Complications Of Iron Overload Research Articles

Impact of Empagliflozin on the Outcomes of β-Thalassemia Major in Patients With Type 2 Diabetes Mellitus: The THALEMPA Observational Study.

Beta-thalassemia major (β-TM) is a genetic disorder characterized by ineffective erythropoiesis and chronic hemolytic anemia, necessitating lifelong blood transfusions and leading to severe complications. This study, termed THALEMPA by the authors, investigated the effect of empagliflozin (EMPA) on β-TM outcomes in patients with type 2 diabetes mellitus (T2DM), focusing on disease severity and associated complications of iron overload and hyperuricemia. This study conducted a single-center prospective observational investigation involving adults diagnosed with β-TM and T2DM. A total of 20 carefully selected patients were stratified into two groups based on their medical condition: the EMPA group, receiving 10 mg of empagliflozin, and a control group, receiving standard care. This focused cohort size was chosen to ensure a detailed, in-depth analysis of the treatment effects within this specific patient population. Over three months, both groups were closely monitored for β-TM outcomes. The study assessed β-TM severity parameters such as hemoglobin levels, blood transfusion frequency, aspartate aminotransferase (AST), alanine aminotransferase (ALT), left ventricular ejection fraction percentage, and spleen size. Additionally, β-TM complications were evaluated through serum ferritin and uric acid levels. Our analysis revealed that EMPA increased hemoglobin levels by up to 0.56 g/dL compared to baseline (P< 0.05). Liver enzyme levels significantly improved with EMPA by the third month. AST and ALT decreased by 36.22% and 33.36%, respectively, from baseline levels (P< 0.05), highlighting EMPA's potential benefits for β-TM severity. Serum ferritin and uric acid levels decreased by 27.93% and 21.29%, respectively, over three months on EMPA (P< 0.05). However, other parameters did not show significant changes post-EMPA. This study demonstrates the significant impact of EMPA treatment over three months on β-TM patients with T2DM, evidenced by notable improvements in hemoglobin levels and reductions in liver enzymes, as well as in complications related to iron overload and hyperuricemia. Future research should confirm these benefits over longer durations and assess broader patient outcomes such as quality of life.

The Genetic Diagnostics of Hemochromatosis: Disparities in Low- Versus High-Income Countries.

This study provides a comprehensive overview of hereditary hemochromatosis (HH), a genetic condition characterized by iron overload due to excessive iron absorption. It elucidates diverse inheritance patterns and clinical manifestations by exploring mutations in critical genes such as HFE (hemochromatosis), HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide), TfR2 (transferrin receptor 2), and FP (ferroportin). The significance of early screening, diagnosis, and personalized management strategies based on genetic classification is emphasized, particularly in terms of high-income vs. low-income countries. Addressing challenges in diagnosis, genetic testing accessibility, and healthcare disparities, the study highlights the importance of early detection, cost-effective screening strategies, and enhancing healthcare outcomes globally. Advanced genetic testing in high-income countries facilitates early diagnosis and management, reducing complications such as liver disease and cardiomyopathy. In contrast, low-income populations face several barriers, including limited access to genetic testing, high costs, and inadequate healthcare infrastructure. Cost-effective serum ferritin (SF) and transferrin saturation (TS) tests and emerging point-of-care (POC) tests offer affordable diagnostic options for low-resource settings. Additionally, the ongoing development of hepcidin measurement methods holds promise for enhancing diagnostic capabilities. Implementing these strategies can aid healthcare providers in improving global HH management and reducing the burden of iron overload complications. Furthermore, the study underscores the need for public health initiatives to raise awareness about HH, promote routine screenings, and advocate for equitable healthcare policies. Collaborative efforts between governments, healthcare organizations, and research institutions are crucial in addressing the global burden of HH. By fostering international cooperation and resource-sharing, it is possible to bridge the gap between high-income and low-income countries, ensuring all individuals have access to the necessary diagnostic and treatment options. This holistic approach can ultimately lead to better health outcomes and improved quality of life for individuals affected by HH worldwide. This comprehensive examination of HH not only illuminates the genetic and clinical aspects of the condition but also provides a roadmap for addressing the multifaceted challenges associated with its diagnosis and management.

