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Objectives: Accurate epidemiological data are crucial for effective disease prevention and treatment. We conducted a large-scale survey to explore the thalassaemia prevalence and spectrum among the two major ethnic groups in Hainan Province. Methods: A total of 399,053 childbearing-age individuals of Li (n = 77,563) and Han(n = 321,490) ethnic groups were recruited from 18 cities and counties in Hainan, and their thalassemia genotypes were systematically screened and statistically analysed. Results: This study revealed a significantly higher thalassaemia carrier rate in the Li (55.39%) than that in the Han (13.13%). Specifically, the carrier rate of α-thalassaemia was 46.39% in the Li and 10.02% in the Han. The predominant α-thalassaemia mutations were – α3.7 and – α42. in Li, whereas the main mutation were – SEA and – α4.2 in Han. For β-thalassaemia, the carrier rates were 1.68% in Li and 2.38% in Han, with CD41-42(-CTTT) the most prevalent mutation in both groups. The carrier rates of β-/α-compound thalassaemia were 7.32% in Li and 0.73% in Han. Additionally, there were regional differences in the distribution of thalassemia among the Li and Han within Hainan Province. Conclusion: Epidemiological characteristics and molecular spectrum of thalassaemia among the Li and Han ethnic groups in Hainan were revealed in this study. These findings can provide a scientific basis to develop and implement prevention strategies for thalassaemia in Hainan. [ABSTRACT FROM AUTHOR]

Haemoglobin (Hb) Malay is variant haemoglobin with a β++ thalassemia phenotype. The prevalence of Hb Malay in the Malaysian population was 5.5%. We describe a 58-year-old male who presented with symptomatic anaemia to the Hospital Universiti Sains Malaysia. Further history revealed that the patient had anaemia since the age of 28, and on regular follow-up at other hospital. Physical examination revealed pallor, jaundice and hepatosplenomegaly. The full blood count and peripheral blood smear showed hypochromic microcytic anaemia with anisopoikilocytosis, and many target cells. High-performance liquid chromatography results showed a β thalassemia trait. However, the diagnosis does not alight with the patient’s condition. Bone marrow aspirate was completed and showed reactive changes and erythroid hyperplasia. A molecular test was then performed for β globin gene mutation detection using Multiplex Amplification Refractory Mutation System (M-ARMS) PCR method. This revealed the result as homozygous codon 19 mutation or Hb Malay. Therefore, in this case report we would like to highlight the laboratory approaches, the challenges faced by the usual haematological investigations and the importance role of molecular testing in the diagnosis of severe anaemia.

Abstract Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2–92.2% for deferiprone and 90–100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.

Background and Objectives: The effective management of chronic diseases, particularly hereditary and rare diseases and thalassaemia, is an important indicator of the quality of healthcare systems. We aimed to assess healthcare services in different countries for thalassaemia patients by using publicly available health indicators and by surveying thalassaemia patients and their caregivers. Materials and Methods: We reviewed official worldwide databases from the WHO, World Bank, and scientific resources, and we used a structured patient-tailored self-completed questionnaire to survey thalassaemia patients and their caregivers in 2023. Results: A total of 2082 participants were surveyed (mean age, 27 years; males, 42%). About 1 in 4 respondents did not complete high-school education, while 24% had a bachelor's degree. About a third of respondents were married and were in either full- or part-time employment. The vast majority (~80%) had initiated transfusion therapy between 1 and 4 years of age. Only 42% reported no delays in receiving blood transfusion, while 47% reported occasional delays and 8% serious delays. About half of patients reported being very satisfied (11%) or satisfied (38%) with the quality of services provided, while 1 in 3 patients reported being unsatisfied or very unsatisfied, and that their access to treatment was difficult or very difficult due to traveling expenses and the high cost of treatment. Conclusions: Important improvements in the care of thalassaemia patients have been documented during the past few decades. Nevertheless, additional focus is required through national healthcare systems to effectively address the many unmet needs revealed by our recent survey, as well as to achieve satisfactory patient outcomes. [ABSTRACT FROM AUTHOR]

Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2–92.2% for deferiprone and 90–100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence. [ABSTRACT FROM AUTHOR]

Transfusion-dependent thalassemia (TDT) is often accompanied by complications related to iron overload and the development of malignant solid tumors or hematological malignancies. The occurrence of Neuroendocrine carcinoma, specifically in the respiratory tract, is very rare, with a prevalence of approximately 25%. Therefore, this study presented a case of a 42-year-old male with a beta-thalassemia major at 28 years, complaining of shortness of breath. This case was reported due to its rarity in providing information about solid tumors in thalassemia patients. The physical examination revealed several symptoms, including tachycardia, tachypnea, anemia, icteric sclera, elevated jugular venous pressure, coarse wet Ronchi in the medial to basal areas of both lungs, hepatomegaly, and splenomegaly (Schuffner 4). The patient regularly received blood transfusions and iron chelation therapy. A thoracic CT scan showed a lung mass and a biopsy of the mass revealed Pulmonary Neuroendocrine Carcinoma with high-grade proliferation and, large cell type. The patient also passed through cisplatin-etoposide chemotherapy for 6 cycles every 21 days. There is almost no data on pulmonary neuroendocrine carcinoma in thalassemia patients, so it is hoped that this case report can provide information about malignant solid tumors that can occur in thalassemia patients.

Thalassaemia is caused by genetic globin defects leading to anaemia, transfusion-dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion-dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality. The therapeutic landscape of thalassaemia may soon include gene therapies as functional cures. An analysis of the adult US thalassaemia population has not been performed since the Thalassemia Clinical Research Network cohort study from 2000 to 2006. The Centers for Disease Control and Prevention supported US thalassaemia treatment centres (TTCs) to compile longitudinal information on individuals with thalassaemia. This dataset provided an opportunity to evaluate iron balance, chelation, comorbidities and demographics of adults with thalassaemia receiving care at TTCs. Two adult cohorts were compared: those over 40 years old (n = 75) and younger adults ages 18-39 (n = 201). The older adult cohort was characterized by higher numbers of iron-related comorbidities and transfusion-related complications. By contrast, younger adults had excess hepatic and cardiac iron and were receiving combination chelation therapy. The ethnic composition of the younger cohort was predominantly of Asian origin, reflecting the demographics of immigration. These findings demonstrate that comprehensive care and periodic surveys are needed to ensure optimal health and access to emerging therapies.

