What causes iron deficiency anemia?

Causes of Iron Deficiency Anemia

The primary causes of iron deficiency anemia include gastrointestinal blood loss, menstrual blood loss, pregnancy, malabsorption, and inadequate dietary intake. 1

Major Causes by Population Group

In Adult Men and Postmenopausal Women

• Gastrointestinal blood loss is the most common cause and requires thorough investigation 2, 1
  • Common sources:
    • Colorectal cancer/polyps
    • Gastric cancer
    • NSAID use
    • Angiodysplasia
    • Inflammatory bowel disease (prevalence 13-90%) 1, 3
    • Peptic ulcer disease

In Premenopausal Women

• Menstrual blood loss is the predominant cause 1
• Pregnancy (iron deficiency affects up to 84% of women in third trimester) 3

Malabsorption Causes

• Celiac disease (2-3% of patients presenting with IDA) 2, 1
• Post-gastrectomy or gastric bypass surgery 1
• Long-term proton pump inhibitor (PPI) therapy 1
• Atrophic gastritis 3

Other Important Causes

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

Laboratory Findings in Iron Deficiency

• Without inflammation:

  • Serum ferritin <30 μg/L 2, 1
  • Transferrin saturation <16% 1

• With inflammation:

  • Serum ferritin up to 100 μg/L may still indicate iron deficiency 2, 1
  • Transferrin saturation <16% 1

• Blood cell changes:

  • Microcytosis (low MCV)
  • Hypochromia (low MCH)
  • Elevated red cell distribution width (RDW) 2

Clinical Approach to Identifying Causes

1. For men and postmenopausal women:

   • Always investigate for GI malignancy 1
   • Upper GI endoscopy with small bowel biopsy
   • Colonoscopy or CT colonography
   • Urinalysis for microscopic hematuria

2. For premenopausal women:

   • Assess menstrual blood loss
   • GI investigation if menstrual loss doesn't adequately explain the degree of iron deficiency 1

Important Pitfalls to Avoid

• Don't dismiss mild anemia as it may still indicate serious underlying disease like GI malignancy 2, 1
• Don't assume a single cause when multiple contributing factors may be present 1
• Don't overlook Cameron lesions during endoscopy in patients with unexplained iron deficiency anemia 1
• Don't miss altered iron markers in patients with inflammatory conditions 1
• Don't forget to check for celiac disease with small bowel biopsies during upper endoscopy 2

Special Considerations

• In areas endemic for malaria and other infections, iron treatment should be approached cautiously to avoid worsening infections 4
• Even non-anemic iron deficiency can cause symptoms like fatigue, irritability, depression, difficulty concentrating, restless legs syndrome (32-40%), and pica (40-50%) 3
• Iron deficiency without anemia affects approximately 38% of nonpregnant reproductive-age women in high-income countries 3

Iron deficiency anemia requires both treatment of the underlying cause and iron replacement therapy. The identification of the cause is crucial, especially in men and postmenopausal women where GI malignancy must be excluded.