Impact of Degree and Duration of Iron Overload on Incidence of Diabetes Mellitus, Cardiac Disease, and Death in Congenital Hemolytic Anemias

Introduction : Iron overload and its complications are recognized to be morbid and fatal in patients with congenital hemolytic anemias. Much of what is assumed regarding the long-term complications of iron overload in these patients is extrapolated from other patient populations, primarily those with hereditary hemochromatosis. In patients with iron overload caused by congenital hemolytic anemias, there has been no study evaluating the dose-response relationship between serum markers of iron overload and long-term health complications. Filling this critical gap was the aim of the present study. Methods :We evaluated outcomes in a 5-hospital observational cohort study of adults with congenital hemolytic anemias diagnosed with iron overload over a 40-year period (1983-2023). Patients were identified via electronic database query, and eligibility was confirmed and data collection performed via manual chart review. Multivariable logistic modeling was used to assess the associations between depth of iron overload (as measured by lifetime peak ferritin measurement) or duration of iron overload (as measured by years of ferritin &amp;gt;500 ng/mL and &amp;gt;1000/mL) and complications of iron overload, including diabetes mellitus, heart disease, malignancy, and bone density disorders (osteopenia and osteoporosis), as well as death. Results : Patients and Iron Overload Exposure: 184 patients with congenital hemolytic anemias developing iron overload were included. Median (range) age was 32 (2-75) years at iron overload diagnosis and 105 patients (57%) were female. The cohort included 94 patients with sickle cell disease (51%), 30 patients with beta-thalassemia major (16%), and 60 patients with another hemolytic anemia (including thalassemia intermedia, hemoglobin H disease, and others). The cohort included a total of 2,139 patient-years of iron overload exposure (mean 11.6 years per patient). Association of Degree and Duration of Iron Overload with Development of Complications: During the observation period, 47 patients (26%) developed diabetes mellitus, 39 patients (21%) developed cardiac disease, 50 patients (27%) developed a bone density disorder, and 16 patients (8.7%) developed malignancy. More years experienced of ferritin &amp;gt;500 ng/mL and &amp;gt;1000 ng/mL were associated with development of diabetes mellitus with adjusted odds ratios (OR) (95% confidence interval [CI]) of 2.65 (1.12-6.08) per 10-year increment, P=0.025 and 3.76 (1.38-9.33) per 10-year increment, P=0.010, respectively (FIGURE 1). Similarly, more years experienced of ferritin &amp;gt;1000 ng/mL were associated with development of cardiac disease (adjusted OR [95% CI] 3.88 [1.51-9.96] per 10-year increment, P=0.005 [FIGURE 2]). Peak lifetime ferritin of &amp;gt;10000 ng/mL was associated with over 7-fold odds of development of both diabetes and cardiac disease ( P=0.013 and P=0.011, respectively; FIGURES 1 &amp; 2). No associations were observed between duration or degree of iron overload and development of malignancy or bone density disease. Association of Degree and Duration of Iron Overload with Death: During the observation period, 33 patients (18%) died. Peak lifetime ferritin of &amp;gt;10000 ng/mL was associated with over 9-fold odds of death (adjusted OR [95% CI], 9.06 [1.85-44.39], P=0.007). More years experienced of ferritin &amp;gt;1000 ng/mL were associated with death (adjusted OR [95% CI], 2.66 [0.99-7.17] per 10-year increment, P=0.053). Conclusions :In models controlling for sex, years of iron overload exposure, and underlying congenital hemolytic anemia, both the degree (as measured by peak lifetime ferritin) and duration (as measured by years of ferritin above 500 or 1000 ng/mL) of iron overload were associated with markedly increased odds of diabetes mellitus and cardiac disease, but not bone density disease or malignancy, in iron overloaded patients with congenital hemolytic anemias. While greater severity of iron overload was in general required for development of heart disease, prolonged exposure to relatively modest iron overload (serum ferritin &amp;gt;500 ng/mL) was associated with 3-fold increased odds of diabetes. Our findings emphasize the need for aggressive iron chelation therapy in these patients, highlight potential differences in risk of complications between these patients and those with hereditary hemochromatosis, and provide novel and valuable prognostic data for clinicians as they counsel patients.

