What Low Ferritin Means
Low ferritin indicates depleted iron stores in the body and is the earliest and most specific marker of iron deficiency, even before anemia develops. 1
Diagnostic Thresholds
In Patients Without Inflammation
- Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and definitively confirms the diagnosis 2, 1
- Ferritin <30 μg/L generally indicates low body iron stores and warrants treatment 1, 3
- Ferritin <45 μg/L provides optimal sensitivity-specificity balance (specificity 0.92) for clinical decision-making 1
- Some evidence suggests ferritin <50 μg/L may still represent iron deficiency, particularly in women 4, 5
In Patients With Inflammation or Chronic Disease
- The diagnostic threshold shifts upward to ferritin <100 μg/L when inflammation is present (elevated CRP/ESR) 2, 1
- Ferritin is an acute-phase reactant that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency 2, 1
- In inflammatory conditions (IBD, chronic kidney disease, heart failure, cancer), ferritin between 30-100 μg/L with transferrin saturation <16% suggests coexisting iron deficiency and anemia of chronic disease 2, 1
Clinical Significance
Symptoms Even Without Anemia
Low ferritin causes significant symptoms before anemia develops, including:
- Fatigue and lethargy 1, 3
- Difficulty concentrating and irritability 3
- Reduced exercise tolerance and aerobic performance 1, 3
- Restless legs syndrome (32-40% of cases) 3
- Pica (40-50% of cases) 3
Progression of Iron Deficiency
- Stage 1 (depleted stores): Low ferritin with normal hemoglobin - this is when ferritin first becomes abnormal 1
- Stage 2 (iron-deficient erythropoiesis): Low ferritin with low transferrin saturation but still normal hemoglobin 1
- Stage 3 (iron deficiency anemia): Low ferritin, low transferrin saturation, and low hemoglobin 3
Diagnostic Algorithm
Step 1: Assess Inflammatory Status
- Measure CRP and ESR to determine if inflammation is present, as this affects ferritin interpretation 2, 1
Step 2: Interpret Ferritin Based on Inflammation
If CRP/ESR are normal:
- Ferritin <15 μg/L → Absolute iron deficiency confirmed; initiate treatment and investigate source of iron loss 1
- Ferritin 15-30 μg/L → Iron deficiency with low stores likely; consider iron supplementation 1
- Ferritin 30-45 μg/L → May still represent iron deficiency; check transferrin saturation 1
If CRP/ESR are elevated:
- Ferritin <100 μg/L with transferrin saturation <16% → Likely true iron deficiency despite inflammation 2, 1
- Ferritin 30-100 μg/L with transferrin saturation <16% → Mixed picture of iron deficiency and anemia of chronic disease 2, 1
- Ferritin >100 μg/L with transferrin saturation <16% → Anemia of chronic disease (inflammatory iron block) 2, 1
Step 3: Calculate Transferrin Saturation
- Formula: (serum iron × 100) ÷ total iron-binding capacity 1
- Transferrin saturation <16% is a sensitive marker of iron deficiency (though specificity is only 40-50%) 2
- Transferrin saturation <20% is the traditional threshold used in chronic disease states 1
Step 4: Consider Soluble Transferrin Receptor (sTfR) if Available
- Elevated sTfR confirms true iron deficiency even in the presence of inflammation 2, 1
- Normal or low sTfR suggests anemia of chronic disease rather than true iron deficiency 2
Common Causes to Investigate
Most Common Etiologies
- Bleeding: Menstrual (most common in premenopausal women), gastrointestinal 3, 6
- Impaired absorption: Atrophic gastritis, celiac disease, bariatric surgery, H. pylori infection 3, 6
- Inadequate dietary intake: Vegetarians, vegans 1
- Pregnancy: Up to 84% of pregnant women in third trimester 3
High-Risk Populations Requiring Screening
- Menstruating females (38% have iron deficiency without anemia) 3
- Pregnant women 3
- Inflammatory bowel disease patients (13-90% affected) 3
- Chronic kidney disease patients (24-85% affected) 3
- Heart failure patients (37-61% affected) 3
- Cancer patients (18-82% affected) 3
- Regular blood donors 1
- Athletes 1
Critical Pitfalls to Avoid
Don't Miss Inflammation
- Always check CRP/ESR when interpreting ferritin - failing to do so will cause you to miss iron deficiency in patients with chronic inflammatory conditions 2, 1
- A "normal" ferritin of 50-100 μg/L may still represent iron deficiency if inflammation is absent 4, 5
Don't Ignore Low Ferritin Without Anemia
- Iron deficiency without anemia (Stage 1) requires treatment - waiting for anemia to develop before treating is inappropriate 1, 3
- Symptoms like fatigue and exercise intolerance occur even with normal hemoglobin 1, 3
Don't Forget to Investigate the Cause
- Low ferritin always requires investigation of the underlying cause (except in obvious cases like heavy menstrual bleeding in young women) 3, 6
- For premenopausal women, test for H. pylori and celiac disease before proceeding to endoscopy 1
- Reserve bidirectional endoscopy for: positive H. pylori/celiac testing, GI symptoms, persistent iron deficiency despite adequate supplementation, or age >50 years 1