Soluble Transferrin Receptor (sTfR) in Iron Deficiency Anemia
Soluble transferrin receptor is a highly valuable diagnostic marker for identifying iron deficiency, particularly when inflammation makes ferritin unreliable, and the sTfR/log ferritin ratio provides superior discrimination in distinguishing iron deficiency anemia from anemia of chronic disease. 1
Primary Diagnostic Role
sTfR is most useful when ferritin is equivocal due to concurrent inflammation or chronic disease. 1 In otherwise healthy subjects, sTfR concentration is a good marker of iron deficiency, but serum ferritin remains the first-line test when inflammation is absent. 1
Key Diagnostic Characteristics
sTfR levels are elevated in iron deficiency anemia but remain normal or low in anemia of chronic disease alone, making it excellent for differentiation between these conditions. 2
sTfR is not affected by inflammation, unlike ferritin which is an acute phase protein and can be falsely elevated despite true iron deficiency. 1, 2
In iron deficiency anemia, sTfR concentrations range from 5.3-9.7 mg/L compared to 1.6-3.0 mg/L in anemia of chronic disease or healthy controls. 3, 4, 5
Clinical Decision Algorithm
When to Use sTfR
Order sTfR testing when:
- Ferritin is 30-100 μg/L with transferrin saturation <16% in the presence of inflammation. 2
- Ferritin is >100 μg/L with transferrin saturation <16% in inflammatory states to identify concurrent iron deficiency. 2
- Chronic inflammatory conditions (rheumatologic disease, inflammatory bowel disease, heart failure) coexist with suspected iron deficiency. 1, 2
Do not routinely order sTfR when:
- Ferritin is <15 μg/L (specificity 0.99 for iron deficiency without sTfR). 1
- No inflammatory markers are present and ferritin <30 μg/L with transferrin saturation <16%. 2
The sTfR/Log Ferritin Ratio
The [sTfR/log₁₀ ferritin] ratio provides superior discrimination compared to either test alone, particularly in chronic disease. 1
- A ratio >1.30 indicates iron deficiency anemia or combined iron deficiency with anemia of chronic disease. 3
- A ratio <0.90 indicates isolated anemia of chronic disease without iron deficiency. 3
- This ratio has diagnostic efficiency of 0.820 compared to 0.884 for sTfR alone and only 0.638 for ferritin alone. 3
Specific Clinical Scenarios
Inflammatory Bowel Disease
- In ulcerative colitis patients, sTfR determination helps make correct diagnosis when iron deficiency and anemia of chronic disease coexist. 2
- When inflammation is present (elevated CRP, leukocytosis), sTfR distinguishes true iron deficiency from anemia of chronic inflammation. 2
Heart Failure
- sTfR is included in diagnostic algorithms for evaluating iron deficiency in congestive heart failure patients, where anemia significantly impacts mortality and hospitalization. 2
- sTfR measurement identifies patients who would benefit from intravenous iron therapy even when ferritin levels are inconclusive. 2
Cystic Fibrosis
- sTfR is the most accurate measure of iron level in CF patients because it is not affected by chronic infection and inflammation. 1
- Annual monitoring is recommended, though the test is not widely available. 1
Important Caveats
Conditions That Elevate sTfR Beyond Iron Deficiency
sTfR can be falsely elevated in conditions with increased erythropoietic drive, including:
These conditions must be excluded (via hemoglobin electrophoresis if microcytosis with normal iron studies) before interpreting elevated sTfR as iron deficiency. 1
Test Availability
- Most UK hospitals and many clinical laboratories do not provide sTfR testing. 1
- When sTfR is unavailable, reticulocyte hemoglobin concentration (CHr) <30 pg can serve as an alternative predictor of response to intravenous iron. 2
Diagnostic Performance
- Sensitivity and specificity for iron deficiency anemia are both 85.6-100% depending on the assay method used. 6, 4
- Different measurement methods (chemiluminescent, immunoturbidimetric, immunonephelometric) have markedly different cutoff points (2.48-6.70 mg/L), which must be considered when interpreting results. 6
- Area under the ROC curve ranges from 0.936-0.944, indicating excellent diagnostic accuracy. 6
When sTfR Does NOT Change Management
- In premenopausal women with non-anemic iron deficiency (ferritin low but hemoglobin normal), GI investigation is generally not warranted as menstrual blood loss is the likely cause—sTfR adds little value here. 1
- When ferritin is <15 μg/L in the absence of inflammation, iron deficiency is confirmed without needing sTfR. 1