Adults with Transfusion-Dependent Thalassemia Have Variable Clinical Profiles Depending on Where They Receive Care: Thalassemia Treatment Center Vs Community

Introduction: Advances in the treatment of transfusion-dependent thalassemia (TDT) have decreased complications and improved survival. Established TDT guidelines have improved outcomes through regular red cell transfusions to maintain a pre-transfusion hemoglobin &amp;gt; 9-9.5 g/dL and chelation to maintain a serum ferritin &amp;lt; 1500 ng/mL, liver iron content &amp;lt; 5 mg/g dry weight and a cardiac T2*&amp;gt; 20 ms. Increased lifespan of individuals with TDT now necessitates adult hematology providers with capacity to manage uncomplicated thalassemia. While it is recommended that thalassemia care be provided through a multidisciplinary thalassemia treatment center (TTC), there are a limited number of TTCs in the United States. As a result many adults with TDT receive care in the community from hematologists with variable knowledge and experience with thalassemia. In this study, we thus sought to evaluate the prior care of patients referred to an adult TTC in order to determine if there was a significant difference in the care provided by a pediatric TTC compared to community hematologists. Methods: We evaluated adult patients (&amp;gt; 18 years old) with a diagnosis of TDT referred to the Penn Comprehensive Adult Thalassemia Program. Patients were either referred from the Children's Hospital of Philadelphia TTC via a dedicated transition program, or from community hematologists (Comm). Data collection was performed via manual chart review. Data collected included the mean of three consecutive pre-transfusion hemoglobin levels prior to the initial visit, serum ferritin, and most recent liver and cardiac iron quantitation by MRI. Results: Of the 94 patients with thalassemia referred to the adult program between 2013 and 2023, 54 had a diagnosis of TDT. Twenty-seven patients were referred each from the TTC and the community. At the initial adult thalassemia center visit, the median age was 38.5 years (TTC) and 28 years (Comm). More patients in the TTC group maintained a pre-transfusion Hgb &amp;gt; 9 g/dL (78% vs 52%). Serum ferritin trended lower in the TTC group (1725 vs 2629 ng/ml, p-value = 0.056). While 67% of the TTC group had a serum ferritin &amp;lt; 1500 ug/mL compared to 41% in the Comm group, there was no significant difference in the liver iron content between both groups (TTC 10.2 vs Comm 12.2 mg/g dry weight). However, 60% of the TTC group compared to 48% in the Comm group had a LIC &amp;lt; 5. Those followed at the TTC possibly have more cardiac iron with 4 vs 1 patient in the TTC vs Comm group having a T2* &amp;lt; 20 ms, likely reflective of more complicated patients being referred to the TTC. Conclusion : Patients managed by a TTC were more likely to be adequately transfused with serum ferritins &amp;lt; 1500 ng/mL. Maintaining a pre-transfusion hemoglobin &amp;gt; 9-9.5 g/dL and a serum ferritin &amp;lt; 1500 ng/mL are known to reduce long-term complications of chronic anemia, ineffective erythropoiesis and iron overload in thalassemia. Thus in order to improve long-term outcomes in patients with TDT, we propose that all adult hematology providers, regardless of care setting should aim to gain knowledge on the management of individuals with thalassemia and establish collaborative care relationships with experts in thalassemia care.

Complications in patients with transfusion dependent thalassemia: A descriptive cross-sectional study.

One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion-dependent beta-thalassemia. This descriptive cross-sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta-thalassemia major with frequent blood transfusions. To evaluate the effect of iron overload on vital body organs, hematologic and blood analysis, echocardiography with measurement of pulmonary artery pressure (PAP) and ejection fraction (EF) tests, bone densitometry, and audiometric tests were performed for all patients. Of the 1010 patients participating in this study, 497 (49%) were males, 513 were (51%) females aged 5-74 years, and the majority of participants (85%) were over 20 years old. This study demonstrated that increasing ferritin levels had no notable correlation with sex, cholesterol, low-density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. However, elevating ferritin levels had significant correlations with increasing triglyceride, phosphorus, thyroid stimulating hormone, alkaline phosphatase, alanine transaminase, and PAPlevels, age, hearing disorders, splenectomy, osteoporosis, and decreasing high-density lipoprotein, body mass index, calcium, and EFlevels. Improvement in beta-thalassemia patients' survival and quality of life can be due to multidisciplinary care in a comprehensive unit through regular follow-up and early complication detection.

