From the Guidelines
To diagnose iron deficiency anemia, serum ferritin is the single most useful marker, and it should be confirmed by iron studies prior to investigation, with a cut-off value of 45 ng/mL, as recommended by the American Gastroenterological Association (AGA) 1.
Diagnosis of Iron Deficiency Anemia
The diagnosis of iron deficiency anemia involves several blood tests, including:
- A complete blood count (CBC) to check for anemia, which will show decreased hemoglobin and smaller, paler red blood cells (microcytic, hypochromic anemia) if iron deficiency is present
- Serum ferritin, which is the most sensitive test for iron stores and is typically below 45 ng/mL in iron deficiency, as per the AGA recommendations 1
- Serum iron, which is decreased in deficiency
- Total iron-binding capacity (TIBC), which is increased in deficiency
- Transferrin saturation, which is calculated as serum iron divided by TIBC, usually below 15% in deficiency
- Soluble transferrin receptor, which is elevated in deficiency
Importance of Serum Ferritin
Serum ferritin is the most useful marker of iron deficiency, and its level should be interpreted with caution, as it can be affected by inflammation and other conditions 1. A ferritin level below 45 ng/mL is indicative of iron deficiency, while a level above 100 ng/mL may indicate iron overload or inflammation.
Additional Tests
In some cases, additional tests may be necessary to confirm the diagnosis of iron deficiency anemia, such as:
- A peripheral blood smear to assess red blood cell morphology
- A bone marrow examination, which is rarely required, but may be necessary to distinguish iron deficiency from other causes of anemia
- Reticulocyte hemoglobin content (CHr) or reticulocyte hemoglobin equivalent (RET-He), which are quick and reliable tests for detecting iron deficiency, but may be limited by lack of routine availability and can be abnormal in inflammation and thalassemia 1
Timing and Preparation of Tests
These tests should be performed before starting iron supplements, as supplementation can affect results. Patients should be fasting for serum iron tests, and timing is important, as iron levels fluctuate throughout the day. The combination of low ferritin, low serum iron, high TIBC, and low transferrin saturation provides the most definitive diagnosis of iron deficiency anemia, as recommended by the British Society of Gastroenterology 1.
From the Research
Diagnostic Tests for Iron Deficiency Anemia
The following tests are indicated for diagnosing iron deficiency (ID) anemia:
- Complete Blood Count (CBC) parameters, such as red blood cell (RBC) count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) 2
- Serum ferritin levels, which is an index of iron stores 3, 4, 5
- Transferrin iron saturation, which measures the amount of iron available for erythropoiesis 5
- Reticulocyte hemoglobin content (CHr), which is an early marker of iron deficient erythropoiesis and can be used for diagnosis and monitoring of iron therapy 6
- Soluble transferrin receptor, which is an index of tissue iron deficiency 5
Limitations of Diagnostic Tests
- CBC parameters alone may not be sufficient for diagnosing iron deficiency anemia, as they may not detect iron depletion until it is severe 4
- Serum iron, transferrin saturation, and ferritin levels can be affected by inflammation, chronic diseases, and the normal aging process, which may lead to false negative results 6
- CHr has a moderate sensitivity and specificity for diagnosing iron deficiency, but its accuracy can be affected by varying cutoff values and conditions that cause iron restricted erythropoiesis 6
Recommendations for Diagnosis
- A combination of CBC parameters and serum ferritin levels can be used to diagnose iron deficiency anemia 2, 3, 4, 5
- CHr can be used as an additional test for diagnosing iron deficiency and monitoring iron therapy, but its results should be interpreted with caution and in conjunction with other tests 6