The predicting formula and scoring system for cardiac iron overload for thalassaemia children: Study from a middle-income country.

Magnetic resonance imaging T2* screening is the gold standard for detecting cardiac iron overload in thalassemia, but its implementation in Indonesia is limited by the high costs. A predicting formula and scoring system based on low-cost investigations is needed. This cross-sectional study was conducted among thalassemia aged 6-18 years at Rumah Sakit Anak dan Bunda RSAB Harapan Kita Indonesia, during October 2017 to April 2019. All subjects were scheduled for clinical examination, laboratory tests, ECGs, echocardiography, tissue Doppler imaging, and MRIT2*. Multivariate logistic regression was used to identify the formula, simplifying to a scoring system, and risk classification for myocardial iron overload using odds ratio (OR) and 95% confidence interval (CI). Significance was set as p<0,05. We recruited 80 children, of those, 8 (10%) were classified as cardiac iron overload based on MRI T2* screening. Multivariate logistic regression showed determinant factors for cardiac iron overload were hemoglobin (95% CI:1.92-369.14), reticulocyte (95% CI:1.14-232.33), mitral deceleration time (DT) (95% CI:1.80-810.62,), and tricuspid regurgitation (TR Vmax) (95% CI:1.87-1942.56) with aOR of 26.65, 14.27, 38.22, and 60.27 respectively. The formula for cardiac iron overload was decided as 9.32 + 3.28 (Hb) + 2.9 (reticulocyte) + 3.64 (DT) + 4.1 (TR Vmax). A scoring system was defined by simplifying the formula of Hb ≤ 8.2 g/L, reticulocyte ≤0.33%, DT ≤ 114.5 cm/s, and TR Vmax ≥ 2.37 m/s were given a score of 1, while others were assigned 0. Total scores of 0 or 1, 2 and 3 or 4 were categorized as low, moderate, and high risk for iron cardiac overload. The cardiac iron overload formula was 9.32 + 3.28 (Hb) + 2.9 (reticulocyte) + 3.64 (DT) + 4.1 (TR Vmax). Variables of Hb ≤ 8.2 g/L, reticulocyte ≤0.33%, DT ≤ 114.5 cm/s, and TR Vmax ≥ 2.37 m/s were given a score of 1, while others were assigned 0. Total scores of 0 or 1, 2, and 3 or 4 were categorized as low, moderate, and high risk for iron cardiac overload.

Comorbidities and complications in adult and paediatric patients with pyruvate kinase deficiency: Analysis from the Peak Registry.

Pyruvate kinase (PK) deficiency, a rare, congenital haemolytic anaemia caused by mutations in the PKLR gene, is associated with many clinical manifestations, but the full disease burden has yet to be characterised. The Peak Registry (NCT03481738) is an observational, longitudinal registry of adult and paediatric patients with PK deficiency. Here, we described comorbidities and complications in these patients by age at most recent visit and PKLR genotype. As of 13 May 2022, 241 patients were included in the analysis. In total, 48.3% had undergone splenectomy and 50.5% had received chelation therapy. History of iron overload (before enrolment/during follow-up) was common (52.5%), even in never-transfused patients (20.7%). Neonatal complications and symptoms included jaundice, splenomegaly and hepatomegaly, with treatment interventions required in 41.5%. Among adults, osteopenia/osteoporosis occurred in 19.0% and pulmonary hypertension in 6.7%, with median onset ages of 37, 33 and 22 years, respectively. Biliary events and bone health problems were common across PKLR genotypes. Among 11 patients who had thromboembolic events, eight had undergone prior splenectomy. Patients with PK deficiency may have many complications, which can occur early in and throughout life. Awareness of their high disease burden may help clinicians better provide appropriate monitoring and management of these patients.

High ferritin is associated with liver and bone marrow iron accumulation: Effects of 1-year deferoxamine treatment in hemodialysis-associated iron overload.

BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.

Myelin endocytosis by brain endothelial cells causes endothelial iron overload and oligodendroglial iron hunger in hypoperfusion-induced white matter injury.

