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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.

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.

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.

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.

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.

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.

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.

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.