What is the etiology and management of iron deficiency without anemia?

Etiology and Management of Iron Deficiency Without Anemia

Iron deficiency without anemia requires thorough investigation for underlying causes and appropriate iron supplementation to prevent progression to anemia and improve quality of life. 1

Etiology

Iron deficiency without anemia can result from several causes:

Common Causes

• Blood Loss:

  • Gastrointestinal bleeding (especially in men and postmenopausal women)
  • Menstrual blood loss (especially menorrhagia in premenopausal women) 1
  • Occult bleeding from GI malignancies 1

• Decreased Iron Absorption:

  • Celiac disease
  • Atrophic gastritis (autoimmune or due to H. pylori) 2
  • Post-bariatric surgery 3

• Increased Iron Requirements:

  • Pregnancy and breastfeeding 1, 4
  • Rapid growth in children and adolescents 5

• Poor Dietary Intake:

  • Inadequate iron-rich foods 1, 4

• Chronic Conditions:

  • Heart failure (37-61% of patients) 4
  • Chronic kidney disease (24-85% of patients) 4
  • Inflammatory bowel disease (13-90% of patients) 4
  • Cancer (18-82% of patients) 4

Diagnostic Approach

Laboratory Testing

• Serum Ferritin: Primary marker for iron stores

  • <30 ng/mL indicates iron deficiency in patients without inflammation 4
  • Higher thresholds (up to 100 ng/mL) may be appropriate in patients with chronic inflammatory conditions 3

• Transferrin Saturation (TSAT):

  • <20% suggests iron deficiency, especially useful when ferritin is inconclusive due to inflammation 3, 4

• Additional Tests:

  • Complete blood count to confirm normal hemoglobin
  • C-reactive protein (CRP) to assess for inflammation that may affect ferritin interpretation 3
  • Reticulocyte hemoglobin concentration (CHr) or soluble transferrin receptor (sTfR) in ambiguous cases 1

Investigation for Underlying Causes

• For men and postmenopausal women:

  • GI endoscopy (upper and lower) to exclude GI malignancy 1
  • Small bowel biopsy to exclude celiac disease 1

• For premenopausal women:

  • Assess menstrual blood loss (pictorial blood loss assessment charts have 80% sensitivity/specificity) 1
  • GI investigation only if upper GI symptoms are present or age >45 years 1

• For all patients:

  • Screen for malabsorption (celiac disease)
  • Evaluate dietary intake
  • Review medication history (especially NSAIDs) 4

Management

Treatment of Underlying Cause

• Address the source of blood loss if identified
• Treat celiac disease or other malabsorption disorders
• Manage menorrhagia in premenopausal women
• Correct dietary deficiencies

Iron Supplementation

• Oral Iron:

  • First-line therapy: Ferrous sulfate 200 mg daily or on alternate days 1, 4
  • Alternative preparations: Ferrous gluconate or ferrous fumarate 1
  • Add ascorbic acid (vitamin C) 250-500 mg twice daily to enhance absorption if response is poor 3
  • Continue for 3 months after normalization of iron stores 3

• Parenteral Iron (indicated for):

  • Intolerance to oral preparations after trying at least two different formulations 1
  • Poor absorption (celiac disease, post-bariatric surgery) 4
  • Chronic inflammatory conditions (CKD, heart failure, IBD, cancer) 4
  • Need for rapid iron repletion 6

Monitoring Response

• Check ferritin and transferrin saturation after 2-4 weeks of therapy 3
• Target ferritin level of at least 100 ng/mL 1
• Monitor for symptoms improvement (fatigue, exercise tolerance, concentration)

Special Considerations

Heart Failure Patients

• Iron deficiency with or without anemia significantly impacts morbidity and quality of life 1
• Consider IV iron therapy for more rapid and effective repletion 2

Chronic Kidney Disease

• Higher ferritin threshold for diagnosis (often <300 ng/mL with TSAT <20%) 1
• May require IV iron and possibly erythropoiesis-stimulating agents 3

Common Pitfalls

• Failing to investigate iron deficiency without anemia, especially in men and postmenopausal women 1
• Misinterpreting ferritin levels in the presence of inflammation 3
• Inadequate duration of iron supplementation 3
• Not addressing the underlying cause 1

By addressing both the underlying cause and providing appropriate iron supplementation, progression to iron deficiency anemia can be prevented, and symptoms related to non-anemic iron deficiency can be improved.