterations in diabetic subjects arising from the intake of synthetic antidiabetic medications.. Consequent to the safety, ease of use, efficacy, and lack of cytotoxic side effects of plants’ herbs, the study of Adansonia digitata's methanolic stem-bark extracts on haematological and antioxidant parameters in streptozotocin-induced diabetic rats is of paramount importance as the extracts' capacity to modify these parameters, will lead to the development of novel drugs that cures anemia, other blood abnormalities, and oxidative stress linked to diabetes as well as other ailments.