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We report a novel large α-globin gene cluster deletion in a Chinese family from the Guangxi Zhuang Autonomous Regionfor the first time. The proband was a 20-year-old male who presented with microcytic hypochromatosis. Routine genetic analysis showed none of the common mutations in theα-globin and β-globin genes. Multiplex ligation-dependent probe amplification (MLPA) of the α-globin chain revealed there was a large deletion, which removed the entire HBA2 and HBA1 genes, HBQ gene, HBZ gene, and major regulatory element HS-40, eliminating more than 134 kb from the α-globin chain. Subsequently, pedigree analysis revealed that the proband inherited the novel deletion from his father. By consultation of literature and databases, it was confirmed as a hitherto undescribed chain deletion and named Laibin deletion (- LB ) for the origin of the proband.

Background: The differential diagnosis between iron deficiency anemia (IDA) and thalassemia trait (TT) remains a significant clinical challenge. This study aimed to develop a machine learning-based multi-class model to differentiate among Microcytic-TT(TT with low mean corpuscular volume), Normocytic-TT (TT with normal mean corpuscular volume), IDA, and healthy individuals., Methods: A comprehensive dataset comprising 1,819 individuals was analyzed using six distinct machine learning algorithms. The eXtreme Gradient Boosting (XGBoost) algorithm was ultimately selected to construct the MultiThal-Classifier (M-THAL) model. SMOTENC (Synthetic Minority Over-sampling Technique for Nominal and Continuous features) was employed to address data imbalance. Model performance was evaluated using various metrics, and SHAP values were applied to interpret the model's predictions.Additionally, external validation was conducted to assess the model's robustness and generalizability., Results: After performing 1000 bootstrap resamples of the test set, the average performance metrics of M-THAL and the 95 % confidence interval(CI) were as follows, sensitivity 90.27 % (95 % CI: 84.88-95.26), specificity 97.87 % (95% CI: 97.10-98.55), PPV 93.42 % (95 % CI: 89.34-96.48), NPV 97.82% (95 % CI: 97.00-98.53), F1-score 91.50 % (95% CI: 87.29-95.34), Youden's index 88.15 % (95 % CI: 82.33-93.70), accuracy 97.06 % (95% CI: 96.06-97.99), and AUC 94.07 % (95 % CI: 91.17-96.84).Feature importance analysis identified mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), red cell distribution width - standard deviation(RDW-SD), and hemoglobin (HGB) were identified as the most important features. External validation confirmed the model's robustness and generalizability., Conclusion: The M-THAL effectively distinguishes Normocytic-TT, Microcytic-TT, IDA, and healthy individuals using hematological parameters, offers a rapid and cost-effective screening tool that can be readily implemented in diverse healthcare settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Psychological and social support is one of the factors that promote resilience in refugee children. Immigrant children with thalassemia have special psychosocial needs in the host country. The comfort model can help identify psychosocial needs. We applied Kolcaba's comfort theory to an 8-year-old Afghan boy with a history of thalassemia in Iran. According to Kolcaba's model, the taxonomy of psychological and social comfort needs were separation from mother, anxiety due to unfamiliarity with the hospital, fear of interaction and preference for silence, different culture and place of living, language barrier. To address his psychospiritual and sociocultural comfort care, we used coaching and comfort food interventions recommended by Kolcaba. The use of Kolcaba's Comfort Theory was helpful in promoting the child's emotional and social comfort in the case of an Afghan refugee child with thalassemia in Iran., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: To compare and find out the relationship between psychological distress, general health and life satisfaction among children with thalassemia and children undergoing dialysis., Method: The current study utilized cross sectional research design. A representative group of children with Thalassemia (n=60) and children undergoing dialysis (n=60) with ages ranging from 6-14 years were included in the sample. The sample was drawn from Children's Hospital and Sundas Foundation from February 2023 to August 2023 through a purposive sampling technique., Results: Psychological distress significantly correlates negatively with general health (-.34**) and life satisfaction (-.44**) in Children with Thalassemia. A significant negative relationship is also observed between psychological distress and general health (-.43**) and life satisfaction (-.54**) in Children undergoing Hemodialysis. Children undergoing hemodialysis experience more psychological distress whereas children with thalassemia have better general health. However, no significant difference was found in life satisfaction. The findings of the present study will be helpful for healthcare professionals and clinical psychologists to develop strategies and training programs which can increase resilience among patients. Training the patients and caregivers regarding how to fight chronic illnesses will lead to an improvement in their quality of life., Conclusion: Psychological distress is higher in children undergoing hemodialysis and general health is also not good but the level of satisfaction is almost equal between the two groups. This is justified that chronic illnesses do not preclude children from leading happy and satisfying lives., Competing Interests: Conflict of Interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Infertility is a common issue that threatens couples worldwide. Infertility can result from the male or female partner alone, or both partners. It can be due to multiple factors related to the patient's overall health or lifestyle. Causes related to patient health can be systemic or related to gonadal dysfunction. One of the systematic causes can be hematological. The two most common hemoglobinopathies that are thought to cause infertility, especially male infertility, are sickle cell disease (SCD) and thalassemia major (TM). These two hemoglobinopathies cause male infertility through pathophysiological alterations. Specifically, they alter the oxygen carrying ability of red blood cells (RBCs), causing tissue hypoxia that affects the normal physiological process of spermatogenesis, eventually inducing infertility. Semen analyses and other systemic blood testing can be used to investigate male infertility. Both hemoglobinopathies can be helped by blood transfusions, which can then alleviate male infertility. This paper aims to explore the relationship between hemoglobinopathies (SCD and TM) and their role in contributing to male infertility, in addition to the role of blood transfusions in addressing male infertility by correcting the root cause., (© 2024. The Author(s).)

