How do I interpret the results of serum ferritin and transferrin saturation in the context of iron deficiency?

Interpreting serum ferritin and transferrin saturation (TSAT) is crucial for diagnosing iron deficiency, with specific thresholds varying based on the patient's clinical context ¹,². Serum ferritin is the primary indicator of total body iron stores [1, 2, (Saboor et al., 2021)]. A low serum ferritin level, typically below 15 micrograms/L or 30 micrograms/L, is generally indicative of iron deficiency ¹,². However, ferritin is an acute phase reactant, meaning its levels can be elevated in the presence of inflammation, infection, liver disease, or malignancy, potentially masking true iron deficiency [1, 2, (Saboor et al., 2021)]. Therefore, it is often recommended to interpret ferritin alongside inflammatory markers like C-reactive protein (CRP) ¹,².

Transferrin saturation (TSAT) reflects the amount of iron available for erythropoiesis and is calculated as (serum iron / total iron-binding capacity) x 100 [1, 2, (Saboor et al., 2021)]. A TSAT below 16% or 20% typically suggests iron deficiency ¹,².

In patients with chronic conditions, the diagnostic thresholds for iron deficiency may differ [3, (Packer et al., 2024)]. For instance, in individuals with chronic kidney disease (CKD), iron deficiency is suggested by a serum ferritin level below 100 micrograms/L, or below 200 micrograms/L if the patient is receiving erythropoiesis-stimulating agents (ESAs), alongside a TSAT below 20% ³. Similarly, in patients with chronic heart failure, iron deficiency is defined as a serum ferritin level less than 100 micrograms/L, or a serum ferritin level between 100-299 micrograms/L combined with a TSAT less than 20% [ (Packer et al., 2024)]. When both serum ferritin and TSAT are low, it strongly indicates iron deficiency ¹,². In cases where ferritin levels are normal or elevated due to inflammation, but TSAT is low, it may suggest functional iron deficiency, particularly in chronic inflammatory states [ (Saboor et al., 2021), (Packer et al., 2024)].