Understanding the Intricacies of Iron Overload Associated with β-Thalassemia: A Comprehensive Review

β-thalassemia, a congenital genetic hematological disorder characterized by the decrease or absence of β-globin chains, leads to a decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia also exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications that arise due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, the therapeutic efficacy of different iron chelators in managing iron overload complications is mentioned briefly, along with the guidelines for their usage in India. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia.

Drug-related problems among transfusion-dependent thalassemia patients: A real-world evidence study.

Introduction: Thalassemia is among the most common genetic disorders globally and many patients suffer from iron overload (IOL) complications that mainly affect the heart, liver and endocrine system. These events may be further complicated by drug-related problems (DRP), an inherent issue among patients with chronic diseases. Objective: The study aimed to evaluate the burden, associated factors and impacts of DRP in transfusion-dependent thalassemia (TDT) patients. Method: Eligible TDT patients under follow-up in a tertiary hospital between 01 March 2020 to 30 April 2021 were interviewed and their medical records were reviewed retrospectively to identify any DRP. DRPs were classified using the Pharmaceutical Care Network Europe (PCNE) classification version 9.1. The incidence and preventability of DRP were assessed and the associated risk factors were estimated by univariate and multivariate logistic regression. Results: A total of 200 patients were enrolled with a median (interquartile range: IQR) age of 28years at enrolment. Approximately 1 in 2 patients were observed to suffer from thalassemia-related complications. Throughout the study period, 308 DRPs were identified among 150 (75%) participants, with a median DRP per participant of 2.0 (IQR 1.0-3.0). Of the three DRP dimensions, treatment effectiveness was the most common DRP (55.8%) followed by treatment safety (39.6%) and other DRP (4.6%). The median serum ferritin level was statistically higher in patients with DRP compared with patients without DRP (3833.02 vs. 1104.98μg/L, p < 0.001). Three risk factors were found to be significantly associated with the presence of DRP. Patients with frequent blood transfusion, moderate to high Medication Complexity Index (MRCI) and of Malay ethnicity were associated with higher odds of having a DRP (AOR 4.09, 95% CI: 1.83, 9.15; AOR 4.50, 95% CI: 1.89, 10.75; and AOR 3.26, 95% CI: 1.43, 7.43, respectively). Conclusion: The prevalence of DRP was relatively high amongst TDT patients. Increased medication complexity, more severe form of the disease and Malay patients were more likely to experience DRP. Hence, more viable interventions targeted to these groups of patients should be undertaken to mitigate the risk of DRP and achieve better treatment outcomes.

HUBUNGAN TINGKAT KEPATUHAN KONSUMSI OBAT KELASI BESI DENGAN KADAR FERRITIN PADA PASIEN THALASSEMIA ANAK DI RSUD DR. MOEWARDI

Thalassemia is a hereditary hemolytic disease caused by mutations in the hemoglobin synthesis chain. Transfusion-dependent thalassemia patients require iron chelation therapy to prevent complications of iron overload. Adherence with regular iron chelation consumption is important for good survival, reducing morbidity and mortality in thalassemia patients. This research is an analysis of an observational study with a cross-sectional approach. This research was conducted at RSUD Dr. Moewardi. The subjects of this study were pediatric thalassemia patients who were taking deferiprone iron chelating drugs. The sample was taken using purposive sampling method, by analysing medical record data and the MMAS-8 questionnaire. Data were examined using the chi-square test with the SPSS application. Results: There were 56 subjects to be analyzed consisting of 23 males and 33 females. Based on the chi-square test, there was a significant relationship between consumption of iron chelating drugs and ferritin levels with p = 0.026. In addition, another study was conducted using the chi-square test regarding nutritional status and duration of thalassemia illness on ferritin levels. The results obtained were p value = 0.977 for the relationship between nutritional status and p value = 0.977 for the long duration of thalassemia illness. It can be concluded that both of them have no significant effect on ferritin levels. Adherence with taking iron chelating drugs has a significant relationship to ferritin levels in thalassemia patients.

