What is the role of soluble transferrin receptor (sTfR) in diagnosing and managing iron deficiency anemia?

Role of Soluble Transferrin Receptor (sTfR) in Diagnosing and Managing Iron Deficiency Anemia

Soluble transferrin receptor (sTfR) is a valuable diagnostic marker for iron deficiency, particularly in the context of chronic inflammatory conditions where ferritin may be unreliable, though it is not widely available in most clinical settings. 1

Diagnostic Value of sTfR

In Uncomplicated Iron Deficiency

• sTfR is a good marker of iron deficiency in otherwise healthy subjects 1
• sTfR concentrations are elevated in iron deficiency anemia (IDA) 1, 2
• The best diagnostic cutoff point between IDA and anemia of chronic disease (ACD) has been reported as 4.7 mg/L 3

In Chronic Disease/Inflammatory States

• sTfR remains valuable when ferritin is unreliable due to inflammation 1
• sTfR levels are not significantly influenced by inflammatory changes, unlike ferritin 3
• All patients with absent bone marrow iron stores show elevated sTfR levels 4

Diagnostic Algorithm Using sTfR

1. Initial Iron Status Assessment:

   • Begin with standard iron studies (serum ferritin, transferrin saturation)
   • If ferritin <15 μg/L: Definitive iron deficiency (specificity 0.99) 1
   • If ferritin <30 μg/L: Likely iron deficiency 1

2. When to Consider sTfR Testing:

   • When inflammation is present (elevated CRP, ESR)
   • When ferritin is 30-100 μg/L with inflammation (possible mixed iron deficiency + ACD) 1
   • When ferritin >100 μg/L with transferrin saturation <16% (possible ACD) 1

3. Interpretation of sTfR Results:

   • Elevated sTfR with normal/high ferritin: Iron deficiency with concomitant inflammation 2
   • Normal sTfR with high ferritin: Likely pure ACD without iron deficiency 2
   • The sTfR/log ferritin ratio provides superior discrimination compared to either test alone 1
   • A sTfR/log ferritin ratio >1.30 suggests iron deficiency 2

Clinical Applications

Heart Failure Patients

• sTfR is recommended in the evaluation algorithm for iron deficiency in chronic heart failure patients 1
• In heart failure patients, sTfR should be considered when transferrin saturation is <20% 1

Inflammatory Bowel Disease

• In ulcerative colitis, sTfR helps distinguish between pure ACD and combined iron deficiency with inflammation 1
• sTfR is particularly useful when ferritin is between 30-100 μg/L in the presence of inflammation 1

Pediatric Populations

• sTfR is useful in assessing iron status in infants and preschool children 1
• sTfR may help identify children requiring iron replacement in areas with high infection prevalence 1
• However, sTfR levels may not be increased in iron-deficient infants less than 1 year of age 1

Practical Considerations and Limitations

• Most UK hospitals and many clinical settings do not routinely provide sTfR testing 1
• Different measurement methods have markedly different cutoff points for IDA diagnosis 5
• Reticulocyte hemoglobin content (CHr) is more widely available on modern hematology analyzers and can be used as an alternative 1
• sTfR can be elevated in conditions with increased erythropoietic drive (hemolytic anemias, thalassemias) 1
• Some studies have found limited sensitivity of sTfR in detecting iron deficiency in chronic disorders 6

Bottom Line for Clinical Practice

When evaluating iron deficiency anemia, especially in the context of chronic disease or inflammation, sTfR provides valuable diagnostic information that complements traditional iron markers. The combination of sTfR with ferritin (as the sTfR/log ferritin ratio) offers the best diagnostic accuracy for detecting iron deficiency in inflammatory states, potentially reducing unnecessary gastrointestinal investigations and guiding appropriate iron replacement therapy.