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Soluble Transferrin Receptor (sTfR)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Sensitive Indicator of Cellular Iron Demand - Key Marker to Differentiate Iron Deficiency vs. Anemia of Chronic Disease)

Synonyms

  • sTfR
  • Soluble transferrin receptor
  • Serum transferrin receptor
  • sTFR
  • sCD71 (CD-71 receptor fragment)
  • Transferrin receptor-1 (TFR1) soluble form

Units of Measurement

  • nmol/L
  • mg/L
  • mg/dL
  • mg/100 mL
  • mg%
  • µg/mL

Unit Conversions

Molecular Weight of sTfR ≈ 85 kDa (85,000 g/mol)

nmol/L ↔ mg/L

1 nmol/L=0.085 mg/L1\ \text{nmol/L} = 0.085\ \text{mg/L}1 nmol/L=0.085 mg/L 1 mg/L=11.76 nmol/L1\ \text{mg/L} = 11.76\ \text{nmol/L}1 mg/L=11.76 nmol/L

mg/dL → mg/L

1 mg/dL=10 mg/L1\ \text{mg/dL} = 10\ \text{mg/L}1 mg/dL=10 mg/L

mg% = mg/dL

µg/mL → mg/L

1 µg/mL=1 mg/L1\ \text{µg/mL} = 1\ \text{mg/L}1 µg/mL=1 mg/L

Description

sTfR is the circulating extracellular fragment of the cellular transferrin receptor (CD71), released into plasma during receptor turnover.

It reflects:

  • Cellular iron requirement
  • Erythropoietic activity
  • Functional iron deficiency

Key Feature

Unlike ferritin, sTfR is NOT affected by inflammation, making it extremely valuable for distinguishing:

  • Iron deficiency anemia (IDA)
     vs.
  • Anemia of chronic disease/inflammation (ACD)

Physiological Role

Transferrin Receptor (TFR1) Functions

  • Located on erythroid precursors & metabolically active cells
  • Binds transferrin → imports iron into cells
  • sTfR in plasma correlates with total cellular receptor mass

Influence on sTfR Levels

  • ↑ when iron availability is low
  • ↑ when erythropoietic activity increases
  • Normal when inflammation causes anemia (ACD)

Clinical Significance

HIGH sTfR

1. Iron Deficiency Anemia

Most sensitive marker of true iron deficiency.

Levels rise because:

  • Cells increase transferrin receptors to capture more iron.

2. Functional Iron Deficiency

Seen in:

  • Chronic kidney disease (CKD)
  • EPO therapy
  • Chronic inflammatory diseases
  • Heart failure

3. Increased Erythropoiesis

  • Hemolytic anemia
  • Thalassemia
  • Polycythemia
  • Post-hemorrhage

4. Pregnancy

Higher demands → mild elevation.

LOW / NORMAL sTfR

Seen in:

  • Anemia of chronic disease (ACD)
  • Iron overload
  • Hypoproliferative anemias (e.g., aplastic anemia)

Normal sTfR effectively rules out iron deficiency in most cases.

Reference Intervals

(Tietz 8E + Mayo + ARUP + WHO iron deficiency panels)

Typical Adult Range

  • 1.0 – 2.5 mg/L
     (= 1000 – 2500 µg/L)
    (= 11.8 – 29 nmol/L)

Iron Deficiency Indicators

  • > 2.5 mg/L → suggests iron deficiency
  • > 4.0 mg/L → high likelihood of IDA
  • > 8–10 mg/L → severe iron deficiency / high erythropoietic drive

Pregnancy

  • Mild rise up to 3.5 mg/L can be normal.

Diagnostic Uses

1. Differentiate IDA vs. ACD

Most important application.

ConditionFerritinsTfR
Iron deficiency anemia↓↑
Anemia of chronic diseaseNormal/↑Normal
Mixed IDA + ACDNormal/↑↑

2. Functional Iron Deficiency in CKD

sTfR ↑ when:

  • Iron stores normal
  • But erythropoietic needs not met

3. Thalassemia / Hemoglobinopathies

Marked elevation due to high erythropoiesis.

4. Monitoring Iron Therapy

sTfR decreases with effective iron supplementation.

5. Pregnancy Iron Status Assessment

Better than ferritin due to inflammatory changes.

Analytical Notes

  • Measured by immunoassay (turbidimetry, ELISA, chemiluminescence)
  • Not influenced by acute inflammation
  • Hemolysis does not significantly affect results
  • Combine with ferritin for accurate iron status
  • sTfR/log ferritin index (sTfR-F index) improves diagnostic accuracy

sTfR / Log Ferritin Index

sTfR-F Index=sTfRlog⁡(Ferritin)\text{sTfR-F Index} = \frac{\text{sTfR}}{\log(\text{Ferritin})}sTfR-F Index=log(Ferritin)sTfR​

  • >2.0 → iron deficiency
  • 1–2 → possible mild deficiency
  • <1 → likely ACD

Clinical Pearls

  • Best marker of true iron deficiency, even with inflammation.
  • High sTfR + normal ferritin = classic for functional iron deficiency.
  • In thalassemia, sTfR is very high due to increased erythropoiesis.
  • Ferritin can be normal in IDA (especially if inflammatory disease present).
  • sTfR rises earlier than ferritin falls in early iron deficiency.

Interesting Fact

About 80% of transferrin receptors in the body reside in erythroid marrow, making sTfR an excellent surrogate of marrow iron demand.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Iron Metabolism
  2. WHO Guidelines on Iron Deficiency Assessment
  3. Mayo Clinic Laboratories - sTfR
  4. ARUP Consult - Iron Studies
  5. BSH Guidelines - Anemia Evaluation
  6. NEJM / Lancet - Iron Deficiency & sTfR Research

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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