What does a Transferrin Saturation (Tsat) of 16% indicate and how is it managed?

Transferrin Saturation of 16%: Interpretation and Management

A TSAT of 16% indicates iron deficiency and warrants iron supplementation if accompanied by anemia (hemoglobin <11 g/dL in women, <13 g/dL in men), as this value falls below the diagnostic threshold of <20% used in most clinical contexts. 1

Diagnostic Interpretation

A TSAT of 16% confirms iron-deficient erythropoiesis and represents inadequate iron availability for red blood cell production. 1

• In healthy individuals without inflammation, TSAT <16% confirms absolute iron deficiency with 93% specificity. 1
• In chronic inflammatory conditions (CKD, heart failure, IBD, cancer), the diagnostic threshold is TSAT <20%, making your value of 16% clearly abnormal. 1
• This value indicates a high proportion of vacant iron-binding sites on transferrin, signaling insufficient iron delivery to the bone marrow. 1

Clinical Context Matters

You must check hemoglobin and ferritin levels alongside TSAT to determine if treatment is indicated. 2

If Anemia is Present (Hb <11 g/dL):

• Iron supplementation is indicated regardless of ferritin levels up to 800 ng/mL. 2
• The combination of TSAT 16% with low ferritin (<30 ng/mL) confirms absolute iron deficiency. 1
• Even with ferritin 30-100 ng/mL, TSAT 16% suggests functional iron deficiency requiring treatment. 1

If No Anemia is Present:

• Isolated low TSAT without anemia does not warrant treatment and supplementation is potentially harmful. 2
• Iron supplementation in the absence of anemia can lead to iron overload and organ damage. 2

Treatment Algorithm

First-Line: Oral Iron Therapy

Start with ferrous sulfate 200 mg twice daily (or 325 mg daily/alternate days) if anemia is present. 2

• This is the cheapest and most effective oral iron option. 2
• Lower doses (80-100 mg elemental iron daily) may be equally effective with better tolerability. 2
• Continue for 3 months after hemoglobin correction to replenish iron stores. 2
• Recheck hemoglobin, ferritin, and TSAT after 8-12 weeks to assess response. 2

Second-Line: Intravenous Iron

Switch to IV iron if: 2

• Oral iron intolerance or gastrointestinal side effects occur
• Malabsorption conditions are present
• Chronic inflammatory conditions exist
• Ongoing blood loss continues
• Rapid correction is needed

Ferric carboxymaltose (Ferinject) 1000 mg over 15 minutes is the preferred IV formulation. 2

Special Population Considerations

Chronic Kidney Disease Patients:

• Target TSAT >20% and ferritin >200 ng/mL to minimize erythropoiesis-stimulating agent (ESA) requirements. 2
• In CKD patients with hemoglobin <10 g/dL, TSAT 16% mandates iron supplementation before or concurrent with ESA therapy. 3
• Absolute iron deficiency in CKD is defined as TSAT <20% and ferritin <100 ng/mL. 3

Heart Failure Patients:

• Consider IV iron if symptomatic, particularly with ferritin <100 μg/L or 100-300 μg/L with TSAT <20%. 4
• Low TSAT is more strongly associated with adverse outcomes in heart failure with preserved ejection fraction. 5
• Oral iron is inadequate in heart failure; IV iron improves functional status and quality of life. 4

Critical Pitfalls to Avoid

Do not treat isolated low TSAT without confirming anemia first. 2 This is the most common error and can lead to iatrogenic iron overload.

Do not rely on TSAT alone—always interpret alongside ferritin and hemoglobin. 1, 4 A single TSAT value in isolation is insufficient for clinical decision-making.

Account for inflammatory status when interpreting results. 1 In chronic inflammatory conditions, ferritin may be falsely elevated despite true iron deficiency, making TSAT a more reliable indicator. 4

Recognize timing issues with testing: 1

• TSAT has diurnal variation (rises morning, falls evening)
• Serum iron increases after meals
• Inflammation and infection decrease serum iron
• Do not check iron parameters within 4 weeks of IV iron infusion

Monitoring Strategy

If treatment is initiated, repeat complete blood count and iron parameters (hemoglobin, ferritin, TSAT) after 8-12 weeks. 2

If no response to oral iron occurs: 2

• Consider switching to IV iron
• Investigate for ongoing blood loss
• Evaluate for malabsorption

Target TSAT ≥20% after iron repletion to ensure adequate iron availability for erythropoiesis. 1