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Total iron-binding capacity (TIBC) is a crucial laboratory test for diagnosing iron metabolism disorders and inflammatory diseases.[1] Iron-binding capacity is the capacity at which transferrin binds with iron.[2] Transferrin, previously known as siderophilin, is the principal plasma transport protein for ferric iron (Fe3+). Transferrin has a molecular weight of 79.6 kDa and comprises 5.5% carbohydrates. Transferrin is a single polypeptide chain with 2 N-linked oligosaccharides and 2 homologous domains, each with a Fe3+-binding site.[3] Transferrin is synthesized mainly in the liver and circulates with a half-life of 8 to 10 days. Transferrin reversibly binds 2 ferric ions with high affinity at physiological pH but lower affinity at decreased pH; this permits iron release within intracellular compartments. After cellular delivery of iron through receptor-mediated endocytosis, apotransferrin is recycled back into circulation.[4] A few clinical indications exist for directly measuring transferrin. However, the indirect laboratory assessment of transferrin concentration may be inferred by TIBC. TIBC may be calculated as total or unsaturated.[5] Depleting bodily iron stores by any mechanism increases circulating levels of transferrin. At optimal health, only one-third of transferrin is saturated with iron, and serum transferrin has an extra binding capacity of 67%, the unsaturated iron-binding capacity (UIBC).[6] TIBC is the total serum iron and UIBC. Percentage transferrin saturation is calculated by dividing serum iron by TIBC and multiplying the result by 100.[7]

Foods contain iron in heme and non-heme forms. Bound elemental iron is released in the stomach through the action of hydrochloric acid. Ferric iron is enzymatically reduced to ferrous iron and is absorbed in the gut by the divalent metal ion transporter located on the apical surface of the intestinal epithelium.[17] Heme iron is absorbed directly through a heme transporter. Absorbed iron is stored with apoferritin within the enterocytes or absorbed into the blood through ferroportin.[18] Ferroportin is a transporter protein on the basolateral surface of enterocytes and many other cells. Ferrous iron is converted to ferric iron by hephaestin before being transported into the blood. The ferric iron is picked up by apotransferrin, a circulating protein that delivers iron to various tissues, primarily the liver and bone.[19] Technically, apotransferrin carrying 1 or 2 ferric ions is transferrin; these terms are frequently used interchangeably due to the noncovalent bond with ferric irons. The majority of iron is incorporated into hemoglobin or myoglobin; some is used to synthesize certain enzymes.[20] Iron is stored in macrophages with the storage protein apoferritin. In healthy individuals, small amounts of iron are lost through epidermal and enterocytic shedding; small amounts are lost in sweat. Menstruation and other forms of bleeding also cause iron loss.[21] The recommended daily iron intake for adults is as follows: Men and non-menstruating women: 8 mg Menstruating women: 18 mg Pregnancy: 27 mg Generally, the total transferrin in the blood is only 33% saturated. The total transferrin saturation falls to 16% or less during iron-deficient states.[22][23]

The assessment of iron-binding capacity within an anemia workup demands a cohesive effort among diverse interprofessional team members, each contributing crucial expertise at various stages of the diagnostic process. Clinicians, serving as the frontline decision-makers, are tasked with ordering the test based on their clinical judgment and suspicion of iron-related disorders. Nurses or phlebotomists, proficient in blood sample collection techniques, ensure the proper procurement of specimens necessary for analysis. In the laboratory setting, pathologists oversee the overall diagnostic process, providing clinical interpretation and guidance. Laboratory assistants support the logistical aspects of sample handling and processing, ensuring samples are properly labeled and prepared for analysis. Technicians, skilled in conducting the iron-binding capacity test, carry out the analytical procedures with precision and accuracy. Effective communication and coordination among these team members are essential to ensure seamless workflow and accurate interpretation of results. Collaboration facilitates the timely identification of iron metabolism disorders, enabling appropriate interventions and patient management strategies. By leveraging the expertise of each team member, healthcare providers can optimize patient care and outcomes in the context of anemia evaluation.