What are the hidden causes and treatment options for ferritin depletion in the absence of blood loss?

Hidden Causes of Ferritin Depletion Without Blood Loss

The most common hidden causes of ferritin depletion without overt blood loss include chronic inflammation, malabsorption conditions (especially celiac disease), and dietary insufficiency, which should be systematically investigated and treated based on the underlying etiology. 1

Diagnostic Approach to Hidden Ferritin Depletion

Initial Assessment

• Complete blood count with MCV, reticulocytes
• Serum ferritin, transferrin saturation (TSAT)
• C-reactive protein (CRP) or other inflammatory markers

Interpretation of Iron Parameters

• In absence of inflammation: ferritin <30 μg/L indicates iron deficiency 1
• With inflammation: ferritin up to 100 μg/L may still represent iron deficiency 1
• TSAT <16% suggests iron deficiency regardless of ferritin level 1

Common Hidden Causes

1. Gastrointestinal Disorders

• Malabsorption syndromes:
  • Celiac disease (screen with tissue transglutaminase antibodies) 1
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 1
  • Autoimmune gastritis
  • Post-bariatric surgery 1

2. Chronic Inflammatory Conditions

• Inflammatory bowel disease
• Rheumatologic disorders
• Chronic infections
• These cause functional iron deficiency through hepcidin upregulation 1

3. Dietary Factors

• Vegetarian/vegan diets (inadequate iron intake)
• Poor dietary intake in elderly
• Excessive consumption of iron absorption inhibitors (tea, coffee, calcium)

4. Medication-Related Causes

• Proton pump inhibitors (reduce iron absorption)
• NSAID use (may cause microbleeding not clinically apparent) 1
• Certain antibiotics (can bind to iron)

5. Excessive Therapeutic Phlebotomy

• Seen in hemochromatosis patients undergoing maintenance phlebotomy 2

6. Rare Causes

• IRIDA (Iron-Refractory Iron Deficiency Anemia) - genetic disorder
• Copper deficiency (impairs iron mobilization)

Treatment Approach

1. Treat Underlying Cause

• Celiac disease: gluten-free diet
• IBD: disease-specific therapy
• Adjust phlebotomy schedule in hemochromatosis

2. Iron Supplementation

Oral Iron

• First-line for mild-moderate deficiency without malabsorption
• Ferrous sulfate 325 mg daily
• Take with vitamin C to enhance absorption
• Avoid taking with calcium, tea, coffee

Intravenous Iron

• Indicated for:
  • Malabsorption conditions
  • Inflammatory states where oral iron is poorly absorbed
  • When rapid repletion is needed
  • Intolerance to oral preparations
• Formulations include ferric carboxymaltose, iron sucrose, ferric derisomaltose 1

3. Monitoring Response

• Repeat hemoglobin in 2-4 weeks
• Ferritin and TSAT should be checked 4-8 weeks after treatment 1
• Avoid checking iron parameters within 4 weeks of IV iron administration 1

Common Pitfalls to Avoid

1. Misinterpreting ferritin levels in inflammation: Ferritin is an acute phase reactant and may be falsely normal or elevated despite iron deficiency 1

2. Incomplete GI evaluation: In men and post-menopausal women with iron deficiency, both upper and lower GI tract should be examined to exclude malignancy 1

3. Overlooking non-GI causes: Focus exclusively on GI bleeding can miss important non-bleeding causes

4. Inadequate treatment duration: Iron stores require months to replete fully; premature discontinuation of therapy is common

5. Failure to address underlying cause: Simply treating with iron without addressing the root cause leads to recurrence

By systematically evaluating these hidden causes and implementing appropriate treatment, ferritin depletion can be effectively managed even in the absence of obvious blood loss.