bims-conane 2025-09-07 papers

bims-conane

Biomed News

on Congenital anemias

Issue of 2025–09–07
nine papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo

Clinical and hematological characteristics of beta-plus thalassemia and uncommon beta-chain hemoglobin variants in Northern Thailand.
Severe Hemolytic Phenotype in Children With Sickle Cell Anemia and Co-Inherited Red Blood Cell Variants.
Genotype clinical phenotype analysis of 35 cases of hereditary spherocytosis in children.
β-thalassemia trait and iron overload: is it time to consider oral iron chelators? Comments on: "A case series of patients with β-thalassemia trait and iron overload: from multifactorial hepcidin suppression to treatment with mini-phlebotomies".
Efficacy and safety of luspatercept in non-transfusion-dependent β-thalassemia: long-term results from the BEYOND study.
Clinical course and pregnancy outcomes in women with hereditary spherocytosis: Insights from a case series.
Genetic mutations of congenital red cell membrane defects in hydrops fetalis.
Outcomes and risk factors for complications in deletional haemoglobin H disease: A retrospective longitudinal cohort study in British Columbia, Canada.
Short-term risks and benefits of hydroxyurea (hydroxycarbamide)-induced transfusion independence in patients with beta-thalassaemia syndromes.

Ann Med. 2025 Dec;57(1): 2551815

Clinical and hematological characteristics of beta-plus thalassemia and uncommon beta-chain hemoglobin variants in Northern Thailand.

Punwadee Rukwong, Rungrote Natesirinilkul, Lalita Sathitsamitphong, Chane Choed-Amphai, Adisak Tantiworawit, Kanda Fanhchaksai, Supawadee Maneekesorn, Pimlak Charoenkwan.

   BACKGROUND: Thalassemia is the most common hereditary anemia worldwide. Beta-thalassemia results from mutations in HBB gene, causing either absent (β0) or decreased (β+) production of β-globin. Mutations causing β+-thalassemia comprise 10-20%of HBB mutations in Thailand. However, their clinical characteristics are poorly characterized.
OBJECTIVES: To describe the clinical and hematological characteristics of patients with β+-thalassemia and uncommon β-chain hemoglobin (Hb) variants.
METHODS: Clinical and hematological data of patients with β+-thalassemia and uncommon β-chain Hb variants at Chiang Mai University Hospital were retrospectively reviewed.
RESULTS: Forty-three patients were included in the study. Three HBB β+-thalassemia mutations: nt-28(A > G), nt-31(A > G), and nt-87(C > A), and four Hb variants: Hb Tak, Hb Dhonburi, Hb Malay, and Hb Hope. Seventeen patients had β+/β0-thalassemia, 11 had Hb E/β+-thalassemia, and 15 had Hb variants. All patients with β+/β0-thalassemia were transfusion dependent. All patients with β+-thalassemia/Hb E had mild disease and were non-transfusion-dependent. Patients with Hb Tak/β0-thalassemia presented with polycythemia. Hb Hope/β0-thalassemia, Hb Hope/Hb E, and Hb Dhonburi/Hb E resulted in mild phenotypes. Patients with Hb Malay/β0-thalassemia required occasional or regular transfusions.
CONCLUSIONS: All HBB mutations causing β+-thalassemia in this study were promoter mutations. β+/β0-thalassemia results in transfusion-dependent thalassemia, whereas β+-thalassemia/Hb E disease is associated with mild disease. Beta-chain Hb variants when coinherited with β-thalassemia mostly result in mild or moderate phenotypes, and the clinical characteristics depend on the type of Hb variant.

Keywords:  Beta-plus thalassemia; beta-chain variant; hemoglobin variant; promoter mutation

DOI:  https://doi.org/10.1080/07853890.2025.2551815
Pediatr Blood Cancer. 2025 Oct;72(10): e31937

Severe Hemolytic Phenotype in Children With Sickle Cell Anemia and Co-Inherited Red Blood Cell Variants.

Meghana Srinivas, Sue Jaspersen, David B Wilson, Monica L Hulbert.

  Remarkable phenotypic variability exists among individuals with sickle cell anemia (SCA), which may be explained by co-inheritance of traits affecting red blood cell (RBC) biology, such as genes affecting globin expression or glucose-6-phosphate dehydrogenase enzyme activity. Here, we describe three children with severe SCA who have co-inherited variants in genes for membrane proteins (SPTA1 and EPB1) and PIEZO1. These cases suggest that variants in RBC membrane proteins may contribute to SCA severity and phenotypic variation. Co-Inheritance of such variants could, in theory, affect outcomes of emerging SCA therapies, including genetic modification treatments.

Keywords:  PIEZO1; elliptocytosis; genetic modifiers; glucose‐6‐phosphate dehydrogenase deficiency; hemolytic anemia; sickle cell anemia; sickle cell disease

DOI:  https://doi.org/10.1002/pbc.31937
Front Pediatr. 2025 ;13 1650295

Genotype clinical phenotype analysis of 35 cases of hereditary spherocytosis in children.