There is a group of beta (β)-thalassemia trait 'carriers' (with heterozygous mutations) who should be asymptomatic with minor abnormalities in their hematological parameters, but experience more severe disease manifestations than predicted based solely on their β-globin genotype. This review focuses on literature describing trans-acting genetic modifiers outside of the α- and β-globin gene clusters that could cause this phenomenon. These genetic modifiers are categorized into: mutations affecting the quantity of alpha-globin products, non-globin mutations affecting erythropoiesis, membranopathies, enzymopathies and erythrocyte-independent modifiers of complications relating to β-thalassemia. Although some genetic determinants seem to correlate more directly with β-thalassemia trait severity, such as mutations in SUPT5H, PIEZO1 and hereditary elliptocytosis, the difficulties of linking the contribution of other modulating factors are elucidated in this review. Targeted next generation sequencing of hemolytic anemias can be helpful but also raises another quandary in interpreting variants of uncertain significance. The accrual of knowledge, along with the increased availability of genetic testing for genetic modifiers has considerable potential for clinical applications such as genetic counselling, decision-making for clinical interventions and prognostication, and perhaps generating new therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: With increasing life expectancy and prevalence of thalassaemia, it has led to a greater need for safe blood, yet the current supply from voluntary donors is insufficient to meet this demand. Thalassaemia recipients face a significant risk of alloimmunization because of repeated exposure to foreign red cell antigens. Study aims to determine high prevalent Rh antigen negative donors in western India donor population along with what percentage of these donors are willing to become dedicated voluntary donors for thalassaemia patients. Study also aims to examine factors influencing their willingness and challenges faced in mobilizing dedicated donors., Method: 700 whole blood donors from western India, following screening for inclusion & exclusion criteria as per Drugs and Cosmetic Act (DCA) 2020 amendment guidelines & were sero-negative for transfusion transmitted infections were enrolled for the study. Red cell phenotyping was performed using Conventional Tube Technique (CTT) for "D", "C", "E", "c", "e" and "K" antigen using known antisera. Donors that were "C" AND/OR "e" antigen negative were contacted telephonically and were counseled and motivated for becoming voluntary blood donors. Statistical analysis assessed correlation between donation frequency, donor's occupation and education., Result: Among 700 donors, 96.6% (n = 676) were males and 3.4% (n = 24) were females. The most predominant blood group was B > O > A > AB. Rh(D) antigen was present in 91.44% (n = 640) and absent in 8.6% (n = 60). Prevalence of other Rh antigens is as follows: "e" (99%) > "C" (85.4%) > "c" (59.1%) > "E" (18.0%). Only 1.15% had "K" antigen positive. The commonest Rh phenotype R 1 R 1 (DCe/DCe) was expressed by 40.57% (n = 283), and the least common r″r (cE/ce), r″r″ (cE/cE) and r'r' (Ce/Ce) was found in 0.14% (n = 1), respectively. 'C' negative, 'e' negative, 'C' and 'e' antigen negative donors constituted 14.8% (n = 104) with 93.2% (n = 97) C-antigen negative, 1.92% (n = 2) e-antigen negative and 4.8% (n = 5) both "C" and "e" antigen negative donors. The commonest phenotypes among C-antigen and e-antigen negative donors were rr (50%) and R z R 2 (1.94%) respectively. Likewise, the most common phenotype amongst both C- and e-antigens negative donors was R 2 R 2 (3.84%). 61.5% of the donors agreed to enroll for voluntary blood donation following telephonic invitation, while 6.8% of them refused permanently. Approximately, 3.9% of the blood donors were willing to donate blood only when needed and 27.8% of them could not be contacted., Conclusion: Creating a database of voluntary donors with known phenotype, especially who lack very common antigens like "C" and "e" and are willing to become dedicated, regular voluntary donors for thalassemic patients can ensure timely administration of safe blood. One of the major challenges for this noble initiative was lack of awareness which can be circumvent effectively with proper counseling efforts., (Copyright © 2024 Socit francophone de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Genetic manipulation of hematopoietic stem cells (HSCs) is being developed as a therapeutic strategy for several inherited disorders. This field is rapidly evolving with several novel tools and techniques being employed to achieve desired genetic changes. While commercial products are now available for sickle cell disease, transfusion-dependent β-thalassemia, metachromatic leukodystrophy and adrenoleukodystrophy, several challenges remain in patient selection, HSC mobilization and collection, genetic manipulation of stem cells, conditioning, hematologic recovery and post-transplant complications, financial issues, equity of access and institutional and global preparedness. In this report, we explore the current state of development of these therapies and provide a comprehensive assessment of the challenges these therapies face as well as potential solutions., Competing Interests: Declaration of competing interest Ashish Gupta is a site principal investigator at University of Minnesota for clinical trials in genome editing for sickle cell disease sponsored by Bluebird Bio (NCT04293185) and Beam Therapeutics (NCT05456880). He is also the site principal investigator at University of Minnesota for clinical trials in genome editing for Hurler syndrome (NCT06149403). He has received consultancy fees from Vertex Pharmaceuticals and is on speaker bureau for Emerging Therapies Solutions. He also has research funding from Jazz Pharmaceuticals for an investigator initiated trial. Akshay Sharma has received consultant fees from Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, Sangamo Therapeutics and Editas Medicine. He is a medical monitor for an RCI BMT clinical trial for which he receives financial compensation. He has also received research funding from CRISPR Therapeutics and honoraria from Vindico Medical Education. Akshay Sharma is also the St. Jude Children's Research Hospital site principal investigator for clinical trials of genome editing for sickle cell disease sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907) and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trials, which includes salary support paid to the investigator's institution. Akshay Sharma has no direct financial interest in these therapies. Jaap Jan Boelens has received consultant fees from Sanofi, Sobi, Merck, Immusoft and Smart Immune, is the MSKCC site PI for Novartis Pharmaceuticals (NCT04443907) and received research funding from Sanofi (for investigator-initiated research). Jaap Jan Boelens is also the chair of an independent data safety monitoring board (for bluebird bio gene therapy trials), for which he receives compensation (CRO; Advanced Clinical). Susan Prockop has received support for the conduct of clinical trials from AlloVir, Atara, and Jasper through Boston Children's Hospital. She has received an honorarium from Pierre Fabre and Regeneron and consults for CellEvolve, Smart Immune and Century. She has IP related to the implementation of third-party viral-specific T cells, with all rights assigned to Memorial Sloan Kettering Cancer Center. Chrystal U. Louis has equity in and is an employee of TScan Therapeutics. The other authors have nothing to disclose., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Thalassemia is a hereditary blood disorder characterized by reduced hemoglobin production, leading to chronic anemia. A major complication of thalassemia is iron overload, primarily due to regular blood transfusions and increased gastrointestinal iron absorption, which can lead to iron overload cardiomyopathy, a significant cause of morbidity and mortality in thalassemia patients. This review aims to provide an in-depth analysis of the pathophysiological mechanisms underlying iron overload cardiomyopathy in thalassemia, examining how excessive iron accumulation disrupts cardiac function through oxidative stress, cellular damage, and altered calcium homeostasis. Clinical manifestations, including fatigue, arrhythmias, and heart failure, are discussed alongside diagnostic strategies such as echocardiography and cardiac MRI for early detection and monitoring. Management approaches focusing on iron chelation therapy, lifestyle modifications, and advanced interventions like gene therapy are explored. The review also highlights the importance of early diagnosis, regular monitoring, and patient adherence to therapy to prevent the progression of cardiomyopathy. Recent advances in treatment and future research directions, including personalized medicine, and gene editing technologies, are presented. Addressing the challenges in managing iron overload in thalassemia patients is crucial for improving outcomes and enhancing quality of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This systematic review aimed to verify if individuals with thalassemia present changes in radiomorphometric indices and fractal analysis that can be accessed using panoramic radiographs., Material and Methods: Observational studies that evaluated cortical and trabecular bone patterns in dental routine radiographs were selected from six bibliographic databases. Risk of bias was analyzed using the Joanna Briggs Institute Critical Appraisal Checklists. Quality of evidence was verified using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Results: Two hundred three studies were initially retrieved from databases. Three cross-sectional studies, encompassing a total of 129 thalassemic patients, were deemed eligible after applying the inclusion criteria. Bone mineral density (BMD) evaluations were performed using panoramic radiographs and considered the following radiomorphometric indexes: mandibular cortical index (MCI), mandibular cortical width (MCW), panoramic mandibular index (PMI). Fractal dimension analysis (FDA) and simple visual estimation (SVE) were also employed. Overall, FDA and MCW from thalassemia individuals were lower than controls., Conclusion: FDA and MCW are frequently altered in patients with thalassemia and may be employed as screening tools for reduced BMD. However, the certainty of evidence for this outcome was very low, mainly due to methodological flaws., (© 2024 Special Care Dentistry Association and Wiley Periodicals LLC.)

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients., (© 2024. The Author(s).)

