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Updated: Jan 14, 2026

A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Should Serum Transferrin Saturation Be Included as a Therapeutic Target in Addition to Serum Ferritin in Treating
Nils Thorm Milman1, Christina Ellervik2,3,4,5
1Department of Clinical Biochemistry, Naestved Hospital, Zealand University Hospital, Naestved, Denmark.
Abstract:
In HFE-hemochromatosis, transferrin saturation (TSAT) indirectly reflects plasma non-transferrin-bound iron (NTBI), which drives iron overload and tissue damage. TSAT above ~75% suggests harmful NTBI levels. Despite its clinical relevance, NTBI remains understudied due to the limitations of current assays. High TSAT levels persist during maintenance therapy, yet some guidelines omit TSAT monitoring, though it correlates with symptoms like fatigue and joint pain. Monitoring TSAT may improve outcomes. Randomized trials comparing ferritin-only versus ferritin-plus-TSAT-guided treatment are needed. Consideration should be given to approaches that minimize plasma NTBI in managing and monitoring patients with hemochromatosis. Until reliable NTBI testing has been established, TSAT should be included in the management of HFE-hemochromatosis.
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