Thalassemia and Nanotheragnostics: Advanced Approaches for Diagnosis and Treatment.

Thalassemia is a monogenic autosomal recessive disorder caused by mutations, which lead to abnormal or reduced production of hemoglobin. Ineffective erythropoiesis, hemolysis, hepcidin suppression, and iron overload are common manifestations that vary according to genotypes and dictate, which diagnosis and therapeutic modalities, including transfusion therapy, iron chelation therapy, HbF induction, gene therapy, and editing, are performed. These conventional therapeutic methods have proven to be effective, yet have several disadvantages, specifically iron toxicity, associated with them; therefore, there are demands for advanced therapeutic methods. Nanotechnology-based applications, such as the use of nanoparticles and nanomedicines for theragnostic purposes have emerged that are simple, convenient, and cost-effective methods. The therapeutic potential of various nanoparticles has been explored by developing artificial hemoglobin, nano-based iron chelating agents, and nanocarriers for globin gene editing by CRISPR/Cas9. Au, Ag, carbon, graphene, silicon, porous nanoparticles, dendrimers, hydrogels, quantum dots, etc., have been used in electrochemical biosensors development for diagnosis of thalassemia, quantification of hemoglobin in these patients, and analysis of conventional iron chelating agents. This review summarizes the potential of nanotechnology in the development of various theragnostic approaches to determine thalassemia-causing gene mutations using various nano-based biosensors along with the employment of efficacious nano-based therapeutic procedures, in contrast to conventional therapies.

Non-Transfusion-Dependent Thalassemia: A Panoramic Review.

Non-transfusion-dependent thalassemia (NTDT) has been considered less severe than its transfusion-dependent variants. The most common forms of NTDT include ß-thalassemia intermedia, hemoglobin E/beta thalassemia, and hemoglobin H disease. Patients with NTDT develop several clinical complications, despite their regular transfusion independence. Ineffective erythropoiesis, iron overload, and hypercoagulability are pathophysiological factors that lead to morbidities in these patients. Therefore, an early and accurate diagnosis of NTDT is essential to ascertaining early interventions. Currently, several conventional management options are available, with guidelines suggested by the Thalassemia International Federation, and novel therapies are being developed in light of the advancement of the understanding of this disease. This review aimed to increase clinicians' awareness of NTDT, from its basic medical definition and genetics to its pathophysiology. Specific complications to NTDT were reviewed, along with the risk factors for its development. The indications of different therapeutic options were outlined, and recent advancements were reviewed.

Advances in screening of thalassaemia.

Thalassaemia is a common hereditary haemolytic anaemia. Mild cases of this disease may be asymptomatic, while patients with severe thalassaemias require high-dose blood transfusions and regular iron removal to maintain life or haematopoietic stem cell transplantation to be cured, imposing an enormous familial and social burden. Therefore, early, timely, and accurate screening of patients is of great importance. In recent years, with the continuous development of thalassaemia screening technologies, the accuracy of thalassaemia screening has also improved significantly. This article reviews the current research on thalassaemia screening.

THALASSEMIA in ASIA 2021: Thalassemia in Guangxi Province, People's Republic of China.

Guangxi Province is located in the southwest of the People's Republic of China (PRC). The province has a population of 50.12 million with a birth rate of 13.31%. Thalassemia is a major health problem in Guangxi Province. About 20.0-25.0% of the population carries thalassemia genes, which is acknowledged to be the highest prevalence in China. National and provincial programs for thalassemia prevention and control have been introduced. Premarital screening and prenatal diagnosis (PND) for the prevention of thalassemic fetuses are available. Blood transfusions, iron chelation therapy, and stem cell transplantation are also available for transfusion-dependent thalassemic patients.

An update on the US adult thalassaemia population: a report from the CDC thalassaemia treatment centres.

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.

A complication risk score to evaluate clinical severity of thalassaemia syndromes.

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase] and left-ventricular ejection fraction (LVEF) for Group A; age (years), age at first chelation (months), ALT and LVEF for Group B; and age (years), mean serum ferritin (SF) levels and LVEF for Group C. The area under the receiver operating characteristic curve was 84·5%, 82·1% and 80·0% for Groups A, Group B and Group C respectively, suggesting the models had good discrimination. Finally, the CoRS for each group was categorised into four risk classes (low, intermediate, high, and very high) using the centiles of its distribution. In conclusion, we have developed a CoRS for TS that can assist physicians in prospectively tailoring patients' treatment.

A Report on the Education, Employment and Marital Status of Thalassemia Patients from a Tertiary Care Center in the Middle East.

