Comprehensive Iron Testing Should Include CBC and Ferritin
When performing iron tests, they should always be combined with a Complete Blood Count (CBC) and ferritin measurement to ensure accurate assessment of iron status. 1
Rationale for Combined Testing
- Laboratory evaluation of iron status should include a CBC and iron parameters (ferritin, transferrin saturation calculated by dividing serum iron by total iron binding capacity) to properly assess iron deficiency or overload 1
- Ferritin reflects storage iron (in liver, spleen, and bone marrow), while transferrin saturation reflects iron that is readily available for erythropoiesis 1
- CBC parameters alone are insufficient for detecting early iron deficiency, as hemoglobin and hematocrit decrease only when severe iron depletion is present 2
- Many individuals with normal CBC values may still have reduced serum iron and ferritin levels, indicating iron depletion that could progress to iron deficiency anemia if not detected early 2
Key Components of Comprehensive Iron Testing
- CBC measurements: Provides information on hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC) 1
- Ferritin: Most sensitive non-invasive indicator of iron stores; low levels indicate iron deficiency while elevated levels may reflect iron overload or inflammation 1, 3
- Transferrin saturation (TSAT): Calculated by dividing serum iron by total iron binding capacity; reflects iron available for erythropoiesis 1
- Serum iron and total iron binding capacity (TIBC): Additional measurements that help calculate TSAT 1
Interpretation of Combined Test Results
- In the absence of inflammation, a ferritin goal of 50 ng/mL is recommended regardless of sex 1
- TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency 1
- Discordant results may occur where ferritin is elevated (due to its acute phase reactivity) while TSAT is low, indicating iron deficiency 1
- CBC parameters like MCV, MCH, and MCHC become abnormal in more advanced iron deficiency and can help confirm the diagnosis 1, 4
Special Considerations
- Ferritin is an acute phase reactant and may be falsely elevated during inflammation, making it less reliable as a sole indicator 1, 3
- Iron parameters should not be evaluated within 4 weeks of intravenous iron administration, as circulating iron interferes with the assay leading to inaccurate results 1
- In patients with suspected iron deficiency but normal ferritin, checking serum iron and total iron binding capacity may be necessary 1
- For patients with chronic kidney disease, both ferritin and TSAT should be measured simultaneously and evaluated together 1
Additional Testing in Specific Situations
- Soluble transferrin receptor (sTfR) may be more sensitive in patients with inflammatory conditions where ferritin is unreliable 1
- Reticulocyte hemoglobin content (CHr or RET-He) can provide a direct assessment of functional iron availability to erythropoietic tissue 1
- C-reactive protein measurement may help assess the contribution of inflammation to elevated ferritin levels 1
- In cases of unexplained iron deficiency, additional testing for celiac disease (tissue transglutaminase antibodies) should be considered 1
By combining CBC, ferritin, and other iron parameters, clinicians can more accurately diagnose iron status abnormalities and provide appropriate treatment before significant clinical consequences develop 2, 3.