Required section · Section 3 of 6

Focused instruction: variability and look-alikes

Calculate transferrin saturation as serum iron divided by TIBC multiplied by 100. Serum iron and saturation have substantial biologic variability, so collection timing, food, and recent oral iron exposure matter when comparing results. The Mayo Clinic Laboratories SFEC catalog entry prefers collection before noon, eight-hour fasting when feasible, and no iron-containing supplement for 24 hours; local assay instructions remain controlling.

Group ferritin elevation by the iron-pattern mechanism and link each pattern to transport measurements and comparison conditions. Acute-phase signaling or cell injury can raise ferritin while TSAT is normal or low and transferrin/TIBC may fall; record C-reactive protein, liver indices, collection time, fasting status, and recent oral iron. Reduced transferrin production can raise calculated TSAT when TIBC is low; review liver context and the measured TIBC. Repeated transfusion or ineffective erythropoiesis can increase both ferritin and TSAT; compare serial values only when treatment history and collection context are available. A compatible hereditary pattern has persistently increased TSAT with ferritin elevation and requires the EASL confirmation pathway.

The Mayo Clinic Laboratories SFEC catalog entry gives collection guidance; EASL Clinical Practice Guidelines on haemochromatosis state that fasting does not improve diagnostic utility but recommend morning sampling. Compare serial TSAT, transferrin/TIBC, and ferritin only with collection context documented. EASL biochemical-suspicion thresholds and its MRI/biopsy confirmation rule are guidance thresholds, not laboratory reference intervals.

Matrix grouping iron patterns by acute-phase signaling or cell injury, reduced transferrin production, increased iron input or ineffective erythropoiesis, and persistent increased circulating availability; each row links ferritin to TSAT or transferrin/TIBC and a collection or serial action. — Figure 1Mechanism-based comparison of ferritin, TSAT, transferrin/TIBC, and collection or serial actions.

Pattern matrix for the iron-overload differential
Mechanism / iron-pattern effect	Ferritin	TSAT and transferrin/TIBC	Collection or serial action
Acute-phase response or cell injury	Often high	TSAT normal or low; transferrin/TIBC may decrease	Record CRP, liver indices, timing; compare serial values
Reduced transferrin production	May be high	TSAT may be high because TIBC is low	Review liver context and measured TIBC before inferring loading
Repeated transfusion or ineffective erythropoiesis	High	TSAT often high	Check transfusion/treatment history and serial trend
Persistent increased circulating iron availability	High	TSAT persistently high with compatible transferrin/TIBC	Use EASL threshold and confirmation pathway; do not diagnose from one panel

Knowledge checks

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Knowledge check 1

Which collection details should be considered when comparing serum iron and transferrin saturation? Select all that apply.

Choose at least 3 options.

Collection time

Food or fasting context

Recent oral iron exposure

ABO blood group

Knowledge check 2

A patient has high ferritin and high saturation with a transfusion history. Which interpretation is most defensible?

Choose one option.

Secondary transfusional iron loading remains in the differential.

The pattern proves HFE-related hemochromatosis.

Measured TIBC can be ignored when saturation is high.

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