Huang Duowen, Guo Xia, Gao Ju.

   Objective: Hereditary spherocytosis (HS) is a common red blood cell membrane disease. It is currently clear that mutations in genes such as ANK1, SPTB, SPTA1, SLC4A1, EPB4.2 can cause the loss of their corresponding encoded proteins. However, there is a lack of reports in China on the association analysis between HS genotypes and clinical phenotypes, aiming to reveal whether there are differences in the corresponding clinical phenotypes of the same disease when genotypes are different.
Methods: 35 children with HS who underwent complete whole exome gene sequencing in the Department of Pediatric Hematology at West China Second Hospital of Sichuan University from February 2014 to February 2024. Grouping according to different mutated genes/mutation types, and statistical analysis of blood routine and liver function indicators between different groups; Mann Whitney test analysis was used for inter group data processing, and significant differences were considered when both sides were p < 0.05.
Results: Compared with the SPTB group, the ANK1 group had significantly lower RBC (p = 0.021) and HGB (p < 0.01), but the differences in other indicators were not statistically significant (p > 0.05).
Conclusions: After excluding potential influencing factors such as splenectomy, the anemia symptoms in ANK1-HS patients were more severe than those in SPTB-HS patients. However, there was no statistically significant difference in indicators between HS patients with different types of gene mutations.

Keywords:  genotype and phenotype; hereditary spherocytosis; pathogenic genes; red blood cell structure; whole exome gene sequencing

DOI:  https://doi.org/10.3389/fped.2025.1650295
Haematologica. 2025 08 28.

β-thalassemia trait and iron overload: is it time to consider oral iron chelators? Comments on: "A case series of patients with β-thalassemia trait and iron overload: from multifactorial hepcidin suppression to treatment with mini-phlebotomies".

Alberto Piperno, Raffaella Mariani.

Not available.

DOI: https://doi.org/10.3324/haematol.2025.288578
Blood Adv. 2025 Aug 28. pii: bloodadvances.2025016554. [Epub ahead of print]

Efficacy and safety of luspatercept in non-transfusion-dependent β-thalassemia: long-term results from the BEYOND study.

Ali T Taher, Vip Viprakasit, Antonis Kattamis, Silverio Perrotta, Paolo Ricchi, John B Porter, Thomas D Coates, Gian Luca Forni, Khaled M Musallam, Oriana Esposito, Richard Pilot, Wen-Ling Kuo, Yinzhi Lai, Marta Reverte, Richard Wei, Luciana Moro Bueno, Maria Domenica Domenica Cappellini.

Chronic anemia due to non-transfusion-dependent β-thalassemia (NTDT) can result in clinical morbidities, particularly with inadequate management. Luspatercept was previously shown to improve hemoglobin levels in patients with NTDT in the phase 2, randomized, double-blind, placebo-controlled BEYOND trial (ClinicalTrials.gov, NCT03342404). Here, we report long-term efficacy and safety results from the final analysis of BEYOND spanning an additional 26 months (~2.2 years) of follow-up. Median treatment duration was 202.8 weeks for luspatercept and 61.1 weeks for placebo. Overall, 94.8% and 22.4% of patients in the luspatercept and placebo arms, respectively, achieved a mean hemoglobin increase from baseline ≥1.0 g/dL during any 12-week interval, with mean durations of response of 1136.0 and 203.3 days, respectively. Patient-reported tiredness and weakness showed sustained improvement with luspatercept treatment. The most common treatment-emergent adverse events in the luspatercept group were headache (45.8% vs 20.4% with placebo), bone pain (43.8% vs 6.1%), back pain (39.6% vs 12.2%), and arthralgia (38.5% vs 16.3%). Treatment-emergent extramedullary hematopoiesis events were reported in 12 (9.0%) and 2 (4.1%) patients receiving luspatercept and placebo, respectively, although differences in treatment exposures prevented informative comparisons. Of the 4 patients receiving luspatercept who reported thromboembolic events, all had >1 risk factor. These results show that luspatercept led to a sustained increase in hemoglobin levels in patients with NTDT for up to ~4.6 years of treatment, with a consistent safety profile and no new safety findings. Luspatercept is a valuable treatment option for patients with NTDT, addressing the need for effective long-term treatment of anemia. NCT03342404.

DOI: https://doi.org/10.1182/bloodadvances.2025016554
Obstet Med. 2025 Aug 26. 1753495X251367094

Clinical course and pregnancy outcomes in women with hereditary spherocytosis: Insights from a case series.

Bhabani Pegu, Panneerselvam Sivaranjani, Murali Subbaiah, Ambalakkuthan Murugesan.

