• Caregivers
• Low and middle income country
• Pakistan
• Psychological wellbeing
• Quality of life
• Thalassemia

• Humans
• Male
• Female
• Quality of Life
• Pakistan
• Adult
• Thalassemia/psychology
• Thalassemia/ethnology
• Caregivers/psychology
• Child
• Middle Aged
• Parents/psychology
• Surveys and Questionnaires
• Adaptation, Psychological
• Stress, Psychological
• Young Adult
• Cross-Sectional Studies

• Humans
• beta-Thalassemia/complications
• beta-Thalassemia/epidemiology
• beta-Thalassemia/therapy
• Blood Glucose
• Blood Glucose Self-Monitoring
• Diabetes Mellitus/epidemiology
• Diabetes Mellitus/etiology
• Iron Overload/complications

• Cardiac iron deposition
• Children
• Clinical factors
• β-thalassemia major

• Humans
• Child
• beta-Thalassemia/complications
• beta-Thalassemia/diagnosis
• beta-Thalassemia/genetics
• Iron Overload/complications
• Iron Overload/diagnosis
• Iron Overload/pathology
• Retrospective Studies
• ROC Curve
• Magnetic Resonance Imaging/methods
• Iron
• Myocardium/pathology

• 2018YFA0507801 National Key Research and Development Program of China

• Humans
• Global Longitudinal Strain
• Cross-Sectional Studies
• Echocardiography/methods
• Ventricular Function, Left
• Ventricular Dysfunction, Left/diagnostic imaging
• Ventricular Dysfunction, Left/epidemiology
• Stroke Volume
• Cardiomyopathies

• beta‐thalassemia
• cardiac complications
• iron chelators
• multiendocrine dysfunction

• HCV
• hepatocellular carcinoma
• liver transplantation
• thalassemia
• transfusion

• Adherence
• Adverse effects
• Deferasirox
• Deferiprone
• Deferoxamine
• Iron chelation

• Humans
• beta-Thalassemia/therapy
• Iron Chelating Agents/therapeutic use
• Deferiprone/therapeutic use
• Deferoxamine/therapeutic use
• Pyridones/therapeutic use
• Iron Overload/etiology
• Thalassemia/therapy
• Iron/therapeutic use

• Cardiovascular magnetic resonance
• Heart failure
• Left ventricular global function index
• Myocardial iron overload
• Thalassemia major

• ferroptosis
• glucosamine
• high-grade serous ovarian cancer (HGSOC)
• hybrid
• linoleic acid

• COVID-19
• Cardiovascular Diseases/diagnostic imaging
• Echocardiography/methods
• Humans
• Pandemics
• Quality of Life
• Stethoscopes

• Data envelopment analysis
• Malaysia
• Management factors
• Technical efficiency
• Thalassaemia treatment

• Novartis Pharma

• ablation
• arrhythmias
• atrial fibrillation
• chelation
• heart
• hemoglobinopathy
• iron
• supraventricular
• thalassemia

Iron homeostasis is regulated by hepcidin, a hepatic hormone that controls dietary iron absorption and plasma iron concentration. Hepcidin binds to the only known iron export protein, ferroportin (FPN), which regulates its expression. The major factors that implicate hepcidin regulation include iron stores, hypoxia, inflammation, and erythropoiesis. When erythropoietic activity is suppressed, hepcidin expression is hampered, leading to deficiency, thus causing an iron overload in iron-loading anemia, such as β-thalassemia. Iron overload is the principal cause of mortality and morbidity in β-thalassemia patients with or without blood transfusion dependence. In the case of thalassemia major, the primary cause of iron overload is blood transfusion. In contrast, iron overload is attributed to hepcidin deficiency and hyperabsorption of dietary iron in non-transfusion thalassemia. Beta-thalassemia patients showed marked hepcidin suppression, anemia, iron overload, and ineffective erythropoiesis (IE). Recent molecular research has prompted the discovery of new diagnostic markers and therapeutic targets for several diseases, including β-thalassemia. In this review, signal transducers and activators of transcription (STAT) and SMAD (structurally similar to the small mothers against decapentaplegic in Drosophila) pathways and their effects on hepcidin expression have been discussed as a therapeutic target for β-thalassemia patients. Therefore, re-expression of hepcidin could be a therapeutic target in the management of thalassemia patients. Data from 65 relevant published experimental articles on hepcidin and β-thalassemia between January 2016 and May 2021 were retrieved by using PubMed and Google Scholar search engines. Published articles in any language other than English, review articles, books, or book chapters were excluded.