Key Clinical Message: Concurrent recurrence of acute disseminated encephalomyelitis (ADEM) and poststreptococcal glomerulonephritis (PSGN) in a thalassemia intermedia patient is rare and underscores the complexity of autoimmune disorders. This case emphasizes the importance of considering ADEM in the differential diagnosis of children presenting with PSGN accompanied by neurological symptoms., Abstract: Post-streptococcal glomerulonephritis (PSGN) is a common group A streptococcal (GAS) infection sequela. The pathophysiology of PSGN involves immune complex deposition, with type 3 hypersensitivity reaction triggered by GAS. Certain neurological conditions may also arise following a GAS infection, possibly due to molecular mimicry in the brain, a pathophysiology similar to rheumatic fever, another common sequel of GAS infection. We present the case of a child with β-thalassemia intermedia who exhibited the classic triad (edema, hypertension, hematuria) of PSGN along with neurological manifestations, including a low glasgow coma scale (GCS) score and seizures. Magnetic resonance imaging (MRI) of the brain indicated changes consistent with acute disseminated encephalomyelitis (ADEM). Initially treated with methylprednisolone, the patient eventually received intravenous immunoglobulin (IVIG) due to lack of response. The patient had a good outcome, with complete resolution of all symptoms and no residual neurological deficits. This case underscores the importance of considering ADEM in the differential diagnosis for patients presenting with neurological signs and symptoms following a recent throat infection with GAS. Furthermore, given the increased risk of infection in thalassemia, patients with thalassemia who have a throat infection and neurological symptoms should be evaluated for the possible presence of ADEM., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Thalassemia is a group of genetic disorders that result in a lack of hemoglobin (Hb) production. Children with thalassemia rely on regular blood transfusions for survival, which places a significant burden on their families and negatively impacts their quality of life (QOL)., Objective: This study aimed to assess QOL from the perspective of parents of thalassemic children in Medina City, Saudi Arabia., Method: A cross-sectional study was conducted among 52 parents in Medina through September and October 2023 using a socio-demographic and clinical characteristic questionnaire and an assessment of parents' QOL., Results: The study was conducted among 52 parents in Medina, with a mean (standard deviation (SD)) age of 44.4 (9.5). Most participants (63.5%) were males, 90.4% were married, and 61.5% had one child with thalassemia. The majority (84.6%) had a blood transfusion every three weeks, and 80.8% had Hb before transfusion less than 9 gm/dL. The mean (SD) QOL and health score was 246.4 (51.2) out of 400. The parent's low income (p<0.001) and being non-Saudi parents (p=0.017) were significant factors for low QOL and health., Conclusion: Parents with thalassemic children revealed moderate QOL and health in Medina City, Saudi Arabia. Low income and expatriation negatively affected the parents' QOL and health. These results emphasize the need for financial support through assistance programs to alleviate the financial burden on these families. Additionally, specialized thalassemia treatment centers should be established to ensure easy access to comprehensive healthcare services., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The College of Medicine Institutional Review Board at Taibah University issued approval STU-22-025. All methods were performed in accordance with the relevant guidelines and regulations (e.g. Declaration of Helsinki). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tobaiqi et al.)

Background: Thalassemia is a hereditary blood disorder that poses significant challenges for affected children and their families. Caregivers, particularly mothers, often experience difficulties in managing their child's condition. Understanding their current experience is crucial for improving care and support., Objective: This study aimed to explore the experiences of mothers caring for children with thalassemia in Banten, Indonesia., Methods: A qualitative descriptive approach was employed, involving semi-structured in-depth interviews with eleven mothers of children diagnosed with thalassemia. Data were collected from April to May 2023. The interviews were audio recorded, and the data were analyzed verbatim using Colaizzi's method to identify key themes related to the experiences., Results: Three themes were developed: 1) Perception of thalassemia as a genetic condition, 2) Emotional, logistical, and practical caregiving challenges, and 3) Support received by mothers in caring for children with thalassemia., Conclusion: The findings highlight the multifaceted challenges faced by mothers of children with thalassemia and emphasize the need for improved communication, emotional support, and care coordination from nurses and healthcare providers. Future research should focus on expanding support systems and exploring effective interventions to enhance the quality of life for families navigating the complexities of chronic illness., Competing Interests: The authors declared no conflict of interest., (© The Author(s) 2024.)

Recent research highlights the significant impact of the gut microbiota on health and disease. Thalassemia, a hereditary blood disorder, requires regular blood transfusions, leading to an accumulation of iron in the body. Such changes could potentially alter the intestinal microbiota, thereby increasing the susceptibility of thalassemic patients to infection. In this study, we analyzed the fecal microbiota of 70 non-transfusion-dependent (NTDT) β-thalassemia/HbE patients and 30 healthy controls. Our findings indicate that iron chelation intervention had no detectable effect on the microbiome profile of thalassemic patients. However, the cross-sectional analysis revealed that the bacterial diversity and community structure in patients were significantly less diverse and distinct compared to those of healthy subjects. Using reference frames, we were also able to demonstrate that bacterial taxa that are known to produce short chain fatty acids, from the genera Alistipes, Coprococcus, and Oscillospira, and those from the family Ruminococcaceae, were less prevalent in the patients. In contrast, bacterial taxa associated with an unhealthy gut, including the genus Clostridium and those from the families Fusobacteriaceae, Enterobacteriaceae, and Peptostrptococcaceae, were more prevalent in patients and found to be correlated with higher levels of ferritin. Collectively, these changes in the microbiota could be regarded as markers of raised ferritin levels, and therefore, awareness should be exercised as they could interfere, albeit indirectly, with the treatment of the co-morbidities of thalassemia., (© 2024. The Author(s).)

Objective: Knowledge, Attitude, and Acceptance regarding Bone marrow transplantation in caregivers of beta-thalassemia major patients., Methods: A cross-sectional study was conducted among the caregivers of pediatric patients with betathalassemia major in blood transfusion centres in Bangalore, India. Their knowledge, attitude, and acceptance regarding bone marrow transplantation were assessed using a validated questionnaire. The study aimed to identify factors that influence caregivers' decision about bone marrow transplantation., Results: The knowledge, attitude, and acceptance of the caregivers towards bone marrow transplantation are shown to depend on gender, education and socio-economic status. The results of this study reveal that male caregivers generally exhibited higher levels of knowledge and had a better attitude towards it as compared to their female counterparts. Higher education and socio-economic status were associated with better knowledge, more favourable attitudes and a higher acceptance towards the procedure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study was carried out to investigate the effects of mobile application based genetic counseling on the psychosocial well-being of thalassemia patients and caregivers., Methods: A randomized controlled trial was conducted with 80 patients, divided equally between the intervention and control groups. Additionally, 192 caregivers were included, with an equal distribution of 96 in the two groups. The intervention group received mobile application based genetic counseling, while the control received standard routine care. Assessments of quality of life, satisfaction, depression, and anxiety were conducted at baseline (T0), one-month post-intervention (T1), and three months post-intervention (T2). Furthermore, data analysis was performed using the Generalized Estimation Equation Model (GEE) approach in SPSS version 25.0., Results: Mobile application based genetic counseling had significant effects on various aspects of the well-being of thalassemia patients and caregivers. These effects include improvements in quality of life, patient satisfaction, reduction in depression, and alleviation of anxiety (p < 0.05)., Conclusion: Mobile application based genetic counseling showed a significant effect in improving psychosocial well-being among patients and caregivers., Practice Implications: The results obtained practical implications for the integration of genetic counseling interventions, particularly through the application of information technology such as Cyber Gen application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neutrophil dysfunction is a form of immune suppression in patients with β-thalassemia (Beta-thal), although data on this are limited. In this study, blood from patients and healthy volunteers was analyzed. Flow cytometry analysis demonstrated an increase in immature neutrophils (CD16- CD62L+) and aged (senescent) neutrophils (CD16+ CD62L-) in Beta-thal patients compared to healthy volunteers. The Beta-thal neutrophils demonstrated less prominent chemotaxis and phagocytosis than healthy neutrophils at the baseline. With phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) stimulations, some of the indicators, including the flow cytometry markers (CD11b, CD62L, CD66b, CD63, apoptosis, and reactive oxygen species) and neutrophil extracellular traps (NETs; detected by anti-citrullinated histone 3 immunofluorescence), were lower than the control. Additionally, low-density neutrophils (LDNs), which are found in the peripheral blood mononuclear cell (PBMC) fraction, were observed in Beta-thal patients but not in the control group. The expression of CD11b, CD66b, CD63, arginase I, and ROS in LDNs was higher than the regular normal-density neutrophils (NDNs). The proliferation rate of CD3+ T cells isolated from the PBMC fraction of healthy volunteers was higher than that of the cells from patients with Beta-thal. The incubation of red blood cell (RBC) lysate plus ferric ions with healthy NDNs transformed the NDNs into the aged neutrophils (decreased CD62L) and LDNs. In conclusion, iron overload induces neutrophil diversity along with some dysfunctions.