Very few reports in the literature have focused on the psychosocial status of patients with thalassemia. The aim of this study was to report on the education, employment, and marital status of thalassemia patients in Lebanon and potential influencing factors. A total of 228 patients from the Chronic Care Center, Hazmieh, Lebanon, were incorporated for the data analysis. Demographic, social, and clinical variables were collected. Statistical analysis was performed using the Pearson χ2 test, Fisher Exact test, and binary logistic regression. In this sample, 54.4% were employed, and 45.6% not employed. Of those employed, 65.3% were male, 62.9% single or divorced, 77.4% splenectomized. University level was reached by 26.3% subjects, 7.9% reached high school level, and 32.5% have a level less than high school. Multivariate analysis revealed higher education was most likely attained by males [odds ratio (OR) = 2.23, 95% confidence interval (95% CI): 0.23-0.86] and those with no heart disease and no joint disease (OR = 27.5, 95% CI: 2.80-270 and OR = 3.40, 95% CI: 0.90-12.7, respectively). For employment, a lower average ferritin was associated with current employment. Neither the type of thalassemia nor transfusion status or type of chelation therapy corresponded with higher education or employment status. In conclusion, this is one of the few studies in the literature to look at education, employment, and marital status of thalassemia patients. Such information is essential to develop effective psychosocial support plans for our thalassemia patients.

Lessons learned from a prenatal diagnosis program for thalassemia in Thailand.

OBJECTIVE: To assess the outcome of a thalassemia screening program at community hospitals by determining the proportion of at-risk couples able to obtain a prenatal diagnosis (PND) in relation to gestational age (GA). METHODS: We accessed records documenting prenatal screening for thalassemia in lower northern Thailand between January 2014 and December 2016. The proportion of at-risk pregnancies able to obtain a PND was determined and median GAs at the time of at-risk notification were compared. Reasons for failures to obtain PNDs were analyzed. RESULTS: Among 4633 screen-positive couples, 259 (5.6%) were identified as at-risk while 23 were excluded due to unconfirmed outcomes. Forty-one declined a PND and were excluded from the final calculations. Of the 195 remaining couples, 140 (71.8%) obtained a PND. Their median GA at the time of at-risk notification was 12.4 (5.6-29.1) weeks, which was earlier than the median GA of 17.7 (6.9-34.6) weeks for couples not undergoing PND (P < .001). Risks for various types of thalassemia and GA were associated with the chances of achieving a PND. CONCLUSION: In practice, one quarter of couples identified as at-risk were unable to obtain a PND. Time-influencing factors seem to be a major determinant.

Optimising management of deferasirox therapy for patients with transfusion-dependent thalassaemia and lower-risk myelodysplastic syndromes.

Effective iron chelation therapy is an important part of treatment in patients with transfusion-dependent thalassaemia and lower-risk myelodysplastic syndromes (MDS). Key strategies for optimising iron chelation therapy include ensuring good adherence and preventing and managing adverse events (AEs). Good adherence to iron chelation therapy with deferoxamine and deferasirox has been linked to improved survival and/or reductions in complications related to iron overload; however, maintaining good adherence to iron chelators can be challenging. Patients with transfusion-dependent thalassaemia or lower-risk MDS showed better adherence to the deferasirox film-coated tablet (FCT) formulation than to the deferasirox dispersible tablet formulation in the ECLIPSE trial, reflecting in part the improved palatability and convenience of deferasirox FCT. As well as affecting adherence, AEs may lead to dose reduction, interruption or discontinuation, resulting in suboptimal iron chelation therapy. Preventing and successfully managing AEs may help limit their impact on adherence, and following dosage and administration recommendations for iron chelators such as deferasirox may help minimise AEs and optimise treatment in patients with transfusion-dependent thalassaemia and lower-risk MDS.

Thalassemia and other hemoglobinopathies among anemic individuals in Metro Manila, Philippines and their intake of iron supplements.

BACKGROUND AND OBJECTIVES: Iron deficiency is the most common cause of anemia worldwide. In Southeast Asia, studies showed that genetic hemoglobin disorders also contribute significantly to the burden of anemia. The study aimed to estimate the proportion of thalassemia and other hemoglobinopathies versus iron deficiency and other causes in a sample of anemic individuals; describe the characteristics of thalassemic subjects in terms of severity of anemia, adequacy of iron stores, and hematological profile; examine the intake of iron supplements among individuals with varying causes of anemia. METHODS AND STUDY DESIGN: A random sample of 101 anemic individuals living in Metro Manila was examined. Hemoglobinopathy was determined using capillary electrophoresis. Iron deficiency was determined using immunoradiometric assay for serum ferritin. A questionnaire was used to obtain information on the use of iron supplements. RESULTS: The most frequent underlying cause of anemia was iron deficiency (37.6%), followed by anemia due to other causes (34.7%), and hemoglobinopathy (27.8%). The most prevalent form of hemoglobinopathy was alpha-thalassemia trait (20.8%), followed by betathalassemia trait (5%), iron deficiency anemia with concomitant HbE (1%), and beta-thalassemia HbE interacting (1%). Thalassemic subjects exhibited mild anemia, had either normal or excessive iron stores, and did not ingest iron supplements. CONCLUSION: The majority of anemia (62.5%) in this sample was due to other causes and hemoglobinopathy, rather than iron deficiency. Genetic hemoglobin disorders appear to be common among anemic individuals. Population screening is needed to determine the real prevalence of the disease. Further investigation is needed to identify other causes of anemia among Filipinos.