Iron chelation therapy.

Iron overload is a pathological condition resulting from a congenital impairment of its regulation, increased intestinal iron absorption secondary to bone marrow erythroid hyperplasia, or a chronic transfusional regimen. In normal conditions, intracellular and systemic mechanisms contribute to maintaining iron balance. When this complex homeostatic mechanism fails, an iron overload could be present. Detecting an iron overload is not easy. The gold standard remains the liver biopsy, even if it is invasive and dangerous. Identifying iron using noninvasive techniques allowed a better understanding of the rate of iron overload in different organs, with a low risk for the patient. Estimating serum ferritin (mg/L) is the easiest and, consequently, the most employed diagnostic tool for assessing body iron stores, even if it could be a not specific method. The most common hematological causes of iron overload are myelodysplastic syndromes, sickle cell disease, and thalassemia. In all of these conditions, three drugs have been approved for the treatment of iron overload: deferiprone, deferoxamine, and deferasirox. These chelators have been demonstrated to help lower tissue iron levels and prevent iron overload complications, improving event-free survival (EFS). Nowadays, the decision to start chelation and which chelator to choose remains the joint decision of the clinician and patient.

Lessons identified from initiating a thalassaemia programme in a conflict setting: a case study from northeast Syria

BackgroundThalassaemia 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.MethodsWe 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 descriptionMSF 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.ConclusionsAlthough 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.

The role of MRI-R2* in the detection of subclinical pancreatic iron loading among transfusion-dependent sickle cell disease patients and correlation with hepatic and cardiac iron loading

ObjectivesPancreatic reserve could be preserved by early assessment of pancreatic iron overload among transfusion-dependent sickle cell disease (SCD) patients. This study aimed to measure pancreatic iron load and correlate its value with patients’ laboratory and radiological markers of iron overload.Materials and methodsSixty-six SCD children and young adults underwent MRI T2* relaxometry using a simple mathematical spreadsheet and laboratory assessment.ResultsThe results indicated moderate-to-severe hepatic iron overload among 65.2% of studied cases. None had cardiac iron overload. Normal-to-mild iron overload was present in the pancreas in 86% of cases, and 50% had elevated serum ferritin > 2500 ug/L. There was no significant correlation between pancreatic R2* level, serum ferritin, and hepatic iron overload. Patients with higher levels of hemolysis markers and lower pre-transfusion hemoglobin levels showed moderate-to-severe pancreatic iron overload.ConclusionChronically transfused patients with SCD have a high frequency of iron overload complications including pancreatic iron deposition, thereby necessitating proper monitoring of the body’s overall iron balance as well as detection of extrahepatic iron depositions.

Supply Chain of Iron Chelators for Thalassaemia in Malaysia: An Overview for Process Optimisation

Iron chelating therapy (ICT) drugs are prescribed to transfusion dependent thalassaemia (TDT) patients to prevent iron overload complications. The high number of TDT patients in Malaysia strained the public healthcare resources. This paper aims to provide an insight on existing supply chain management of ICT medicines in Malaysia and to explore ways for a more efficient system. A rapid review of literatures was conducted in electronic databases (PubMed, Emerald, Scopus and ScienceDirect) and other relevant Malaysian government documents. Supply of ICT to thalassaemia patients is publicly funded but much availability of oral ICT is restricted due to financial consideration. ICT in Malaysia is supplied through central procurement but purchasing and inventory management are decentralised to each hospital. Vendor-managed inventory system is an ideal option to the inventory management practice in Malaysian public healthcare facilities as it could provide better efficiency and reduces inventory management costs.

