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Beta (β)-thalassemia and sickle cell disease (SCD) are characterized by a hypercoagulable state, which can significantly influence organ complication and disease severity. While red blood cells (RBCs) and erythroblasts continue to play a central role in the pathogenesis of thrombosis in β-thalassemia and SCD, additional factors such as free heme, inflammatory vasculopathy, splenectomy, among other factors further contribute to the complexity of thrombotic risk. Thus, understanding the role of the numerous factors driving this hypercoagulable state will enable healthcare practitioners to enhance preventive and treatment strategies and develop novel therapies for the future. We herein describe the pathogenesis of thrombosis in patients with β-thalassemia and SCD. We also identify common mechanisms underlying the procoagulant profile of hemoglobinopathies translating into thrombotic events. Finally, we review the currently available prevention and clinical management of thrombosis in these patient populations., (© 2024 Wiley Periodicals LLC.)

Thalassaemia, caused by over 250 mutations in the beta globin gene, changes the haematopoietic stem cell (HSC) differentiation, leading to ineffective erythropoiesis. This Wider Perspective article overlooks its underlying nature as a benign HSC disorder with a significant impact on the erythroid cell lineage. The simplicity of managing symptoms through transfusions and iron chelation therapy has shifted the focus away from the development of cell-based treatments. The identification of the beta039 mutation by Chang and Kan in 1979 marked a turning point, suggesting as main approach the molecular level by correcting the beta globin chain imbalances through gene insertion and editing. However, challenges of technology have delayed the implementation of these strategies for over four decades. In contrast, the past two decades have witnessed significant advances in the treatment of HSC disorders of the myeloid clone which are driven by a 'target cell strategy'. Many current and innovative treatments for thalassaemia are now adopting this approach, highlighting the importance of identifying suitable candidates through risk stratification. This manuscript explores the evolving understanding of thalassaemia syndromes as congenital HSC disorders of the erythroid clone and examines the implications of this perspective for the development of future treatments., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Iron is an essential nutrient and a constituent of ferroproteins and enzymes crucial for human life. Generally, nonmenstruating individuals preserve iron very efficiently, losing less than 0.1% of their body iron content each day, an amount that is replaced through dietary iron absorption. Most of the iron is in the hemoglobin (Hb) of red blood cells (RBCs); thus, blood loss is the most common cause of acute iron depletion and anemia worldwide, and reduced hemoglobin synthesis and anemia are the most common consequences of low plasma iron concentrations. The term iron deficiency (ID) refers to the reduction of total body iron stores due to impaired nutrition, reduced absorption secondary to gastrointestinal conditions, increased blood loss, and increased needs as in pregnancy. Iron deficiency anemia (IDA) is defined as low Hb or hematocrit associated with microcytic and hypochromic erythrocytes and low RBC count due to iron deficiency. IDA most commonly affects women of reproductive age, the developing fetus, children, patients with chronic and inflammatory diseases, and the elderly. IDA is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39% and 48.1% in developing countries). The diagnosis, management, and treatment of patients with ID and IDA change depending on age and gender and during pregnancy. We herein summarize what is known about the diagnosis, treatment, and prevention of ID and IDA and formulate a specific set of recommendations on this topic., Competing Interests: Patricia Aguilar Martinez: Nothing to Disclose. Dorine Swinkels: Nothing to Disclose. Sule Unal: Nothing to Disclose. Fabiana Busti: Nothing to Disclose. Myka Sanchez: Co‐Founder of SME BLOODGENETICS SL (a genetic company www.bloodgenetics.com); Participation in 2 clinical trials one for IRIDA (KEROS THERAPEUTICS), one for atransferrinemia (SanquinBlood Netherland). Achille Iolascon: Nothing to Disclose. Ali Taher—Outside Work: Novartis Pharmaceuticals: Consultancy, Research funding; Bristol‐Myers Squibb (Celgene): Consultancy, Research funding; Ionis Pharmaceuticals: Consultancy, Research Funding; Vifor: Consultancy, Research Funding; Agios: Consultancy. Rayan Bou Fakhredin: Nothing to Disclose. Graça Porto: Nothing to Disclose. Immacolata Andolfo: Nothing to Disclose. Roberta Russo: Nothing to Disclose. Martina Muckenthaler Silence Therapeutics PLC, Editorial Board/Blood Journal/HemaSphere. Malcolm. G. Munro: Consultancies Pharmacosmos, Vifor, Daichi‐Sankyo, Shield Therapeutics, Myovant, Abbvie; Immediate Past Chair, FIGO Menstrual Disorders Committee. Tomas Ganz: shareholder and scientific advisor of Intrinsic LifeSciences, and consultant for Ionis Pharmaceuticals, Disc Medicine, Silence Therapeutics, Chugai, Vifor, Akebia, Dexcel, and Avidity Bio., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Advances in understanding the disease process in β-thalassemia supported development of various treatment strategies that resulted in improved survival. Improved survival, however, allowed multiple morbidities to manifest and cemented the need for frequent, lifelong treatment. This has directly impacted patients' health-related quality of life and opened the door for various psychiatric and cognitive disorders to potentially develop. In this review, we summarize available evidence on quality of life, depression and anxiety, suicidality, and cognitive impairment in adult patients with β-thalassemia while sharing our personal insights from experience in treating patients with both transfusion-dependent and non-transfusion-dependent forms., Competing Interests: Declaration of competing interest K.M.M. reports consultancy fees from Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, CRISPR Therapeutics, Vifor Pharma, and Pharmacosmos; and research funding from Agios Pharmaceuticals and Pharmacosmos. A.T.T. reports consultancy fees from Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, Vifor Pharma, and Pharmacosmos; and research funding from Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, Vifor Pharma, and Pharmacosmos. The remaining authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