Thalassaemia is a typically monogenic disease caused by mutations or deletions in the globin gene and has a high prevalence in southern China. Prenatal screening for thalassaemia can be effective in reducing the incidence of thalassaemia. Haematologic parameters of pregnant thalassaemia carriers are diverse and potentially valuable for identifying different types of genotypes. By comparing and evaluating haematological parameters, formulas in the literature, we tried to reveal differences between pregnant women carrying different types of thalassaemia genes. The Mentzer formula (MCV/RBC) showed a strong ability to differentiate thalassaemia genotypes in pregnant women. In addition, combined with haemoglobin electrophoresis HbA2 can further distinguish the –α/αα, αTα/αα, –/αα, β+/N and β0/N groups. HbA2 divides them into two groups. Based on the Mentzer formula, we can further decide which type of thalassaemia to screen (α/β and the subgroups) for genotyping. Therefore, this simpler and more cost-effective workflow has great potential for application in screening pregnant women for thalassaemia carriers. What is already known on this subject? Currently, it is known that thalassaemia gene carriers have abnormal blood indicators. Many findings describe their important values in distinguishing thalassaemia and other blood diseases. They combined different metrics as an algorithm to distinguish thalassaemia and iron deficiency anaemia. Prenatal screening is an effective method to reduce the incidence of thalassaemia. The current main method is PCR. Due to technical and financial constraints, many backward places cannot use this technology. The necessity for prenatal screening for thalassaemia has been overlooked. Whatthe results of this study add? Among these algorithms, Mentzer formula revealed differences in haematological parameters during pregnancy between normal individuals and thalassaemia carriers. Combining the HbA2, thalassaemia carriers can be distinguished from normal individuals, including –α/αα, αTα/αα, –/αα, β0/N and β+/N. What are the implications of these findings for clinical practice and/or further research? We provide another tool for these hospitals that donot have Hb electrophoresis test and PCR. Then the clinical doctor can get some evidence and suggest women go to another big hospital for essential tests. It is an excellent suggestion. In the future, we will collect more specific gene types and further investigate their potential relationship using these formulas. [ABSTRACT FROM AUTHOR]

Thalassemia is a hereditary blood disorder characterized by a deficiency in the oxygen-carrying protein (haemoglobin) and a reduced number of red blood cells in the body compared to normal. Mild forms of thalassemia may not necessitate treatment, while severe cases may require blood transfusions or a stem-cell transplant from a donor. Wheatgrass extract is seen as a supplementary treatment option for thalassemia, although research in this field is still in its early stages. Wheatgrass is a low-calorie substance but rich in essential nutrients, including antioxidants like glutathione, vitamin C, and vitamin E that plays a crucial role in combating harmful free radicals in the body, reducing oxidative stress, and providing protection against conditions such as arthritis, cancer, and neurodegenerative diseases. The proposed mechanism behind wheatgrass extract involves the swift absorption of chlorophyll and its action at the cellular level in the bone marrow, facilitating heme production. Treatment with wheatgrass tablets has been found to maintain serum ferritin levels and increase HbF levels in children with thalassemia who undergo frequent blood transfusions. However, it does not appear to reduce the frequency of blood transfusions required. Wheatgrass tablets also contribute to an improved quality of life for children with thalassemia. The present study aims to investigate the effectiveness of wheatgrass therapy in patients with transfusion-dependent anemia, further extensive studies involving a larger patient population would be necessary. [ABSTRACT FROM AUTHOR]

Abstract Objective: To develop the methods for an extended reporting of anaemia and to measure the status of the key contextual underlying factors of anaemia. Design: Statistical appraisal of Hb v. key influencers of anaemia in Bangladesh – the intake of animal source food (ASF), concentration of Fe in the drinking groundwater (GWI) and the prevalence of congenital Hb disorder (CH) are conducted. The primary data of the National Micronutrient Survey 2011–2012 and the British Geological Survey 2001 are analysed to assess the intake of ASF and the GWI concentration, respectively. The prevalence of thalassaemia from a national survey is used to appraise the CH. ASF is evaluated relative to the 97·5th percentile intake and group scores are assigned. Association of the GWI and Hb is examined by the linear fit and the mspline fit and the group scores are allocated. Group score is allocated for the prevalence of thalassaemia. Inflammation-adjusted ferritin is considered to report Hb. Setting: A nationwide survey in Bangladesh. Participants: Preschool children (6–59 months), school-age children (6–14 years) and non-pregnant non-lactating women (NPNLW, 15–49 years). Results: The extended reporting to the prevalence of anaemia in Bangladeshi preschool children, school children and women is – anaemia 33 % (ASF: 2·08; GWI: 1·75; CH: 2), anaemia 19 % (ASF: 1·98; GWI: 1·56; CH: 2) and anaemia 26 % (ASF: 2·16; GWI: 1·58; CH: 2), respectively. Conclusion: The extended reporting of anaemia is a useful tool to understand the status of the key influencers of anaemia, to design the context-customised intervention and to monitor the intervention.

Abstract The quantification of haemoglobin A2 by high‐performance liquid chromatography (HPLC) was compared with quantification by capillary electrophoresis for control subjects and patients with sickle cell trait or sickle cell anaemia. Significant differences were found, with estimated values being higher by HPLC for control subjects and higher by capillary electrophoresis for sickle cell trait and sickle cell anaemia patients. There is an ongoing need for improved standardisation and alignment of methods.

Background: Haemoglobinopathies, including sickle cell disease and β-thalassaemia, are monogenic disorders with a relatively higher prevalence among malaria-endemic areas in Africa. Despite this prevalence, most African countries lack the necessary resources for diagnosing and managing these debilitating conditions. Aim: This study provides a critical review of newborn screening for detecting haemoglobinopathies in Africa, highlighting challenges and proposing strategies for improved diagnosis and management. Methods: A literature search on haemoglobinopathies in Africa was conducted in PubMed, Google Scholar and ScienceDirect, using specific keywords and Boolean operators, including articles published from January 1981 to December 2022. Results: The data show that sickle cell disease is prevalent among populations in Central and West Africa; however, β-thalassaemia is prevalent among people in the northern parts of Africa. Newborn screening pilot initiatives for haemoglobinopathies were being implemented in Angola, Nigeria, Ghana, the Democratic Republic of Congo and the Republic of Benin. The cost of testing, lack of sufficient and accessible medical records, and inadequacy in healthcare infrastructure pose significant challenges in bridging the gaps in newborn screening. Furthermore, the stigmatisation and lack of awareness of haemoglobinopathies and access to newborn screening programmes pose additional challenges. Conclusion: This review highlights the challenges associated with haemoglobinopathy testing, effective strategies for mitigating these challenges, and future perspectives for expanding efforts toward detecting and managing these disorders across Africa. Providing affordable diagnostic tools, mobile clinics, government subsidies, education campaigns, and the implementation of electronic medical records systems could help bridge the gaps in newborn screening in Africa. What this study adds: The study presents a comprehensive view of newborn screening of haemoglobinopathies in Africa, provides a detailed outline of the challenges faced by newborn screening for haemoglobinopathies in Africa, and offers strategies for better diagnosis and care.

