Diagnostic Cutoff Values for Iron Deficiency Anemia
The diagnostic cutoff for iron deficiency anemia depends on the inflammatory status of the patient, with serum ferritin <30 μg/L in non-inflammatory states and <100 μg/L in inflammatory conditions, while transferrin saturation <16% indicates iron deficiency regardless of inflammation. 1
Ferritin Cutoff Values
- In patients without clinical, endoscopic, or biochemical evidence of inflammation, serum ferritin <30 μg/L is diagnostic of iron deficiency 1, 2
- In the presence of inflammation (elevated CRP, leukocytosis), serum ferritin up to 100 μg/L may still be consistent with iron deficiency 1
- A serum ferritin <15 μg/L indicates absolute iron deficiency with high specificity (99%), regardless of inflammatory status 1
- A ferritin value above 150 μg/L essentially rules out absolute iron deficiency, even in the presence of inflammation 1
- A ferritin cutoff of 45 μg/L provides a specificity of 92% for iron deficiency and may warrant consideration of gastrointestinal investigation, especially with chronic inflammation 1
Transferrin Saturation Cutoff Values
- Transferrin saturation (TSAT) <16% is a sensitive marker of iron deficiency, though with lower specificity (40-50%) 1, 2
- TSAT <20% with serum ferritin >100 μg/L is diagnostic of anemia of chronic disease 1
- If serum ferritin is between 30-100 μg/L and TSAT <16%, a combination of true iron deficiency and anemia of chronic disease is likely 1
Serum Iron Levels
- Low serum iron alone is not a reliable indicator of iron deficiency as it fluctuates throughout the day and is affected by many factors 3
- Serum iron should be interpreted in conjunction with other iron parameters like ferritin and transferrin saturation 3
- Measurement of iron, transferrin, and transferrin saturation provides little additional information beyond ferritin in iron deficiency evaluation 3
Special Clinical Scenarios
Inflammatory Conditions
- In cancer patients, functional iron deficiency is defined as TSAT between 20-50% and ferritin between 30-800 ng/mL 1
- In inflammatory bowel disease, iron deficiency is diagnosed when ferritin is <30 μg/L in the absence of inflammation or <100 μg/L with inflammation 1
- For patients with chronic kidney disease, heart failure, or cancer, higher ferritin thresholds may be needed to diagnose iron deficiency 2
Non-anemic Iron Deficiency
- Non-anemic iron deficiency is characterized by depleted iron stores (hypoferritinemia) but normal hemoglobin concentration 1
- For non-anemic iron deficiency, ferritin <10 μg/L represents depleted iron stores, 10-30 μg/L confirms iron deficiency, and 30-50 μg/L might indicate functional iron deficiency 4
Additional Diagnostic Parameters
- Mean corpuscular hemoglobin (MCH) is a more reliable marker of iron deficiency than mean corpuscular volume (MCV) as it is less dependent on storage and counting machine used 1
- Reticulocyte hemoglobin content (CHr <28 pg) and increased percentage of hypochromic red blood cells (>5%) are markers of both absolute and functional iron deficiency 1
- Soluble transferrin receptor (sTfR) increases with iron deficiency without being influenced by inflammation, making it a good supplement to ferritin measurement 3
- The transferrin/log(ferritin) ratio with a cutoff value of 1.70 can help diagnose iron deficiency when ferritin levels are inconclusive (20-100 μg/L) 5
Common Pitfalls in Diagnosis
- Relying solely on ferritin <15 μg/L as diagnostic criteria will miss many cases of iron deficiency, as this cutoff has high specificity but low sensitivity 6, 3
- Normal or elevated ferritin in the presence of inflammation (elevated CRP) should be interpreted with caution as it may mask underlying iron deficiency 1, 4
- Microcytosis and hypochromia lose sensitivity for iron deficiency in the presence of chronic disease, thalassemia, or vitamin B12/folate deficiency 1
- Failure to consider the inflammatory status of the patient when interpreting ferritin levels is a common error that leads to missed diagnoses of iron deficiency 1