Awareness about thalassemia and its management among the caregivers of the thalassemia patients of Punjab and Chandigarh, India

Background: β-thalassemia is an autosomal recessive condition that causes a reduction in the production of haemoglobin. Despite their short lifespans, thalassemia patients must rely on routine blood transfusions throughout their lives. They suffer from a variety of health issues, the majority of which are caused by iron overload complications. It places a significant financial and psychological strain on both patients and their caregivers, and their perceived knowledge of the disease play a significant role in controlling and enhancing their health-related quality of life. Objective: To determine if caregivers of transfusion-dependent thalassemia patients are aware of thalassemia and how to manage it. Methods: The study examined the caregivers of 105 North Indian thalassemia patients who got blood transfusions on a regular basis in hospitals in Patiala, Punjab, and Chandigarh. With prior informed consent, caregivers were interviewed to evaluate their knowledge of thalassemia and its management with their socio-demographic characteristics. The knowledge of each caregiver was rated using a scoring system and was correlated to the caregiver's SES and education. The data was analysed using the SPSS version 20. Results: The majority of caregivers had sufficient knowledge about thalassemia and their comorbidities, premarital screening, treatment modalities, iron overload, and chelation therapy.

Addison's disease in a lady with hemoglobin H disease

Hemoglobin H (HbH) disease is alpha (α)-thalassemia characterized by the inactivation of three of four α-globin genes due to deletions with or without nondeletional α-thalassemia. HbH disease is not necessarily a benign disorder as has been generally thought. Here, we report a 33-year-old female who has a lifelong history of anemia without blood transfusions. but when she got married, during pregnancies developed symptomatic moderate-to-severe anemia necessitating infrequent blood transfusions. Later due to symptomatic anemias and increasing the frequency of blood transfusions, she underwent splenectomy, 3 years from splenectomy she developed a gradual dark skin discoloration with frequent hypotension and was diagnosed with Addison's disease which is a rare endocrine complication of thalassemia-induced iron overload.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

SARS-CoV-2 infection in patients with β-thalassemia: The French experience.

IntroductionBecause of iron overload complications, thrombosis and infectious predisposition, patients with severe forms of thalassemia are likely to be at increased risk of COVID-19 complications.ResultsA national survey conducted during the year 2020 across the French reference centers for hemoglobinopathies identified 16 cases of COVID-19 confirmed by RT-PCR in beta-thalassemia patients. Their age ranged from 11 months to 60 years. 15 patients were transfusion-dependent and 6 were splenectomized. Concerning iron overload related complications, none had diabetes or cirrhosis and only one had experienced heart failure. All 4 pediatric patients were pauci-symptomatic during the viral episode. Three patients (41, 49 and 57 years old) developed COVID-19 pneumonia requiring oxygen therapy without the need for mechanical ventilation. Neutropenia (absolute neutrophils count < 0.5 10 9/L) was observed in 2 patients receiving long-term treatment with hydroxycarbamide and deferiprone. No thrombosis event, organ failure or death occurred. All patients recovered.ConclusionSeverity of COVID-19 in this population of young and middle-aged patients appeared increased compared to the general population but remained mild to moderate as already described in the few series reported in the literature. Occurrence of adverse events related to chronic treatment administered in thalassemia disease may be favored by the infectious episode.

Isolation and Chelation Activity of Plant Phenolic Root Exudates As Potential Clinical Iron Chelators

