-
Cureus Feb 2024Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This...
Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This report presents a case of a 42-year-old woman with a history of spontaneous abortion, associated with postpartum bleeding, chronic anemia, and premature menopause. After five years, she consulted due to alterations in the state of consciousness and severe symptomatic hyponatremia, with a diagnosis of hypopituitarism, explained by a late Sheehan syndrome. During hospitalization, she developed non-immune hemolytic anemia associated with a positive osmotic fragility test. A diagnosis of hereditary spherocytosis/elliptocytosis was made. We correlate blood hypoosmolarity as a trigger with the in vitro hypotonic solution of the osmotic fragility test for the diagnosis of this disease. This association is not reported in the literature; in our case, we show the concomitant improvement of anemia with the increase in sodium levels and hormonal replacement.
PubMed: 38435165
DOI: 10.7759/cureus.53417 -
HemaSphere Jan 2024
PubMed: 38434532
DOI: 10.1002/hem3.31 -
International Journal of Molecular... Feb 2024The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid...
The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid cells. Reticulocytes and other erythroid precursors may adapt their biosynthetic mechanisms to cell defects or to changes in the bone marrow environment. Our aim was to perform a comparative study of the mRNA levels of and in reticulocytes from healthy individuals and from patients with hereditary spherocytosis (HS), sickle cell disease (SCD) and β-thalassemia (β-thal), and to study the association between their transcript levels and the reticulocyte maturity indices. In controls, the enzyme mRNA levels were significantly correlated with reticulocyte maturity indices for all genes except for . HS, SCD and β-thal patients showed younger reticulocytes, with higher transcript levels of all enzymes, although with different patterns. β-thal and HS showed similar reticulocyte maturity, with different enzyme mRNA levels; SCD and HS, with different reticulocyte maturity, presented similar enzyme mRNA levels. Our data suggest that the transcript profile for these antioxidant enzymes is not entirely related to reticulocyte maturity; it appears to also reflect adaptive mechanisms to abnormal erythropoiesis and/or to altered erythropoietic environments, leading to reticulocytes with distinct antioxidant potential according to each anemia.
Topics: Humans; Reticulocytes; beta-Thalassemia; Antioxidants; RNA, Messenger; Superoxide Dismutase-1; Spherocytosis, Hereditary; Anemia, Sickle Cell
PubMed: 38396832
DOI: 10.3390/ijms25042159 -
Sisli Etfal Hastanesi Tip Bulteni 2023The objective of the study is to present the demographic characteristics, clinical and laboratory features and outcome of our patients with hereditary spherocytosis (HS).
OBJECTIVES
The objective of the study is to present the demographic characteristics, clinical and laboratory features and outcome of our patients with hereditary spherocytosis (HS).
METHODS
Demographic, clinical, and laboratory data; complications; and splenectomy results were analyzed retrospectively. The severity of the disease was scaled according to Eber's criteria.
RESULTS
Sixty-nine patients (42 boys, 27 girls, median age: 3 years) were eligible. Sixty-eight percent of the patients had a history of neonatal jaundice. The complaints at admission were jaundice (71%), fatigue (27.5%), fainting (4.3%), and pallor (4.3%). The median follow-up duration was 8.5 years. According to Eber's criteria, three (4.3%), 57 (82.6%), and nine (13.1%) patients had mild, moderate, and severe diseases, respectively. Thirty-six patients (52.1%) had a splenectomy. Following splenectomy, we observed a significant rise in hemoglobin levels and a decline in indirect bilirubin levels. Post-operative thrombocytosis was common, with a tendency to fall and stabilize after 1 month. There were no thromboembolic complications.
CONCLUSION
In spite of the high rate of consanguinity, familial history of HS, and neonatal jaundice in our study group, the majority of the HS patients were identified relatively late, about 3 years. This finding shows that HS might be insufficiently acknowledged by primary care. Splenectomy, in selected cases, may reduce the need for transfusions. Post-splenectomy transient thrombocytosis is common and has a benign course.
PubMed: 38268662
DOI: 10.14744/SEMB.2023.60370 -
Biomolecules Dec 2023Piezo1 is a mechanosensitive ion channel required for various biological processes, but its regulation remains poorly understood. Here, we used erythrocytes to address...
Piezo1 is a mechanosensitive ion channel required for various biological processes, but its regulation remains poorly understood. Here, we used erythrocytes to address this question since they display Piezo1 clusters, a strong and dynamic cytoskeleton and three types of submicrometric lipid domains, respectively enriched in cholesterol, GM1 ganglioside/cholesterol and sphingomyelin/cholesterol. We revealed that Piezo1 clusters were present in both the rim and the dimple erythrocyte regions. Upon Piezo1 chemical activation by Yoda1, the Piezo1 cluster proportion mainly increased in the dimple area. This increase was accompanied by Ca influx and a rise in echinocytes, in GM1/cholesterol-enriched domains in the dimple and in cholesterol-enriched domains in the rim. Conversely, the effects of Piezo1 activation were abrogated upon membrane cholesterol depletion. Furthermore, upon Piezo1-independent Ca influx, the above changes were not observed. In healthy donors with a high echinocyte proportion, Ca influx, lipid domains and Piezo1 fluorescence were high even at resting state, whereas the cytoskeleton membrane occupancy was lower. Accordingly, upon decreases in cytoskeleton membrane occupancy and stiffness in erythrocytes from patients with hereditary spherocytosis, Piezo1 fluorescence was increased. Altogether, we showed that Piezo1 was differentially controlled by lipid domains and the cytoskeleton and was favored by the stomatocyte-discocyte-echinocyte transformation.