AIMS: Hypoperfusion induces significant white matter injury in cerebral vascular disorders, including arteriosclerotic cerebral small vessel disease (aCSVD), which is prevalent among the elderly. Iron transport by blood vessel endothelial cells (BVECs) from the periphery supports oligodendrocyte maturation and white matter repair. This study aims to elucidate the association between iron homeostasis changes and white matter injury severity, and explore the crosstalk between BVECs and oligodendroglial lineage cells. METHODS: In vivo: C57BL/6 mice were subjected to unilateral common carotid artery occlusion (UCCAO). In vitro: BVECs with myelin pretreatment were co-cultured with oligodendrocyte progenitor cells (OPCs) or organotypic cerebellar slices subjected to oxygen and glucose deprivation. RESULTS: Circulatory iron tends to be stored in aCSVD patients with white matter injury. Myelin debris endocytosis by BVECs impairs iron transport, trapping iron in the blood and away from the brain, worsening oligodendrocyte iron deficiency in hypoperfusion-induced white matter injury. Iron accumulation in BVECs triggers ferroptosis, suppressing iron transport and hindering white matter regeneration. Intranasal holo-transferrin (hTF) administration bypassing the BBB alleviates oligodendrocyte iron deficiency and promotes myelin regeneration in hypoperfusion-induced white matter injury. CONCLUSION: The iron imbalance between BVECs and oligodendroglial lineage cells is a potential therapeutic target in hypoperfusion-induced white matter injury.

Transfusional hemosiderosis in childhood cancer patients and survivors.

BACKGROUND: Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. OBJECTIVE: This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. METHODS: This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. RESULTS: Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p = .0043) and pituitary iron (p = .0101). In the 73 off-therapy patients, ferritin levels were lower (p = .0008) with higher correlation with liver iron concentration (LIC) (p = .0016) than on-therapy patients. Fifty-eight subjects were treated for IO. CONCLUSION: In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.

[Clinical analysis on the impact of pretransplant iron overload on allogeneic hematopoietic stem cell transplantation for patients with acquired severe aplastic anemia in pediatric].

This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children's Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 µg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34(+) cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade Ⅲ-Ⅳ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.

Association of serum iron metabolism with muscle mass and frailty in older adults: A cross-sectional study of community-dwelling older adults.

This study aimed to explore the correlation between serum ferritin and additional biomarkers associated with iron metabolism, as well as their connection to muscle atrophy and frailty in the community-dwelling middle-aged and elderly population. The study included 110 middle-aged and elderly participants. Participants were categorized into an iron accumulation group (31 cases) and a normal iron group (79 cases) based on the standard ferritin values for men and women. Based on the criteria of the Asian Working Group on Muscular Dystrophy, participants were classified into a sarcopenia group (31 cases) and a non-sarcopenia group (79 cases). Using the Fried frailty syndrome criteria, participants were categorized into non-frailty (7 cases), pre-frailty (50 cases), and frailty (53 cases) groups. We employed multiple linear regression, binary logistic regression, partial correlation analysis, and ordinal logistic regression to assess the associations between iron metabolism indices and the presence of muscle atrophy and frailty. Compared with the normal iron group, the iron overload group had significantly higher ferritin, weight loss, fatigue, slow gait, and frailty scores (P < .05). Among the 3 models we set, ferritin was not significantly correlated with muscle mass in models 1 and 3 (P > .05), ferritin was positively correlated with muscle mass in model 2 (Pmodel2 = .048), but Transferrin saturation was positively correlated with muscle mass in all 3 models (Pmodel1 = .047, Pmodel2 = .026, Pmodel3 = .024). Ferritin, body mass index and iron overload were the influencing factors of sarcopenia (Pferritin = .027, PBMI < .001, Piron overload = .028). Ferritin was positively correlated with weight loss, fatigue, slow gait, frailty score, and frailty grade (P < .05). Age, gender and ferritin were the influencing factors of frailty classification (P < .05). Disrupted iron metabolism can lead to decreased muscle mass and function among the middle-aged and elderly, increasing frailty risk. It's crucial to prioritize community-based frailty screening and prevention, focusing on iron utilization as well as storage, since accelerating the body's iron metabolism cycle might influence muscle health more significantly than iron reserves.