β-thalassemias are genetic disorders causing an imbalance in hemoglobin production, leading to varying degrees of anemia, with two clinical phenotypes: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Red blood cell transfusions and iron chelation therapy are the conventional treatment options for the management of β-thalassemia. Currently available conventional therapies in thalassemia have many challenges and limitations. Accordingly, multiple novel therapeutic approaches are currently being developed for the treatment of β-thalassemias. These strategies can be classified into three categories based on their efforts to address different aspects of the underlying pathophysiology of β-thalassemia: correction of the α/β globin chain imbalance, addressing ineffective erythropoiesis, and targeting iron dysregulation. Managing β- thalassemia presents challenges due to the many complications that can manifest, limited access and availability of blood products, and lack of compliance/adherence to treatment. Novel therapies targeting ineffective erythropoiesis and thus improving anemia and reducing the need for chronic blood transfusions seem promising. However, the complex nature of the disease itself requires personalized treatment plans for each patient. Collaborations and partnerships between thalassemia centers can also help share knowledge and resources, particularly in regions with higher prevalence and limited resources. This review will explore the different conventional treatment modalities available today for the management of β-thalassemia, discuss the unmet needs and challenges associated with them in addition to exploring the role of some novel therapeutic agents in the field., (Copyright © 2023 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

β-thalassemia is a monogenic disorder characterized by decreased hemoglobin production, resulting in chronic anemia. There are several factors affecting the clinical presentation of patients with β-thalassemia, and several complications such as iron overload or ineffective erythropoiesis have been linked to this disease. Until nowadays, several conservative therapies namely blood transfusions, iron chelation, and the FDA-approved drug Luspatercept have been adopted alongside other debatable permanent cures. Other clinical trials are being conducted to develop better and safer management techniques for these patients. This review will discuss the different treatment strategies of β-thalassemia including novel therapies, besides all possible curative therapies that are being developed for this disease.

