What are the causes of iron deficiency anemia?

Causes of Iron Deficiency Anemia

Iron deficiency anemia is most commonly caused by chronic blood loss from the gastrointestinal tract in men and postmenopausal women, while menstrual blood loss is the predominant cause in premenopausal women. 1

Major Causes by Category

Blood Loss

• Gastrointestinal blood loss - a leading cause in men and postmenopausal women 1
  • Colorectal cancer/polyps 1
  • Gastric cancer 1
  • Peptic ulcer disease 1
  • Esophagitis/esophageal cancer 1
  • NSAID-induced mucosal damage 1
  • Angiodysplasia 1
  • Inflammatory bowel disease (ulcerative colitis, Crohn's disease) 1, 2
• Menstrual blood loss - the most common cause in premenopausal women 1, 2
• Other bleeding sources
  • Urinary tract bleeding (e.g., renal cell carcinoma) 1
  • Epistaxis (nosebleeds) 1
  • Blood donation 1

Malabsorption

• Celiac disease (found in 3-5% of IDA cases) 1, 2
• Previous gastrectomy (partial or total) 1
• Gastric atrophy 1
• Bariatric surgical procedures 2
• Chronic PPI therapy (impairs iron absorption due to hypochlorhydria) 1
• Bacterial overgrowth 1
• Gut resection or bypass 1

Dietary Factors

• Poor dietary iron intake 1, 2
• Vegetarian/vegan diets with insufficient iron-rich foods 2

Increased Iron Requirements

• Pregnancy (affects up to 84% of women in third trimester) 2
• Growth periods in children and adolescents 3

Chronic Inflammatory Conditions

• Inflammatory bowel disease (13-90% prevalence) 2
• Chronic kidney disease (24-85% prevalence) 2
• Heart failure (37-61% prevalence) 2
• Cancer (18-82% prevalence) 2

Less Common Causes

• Intestinal parasites (e.g., hookworm) 1
• Hereditary hemorrhagic telangiectasia 1
• Meckel's diverticulum 1
• Lymphoma and other small bowel tumors 1
• Whipple's disease 1
• Lymphangiectasia 1

Clinical Pearls and Pitfalls

• Approximately one-third of men and postmenopausal women with IDA have an underlying pathological abnormality, most commonly in the GI tract 1
• Multiple causes may coexist in the same patient - finding one cause should not deter further investigation, particularly in older age groups 1
• GI malignancies can present with IDA even in the absence of specific symptoms, making thorough investigation crucial 1
• Serum ferritin is the most powerful test for diagnosing iron deficiency, but may be falsely normal in inflammatory conditions 1
• A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) strongly suggests iron deficiency even with equivocal iron studies 1
• All patients with unexplained IDA should be screened for celiac disease and microscopic hematuria 1
• Endurance athletes have an increased risk of iron deficiency, possibly due to elevated hepcidin levels 1

Investigation Approach

• Detailed history to identify risk factors and potential causes 1
• Confirmation of iron deficiency through serum ferritin and other iron studies 1
• Urinalysis to exclude renal tract pathology 1
• Screening for celiac disease (serological testing or small bowel biopsy) 1
• Bidirectional GI endoscopy (gastroscopy and colonoscopy) in men and postmenopausal women 1
• Consider CT colonography as an alternative to colonoscopy in patients with significant comorbidities 1
• Wireless capsule endoscopy for recurrent or refractory cases to assess the small bowel 1

Iron deficiency anemia requires both appropriate iron replacement therapy and thorough investigation to identify and treat the underlying cause, which is essential for preventing recurrence and improving long-term outcomes 1, 2.