В статье рассмотрены генетические основы гемоглобинопатий, методы и средства анализа для диагностики носителей гемоглобинопатий, молекулярные причины α-талассемии, молекулярная основа и гетерогенность гемоглобинопатий на примере β-талассемии, а также промежуточная β-талассемия, связанная с дополнительными генами α-глобина. Гемоглобинопатии являются наиболее распространенными моногенными наследственными заболеваниями, создающими главную проблему здравоохранения во многих странах мира. Как показывает статистика, большинство гемоглобинопатий, носители рецессивного наследования и они обычно клинически бессимптомны. Программы пре-концепционного и антенатального скрининга на носительство с возможностью пренатальной диагностики считаются результативными во многих эндемичных странах. С развитием генетических инструментов исследования следующего поколения, таких как матричный анализ и секвенирование, в дополнение к современному скринингу на гематологическом, биохимическом и генетическом уровне, было обнаружено все большее число редких перестроек и новых факторов, влияющих на тяжесть заболевания за последние годы. В обзоре обобщены основные требования к адекватному скрининговому анализу носителей болезни, важность корреляции генотип-фенотип и то, как это может привести к не выявленным исключительным взаимодействиям, вызывающим клинически более тяжелый фенотип у бессимптомных носителей.

Patients with thalassemia and sickle cell disease (SCD) require blood transfusions as part of their supportive care. However, one of the most serious side effects of this treatment is the risk of red cell alloimmunization. The goal of this study was to assess the prevalence and Specificity of red cell alloimmunization in Egyptian thalassemia and sickle cell anaemia patients. This study included 200 multi transfused Egyptian patients, one hundred and forty patients with transfusion dependent thalassaemia and sixty patients with sickle cell anaemia, who were attending the Paediatric Children Hospital-Cairo University at the period from March 2019 to October 2019. Alloantibody identification was made by Diamed- ID microtyping system. In the studied groups both thalassemia and sickle patients, the prevalence of alloimmunization was 22/200 (11%) patients. The two most often alloantibodies were, antibodies against Kell antigen (37%) and against E antigen (30%). The prevalence of alloimmunization was more in females in comparison to males, but it did not reach statistical significance and patients with thalassemia major had higher alloimmunization rates than other studied groups but was not statistically significant. In the D negative patients in the research group, alloimmunization demonstrated a statistically significant difference (p = 0.01). Age, gender, age of transfusion onset and splenectomy were not contributing factors to the antibody presence in the group of patients being investigated. Before receiving blood transfusions, extended red blood cell phenotyping should be thought of as a crucial procedure for hemoglobinopathies patients who would likely have several transfusions. It is advised that haemoglobinopathies patients in Egypt be checked through phenotyping of RBC units for Kell and all Rh antigens to be phenotyped before starting transfusion in these patients which is also standard of care for these patients presently. [ABSTRACT FROM AUTHOR]

The fourteenth annual ASCAT conference was held 21-23 October 2019. The theme of the conference was 'Sickle Cell and Thalassaemia disorders new treatment horizon; while ensuring patient safety and delivering excellence in routine patient care.' Over the three-day conference, topics on current and novel models of care, advances in bone marrow transplant and gene therapy, as well as the psychosocial aspects of mind, body and health related quality of life were discussed. In addition, blood transfusion, apheresis, iron chelation therapy and acute haemolytic complications were presented. Quality standards in the diagnosis and treatment of sickle cell and thalassaemia were reviewed. Experts from Europe, the United Kingdom, the Middle East, the United States and Africa reported up-to-date scientific data, guides to comprehensive care, and current research into developing cures and advancing current therapy were described. In addition, oral and poster presentations on novel research from all over the world were shown during the conference.

Abstract Background Thalassaemia affects many families in Northeast Syria, an area devastated by over a decade of conflict which has significantly impacted their health system. People with thalassaemia require holistic multidisciplinary care for the clinical complications of thalassaemia. The risks of thalassaemia treatment include blood-borne viral infections secondary to unsafe transfusion, increased vulnerability to serious bacterial infection following splenectomy, and complications of both iron overload and iron chelation therapy. Médecins Sans Frontières (MSF) provided outpatient thalassaemia care programmes in northeast Syria between April 2017 October 2019 in a complex conflict context challenged by population displacement, the destruction of medical facilities, and periods of insecurity. Methods We performed a secondary descriptive analysis of the thalassaemia cohort data to describe basic clinical and demographic characteristics of the patient population. A desk review of internal and publicly available documents was supplemented by informal interviews with MSF staff to describe and analyse the programmatic approach. Case description MSF delivered programmes with thalassaemia investigations, provision of blood transfusion, iron chelation therapy, and psychosocial support. Thalassemia programmes were novel for the organisation and operational learning took place alongside service implementation. Lessons were identified on equipment procurement and the requirements for the implementation of vital investigations (including ferritin testing), to inform clinical decision making. Lessons included the importance of supply planning for sufficient blood products to meet diverse clinical needs in a conflict area, so those with thalassaemia have continued access to blood products among the competing priorities. Iron chelation therapy met a large need in this cohort. Adapted protocols were implemented to balance social factors, hygiene considerations, toxicity, tolerability, and adherence to therapy. Wider service needs included considerations for family planning advice and services, continuity of care and patient access through decentralised services or laboratory access, psychosocial support, and improved data collection including quality of life measurements to understand the full impact of such programmes. Conclusions Although this type of programming was not “routine” for the organisation, MSF demonstrated that life-sustaining thalassaemia care can be provided in complex conflict settings. International non-governmental organisations can consider this care possible in similar contexts.

Objective: To evaluate the value of next-generation sequencing (NGS) in the prevention and management of thalassemia. Methods: A systematic search was performed in eight databases including China Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang database, PubMed, EMBASE, Web of Science, and Cochrane Library from the inception to 1 June 2022. Stata 17.0 and Review Manager 5.4 were used for the meta-analysis. Results: Nine studies containing 14794 participants were included in the meta-analysis. Compared with the routine genetic testing (including Gap-PCR and reverse dot blot), NGS had higher detection rates in screening thalassemia (RR 1.22, 95% CI 1.13-1.31, P0.05). Conclusions: Compared with routine genetic testing, NGS had a higher detection rate in general, particularly in the detection of α-thalassemia.

Thalassaemia International Federation (TIF), representing the united voice of people with thalassaemia and their families globally, has been striving for more than three decades to empower research, by academic communities and industry, to focus on developing a safe and effective curative approach for thalassaemia. Such a cure would lead to new lives with equal opportunities and challenges, as for every other person not suffering from a severe chronic disease. A gene therapy product was finally authorised in May 2019 by the European Medicinal Agency, thus marking a milestone in the history of the disease. However, after this conditional authorization, everyone focused on numbers and opted for cost of illness and cost-effectiveness studies, inadmissibly ignoring patients’ voices and needs. The product was finally withdrawn from Europe, despite the fact that all implicated stakeholders, including governments, academia and industry always knew that an innovative and complex therapy would be expensive but always supported and fought for its development. In this article, TIF expresses its view on this issue, including some thoughts on how to address the high cost of innovative therapies.