   Background: Hereditary spherocytosis (HS) is a genetic haemolytic anaemia, mainly inherited in an autosomal dominant manner. Management varies by severity, and limited data exist on HS in pregnancy in India; this study assesses clinical and obstetric outcomes in affected women.
Methods: This retrospective study at JIPMER from 2014 to 2020 included 10 pregnant women with confirmed HS identified from labour room records. Data on demographics, medical and obstetric history, clinical presentation, pregnancy course, delivery details, complications, maternal and neonatal intensive care unit admissions, laboratory findings and postpartum outcomes were collected using a structured proforma.
Results: This case series of 10 pregnant women with HS highlights anaemia, jaundice, and weakness as common symptoms confirmed by laboratory findings. Most had term vaginal deliveries; one required caesarean section due to complications. Neonatal outcomes were favourable, with no neonatal HS cases. Anaemia was more pronounced in women without splenectomy, while splenectomised patients showed greater hematologic stability. Bone marrow findings indicated compensatory erythroid hyperplasia. Diagnosis relied on clinical and haematological criteria, as genetic testing was not performed.
Conclusion: HS in pregnancy is rare but manageable with appropriate antenatal care. This study confirms its classical presentation in the Indian population and supports early diagnosis, Eosin-5-maleimide testing and supportive management. Genetic testing and improved postnatal surveillance are recommended.

Keywords:  Hereditary spherocytosis; anaemia; blood transfusion; pregnancy outcome

DOI:  https://doi.org/10.1177/1753495X251367094
Fetal Diagn Ther. 2025 Aug 22. 1-12

Genetic mutations of congenital red cell membrane defects in hydrops fetalis.

Patcharee Komvilaisak, Khunton Wichajarn, Chanoknun Jaruk, Ratana Komvilaisak, Nongnuch Sirachainan, Napat Laoaroon, Junya Jirapradittha, Pongsatorn Paopongsawan, Pakaphan Kiatchoosakun, Kunanya Suwannying.

Hereditary pyropoikilocytosis (HPP) is a rare genetic disorder causing severe fetal anemia, often leading to hydrops fetalis. This study evaluates intrauterine blood transfusion (IUT) efficacy and associated genetic mutations in Northeastern Thai patients. Eight fetuses with hydrops fetalis were identified between 17 and 30+6 weeks' gestation, with initial hematocrit levels of 8.7 to 16.7%. IUTs were performed at 20-36 weeks, guided by fetal hematocrit, middle cerebral artery peak systolic velocity (MCA-PSV), and fetal hemodynamic status. Five cases progressed uneventfully following IUTs, although three resulted in premature delivery. Four cases reached term, with two infants born at normal weight and two at low birth weight. Among premature cases, three had birth weights below the 10th percentile for gestational age, and one had normal weight. Five patients remain transfusion-dependent. Genetic analysis revealed homozygous Spectrin Providence in four patients, homozygous Spectrin Buffalo in one, compound heterozygous Spectrin Providence/Buffalo in two, and Spectrin Providence with SPTB c.6171_6182delinsACCCCAGCT (novel) in one. Three cases developed severe complications, including severe birth asphyxia, persistent pulmonary hypertension, and multiple organ failure, leading to death. Conclusions This study identified SPTB gene mutations associated with hereditary pyropoikilocytosis (HPP). Early detection of hydrops fetalis caused by severe anemia, along with confirmation of the underlying genetic mutation, is essential for timely and effective clinical intervention. Intrauterine transfusion remains a viable therapeutic option to sustain pregnancy and enhance fetal survival. Further research is needed to refine the management strategies for HPP-associated hydrops fetalis and to improve perinatal outcomes.

DOI: https://doi.org/10.1159/000548041
Br J Haematol. 2025 Aug 26.

Outcomes and risk factors for complications in deletional haemoglobin H disease: A retrospective longitudinal cohort study in British Columbia, Canada.

Jacqueline Blunt, Melissa Braschel, Heather McCartney, Navdeep Sandhu, Hayley Merkeley, Ali Amid.



Keywords:  alpha‐thalassaemia; clinical outcome; iron overload; transfusion

DOI:  https://doi.org/10.1111/bjh.70123
Br J Haematol. 2025 Aug 29.

Short-term risks and benefits of hydroxyurea (hydroxycarbamide)-induced transfusion independence in patients with beta-thalassaemia syndromes.

B R Sevanthini, Santhosh Hegde, Tejashree Sridhar, Deepa Trivedi, Mohan Reddy, Vaibhav Shah, Vidhi Mayur Panchamia, T Geetha, Dharmik Vora, H Pushpa, Rajat Kumar Agarwal, Lawrence Faulkner.

  Clinical outcomes of hydroxyurea (hydroxycarbamide)-induced transfusion independence in patients with β-thalassaemia syndromes.

Keywords:  fetal haemoglobin (HbF); hydroxyurea (HU; hydroxycarbamide); pulmonary hypertension (PAH); sickle cell anaemia (SCA); transfusion‐dependent thalassaemia (TDT)

DOI:  https://doi.org/10.1111/bjh.70109