Objective: In thalassemia major, repeated blood transfusions result in iron overload causing organ damage. The objective of this study was assessment of liver enzymes in patients with Thalassemia major and to observe their association with ferritin., Method: A cross-sectional study was performed, at Islamabad Medical and Dental College and its affiliated Akbar Niazi Teaching Hospital from November 2021 till August 2022. Serum ferritin, AST, ALT, and total bilirubin levels were determined, in 135 patients of beta thalassemia major receiving transfusions. Data analysis was performed using SPSS Version 20. For categorical variables, calculation of frequencies and percentages was performed. Mean (± standard deviation) was determined for quantitative variables. ANOVA with post hoc Tukey's test was used for determining association between liver enzymes and serum ferritin. A p-value of <0.05 was considered significant. The correlation between ferritin and LFTs was determined by Pearson's correlation coefficient., Results: Patients had an age range of 7-30 years, and males constituted 51% of sample. Mean level of ferritin was 6062.61 + 3641.79 ng/ml, with an insignificant difference between the genders ( p =0.366). The levels of AST, ALT and bilirubin were perceived to show a significant increase in patients with ferritin levels >5000ng/ml, when compared with patients having ferritin levels < 2,500 ng/ml. A significant positive correlation of increasing serum ferritin levels was observed with ALT (r= 0.682), to a lesser extent with AST (r = 0.532), and only a weak correlation with serum bilirubin (r = 0.350)., Conclusion: Liver damage was caused by increased iron deposition. LFTs should be performed regularly to detect and reduce liver damage by increasing chelation therapy, thereby reducing morbidity and mortality due to thalassemia., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Third-generation sequencing (TGS) based on long-read technology has been gradually used in identifying thalassemia and hemoglobin (Hb) variants. The aim of the present study was to explore genotype varieties of thalassemia and Hb variants in Quanzhou region of Southeast China by TGS., Methods: Included in this study were 6,174 subjects with thalassemia traits from Quanzhou region of Southeast China. All of them underwent common thalassemia gene testing using the DNA reverse dot-blot hybridization technology. Subjects who were suspected as rare thalassemia carriers were further subjected to TGS to identify rare or novel α- and β-globin gene variants, and the results were verified by Sanger sequencing and/or gap PCR., Results: Of the 6,174 included subjects, 2,390 (38.71%) were identified as α- and β-globin gene mutation carriers, including 40 carrying rare or novel α- and β-thalassemia mutations. The α CD30(-GAG) α and Hb Lepore-Boston-Washington were first reported in Fujian province Southeast China. Moreover, the β CD15(TGG> TAG) , β IVS-II-761 , β 0 -Filipino(~ 45 kb deletion), and Hb Lepore-Quanzhou were first identified in the Chinese population. In addition, 35 cases of Hb variants were detected, the rare Hb variants of Hb Jilin and Hb Beijing were first reported in Fujian province of China. Among them, one case with compound ααα anti3.7 and Hb G-Honolulu variants was identified in this study., Conclusion: Our findings may provide valuable data for enriching the spectrum of thalassemia and highlight the clinical application value of TGS-based α- and β-globin genetic testing., (© 2024. The Author(s).)

Background: The current investigation aims to analyze the occurrence of thalassemia in patients who participated in hemoglobin A1c (HbA1c) testing in clinical laboratory showing high hemoglobin F (HbF) level (≥ 1.5%) or abnormal Hb peak and predict the main influence factors by using different statistical models., Methods: The current investigation is a single-center retrospective cohort study. HbA1c concentration was detected by using TOSOH HLC-723G8 glycated hemoglobin analyzer. SNaPshot SNP (Single Nucleotide Polymorphism) typing and AccuCopy technology were employed to detect mutations in thalassemia-related pathogenic genes., Results: A total of 126 patients endured high HbF levels or abnormal Hb peak during HbA1c detection, and 66.7% of subjects (n = 84) showed thalassemia mutations. Three heterozygosity mutations, including c.52A>T (p.K18*), c.-78A>G, and c.126&#95;129delCTTT(p.F42Lfs*19) present in HBB gene, were also identified. -- SEA /αα mutation demonstrated the youngest ages (p < 0.001). 17 M (p < 0.001) and 41/42 M (p < 0.01) mutations with β-thalassemia showed higher HbF levels compared with patients without thalassemia mutations. Except for -α 3.7 , mutations in thalassemia showed lower levels of mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) compared with patients without thalassemia mutations. Patients with thalassemia mutations showed younger age (p < 0.001), lower Hb (p < 0.001), MCV and MCH levels (p < 0.001), higher red blood cell (RBC) count (p < 0.001), and platelet distribution width (PDW) level (p = 0.007) than patients without thalassemia mutations. Three statistical models indicate MCV is the most valuable independent factor for predicting thalassemia and ROC (receiver operating characteristic) curves analysis of AUC (Area Under the Curve) of 0.855 (95% CI [0.787-0.923], p < 0.001) with MCV., Conclusion: High HbF level (≥ 1.5%) or abnormal Hb peak present in HbA1c testing indicated high incident rate of thalassemia. MCV is the most valuable independent predicting factor for subjects having thalassemia., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Objective: Thalassemia is a Mendelian-inherited blood disorder with severe consequences, including disability and mortality, making it a significant public health concern. Therefore, there is an urgent need for precise diagnostic technologies. We introduce two innovative diagnostic techniques for thalassemia, SNPscan and CNVplex, designed to enhance molecular diagnostics of thalassemia., Methods: The SNPscan and CNVplex assays utilize variations in PCR product length and fluorescence to identify multiple mutations. In the SNPscan method, we designed three probes per locus: two 5' and one 3', and incorporated allele identification link sequences into one of the 5' probes to distinguish the alleles. The detection system was designed for 67 previously reported loci in the Chinese population for a specific genetic condition. CNVplex identifies deletion types by analyzing the specific positions of probes within the globin gene. This innovative approach enables the detection of six distinct deletional mutations, enhancing the precision of thalassemia diagnostics. We evaluated and refined the methodologies in a training cohort of 100 individuals with confirmed HBA and HBB genotypes. The validation cohort, consisting of 1647 thalassemia patients and 100 healthy controls, underwent a double-blind study. Traditional diagnostic techniques served as the control methods., Results: In the training set of 100 samples, 10 mutations (Hb QS, Hb CS, Hb Westmead, CD17, CD26, CD41-42, IVS-II-654, -- SEA , -α 3.7 and -α 4.2 ) were identified, consistent with those identified by traditional methods. The validation study showed that SNPscan/CNVplex offered superior molecular diagnostic capabilities for thalassemia, with 100% accuracy compared to 99.43% for traditional methods. Notably, the assay identified three previously undetected mutations in 10 cases, including two deletion mutations (Chinese G γ( A γδβ) 0 del and SEA-HPFH), and one non-deletion mutation (Hb Q-Thailand)., Conclusions: The SNPscan/CNVplex assay is a cost-effective and user-friendly tool for diagnosing thalassemia, demonstrating high accuracy and reliability, and showing great potential as a primary diagnostic method in clinical practice., (© 2024 John Wiley & Sons Ltd.)

Patients with sickle cell disease (SCD) in Germany exhibit a substantial genetic diversity in the β-globin genotype. Data collected by the national German SCD registry reflect this diversity and allowed us to analyze the phenotypes associated with different SCD genotypes. Our study focused on 90 patients with HbS/β-thalassaemia (HbS/β-thal) and compared these to patients with HbSS and HbSC. Patients with HbS/β-thal were classified into three groups: HbS/β 0 -thal (no HbA), HbS/β + -thal (HbA < 14%), and HbS/β ++ -thal (HbA≥14%). In comparison to HbSS, patients with HbS/β ++ -thal had higher Hb-levels, lower hemolytic activity and rarely required red blood cell transfusions. HbS/β 0 -thal and HbS/β + -thal closely resembled each other and are jointly referred to as HbS/β 0/+ -thal. Compared to HbSS, patients with HbS/β 0/+ -thal experienced a similar frequency of vasoocclusive crises and degree of hemolysis. However, the frequency of red blood cell transfusions (0.6 vs. 0.39/year, p = .0049) and splenic sequestration crises (42.4 vs. 15.5% of patients, p = 3.799e-05) was higher in HbS/β 0/+ -thal than in HbSS, but close to zero in HbS/β ++ -thal. In conclusion, the level of HbA expression determines the phenotype of HbS/β + -thal. HbS/β-thal expressing no or little HbA is hematologically similar to HbSS, but causes a previously unknown high risk of splenic sequestration., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies., Methods: A total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine., Results: HBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P < 0.05). The threshold for HBsAb positivity may be reached when the immunization duration reaches approximately 30 months. A subgroup analysis revealed that the HBsAb positivity rate was lower in children with β-thalassemia minor compared to those with α-thalassemia minor (P = 0.001, 95% CI: 0.097 ∼ 0.536). Adverse reactions after hepatitis B vaccination were dominated by general reactions, with a statistically significant difference in injection-site redness and swelling between the thalassemia and control groups (P < 0.05)., Conclusions: The immunization response to the hepatitis B vaccine in children with thalassemia minor was comparable to healthy children, with no abnormal adverse effects seen., (© 2024. The Author(s).)

