Laboratory Evaluation for Low Ferritin
When ferritin is low, confirm iron deficiency with additional iron studies (transferrin saturation and/or hemoglobin) and investigate the underlying cause through targeted testing based on patient demographics and risk factors.
Initial Confirmatory Testing
Serum ferritin is the most specific indicator of depleted iron stores, but should be interpreted alongside other markers to confirm iron deficiency and assess its severity 1.
Core Iron Panel
Transferrin saturation (TSAT): Calculate as (serum iron ÷ total iron-binding capacity) × 100 1
Hemoglobin/Hematocrit: Essential to distinguish iron deficiency from iron-deficiency anemia 1
Complete blood count (CBC): Assess for microcytic anemia pattern 2
Ferritin Interpretation Thresholds
The diagnostic threshold varies by population and inflammation status:
- Standard populations: Ferritin <15 μg/L confirms iron deficiency (98% specificity in women of childbearing age) 1
- Higher sensitivity threshold: <12 μg/L provides 100% specificity but lower sensitivity (61%) 1
- Physiologically-based thresholds: Recent evidence suggests ~20 μg/L for children and ~25 μg/L for non-pregnant women may be more appropriate 3
- General screening: <30 ng/mL is commonly used in individuals without inflammatory conditions 2
Critical caveat: Ferritin is an acute-phase reactant—infection, inflammation, liver disease (hepatitis, cirrhosis), neoplasia, or arthritis can falsely elevate ferritin and mask depleted iron stores 1.
Inflammatory Marker Assessment
When ferritin is borderline or unexpectedly normal despite clinical suspicion:
- C-reactive protein (CRP): Exclude inflammation (CRP >5.0 mg/L suggests acute-phase response) 3
- White blood cell count: Rule out infection (>10.0×10⁹/L) 3
- Liver enzymes (ALT/AST): Exclude liver disease that could elevate ferritin (>70 IU/L cutoff) 3
If inflammation is present, transferrin saturation becomes more reliable than ferritin alone for assessing iron status 1.
Etiologic Investigation
Identify and address the underlying cause—this is essential for effective treatment:
Bleeding Assessment
Menstruating women:
- Detailed menstrual history (heavy menstrual bleeding is the most common cause in reproductive-age women) 2
- Consider gynecologic evaluation if bleeding is excessive
Gastrointestinal bleeding:
Malabsorption Screening
- Celiac disease: Tissue transglutaminase antibodies (IgA) with total IgA 2
- Atrophic gastritis: Consider if history of autoimmune disease 2
- Post-bariatric surgery: Document surgical history 2
Chronic Disease Evaluation
- Inflammatory bowel disease: If GI symptoms present (affects 13-90% of IBD patients) 2
- Chronic kidney disease: Serum creatinine/eGFR (24-85% prevalence in CKD) 2
- Heart failure: BNP/NT-proBNP if cardiac symptoms (37-61% prevalence in HF) 2
- Cancer screening: Age-appropriate malignancy evaluation (18-82% prevalence in cancer patients) 2
Dietary Assessment
- Nutritional intake: Particularly important in vegetarians/vegans (lower bioavailability of non-heme iron) 1
- Pregnancy status: Iron deficiency affects up to 84% of third-trimester pregnancies 2
Special Population Considerations
Children (6 months-17 years)
- Average ferritin ~30 μg/L for ages 6-24 months 1
- Erythrocyte protoporphyrin has limited utility (42% sensitivity, 61% specificity) 1
- Screen for lead poisoning if elevated protoporphyrin 1
Chronic Kidney Disease Patients
- Target ferritin >200 ng/mL when using ESAs (allows lower ESA doses) 1
- Maintain TSAT >20% for optimal erythropoiesis 1
- Monitor both ferritin and TSAT together with hemoglobin and ESA dose 1
Pregnancy
- Normal ferritin in first/second trimester may not predict adequate iron status later in pregnancy 1
- Increased screening frequency recommended 2
Monitoring After Diagnosis
Once iron deficiency is confirmed and treatment initiated: