bims-conane Biomed News
on Congenital anemias
Issue of 2024–07–28
eightteen papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Molecular glue degrader for sickle cell disease.
  2. Heme- and iron-activated macrophages in sickle cell disease: an updated perspective.
  3. Post-GWAS Validation of Target Genes Associated with HbF and HbA2 Levels.
  4. A critical review of therapeutic interventions in sickle cell disease: Progress and challenges.
  5. Safety and efficacy studies of CRISPR/Cas9 treatment of sickle cell disease in clinically relevant conditions highlights disease-specific responses.
  6. Retrospective Cohort Study of Sickle Cell Disease and Large Vessel Retinal Vascular Occlusion Risk in a National US Database.
  7. Significant pituitary siderosis is common in transfusion dependent sickle cell disease.
  8. Prospective study of complement activation and thromboinflammation within sickle cell disease and its complications.
  9. Differential sensitivity to hypoxia enables shape-based classification of sickle cell disease and trait blood samples at point of care.
  10. Splenic complications in pediatric sickle cell disease: A retrospective cohort review.
  11. Outcome of pregnancy in sickle cell anemia patients with COVID-19 infection.
  12. Hypertonicity and/or acidosis induce marked rheological changes under hypoxic conditions in sickle trait red blood cells.
  13. Disease burden, management strategies, and unmet needs in α-thalassemia due to hemoglobin H disease.
  14. Serum visfatin level in β-thalassemia and its correlation with disease severity.
  15. Erythropoiesis in the mammalian embryo.
  16. Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis.
  17. The effect of blood transfusion on serum hepcidin levels in chronically transfused patients of β-thalassemia major: An observational study in a tertiary care centre in Western Maharashtra.
  18. Luspatercept for non-deletional hemoglobin H disease.
  1. Nat Rev Drug Discov. 2024 Jul 23.
    Molecular glue degrader for sickle cell disease.
    Katie Kingwell.
      
    DOI:  https://doi.org/10.1038/d41573-024-00122-3
  2. Curr Opin Hematol. 2024 Jul 17.
    Heme- and iron-activated macrophages in sickle cell disease: an updated perspective.
    Shobana Navaneethabalakrishnan, Xiuli An, Francesca Vinchi.
       PURPOSE OF REVIEW: Sickle cell disease (SCD) is a hereditary blood disorder due to a single-point mutation in the β-globin gene. The ensuing hemoglobin has the tendency to polymerize upon deoxygenation, leading to the typical sickle shape of red blood cells. While the primary pathology of sickle cell disease is a direct consequence of altered red blood cells, emerging evidence highlights the central role of macrophages in mediating hemoglobin scavenging, perpetuating oxidative stress and inflammation, and causing endothelial dysfunction and tissue remodeling.
    RECENT FINDINGS: Recent research uncovered the impact of heme and iron overload on macrophage polarization and functions in sickle cell disease, and its implication for chronic inflammation and tissue damage in vital organs such as the liver, spleen, lungs and kidneys. By providing a thorough understanding of the dynamic interactions between macrophages and various cellular components within the sickle cell disease milieu, these studies have laid the foundation for the identification of macrophage-related cellular and molecular mechanisms potentially targetable for therapeutic purposes to attenuate sickle complications.
    SUMMARY: This review provides a current update about recent discoveries on heme/iron-activated macrophages in SCD, shedding light on their critical role in disease pathophysiology. Ultimately, it proposes avenues for future research aimed at addressing the relevance of these cells for other sickle complications and at targeting them to mitigate disease morbidity and improve patient outcomes.
    DOI:  https://doi.org/10.1097/MOH.0000000000000836
  3. Cells. 2024 Jul 12. pii: 1185. [Epub ahead of print]13(14):
    Post-GWAS Validation of Target Genes Associated with HbF and HbA2 Levels.
    Cristian Antonio Caria, Valeria Faà, Susanna Porcu, Maria Franca Marongiu, Daniela Poddie, Lucia Perseu, Alessandra Meloni, Simona Vaccargiu, Maria Serafina Ristaldi.
      Genome-Wide Association Studies (GWASs) have identified a huge number of variants associated with different traits. However, their validation through in vitro and in vivo studies often lags well behind their identification. For variants associated with traits or diseases of biomedical interest, this gap delays the development of possible therapies. This issue also impacts beta-hemoglobinopathies, such as beta-thalassemia and sickle cell disease (SCD). The definitive cures for these diseases are currently bone marrow transplantation and gene therapy. However, limitations regarding their effective use restrict their worldwide application. Great efforts have been made to identify whether modulators of fetal hemoglobin (HbF) and, to a lesser extent, hemoglobin A2 (HbA2) are possible therapeutic targets. Herein, we performed the post-GWAS in vivo validation of two genes, cyclin D3 (CCND3) and nuclear factor I X (NFIX), previously associated with HbF and HbA2 levels. The absence of Ccnd3 expression in vivo significantly increased g (HbF) and d (HbA2) globin gene expression. Our data suggest that CCND3 is a possible therapeutic target in sickle cell disease. We also confirmed the association of Nfix with γ-globin gene expression and present data suggesting a possible role for Nfix in regulating Kruppel-like transcription factor 1 (Klf1), a master regulator of hemoglobin switching. This study contributes to filling the gap between GWAS variant identification and target validation for beta-hemoglobinopathies.
    Keywords:  CCND3; NFIX; beta-hemoglobinopathies
    DOI:  https://doi.org/10.3390/cells13141185
  4. Arch Pharm (Weinheim). 2024 Jul 19. e2400381
    A critical review of therapeutic interventions in sickle cell disease: Progress and challenges.
    Chandu Ala, Renuka Parshuram Joshi, Pragya Gupta, Sangam Giri Goswami, Sivaprakash Ramalingam, Chandra Sekhar Kondapalli Venkata Gowri, Murugesan Sankaranarayanan.
      Sickle cell disease (SCD) is an autosomal recessive genetic disorder that occurs due to the point mutation in the β-globin gene, which results in the formation of sickle hemoglobin (HbS) in the red blood cells (RBCs). When HbS is exposed to an oxygen-depleted environment, it polymerizes, resulting in hemolysis, vaso-occlusion pain, and impaired blood flow. Still, there is no affordable cure for this inherited disease. Approved medications held promise but were met with challenges due to limited patient tolerance and undesired side effects, thereby inhibiting their ability to enhance the quality of life across various individuals with SCD. Progress has been made in understanding the pathophysiology of SCD during the past few decades, leading to the discovery of novel targets and therapies. However, there is a compelling need for research to discover medications with improved efficacy and reduced side effects. Also, more clinical investigations on various drug combinations with different mechanisms of action are needed. This review comprehensively presents therapeutic approaches for SCD, including those currently available or under investigation. It covers fundamental aspects of the disease, such as epidemiology and pathophysiology, and provides detailed discussions on various disease-modifying agents. Additionally, expert insights are offered on the future development of pharmacotherapy for SCD.
    Keywords:  disease‐modifying agents; fetal hemoglobin (HbF); hemoglobinopathy; sickle cell disease; vaso‐occlusive crisis
    DOI:  https://doi.org/10.1002/ardp.202400381
  5. Mol Ther. 2024 Jul 22. pii: S1525-0016(24)00470-2. [Epub ahead of print]
    Safety and efficacy studies of CRISPR/Cas9 treatment of sickle cell disease in clinically relevant conditions highlights disease-specific responses.
    Giacomo Frati, Megane Brusson, Gilles Sartre, Bochra Mlayah, Tristan Felix, Anne Chalumeau, Panagiotis Antoniou, Giulia Hardouin, Jean-Paul Concordet, Oriana Romano, Giandomenico Turchiano, Annarita Miccio.
      Fetal hemoglobin (HbF) reactivation expression through CRISPR/Cas9 is a promising strategy for the treatment of sickle cell disease (SCD). Here, we describe a genome editing strategy leading to reactivation of HbF expression by targeting the binding sites (BSs) for the LRF repressor in the γ-globin promoters. CRISPR/Cas9 treatment in healthy donor (HD) and patient-derived HSPCs resulted in a high frequency of LRF BS disruption and potent HbF synthesis in their erythroid progeny. LRF BS disruption did not impair HSPC engraftment and differentiation, but was more efficient in SCD than in HD cells. However, SCD HSPCs showed a reduced engraftment and a myeloid bias compared to HD cells. We detected off-target activity and chromosomal rearrangements, particularly in SCD samples (likely because of the higher overall editing efficiency), but did not impact the target gene expression and HSPC engraftment and differentiation. Transcriptomic analyses showed that the editing procedure results in the upregulation of genes involved in DNA damage and inflammatory responses, which was more evident in SCD HSPCs. This study provides evidences of efficacy and safety for an editing strategy based on HbF reactivation and highlights the need of performing safety studies in clinically relevant conditions, i.e., in patient-derived HSPCs.
    Keywords:  CRISPR/Cas9; genotoxicity; hematopoietic stem cells; hemoglobinopathies; sickle cell disease
    DOI:  https://doi.org/10.1016/j.ymthe.2024.07.015
  6. Ophthalmol Retina. 2024 Jul 19. pii: S2468-6530(24)00336-1. [Epub ahead of print]
    Retrospective Cohort Study of Sickle Cell Disease and Large Vessel Retinal Vascular Occlusion Risk in a National US Database.
    Gabriel T Kaufmann, Matthew Russell, Priya Shukla, Rishi P Singh, Katherine E Talcott.
       OBJECTIVE: To determine if differences exist in the risk of developing large vessel retinal vascular occlusions in patients with sickle cell states.
    DESIGN: Retrospective cohort study.
    PARTICIPANTS: Patients with sickle cell disease or trait evaluated by an ophthalmologist were compared to matched controls without sickle cell disease or trait also evaluated by an ophthalmologist.
    METHODS: This study used deidentified data from a national database (2006-2024), using International Classification of Diseases 10 codes to select for retinal vascular occlusions. Propensity score matching was performed with respect to age, sex, race, ethnicity, smoking, hypertension, diabetes, dyslipidemias, and obesity, resulting in HbSS, HbSC, and sickle cell trait (SCT) cohorts and matched control cohorts.
    MAIN OUTCOME MEASURES: Risk ratios and 95% confidence intervals (CI) of retinal vascular occlusion diagnosis, including central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), central retinal venous occlusion (CRVO), branch retinal venous occlusion (BRVO), and corneal dystrophy as a negative control, given sickle cell disease or trait.
    RESULTS: After propensity score matching, HbSS (n=10,802, mean ± standard deviation age of 38.6 ± 20.6 years), HbSC (n=4,296, 34.3 ± 17.8 years), and SCT (n=15,249, 39.8 ± 23.7 years) cohorts were compared to control cohorts (n=10,802, 38.7 ± 20.7 years; n=4,296, 34.6 ± 18.0 years; n=15,249, 39.9 ± 23.8 years, respectively). Patients with sickle cell disease (HbSS) had higher risk of developing any retinal vascular occlusion (RR 2.33; 95% CI 1.82-3.00), CRAO (RR 2.71; 95% CI 1.65-4.47) and BRAO (RR 4.90; 95% CI 2.48-9.67) than matched controls. Patients with HbSC disease had higher risk (RR 3.14; 95% CI 1.95-5.06) of developing any retinal vascular occlusion than matched controls without sickle cell disease. Patients with sickle cell trait did not have higher risk of developing retinal vascular occlusions (RR 1.01; 95% CI 0.81-1.26) than matched controls.
    CONCLUSIONS: In a retrospective cohort study, patients with HbSS sickle cell disease have an increased risk of developing retinal vascular occlusions, and more specifically CRAO and BRAO compared to patients without sickle cell disease.
    Keywords:  Retinal vascular occlusion; retinal artery occlusion; retinal vein occlusion; sickle cell disease
    DOI:  https://doi.org/10.1016/j.oret.2024.07.013
  7. Blood. 2024 Jul 24. pii: blood.2024025462. [Epub ahead of print]
    Significant pituitary siderosis is common in transfusion dependent sickle cell disease.
    Akhila Vadivelan, Eamon Doyle, Susan Carson, Christopher C Denton, Saranya Veluswamy, Thomas C Hofstra, Thomas D Coates, John C Wood.
      Chronically transfused sickle cell patients typically don't exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction.
    DOI:  https://doi.org/10.1182/blood.2024025462
  8. Hemasphere. 2024 Jul;8(7): e135
    Prospective study of complement activation and thromboinflammation within sickle cell disease and its complications.
    Christos Varelas, Efthymia Vlachaki, Philippos Klonizakis, Despoina Pantelidou, Fani Minti, Michael Diamantidis, Nikolaos Sabanis, Evdoxia Koravou, Ioanna Christodoulou, Despina Papadopoulou, Stamatia Theodoridou, Tasoula Touloumenidou, Apostolia Papalexandri, Ioanna Sakellari, Sofia Vakalopoulou, Vasilis Perifanis, George Vassilopoulos, Ioannis Mitroulis, Eleni Gavriilaki.
      
    DOI:  https://doi.org/10.1002/hem3.135
  9. Bioeng Transl Med. 2024 Jul;9(4): e10643
    Differential sensitivity to hypoxia enables shape-based classification of sickle cell disease and trait blood samples at point of care.
    Claudy D'Costa, Oshin Sharma, Riddha Manna, Minakshi Singh, Samrat Singh, Srushti Singh, Anish Mahto, Pratiksha Govil, Sampath Satti, Ninad Mehendale, Yazdi Italia, Debjani Paul.
      Red blood cells (RBCs) become sickle-shaped and stiff under hypoxia as a consequence of hemoglobin (Hb) polymerization in sickle cell anemia. Distinguishing between sickle cell disease and trait is crucial during the diagnosis of sickle cell disease. While genetic analysis or high-performance liquid chromatography (HPLC) can accurately differentiate between these two genotypes, these tests are unsuitable for field use. Here, we report a novel microscopy-based diagnostic test called ShapeDx™ to distinguish between disease and trait blood in less than 1 h. This is achieved by mixing an unknown blood sample with low and high concentrations of a chemical oxygen scavenger and thereby subjecting the blood to slow and fast hypoxia, respectively. The different rates of Hb polymerization resulting from slow and fast hypoxia lead to two distinct RBC shape distributions in the same blood sample, which allows us to identify it as healthy, trait, or disease. The controlled hypoxic environment necessary for differential Hb polymerization is generated using an imaging microchamber, which also reduces the sickling time of trait blood from several hours to just 30 min. In a single-blinded proof-of-concept study conducted on a small cohort of clinical samples, the results of the ShapeDx™ test were 100% concordant with HPLC results. Additionally, our field studies have demonstrated that ShapeDx™ is the first reported microscopy test capable of distinguishing between sickle cell disease and trait samples in resource-limited settings with the same accuracy as a gold standard test.
    Keywords:  RBC shape; diagnostics; hemoglobin polymerization; shape‐based classifier; sickle cell anemia; smartphone microscopy
    DOI:  https://doi.org/10.1002/btm2.10643
  10. Pediatr Blood Cancer. 2024 Jul 25. e31219
    Splenic complications in pediatric sickle cell disease: A retrospective cohort review.
    Alex George, Shannon E Conneely, Ross Mangum, Titilope Fasipe, Philip J Lupo, Michael E Scheurer.
       OBJECTIVE: To delineate the natural history of splenic complications other than loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children's Hospital.
    METHODS: We determined the dates of diagnoses of splenic complications, the number of acute splenic sequestration crises (ASSC), and hydroxyurea treatment in pediatric patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC.
    RESULTS: The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of splenic complications was highest in patients with hemoglobin Sβ0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sβ+. The overall event rate of ASSC was 8.3 per 100 patient-years. The event-rate was 28.4 for hemoglobin Sβ0, 10.9 for hemoglobin SS, and 3.5 for hemoglobin SC. Patients with hemoglobin SS and hemoglobin Sβ0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event rates of 14.2 and 3.1, respectively. The event rate was also higher for children who started hydroxyurea before age 2 years than for those who started after this age (19.8 and 9.2, respectively).
    CONCLUSIONS: The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sβ0 having the most severe complications. Hydroxyurea therapy is associated with increased incidence of ASSC, particularly when initiated before 2 years of age.
    Keywords:  acute splenic sequestration crises; hydroxyurea; hypersplenism; sickle cell disease; splenectomy; splenomegaly
    DOI:  https://doi.org/10.1002/pbc.31219
  11. Asian J Transfus Sci. 2024 Jan-Jun;18(1):18(1): 144-147
    Outcome of pregnancy in sickle cell anemia patients with COVID-19 infection.
    Vaidyanathan Gowri, Tamima Al Dughaishi, Deepti Geetha, Marwa Al Riyami, Radhiya Alburaidi, Salam Al Kindi.
      Sickle cell anemia (SCA) is a multisystem disease, associated with increased risk for infection and thromboembolic disease, and pregnancy is a stressor for patients with SCA. In general, coronavirus disease 2019 (COVID-19) infection in SCA is associated with a favorable outcome. Literature of pregnancy in SCA with COVID is scarce. We report a case series study of pregnant women with SCA, who are confirmed positive for COVID-19 from May 2020 to March 2021. These patients showed generally mild-to-moderate disease and presented predominantly with fever and painful crisis. They showed a significant drop in Hb from baseline, and they received low-molecular-weight heparin prophylaxis (LMWH) and blood transfusion. The outcome of pregnancy is satisfactory, although the mean birth weight was significantly lower than that reported from the same SCA population.
    Keywords:  Coronavirus disease 2019; pregnancy; severe acute respiratory syndrome coronavirus 2; sickle cell anemia
    DOI:  https://doi.org/10.4103/ajts.ajts_164_21
  12. Br J Haematol. 2024 Jul 25.
    Hypertonicity and/or acidosis induce marked rheological changes under hypoxic conditions in sickle trait red blood cells.
    Patrick Ellsworth, Izabela J Pawlinski, Rachel Sielaty, Anton Ilich, Yuriy Prokopenko, Chatphatai Moonla, Dougald M Monroe, Rafal Pawlinski, Nigel S Key.
      Deformability and sickling of red blood cells (RBCs) from individuals with sickle cell trait (SCT) was evaluated under harsh biophysical conditions that mimic certain vascular beds in vivo. RBC deformability in osmotic-gradient ektacytometry was decreased in HbAS (SCT) compared to HbAA (wild-type) RBCs at supraphysiological osmolalities. RBC deformability was also measured by oxygen-gradient ektacytometry. Whereas RBC sickling was not observed under isotonic and neutral pH conditions, hypertonicity and acidosis alone or in combination induced reversible sickling of SCT RBC. These data suggest that hyperosmolality and/or acidosis enhance hypoxia-induced sickling of SCT RBC.
    Keywords:  hypoxia; red cell; rheology; sickle cell trait
    DOI:  https://doi.org/10.1111/bjh.19669
  13. Am J Hematol. 2024 Jul 22.
    Disease burden, management strategies, and unmet needs in α-thalassemia due to hemoglobin H disease.
    Ashutosh Lal, Vip Viprakasit, Elliott Vichinsky, Yongrong Lai, Meng-Yao Lu, Antonis Kattamis.
      Alpha-thalassemia is an inherited blood disorder caused by impaired α-globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α-globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notably, non-deletional mutations cause a greater degree of ineffective erythropoiesis and hemolysis, higher transfusion burden, and increased complication risks versus deletional mutations. There are limited treatment options for HbH disease, and effective therapies are needed. This review discusses the pathophysiology of HbH disease, current management strategies, unmet needs, and emerging treatment options.
    DOI:  https://doi.org/10.1002/ajh.27440
  14. J Med Life. 2024 Mar;17(3): 314-317
    Serum visfatin level in β-thalassemia and its correlation with disease severity.
    Himadri Shukla, Anurag Singh, Rashmi Kushwaha, Shailendra Prasad Verma, Nishant Verma, Uma Shankar Singh.
      Thalassemia is a group of genetic hematological conditions characterized by the defective synthesis of one or more hemoglobin chains. This genetic anomaly alters globin chain balance, causing hemolysis, ineffective erythropoiesis, and chronic inflammatory diseases. The proinflammatory adipocytokine visfatin is predominantly produced in visceral adipose tissue. Its evaluation in individuals with thalassemia may provide valuable insights into the assessment of disease severity. The aim of this study was to investigate the potential role of visfatin in the development of β-thalassemia and its association with the severity of the illness. The study included 40 patients with β-thalassemia and ten healthy individuals matched by age and sex. Serum visfatin level was measured using ELISA. We found that individuals with β-thalassemia major had significantly higher levels of serum visfatin than those with β-thalassemia minor and the control group (P < 0.001). A receiver operating characteristic curve revealed that serum visfatin levels were different in the three groups. Our results suggest that the serum level of visfatin is significantly correlated with the severity of β-thalassemia.
    Keywords:  beta-thalassemia; hematological disorders; inflammation; visfatin
    DOI:  https://doi.org/10.25122/jml-2023-0354
  15. Exp Hematol. 2024 Jul 22. pii: S0301-472X(24)00142-5. [Epub ahead of print] 104283
    Erythropoiesis in the mammalian embryo.
    James Palis.