Background and Objectives : Adrenal insufficiency (AI) can be a significant concern in patients with transfusion-dependent homozygous beta thalassemia (bThal) due to the chronic disease burden and frequent blood transfusions that these patients require. The prevalence of AI in this population remains unclear, with studies often lacking control groups for comparison. This meta-analysis aimed to estimate the proportion of patients with transfusion-dependent bThal who exhibit evidence of AI. Materials and Methods : A systematic review following PRISMA guidelines identified 19 studies for analysis. Results : Despite the variability in the diagnostic methods used to ascertain AI, the meta-analysis revealed that approximately one-third of patients had evidence of AI, with the prevalence rising to 50% in studies focused on adults with bThal. Conclusions : These findings suggest an increased risk of AI in patients with bThal compared to the general population. Clinicians should consider tailored management strategies, including glucocorticoid coverage during surgical procedures, to mitigate the risk of adrenal crises in this vulnerable patient group. Further research is needed to optimize adrenal surveillance and management in patients with bThal.

Background: CMRtools is a software package that can be used to measure T2* values to diagnose liver iron overload, however, its accuracy in terms is affected by multiple factors, including goodness-of-fit (R 2 value), the number of echo time (TE) images, and the liver iron concentration (LIC). To investigate the effects of the R 2 value, the number of TE images, and the LIC on the accuracy of CMRtools software for measuring T2* values to diagnose liver iron overload (LIO)., Materials and Methods: CMRtools software was used to measure liver T2* values among 108 thalassemia patients via the truncation method, and the R 2 values, the number of TE images, and T2* values were recorded. These values were subsequently converted into liver iron concentration (LIC T ) values. The LIC F (derived from MRI-R2/FerriScan) was used as a reference, and the diagnostic accordance rate (DAR) was compared between R 2 value subgroups, between TE image number subgroups, and between LIC subgroups., Results: The greater the R 2 value was, the greater the standardized DAR (SDAR) was ( p  < 0.05). The SDAR are not identical between each TE image number subgroup ( p  > 0.05). However, the relationship between TE image number subgroups and SDAR was analysed using Spearman's correlation, and it was found to be positively correlated ( r s  = 0.729, p  = 0.017). The SDAR are not identical between each LIC subgroup ( p  > 0.05), furthermore, the relationship between LIC subgroup and SDAR was found irrelevant ( p  = 0.747)., Conclusion: The accuracy of CMRtools software for diagnosing LIO in patients with thalassemia can be improved by artificially controlling the number of TE images to be fitted and selecting higher R 2 values., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Peng, Xu, Tang, Zhang, Huang, Liang, Ning and Peng.)

Over the last few years, several mechanisms that are involved in congenital diseases characterized by ineffective erythropoiesis have been described. Therefore, multiple new target drugs are being developed in preclinical models against the main regulators of normal erythropoiesis. Above all, the key mechanism that regulates systemic iron homeostasis, represented by the hepcidin-ferroportin axis, is considered to be the target for new therapies. The main hypothesis is that iron restriction, through blocking ferroportin (the unique iron transporter in mammals) in such diseases, ameliorates erythropoiesis. The action of vamifeport is different from the currently approved drugs in this setting since it acts straight on the ferroportin-hepcidin axis. The data presented in the sickle cell disease (SCD) Townes mouse model showed a preclinical proof-of-concept for the efficacy of oral ferroportin inhibitor. Vamifeport reduced hemoglobin concentration in red blood cells (RBCs) and diminished intravascular hemolysis and inflammation, improving hemodynamics and preventing vascular occlusive crises. On this basis, clinical trials were commenced in patients with SCD, non-transfusion-dependent (NTD) thalassemia and transfusion-dependent (TD) thalassemia. Preliminary data in NTD thalassemic patients also confirm the safety and efficacy in decreasing iron level. In conclusion, vamifeport represents a new option in the panorama of drugs targeting the hepcidin-ferroportin axis, but its efficacy is still under investigation as a single agent.

Background: Hemoglobinopathies, such as sickle cell disease and thalassemia, are genetic disorders that affect hemoglobin structure or production, leading to various health complications, including an increased risk of infections. Vaccinations play a crucial role in managing these conditions by providing essential protection against preventable diseases. Ensuring timely and appropriate immunizations is vital for reducing infection-related morbidity and improving the overall health and quality of life for affected individuals., Objectives: Our objective was to assess vaccination coverage, as well as knowledge, attitudes, and practices toward vaccination in Greek patients with hemoglobinopathies., Design and Methods: A nationwide survey of hemoglobinopathy patients in Greece using a 37-item questionnaire was conducted anonymously via Google Forms. It covered demographics, previous vaccinations, vaccine-preventable infections, beliefs about vaccines, and antibiotic prophylaxis post-splenectomy. The survey was distributed through Thalassemia and Sickle Cell Units and organizations., Results: Participants were predominantly university-educated married women aged 30-50 years with transfusion-depended thalassemia ( n  = 149, 60.5%) or sickle cell anemia ( n  = 52, 21.1%). Reported childhood vaccination rates aligned with Greece's national immunization program. However, adult coverage was suboptimal across all age groups for measles (10%), varicella (27%), zoster (2% for over 50 years old individuals), hepatitis A (13.9% of those with chronic liver disease) and hepatitis B (41%), pneumococcal (81.3%), meningococcal (37%), tetanus (20.3%), and influenza (67.1%) vaccines compared to guidelines. Participants relied predominantly on healthcare providers for vaccine information but perceived limited engagement. Those over age 50 demonstrated lower adult vaccination rates and higher misconceptions compared to younger cohorts., Conclusion: Addressing educational and access gaps could help protect this vulnerable population. Our findings highlight the need for coordinated efforts to optimize adult immunization for those with hemoglobinopathies., (© The Author(s), 2024.)

Background: VEXAS syndrome encompasses a wide range of rheumatological and hematological manifestations, which often features myelodysplastic syndrome accompanied by either macrocytic anemia or macrocytosis., Case Report: A 61-year-old Sicilian male was referred for a microcytic anemia associated with skin lesions, recurrent fever, involuntary weight loss, recurrent superficial venous thrombosis, migratory polyarthritis and a lung nodule. A hemoglobin electrophoresis uncovered a minor beta-thalassemia contributing to the anemia in addition to the chronic inflammation and vitamin B9/B12 deficiencies. A bone marrow aspiration demonstrated the presence of vacuoles in erythroid and myeloid precursors, as well as dysplasia in all three lineages. This led us to consider VEXAS syndrome which was confirmed by the presence of UBA1 mutation type p.M41T. Low-dose steroids and sarilumab (200 mg every 3 weeks) therapy led to a transient partial remission., Conclusion: The pivotal insight from this observation centers around the microcytic characteristic of the anemia, with the confounding factor being minor thalassemia, whereas the type of anemia typically associated with VEXAS is macrocytic. This finding may be of particular relevance to patients from regions with endemic thalassemia. Consequently, the presence of microcytic anemia should not hinder clinicians from considering VEXAS syndrome in the appropriate clinical context.

