Iron deficiency is the most common nutritional deficiency globally, affecting over 1 billion people. It progresses through stages โ from depleted stores to iron-deficient erythropoiesis to overt iron deficiency anaemia โ and different lab tests detect different stages.
Ferritin: The First to Fall
Ferritin is the main iron storage protein and the earliest marker of iron depletion, falling before haemoglobin drops. Normal adult ranges: males 20โ250 ng/mL, females 10โ120 ng/mL. A ferritin below 12 ng/mL virtually confirms iron deficiency in the absence of inflammation.
Ferritin is an acute-phase reactant โ it rises during infection, inflammation, and liver disease, masking true deficiency. A ferritin of 50โ100 ng/mL may still indicate true deficiency in a patient with chronic inflammation.
Serum Iron and TIBC
Serum iron measures iron circulating bound to transferrin. Total Iron Binding Capacity (TIBC) measures transferrin's capacity to carry iron โ it rises when iron stores are depleted (more transferrin is produced to capture scarce iron). In iron deficiency: serum iron is LOW, TIBC is HIGH, transferrin saturation is LOW (< 16%).
- Serum iron normal: males 65โ175 ยตg/dL, females 50โ170 ยตg/dL
- TIBC normal: 250โ370 ยตg/dL
- Transferrin saturation = (Serum Iron รท TIBC) ร 100
- Saturation < 16% confirms iron-deficient erythropoiesis
CBC Changes in Iron Deficiency
As iron deficiency progresses, red blood cell production is affected. The CBC shows: low haemoglobin and haematocrit, low MCV (microcytic cells, < 80 fL), low MCH (hypochromic cells), elevated RDW (variable cell sizes, > 14.5%) โ one of the earliest CBC changes.
Staging Iron Deficiency
Understanding the stage helps guide treatment:
- Stage 1 โ Depletion: Low ferritin only; Hgb normal; no symptoms
- Stage 2 โ Iron-deficient erythropoiesis: Low ferritin + high TIBC + low saturation; Hgb still normal
- Stage 3 โ Iron deficiency anaemia: Low Hgb + microcytic hypochromic cells; symptomatic
Treatment Response
With oral iron supplementation, reticulocytes rise within 5โ10 days, haemoglobin begins to rise within 2โ4 weeks, and ferritin normalises after 3โ6 months of continued therapy. Always treat the underlying cause โ blood loss, poor absorption, or inadequate intake.
Always investigate the cause of iron deficiency in adult males and post-menopausal women, as gastrointestinal blood loss (colorectal cancer) must be excluded.
References & Sources
Medical Advisory
Expert oversight & content review
Dr. Naeem Mahmood Ashraf
PhD Biochemistry & Biotechnology
University of Punjab, Lahore
Dr. Naeem Mahmood Ashraf is a distinguished biochemist and biotechnologist at the University of Punjab, Lahore, Pakistan. With a PhD in Biochemistry & Biotechnology and over 45 peer-reviewed publications (h-index: 10), Dr. Ashraf brings deep expertise in clinical biochemistry, genomics, and computational biology to LabSense AI. His research bridges laboratory science and patient care, ensuring all interpretations follow WHO, IFCC, and AACC international standards.
Credentials
Areas of Expertise