      Red blood cells (RBCs) comprise a critical component of the cardiovascular network, which constitutes the first functional organ system of the developing mammalian embryo. Examination of circulating blood cells in mammalian embryos revealed 2 distinct types of erythroid cells- large, nucleated 'primitive' erythroblasts followed by smaller, enucleated 'definitive' erythrocytes. This review describes the current understanding of primitive and definitive erythropoiesis gleaned from studies in mouse and human embryos and induced pluripotent stem cells (iPSCs). Primitive erythropoiesis in the mouse embryo comprises a transient wave of committed primitive erythroid progenitors (primitive erythroid colony-forming cells, EryP-CFC) in the early yolk sac that generates a robust cohort of precursors that mature in the bloodstream and enucleate. In contrast, definitive erythropoiesis has 2 distinct developmental origins. The first comprises a transient wave of definitive erythroid progenitors (burst-forming units erythroid, BFU-E) that emerge in the yolk sac and seed the fetal liver where they terminally mature to provide the first definitive RBCs. The second comprises hematopoietic stem cell (HSC)-derived BFU-E that terminally mature at sites colonized by HSCs particularly the fetal liver and subsequently the bone marrow. Primitive and definitive erythropoiesis are derived from endothelial identity precursors with distinct developmental origins. While they share prototypical transcriptional regulation, they are also characterized by distinct lineage-specific factors. The exquisitely timed, sequential production of primitive and definitive erythroid cells is necessary for the survival and growth of the mammalian embryo.
    Keywords:  definitive; erythropoiesis; primitive; yolk sac
    DOI:  https://doi.org/10.1016/j.exphem.2024.104283
  16. Orphanet J Rare Dis. 2024 Jul 24. 19(1): 278
    Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis.
    Chongjun Wu, Yixin Yan, Ting Xiong, Wen Jiang, Jing Xu, Yanfei Rao, Jianyun Ao, Chun Xu, Xuehong Li, Longwang Qi, Wenhong Zheng, Wenjin Li, Zhongjin Xu, Yu Yang, Zhenjiang Li.
       OBJECTIVE: This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype-phenotype correlations in Chinese patients with hereditary spherocytosis (HS).
    METHODS: Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).
    RESULTS: A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.
    CONCLUSION: This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.
    Keywords:   ANK1 ; SPTB ; Hereditary spherocytosis; Pediatric and adult
    DOI:  https://doi.org/10.1186/s13023-024-03290-y
  17. Asian J Transfus Sci. 2024 Jan-Jun;18(1):18(1): 73-78
    The effect of blood transfusion on serum hepcidin levels in chronically transfused patients of β-thalassemia major: An observational study in a tertiary care centre in Western Maharashtra.
    Sujay Bhowmik, Amit Kumar Biswas, Ajay Kumar Baranwal, Amit Ajay Pawar, Ujjwal Dimri.
       INTRODUCTION: Hepcidin is the key regulator of systemic iron homeostasis. In iron-loading anemias, hepcidin levels are regulated by opposite forces of erythropoiesis and iron overload. In β-thalassemia major patients, transfusions are the predominant cause of iron overload; in such chronically transfused patients, hepcidin concentrations are significantly higher than nontransfused patients, due to both increased iron load of transfusions and the suppression of ineffective erythropoiesis.
    AIM: This study aims to evaluate the effect of blood transfusions on serum hepcidin levels in chronically transfused patients of β-thalassemia major and correlate with hemoglobin and serum ferritin levels of pre- and posttransfusion.
    MATERIALS AND METHODS: Thirty-three β-thalassemia major patients requiring monthly transfusions were included in the study. Blood samples, collected pretransfusion and 7 days posttransfusion, were evaluated for hemoglobin, serum ferritin, and serum hepcidin using enzyme immunoassay.
    STATISTICAL ANALYSIS: Data were statistically analyzed through SPSS software and P < 0.05 is considered statically significant.
    RESULTS: Posttransfusion levels of hemoglobin, serum ferritin, and serum hepcidin increased. Posttransfusion levels of hepcidin were near normal levels. Pre- and posttransfusion hepcidin concentrations were significantly associated with hemoglobin levels.
    CONCLUSION: Serum hepcidin concentrations vary depending on the degree of erythropoiesis drive and level of anemia. We found that the serum hepcidin levels decrease over the inter-transfusion interval and transfusions cause suppression of ineffective erythropoiesis by the increase in hemoglobin. Posttransfusion values of hepcidin in our study were closer to normal levels which may be due to lower erythropoietic drive posttransfusion. We suggest that the measurement of serum hepcidin in chronically transfused β-thalassemia patients can be used as a follow-up investigation for better management of these patients.
    Keywords:  hepcidin; iron overload; transfusion-dependent thalassemia; β-thalassemia major
    DOI:  https://doi.org/10.4103/ajts.ajts_160_22
  18. Pediatr Blood Cancer. 2024 Jul 23. e31224
    Luspatercept for non-deletional hemoglobin H disease.
    Yuan-Ning Yang, Yen-Yin Chou, Chao-Neng Cheng.
      
    DOI:  https://doi.org/10.1002/pbc.31224
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