Impact of Serum Ferritin and Iron Overload on Acute Myeloid Leukemia Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the iron overload among individuals with acute myeloid leukemia (AML) who have not received red blood cell transfusions. METHODS: A comprehensive search was conducted in Embase, PubMed, PubMed Central, Web of Science, NIH, and Blood Library databases up to September 2023. The search strategy included keywords related to AML, iron overload, serum ferritin, survival, outcomes, and inflammation. Manual searches through included articles and relevant references were also performed. From 1650 initial articles, 16 studies involving 8752 patients met the inclusion criteria for systematic review. Statistical analysis used hazard ratios (HR) and confidence intervals (CI).  Results: The systematic review and meta-analysis revealed a statistically significant association between high serum ferritin (SF) levels and poor outcomes in AML patients before starting chemotherapy. Elevated SF levels (>1000 mg/L) were associated with lower overall survival (OS) and event-free survival (EFS) (HR for OS: 1.99, 95% CI: 1.48-2.66; HR for EFS: 2.29, 95% CI: 1.73-3.05). Elevated SF levels were inversely correlated with the gradual onset of infections, indicating an increased risk of early mortality (p<0.05). CONCLUSION: Elevated serum ferritin levels are significantly associated with poor outcomes in AML patients before treatment initiation. These findings highlight the importance of monitoring iron levels in these patients to improve prognostic assessments and treatment strategies.

Macrophage-derived extracellular vesicles represent a promising endogenous iron-chelating therapy for iron overload and cardiac injury in myocardial infarction.

BACKGROUND: Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts. RESULTS: In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver. CONCLUSIONS: These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases.

Skin complications during iron chelation therapy for beta-thalassemia: overview and treatment approach.

Thalassemia is an inherited genetic disorder of hemoglobin that affects a large population worldwide, and it is estimated that between 50,000 and 60,000 infants with thalassemia are born each year. The most common treatment for thalassemia is blood transfusion, which leads to iron overload. This in itself is a serious clinical condition, and is commonly managed with iron chelation therapy. However, iron chelators can cause various skin complications, including hyperpigmentation, skin rash, itching, and photosensitivity. These skin side effects can impact patients' quality of life. Therefore, this article provides a comprehensive overview of skin complications caused by iron chelators, along with a proposed comprehensive approach to their management in patients with beta-thalassemia. Key strategies include patient education, regular skin assessment, sun protection measures, symptomatic relief with topical corticosteroids and antihistamines, and consideration of treatment modification if severe complications occur. Collaboration between hematologists and dermatologists, along with psychological support and regular follow-up, is an essential component of this multidisciplinary approach. By implementing these strategies, healthcare providers can optimize skin care for patients with beta-thalassemia treated with iron chelators and improve their quality of life.

Astragaloside IV attenuates ferroptosis and protects against iron overload-induced retinal injury.

Retinal injury may be exacerbated by iron overload. Astragaloside IV (AS-IV) has potential applications in the food and healthcare industry to promote eye health. We sought to determine the mechanisms responsible for the protective effects of AS-IV on photoreceptor and retinal pigment epithelium cell death induced by iron overload. We conducted in vitro and in vivo experiments involving AS-IV pretreatment. We tested AS-IV for its ability to protect iron-overload mice from retinal injury. In particular, we analyzed the effects of AS-IV on iron overload-induced ferroptosis in 661W and ARPE-19 cells. AS-IV not only attenuated iron deposition and retinal injury in iron-overload mice but also effectively reduced iron overload-induced ferroptotic cell death in 661W and ARPE-19 cells. AS-IV effectively prevented ferroptosis by inhibiting iron accumulation and lipid peroxidation. In addition, inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) eliminated the protective effect of AS-IV against ferroptosis. The results suggest that ferroptosis might be a significant cause of retinal cell death associated with iron overload. AS-IV provides protection from iron overload-induced ferroptosis, partly by activating the Nrf2 signaling pathway.

[MRI-Based Assessment of Hepatic Iron Overload and Steatosis in Patients Undergoing Hemodialysis:Current Status,Challenges,and Perspectives].