Thalassaemia constitutes an especially prevalent human monogenic illness caused by a lack of synthesis of the α- or β-globin chains. The clinical impact of β-thalassaemia is worse since it consists of the same pair gene configuration, thalassaemia major, causing significant health discouragement and loss of life due to life threateningly insufficient haemoglobin (Hb) levels. Only a few nations have successfully reduced the prevalence of β-thalassaemia major, even though comprehensive screening, group counselling, pre-natal detection and public education can all be used. Since over ½ century ago, the fundamental elements of treatment for thalassaemia major have been iron chelation and hypertransfusion. The globin chain that makes up the adult Hb molecule is missing or synthesised at a reduced rate in β-thalassemia. The aberrant buildup of the α-globin chain and faulty formation of red blood cells (RBCs) leading to RBC haemolysis are the outcomes of this genetic abnormality. Since allogeneic haematopoietic stem cell transplantation (Allo-HSCT) has been a well-established gene replacement therapy for individuals with thalassaemia major for several years, it has had very successful outcomes for patients with access to it. Over the past 20 years, the consequences for more susceptible patients have also steadily improved, leading to 80%–90% longer-term life expectancy amongst this group of patients. However, providing Allo-HSCT as a treatment for these patients globally presents numerous difficulties. Replacing genes in autologous HSCs employing viral vectors has been possible in recent years.

Introduction Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. Methods This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. Results Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in “categories” with different levels of adherence (n = 29) or “quantitatively” as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. Conclusions Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messages Predictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort. Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes. Inadequate adherence to ICT is associated with increased lifetime health costs. There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.

Introduction Around 5% of the world’s population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be

Background: Hyperfunctional platelets play important roles in thromboembolism in patients with β-thalassaemia/ haemoglobin E (β-thal/HbE). Our previous study revealed ex vivo inhibitory effects of deferiprone on normal platelets. Herein, we aimed to investigate the in vivo effects on platelets in patients with β-thal/HbE. Methods: A prospective, self-controlled clinical study on 30 patients with β-thal/HbE who had received therapeutic deferiprone (20.8–94.5 mg/kg/day) was conducted. The study included a 4-week washout period followed by 4 and 12 weeks of deferiprone treatment. Platelet aggregation was performed by a turbidimetric method. Levels of deferiprone and soluble platelet (sP)-selectin in serum were measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kit, respectively. Results: The washout period significantly enhanced platelet hyperactivity both in patients who had undergone splenectomy and in those who had not. At 2 hours following the administration of a single dose of deferiprone, platelet sensitivity to ADP and arachidonic acid was significantly reduced. The inhibitory effects of deferiprone were gradually increased over the period of 4 and 12 weeks. Deferiprone also depressed sP-selectin levels, but the effect was stable over longer follow-up periods. Correlation analysis demonstrated the relationship between serum levels of deferiprone, sP-selectin, and platelet activities induced by ADP and arachidonic acid. Conclusion: We first demonstrated the in vivo antiplatelet effect and benefit of short-term treatment of deferiprone in patients with β-thal/HbE. The impact on thrombotic outcomes deserves further study.

Abstract Background Childhood anaemia is one of the most common public health problems worldwide. Here, we aim to describe the knowledge and practices on childhood anaemia, thalassaemia and iron deficiency among mothers of children aged between 6 and 59 months in a suburban district of Sri Lanka. Methods We performed a cross-sectional survey in the Gampaha District of Sri Lanka from December 2020 to February 2021. One well-baby clinic each from four Medical Officer of Health areas in the district was selected using stratified random sampling. Mothers of all children aged between 6 and 59 months attending well-baby clinics were recruited until the sample size was achieved. Data were collected using a self-administered questionnaire and analysed using logistic regression. Results A total of 392 mothers were recruited; 53% of their children were males. Only 33% of mothers had an accurate understanding of anaemia, while 71% and 28%, respectively, could name at least one symptom and two causes of anaemia; 12% could not name a single food rich in iron. Only 13% of mothers knew that thalassaemia is a cause of anaemia, and 14% had been screened for thalassaemia. Logistic regression analysis that examined for factors associated with higher knowledge of anaemia revealed that an accurate understanding of anaemia was associated with maternal age over 30 years (p

Haemoglobin disorders are hereditary, lifelong and characterised by the need for multifaceted management. The question of quality in meeting standards of care that are likely to bring the best possible outcomes for patients is a necessary consideration. The concept of reference centres supporting peripheral treatment centres in a formal networking relationship is a response to the real needs of patients and a practical solution in public health terms. In this report, a team of advisors of Thalassaemia International Federation (TIF) attempts to suggest a set of standards for haemoglobinopathy reference centres, also based on the founding principles of TIF, aiming to act as a guideline for its member associations and professional collaborators. The standards described herein can form the basis of an accreditation process and also serve as a guide for those who would advocate for quality improvement for thalassaemia services.

Abstract Aim To explore the experiences of Jordanian nurses regarding the psychosocial care needs of children with thalassaemia and their families. Design A descriptive phenomenological approach was employed. Methods A purposive sampling strategy was used to select 10 nurses who had experience in caring for children with thalassaemia. Unstructured, face‐to‐face interviews were conducted. Coliazzi's data analysis process was applied. Results The analysis revealed three major themes: (1) valuing psychosocial support; (2) caring for paediatric patients needs certain competencies in nurses and (3) barriers to providing psychosocial care. Nurses expressed the importance of providing psychosocial care. A lack of specialists in psychosocial care as well as a lack of screening tools, and entertainment facilities for children was identified to be impeding effective psychosocial care. Implementing training programmes for nurses concerning providing psychosocial care and making the appropriate changes in nursing curricula at the educational level are recommended.