We retrospectively collected all ultrasound imaging data of our thalassemia patients over a period of 10 years with the aim of assessing the prevalence and the risk factors of renal stones and cysts. Moreover, we assessed the incidence of renal-cell carcinoma (RCC) among thalassemia patients (133 with thalassemia major (TM) and 157 with thalassemia intermedia (TI)) and its association with demographic and clinical findings. Renal stones were detected in 15.2% of patients. In the multivariable Cox regression analysis, the independent predictors were blood consumption, splenectomy, and proteinuria. Renal cysts were detected in 18.4% of patients. In the multivariable analysis, age emerged as the only independent predictor. After the first detection, 35% of the patients showed changes in the number, size, or grading of renal cysts. During the study period, the crude incidence rate of RCC was 75.9 cases per 100,000 person-years. The most frequent histological subtype (80%) included clear-cell RCC. In total, 80% of patients with RCC had TM and all were positive for hepatitis C virus antibodies. Thalassemia patients are significantly affected by asymptomatic renal diseases such as stones, cysts, and cancer, suggesting the need for regular screening by imaging.

Thalassemia is a hemoglobin disease characterized by reduced or complete absence of the production of the α/β globin gene. Currently, the detection of β-thalassemia carriers is based on differences in blood cell parameters. However, β-thalassemia carriers cannot be distinguished from α- and β-thalassemia co-inherited carriers based solely on hematological findings, and the differential diagnosis must rely on molecular diagnosis. We report a 32-year-old male from Yunnan Province, who had abnormal hemoglobin E without obvious anemia. A rare α CS (CD142, TAA→CAA) combined with a βE (CD26, GAG→AAG) double heterozygous mutation was identified in the proband by PCR-reverse dot blot (PCR-RDB) and DNA sequencing. Additionally, a family lineage analysis was performed. This study complements the spectrum of rare thalassemia gene variants and is critical for clinical genetic counseling., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: Thalassemia, an inherited quantitative globin disorder, is the most prevalent monogenic disease globally. While severe alpha thalassemia results in intrauterine death, β-thalassemia manifests during childhood due to the "second conversion of hemoglobin", garnering increased attention in recent decades., Methods: In this study, a bibliometric analysis was conducted of thalassemia articles published in the Web of Science Core Collection database between 2013 and 2023 to establish a comprehensive overview and to identify emerging trends. A total of 5655 studies published between 2013 and 2023 were systematically retrieved, and annual publications demonstrated a steady increase, maintaining a high level over the past decade., Results: The United States contributed the highest number of publications, followed by China. Notably, the journal Blood emerged as the leading authority in β-thalassemia research. Analysis of research hotspots revealed that the pathogenesis of β-thalassemia is primarily linked to iron overload, anemia, gene mutations, and ineffective erythropoiesis. Furthermore, recent studies focusing on gene editing therapies present promising avenues for future investigation., Conclusion: These findings grasp the research status of β-thalassemia and shed new light on future research frontiers., Competing Interests: The authors report no conflicts of interest in this work. This paper has been uploaded to Research Square as a preprint: https://www.researchsquare.com/article/rs-3350136/v1.This paper has also been uploaded to OUCI as a preprint: https://ouci.dntb.gov.ua/en/works/ldwdnRn4/., (© 2024 Lv et al.)

Although the survival of patients with transfusion-dependent thalassemia (TD-TM) is reportedly inferior after haploidentical hematopoietic stem cell transplantation (HSCT), the heterogeneity of transplantation approaches in studies suggests the need to assess the effect of conditioning regimen on matched and haploidentical transplantation outcomes. A novel post-transplantation cyclophosphamide (PTCy)-based approach for patients with TD-TM undergoing haploidentical HSCT was reported in our prior study. Here we aimed to retrospectively evaluate the real-world efficacy and safety of graft-versus-host disease (GVHD) prophylaxis in patients with TD-TM after HSCT from matched donors and haploidentical donors (HIDs). In this retrospective multicenter study, among 238 patients with TD-TM who underwent HSCT, 160 underwent peripheral blood HSCT, using uniform GVHD prophylaxis with PTCy, methotrexate, and cyclosporine, at member centers of the Bone Marrow Failure Working Group of Hunan Province between 2019 and 2023. The median age of the cohort at transplantation was 6 years (95% confidence interval [CI], 6 to 7 years). The 160 donors included 99 (61.9%) haploidentical family members, 13 matched sibling donors, and 48 matched or mismatched unrelated donors. The engraftment rate was 98.8% (95% CI, 96.1% to 97.7%). HSCT from HIDs had a lower risk of mixed chimerism (HR, .078; P = .022). Within 100 days after transplantation, 31 patients (19.6%; 95% CI, 14.0% to 26.3%) had grade II-IV acute GVHD (aGVHD), 9 of whom had grade III-IV aGVHD (5.7%; 95% CI, 2.9% to 10.1%). HIDs were significantly associated with a higher risk of grade II-IV aGVHD (HR, 3.973; P = .009). Nineteen patients (11.9%; 95% CI, 7.6% to 17.6%) developed late aGVHD after a median of 516 days (95% CI, 407 to 709 days). Twenty-six patients (16.5%; 95% CI, 11.3% to 22.8%) exhibited any 1 of the diagnostic, distinctive, or atypical features of chronic GVHD (cGVHD) according to the 2014 National Institutes of Health (NIH) criteria after a median of 690 days (95% CI, 496 to 902 days). Among these 26 patients, 7 had NIH-defined cGVHD, 14 had only 1 distinctive sign with no histologic evidence, and 5 had only atypical cGVHD signs. Of the 26 patients, 5 were classified with overlap syndrome. Of 21 patients classified with NIH-defined and potential cGVHD, 3 had moderate cGVHD and 1 had severe cGVHD. Logistic regression analyses identified that grade II-IV aGVHD independently predicted subsequent cGVHD (HR, 3.920; P = .006). The rates of cGVHD were similar in the matched donor and HID groups. Thalassemia-free survival (TFS) and event-free survival (EFS) were 97.5% (95% CI, 94.2% to 99.2%) and 90.6% (95% CI, 85.4% to 94.4%), respectively, after a median of 690 days (95% CI, 496 to 902 days). TFS rates were similar in the matched donor and HID groups (P = .549). The EFS rate was significantly higher in the matched donor group compared to the HID group (P = .033). Our study suggests that when PTCy-based uniform GVHD prophylaxis is administered, HSCT from matched donors and HIDs results in a low incidence of severe GVHD and treatment-related mortality with satisfactory survival., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

A 20-year-old pregnant woman at 12 week gestation with a history of thalassemia was admitted to the hospital with Hb 60g/L. She received two transfusions of 2 units of negative crossmatched washed red blood cells (RBCs) each, but shortly after she experienced a transfusion reaction. Symptoms included chest tightness, dyspnea, chills, and soy sauce colored urine. A post-transfusion specimen was sent to the blood type reference laboratory (BTRL) for investigation, which revealed the presence of anti-Le a and anti-Le b antibodies causing the immediate acute hemolytic transfusion reaction; interestingly, the patient's Le a antibody was found to be IgM, while the Le b antibody was both IgM and IgG. This combination of antibodies is rare and highlights the potential for clinically insignificant Lewis cold antibodies to cause serious reactions. It is important to not overlook these antibodies and to select antigen-negative units rather than relying solely on blood crossmatching. The use of polybrene in crossmatching blood tests may have limitations in the presence of Lewis antibodies, so alternative methods should be considered in difficult cases to ensure safe and effective transfusions. This case emphasizes the need for thorough testing and careful selection of blood products to reduce the risk of transfusion reactions and improve overall transfusion safety., (© 2024 by the Association of Clinical Scientists, Inc.)

