Divide or subtract: transferrin saturation versus unbound iron binding capacity (UIBC)

Transferrin saturation in plasma (P-TSAT) is 100 × P-iron/P-total iron binding capacity (P-TIBC). It is still used to diagnose iron deficiency, although P-ferritin is considered to be a better test. Both tests are sensitive to inflammation: P-TSAT decreases and P-ferritin increases. Unbound iron binding capacity in plasma (P-UIBC), which is P-TIBC minus P-iron, has a better diagnostic accuracy for iron deficiency than P-TSAT. However, how P-UIBC reacts in inflammation is less well known. We used cross-sectional data from 21681 patients to study how P-UIBC, P-TSAT, and P-ferritin varied with P-CRP. In a subpopulation of 8928 patients without inflammation (P-CRP ≤ 1 mg/L), we compared the diagnostic accuracy of P-TSAT and P-UIBC, using P-ferritin less than 15, 20, and 30 µg/L as reference standards for iron deficiency. We also estimated which values of P-UIBC and P-TSAT corresponded to a P-ferritin of 15, 20, and 30 µg/L. P-UIBC varied much less with P-CRP than did P-TSAT and P-ferritin. P-UIBC had better diagnostic accuracy than P-TSAT. Using P-ferritin < 20 µg/L as a reference standard, the areas under the ROC curves were 0.894 (95% confidence interval 0.883-0.905) for P-UIBC and 0.850 (0.836-0.864) for P-TSAT. At various ages, the values corresponding to a P-ferritin of 20 µg/L varied around 60 µmol/L for P-UIBC and around 20% for P-TSAT. In conclusion, when diagnosing iron deficiency, calculating P-UIBC is a better way of using P-iron and P-TIBC than calculating P-TSAT.