Introduction:Hemoglobinopathies such as β-Thalassemia (Thal) and other genetic disorders such as neurodegeneration with brain iron accumulation have complications of iron overload, which can impair vital processes such as cardiac and neurological function. In Thal, ineffective erythropoiesis leads to elevated gastrointestinal iron absorption and in severe cases may necessitate blood transfusions exacerbating the condition. Iron chelating agents such as deferoxamine (DFO), deferiprone, and deferasirox must be used, but can have unwanted side effects. While effective in treating iron overload, the increased risk of side effects at higher doses highlights the importance of finding new potent iron-chelating agents, either as replacements or as adjuvants. Plant based treatments may be better tolerated by patients, offering an alternative therapeutic approach. Plant secondary metabolites secreted from roots under iron limiting conditions may provide a novel source for this bioactivity. Plants rich in phenolic compounds and those tolerating alkaline soils, which necessitate efficient mobilization of soil-precipitated iron, are our focus here. The aim of this project is to functionally and analytically characterize naturally occurring plant root exudates as possible clinical iron chelators.Methods : We cultivated Populus trichocarpa ( Poplar), Thuja plicata (Western red-cedar), and Lavendula X intermedia (Lavender) cuttings under iron normal and iron limiting conditions. From their roots, exudates were isolated to characterize and determine their effectiveness as iron chelators. Total phenolic concentrations of exudates were evaluated using Folin-Ciocalteu reagent. The ferrozine assay was used as a competition assay to characterize total iron binding ability of root exudates and standard chelators, which was sensitive enough to differentiate chelation effectiveness between DFO, EDTA, and isolated root exudates at 800 nM. Furthermore, known plant iron chelators chlorogenic acid (CA), a phenolic, and the more lipophilic β-thujaplicin (hinokitiol) were compared to DFO, then used tomodel root exudates in a cell culture bioassay. The bioassay was developed using monocytic THP-1 cells (as an RE system model) to quantify intra- and extracellular iron, comparing iron uptake in cells exposed to varying concentrations of iron chelators as a way of evaluating chelation strengths of crude root exudates, β-thujaplicin, and CA in comparison to DFO.Results:Total phenolic production in P. trichocarpa root exudates increased significantly (p < 0.05) in response to iron depletion after 12 hrs. Iron binding ability increased almost four-fold upon iron depletion. In the ferrozine competition assay, iron depleted root exudates inhibited iron binding by 15% whereas iron normal exudates inhibited by only 4%. Iron binding of root exudates was similar to EDTA (13% inhibition) and about half that of DFO (30% inhibition). In the THP-1 cell bioassay, DFO and CA showed comparable trends of chelation activity. Cells exposed to either 50 or 100 μM CA or DFO reduced intracellular iron by at least 47% or 89%, respectively. However, at 50 and 100 µM β-thujaplicin increased iron uptake by 82 to 86% respectively. Further testing of plant root exudates is ongoing.Conclusions: Exposing P. trichocarpa to an iron deficient environment resulted in plants that secreted root exudates with significantly higher level of phenolics and increased iron chelation ability. This was shown in the ferrozine competition assay where iron depleted root exudates showed higher binding affinity for iron when compared to the iron normal exudates resulting in an iron chelation ability similar to the known iron chelator EDTA. In the bioassay using THP-1 monocytic cells, testing the plant phenolic CA, there was reduction of intracellular iron comparable to DFO, whereas the lipophilic chelator β-thujaplicin increased cellular iron. Consequently, chelators such as CA exclude iron from being taken up by the cells, while more lipophilic chelators, like β-thujaplicin enable transport through membranes, and thus have the capacity to transport iron both into and out of cells. Thus, we have shown that plant root exudates can yield potential iron chelators and that in general plant phenolics have iron chelation capacity comparable to the classic iron chelator DFO. DisclosuresWalter:Apopharma: Research Funding.

Sickle Cell Disease and the Adherence to Guidelines for Use of Blood Transfusions

