iron studies interpretation

the components

analyte	physiology	clinical significance
Ferritin	Intracellular iron storage protein.	Best non-invasive test for iron stores. Acute Phase Reactant (False $\uparrow$ in inflammation).
Serum Iron	Iron bound to transferrin in blood.	Highly variable (diurnal). Low utility alone.
Transferrin / TIBC	Transport protein for iron.	Increases when body is “hungry” for iron.
Transferrin Saturation (Tsats)	% of transferrin sites occupied by iron. $(Iron/TIBC)\times 100$.	< 20%: Iron Deficiency. > 45-50%: Iron Overload.

interpretation patterns

profile	ferritin	serum iron	TIBC / transferrin	tsats
Iron Deficiency Anemia (IDA)	Low (< 30)	Low	High	Low (< 20%)
Anemia of Chronic Disease (ACD)	Normal / High (> 100)	Low	Low / Normal	Normal / Low
Mixed (IDA + Inflammation)	Normal (30–100)	Low	Normal / High	Low (< 20%)
Iron Overload (Hemochromatosis)	High (> 300)	High	Low	High (> 45-55%)
Pregnancy	Often Low	Normal	High	Low

evidence based diagnosis

iron deficiency anemia (ida)

• Gold Standard: Bone marrow biopsy (rarely done).
• Ferritin < 15 $\mu$g/L: Specificity 99% for IDA (Diagnostic).
• Ferritin < 30 $\mu$g/L: Sensitivity 92%, Spec 98%.
• Ferritin 30–100 $\mu$g/L: “Grey Zone”.
  • If inflammation present (CRP elevated), IDA is still possible.
  • Soluble Transferrin Receptor (sTfR): Can distinguish. High in IDA, Normal in ACD.

haemochromatosis

• Screening: Transferrin Saturation (Tsats).
  • Cut-off: > 45% (Sensitivity > 90%).
  • Ferritin alone is a poor screen (often raised by alcohol, fatty liver, metabolic syndrome).
• Diagnosis: HFE Genotyping (C282Y homozygosity).

decision flowchart

graph TD
    A[Patient with Anemia] --> B[Check Ferritin]
    B -- < 30 --> C[**Iron Deficiency**]
    B -- > 100 --> D[Check Tsats]
    B -- 30-100 --> E{Inflammation?}
    E -- Yes (High CRP) --> F[Check Soluble Transferrin Receptor\nor Trial of Iron]
    E -- No --> C
    D -- < 20% --> G[**Anemia of Chronic Disease**]
    D -- > 45% --> H[**Iron Overload?**\nCheck Genotype]
    D -- 20-45% --> I[Other Causes\n(Hemolysis, Renal, Marrow)]

pearls & pitfalls

• The “Inflamed” Ferritin: In CKD, Heart Failure, or Rheumatoid Arthritis, a Ferritin of 50–100 may essentially represent functional iron deficiency.
• Diurnal Variation: Serum iron peaks in the morning and drops in the evening. This affects Tsats. Always measure fasting/AM if equivocal.
• Oral Iron: Wait 24–48h after an oral iron dose before measuring iron/Tsats (transient spike).