What are the primary causes of iron deficiency anemia?

Causes of Iron Deficiency Anemia

Primary Causes by Patient Population

Gastrointestinal blood loss is the leading cause in men and postmenopausal women, while menstrual blood loss is the most common cause in premenopausal women. 1

In Men and Postmenopausal Women

• GI tract bleeding accounts for approximately one-third of cases and represents the most critical diagnostic consideration due to malignancy risk 1, 2
  • Colorectal cancer (most common malignancy) 1
  • Gastric cancer (occurs at 1/7 the frequency of colorectal cancer) 3
  • Peptic ulcer disease 1
  • NSAID-induced mucosal damage 1

In Premenopausal Women

• Menstrual blood loss is the predominant cause 1
• Heavy menstrual bleeding affects 38% of reproductive-age women with iron deficiency without anemia, and 13% with iron-deficiency anemia 4
• Pregnancy increases iron requirements dramatically, with up to 84% of women developing iron deficiency during the third trimester 4

Malabsorption Disorders

• Celiac disease is found in 2-5% of iron deficiency anemia cases and requires mandatory screening 1, 5
• Atrophic gastritis and previous gastrectomy impair acid production necessary for iron absorption 1, 3
• Chronic PPI therapy reduces gastric acid and decreases iron absorption 1
• Bariatric surgery (gastric bypass or sleeve gastrectomy) causes both reduced intake and malabsorption 3, 4
• Bacterial overgrowth, gut resection, and small bowel tumors contribute to malabsorption 1

Other Bleeding Sources

• Urinary tract bleeding 1
• Epistaxis (chronic or recurrent) 1
• Frequent blood donation 1

Inadequate Dietary Intake

• Insufficient dietary iron intake, particularly in vegetarians and populations with limited access to iron-rich foods 4
• This is more common in developing countries but can occur in high-income settings with restrictive diets 6

Chronic Inflammatory Conditions

These conditions create functional iron deficiency through hepcidin-mediated iron sequestration, though absolute deficiency often coexists:

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

Critical Clinical Pitfalls

• Multiple causes frequently coexist in the same patient—finding one cause (such as menstruation) should not stop investigation if the degree of anemia seems disproportionate or if the patient is male or postmenopausal 1, 2, 5
• NSAID use is an extremely common contributing factor that must be specifically addressed in the history, as it causes occult GI bleeding even without overt ulceration 2
• Approximately one-third of men and postmenopausal women have underlying GI pathology, with malignancy being the most serious concern 2

Investigation Priority

• Bidirectional endoscopy (gastroscopy and colonoscopy) is mandatory in men and postmenopausal women unless an obvious alternative cause is identified 2, 3
• Serological celiac disease screening with tissue transglutaminase antibody (IgA) and total IgA levels should be performed in all patients 5, 3
• Premenopausal women under age 40 with typical menstrual blood loss may not require endoscopy initially 3