What are the common causes of iron‑deficiency anemia?

Common Causes of Iron Deficiency Anemia

Iron deficiency anemia results from four primary mechanisms: blood loss (most common in adults), malabsorption, inadequate dietary intake, and increased physiological demand—with gastrointestinal bleeding being the leading pathological cause in men and postmenopausal women, while menstruation accounts for most cases in premenopausal women. 1, 2

Blood Loss (Most Common Pathological Cause)

Gastrointestinal Sources

• Colorectal and gastric cancers account for approximately one-third of pathological findings in men with iron deficiency anemia and warrant urgent investigation even without GI symptoms 2
• Peptic ulcer disease and NSAID-induced mucosal injury produce occult blood loss without overt symptoms 1, 2
• Angiodysplasia and vascular malformations should be considered when initial endoscopy is unrevealing 2
• Chronic NSAID use—including over-the-counter products that patients frequently fail to report—causes occult bleeding even without ulceration 1, 2, 3

Gynecological Blood Loss

• Menstruation is the leading cause in premenopausal women, requiring an additional 0.3–0.5 mg of elemental iron daily during reproductive years 2, 3

Other Bleeding Sources

• Urinary tract bleeding (particularly renal cell carcinoma) must be excluded with urinalysis in all patients with unexplained iron deficiency 1, 2
• Recurrent epistaxis and frequent blood donation gradually deplete iron stores 1, 2, 3
• Hookworm infection causes chronic GI blood loss, though uncommon in high-income settings 2, 3

Malabsorption Disorders

Celiac Disease

• Celiac disease is responsible for 3–5% of all iron deficiency anemia cases and must be screened in every patient regardless of age or sex 4, 2, 3
• Screening should include tissue transglutaminase antibody testing plus duodenal biopsies during upper endoscopy, even if serology is negative 4, 2

Medication-Induced Malabsorption

• Chronic proton pump inhibitor therapy impairs iron absorption through hypochlorhydria 1, 2, 3

Surgical Causes

• Prior gastrectomy, gastric bypass, or bariatric procedures cause malabsorption via multiple mechanisms 1, 2, 3
• Atrophic gastritis reduces gastric acid secretion, limiting conversion of dietary iron to its absorbable form 2

Other Malabsorptive Conditions

• Small bowel bacterial overgrowth, extensive gut resection, and small bowel tumors contribute to iron malabsorption 1, 2

Inadequate Dietary Intake

• Low socioeconomic status is associated with poor dietary iron intake due to limited access to iron-rich foods 2, 3
• Vegetarian diets provide little heme iron (the most bioavailable form); concurrent vitamin C intake can partially offset this deficiency 2
• Even when dietary insufficiency is identified, a full gastrointestinal work-up remains essential in adult males and postmenopausal women 2

Increased Physiological Demand

Pregnancy and Growth

• Pregnancy requires an average of 3 mg of elemental iron daily throughout gestation to meet fetal growth and maternal blood loss at delivery 2, 3
• Infants and children—especially preterm or low-birth-weight infants—have high iron requirements for growth and are at heightened risk for deficiency 2

Critical Diagnostic Considerations

Multiple Concurrent Etiologies

• Iron deficiency is often multifactorial: dual pathology occurs in 1–10% of cases, so investigation must continue after the first cause is identified 1, 4, 2, 3
• Approximately one-third of men and postmenopausal women with iron deficiency anemia have an underlying pathological GI abnormality 4

Common Pitfalls to Avoid

• Minor endoscopic findings (e.g., small hiatal hernia) should not be accepted as the sole explanation without completing lower GI evaluation 2
• Clinicians must explicitly inquire about all NSAID use, including over-the-counter products, because patients frequently omit this information 2, 3
• Failure to screen for celiac disease results in missed diagnoses in approximately 3–5% of cases 2

Specific Risk Factors to Elicit in History

• Chronic overt blood loss (nosebleeds, menstruation), blood donation, inadequate dietary intake, long-term NSAID usage, and previous resectional or bypass surgery of the GI tract 1
• Long-term PPI therapy may contribute to iron deficiency risk 1
• Iron deficiency is common in endurance athletes—the mechanism is uncertain, but high hepcidin levels may contribute 1

Physical Examination Findings

• Angular stomatitis, glossitis, koilonychia, restless legs syndrome, pagophagia (craving for ice), and blue sclerae reflect chronic iron deficiency 1, 4
• Hereditary hemorrhagic telangiectasia may be evident on physical examination 1