Abstract Background Haemoglobinopathies and G6PD deficiency are inherited disorders found mostly in malaria-endemic areas among different tribal groups of India. However, epidemiological data specific to Particularly Vulnerable Tribal Groups (PVTGs), important for planning and implementing malaria programmes, is limited. Therefore, the present community-based study aimed to assess the prevalence of haemoglobinopathies and G6PD deficiency among the 13 PVTGs found in the state of Odisha, reporting the maximum malaria cases in the country. Methods This cross-sectional study was conducted from July 2018 to February 2019 in 12 districts, home to all 13 PVTGs, in an estimated sample size of 1461, selected two-stage sampling method. Detection of haemoglobinopathies was done by the variant analyser. Screening of G6PD deficiency was carried out using DPIP method followed by quantification using spectrophotometry. The PCR–RFLP technology was used to determine variant of G6PD deficiency and haplotype analysis of sickle cell, while ARMS-PCR and GAP-PCR was used for detecting the mutation pattern in β-thalassaemia and α-thalassaemia respectively. The diagnosis of malaria was done by Pf-PAN RDT as point of care, followed by nPCR for confirmation and Plasmodium species identification. Results The prevalence of sickle cell heterozygotes (AS) was 3.4%, sickle cell homozygous (SS) 0.1%, β-thalassaemia heterozygotes 0.3%, HbS/β-thalassaemia compound heterozygote 0.07%, HbS-α-thalassaemia 2.1%, G6PD deficiency 3.2% and malaria 8.1%. Molecular characterization of βS revealed the presence of Arab-Indian haplotype in all HbS cases and IVS 1–5 G → C mutation in all β-thalassaemia cases. In case of α-thal, αα/α-3.7 gene deletion was most frequent (38%), followed by αα/α-4.2 (18%) and α-3.7/α-3.7 (4%). The frequency of G6PD Orissa (131C → G) mutation was found to be 97.9% and G6PD Mediterranean (563C → T) 2.1%. Around 57.4% of G6PD deficient individuals and 16% of the AS were found to be malaria positive. Conclusion The present study reveals wide spread prevalence of sickle cell anaemia, α-thalassaemia, G6PD deficiency and malaria in the studied population. Moderate to high prevalence of G6PD deficiency and malaria warrants G6PD testing before treating with primaquine (PQ) for radical cure of Plasmodium vivax. Screening and counselling for HbS is required for the PVTGs of Odisha.

Haemoglobinopathies, including thalassaemias and sickle-cell syndromes, are demanding, lifelong conditions that pose a significant burden to patients, families, and healthcare systems. Despite the therapeutic advances and the resulting improvements in prognosis accomplished in past decades, these patients still face important challenges, including suboptimal access to quality care in areas with developing economies, changing epidemiology due to massive migration flows, an evolving clinical spectrum due to ageing in well-treated patients, and limited access to novel high-cost therapies. We herein describe the organization of healthcare services for haemoglobinopathies in Cyprus—with particular focus on beta-thalassaemia, the most prevalent condition in this region—along with selected patient outcomes. This report aims at underscoring the fact that nationally funded and well-coordinated prevention and care programmes for chronic and complex conditions, such as haemoglobinopathies, with active involvement from patient organizations lead to effective disease control and excellent outcomes in survival, quality of life, social adaptation, and public health savings, and allow timely and effective responses to emerging crises, such as the COVID-19 pandemic. The Cyprus paradigm could therefore serve as a blueprint for the organization or adaptation of haemoglobinopathy programs in other countries since these disorders are still widely occurring.

The iron chelating orphan drug deferiprone (L1), discovered over 40 years ago, has been used daily by patients across the world at high doses (75–100 mg/kg) for more than 30 years with no serious toxicity. The level of safety and the simple, inexpensive synthesis are some of the many unique properties of L1, which played a major role in the contribution of the drug in the transition of thalassaemia from a fatal to a chronic disease. Other unique and valuable clinical properties of L1 in relation to pharmacology and metabolism include: oral effectiveness, which improved compliance compared to the prototype therapy with subcutaneous deferoxamine; highly effective iron removal from all iron-loaded organs, particularly the heart, which is the major target organ of iron toxicity and the cause of mortality in thalassaemic patients; an ability to achieve negative iron balance, completely remove all excess iron, and maintain normal iron stores in thalassaemic patients; rapid absorption from the stomach and rapid clearance from the body, allowing a greater frequency of repeated administration and overall increased efficacy of iron excretion, which is dependent on the dose used and also the concentration achieved at the site of drug action; and its ability to cross the blood–brain barrier and treat malignant, neurological, and microbial diseases affecting the brain. Some differential pharmacological activity by L1 among patients has been generally shown in relation to the absorption, distribution, metabolism, elimination, and toxicity (ADMET) of the drug. Unique properties exhibited by L1 in comparison to other drugs include specific protein interactions and antioxidant effects, such as iron removal from transferrin and lactoferrin; inhibition of iron and copper catalytic production of free radicals, ferroptosis, and cuproptosis; and inhibition of iron-containing proteins associated with different pathological conditions. The unique properties of L1 have attracted the interest of many investigators for drug repurposing and use in many pathological conditions, including cancer, neurodegenerative conditions, microbial conditions, renal conditions, free radical pathology, metal intoxication in relation to Fe, Cu, Al, Zn, Ga, In, U, and Pu, and other diseases. Similarly, the properties of L1 increase the prospects of its wider use in optimizing therapeutic efforts in many other fields of medicine, including synergies with other drugs. [ABSTRACT FROM AUTHOR]

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Objective: To develop the methods for an extended reporting of anaemia and to measure the status of the key contextual underlying factors of anaemia. Design: Statistical appraisal of Hb v. key influencers of anaemia in Bangladesh – the intake of animal source food (ASF), concentration of Fe in the drinking groundwater (GWI) and the prevalence of congenital Hb disorder (CH) are conducted. The primary data of the National Micronutrient Survey 2011–2012 and the British Geological Survey 2001 are analysed to assess the intake of ASF and the GWI concentration, respectively. The prevalence of thalassaemia from a national survey is used to appraise the CH. ASF is evaluated relative to the 97·5th percentile intake and group scores are assigned. Association of the GWI and Hb is examined by the linear fit and the mspline fit and the group scores are allocated. Group score is allocated for the prevalence of thalassaemia. Inflammation-adjusted ferritin is considered to report Hb. Setting: A nationwide survey in Bangladesh. Participants: Preschool children (6–59 months), school-age children (6–14 years) and non-pregnant non-lactating women (NPNLW, 15–49 years). Results: The extended reporting to the prevalence of anaemia in Bangladeshi preschool children, school children and women is – anaemia 33 % (ASF: 2·08; GWI: 1·75; CH: 2), anaemia 19 % (ASF: 1·98; GWI: 1·56; CH: 2) and anaemia 26 % (ASF: 2·16; GWI: 1·58; CH: 2), respectively. Conclusion: The extended reporting of anaemia is a useful tool to understand the status of the key influencers of anaemia, to design the context-customised intervention and to monitor the intervention. [ABSTRACT FROM AUTHOR]

Background and Objectives: The effective management of chronic diseases, particularly hereditary and rare diseases and thalassaemia, is an important indicator of the quality of healthcare systems. We aimed to assess healthcare services in different countries for thalassaemia patients by using publicly available health indicators and by surveying thalassaemia patients and their caregivers. Materials and Methods: We reviewed official worldwide databases from the WHO, World Bank, and scientific resources, and we used a structured patient-tailored self-completed questionnaire to survey thalassaemia patients and their caregivers in 2023. Results: A total of 2082 participants were surveyed (mean age, 27 years; males, 42%). About 1 in 4 respondents did not complete high-school education, while 24% had a bachelor’s degree. About a third of respondents were married and were in either full- or part-time employment. The vast majority (~80%) had initiated transfusion therapy between 1 and 4 years of age. Only 42% reported no delays in receiving blood transfusion, while 47% reported occasional delays and 8% serious delays. About half of patients reported being very satisfied (11%) or satisfied (38%) with the quality of services provided, while 1 in 3 patients reported being unsatisfied or very unsatisfied, and that their access to treatment was difficult or very difficult due to traveling expenses and the high cost of treatment. Conclusions: Important improvements in the care of thalassaemia patients have been documented during the past few decades. Nevertheless, additional focus is required through national healthcare systems to effectively address the many unmet needs revealed by our recent survey, as well as to achieve satisfactory patient outcomes.

