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Related Concept Videos

Complexation Equilibria: The Chelate Effect01:19

Complexation Equilibria: The Chelate Effect

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In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
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Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...
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Extraction: Advanced Methods00:56

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Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...
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Masking and Demasking Agents01:19

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EDTA titrations may necessitate masking and demasking agents to temporarily protect a particular metal ion in a mixture from the EDTA reaction. These agents facilitate the sequential analysis of the metal ions by forming stable complexes with some—but not all—metal ions during certain steps.
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EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
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Antidotes01:17

Antidotes

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Antidotes are medicinal substances used to counteract the harmful effects of toxins or drugs in the body. They function in various ways, each uniquely designed to combat specific toxic compounds.
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Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload
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Thalassemia Intermedia: Chelator or Not?

Yen-Chien Lee1,2, Chi-Tai Yen3, Yen-Ling Lee1

  • 1Department of Medical Oncology, Tainan Hospital, Ministry of Health and Welfare, Executive Yuan, Tainan 70043, Taiwan.

International Journal of Molecular Sciences
|September 9, 2022
PubMed
Summary

Iron overload is common in thalassemia intermedia (TI), a genetic blood disorder. Current research on iron chelation therapy in TI shows mixed results, highlighting the need for further studies on treatment effectiveness and optimal hemoglobin targets.

Keywords:
HbH diseaseiron chelation therapyiron overloadliver iron concentration (LIC)non-transfusion-dependent thalassemia (NTDT)pulmonary hypertensionthalassemia intermedia (TI)β-TI

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Area of Science:

  • Hematology
  • Genetic Disorders
  • Pharmacology

Background:

  • Thalassemia intermedia (TI) is a common genetic blood disorder, encompassing conditions like β-TI hemoglobin, E/β-thalassemia, and hemoglobin H (HbH) disease.
  • TI patients experience iron overload due to increased intestinal absorption, raising questions about iron chelation therapy's role in managing morbidity and mortality.
  • The life expectancy of TI patients now approaches that of thalassemia major (TM) patients due to advancements in treatment.

Purpose of the Study:

  • To review existing literature on iron-chelation-related thalassemia intermedia up to August 2022.
  • To evaluate the relationship between iron chelation therapy and patient outcomes in TI.
  • To identify thresholds for initiating and stopping iron chelation therapy in TI patients.

Main Methods:

  • Systematic review of available articles concerning iron chelation therapy in thalassemia intermedia.
  • Analysis of studies focusing on ferritin levels and associated morbidities in TI patients.
  • Examination of intervention studies involving iron chelation therapy, including a subgroup requiring regular transfusions.

Main Results:

  • Osteoporosis was the most frequent morbidity in TI patients, particularly those who had undergone splenectomy.
  • Suggested thresholds for initiating iron chelation therapy were Liver Iron Concentration (LIC) ≥ 5 mg/g/dw by MRI or ferritin > 300 ng/mL.
  • Suggested thresholds for stopping iron chelation therapy were a ferritin level ≤ 300 ng/mL. No studies demonstrated improved overall survival rates with iron chelation therapy.
  • Morbidities and mortality in TI may not solely be attributed to iron overload, with hypoxemia and hemolysis potentially playing significant roles.

Conclusions:

  • Further head-to-head studies are needed to compare various treatment modalities for TI, including hydroxyurea, fetal hemoglobin-inducing agents, hypertransfusion, and iron chelation therapy.
  • Research should differentiate between β-TI and HbH disease in treatment studies.
  • Determining target hemoglobin levels for both β-TI and HbH disease is crucial for optimizing patient management.