What are the primary causes of Iron Deficiency Anemia (IDA)?

Primary Causes of Iron Deficiency Anemia

Iron deficiency anemia results from four major mechanisms: blood loss (most common in adults), malabsorption, inadequate dietary intake, and increased physiological demands. 1, 2

Blood Loss (Leading Cause in Adults)

Gastrointestinal Sources

• Gastrointestinal bleeding is the predominant cause in men and postmenopausal women, accounting for approximately one-third of cases with identifiable pathological abnormalities 1, 3
• Specific GI sources include:
  • Colorectal cancer and gastric cancer 1
  • Peptic ulcer disease 1
  • NSAID-induced mucosal damage (a frequently overlooked contributing factor that must be addressed) 1, 3
  • Inflammatory bowel disease (causes anemia in 13-90% of IBD patients) 2

Menstrual Blood Loss

• Heavy menstrual bleeding is the most common cause of IDA in premenopausal women 1, 4
• Approximately 38% of nonpregnant reproductive-age women have iron deficiency without anemia, and 13% have iron-deficiency anemia 2

Other Bleeding Sources

• Urinary tract bleeding, epistaxis, and frequent blood donation can contribute to iron depletion 1

Malabsorption Disorders

Gastrointestinal Conditions

• Celiac disease is found in 3-5% of IDA cases and represents a critical diagnosis not to miss 1, 3
• Previous gastrectomy, gastric atrophy (autoimmune or Helicobacter pylori-related), and chronic proton pump inhibitor therapy impair iron absorption 1, 5
• Post-bariatric surgical procedures significantly reduce iron absorption 2
• Bacterial overgrowth, gut resection or bypass, and small bowel tumors also contribute 1

Inadequate Dietary Intake

• Poor dietary iron intake is infrequent in developed countries but represents a major public health problem in developing regions 6
• This cause is more relevant in pediatric populations and areas with limited access to iron-rich foods 7, 6

Increased Physiological Demands

Pregnancy

• Iron deficiency affects up to 84% of pregnant women during the third trimester in high-income countries 2
• Pregnancy increases iron requirements substantially, making it a common cause of IDA 7, 4

Chronic Inflammatory Conditions

• Chronic kidney disease: 24-85% prevalence of iron deficiency 2
• Heart failure: 37-61% prevalence 2
• Cancer: 18-82% prevalence 2
• These conditions create functional iron deficiency through inflammatory mechanisms 5, 2

Critical Clinical Considerations

Multiple causes frequently coexist in the same patient—finding one cause should never stop further investigation. 1, 3 For example, a patient may have both celiac disease and concurrent GI malignancy (occurs in 10-15% of celiac cases) 8

High-Risk Populations Requiring Screening

• All men and postmenopausal women with IDA require bidirectional GI endoscopy (gastroscopy and colonoscopy) unless an obvious alternative cause is identified 1, 3
• Premenopausal women with risk factors beyond menstruation (NSAID use, family history of GI malignancy, alarm symptoms) 1
• Patients with chronic inflammatory conditions (CKD, HF, IBD, cancer) 2
• Pregnant women, particularly during second and third trimesters 2

Rare Causes

• Iron-refractory iron deficiency anemia due to TMPRSS6 mutations occurs very rarely 5