bims-conane 2025-05-18 papers

bims-conane

Biomed News

on Congenital anemias

Issue of 2025–05–18
eight papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo

Thalidomide Treatment for Thrombocytopenia Secondary to Hypersplenism in Children with Transfusion-Dependent β-Thalassemia: A Case Series.
Genetic polymorphism of novel SNP rs5006884 in OR51B6 and SNP rs4499252 in AHSP among transfusion-dependent and non-transfusion-dependent β-thalassemia/Hb E patients in Thailand: a multivariate analysis of clinical and genetic polymorphism.
Clinicohematological and molecular analysis of hemoglobin D syndrome and unknown variants in the hemoglobinopathy spectrum of Sindh, Pakistan.
Diagnosis and management of severe SPTA1-associated congenital anaemia in a family cohort affected by two founder variants.
The double edge of erythropoietic modulation in thalassaemia.
Case Report: Post-splenectomy bulky pelvic splenosis in an adolescent with hereditary spherocytosis.
Hematological ratios and cytokine profiles in heterozygous beta-thalassemia.
Clinical usefulness of next-generation sequencing-based target gene sequencing in diagnosis of inherited bone marrow failure syndrome.

Mediterr J Hematol Infect Dis. 2025 ;17(1): e2025037

Thalidomide Treatment for Thrombocytopenia Secondary to Hypersplenism in Children with Transfusion-Dependent β-Thalassemia: A Case Series.

Xiaoqing Gong, Jian Xiao, Wenqiang Kong, Xiaodong Liu, Kun Yang.



Keywords:  Hypersplenism; Thrombocytopenia; Transfusion-dependent β-thalassemia

DOI:  https://doi.org/10.4084/MJHID.2025.037
Ann Hematol. 2025 May 16.

Genetic polymorphism of novel SNP rs5006884 in OR51B6 and SNP rs4499252 in AHSP among transfusion-dependent and non-transfusion-dependent β-thalassemia/Hb E patients in Thailand: a multivariate analysis of clinical and genetic polymorphism.

Chidchanok Mahabhol, Lalana Yothindamrongkul, Nicha Nuntanajaroenkul, Purima Nawasod, Wanicha Tepakhan, Rossarin Karnpean, Panjarat Sowithayasakul, Nisa Makruasi, Therdkiat Trongwongsa, Wittaya Jomoui.

  Compound heterozygous β-thalassemia and Hb E, a prevalent and severe form of thalassemia in Southeast Asia, manifests in two major clinical forms: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). This study investigates the association of genetic polymorphisms rs5006884 in OR51B6, rs4499252 in AHSP, rs9399137 in HBS1L-MYB, and rs4671393 in BCL11A with clinical severity and transfusion dependency in β-thalassemia/Hb E patients in Thailand. A total of 189 samples, including 58 TDT, 58 NTDT, 33 homozygous Hb E, and 40 wild-type individuals, were analyzed. Genotyping of the four single nucleotide polymorphisms (SNPs) was conducted using the rhAmp SNP Genotyping assay. Multivariate regression models were developed to evaluate the combined effects of genetic and clinical factors on transfusion dependency. The results showed that OR51B6 SNP rs5006884 TT genotype was significantly more frequent in the NTDT group (P < 0.05), suggesting a strong association with reduced transfusion dependency. Conversely, the AHSP SNP rs4499252 GG genotype was significantly less frequent in the homozygous Hb E group (P < 0.05) compared to other groups. Multivariate analyses highlighted hemoglobin (Hb) levels as a robust predictor of transfusion dependency, with specific HBB mutations including HBB:c.59 A > G, HBB:c.-78 A > G, HBB:c.316-197 C > T, and NC_000011.10:g.5224302_5227791del being significantly associated with NTDT (P < 0.05). Furthermore, rs5006884 in OR51B6 also played a significant role in NTDT in multivariate analyses. In contrast, SNPs in BCL11A (rs4671393), HBS1L-MYB (rs9399137), and AHSP (rs4499252) showed no significant independent associations with transfusion dependency or disease severity in this cohort. This study explores rs5006884 in OR51B6 and rs4499252 in AHSP in TDT and NTDT patients for the first time. These findings elucidate the interplay of genetic and clinical factors influencing β-thalassemia severity, paving the way for personalized management strategies to mitigate transfusion requirements.

