How is iron deficiency calculated in the absence of ferritin (iron storage protein) levels?

From the Guidelines

Iron deficiency can be accurately assessed without ferritin by using a combination of laboratory parameters, including transferrin saturation, soluble transferrin receptor, and reticulocyte hemoglobin content, as evidenced by the most recent study 1. When ferritin testing is unavailable, clinicians should evaluate these alternative parameters to diagnose iron deficiency.

• Transferrin saturation < 20% has high sensitivity for diagnosing absolute or functional iron deficiency, as noted in the study 1.
• Soluble transferrin receptor (sTfR) is elevated in those with iron deficiency and not affected by inflammation, making it a useful marker in patients with inflammatory conditions 1.
• Reticulocyte hemoglobin content is a direct assessment of the functional availability of iron to the erythropoietic tissue and can be used to detect iron deficiency, as discussed in the study 1. A typical pattern suggesting iron deficiency includes low transferrin saturation, elevated sTfR, and low reticulocyte hemoglobin content. For treatment, oral or intravenous iron supplementation may be recommended, with the goal of achieving a transferrin saturation > 20% and a ferritin level > 50 ng/mL, as suggested by the study 1. Treatment should continue for 3-6 months after hemoglobin normalizes to replenish iron stores. While these parameters can strongly suggest iron deficiency, they are less specific than ferritin, as conditions like thalassemia and anemia of chronic disease can present with similar findings, potentially necessitating additional testing in unclear cases, as noted in the study 1.

From the Research

Iron Deficiency Calculation without Ferritin

To calculate iron deficiency without ferritin, several other biomarkers and tests can be used, including:

• Haemoglobin concentration
• Haematocrit
• Mean cellular volume (MCV)
• Mean cellular haemoglobin
• Percentage of hypochromic erythrocytes
• Transferrin saturation (TSAT)
• Soluble transferrin receptor (sTfR)
• sTfR/logFerr index (sTfR-F index)
• Reticulocyte hemoglobin content (CHr)

Diagnostic Criteria

The diagnostic criteria for iron deficiency without anaemia include:

• Low TSAT (<16%) 2
• Low ferritin (<30 µg/l) 3, 4
• Low transferrin saturation (<20%) 4
• Elevated sTfR-F index (>1.35) 2
• Low CHr (<28 pg) 2

Limitations and Challenges

There are limitations and challenges in diagnosing iron deficiency without ferritin, including:

• False negative results due to acute phase reaction 3
• Diagnostic uncertainty in patients with chronic inflammatory conditions 4
• Need for multiple biomarkers and tests to confirm diagnosis 2

Alternative Tests

Alternative tests that can be used to diagnose iron deficiency without ferritin include:

• Bone marrow evaluation to assess iron stores 5
• Serum transferrin receptors to assess iron-deficient erythropoiesis 2
• Reticulocyte hemoglobin content (CHr) to assess iron-restricted erythropoiesis 2