What is Transferrin Saturation?
Transferrin saturation (TSAT) is the percentage of iron-binding sites on transferrin that are occupied by iron, calculated as (serum iron ÷ TIBC) × 100, and it directly reflects the amount of iron available for red blood cell production rather than total body iron stores. 1
Calculation and Measurement
TSAT is calculated using the formula: TSAT (%) = (serum iron / TIBC) × 100, where TIBC (total iron-binding capacity) measures the iron-binding capacity within serum and reflects the availability of iron-binding sites on transferrin. 1
Transferrin can be converted to TIBC using the formula: TIBC (μmol/L) = Transferrin (g/L) × 25.1. 1
Laboratory evaluation following IV iron should include a CBC and iron parameters (ferritin, TSAT) 4 to 8 weeks after the last infusion—iron parameters should not be evaluated within 4 weeks of a total dose iron infusion, as circulating iron interferes with the assay leading to spurious results. 2, 1
Clinical Interpretation in Your Patient's Context
Normal Range and Diagnostic Thresholds
Normal TSAT range in adults is typically 20-50%. 1
TSAT <20% indicates iron-deficient erythropoiesis (insufficient iron available for hemoglobin synthesis), regardless of ferritin levels. 1
TSAT >50% may indicate iron overload conditions such as hereditary hemochromatosis. 1
Assessing Iron Overload vs. Functional Iron Deficiency
In your patient with hand pain (possible hemochromatosis arthropathy), elevated ALT, and high ferritin, the TSAT is the critical discriminator:
If TSAT >50%: This suggests true iron overload (hereditary hemochromatosis), where both ferritin and TSAT are elevated. 1 The elevated ALT reflects hepatic iron deposition, and hand pain suggests iron arthropathy affecting metacarpophalangeal joints. 3
If TSAT <20% with ferritin >100 ng/mL: This defines functional iron deficiency despite elevated ferritin—the high ferritin reflects inflammation (acute phase reactant) and iron sequestration, while low TSAT indicates iron is trapped in storage sites and unavailable for erythropoiesis due to hepcidin activation. 1 The elevated ALT may reflect underlying chronic liver disease or inflammation driving the functional iron deficiency. 3
Why TSAT is More Reliable Than Ferritin Alone
TSAT is less affected by inflammation than ferritin, making it a more reliable marker of iron status in inflammatory conditions. 1
Ferritin <100 ng/mL has only 35-48% sensitivity for detecting iron deficiency, whereas TSAT <20% demonstrates 93% specificity for true iron deficiency. 1
TSAT directly reflects iron availability for erythropoiesis, whereas ferritin measures total body iron stores—TSAT is an indicator of iron-deficient erythropoiesis rather than iron depletion. 1
Factors Affecting TSAT Measurement
Physiologic Variation
Diurnal variation: TSAT levels rise in the morning and fall at night due to circadian rhythm of serum iron concentration. 4
Recent meals: Serum iron concentration increases after each meal, affecting TSAT. 4
Day-to-day variation: TSAT has greater variation within individuals than hemoglobin concentration. 4
Pathologic Factors
Inflammation and infection: Can decrease serum iron concentration and lower TSAT acutely or chronically. 4
Chronic inflammatory conditions (CKD, heart failure, IBD, cancer): Hepcidin activation traps iron in storage sites, lowering TSAT despite adequate or elevated ferritin. 1
Diagnostic Algorithm for Your Patient
Step 1 – Measure complete iron panel:
- Serum iron, TIBC, TSAT, ferritin, and inflammatory markers (CRP). 1
Step 2 – Interpret TSAT in context:
| TSAT Result | Ferritin | Interpretation | Next Steps |
|---|---|---|---|
| >50% | Elevated | Iron overload (hemochromatosis) | HFE gene testing, liver imaging, consider liver biopsy for hepatic iron concentration [3] |
| <20% | >100 ng/mL | Functional iron deficiency with inflammation | Evaluate for chronic inflammatory conditions (CKD, heart failure, IBD, malignancy); consider IV iron [1] |
| 20-50% | Elevated | Inflammation without iron deficiency | Investigate cause of elevated ALT and ferritin (liver disease, malignancy) [3] |
Step 3 – Additional evaluation:
For suspected hemochromatosis (TSAT >50%): HFE mutation testing (C282Y, H63D), liver MRI for iron quantification, and assess for end-organ damage (diabetes, cardiomyopathy). 3
For functional iron deficiency (TSAT <20%, ferritin >100): Evaluate for chronic kidney disease (creatinine, eGFR), heart failure (BNP, echocardiogram), inflammatory bowel disease, or malignancy. 1
Common Pitfalls to Avoid
Do not interpret a single TSAT value in isolation—consider clinical context, timing of blood draw, recent meals, and inflammatory conditions. 4
Do not rely on ferritin alone in the setting of elevated ALT or suspected inflammation—ferritin can be falsely elevated as an acute phase reactant while true iron deficiency exists. 1
Do not assume iron overload based solely on elevated ferritin—TSAT >50% is required to confirm true iron overload versus inflammation-driven ferritin elevation. 1, 3
Do not measure iron parameters within 4 weeks of IV iron administration—circulating iron produces falsely elevated results. 2, 1
In chronic inflammatory states, ferritin up to 100-300 ng/mL may still indicate true iron deficiency—TSAT <20% is the more reliable indicator in this context. 1