Keywords:  Beta-thalassemia; Biomedical; Hemoglobin E; Polymorphism; Transfusion dependent

DOI:  https://doi.org/10.1007/s00277-025-06403-0
PLoS One. 2025 ;20(5): e0320354

Clinicohematological and molecular analysis of hemoglobin D syndrome and unknown variants in the hemoglobinopathy spectrum of Sindh, Pakistan.

Sunila Tashfeen, Ikram Din Ujjan, Hina Shaikh, Muhammad Arif Sadiq, Feriha Fatima Khidri, Ali Raza Rajput, Ali Muhammad Waryah.

OBJECTIVES: Hemoglobinopathies are prevalent monogenic disorders resulting from genetic abnormalities in globin genes, significantly impacting health. β-thalassemia is particularly common in Pakistan, but data on other hemoglobin variants remain limited. This study aimed to investigate HbD syndrome, identify unknown variants, and examine the clinicohematological and molecular profiles of hemoglobinopathies in Sindh, Pakistan.
METHODS: A prospective cross-sectional study was conducted from January 2021 to January 2023 at Liaquat University of Medical and Health Sciences (LUMHS), Jamshoro, Pakistan. Blood samples were collected from across Sindh, Pakistan and analyzed for hemoglobinopathies using hematological tests (CBC, peripheral blood smear), cation exchange high-performance liquid chromatography (CE-HPLC) and molecular analysis to confirm HbD and identify rare variants. Data were analyzed using SPSS v. 27.
RESULTS: Out of 4783 chromatograms analyzed, 1563 (32.7%) were diagnosed with hemoglobinopathies. The most common conditions included β-thalassemia (81.4%), hemoglobin (Hb) variants (11.2%), and hereditary persistence of fetal hemoglobin (7.4%). HbD was found in 2.1% of cases, with HbD syndromes being the most prevalent among Hb variants (56.6%). Sickle cell disorders followed with a frequency of 32%, and HbQ, HbE, and HbC were less common. Molecular analysis confirmed the HbD Punjab variant and identified an additional four mutations, i.e., one rare β-thalassemia mutation and three Hb variants including Hb Hinsdale, Hb Renert and Hb Takasago.
CONCLUSION: Hb D Punjab is the most prevalent hemoglobin variant in Sindh, Pakistan, followed by HbS and HbQ. Molecular analysis is essential for accurate diagnosis and identifying rare variants. Integrating HbD detection into screening programmes and genetic counselling can help prevent hemoglobinopathies. (S1 Abstract Graphic).

DOI: https://doi.org/10.1371/journal.pone.0320354
BMJ Case Rep. 2025 May 12. pii: e265190. [Epub ahead of print]18(5):

Diagnosis and management of severe SPTA1-associated congenital anaemia in a family cohort affected by two founder variants.

Sarena Hayer, Trisha Wong, Cori Feist, Raphael C Sun, Todd Williams, Evan B Shereck, Andrew H Chon.

  Hereditary spherocytosis due to mutations in the SPTA gene is a rare cause of fetal anaemia which can present as hydrops fetalis. We present a unique family cohort demonstrating severe transfusion-dependent anaemia with prenatal onset due to two SPTA1 founder variants which were diagnosed over several years as genetic testing capabilities advanced. Each patient was managed antenatally with fetal blood sampling (FBS) and intrauterine transfusions (IUT) with varying levels of success. Out of six affected pregnancies, two resulted in fetal demise, two resulted in postnatal demise and two long-term survivors required bone marrow transplant. While FBS and IUT are key in the antenatal management, multidisciplinary care is essential given the long-term complex medical comorbidities among postnatal survivors.