Introduction

Bleeding and thrombotic events are known to occur in beta-thalassemia major (BTM) patients and have been attributed to hepatic iron overload associated with multiple blood transfusions. We evaluated hemostatic parameters in children with BTM who had no previous history of bleeding or thrombotic episodes.

Materials and Methods

Hemostatic parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation, protein C and S, iron profile, and liver function tests were evaluated in 54 children (median age = 12 months, age range = 4-144 months) with BTM and 15 age and sex-matched controls.

Results

The mean PT and APTT of patients were significantly higher (P=0.016 and P <.001) than that of controls. Mean protein C, protein S activity and platelet aggregability with adenosine 5-diphosphate (ADP) as an agonist in patients were significantly lower (P <.001, P <.001 and P=0.007, respectively) than that in controls. Mean serum ferritin in BTM children was not significantly elevated to be associated with hepatic dysfunction.

Conclusion

Deranged hemostatic parameters indicative of bleeding and thrombotic tendencies are observed in BTM children from an early age and may not be solely due to hyperferritinemia-associated hepatic dysfunction. Despite the presence of deranged hemostatic parameters, a state of balance exists between bleeding and thrombosis, and an imbalance may lead to bleeding or thrombotic events at a later age.

• activated partial thromboplastin time
• beta-thalassemia major
• bleeding
• hepatic dysfunction
• hyperferritinemia
• platelet aggregation
• protein c
• protein s
• prothrombin time
• thrombosis

• Pediatrics
• Thalassemia
• Transfer of care
• Transition
• Underrepresented populations

• chelation
• diamond-blackfan
• rare anaemia
• sideroblastic anaemia
• thalassaemia
• transfusion

• FTIR
• Infrared spectroscopy
• Iron accumulation
• Iron overload
• Vibrational spectroscopy

• Animals
• Iron
• Iron Overload/diagnosis
• Iron-Dextran Complex
• Principal Component Analysis
• Rats
• Spectroscopy, Fourier Transform Infrared

Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain synthesis. Patients with β-thalassemia display variable clinical severity which ranges from asymptomatic features to severe transfusion-dependent anemia and complications in multiple organs. They not only are at increased risk of blood-borne infections resulting from multiple transfusions, but they also show enhanced susceptibility to infections as a consequence of coexistent immune deficiency. Enhanced susceptibility to infections in β-thalassemia patients is associated with the interplay of several complex biological processes. β-thalassemia-related abnormalities of the innate immune system include decreased levels of complement, properdin, and lysozyme, reduced absorption and phagocytic ability of polymorphonuclear neutrophils, disturbed chemotaxis, and altered intracellular metabolism processes. According to available literature data, immunological abnormalities observed in patients with thalassemia can be caused by both the disease itself as well as therapies. The most important factors promoting such alterations involve iron overload, phenotypical and functional abnormalities of immune system cells resulting from chronic inflammation oxidative stress, multiple blood transfusion, iron chelation therapy, and splenectomy. Unravelling the mechanisms underlying immune deficiency in β-thalassemia patients may enable the designing of appropriate therapies for this group of patients.

• anemia
• immunological disturbances
• β-thalassemia

• Adaptive Immunity
• Biomarkers
• Disease Susceptibility/immunology
• Genetic Predisposition to Disease
• Humans
• Immune System/immunology
• Immune System/metabolism
• Immunity, Innate
• beta-Thalassemia/genetics
• beta-Thalassemia/immunology

• Autopsy
• iron overload
• secondary hemosiderosis
• β-thalassemia major (β-TM)

• Immuno-senescence
• Neutrophils
• Oxidative biomarkers
• Thalassemia
• Transfusion

• Adult
• Antigens, CD/blood
• Blood Component Transfusion
• Cellular Senescence
• Chelation Therapy
• Female
• Ferritins/blood
• Humans
• Immunophenotyping
• Iron Chelating Agents/therapeutic use
• Leukocyte Count
• Lipid Peroxidation
• Male
• Middle Aged
• Neutrophil Activation
• Neutrophils/chemistry
• Neutrophils/classification
• Neutrophils/immunology
• Respiratory Burst
• Splenectomy
• Toll-Like Receptor 4/blood
• Young Adult
• beta-Thalassemia/blood
• beta-Thalassemia/immunology
• beta-Thalassemia/therapy

• Emergency department
• Iron overload
• Resuscitation
• Thalassemia

• beta-thalassemia major
• biventricular function
• reference values

• Thalassaemia major
• foetal outcome
• hypo-gonadotrophic hypogonadism
• pregnancy
• reproductive health

To determine whether serum ferritin, liver transaminases, and regularity and type of iron chelation protocol can be used to predict liver iron load as assessed by T2* magnetic resonance imaging (MRI) in patients with beta thalassemia major (TM).

