Causes of Low Ferritin
Low ferritin indicates depleted iron stores and is highly specific for iron deficiency, with a ferritin ≤15 μg/L confirming absolute iron deficiency in the absence of inflammation. 1
Primary Causes of Low Ferritin
Blood Loss
- Menstrual bleeding is the leading cause in reproductive-age women, with approximately 38% having iron deficiency without anemia and 13% having iron-deficiency anemia 2
- Gastrointestinal bleeding from any source (ulcers, polyps, malignancy, inflammatory bowel disease) is a major cause, particularly in men and postmenopausal women 2
- Nonsteroidal anti-inflammatory drug use increases gastrointestinal bleeding risk 2
Malabsorption
- Celiac disease is a critical cause to identify, as low ferritin without anemia can be an early and silent sign of celiac disease, occurring in 6% of patients with isolated low ferritin 3
- Atrophic gastritis impairs iron absorption through reduced gastric acid production 2
- Post-bariatric surgery patients have impaired iron absorption due to bypassed duodenum and reduced gastric acid 2
- Inflammatory bowel disease (13-90% prevalence of iron deficiency) causes both malabsorption and blood loss 2
Inadequate Dietary Intake
- Vegetarians and vegans are at higher risk due to lower bioavailability of non-heme iron from plant sources 1
- Inadequate dietary iron intake particularly in populations with limited access to iron-rich foods 2
Increased Physiologic Demand
- Pregnancy, especially third trimester, affects up to 84% of pregnant women in high-income countries 2
- Athletes, particularly female athletes (15-35% prevalence), have increased iron losses through sweat, hemolysis, and gastrointestinal microbleeding 1
Special Diagnostic Considerations
Inflammation Confounds Ferritin Interpretation
- In the absence of inflammation, ferritin <15 μg/L indicates absolute iron deficiency 4
- With active inflammation (elevated CRP, ESR), ferritin is an acute-phase reactant and may be falsely elevated; the threshold increases to <30-100 μg/L to indicate iron deficiency 4
- Combined iron deficiency and anemia of chronic disease is likely when ferritin is 30-100 μg/L with transferrin saturation <16% in the presence of inflammation 4
Key Laboratory Patterns
- Transferrin saturation <16% is a sensitive marker for iron deficiency, though specificity is only 40-50% 4
- Under normal conditions, 1 μg/L of serum ferritin equals approximately 10 mg of stored iron 1
- Ferritin specificity is 98% when ≤15 μg/L for diagnosing depleted iron stores 1
Clinical Pitfalls to Avoid
Don't Miss Gastrointestinal Pathology
- Helicobacter pylori gastritis (24% vs 17.6%) and celiac disease (6% vs 2.2%) are significantly more common in patients with low ferritin without anemia compared to those with normal ferritin 3
- Gastrointestinal investigation is justified when ferritin ≤50 μg/L in both anemic and non-anemic elderly patients, as most lack classic gastrointestinal symptoms 5
Recognize Iron Deficiency Before Anemia Develops
- Iron deficiency without anemia causes fatigue, reduced physical performance, cognitive impairment, restless legs syndrome (32-40%), pica (40-50%), and exercise intolerance 1, 2
- Rapid recurrence of iron deficiency in asymptomatic patients should raise suspicion for subclinical inflammatory activity, particularly in IBD 4
Don't Confuse Serum Iron with Iron Stores
- Serum iron reflects circulating iron, not total body stores; ferritin remains the best indicator of iron stores in the absence of inflammation 6
- Low ferritin indicates depleted iron stores regardless of serum iron level, with ferritin of 21 ng/mL representing early iron store depletion 6
High-Risk Populations Requiring Screening
- Menstruating females with heavy menstrual bleeding 1
- Pregnant women, particularly second and third trimesters 2
- Inflammatory bowel disease patients (13-90% prevalence) 2
- Chronic kidney disease (24-85% prevalence) 2
- Heart failure patients (37-61% prevalence) 2
- Cancer patients (18-82% prevalence) 2
- Athletes, especially female endurance athletes 1