Sri Lanka, a country with 22 million people, has nearly 2000 thalassemia patients with severe thalassemia, two-thirds of whom have beta thalassemia major (TM). The current prevention program based on promoting “safe marriages”, which has been in existence for over 15 years, has failed to reduce thalassemia major births. We set about to examine the cost-effectiveness of novel policy options for thalassemia prevention in Sri Lanka. Methods: The current cost for treatment of a thalassemia major patient (USD 2602/yr) was compared against the cost per reduction of single birth with three novel strategies, namely intensifying the screening in the current five districts combined with an education program (policy option 1), a nationwide screening program (policy option 2), and antenatal screening combined with the termination of pregnancy (policy option 3). The incremental cost-effectiveness ratio (ICER) of the different strategies was calculated. Results: The status quo was considered to reduce one TM birth whilst the new policy options were able to reduce births by 14, 35, and 48, respectively. The costs incurred for the program for a year for status quo and the three novel programs were USD 104,788, 173,884, 781,372, and 904,186 respectively. Cost per prevention of a thalassemia major birth was USD 87,324, 12,420, 22,324, and 20,084, respectively. The lifetime cost per treatment of a thalassemia major patient was USD 34,653. Conclusions: Given the current legal restriction on termination of pregnancy for fetal indications, policy option 2, an island-wide screening with mass education, is the most cost-effective and will be expected to deliver a substantial reduction in new births.

Thalassaemia International Federation (TIF), representing the united voice of people with thalassaemia and their families globally, has been striving for more than three decades to empower research, by academic communities and industry, to focus on developing a safe and effective curative approach for thalassaemia. Such a cure would lead to new lives with equal opportunities and challenges, as for every other person not suffering from a severe chronic disease. A gene therapy product was finally authorised in May 2019 by the European Medicinal Agency, thus marking a milestone in the history of the disease. However, after this conditional authorization, everyone focused on numbers and opted for cost of illness and cost-effectiveness studies, inadmissibly ignoring patients’ voices and needs. The product was finally withdrawn from Europe, despite the fact that all implicated stakeholders, including governments, academia and industry always knew that an innovative and complex therapy would be expensive but always supported and fought for its development. In this article, TIF expresses its view on this issue, including some thoughts on how to address the high cost of innovative therapies. [ABSTRACT FROM AUTHOR]

Haemoglobin disorders are hereditary, lifelong and characterised by the need for multi-faceted management. The question of quality in meeting standards of care that are likely to bring the best possible outcomes for patients is a necessary consideration. The concept of reference centres supporting peripheral treatment centres in a formal networking relationship is a response to the real needs of patients and a practical solution in public health terms. In this report, a team of advisors of Thalassaemia International Federation (TIF) attempts to suggest a set of standards for haemoglobinopathy reference centres, also based on the founding principles of TIF, aiming to act as a guideline for its member associations and professional collaborators. The standards described herein can form the basis of an accreditation process and also serve as a guide for those who would advocate for quality improvement for thalassaemia services. [ABSTRACT FROM AUTHOR]

Background: Thalassaemia affects many families in Northeast Syria, an area devastated by over a decade of conflict which has significantly impacted their health system. People with thalassaemia require holistic multidisciplinary care for the clinical complications of thalassaemia. The risks of thalassaemia treatment include blood-borne viral infections secondary to unsafe transfusion, increased vulnerability to serious bacterial infection following splenectomy, and complications of both iron overload and iron chelation therapy. Médecins Sans Frontières (MSF) provided outpatient thalassaemia care programmes in northeast Syria between April 2017 October 2019 in a complex conflict context challenged by population displacement, the destruction of medical facilities, and periods of insecurity. Methods: We performed a secondary descriptive analysis of the thalassaemia cohort data to describe basic clinical and demographic characteristics of the patient population. A desk review of internal and publicly available documents was supplemented by informal interviews with MSF staff to describe and analyse the programmatic approach. Case description: MSF delivered programmes with thalassaemia investigations, provision of blood transfusion, iron chelation therapy, and psychosocial support. Thalassemia programmes were novel for the organisation and operational learning took place alongside service implementation. Lessons were identified on equipment procurement and the requirements for the implementation of vital investigations (including ferritin testing), to inform clinical decision making. Lessons included the importance of supply planning for sufficient blood products to meet diverse clinical needs in a conflict area, so those with thalassaemia have continued access to blood products among the competing priorities. Iron chelation therapy met a large need in this cohort. Adapted protocols were implemented to balance social factors, hygiene considerations, toxicity, tolerability, and adherence to therapy. Wider service needs included considerations for family planning advice and services, continuity of care and patient access through decentralised services or laboratory access, psychosocial support, and improved data collection including quality of life measurements to understand the full impact of such programmes. Conclusions: Although this type of programming was not "routine" for the organisation, MSF demonstrated that life-sustaining thalassaemia care can be provided in complex conflict settings. International non-governmental organisations can consider this care possible in similar contexts. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis is a rare disorder in which hematopoietic cells proliferate in tissues other than the bone marrow as a result of a range of hematologic illnesses. Our case is unique in that it covers a number of extramedullary hematopoiesis sites in a 15-year-old girl, some of which are uncommon.

Introduction: Thalassaemia and other structural haemoglobinopathies are the major genetic disorders that cause significant morbidity in children. Haemoglobinopathies need to be diagnosed at the earliest in order to offer suitable treatment, carrier identification and counselling which will help to decrease the incidence of haemoglobinopathies. Aim: To study the clinicohaematological spectrum of children with thalassaemia and other haemoglobinopathies, followed by family screening and counselling. Materials and Methods: This retrospective cross-sectional study was taken up at Department of Pathology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India from January 2018 to December 2020, during which records of 235 cases were studied, out of which 100 were the children visiting Institute and 135 were the parents and siblings of these children. Diagnosis of these cases was followed by counselling for these families. Results were calculated by data analysis. Percentages were calculated from the frequency of the variables. Results: Amongst the records of 235 cases studied, β-thalassaemia major was the most common haemoglobinopathy found in 75 patients, followed by sickle cell anaemia in 10 patients. β-thalassaemia trait was the most common haemoglobinopathy among the parents of these children, which was found in 125 individuals. Conclusion: β-thalassaemia major is the most common disorder amongst the children with haemoglobinopathy, followed by sickle cell anaemia. β-thalassaemia trait is a common entity amongst the carriers of haemoglobinopathy.