Advances in understanding the underlying pathophysiology of β-thalassemia have enabled efforts toward the development of novel therapeutic modalities. These can be classified into three major categories based on their ability to target different features of the underlying disease pathophysiology: correction of the α/β globin chain imbalance, targeting ineffective erythropoiesis, and targeting iron dysregulation. This article provides an overview of these different emerging therapies that are currently in development for β-thalassemia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The diversity of disease-related complications among patients with β-thalassemia is complicated by the wide spectrum of genotypes and clinical risk factors. The authors herein present the different complications seen in patients with β-thalassemia, the pathophysiology underlying these complications and their management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Erythropoiesis is the physiological process that results in the production of red blood cells (RBCs). In conditions of pathologically altered erythropoiesis or ineffective erythropoiesis, as in the case of β-thalassemia, the reduced ability of erythrocytes to differentiate, survive and deliver oxygen stimulates a state of stress that leads to the ineffective production of RBCs. We herein describe the main features of erythropoiesis and its regulation in addition to the mechanisms behind ineffective erythropoiesis development in β-thalassemia. Finally, we review the pathophysiology of hypercoagulability and vascular disease development in β-thalassemia and the currently available prevention and treatment modalities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Pregnancy in women with sickle cell disease (SCD) has been identified as high risk owing to increased incidence of materno-fetal complications across various studies and reports. These complications include consequences related to the underlying hemoglobinopathy; chronic anemia/associated inflammation, and pregnancy related including the risk for thromboembolism, bleeding and maternal mortality. Outcomes of neonates born to women with SCD has been suboptimal over the years with recent improvement due to strict monitoring, preventive and therapeutic measures. Much is yet to be unraveled regarding the optimal management of women with SCD during pregnancy, identifying target hemoglobin, delivery mode or timing among others., Areas Covered: This review includes a summary of available data of the maternal and fetal outcomes; in addition to current recommendations for monitoring and management of women with SCD during pregnancy., Expert Opinion: To have a successful pregnancy, women should be closely monitored, and interventions provided as needed to guarantee adequate management of anemia, as well as prevention, diagnosis and management of disease. They should also be educated regarding their reproductive health, emphasizing that pregnancy is possible, and achieving optimal results depends on providing adequate care in a health care facility with expertise in high-risk pregnancies and SCD.

A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents.

β-thalassemia and sickle cell disease (SCD) are inherited hemoglobinopathies that result in both quantitative and qualitative variations in the β-globin chain. These in turn lead to instability in the generated hemoglobin (Hb) or to a globin chain imbalance that affects the oxidative environment both intracellularly and extracellularly. While oxidative stress is not among the primary etiologies of β-thalassemia and SCD, it plays a significant role in the pathogenesis of these diseases. Different mechanisms exist behind the development of oxidative stress; the result of which is cytotoxicity, causing the oxidation of cellular components that can eventually lead to cell death and organ damage. In this review, we summarize the mechanisms of oxidative stress development in β-thalassemia and SCD and describe the current and potential antioxidant therapeutic strategies. Finally, we discuss the role of targeted therapy in achieving an optimal redox balance.

The β-thalassaemias are a group of inherited disorders of haemoglobin synthesis characterised by chronic anaemia of varying severity. Currently available conventional therapies in thalassaemia have many challenges and limitations. A better understanding of the pathology of β-thalassaemia has led to the development of new treatment options, most of which are currently in clinical trials. These could have the potential of reducing red blood cell transfusion burden, raising haemoglobin levels, and improving patients' overall quality of life. In this review, we will provide an overview of the novel therapeutic approaches that are currently under development to advance the care of β-thalassaemia patients.

Introduction : Fanconi anemia (FA) is a rare congenital disease that belongs to the family of congenital trilinear bone marrow failure. Most FA patients will suffer bone marrow failure and the main treatment relies on supportive measures or more recently on the use of hematopoietic stem cell transplant. The improvements seen in the management of FA has led women to reach childbearing age and have successful pregnancies. However, these pregnancies are associated with increased complications such as preterm delivery, cesarean delivery, eclampsia and others. Areas covered : This review highlights on the outcome of pregnancies in FA patients reported in the literature along with practical recommendations. Expert opinion : Multidisciplinary efforts are required to optimize the management of pregnancy in FA patients. Moreover, the development of a set of recommendations to optimize the treatment is highly necessary.

The treatment landscape for patients with β-thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusion-dependent β-thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost. Patients with non-transfusion-dependent β-thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in β-thalassemia, including the α/non-α-globin chain imbalance, ineffective erythropoiesis, and iron dysregulation., (© 2021 Wiley Periodicals LLC.)

