From the Guidelines
Elevated TSAT with normal ferritin levels can occur due to functional iron deficiency, where there is a need for a greater amount of iron to support hemoglobin synthesis than can be released from iron stores, despite adequate iron stores, as indicated by normal serum ferritin levels 1. This condition can be caused by pharmacological stimulation of erythropoiesis by Epoetin, leading to a decrease in TSAT levels consistent with iron deficiency despite normal or elevated serum ferritin. Some key points to consider in this scenario include:
- The distinction between absolute and functional iron deficiency is crucial in understanding what constitutes adequate TSAT and serum ferritin levels in Epoetin-treated patients 1.
- Functional iron deficiency can occur in the presence of adequate iron stores, as indicated by normal serum ferritin levels, but with a need for a greater amount of iron to support hemoglobin synthesis 1.
- A common clinical problem is distinguishing between functional iron deficiency and an inflammatory iron block, since the TSAT may be < 20% and serum ferritin may be 100 to 700 ng/mL in both situations 1.
- If it is not clear which of these conditions exists, it is recommended that weekly IV iron (50 to 125 mg) be given for up to 8 to 10 doses to assess the erythropoietic response 1. In clinical practice, it is essential to consider the patient's overall clinical context, including their medical history, current medications, and laboratory results, to determine the underlying cause of elevated TSAT with normal ferritin levels and to guide further evaluation and management.
From the Research
Elevated TSAT and Normal Ferritin
- TSAT (transferrin saturation) and ferritin are two important markers used to assess iron status in the body.
- Elevated TSAT with normal ferritin levels can be observed in certain conditions, as seen in studies 2, 3, 4, 5, 6.
- A study published in Haematologica 2 found that elevated TSAT (>80%) was associated with inferior clinical outcomes in patients with myelodysplastic syndromes, regardless of ferritin levels.
- Another study published in PloS one 3 found that patients with low TSAT (<20%) and high ferritin levels had a higher risk of cerebrovascular and cardiovascular disease, while patients with high TSAT and low ferritin had a lower risk.
- A study in the European journal of heart failure 4 suggested that a low TSAT (<20%) is a reliable indicator of the effect of intravenous iron on reducing major heart failure events, regardless of serum ferritin levels.
- The diagnosis and management of hereditary hemochromatosis, a genetic disorder associated with iron overload, often involve laboratory testing for serum ferritin and TSAT, as well as genetic testing for the HFE mutation 5.
- A recent study published in Circulation. Heart failure 6 found that low TSAT, but not ferritin concentrations, was significantly associated with adverse outcomes in heart failure patients.
Possible Explanations
- Elevated TSAT with normal ferritin levels may indicate the presence of oxidative stress or iron overload, as suggested by the study in Haematologica 2.
- It is also possible that TSAT is a more sensitive marker of iron status than ferritin, as suggested by the study in the European journal of heart failure 4.
- The relationship between TSAT, ferritin, and clinical outcomes is complex and may depend on various factors, including the underlying disease or condition, as seen in the studies 2, 3, 4, 5, 6.