Introduction: Thalassaemia is a common genetic blood disorder. Knowledge, awareness, attitude towards, and intention to screen for thalassaemia among Malaysians is poor. Screening for thalassaemia in unmarried individuals plays a key role in preventing thalassaemia major births. Methods: A cross-sectional study was conducted on unmarried individuals aged 18 years and older in Kota Bharu, Kelantan, Malaysia. A questionnaire was used to collect the general data of the participants, their knowledge of thalassaemia, attitude towards thalassaemia, and intention to screen for thalassaemia. Results: A total of 278 respondents were included in this study. The mean (SD) knowledge score was 8.8 (4.99) out of a possible score of 21, with higher scores indicating better knowledge. The factor associated with good knowledge of thalassaemia was being a professional. Most respondents agreed that unmarried individuals should be screened for thalassaemia before marriage. Conclusion: In conclusion, knowledge of thalassaemia among unmarried individuals who were not professionals was low.

Introduction: Haemoglobinopathies are qualitative disorders of Haemoglobin (Hb) resulting from structural defects in the amino acid sequence of one of the globin chains, whereas, thalassaemia results from quantitative defects in the synthesis of one or more of the globin chain subunits of the Hb tetramer. Cation ExchangeHigh Performance Liquid Chromatography (CE-HPLC) is one of the methods for initial screening of Hb variants like HbS, HbD, HbE etc and for quantification of HbF, HbA and HbA2 levels. Aim: To find out the prevalence of haemoglobinopathies in patients of a Government paediatric tertiary care hospital in south India. Materials and Methods: In this retrospective, cross-sectional study, all laboratory requests, in the period from August 2019 to July 2021, for Hb variant analysis by HPLC were collected, irrespective of provisional diagnosis. The Hb variant analysis was carried out by CE-HPLC on the Bio-Rad D-10 analyser. This study was conducted in a Government Paediatric tertiary care hospital in Southern India for patients who had any clinical or familial suspicion of haemoglobinopathies. The Statistical analysis was performed using Microsoft Excel 2010. Results: Total data of 704 laboratory requests for Hb Variant analysis were obtained. Out of 704 laboratory request, 585 were from children younger than 12 years of age and 119 were parental screening. There were 164 abnormal chromatograms. Out of 164 patients, 91 were female patients and 73 were male patients. Out of 164 abnormal chromatograms, 97 (59.15%) were betathalassaemia trait, 18 (10.98%) were beta-thalassaemia major, 13 (7.93%) were sickle cell trait, 2 (1.22%) were sickle cell disease, 21 (12.80%) were HbE trait, 2 (1.22%) were homozygous HbE, 2 (1.22%) were HbD trait, 3 (1.83%) were Hereditary Persistence of Foetal Hb (HPFH)/delta beta-thalassaemia, 2 (1.22%) were HbJ trait, 1 (0.61%) was HbE beta-thalassaemia, 1 (0.61%) was sicklebeta-thalassaemia and 2 (1.22%) were alpha thalassaemia. Conclusion: From this study, beta-thalassaemia trait and betathalassaemia major were found to be the first and second most prevalent haemoglobinopathies in children below 12 years of age. This data suggests the importance of premarital and antenatal screening procedures that can help in reducing the possibility of such haemoglobinopathies in the future generation, suffering and burden of disease to the family and society.

Background: Haemoglobinopathies, including sickle cell disease and β-thalassaemia, are monogenic disorders with a relatively higher prevalence among malaria-endemic areas in Africa. Despite this prevalence, most African countries lack the necessary resources for diagnosing and managing these debilitating conditions. Aim: This study provides a critical review of newborn screening for detecting haemoglobinopathies in Africa, highlighting challenges and proposing strategies for improved diagnosis and management. Methods: A literature search on haemoglobinopathies in Africa was conducted in PubMed, Google Scholar and ScienceDirect, using specific keywords and Boolean operators, including articles published from January 1981 to December 2022. Results: The data show that sickle cell disease is prevalent among populations in Central and West Africa; however, β-thalassaemia is prevalent among people in the northern parts of Africa. Newborn screening pilot initiatives for haemoglobinopathies were being implemented in Angola, Nigeria, Ghana, the Democratic Republic of Congo and the Republic of Benin. The cost of testing, lack of sufficient and accessible medical records, and inadequacy in healthcare infrastructure pose significant challenges in bridging the gaps in newborn screening. Furthermore, the stigmatisation and lack of awareness of haemoglobinopathies and access to newborn screening programmes pose additional challenges. Conclusion: This review highlights the challenges associated with haemoglobinopathy testing, effective strategies for mitigating these challenges, and future perspectives for expanding efforts toward detecting and managing these disorders across Africa. Providing affordable diagnostic tools, mobile clinics, government subsidies, education campaigns, and the implementation of electronic medical records systems could help bridge the gaps in newborn screening in Africa. What this study adds: The study presents a comprehensive view of newborn screening of haemoglobinopathies in Africa, provides a detailed outline of the challenges faced by newborn screening for haemoglobinopathies in Africa, and offers strategies for better diagnosis and care. [ABSTRACT FROM AUTHOR]

Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients. This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943. Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature (N = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection. EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM. Extramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before. There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities. More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines. [ABSTRACT FROM AUTHOR]

Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence (n = 29) or "quantitatively" as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients. Predictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort. Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes. Inadequate adherence to ICT is associated with increased lifetime health costs. There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients. [ABSTRACT FROM AUTHOR]

Haemoglobinopathies, including thalassaemias and sickle-cell syndromes, are demanding, lifelong conditions that pose a significant burden to patients, families, and healthcare systems. Despite the therapeutic advances and the resulting improvements in prognosis accomplished in past decades, these patients still face important challenges, including suboptimal access to quality care in areas with developing economies, changing epidemiology due to massive migration flows, an evolving clinical spectrum due to ageing in well-treated patients, and limited access to novel high-cost therapies. We herein describe the organization of healthcare services for haemoglobinopathies in Cyprus--with particular focus on beta-thalassaemia, the most prevalent condition in this region--along with selected patient outcomes. This report aims at underscoring the fact that nationally funded and well-coordinated prevention and care programmes for chronic and complex conditions, such as haemoglobinopathies, with active involvement from patient organizations lead to effective disease control and excellent outcomes in survival, quality of life, social adaptation, and public health savings, and allow timely and effective responses to emerging crises, such as the COVID-19 pandemic. The Cyprus paradigm could therefore serve as a blueprint for the organization or adaptation of haemoglobinopathy programs in other countries since these disorders are still widely occurring. [ABSTRACT FROM AUTHOR]