Beta-thalassemia intermedia (β-TI) is associated with vascular dysfunction. We used digital thermal monitoring (DTM), a non-invasive tool that evaluates vascular function based on changes in fingertip temperature during and after cuff occlusion on β-TI patients. Thirty-three patients (18 years and older) were recruited in this study and divided into 3 groups: thalassemia, anemic controls, and healthy controls. Exclusion criteria included factors that are known to be associated with vascular damage. Patients underwent DTM and results were extracted as vascular reactivity index (VRI), a measure of how well the circulatory system responds to stimuli that require adjustments of blood flow. One-way analysis of variance (ANOVA) was used to test the mean difference in VRI between the 3 groups. A multiple linear regression was also carried out with VRI as the outcome of interest and a function of covariates that were thought to be of clinical relevance to VRI. The frequency, mean VRI ± standard error (SE) for the thalassemic group were (N = 16), mean = 2.243 ± 0.111; for anemic controls (N = 9), mean = 2.374 ± 0.162; and for the controls (N = 8), mean = 2.338 ± 0.092. ANOVA test indicated a non-significant difference in mean VRI between the three groups (P value = 0.731). Multiple linear regression couldn't detect any significant association between VRI and any of the predictors including the groups. Our study did not show a significant difference in VRI between the 3 study groups. Prospective studies of larger sample size are warranted to establish DTM as a possible non-invasive tool used to evaluate vascular function in β-TI patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: β-thalassemia is one of the most common inherited monogenic diseases. Many patients are dependent on a lifetime of red blood cell (RBC) transfusions and iron chelation therapy. Although treatments have a significant impact on quality of life (QoL), life expectancy, and long-term health outcomes have improved in recent decades through safer RBC transfusion practices and better iron chelation strategies. Advances in the understanding of the pathology of β-thalassemia have led to the development of new treatment options that have the potential to reduce the RBC transfusion burden in patients with transfusion-dependent (TD) β-thalassemia and improve QoL., Areas Covered: This review provides an overview of currently available treatments for patients with TD β-thalassemia, highlighting QoL issues, and providing an update on current clinical experience plus important practical points for two new treatments available for TD β-thalassemia: betibeglogene autotemcel (beti-cel) gene therapy and the erythroid maturation agent luspatercept, an activin ligand trap., Expert Opinion: Approved therapies, including curative gene therapies and supportive treatments such as luspatercept, have the potential to reduce RBC transfusion burden, and improve clinical outcomes and QoL in patients with TD β-thalassemia. Cost of treatment is, however, likely to be a significant barrier for payors and patients.

Oxidative damage by reactive oxygen species (ROS) is one of the main contributors to cell injury and tissue damage in thalassemia patients. Recent studies suggest that ROS generation in non-transfusion-dependent (NTDT) patients occurs as a result of iron overload. Among the different sources of ROS, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes and cytochrome P450 (CYP450) have been proposed to be major contributors for oxidative stress in several diseases. However, the sources of ROS in patients with NTDT remain poorly understood. In this study, Hbb th3/+ mice, a mouse model for β-thalassemia, were used. These mice exhibit an unchanged or decreased expression of the major NOX isoforms, NOX1, NOX2 and NOX4, when compared to their C57BL/6 control littermates. However, a significant increase in the protein synthesis of CYP4A and CYP4F was observed in the Hbb th3/+ mice when compared to the C57BL/6 control mice. These changes were paralleled by an increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP4A and CYP4F metabolite. Furthermore, these changes corroborate with onset of ROS production concomitant with liver injury. To our knowledge, this is the first report indicating that CYP450 4A and 4F-induced 20-HETE production mediates reactive oxygen species overgeneration in Hbb th3/+ mice through an NADPH-dependent pathway.

Introduction: Many patients with inherited or acquired benign hematological disorders are at increased risk of developing severe complications from COVID-19. These patients, therefore, require specific advice regarding isolation and changes to their usual treatment schedules. Their disease can also be associated with significant burden, and they necessitate life-long and regular access to therapy, and regular follow-up consultations and hospital visits. The current COVID-19 pandemic is therefore presenting many challenges for these patients, their families, and health-care professionals., Areas Covered: This review provides an overview of the reported COVID-19 cases in the literature in patients with certain benign hematological disorders including thalassemia, sickle cell disease, hemophilia, immune thrombocytopenia, venous thromboembolism, and aplastic anemia. The review also outlines some recommendations on how to manage these patients if they are infected with SARS-CoV-2. To review the literature on benign hematological disorders and COVID-19, a bibliographic search was performed using PubMed for articles published between January 2020 and June 2020., Expert Opinion: International efforts must be made to continue reporting and better understanding the effects of SARS-CoV-2 infection in these patients and accordingly develop a set of recommendations to optimize the treatment of future infected patients.

Thalassemia is characterized by a defect in the synthesis of one or more of the globin subunits of hemoglobin. This defect results in imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. With advances in diagnosis, treatment, and transfusion support, the prognosis of patients with thalassemia has improved over the past few decades. An increasing number of patients with thalassemia is living with long-term complications, including cardiomyopathy, chronic liver disease, endocrinopathy, and infections. In this paper, we review common complications that bring the patient with thalassemia to urgent or emergent medical attention. We also discuss the aspects of emergency care that are most relevant while caring for the patient with thalassemia in the emergency department.

Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defined. Moreover, during the last decade there has been a lack of proper understanding of the impact of rare anemias on maternal and fetal outcomes. In addition, there are no clear-cut guidelines outlining the pathophysiological trends and management options unique to this special population. Here, we present on behalf of the European Hematology Association, evidence- and consensus-based guidelines, established by an international group of experts in different fields, including hematologists, gynecologists, general practitioners, medical geneticists, and experts in rare inherited anemias from various European countries for standardized and appropriate choice of therapeutic interventions for the management of pregnancy in rare inherited anemias, including Diamond-Blackfan Anemia, Congenital Dyserythropoietic Anemias, Thalassemia, Sickle Cell Disease, Enzyme deficiency and Red cell membrane disorders., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Very few reports in the literature have focused on the psychosocial status of patients with thalassemia. The aim of this study was to report on the education, employment, and marital status of thalassemia patients in Lebanon and potential influencing factors. A total of 228 patients from the Chronic Care Center, Hazmieh, Lebanon, were incorporated for the data analysis. Demographic, social, and clinical variables were collected. Statistical analysis was performed using the Pearson χ 2 test, Fisher Exact test, and binary logistic regression. In this sample, 54.4% were employed, and 45.6% not employed. Of those employed, 65.3% were male, 62.9% single or divorced, 77.4% splenectomized. University level was reached by 26.3% subjects, 7.9% reached high school level, and 32.5% have a level less than high school. Multivariate analysis revealed higher education was most likely attained by males [odds ratio (OR) = 2.23, 95% confidence interval (95% CI): 0.23-0.86] and those with no heart disease and no joint disease (OR = 27.5, 95% CI: 2.80-270 and OR = 3.40, 95% CI: 0.90-12.7, respectively). For employment, a lower average ferritin was associated with current employment. Neither the type of thalassemia nor transfusion status or type of chelation therapy corresponded with higher education or employment status. In conclusion, this is one of the few studies in the literature to look at education, employment, and marital status of thalassemia patients. Such information is essential to develop effective psychosocial support plans for our thalassemia patients.

Hemoglobinopathies are among the most common monogenic diseases worldwide. Approximately 1-5% of the global population are carriers for a genetic thalassemia mutation. The thalassemias are characterized by autosomal recessive inherited defects in the production of hemoglobin. They are highly prevalent in the Mediterranean, Middle East, Indian subcontinent, and East and Southeast Asia. Due to recent migrations, however, the thalassemias are now becoming more common in Europe and North America, making this disease a global health concern. Currently available conventional therapies in thalassemia have many challenges and limitations. A better understanding of the pathophysiology of β-thalassemia in addition to key developments in optimizing transfusion programs and iron-chelation therapy has led to an increase in the life span of thalassemia patients and paved the way for new therapeutic strategies. These can be classified into three categories based on their efforts to address different features of the underlying pathophysiology of β-thalassemia: correction of the globin chain imbalance, addressing ineffective erythropoiesis, and improving iron overload. In this review, we provide an overview of the novel therapeutic approaches that are currently in development for β-thalassemia.

Introduction: The thalassemias are among the most  common inherited monogenic diseases worldwide, characterized by autosomal recessive inherited defects in the production of hemoglobin. Currently available conventional therapies have many challenges and limitations. Advances in understanding the underlying pathophysiology of β-thalassemia enabled clinicians and researchers to move toward the development of novel therapeutic modalities. These can be classified into three categories based on their efforts to address different features of the underlying pathophysiology of β-thalassemia: correction of the globin chain imbalance, addressing ineffective erythropoiesis, and improving iron overload., Areas Covered: In this review, we will provide an overview of the novel therapeutic approaches that are currently in development for β-thalassemia., Expert Opinion: A thorough understanding of the pathophysiology and overall disease burden of β-thalassemia has aided clinicians and scientists to optimize disease management approaches and construct a plan for the development of novel therapies, with ultimate goals of prolonging longevity, reducing symptom burden, improving compliance and adherence for a better quality of life.