Topics: Humans; Cholesterol; Cytoskeleton; Erythrocytes; G(M1) Ganglioside; Microtubules; Lipid Bilayers; Ion Channels
PubMed: 38254651
DOI: 10.3390/biom14010051 -
Children (Basel, Switzerland) Nov 2023Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there...
BACKGROUND
Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there is a lack of comprehensive teaching models for pediatric cholecystectomy. Drawing inspiration from standardized outpatient procedures, this study aimed to assess the clinical outcomes and feasibility of teaching programs and an Enhanced Recovery After Surgery (ERAS) protocol following ambulatory laparoscopic cholecystectomy in pediatric patients.
METHODS
In 2015, an ERAS pathway for laparoscopic cholecystectomy (LC) was implemented, focusing on admission procedures, surgery timing, anesthetic choices, analgesia, postoperative feeding, mobilization, and pain assessment. Day-case surgery was not applicable for acute cholecystitis, choledochal lithiasis, sickle cell disease, and hereditary spherocytosis cases. The protocol was employed for a group of attending surgeons and fellows, as well as a group of residents under the supervision of experienced surgeons. A retrospective analysis was conducted to evaluate the feasibility and effectiveness of ambulatory cholecystectomy in children and its utilization in training pediatric surgical trainees.
RESULTS
Between 2015 and 2020, a total of 33 patients were included from a cohort of 162 children who underwent LC, with 15 children operated on by senior surgeons and 18 by young surgeons. The primary diagnoses were symptomatic gallbladder lithiasis ( = 32) and biliary dyskinesia ( = 1). The median age at the time of surgery was 11.3 years (interquartile range (IQR) 4.9-18), and the median duration of surgery was 54 min (IQR 13-145). One intraoperative complication occurred, involving gallbladder rupture and the dissemination of lithiasis into the peritoneal cavity. Three patients (9%) required an overnight stay, while no postoperative complications or readmissions within 30 days were observed. ERAS was successfully implemented in 30 patients (91%). No significant differences in surgical outcomes were noted between senior and young surgeons. At an average follow-up of 55 months, no long-term sequelae were identified.
CONCLUSIONS
These findings align with the current trend of increasing use of outpatient laparoscopic cholecystectomy and underscore its feasibility in the pediatric population. The application of a structured ERAS protocol appears viable and practical for training the next generation of pediatric surgeons.
LEVEL OF EVIDENCE
Level III.
PubMed: 38136083
DOI: 10.3390/children10121881 -
Frontiers in Genetics 2023Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the...
Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the most common erythrocytic gene, spectrin β (), variants are located in exons and give rise to mRNA defects. However, the genetic characteristics and pathogenic mechanisms of intronic variants are not completely understood. This study aimed to analyse a rare intronic inversion variant in the gene associated with HS, and explore the impact of the variant on mRNA splicing. The clinical manifestations of the patient were summarised and analysed for spherocytosis phenotype diagnosis. The pathogenic variant was identified in the proband using targeted next-generation and Sanger sequencing. RNA sequencing was performed to analyse whether gene splicing and expression were affected. Targeted next-generation sequencing identified a novel disease-associated intronic inversion variant of the gene in the proband. The inversion variant was located between intron 19 and 20, and contained the entire exon 20 and partial sequences of adjacent introns. Sanger sequencing confirmed that the intronic inversion variant only appeared in the genome of the proband, not in his parents. RNA sequencing revealed that the variant could result in the skipping of exon 20 and reduced expression of mRNA. This study identifies a rare intronic inversion variant in the gene associated with hereditary spherocytosis. The pathogenic variant can lead to exon 20 skipping and decreased gene expression. This finding has not been previously reported in any literature. This study can expand the intronic variant spectrum of the gene, deepen our understanding of HS pathogenesis, and contribute to the genetic diagnosis and clinical management of patients.
PubMed: 38111681
DOI: 10.3389/fgene.2023.1309040 -
Applied Bionics and Biomechanics 2023[This retracts the article DOI: 10.1155/2022/6228965.].
[This retracts the article DOI: 10.1155/2022/6228965.].
PubMed: 38075143
DOI: 10.1155/2023/9846792 -
International Journal of Molecular... Nov 2023Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS),...
Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS), are often underdiagnosed, partly due to their sometimes mild and asymptomatic courses. In addition to a broad clinical spectrum, this is also due to the occasionally complex diagnostics that are not available to every patient. To test whether next-generation sequencing (NGS) could replace time-consuming spherocytosis-specific functional tests, 22 consecutive patients with suspected red cell membranopathy underwent functional blood tests. We were able to identify the causative genetic defect in all patients with suspected HS who underwent genetic testing ( = 17). The sensitivity of the NGS approach, which tests five genes ( (gene product: ankyrin1), (erythrocyte membrane protein band4.2), (band3), (α-spectrin), and (β-spectrin)), was 100% (95% confidence interval: 81.5-100.0%). The major advantage of genetic testing in the paediatric setting is the small amount of blood required (<200 µL), and compared to functional assays, sample stability is not an issue. The combination of medical history, basic laboratory parameters, and an NGS panel with five genes is sufficient for diagnosis in most cases. Only in rare cases, a more comprehensive functional screening is required.
Topics: Humans; Child; Ankyrins; Mutation; Spherocytosis, Hereditary; Spectrin; Cytoskeletal Proteins; High-Throughput Nucleotide Sequencing
PubMed: 38069343
DOI: 10.3390/ijms242317021 -
Human Vaccines & Immunotherapeutics Dec 2023
Topics: Humans; COVID-19; COVID-19 Vaccines; Hemolysis; Spherocytosis, Hereditary; mRNA Vaccines
PubMed: 37992397
DOI: 10.1080/21645515.2023.2286117