Guidelines for quantifying iron overload

Abstract

Both primary and secondary iron overload are increasingly prevalent in the United States because of immigration from the Far East, increasing transfusion therapy in sickle cell disease, and improved survivorship of hematologic malignancies. This chapter describes the use of historical data, serological measures, and MRI to estimate somatic iron burden. Before chelation therapy, transfusional volume is an accurate method for estimating liver iron burden, whereas transferrin saturation reflects the risk of extrahepatic iron deposition. In chronically transfused patients, trends in serum ferritin are helpful, inexpensive guides to relative changes in somatic iron stores. However, intersubject variability is quite high and ferritin values may change disparately from trends in total body iron load over periods of several years. Liver biopsy was once used to anchor trends in serum ferritin, but it is invasive and plagued by sampling variability. As a result, we recommend annual liver iron concentration measurements by MRI for all patients on chronic transfusion therapy. Furthermore, it is important to measure cardiac T2* by MRI every 6-24 months depending on the clinical risk of cardiac iron deposition. Recent validation data for pancreas and pituitary iron assessments are also presented, but further confirmatory data are suggested before these techniques can be recommended for routine clinical use.

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

“…2,3 Nonetheless, because a single measurement only reflects the labile iron species present during the previous 24-48 hours, repeated measurements are imperative to assess a potential risk of impending NTBI toxicity. 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.…”

“…However, it is well known that as an acute phase reactant, serum ferritin levels are influenced by factors such as inflammation and liver disease and are not, therefore, exclusively indicative of toxic parenchymal iron overload. 17 Moreover, with the introduction of T2*-weighted magnetic resonance imaging for the assessment of tissue iron overload, 18 it became clear that organs such as the heart and endocrine glands load iron differently compared to the liver and non-commensurately with serum ferritin. Studies of plasma NTBI in patients with thalassemia major suggest that NTBI may be an important early indicator of extra-hepatic iron toxicity.…”

T2* MRI Correlates with R2 Liver Iron Concentration in Transfusion Dependent Thalassaemia

“…This population appears to be prone to the greatest degree of discrepancy in all validation studies. Assessment of patients falling into the category of severe iron overload is important because whilst cardiac and liver iron concentrations are often discordant, LIC>15mg/g have been found to correlate with increased risk of cardiac disease and premature death [15]. However, whilst it is crucial to identify those patients with high LIC in order to implement aggressive chelation therapy, accurate assessment of LIC is more relevant in patients with lower LIC to facilitate chelation dose modifications and thus avoid excessive exposure and unnecessary toxicity.…”

Iron overload in patients with rare hereditary hemolytic anemia: Evidence‐based suggestion on whom and how to screen

“…Ideally, to interpret TSAT measurements, patients should withhold iron chelation for at least 1 day before measurement, as the presence of iron chelation in the bloodstream may influence the results 3. Notably, patients with LIC ≥ 7 mg/g, despite low ferritin levels, did have very high TSAT levels suggesting that TSAT may be helpful in recognizing patients with iron overload despite a low ferritin.…”