The thalassemias constitute a variable group of anemias that result from autosomal recessive inherited defects in the production of hemoglobin. The life expectancy of thalassemia patients has been extended over the last decades as a result of key milestones being achieved in optimizing management with transfusion and iron chelation therapy. Such advances have prolonged the survival of thalassemia patients and improved their overall quality of life. However, this increase in life expectancy has led to the manifestation of several morbidities, including multiple types of solid and hematologic malignancies. In this review we report the different types of solid and hematological malignancies that can develop in thalassemia patients, in addition to the possible predisposing factors and mechanisms behind their development., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The pathogenesis of multiple sclerosis is characterized by a cascade of pathobiologic events, ranging from focal lymphocytic infiltration and microglia activation to demyelination and axonal degeneration. MS has several of the hallmarks of an inflammatory autoimmune disorder, including breakdown of the BBB. Gadolinium-enhanced MR imaging is currently the reference standard to detect active inflammatory lesions in MS. Knowledge of the patterns and mechanisms of contrast enhancement is vital to limit the radiologic differential diagnosis in the staging and evaluation of MS lesion activity. The aim of this review was the following: 1) to outline the pathophysiology of the effect of lymphocyte-driven inflammation in MS, 2) to describe the effects of gadolinium on the BBB and glymphatic system, and 3) to describe gadolinium enhancement patterns and artifacts that can mimic lesions in MS., (© 2018 by American Journal of Neuroradiology.)

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., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

The presence of a high incidence of thrombotic events, mainly in nontransfusion-dependent β-thalassemia syndromes, has led to the identification of a hypercoagulable state in thalassemia patients. This article highlights the mechanisms leading to hypercoagulability in thalassemia. It also discusses the clinical experience and available evidence on prevention and management approaches., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Patients with non-transfusion-dependent thalassemia (NTDT) experience many clinical complications despite their independence from frequent transfusions. Morbidities in NTDT stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload (IOL), and hypercoagulability. Ineffective erythropoiesis and hemolysis are associated with chronic hypoxia and a hypercoagulable state. The latter are linked to a high prevalence of thromboembolic and cerebrovascular events, as well as leg ulcers and pulmonary hypertension. IOL in NTDT patients is a cumulative process that can lead to several iron-related morbidities in the liver (liver fibrosis), kidneys, endocrine glands (endocrinopathies), and vascular system (vascular disease). This review sheds light on the pathophysiology underlying morbidities associated with NTDT and summarizes the mainstays of treatment and some of the possible future therapeutic interventions., Competing Interests: Joseph Sleiman, Ali Tarhini, Rayan Bou-Fakhredin, and Antoine N. Saliba have no conflicts of interest to disclose. Ali T. Taher receives research funding and honoraria from Novartis Pharmaceuticals, and research funding from Celgene and Roche. Maria Domenica Cappellini is an advisory board member for Novartis Pharmaceuticals, Sanofi-Genzyme, and Celgene Corporation.

The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is increasing, the two well recognized HCC risk factors in thalassemia being iron overload and chronic hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, whereas chronic hepatitis leads to necroinflammation that can accelerate progression to HCC. We hereby report the case of a non transfused, hepatitis C-negative, β-thalassemia intermedia (β-TI) patient from our practice who had evidence of significant iron overload, suggesting the importance of increased iron burden as a HCC risk factor in this patient population. As such, screening thalassemia patients using magnetic resonance imaging (MRI)-based liver iron concentration (LIC) measurement and liver ultrasound is strongly recommended for early detection of iron overload and HCC, respectively. Data appears to be lacking on HCC treatment outcomes in patients who have thalassemia, but an approach tailored to each patient's comorbidities is key to treatment success. The prognosis of these patients can be improved by multicenter studies investigating novel HCC therapeutic targets in the thalassemia realm.

Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient's needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT., Competing Interests: Rayan Bou-Fakhredin, Abdul-Hamid Bazarbachi, Bachar Chaya and Joseph Sleiman have no conflicts of interest to disclose. Ali T. Taher receives research funding and honoraria from Novartis Pharmaceuticals, and research funding from Celgene and Roche. Maria Domenica Cappellini is an advisory board member for Novartis Pharmaceuticals, Sanofi-Genzyme, and Celgene Corporation.

