Iron Deficiency Anemia: Laboratory Parameters
In iron deficiency anemia, hemoglobin, MCV, MCH, ferritin, serum iron, and transferrin saturation are LOW, while RDW, TIBC, erythrocyte protoporphyrin, and serum transferrin receptor are HIGH. 1
Low Parameters in Iron Deficiency Anemia
Hemoglobin (Hb)
Mean Cell Volume (MCV) - Microcytosis
- Low MCV indicates microcytic red blood cells, a hallmark of iron deficiency anemia 1
- MCV falls below the 5th percentile for age-matched reference populations 1
- Important caveat: MCV can be falsely normal in iron deficiency when coexisting vitamin B12/folate deficiency, chronic disease, or thalassemia are present 1
Mean Cell Hemoglobin (MCH) - Hypochromia
- MCH is probably a more reliable marker than MCV as it is less dependent on storage conditions and counting machines 1
- MCH is reduced in both absolute and functional iron deficiency 1
- MCH may be more sensitive for detecting iron deficiency than MCV 1
Serum Ferritin (SF)
- <15 μg/L: Highly specific for absent iron stores (specificity 0.99) 1
- <30 μg/L: Generally indicative of low body iron stores 1
- <45 μg/L: Optimal cut-off balancing sensitivity and specificity (specificity 0.92) for clinical practice 1
- Critical caveat: Ferritin is an acute phase protein and can be falsely elevated during inflammation, infection, or chronic disease 1
- In inflammatory conditions, ferritin <45 μg/L should raise suspicion for iron deficiency 1
- Ferritin >150 μg/L makes absolute iron deficiency unlikely even with inflammation 1
Serum Iron
- Reduced serum iron concentration is characteristic of iron deficiency 1
- Important limitation: Significant day-to-day variation makes this less reliable than other markers 1
Transferrin Saturation
- <20%: Indicates iron deficiency 2
- Calculated as: (serum iron/total iron binding capacity) × 100 2
- Low transferrin saturation reflects inadequate iron available for erythropoiesis 1
Reticulocyte Hemoglobin (Retic-Hb)
- Low reticulocyte hemoglobin indicates insufficient iron for new red blood cell production 1
High Parameters in Iron Deficiency Anemia
Red Blood Cell Distribution Width (RDW)
- >14.0%: Indicates increased variation in red blood cell size (anisocytosis) 1
- Diagnostic utility: Low MCV + RDW >14.0% suggests iron deficiency anemia, while low MCV + RDW ≤14.0% suggests thalassemia minor 1
- RDW corresponds to the 95th percentile of reference populations 1
Total Iron Binding Capacity (TIBC)
- Raised TIBC reflects increased transferrin production as the body attempts to capture more iron 1
Erythrocyte Protoporphyrin
- Adults: >30 μg/dL whole blood or >70 μg/dL red blood cells 1
- Children 1-2 years: >80 μg/dL red blood cells 1
- Protoporphyrin accumulates when insufficient iron is available for hemoglobin synthesis 1
- Important caveat: Also elevated in infection, inflammation, and lead poisoning 1
- Sensitivity is only 42% and specificity 61% in children and adolescents 1
Serum Transferrin Receptor (sTfR)
- Increased sTfR concentration indicates iron-deficient erythropoiesis 1
- Limitation: Also elevated with increased erythropoietic drive (hemolytic anemias, thalassemias, Hb E) 1
- The [sTfR/log₁₀ ferritin] ratio provides superior discrimination, particularly in chronic disease 1
- Practical limitation: Most hospitals do not routinely offer this test 1
Percentage of Hypochromic Red Cells
- Raised percentage reflects inadequate hemoglobinization of red blood cells 1
Red Cell Zinc Protoporphyrin
- Elevated levels indicate iron-deficient erythropoiesis 1
Key Diagnostic Approach
The most specific single test for iron deficiency is serum ferritin <15 μg/L in the absence of inflammation 1. However, because ferritin can be falsely normal with concurrent inflammation, **combining ferritin with transferrin saturation <20% improves diagnostic accuracy** 2. When MCV and MCH are low with RDW >14.0%, this pattern strongly suggests iron deficiency anemia rather than thalassemia 1.
Common pitfall: Do not rely on hemoglobin alone to screen for iron deficiency, as less than 50% of anemic individuals actually have iron deficiency as the cause 1. Additional iron studies are essential for accurate diagnosis 1.