Levels of non‐transferrin‐bound iron as an index of iron overload in patients with thalassaemia intermedia

Abstract

SummaryNon-transferrin-bound iron (NTBI) was evaluated as an index of iron overload in a cross-sectional randomised study in 74 non-transfused patients with thalassaemia intermedia (TI). Mean NTBI (2AE92 ± 3AE43 lmol/l), serum ferritin (1023 ± 780 ng/ml) and liver iron concentration (LIC; 9AE0 ± 7AE4 mg Fe/g dry weight) were increased above reference-range levels. Significant positive correlations occurred between mean NTBI and LIC (Pearson correlation 0AE36; P = 0AE002) and serum ferritin (Pearson correlation 0AE421; P < 0AE0001); with higher levels observed in splenectomised patients. NTBI assessment has potential as a simple reliable approach to determining iron status in TI.

Non-transfusion-dependent thalassemias

“…It has also been suggested that the spleen may be a reservoir of excess iron and may have a possible scavenging effect on iron free species such as non-transferrin bound iron, which may explain the higher serum level of this free iron species in splenectomized NTDT patients 41 and the observation that splenectomized patients have a higher rate of iron-related organ morbidity than their non-splenectomized peers. 30 Splenectomy also places NTDT patients of all ages at risk of morbidity and mortality due to infection.…”

“…27 This in turn leads to depletion of macrophage iron, relatively lower levels of serum ferritin, and preferential portal and hepatocyte iron loading (increased liver iron concentration), 40 with subsequent release into the circulation of free iron species (labile plasma iron and non-transferrin bound iron with a consequent increase in intracellular labile iron pool) that can cause target-organ damage. 41 By contrast, regularly transfused patients do not have low hepcidin levels, and iron is preferentially distributed to the reticuloendothelial system, thereby stimulating ferritin synthesis and its release into circulation, resulting in high serum ferritin levels. It should be noted that apart from this primary source of iron overload in NTDT patients, they can eventually accumulate iron from occasional or more frequent transfusions which may be indicated as illustrated in the management section.…”

“…42 Nonetheless, iron overload in NTDT patients is a cumulative process as evident from studies documenting positive correlations between iron overload indices and advancing age. 25,41,[43][44][45] Thus, a considerable proportion of NTDT patients eventually accumulate iron to liver iron concentration thresholds of clinical significance. 25,40,42,46,47 An association between iron loading evident from longitudinal elevations in serum ferritin level and worsening of hepatic fibrosis in patients with β-thalassemia intermedia has been established.…”

Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy

“…was associated with an increased rate of morbidity in patients with bT intermedia, with an increased incidence of vascular morbidity and an earlier appearance of endocrine and bone disease (23). Moreover, the need for iron chelation therapy in these patients who have never been transfused or have received only occasional transfusions has just recently started to emerge after documenting substantially high LIC and non-transferrin-bound iron values in such patients (24,25).…”

Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders

“…18 The majority of the assays in the current round robin have given useful insights into the efficacy of iron chelation in transfusional siderotic patients and of phlebotomy in patients with HH. 2,3,9,13,[19][20][21][22][37][38][39][40] Despite this finding, in the absence of studies that assess the independent relation of assay levels to clinical outcome in these various categories of patients, the clinically most relevant assay formats and their decision limits remain unknown.…”