This cross-sectional study, conducted from March 1, 2014 to March 1, 2015, involved 90 patients with beta TM on regular packed red blood cell transfusion. Liver and cardiac iron load were evaluated with T2* MRI. Compliance with iron-chelating agents, deferoxamine or deferasirox, and regularity of their use, as well as serum ferritin and liver transaminase levels were assessed.

Patients with high serum ferritin were 2.068 times (95% confidence interval 1.26-3.37) more likely to have higher liver or cardiac iron load. High serum aspartate aminotransferases and irregular use of iron chelating agents, but not their type, predicted higher cardiac iron load. In a multiple regression model, serum ferritin level was the only significant predictor of liver and myocardial iron load.

Higher serum ferritin strongly predicted the severity of cardiac and liver iron load. Irregular use of chelator drugs was associated with a higher risk of cardiac and liver iron load, regardless of the type of chelating agent.

• fertility preservation
• genetic diseases
• ovarian tissue cryopreservation
• sickle cell disease
• thalassemia

• Adolescent
• Adult
• Anemia, Sickle Cell/complications
• Case-Control Studies
• Child
• Child, Preschool
• Cryopreservation/methods
• Female
• Fertility Preservation/methods
• Humans
• Infant
• Infertility, Female/therapy
• Oocytes/cytology
• Oocytes/physiology
• Ovarian Follicle/cytology
• Ovarian Follicle/physiology
• Young Adult
• beta-Thalassemia/complications

• Beta cell function
• Glucose dysregulation
• Pancreatic iron
• Thalassemia

• Adolescent
• Adult
• Child
• Diabetes Mellitus/diagnosis
• Diabetes Mellitus/physiopathology
• Glucose Tolerance Test
• Humans
• Insulin Resistance/physiology
• Insulin Secretion/physiology
• Insulin-Secreting Cells/physiology
• Iron/analysis
• Iron/metabolism
• Liver/chemistry
• Pancreas/chemistry
• Pancreas/metabolism
• Risk Factors
• Young Adult
• beta-Thalassemia/physiopathology

Endocrinopathies are common in patients with β-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in β-thalassemia major based on a meta-analysis.

PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in β-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with β-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted.

A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in β-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in β-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias.

High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in β-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

Thalassemia incorporates a broad clinical spectrum characterized by decreased or absent production of normal hemoglobin leading to decreased red blood cell survival and ineffective erythropoiesis. Chronic iron overload remains an inevitable complication resulting from regular blood transfusions (transfusion-dependent) and/or increased iron absorption (mainly non-transfusion-dependent thalassemia), requiring adequate treatment to prevent the significant associated morbidity and mortality. Iron chelation therapy has become a cornerstone in the management of thalassemia patients, leading to improvements in their outcome and quality of life. Deferasirox (DFX), an oral iron chelating agent, is approved for use in transfusion dependent and non-transfusion-dependent thalassemia and has shown excellent efficacy in this setting. We herein present an updated review of the role of deferasirox in thalassemia, exploring over a decade of experience, which has documented its effectiveness and convenience; in addition to its manageable safety profile.

• Deferasirox
• Iron chelation therapy
• Iron overload
• Liver iron concentration
• Non-transfusion dependent thalassemia
• Serum ferritin
• Transfusion dependent thalassemia

Thalassemia is a common genetic disease in Iran, especially in the north and south of Iran. The present study sought to determine the survival rate of patients with thalassemia in highly endemic regions of Iran and its variation in patients born before and after 1971.

The present historical cohort study extracted data from the health records of patients with beta-thalassemia major, beta-thalassemia intermedia, and sickle beta-thalassemia who had presented to thalassemia treatment centers in the past years. The collected data were analyzed using the Kaplan-Meier test, the log-rank test, and the chi-square test.

Of the total of 5,491 medical records (2,647 men and 2,634 women; mean age, 23.81±11.32 years), 3,936 belonged to patients with beta-thalassemia major, and 999 and 89 to patients with beta-thalassemia intermedia and sickle beta-thalassemia, respectively. In 467 cases, the type of thalassemia was not clear. The cumulative survival rate was calculated as 0.92, 0.83, 0.74, and 0.51 by ages 25, 35, 45, and 55, respectively. The hazard ratio of death was 4.22 (p<0.05) for beta-thalassemia major and 0.77 for beta-thalassemia intermedia (p=0.70). It was calculated as 1.45 for men patients and as 3.82 for single patients.

