What Laboratory Tests Are Included in Iron Studies
Iron studies typically include four core tests: serum ferritin, serum iron, total iron-binding capacity (TIBC), and transferrin saturation (calculated from serum iron and TIBC). 1, 2
Core Components of Iron Studies
Primary Tests
Serum ferritin is the most sensitive and specific test for assessing iron stores, with levels <15 μg/L indicating depleted iron stores and <30 μg/L generally indicating low body iron stores 3, 1
Serum iron measures the total amount of circulating iron bound to transferrin in the bloodstream 3, 2
Total iron-binding capacity (TIBC) measures the blood's capacity to bind iron with transferrin; this value increases when iron stores are depleted 3, 2
Transferrin saturation is calculated as (serum iron × 100)/TIBC and reflects iron immediately available for hemoglobin synthesis, with values <16-20% suggesting iron deficiency 3, 1, 2
Additional Tests Often Included
Erythrocyte protoporphyrin concentration detects early changes in iron status and is considered a biochemical test that identifies iron deficiency before anemia develops 3, 1
Complete blood count (CBC) with red cell indices (hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin) is recommended as the first step in evaluating for iron deficiency, though these are late indicators 1, 4
Red cell distribution width (RDW) when elevated (>14.0%) with microcytosis strongly suggests iron deficiency anemia 1, 4
Interpretation Algorithm
Step 1: Assess Ferritin First
- Ferritin <15 μg/L has 99% specificity for iron deficiency in the absence of inflammation 3
- Ferritin <45 μg/L provides 92% specificity and is a reasonable threshold for investigation 3
- Critical caveat: Ferritin is an acute-phase reactant and can be falsely elevated in inflammatory conditions, chronic infections, liver disease, or malignancies, potentially masking true iron deficiency 3, 1, 2
Step 2: Add Transferrin Saturation
- Transferrin saturation <16-20% confirms iron deficiency when combined with low ferritin 3, 1
- This test is less affected by inflammation than ferritin alone 1
- Among nonpregnant women, transferrin saturation <16% has 93% specificity for iron deficiency 3
Step 3: Adjust for Inflammation
- In patients with chronic inflammatory conditions, chronic kidney disease, heart failure, or inflammatory bowel disease, use ferritin <100 μg/L as the diagnostic threshold 1, 2, 4
- Ferritin values >150 μg/L are unlikely to occur with absolute iron deficiency, even with inflammation present 3
Common Pitfalls to Avoid
Do not rely solely on hemoglobin and hematocrit for diagnosing iron deficiency, as these are late indicators that only become abnormal after iron stores are depleted and erythropoiesis is impaired 3, 1, 2
Do not ignore inflammatory markers when interpreting ferritin levels; chronic disease, infection, hepatitis, cirrhosis, neoplasia, or arthritis can raise ferritin independent of iron status 3, 1
Do not check iron parameters within 4 weeks of receiving IV iron, as circulating iron interferes with assays and produces falsely elevated results 1
Recognize that serum iron has significant diurnal variation (rises in morning, falls at night) and increases after meals, making it less reliable as a standalone test 3
Day-to-day variation in serum iron is substantial, greater than for hemoglobin or hematocrit, which limits its diagnostic utility when measured in isolation 3
In men and postmenopausal women with iron deficiency anemia, do not assume dietary insufficiency; approximately 62% have gastrointestinal bleeding from lesions requiring further investigation 3, 1
Advanced or Specialized Tests
Serum transferrin receptor (sTfR) reflects cellular iron deficits and is less affected by inflammation, though most hospitals do not routinely offer this test 3, 5
Percent hypochromic red blood cells can identify functional iron deficiency but requires specialized equipment and is time-sensitive 1
Reticulocyte hemoglobin content provides information about recent iron availability for erythropoiesis 3