▪Background:An expert panel convened by the NHLBI in 2014 provided guidelines and indications for blood transfusions in patients with sickle cell disease (SCD). These recommendations were to help conserve the use of blood transfusions in SCD in order to reduce the complications of iron overload, transmission of blood-borne pathogens and development of alloantibodies. We retrospectively reviewed the charts of SCD patients who received blood during inpatient admissions and evaluated the indications for transfusions in this population.Methods:The hospital database was screened for admissions of patients with the diagnosis of SCD (HbSS, HbSβ0, HbSβ+, HbSC) who were billed for a blood transfusion between 8/1/2015 to 8/31/2016. All patients were >18 years of age. Each chart was reviewed individually to assess the clinical setting and reasons for transfusion. The following parameters were documented: age, sex, length of hospital stay (LOS), hemoglobin (Hgb) at time of transfusion, baseline Hgb, reticulocyte count, total bilirubin, number of units transfused, documented reason for transfusion, immediate reaction to transfusion, presence of alloantibodies and ferritin level. We defined the infusion of blood as a transfused event which included single or multiple units of blood. We excluded transfusions given for acute bleeding.Results:There were a total of 200 decisions to transfuse blood for 87 patients between 8/1/2015 to 8/31/2016. 72% of the patients had HbSS disease. HbSB0, HbSB+, HbSC, and unknown genotype constituted 14%, 19%, 6% and 7% of the cohort, respectively. Mean age was 30.6 years and 76% were female. A total of 434 units were transfused. The most common reasons for transfusion that deviated from guidelines were uncomplicated pain crises and a fall in Hgb (> 2g/dl, >1.5 g/dl) which accounted for 65.5% (n = 237 units) of the transfusion events (Pain 27%, Hgb drop > 2 gm 20.5% and Hgb drop > 1.5 gm 17.5%). The most common indicated guideline reasons for transfusion were symptomatic anemia and acute chest syndrome and only accounted for 12.5% and 10%, respectively of transfusions in this cohort. The mean Hgb at which patients were transfused was 6.6 g/dl, with a median value of 6.5 g/dl. The mean Hgb of those transfused for drop in hemoglobin and symptomatic anemia were 5.9 g/dl and 5.7 g/dl, respectively. The mean level of ferritin in this cohort was 2483. 15/87(17%) of patients had allo-antibodies. There was a 2% occurrence of immediate allergic blood transfusion reaction. The average LOS for all patients was 9.0 days. The average LOS for patient who received blood for uncomplicated pain or drop in Hgb was 8.9 days.Conclusion:In this group of patients with SCD, the majority of the inpatient transfusions were not indicated by national guidelines. Only 34.5% of transfusion events met expert panel recommendations. There was significant iron overload and development of allo-antibodies noted in our cohort. It is possible that there was a lack of documentation of symptoms due to anemia in those who received blood for a drop in hemoglobin. Regardless, there appears to be a significant number of unnecessary transfusions in SCD patients. We plan to develop and implement an educational program for care providers as to increase adherence to guidelines for transfusions in SCD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical Complications of Iron Overload in Patients with Myelodysplastic Syndromes: a literature review

Myelodysplastic Syndromes (MDS) are a group of heterogeneous hematologic disorders characterized by bone marrow involvement. Iron overload is the result of multiple transfusions and high levels of apoptosis. Based on a literature review, ferritin was identified as an important marker of iron accumulation in organs such as liver, heart and pancreas in patients with MDS. Some studies also demonstrated that iron overload caused cell cycle arrest causing apoptosis and progression to leukemia, high levels of reactive oxygen species and low levels of HIF-1a, causing apoptosis, being related to the presence of cytopenia in MDS.

Serum Hepcidin and Growth Differentiation Factor 15 In Patients with β-thalassemia and Its Relation to Blood Transfusion

Background: Serum Hepcidin level drop is a main feature of chronic hemolytic anemia like β-thalassemia as an example. It is assumed that Hepcidin is influenced by anemia, iron overload due to repeated blood infusions and inflammation due to iron disposition in tissues. Main purpose of our research: To measure plasma levels of the iron regulatory hormones; hepcidin and GDF-15 in β-thalassemic patients during intravenous blood infusion in order to assist clinical monitoring. Methodology: 30 cases previously diagnosed as a β-thalassemia major (group I) and 20 normal individuals of the same age and gender group (group II). The samples were collected immediately before and 8 days after transfusion. Hepcidin and GDF-15 levels were estimated using ELISA kit that is commercially available. Results: As regard to serum Hepcidin level in both control and patient group was similar before the transfusion. The hepcidin level increased significantly after transfusion in both groups but in was significantly higher in patient group. Hb and hepcidin increased significantly post-transfusion. The pre- and post-transfusion hepcidin showed significant correlation with Hb, Iron, and Ferritin in thalassemia patients. The pre-transfusion Growth Differentiation Factor-15 was shooting in cases with β-thalassemia than presumably healthy control. The GDF-15 level decreased significantly after transfusion and it was significantly correlated with Hb and hepcidin levels. In conclusion: Hepcidin serum level assessment can be used to monitor patients with iron-loading anemia and identify the patients prone to iron overload complications and iron toxicity.