The present study showed relatively high survival rates in patients with thalassemia. The survival of patients was unfavorable in poorer regions (Zahedan and Iranshahr). Factors including women gender, a higher level of education, being married, and living in metropolises decreased the risk of death at younger ages and improved survival.

• Beta-thalassemia
• Gender
• Iran
• Prevalence
• Survival

• Beta thalassemia
• Bioethics
• Genetics
• History of medicine
• Precision medicine
• Primary immunodeficiency
• Spinal muscular atrophy
• X-severe combined immunodeficiency

• Algorithms
• Anemia, Sickle Cell/complications
• Biomarkers
• Humans
• Iron/metabolism
• Iron Chelating Agents/therapeutic use
• Iron Overload/diagnosis
• Iron Overload/etiology
• Iron Overload/metabolism
• Iron Overload/therapy
• Liver/diagnostic imaging
• Liver/metabolism
• Liver/pathology
• Magnetic Resonance Imaging/methods
• Pancreas/diagnostic imaging
• Pancreas/metabolism
• Pancreas/pathology

• R01 DK097115 NIDDK NIH HHS
• UL1 TR000130 NCATS NIH HHS

To evaluate efficacy, safety and utilization pattern of deferasirox in paediatric patients of transfusion dependant β Thalassemia Major at a tertiary care teaching hospital in Gujarat.

This observational, prospective-retrospective, single centre, continuous study was conducted in a tertiary care teaching hospital among paediatric patients of transfusion dependent β Thalassemia Major. Patients treated with deferasirox for not more than 12 weeks were enrolled. Details of blood transfusions, relevant investigations performed every 3 weeks and 3 months and drugs used were recorded in a pretested case record form. Parents were provided with a diary to record the details of ADRs. Data were analyzed for demographic characteristics, number and mean volume of blood transfusions, changes in serum ferritin and iron levels, number and types of ADRs and progression, causality, severity and preventability of ADRs.

Of the 60 patients enrolled, one patient was lost to follow up and four withdrew their consent. Of the remaining 55 patients, 36 were boys and 19 were girls (mean age: 6 ± 3.14 years), including patients of 1-3 years (11), 4-6 years (24), 7-10 years (12) and 11-12 years (8). Thirty six patients were born of consanguineous marriages. Adherence to blood transfusion guidelines and deferasirox prescribing and administration guidelines was observed. A serial and significant decrease in mean serum ferritin and serum iron at 3 weeks and 3 months with deferasirox treatment was observed in all age groups except that of 11-12 years. A total of 117 ADRs were observed in 52 patients from 19498 doses, most common being diarrhea (24), raised serum creatinine (15), raised hepatic enzymes (14), abdominal pain (14) and rashes (14). A reduction in dose was required in 32 cases, while a temporary stoppage was indicated in 41 cases. Deferasirox was the possible and probable cause of 65 and 51 ADRs respectively as assessed by WHO-UMC scale. Majority of ADRs were definitely preventable and mild in nature.

β Thalassemia Major is more common in males. A rational prescribing of deferasirox was observed. Deferasirox effectively reduced serum ferritin and serum iron levels in these patients.

• Adverse drug reactions
• blood transfusion
• deferasirox
• iron chelators
• thalassemia

• deferasirox
• deferiprone
• deferoxamine
• iron chelation
• magnetic resonance imaging
• transfusional iron overload

• Beta globin
• Hemoglobin
• Iron overload
• Sickle cell disease
• β-thalassemia

• Taiwan
• complication
• national health insurance
• survival
• thalassemia major

• Adolescent
• Adult
• Chelation Therapy/mortality
• Child
• Child, Preschool
• Cohort Studies
• Combined Modality Therapy
• Erythrocyte Transfusion/mortality
• Female
• Hematopoietic Stem Cell Transplantation/mortality
• Humans
• Infant
• Infant, Newborn
• Longitudinal Studies
• Male
• Middle Aged
• Prognosis
• Survival Rate
• Taiwan/epidemiology
• Young Adult
• beta-Thalassemia/complications
• beta-Thalassemia/epidemiology
• beta-Thalassemia/mortality
• beta-Thalassemia/therapy