Thalassemia encompasses a group of inherited hemoglobin disorders characterized by reduced or absent production of the α- or β-globin chains, leading to anemia and other complications. Current management relies on lifelong blood transfusions and iron chelation, which is burdensome for patients. This review summarizes the emerging therapeutic potential of modulating microRNAs (miRNAs) to treat thalassemia. MiRNAs are small non-coding RNAs that regulate gene expression through sequence-specific binding to messenger RNAs (mRNAs). While they commonly repress gene expression by binding to the 3' untranslated regions (UTRs) of target mRNAs, miRNAs can also interact with 5'UTRs and gene promoters to activate gene expression. Many miRNAs are now recognized as critical regulators of erythropoiesis and are abnormally expressed in β-thalassemia. Therapeutically restoring levels of deficient miRNAs or inhibiting overexpression through miRNA mimics or inhibitors (antagomir), respectively, has shown preclinical efficacy in ameliorating thalassemic phenotypes. The miR-144/451 cluster is especially compelling for targeted upregulation to reactivate fetal hemoglobin synthesis. Advances in delivery systems are addressing previous challenges in stability and targeting of miRNA-based drugs. While still early, gene therapy studies suggest combinatorial approaches with miRNA modulation may provide synergistic benefits. Several key considerations remain including enhancing delivery, minimizing off-target effects, and demonstrating long-term safety and efficacy. While no miRNA therapies have yet progressed to clinical testing for thalassemia specifically, important lessons are being learned through clinical trials for other diseases and conditions, such as cancer, cardiovascular diseases, and viral. If limitations can be overcome through multi-disciplinary collaboration, miRNAs hold great promise to expand and transform treatment options for thalassemia in the future by precisely targeting pathogenic molecular networks. Ongoing innovations, such as advancements in miRNA delivery systems, improved targeting mechanisms, and enhanced understanding of miRNA biology, continue to drive progress in this emerging field towards realizing the clinical potential of miRNA-based medicines for thalassemia patients., Competing Interests: The authors declare no conflict of interest in the development and submission of this manuscript., (Copyright 2024, Rujito et al.)

In the last ten years, a consistent number of clinical studies have evaluated different gene approaches for the treatment of patients with sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT). Initial studies of gene therapy for hemoglobinopathies involved the use of lentiviral vectors to add functional copies of the gene encoding β-globin in defective CD34 cells; more recently, gene editing techniques have been used involving either CRISPR-Cas9, transcription activation-like effector protein nuclease, zinc finger nuclease, and base editing to either induce fetal hemoglobin production at therapeutic levels or to genetically repair the underlying molecular defect causing the disease. Here, we review recent gene editing studies that have started the development of a new era in the treatment of hemoglobinopathies and, in general, monoallelic hereditary diseases., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Introduction: Sickle cell disease is the most common hereditary hemoglobinopathy followed by beta-thalassemia. Until recently, allogeneic stem cell transplantation was the only curative approach. Based on the Crispr-Cas9-technology enabling targeting specific genes of interest, fetal hemoglobin which is normally shut-off after birth can be switched on and sufficient levels can alleviate symptoms in sickle cell disease and avoid transfusions in beta-thalassemia. Two first-in-human clinical studies in sickle cell disease and beta-thalassemia aiming to increase the level of fetal hemoglobin by using Crispr-Cas9 to modify autologous hematopoietic stem cells in patients aged 12-35 years have proved safety and efficacy and have shown promising clinical outcomes., Areas Covered: The paper summarizes the outcome of the results of the two recently published clinical studies and compares them with the other available curative approaches., Expert Opinion: Based on the currently available safety and efficacy data of the two published clinical results on gene therapy with Crispr-Cas9 modified autologous stem cells (exagamglogene autotemcel), it can be anticipated that this approach will add significantly to the therapeutic options for patients with sickle cell disease and beta-thalassemia and can be considered for all patients above 12 years of age independent of a suitable allogeneic stem cell donor.

Objective: To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients., Materials and Methods: This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland-Altman analysis were performed., Results: 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver., Conclusion: MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with pharmaceutical companies, biomedical device manufacturers or other corporations whose products or services may be related to the subject matter of the article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Free iron in human serum or non-transferrin-bound iron (NTBI) can generate free radicals and lead to oxidative damage. Moreover, it is highly toxic to various tissues and a vital biomarker related to the iron-loading status of thalassemia and Alzheimer's patients. In NTBI in healthy individuals, NTBI levels are typically less than 1 µM; current NTBI analysis usually requires advanced instrumentation and many-step sample pretreatment. To address this issue, we employed our invented BODIPY derivative, BODIPY-PH, as a fluorescence probe and trapped it onto the microcentrifuge tube lid using tapioca starch. The fluorescence intensity of BODIPY-PH increased with increasing NTBI concentration (turn-on). The developed portable reaction chamber facilitates rapid analysis (∼5 min) using small sample volumes (10 μL sample in a total volume of 600 μL). Under optimum conditions, using the sample-developed portable fluorescence device and fluorescence spectrometer, we achieved impressive limits of detection (LOD) of 0.003 and 0.0015 μM, respectively. Furthermore, the developed sensors show relatively high selectivity toward Fe 3+ over other metal ions and biomolecules (i.e., Fe 2+ , Cr 3+ , Cu 2+ , and glucose). The sensor performance in serum samples of thalassemia patients exhibited no significant difference compared to the labeled value (obtained from standard methods). Overall, the developed fluorescence sensor is suitable for determining NTBI and offers high sensitivity, high selectivity, and a short incubation time (5 min). Moreover, the method requires a limited number of reagents, is simple to use, and uses low-cost equipment to determine NTBI in human serum samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Increased liver stiffness (LS) can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, LS, and serum ferritin level in transfusion-dependent patients. We recruited all 70 transfusion-dependent patients, whose median age was 15, referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE). Thalassemia beta affected the majority of the patients. The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64-0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24-0.65). We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to management guideline will help in deciding for aggressive adjustment of iron chelating medication and increased awareness of patients having severe hemochromatosis.

Objectives: The aim of this cross-sectional study was to investigate the association of left atrial (LA) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in a cohort of patients with β-thalassemia major (β-TM)., Materials and Methods: We considered 264 β-TM patients (133 females, 36.79 ± 11.95 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. Moreover, we included 35 sex- and age-matched healthy controls (14 females, mean age 37.36 ± 17.52 years). Reservoir, conduit, and booster LA functions were analysed by CMR feature tracking using dedicated software., Results: Compared to the healthy control group, β-TM patients demonstrated lower LA reservoir strain and booster strains, as well as LA reservoir and booster strain rates. However, no differences were found in LA conduit deformation parameters. In β-TM patients, ageing, sex, and left ventricle (LV) volume indexes were independent determinants of LA strain parameters. The number of segments with late gadolinium enhancement (LGE) significantly correlated with all LA strain parameters, with the exception of the LA conduit rate. Patients with cardiac complications exhibited significantly impaired strain parameters compared to patients without cardiac complications., Conclusion: In patients with β-TM, LA strain parameters were impaired compared to control subjects, and they exhibited a significant correlation with the number of LV segments with LGE. Furthermore, patients with cardiac complications had impaired left atrial strain parameters. Clinical relevance statement In patients with β-thalassemia major, left atrial strain parameters were impaired compared to control subjects and emerged as a sensitive marker of cardiac complications, stronger than cardiac iron levels., Key Points: • Compared to healthy subjects, β-thalassemia major patients demonstrated significantly lower left atrial reservoir strain and booster strains, as well as left atrial reservoir and booster strain rates. • In β-thalassemia major, ageing, sex, and left ventricular volume indexes were independent determinants of left atrial strain parameters, while left atrial strain parameters were not correlated with myocardial iron overload. • An independent association between reduced left atrial strain parameters and a history of cardiac complications was found in β-thalassemia major patients., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: Thalassemia represents a significant public health challenge globally. However, the global burden of thalassemia and the disparities associated with it remain poorly understood. Our study aims to uncover the long-term spatial and temporal trends in thalassemia at global, regional, and national levels, analyze the impacts of age, time periods, and birth cohorts, and pinpoint the global disparities in thalassemia burden., Methods: We extracted data on the thalassemia burden from the Global Burden of Disease Study (GBD) 2019. We employed a joinpoint regression model to assess temporal trends in thalassemia burden and an age-period-cohort model to evaluate the effects of age, period, and cohort on thalassemia mortality., Results: From 1990 to 2019, the number of thalassemia incident cases, prevalent cases, mortality cases, and disability-adjusted life years (DALYs) decreased by 20.9%, 3.1%, 38.6%, and 43.1%, respectively. Age-standardized rates of incidence, prevalence, mortality, and DALY declined across regions with high, high-middle, middle, and low-middle sociodemographic index (SDI), yet remained the highest in regions with low SDI and low-middle SDI as well as in Southeast Asia, peaking among children under five years of age. The global prevalence rate was higher in males than in females. The global mortality rate showed a consistent decrease with increasing age., Conclusion: The global burden of thalassemia has significantly declined, yet notable disparities exist in terms of gender, age groups, periods, birth cohorts, SDI regions, and GBD regions. Systemic interventions that include early screening, genetic counseling, premarital health examinations, and prenatal diagnosis should be prioritized in regions with low, and low-middle SDI, particularly in Southeast Asia. Future population-based studies should focus specifically on thalassemia subtypes and transfusion requirements, and national registries should enhance data capture through newborn screening., (© 2024 Wiley Periodicals LLC.)