Keywords:  Congenital disorders; Genetic screening / counselling; Haematology (incl blood transfusion); Materno-fetal medicine; Pregnancy

DOI:  https://doi.org/10.1136/bcr-2025-265190
Br J Haematol. 2025 May 13.

The double edge of erythropoietic modulation in thalassaemia.

Paolo Ricchi.

  Luspatercept has emerged as a valuable therapeutic option for patients with transfusion-dependent β-thalassaemia, enabling significant reduction in transfusion requirements. In the report by Zaidel et al., a paradoxical clinical scenario is described in which treatment with luspatercept was associated with progressive splenomegaly, thrombocytopenia, increased haemolysis and a marked rise in reticulocytes and nucleated red blood cells, promptly reversible upon drug discontinuation. Luspatercept usually enhances late-stage erythroid maturation, but, in rare cases like this, seems to trigger or exacerbate extramedullary haematopoiesis (EMH) and/or splenic sequestration. The report underscores the importance of close monitoring and a deeper understanding of individual susceptibility to optimize the safe use of luspatercept in thalassaemia. Further studies are needed to clarify the underlying mechanisms and to identify patients at risk for EMH-related complications during luspatercept treatment. Commentary on: Zaidel et al. Acute splenomegaly, haemolysis, and thrombocytopenia following luspatercept initiation in a patient with transfusion-dependent thalassaemia: A case report. Br J Haematol 2025 (Online ahead of print). doi: 10.1111/bjh.20131.

Keywords:  drugs; erythropoiesis; thalassaemia

DOI:  https://doi.org/10.1111/bjh.20142
Front Pediatr. 2025 ;13 1581533

Case Report: Post-splenectomy bulky pelvic splenosis in an adolescent with hereditary spherocytosis.

Benedetta Elena Di Majo, Nicolò Peccatori, Alessandra Inzoli, Luca Degrate, Marta Jaconi, Michele Ratti, Alessandra Casiraghi, Giulia Maria Ferrari, Debora Sala, Andrea Biondi, Paolo Passoni, Paola Corti.

  Splenectomy is a well-established therapeutic approach for pediatric hematologic disorders, especially in the case of hereditary spherocytosis (HS). In addition to the commonly acknowledged short- and long-term infectious and thrombotic complications, also splenosis represents a rare but noteworthy complication of splenectomy. Splenosis is characterized by the auto-transplantation and growth of splenic tissue in ectopic locations, following trauma or splenectomy. This condition can mimic malignancies, posing diagnostic challenges. We report the case of a 16-year-old girl with HS who presented with fever, abdominal pain, and a history of laparoscopic splenectomy ten years early. Imaging revealed a vascularized pelvic mass, initially suspected to be malignant. Diagnostic laparoscopy and histopathological analysis confirmed the mass as pelvic splenosis. The patient was asymptomatic, prompting a conservative management approach with regular follow-up. This case highlights the importance of considering splenosis in differential diagnoses for pelvic masses in patients with prior splenectomy, to ensure appropriate management and avoid unnecessary interventions.

Keywords:  hereditary spherocytosis; pediatric; spleen; splenectomy; splenosis

DOI:  https://doi.org/10.3389/fped.2025.1581533
Hematol Transfus Cell Ther. 2025 May 12. pii: S2531-1379(25)00113-0. [Epub ahead of print]47(3): 103845

Hematological ratios and cytokine profiles in heterozygous beta-thalassemia.

Ana Carolina Marques Ciceri, Laura Eduarda de Oliveira, Ana Luísa Richter, José Antonio Mainardi de Carvalho, Maylla Rodrigues Lucena, Guilherme Wataru Gomes, Maria Stella Figueiredo, Magnun Nueldo Nunes Dos Santos, Vera Lúcia Nascimento Blaia-D'Avila, Rodolfo Delfini Cançado, Elvira Maria Guerra-Shinohara, Clóvis Paniz.

