What are the causes of chronic iron deficiency anemia?

Causes of Chronic Iron Deficiency Anemia

Gastrointestinal blood loss is the most common cause of chronic iron deficiency anemia in adult men and postmenopausal women, requiring thorough investigation of the GI tract. 1

Primary Causes of Chronic Iron Deficiency Anemia

Gastrointestinal Causes

• Occult GI Blood Loss:

  • Colorectal cancer/polyps
  • Gastric cancer
  • NSAID use (common cause)
  • Angiodysplasia
  • Inflammatory bowel disease (13-90% of IBD patients) 1
  • Peptic ulcer disease
  • Esophagitis/esophageal cancer
  • Cameron lesions (often missed during routine endoscopy) 1

• Malabsorption:

  • Celiac disease (affects 2-3% of patients with IDA) 1
  • Post-gastrectomy or gastric bypass surgery 1
  • Bacterial overgrowth
  • Whipple's disease
  • Gut resection or bypass

Gynecological Causes

• Heavy menstrual bleeding (most common cause in premenopausal women) 1, 2

Medication-Related Causes

• NSAID use (causing GI bleeding) 3, 1
• Long-term proton pump inhibitor (PPI) therapy (reducing iron absorption) 1

Other Causes

• Pregnancy (increased iron requirements) 2
• Chronic inflammatory conditions:
  • Chronic kidney disease (24-85% of patients) 2
  • Heart failure (37-61% of patients) 2
  • Cancer (18-82% of patients) 2
• Inadequate dietary iron intake 3
• Endurance athletics 1
• Hematuria (renal tract pathology) 1

Diagnostic Approach

Laboratory Evaluation

• Serum ferritin is the most powerful test for iron deficiency 3
  • <12 μg/dL is diagnostic of iron deficiency
  • <30 μg/mL indicates iron deficiency in patients without inflammation 1
  • <100 μg/mL may indicate iron deficiency in patients with concurrent inflammation, malignancy, or hepatic disease 3, 1
• Transferrin saturation <16% indicates iron deficiency 1
• Complete blood count showing microcytosis (low MCV) is characteristic but may be absent in combined deficiencies 3
• Elevated red cell distribution width (RDW) may indicate combined deficiencies 3

Gastrointestinal Evaluation

• GI investigations should be considered in all patients with confirmed IDA unless there is a history of significant non-GI blood loss 3
• Upper GI endoscopy with small bowel biopsies and colonoscopy should be performed to investigate gastrointestinal blood loss 1
• Small bowel evaluation (capsule endoscopy, CT, or MRI enterography) should be considered if:
  • Symptoms suggest small bowel disease
  • Hemoglobin cannot be restored with iron therapy
  • Red flags are present (weight loss, abdominal pain, elevated CRP) 1

Common Pitfalls in Diagnosis and Management

• Assuming a single cause when multiple contributing factors may be present 1
• Dismissing mild anemia as insignificant when it may indicate serious underlying disease 1
• Not thoroughly investigating iron deficiency anemia in men and postmenopausal women, even when other potential causes are identified 1
• Overlooking Cameron lesions during routine endoscopy 1
• Failing to consider iron deficiency in patients with inflammatory conditions where standard markers may be altered 1
• Incomplete investigation of the gastrointestinal tract 3
• Not considering celiac disease as a cause of iron deficiency anemia 1

Management Considerations

• Treatment should address the underlying cause of iron deficiency
• Oral iron supplementation with 100-200 mg elemental iron daily for 3-6 months to replenish iron stores 1
• Consider intravenous iron when oral therapy is ineffective, patient experiences intolerable side effects, intestinal malabsorption is present, or prolonged inflammation exists 1, 4
• Eradication of Helicobacter pylori if present, especially in recurrent cases 1
• Acid suppression therapy for peptic ulcer disease 1
• Gluten-free diet for celiac disease 1

Remember that even when a dietary cause is suspected, a full GI investigation is still required, especially in men and postmenopausal women, as iron deficiency may indicate serious underlying pathology such as gastrointestinal malignancy 3, 1.