Hemoglobin (Hb) disorders are among the most prevalent inherited diseases. Despite a limited number of involved genes, these conditions represent a broad clinical and prognostic spectrum. The menu of laboratory tests is extensive. From widely available modalities, for example, complete blood count to rather sophisticated molecular technologies, the investigation of Hb disorders recapitulates an increasing complexity of laboratory workup in other medical fields. This review highlights a current state of biochemical and molecular investigation of Hb disorders and offers a glimpse on technologies that are yet to be fully embraced in clinical practice., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with β-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6-378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted., (© 2024. The Author(s).)

Objective: To summarize and analyze the clinical characteristics of the Hb Phnom Penh ( HBA1 :c.354&#95;355insATC) variant in the Chinese population, and to guide clinical diagnosis and genetic counseling for hemoglobin disorders., Methods: Peripheral blood samples were collected from patients, and hematological parameters, hemoglobin electrophoresis, and glycated hemoglobin chromatography were analyzed. PCR combined with reverse dot blot hybridization (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), Sanger sequencing, and third-generation sequencing (TGS) were performed to determine the gene variant., Results: A total of 20 cases were examined, which included 11 neonates, 5 infants aged from 1 month to 6 months, and 4 adults. Hb Bart's band was measured in 14 infants. Thirteen infants (9 neonates and 4 infants of 1 month old) showed low levels of Hb Bart's bands (<1%), while one newborn exhibited a significantly elevated level of the Hb Bart's band (13.8%). Two adult patients were tested for glycated hemoglobin and had high levels at 7.0% and 7.2%, respectively, despite having normal blood glucose levels and no history of diabetes, indicating the presence of abnormal hemoglobin. Genetic testing confirmed that all 20 cases carried the HBA1 :c.354&#95;355insATC mutation, with one case being a compound mutation of - SEA /αα Phnom Penh ., Conclusion: The HBA1 :c.354&#95;355insATC mutation leads to the production of abnormal hemoglobin (Hb Phnom Penh). Infants may exhibit low levels of Hb Bart's bands on hemoglobin electrophoresis, which have no salient pathological significance. The detection of abnormal HbA1c values suggests that this abnormal haemoglobin may be present.

Objective: To analyze the hematological phenotype and genotype of HbA2 : c.96-2A > G carriers., Methods: The blood routine parameters and hemoglobin electrophoresis of rare cases were analyzed and identified by PCR combined with reverse dot blot (RBD-PCR), GAP-PCR and DNA sequencing., Results: Among the 7 patients, one adult patient had normal hemoglobin levels, with slightly decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Hb Bart's band was found in 6 neonates by hemoglobin electrophoresis, of which the content of Hb Bart's band in 1 neonate was 15.80%, and the content of Hb Bart's band in the other 5 neonates was 0.30%-0.90%. The results of genetic analysis showed that all the 7 patients had HbA2 : c.96-2A > G (IVS-I-116A > G) mutation, in which 1 case was compounded with - SEA deletion., Conclusion: HbA2 : c.96-2A > G mutation carriers exhibit the phenotype of α-thalassemia, and when the HbA2 :c.96-2A > G mutation is combined with - SEA deletion, an intermediate phenotype of anemia is produced.

Objective: To describe a novel α-thalassemiadeletion identified from a newborn by third-generation sequencing (TGS)., Case Report: The proband, a newborn subject to neonatal capillary electrophoresis (CE) screening, exhibited suspected α 0 -thalassemia carrier status (Hb Bart's 3.0%). Notably, both parents had negative results on thalassemia screening during pregnancy. Multiplex ligation-dependent probe amplification (MLPA) presented a deletion between probes 364nt and 472 nt that extended from the HBZ gene to the downstream region of the RGS11 gene. Subsequently, TGS determined the approximated break position of this deletion, indicating a length exceeding 145 kb (chr16:127,815-273,190 del 145376 bp). Sanger sequencing validated the upstream and downstream breakpoints of this deletion. Only maternal data were available for pedigree analysis, with the father's sample lacking. MLPA showed no deletion in the mother, suggesting possible paternal inheritance. The deletion was named Guigang deletion (-- Guigang ) after the proband's city of origin, Guigang., Conclusions: We reported a novel α-thalassemiadeletion and provided insights into the hematological phenotype and molecular analysis. These findings have implications for genetic counseling and prenatal diagnosis.

Background: Thalassemia is a prevalent monogenic blood disorder, clinically classified into alpha- and beta-thalassemia, characterized by the imbalance of the alpha- and beta-globin chains that constitute adult hemoglobin. Copy number variations (CNVs) and single nucleotide variants in globin genes are the primary genetic defects causing thalassemia., Case Report: During a prenatal examination, a pregnant woman was suspected to be a carrier of thalassemia, exhibiting microcytic hypochromic anemia and abnormal hemoglobin constituents. Gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (PCR-RDB) techniques did not detect any common thalassemia mutations. We conducted hematological examination and further genetic analyses on the proband's family with three generations. Multiplex ligation-dependent probe amplification (MLPA) was employed to identify CNVs, targeted next-generation sequencing was used to screen for potential pathogenic variants, which were subsequently validated by Sanger sequencing. The hematological parameters of the proband, her father and her son all indicated they were beta-thalassemia carriers. MLPA results revealed a large deletion in beta-globin cluster. Further investigation confirmed the presence of a novel 8.2 kb deletion (NC&#95;000011.10:g.5224208&#95;5232469del) in the proband, her father, and her son, specifically covering the entire HBB gene while not impacting other globin genes., Conclusion: We found a novel 8.2 kb deletion leading to beta-thalassemia in a Chinese family in which three generations had been affected. This novel deletion may broaden the spectrum of known mutations in thalassemia and provide a reference for clinically suspected cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: The α-globin fusion gene between the HBA2 and HBAP1 genes, is clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combined with α 0 -thalassemia (α 0 -thal). In this study, we evaluate the red blood cell parameters of α-thalassemia fusion gene in southern China., Method: Study samples suspected of α-thalassemia fusion gene were collected and confirmed by PCR-sequencing from one medical lab center in southern China. Their genotypes and phenotypes were analyzed., Results: A total of 266 cases of α-thalassemia fusion gene were confirmed in our lab from 2017 to 2023, most of them were from Hainan province (169 cases) and Huadu district of Guangzhou (21 cases), the nationality of 143 cases from Hainan was identified, with 71.3% (102/143) being from the Li minority. The Hb, MCV, MCH for αα/(αα) fusion in adult males were 143.5±11.83g/L, 81.51±4.39 fl, and 26.26±1.29 pg, respectively; and in females, they were 126.69±12.89 g/L, 80.10±4.05 fl, 25.8±2.04 pg, respectively. All 12 cases (αα) Fusion / -- SEA showed anemia with decreased Hb, MCV and MCH., Conclusion: The carriers of α-globin fusion gene heterozygotes are clinically silent and exhibit an α + phenotype. Individuals with (αα) Fusion / --SEA show apparent anemia. This α-globin fusion gene is relatively common in southern China, specifically among the Li minority of Hainan province. Therefore, it should be taken into account for genetic counseling purposes.