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Infiltrative Cardiomyopathies
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Arthur Qi, Quynh Nguyen, Haran Yogasundaram, Gavin Y. Oudit
Iron overload is defined as the accumulation of excessive iron in the body, which can be caused by both inherited and acquired etiologies.43 Importantly, the human body lacks a physiologic mechanism for the excretion of excess iron. Primary hemochromatosis is a prototypical inherited cause of iron overload and is caused by mutations in genes involved in iron metabolism.40 There are four types of hereditary hemochromatosis (Table 36.1). Type 1 is characterized by autosomal recessive mutations in the HFE gene which encodes a protein responsible for regulating hepcidin production. In type 1 hemochromatosis, increased iron absorption from the diet results in excessive iron accumulation in cells. A similar mechanism occurs in type 2 hemochromatosis, which is caused by autosomal recessive mutations in the HJV gene that codes for an iron regulatory protein named hemojuvelin. Defects in iron transporter proteins such as transferrin and ferroportin can give rise to autosomal recessive type 3 and autosomal dominant type 4 hemochromatosis, respectively.40
Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
In both primary haemochromatosis due to increased intestinal absorption of iron, and in chronic haemolytic anaemias treated by transfusion, excess iron may be deposited in the myocardium. One in 200 Caucasian people in the US and Australia have hereditary haemochromatosis. It is due to a mutation in a gene called HFE and has autosomal recessive inheritance. Iron overload can also be acquired by receiving numerous blood transfusions, getting iron shots or injections, or consuming high levels of supplemental iron. Iron overload can occur in sickle cell disease, thalassaemia, X-linked sideroblastic anaemia, enzyme deficiencies (pyruvate kinase; glucose-6-phosphate dehydrogenase) and very rare protein transport disorders aceruloplasminaemia and atransferrinaemia.
Selected topics
Published in Henry J. Woodford, Essential Geriatrics, 2022
Iron deficiency anaemia (IDA) constitutes around 17–20% of anaemia in community-dwelling people aged over 65.1 It may be due to inadequate dietary iron, malabsorption or blood loss. It is associated with red blood cell microcytosis (mean cell volume [MCV] < 80 fL), which may also be seen in anaemia of chronic disease, sideroblastic anaemia and haemoglobin disorders (e.g. thalassaemia). It may present with normocytosis when coupled with deficiency in folate or vitamin B12. In addition to microcytosis, a low ferritin, serum iron and transferrin saturation ratio and a raised total iron-binding capacity all suggest IDA. Of these additional tests, a serum ferritin level is most helpful. A ferritin concentration < 12 mcg/dL always indicates iron deficiency, but a level of 12–45 mcg/dL is also suggestive.8 Ferritin is an acute-phase reactant and may be in the normal range if an inflammatory process is also present (i.e. 45–100 mcg/dL).9 Transferrin and serum iron fall in inflammatory states and transferrin saturation is low in chronic disease.10 These tests may be more helpful when iron overload is suspected. Transferrin saturation < 20% can indicate iron deficiency, while transferrin saturation > 50% suggests iron overload. Bone marrow examination would reveal decreased bodily iron stores.
Economic and clinical burden of managing transfusion-dependent β-thalassemia in the United States
Published in Journal of Medical Economics, 2023
Chuka Udeze, Kristin A. Evans, Yoojung Yang, Timothy Lillehaugen, Janna Manjelievskaia, Urvi Mujumdar, Nanxin Li, Biree Andemariam
The extent of iron overload observed in this patient population is notable. Chronic iron overload can arise from the pathophysiology of the disease, as well as from the use of regular RBCTs, and is associated with high morbidity and mortality9. ICT is recommended for the management of chronic iron overload in patients with TDT9, with certain chelators demonstrating long-term safety and efficacy in patients as young as 2 years old18. Consequently, the high prevalence of iron overload (87.9%) observed in patients of all ages, despite frequent claims for ICT, suggests that many patients may still experience elevated iron levels while being treated with ICT. Further, the numerically higher prevalence of iron overload in younger (0 to 11 years: 93.1%) vs. older patients (≥36 years: 82.5%) suggests that better management of this clinical complication may be warranted, particularly in pediatric patients with TDT.
An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment
Published in Hemoglobin, 2023
Mohammadreza Saeidnia, Pooria Fazeli, Arghavan Farzi, Maryam Atefy Nezhad, Mojtaba Shabani-Borujeni, Mehran Erfani, Gholamhossein Tamaddon, Mehran Karimi
As noted previously, iron overload is initially responsible for complications in β-thal patients, such as organ injury even in NTDT (β-TI) patients. Transfusion-dependent thalassemia patients undergo continuous transfusion and iron overload will occur quickly; in the case of NTDT patients, secondary iron overload accumulation is mediated by elevated iron absorption that evolves from food digestion in the gastrointestinal tract. Phlebotomy and iron chelation are the sole candidates for iron overload treatment. Even though phlebotomy is an extremely effective option for iron chelating, it is not suitable for β-thal patients [except after bone marrow transplantation (BMT)]. The NTDT patients cannot maintain a stable Hb level, and they become symptomatic after phlebotomy. Transfusion may be an appropriate intervention for outpatients; nevertheless, its potency for rapidly reducing cardiac iron overload is not plausible. Therefore, the best therapy for iron overload in β-thal patients is iron chelator drugs. The purpose of using chelation therapy is to achieve LIC of 3 mg/g dry weight or for serum FER level to achieve 300.0 ng/mL. The most common drugs prescribed for chelation therapy include deferoxamine (DFO), (injectable), deferiprone (DFP), and deferasirox (DFX) (oral usage); after the introduction of these oral drugs, prescriptions of DFO have decreased in North America and Europe owing to the difficulty of patient compliance with the regimen [42].
SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control
Published in Journal of Dietary Supplements, 2023
Sreus A.G. Naidu, Roger A. Clemens, A. Satyanarayan Naidu
In human physiology, the dietary iron absorption is regulated in the GI tract via hepcidin from macrophages and eventually contributes to the surge in serum ferritin levels (24). Free iron compounds such as ‘non-transferable bound iron’ and ‘labile plasma iron’ accumulate in plasma and cells via saturated iron-storage proteins (ISPs) (25). Iron is potentially toxic due to its redox activity. Insufficient iron supply to erythroid cells, the major iron consumer in the body, leads to various forms of anemia. On the other hand, iron overload (hemochromatosis) may lead to tissue damage and diseases of liver, pancreas, and heart. Therefore, Fe-R-H is tightly regulated at the cellular and systemic level by iron regulatory proteins (IRP1, IRP2) and hepcidin (26). The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor responds to oxidative/electrophilic stress and regulates several genes involved in iron metabolism, heme synthesis, Hb catabolism, iron storage, and iron export (27).