Sri Lanka, a country with 22 million people, has nearly 2000 thalassemia patients with severe thalassemia, two-thirds of whom have beta thalassemia major (TM). The current prevention program based on promoting "safe marriages", which has been in existence for over 15 years, has failed to reduce thalassemia major births. We set about to examine the cost-effectiveness of novel policy options for thalassemia prevention in Sri Lanka. Methods: The current cost for treatment of a thalassemia major patient (USD 2602/yr) was compared against the cost per reduction of single birth with three novel strategies, namely intensifying the screening in the current five districts combined with an education program (policy option 1), a nationwide screening program (policy option 2), and antenatal screening combined with the termination of pregnancy (policy option 3). The incremental cost-effectiveness ratio (ICER) of the different strategies was calculated. Results: The status quo was considered to reduce one TM birth whilst the new policy options were able to reduce births by 14, 35, and 48, respectively. The costs incurred for the program for a year for status quo and the three novel programs were USD 104,788, 173,884, 781,372, and 904,186 respectively. Cost per prevention of a thalassemia major birth was USD 87,324, 12,420, 22,324, and 20,084, respectively. The lifetime cost per treatment of a thalassemia major patient was USD 34,653. Conclusions: Given the current legal restriction on termination of pregnancy for fetal indications, policy option 2, an island-wide screening with mass education, is the most cost-effective and will be expected to deliver a substantial reduction in new births. [ABSTRACT FROM AUTHOR]

Background: Haemoglobinopathies and G6PD deficiency are inherited disorders found mostly in malaria-endemic areas among different tribal groups of India. However, epidemiological data specific to Particularly Vulnerable Tribal Groups (PVTGs), important for planning and implementing malaria programmes, is limited. Therefore, the present community-based study aimed to assess the prevalence of haemoglobinopathies and G6PD deficiency among the 13 PVTGs found in the state of Odisha, reporting the maximum malaria cases in the country. Methods: This cross-sectional study was conducted from July 2018 to February 2019 in 12 districts, home to all 13 PVTGs, in an estimated sample size of 1461, selected two-stage sampling method. Detection of haemoglobinopathies was done by the variant analyser. Screening of G6PD deficiency was carried out using DPIP method followed by quantification using spectrophotometry. The PCR–RFLP technology was used to determine variant of G6PD deficiency and haplotype analysis of sickle cell, while ARMS-PCR and GAP-PCR was used for detecting the mutation pattern in β-thalassaemia and α-thalassaemia respectively. The diagnosis of malaria was done by Pf-PAN RDT as point of care, followed by nPCR for confirmation and Plasmodium species identification. Results: The prevalence of sickle cell heterozygotes (AS) was 3.4%, sickle cell homozygous (SS) 0.1%, β-thalassaemia heterozygotes 0.3%, HbS/β-thalassaemia compound heterozygote 0.07%, HbS-α-thalassaemia 2.1%, G6PD deficiency 3.2% and malaria 8.1%. Molecular characterization of βS revealed the presence of Arab-Indian haplotype in all HbS cases and IVS 1–5 G → C mutation in all β-thalassaemia cases. In case of α-thal, αα/α-3.7 gene deletion was most frequent (38%), followed by αα/α-4.2 (18%) and α-3.7/α-3.7 (4%). The frequency of G6PD Orissa (131C → G) mutation was found to be 97.9% and G6PD Mediterranean (563C → T) 2.1%. Around 57.4% of G6PD deficient individuals and 16% of the AS were found to be malaria positive. Conclusion: The present study reveals wide spread prevalence of sickle cell anaemia, α-thalassaemia, G6PD deficiency and malaria in the studied population. Moderate to high prevalence of G6PD deficiency and malaria warrants G6PD testing before treating with primaquine (PQ) for radical cure of Plasmodium vivax. Screening and counselling for HbS is required for the PVTGs of Odisha. [ABSTRACT FROM AUTHOR]

Aim: To explore the experiences of Jordanian nurses regarding the psychosocial care needs of children with thalassaemia and their families. Design: A descriptive phenomenological approach was employed. Methods: A purposive sampling strategy was used to select 10 nurses who had experience in caring for children with thalassaemia. Unstructured, face‐to‐face interviews were conducted. Coliazzi's data analysis process was applied. Results: The analysis revealed three major themes: (1) valuing psychosocial support; (2) caring for paediatric patients needs certain competencies in nurses and (3) barriers to providing psychosocial care. Nurses expressed the importance of providing psychosocial care. A lack of specialists in psychosocial care as well as a lack of screening tools, and entertainment facilities for children was identified to be impeding effective psychosocial care. Implementing training programmes for nurses concerning providing psychosocial care and making the appropriate changes in nursing curricula at the educational level are recommended. [ABSTRACT FROM AUTHOR]

Plain English Summary What is the problem? With advancements in medical care, more people with transfusion dependent thalassaemia (TDT) reached adulthood, something which was uncommon decades ago. They should have similar physical-mental capabilities as people without TDT. However, the stigma of their condition has remained and their potential capabilities have often been underestimated by the public. We need to understand their adult life in order to assist them further. What did we do? We surveyed 196 TDT patients, using a set of questionnaires. We enquired of their perceptions about their health status and quality of life (QOL: physical, mental, social relationship, environment). We asked them open questions on challenges they were facing during adulthood and employment. What did we find? Some participants (45%) were found to have other medical problems and that they could be feeling unwell at least three days in a month. Participants scored above 60 out of 100 for all of the QOL aspects (a higher score denotes a better QOL). We noted some continued to lose career advancement opportunities, face discrimination and had difficulties managing their health, in a rather non-supportive community. What is our conclusion? People with TDTs were doing relatively well as young adults. Life challenges persist. More qualitative studies are needed to understand their challenges better and to look for more tailored supportive approaches.

Haemoglobinopathies are the commonest monogenic diseases worldwide and are caused by variants in the globin gene clusters. With over 2400 variants detected to date, their interpretation using the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) guidelines is challenging and computational evidence can provide valuable input about their functional annotation. While many in silico predictors have already been developed, their performance varies for different genes and diseases. In this study, we evaluate 31 in silico predictors using a dataset of 1627 variants in HBA1, HBA2, and HBB. By varying the decision threshold for each tool, we analyse their performance (a) as binary classifiers of pathogenicity and (b) by using different non-overlapping pathogenic and benign thresholds for their optimal use in the ACMG/AMP framework. Our results show that CADD, Eigen-PC, and REVEL are the overall top performers, with the former reaching moderate strength level for pathogenic prediction. Eigen-PC and REVEL achieve the highest accuracies for missense variants, while CADD is also a reliable predictor of non-missense variants. Moreover, SpliceAI is the top performing splicing predictor, reaching strong level of evidence, while GERP++ and phyloP are the most accurate conservation tools. This study provides evidence about the optimal use of computational tools in globin gene clusters under the ACMG/AMP framework.