Long-term treatment of anemia involving frequent blood transfusions and intravenous iron administration increases the risks of hepatic iron overload and steatosis in the patients undergoing hemodialysis.Pathological accumulation of iron damages hepatocytes,not only elevating the risks of progressive hepatic fibrosis and cirrhosis but also potentially accelerating the process of hepatic steatosis.Iron overload and steatosis may interact with each other,exacerbating liver damage and ultimately leading to further deterioration of hepatic fibrosis and cirrhosis.MRI characterized by non-invasiveness and high repeatability,enables the simultaneous quantitative assessment of hepatic iron and fat content,providing crucial information for early diagnosis and intervention of liver diseases.In recent years,researchers have achieved significant advances in the application of MRI in the diagnosis and treatment of liver diseases.MRI can accurately reflect the extent of hepatic iron overload and steatosis in patients and predict the risk of liver diseases.This article reviews the latest advances,challenges,and perspectives in the application of MRI in assessing hepatic iron overload and steatosis in the patients undergoing hemodialysis,aiming to offer valuable references for clinical practice.

SiO 2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model.

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model. Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.

Clinical efficacy of thalidomide for various genotypes of beta thalassemia.

OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of ß-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. METHODS: From our initial sample of 52 patients, we observed 48 patients with ß-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with ßCD41-42/ßCD17 and 6 cases with ßCD41-42/ß-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001). CONCLUSION: In this study, we identified 10 ß-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.

Cross-sectional study on the impact of cardiac and hepatic iron overload, as measured by MRI T2*, on the quality of life in children with severe beta-thalassemia major.

A cross-sectional study to explore the correlation between cardiac and hepatic iron overload and its impact on the quality of life in children diagnosed with severe beta-thalassemia major (ß-TM). A cohort of 55 pediatric patients with ß-TM, diagnosed via genetic testing at the Affiliated Hospital of Guangdong Medical University from January 2015 to January 2022, was included in this study. The assessment of cardiac and hepatic iron overload was conducted using the magnetic resonance imaging T2* technique. The Chinese version of the Pediatric Quality of Life Inventory (PedsQL) 4.0. Pearson correlation analysis was utilized to assess the relationships between the cardiac and hepatic T2* values and between these T2* values and the total scores of PedsQL 4.0. Analysis showed no significant correlation between cardiac and hepatic T2* values. However, a significant relationship was observed between cardiac T2* values and PedsQL 4.0 total scores (r = 0.313, P < .05), indicating that cardiac, but not hepatic, iron overload is associated with the quality of life. This study highlights the absence of correlation between cardiac and hepatic iron overload levels and demonstrates a significant impact of cardiac iron overload on the quality of life in children with ß-TM. These findings suggest the need for a focused approach to cardiac health in managing ß-TM.

Iron Chelators and Alzheimer's Disease Clinical Trials.

Alzheimer's disease (AD) is a major neurodegenerative disorder impacting millions of people with cognitive impairment and affecting activities of daily living. The deposition of neurofibrillary tangles of hyperphosphorylated tau proteins and accumulation of amyloid-ß (Aß) are the main pathological characteristics of AD. However, the actual causal process of AD is not yet identified. Oxidative stress occurs prior to amyloid Aß plaque formation and tau phosphorylation in AD. The role of master antioxidant, glutathione, and metal ions (e.g., iron) in AD are the frontline area of AD research. Iron overload in specific brain regions in AD is associated with the rate of cognitive decline. We have presented the outcome from various interventional trials involving iron chelators intended to minimize the iron overload in AD. To date, however, no significant positive outcomes have been reported using iron chelators in AD and warrant further research.

Anemia and iron overload as prognostic markers of outcomes in ß-thalassemia.

INTRODUCTION: Ineffective erythropoiesis and subsequent anemia as well as primary and secondary (transfusional) iron overload are key drivers for morbidity and mortality outcomes in patients with ß-thalassemia. AREAS COVERED: In this review, we highlight evidence from observational studies evaluating the association between measures of anemia and iron overload versus outcomes in both non-transfusion-dependent and transfusion-dependent forms of ß-thalassemia. EXPERT OPINION: Several prognostic thresholds have been identified with implications for patient management. These have also formed the basis for the design of novel therapy clinical trials by informing eligibility and target endpoints. Still, several data gaps persist in view of the challenge of assessing prospective long-term outcomes in a chronic disease. Pooling insights on the prognostic value of different measures of disease mechanism will be key to design future scoring systems that can help optimize patient management.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients.

INTRODUCTION: Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. MATERIAL AND METHOD: MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. RESULT: Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). CONCLUSION: An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.