Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload

Abstract

Ferritin levels and trends are widely used to manage iron overload and assess the efficacy of prescribed iron chelation in patients with transfusional iron loading. A retrospective cohort study was conducted in 134 patients with transfusion-dependent anemia, over a period of up to 9 years. To determine whether the trends in ferritin adequately reflect the changes in total body iron, changes in ferritin between consecutive liver iron measurements by magnetic resonance imaging (MRI) were compared to changes in liver iron concentrations (LIC), a measure of total body iron. The time period between two consecutive LIC measurements was defined as a segment. Trends in ferritin were considered to predict the change in LIC within a segment if the change in one parameter was less than twofold that of the other, and was in the same direction. Using the exclusion criteria detailed in methods, the trends in ferritin were compared to changes in LIC in 358 segments. An agreement between ferritin trends and LIC changes was found in only 38% of the 358 segments examined. Furthermore, the change in ferritin was in opposite direction to that of LIC in 26% of the segments. Trends in ferritin were a worse predictor of changes in LIC in sickle cell disease than in thalassemia (P < 0.01). While ferritin is a convenient measure of iron status; ferritin trends were unable to predict changes in LIC in individual patients. Ferritin trends need to be interpreted with caution and confirmed by direct measurement of LIC.

Long-term Erythrocytapheresis Is Associated With Reduced Liver Iron Concentration in Sickle Cell Disease

“…These results are consistent with the previous reports of serum ferritin having a linear relationship with LIC at levels <1500 ng/mL. 14,15 In this study it appears that the impact of simple transfusion was obviated by LTE. We found no association between simple transfusion and serum ferritin or LIC.…”

“…14-16 A recent study found agreement between serum ferritin trends and MRI measures of LIC in only 38% of subjects, suggesting that MRI measures may be superior for identifying iron overload as compared with serum ferritin alone. 15 Data from chronically transfused SCD patients from the STOP and STOP2 trials, most of whom were on chelation therapy, consistently showed that ferritin levels <1500 ng/mL correlated with low LIC, whereas ferritin levels of >3000 ng/ mL predicted LIC > 10 mg/g DW. 14 This may be explained by rapid serum ferritin level changes at lower iron load (< 1500 ng/mL) with a slower and less predictable rate of change at moderate iron load (1500 to 3000 ng/mL).…”

Thalassemia 2016: Modern medicine battles an ancient disease

“…Serum parameters (serum iron and transferrin saturation) gave way to the widely available serum ferritin, which is inexpensive and useful for routine clinical assessment. However ferritin is subject to many variations, and even when measured frequently, may not accurately reflect tissue iron burden [39]. Recently, scientific studies have led to better understanding of iron trafficking, including how iron accumulates in tissues which were not intended to store iron [40].…”

Welder’s pulmonary hemosiderosis associated with systemic iron overload following exacerbation of acute adult T-cell leukemia/lymphoma

“…However, increased serum ferritin is caused by several conditions, including inflammatory diseases, tissue damage, hematological malignancy, and immunodeficiency, and it does not accurately assess iron overload. 10,11 According to the clinical course shown in Fig. 4, the ferritin level did not improve following therapy for ATLL.…”