   INTRODUCTION: β-Thalassemia is defined by a reduced or complete absence of β-globin chain synthesis in hemoglobin, leading to hemolytic anemia. Heterozygous β-thalassemia, also known as β-thalassemia trait (hBTh), the mildest form of this anemia, typically does not cause symptoms in carriers. However, it may lead to changes in the immune system, including an increase in total leukocyte, neutrophil, and lymphocyte counts.
OBJECTIVE: This study aimed to evaluate various immune and inflammation markers, including neutrophil/lymphocyte, derived neutrophil/lymphocyte, lymphocyte/monocyte, platelet/lymphocyte, neutrophil/platelet ratios, systemic immune-inflammation index, systemic inflammation response index, neutrophil/natural killer cell ratio (NNKR), and inflammatory cytokines in β-thalassemia trait carriers.
METHOD: A retrospective observational study was conducted, including 50 β-thalassemia trait individuals and 100 healthy controls.
RESULTS: Leukocyte, neutrophil and reticulocyte counts, and interleukin 6 levels were higher in carriers compared to controls. Notably, the β-thalassemia trait group had increased neutrophil/platelet, neutrophil/lymphocyte and derived neutrophil/lymphocyte ratios, and the systemic immune-inflammation and systemic inflammation response indexes were higher compared to the controls.
CONCLUSIONS: β-thalassemia trait shows a more pronounced inflammatory profile as indicated by hematological ratios. These ratios, therefore are potentially cost-effective and easily applicable markers for monitoring patients with the β-thalassemia trait.

Keywords:  Hematologic ratios; Hemolytic anemia; Heterozygotic thalassemia; Inflammation; Β-thalassemia

DOI:  https://doi.org/10.1016/j.htct.2025.103845
Ann Hematol. 2025 May 13.

Clinical usefulness of next-generation sequencing-based target gene sequencing in diagnosis of inherited bone marrow failure syndrome.

Young Dai Kwon, Kyung Taek Hong, Juyeon Lee, Yoon Sunwoo, Yeseul Kim, Sung Im Cho, Hyun Jin Park, Bo Kyung Kim, Jee-Soo Lee, Jung Yoon Choi, Moon-Woo Seong, Hyoung Jin Kang.

  Inherited bone marrow failure syndromes are genetic hematologic disorders with increased cancer risk. Accurate diagnosis is crucial for appropriate management. This study assessed the clinical usefulness of next-generation sequencing (NGS)-based target gene sequencing in pediatric and AYA (adolescent and young adult) patients with hematologic abnormalities. From December 2019 to June 2023, 93 patients with suspected congenital hematologic diseases at a single institution underwent NGS-based testing. Medical records were retrospectively reviewed. The median age at diagnosis was 9.3 years (range 0.2-31.4), with 59.1% males. Indications for testing included specific medical histories (28 patients), persistent cytopenia or recurrent neutropenic fever (22 patients), changes in cytopenia patterns (11 patients), and other reasons (32 patients). Pathogenic variants were identified in 9/28 (32.1%), 3/22 (13.6%), 4/11 (36.4%), and 0/32 (0%). Overall, 16 patients (17.2%) had pathogenic variants, including FANCA, BRCA2, PMS2, ELANE, G6PC3 and VPS13B in patients with idiopathic neutropenia, and GATA2 in patients with suspected myelodysplastic syndrome. Genetic findings led to diagnostic revisions in 12 patients (12.9%), including reclassification of aplastic anemia (AA) as Fanconi anemia, Diamond-Blackfan anemia, or Shwachman-Diamond syndrome, prompting hematopoietic stem cell transplantation and altering cancer surveillance. Pathogenic variants were more frequently observed in patients with a specific medical history or changes in cytopenia, and in those with additional clinical features (cytogenetic abnormalities or non-severe AA). This study demonstrated the diagnostic usefulness of NGS-based target gene sequencing for pediatric and AYA patients with suspected genetic hematologic disorders, supporting the need for multicenter studies and standardized guideline development.

Keywords:  Cytopenia; Inherited bone marrow failure syndrome; Next-generation sequencing

DOI:  https://doi.org/10.1007/s00277-025-06392-0