Background: The spectrum of thalassemias is wide ranging from thalassemia minor, which consists of mild hypochromic microcytic anemia without obvious clinical manifestations, to thalassemia major (TM), which is characterized by severe anemia since the first years of life and is transfusion dependent. Thalassemia intermedia (TI) describes those patients with mild or moderate anemia., Objective: To describe the genetic features and major clinical complications of TI, and the therapeutic approaches available in the management of this disease., Methods: Publications from potentially relevant journals were searched on Medline., Results and Discussion: Over the past decade, the understanding of TI has increased with regard to pathophysiology and molecular studies. It is now clear that clinical presentation and specific complications make TI different from TM. It is associated with greater morbidity, a wider spectrum of organ dysfunction and more complications than previously thought., Conclusion: TI is not a mild disease. The interplay of three hallmark pathophysiologic factors (ineffective erythropoiesis, chronic anemia, and iron overload) leads to the clinical presentations seen in TI. New treatment modalities are currently being investigated to broaden the options available for TI management.

Introduction: Iron deficiency is a frequent comorbidity of chronic diseases such as inflammatory bowel disease that can severely impact the health and quality of life of affected individuals. It can exist as a silent condition and manifest in non-specific symptoms even in the absence of anemia. Even though iron deficiency anemia is the most common complication and extra-intestinal manifestation of inflammatory bowel disease, the majority of inflammatory bowel disease patients who are diagnosed with iron deficiency anemia are not treated. Areas covered: In this review, we discuss iron deficiency and iron deficiency anemia in patients with inflammatory bowel disease, and review diagnostic and therapeutic options. Expert commentary: We invite international gastroenterological societies and associations to refine the practice guidelines and include iron deficiency as a potential morbidity associated with IBD in analogy to arthritis, uveitis or any other extra intestinal manifestations. There should a more unanimous agreement among different societies on the specific diagnostic cutoff values for C-reactive protein levels, serum ferritin, and transferrin saturation in order to differentiate iron deficiency anemia from anemia of chronic disease.

Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.

The presence of elevated numbers of circulating microparticles (MPs) has been hypothesized to be responsible for the occurrence of thromboembolic events (TEEs) in thalassemic patients. Our aim is to evaluate the presence and the thrombotic risk of circulating MPs in thalassemia patients and to determine the difference in MPs between β-thalassemia major (β-TM) and thalassemia intermedia (TI). The percentage of the annexin-labeled MPs, platelet-derived MPs (PMPs), erythrocyte-derived MPs (RMPs), and endothelial-derived MPs (EMPs) was measured by flow cytometry, in 87 thalassemia patients (39 β-TM and 48 TI). By multiple regression analysis, we then assessed the various independent risk factors for the occurrence of TEE. The thalassemic patients who experienced TEE had a significantly higher platelet count, higher percentage of annexin-labeled MPs, and higher percentage of PMPs (p value = 0.014, 0.003, and 0.014, respectively). There was no significant difference between β-TM and TI patients at the level of any of the studied MPs. The predictive risk factors for TEE in thalassemic patients were splenectomy, total and direct bilirubin, the RMPs, and the EMPs (OR = 10.07 (CI = 3.7-27.1), 4.3 (CI = 2.1-8.7), 1.4 (CI = 1.5-6.2), 1.6 (CI = 1.1-2.2), 3.0 (CI = 1.9-4.9), respectively). In conclusion, the elevated numbers of circulating MPs is a risk factor for the TEE in thalassemia patients.

This article evaluates the most relevant state-of-the-art magnetic resonance (MR) techniques that are clinically available to investigate multiple sclerosis (MS). The presence of hypo- and hyperintense lesions on T1- and T2-weighted magnetic resonance imaging (MRI) sequences in white matter (WM) is a common finding that is occasionally a diagnostic challenge for the radiologist. The technical requirements and how they may help to understand, classify or follow-up these pathologies are briefly summarized. The gold standard for MS diagnosis is pathological correlation. Yet due to limited availability of biopsy and autopsy material, there is a high demand for imaging as a diagnostic as well as prognostic indicator. With the progress in MRI during the last decade, MRI now plays a leading role in the diagnosis and follow-up of MS. A number of correlative pathological and MR studies have helped to define pathological substrates of MS in focal lesions and normal appearing white matter (NAWM). Vascular spaces mimicking MS lesions have been minimized by the enhanced differentiation of WM and grey (GM) matter parenchyma. The aim of this article is to enhance the current understanding of histopathology and radiological characteristics of MS lesions in space and time., (© 2016 The Royal Australian and New Zealand College of Radiologists.)