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Blood Cells, Molecules & Diseases Nov 2023We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests...
Next generation sequencing (NGS) interest in deciphering erythrocyte molecular defects' association in red cell disorders: Clinical and erythrocyte phenotypes of patients with mutations inheritance in PIEZO1, Spectrin ß1, RhAG and SLC4A1.
We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests confirmed the hemolysis with increased total and indirect bilirubin. The usual hemolysis diagnosis tests were normal (DAT, G6PD, PK, Hb electrophoresis) except cytology and ektacytometry suggesting an association of multiple red blood cell (RBC) membrane disorders. This led us to propose a molecular screening analysis using targeted-Next Generation Sequencing (t-NGS) with a capture technique on 93 genes involved in RBC and erythropoiesis defects. We identified 4 missense heterozygous allelic variations, all of them were described without any significance (VUS) in the SLC4A1, RhAG, PIEZO1 and SPTB genes. The study of the familial cosegregation and research functional tests allowed to decipher the role of at least two by two genes in the phenotype and the hemolytic disease of this young patient. Specialized t-NGS panel (or virtual exome/genome sequencing) in a disease-referent laboratory and the motivated collaboration of clinicians, biologists and scientists should be the gold standard for improving the diagnosis of the patients affected with RBC diseases or rare inherited anemias.
Topics: Humans; Spherocytosis, Hereditary; Spectrin; High-Throughput Nucleotide Sequencing; Hemolysis; Mutation; Erythrocytes; Hematologic Diseases; Phenotype; Anion Exchange Protein 1, Erythrocyte; Ion Channels
PubMed: 37516005
DOI: 10.1016/j.bcmd.2023.102780 -
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 -
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 -
Genetic Testing and Molecular Biomarkers Jan 2024Hereditary spherocytosis (HS) is a common hereditary hemolytic disease. This study aimed to explore the correlation between the phenotype and mutant genotype of HS to...
Hereditary spherocytosis (HS) is a common hereditary hemolytic disease. This study aimed to explore the correlation between the phenotype and mutant genotype of HS to improve the clinical understanding of HS. This study reported a case of spontaneous mutation of the ANK1 gene in HS, reviewed previous studies on the genotype-phenotype correlation of HS, statistically analyzed the main types of gene mutations in HS, and summarized the clinical data of patients. This patient had clinical manifestations of anemia, splenomegaly, peripheral blood smear with increased spherocytosis, and bilirubin, confirmed as ANK1 gene mutant HS by gene detection. In addition, this study included 14 previous studies on genotype-phenotype correlation, collected data, and determined that the ANK1 and SPTB genes were the most common types of gene mutations in HS patients. The mutant HS of the ANK1 gene would lead to lower hemoglobin levels. The results of this study showed that ANK1 and SPTB were the most common types of gene mutations in HS patients. Compared with patients with the SPTB genotype HS, patients with ANK1 mutant HS had more severe extravascular hemolysis, and a higher proportion needed splenectomy in early childhood.
Topics: Child, Preschool; Humans; Genotype; Phenotype; Mutation; Spherocytosis, Hereditary
PubMed: 38294355
DOI: 10.1089/gtmb.2023.0307 -
Frontiers in Pediatrics 2024
PubMed: 38633330
DOI: 10.3389/fped.2024.1403651 -
Perioperative Medicine (London, England) Jun 2024Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications... (Review)
Review
BACKGROUND
Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications resulting from hemolysis. Despite being the most prevalent cause of hereditary chronic hemolysis, the standards of surgical management are based solely on expert opinion.
OBJECTIVE
We analyze the risk of hemolysis in HS patients after cardiac surgery based on a systematic review of the literature. We also describe a case of a patient with hereditary spherocytosis who underwent aortic valve repair.
METHODS
This systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42023417666) and included records from Embase, MEDLINE, Web of Science, and Google Scholar databases. The case study investigates a 38-year-old patient who underwent surgery for an aortic valve defect in mid-2022.
RESULTS
Of the 787 search results, 21 studies describing 23 cases of HS undergoing cardiac surgery were included in the final analysis. Hemolysis was diagnosed in five patients (one coronary artery bypass graft surgery, two aortic valve bioprosthesis, one ventricular septal defect closure, and one mitral valve plasty). None of the patients died in the perioperative period. Also, no significant clinical hemolysis was observed in our patient during the perioperative period.
CONCLUSIONS
The literature data show that hemolysis is not common in patients with HS undergoing various cardiac surgery techniques. The typical management of a patient with mild/moderate HS does not appear to increase the risk of significant clinical hemolysis. Commonly accepted beliefs about factors inducing hemolysis during cardiac surgery may not be fully justified and require further investigation.
PubMed: 38858770
DOI: 10.1186/s13741-024-00411-w -
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 -
Blood Advances Sep 2023Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism...
Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism behind this benefit remain largely overlooked. Here, we compared 7 nonsplenectomized and 13 splenectomized patients with mutations in the β-spectrin or the ankyrin gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium, and extracellular vesicle release were largely but not completely restored by splenectomy, whereas cryohemolysis was not. Affected RBCs exhibited decreases in β-spectrin and/or ankyrin contents and slight alterations in spectrin membrane distribution, depending on the mutation. These modifications were found in both splenectomized and nonsplenectomized patients and poorly correlated with RBC functionality alteration, suggesting additional impairments. Accordingly, we found an increased abundance of septins, small guanosine triphosphate-binding cytoskeletal proteins. Septins-2, -7, and -8 but not -11 were less abundant upon splenectomy and correlated with the disease severity. Septin-2 membrane association was confirmed by immunolabeling. Except for cryohemolysis, all parameters of RBC morphology and functionality correlated with septin abundance. The increased septin content might result from RBC maturation defects, as evidenced by (1) the decreased protein 4.2 and Rh-associated glycoprotein content in all patient RBCs, (2) increased endoplasmic reticulum remnants and endocytosis proteins in nonsplenectomized patients, and (3) increased lysosomal and mitochondrial remnants in splenectomized patients. Our study paves the way for a better understanding of the involvement of septins in RBC membrane biophysical properties. In addition, the lack of restoration of septin-independent cryohemolysis by splenectomy may call into question its recommendation in specific cases.
Topics: Humans; Spectrin; Septins; Splenectomy; Ankyrins; Spherocytosis, Hereditary; Erythrocytes
PubMed: 36753606
DOI: 10.1182/bloodadvances.2022009114 -
Cureus Aug 2023Introduction The utilization of robot-assisted technique for splenectomy has recently gained popularity especially in patients undergoing splenectomy for hematological...
Introduction The utilization of robot-assisted technique for splenectomy has recently gained popularity especially in patients undergoing splenectomy for hematological indications owing to its magnification of and easy manipulation of internal abdominal organs. Moreover, robotic splenectomy emerged as an essential teaching module before approaching more complex robotic procedures. Methods A total of 43 elective splenectomies were performed for hematological indications in Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) between January 2018 to July 2023 of which 14 patients underwent robotic splenectomy. All patients underwent lateral approach of robotic splenectomy with a modification of avoiding the lesser sac dissection. Prospectively maintained data were retrospectively analyzed and results were recorded in terms of intra-operative time taken, blood loss, need for blood and blood product transfusion and postoperative morbidity and mortality. Results The indications for patients who underwent robotic splenectomy include idiopathic thrombocytopenic purpura in eight patients, autoimmune hemolytic anemia in three patients, Evans syndrome in one patient and hereditary spherocytosis in two patients. The median splenic diameter was 14.8cm and the median platelet count before the operation was 10,800 cells/cubic millimeter (7000-3,20,000). The mean operative time was 92 minutes and blood loss was 40ml. The median duration of hospital stay was 2.4 days. All 14 patients had therapeutic success and there was no procedure-related mortality or morbidity. Conclusion Robotic splenectomy using the modified lateral approach can safely be performed with comparable operative time, blood loss and overall morbidity. However further studies are mandatory to confirm the advantage of this modified technique of lateral approach of robotic splenectomy.
PubMed: 37736466
DOI: 10.7759/cureus.43820 -
Indian Journal of Hematology & Blood... Jul 2023Diagnosis of Hereditary spherocytosis (HS) often requires time-consuming and/or expensive tests. Cryohemolysis test (CHT) is a simple and easy to perform test with high...
Diagnosis of Hereditary spherocytosis (HS) often requires time-consuming and/or expensive tests. Cryohemolysis test (CHT) is a simple and easy to perform test with high predictive value for HS diagnosis. In this prospective study, we evaluated the diagnostic utility of CHT for the diagnosis of HS. We included 60 suspected HS patients, 18 patients with Autoimmune hemolytic anemia (AIHA) and 120 healthy controls. Among the 60 suspected cases, there were 36 HS cases and 24 with other hemolytic anemias. The mean CHT (%) ± SD for controls, AIHA, other hemolytic anemias, and HS was 6.63 ± 2.79, 6.79 ± 4.36, 6.61 ± 2.76 and 26.7 ± 8.9, respectively. The CHT % was significantly higher in HS group when compared to controls ( = < 0.0001), AIHA ( = < 0.0001) and other hemolytic anemia groups ( = < 0.0001). At a CHT cut off of > 18.3%, the sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of HS in our study were 97.1%, 94.4%, 97.2% and 90.3%, respectively. CHT is a simple and sensitive test for the diagnosis of HS but remains underutilized. The addition of CHT in the diagnostic workup of HS will be very useful, especially in a resource limited setting.
PubMed: 37304467
DOI: 10.1007/s12288-022-01615-0