Etiologies of Iron Deficiency Anemia

Blood Loss

Gastrointestinal blood loss is the leading cause of iron deficiency anemia in men and postmenopausal women, with malignancy, peptic ulcer disease, inflammatory bowel disease, and portal hypertensive gastropathy being major causes 1, 2, 3
Menstrual blood loss is the most common cause of iron deficiency anemia in premenopausal women 1
Urinary tract bleeding, including renal cell carcinoma, can cause chronic blood loss 5, 1
Epistaxis, particularly in hereditary hemorrhagic telangiectasia, can contribute to iron deficiency anemia 5
Blood donation can deplete iron stores, especially with repeated donations 5, 1

Celiac disease is found in 3-5% of iron deficiency anemia cases and should be routinely excluded in all age groups 5, 1
Atrophic gastritis, including autoimmune and Helicobacter pylori-related forms, impairs iron absorption 5
Post-surgical states, such as previous gastrectomy, gastric bypass, or intestinal resection, disrupt duodenal/proximal jejunal absorption 2, 5
Chronic proton pump inhibitor therapy can cause dose-dependent iron deficiency through hypochlorhydria, with an adjusted odds ratio of 2.49 for high-dose use 5, 6

Dietary insufficiency, particularly in developing countries, can lead to iron deficiency anemia 4
Malnutrition can affect iron availability 4

Pregnancy increases physiological requirements for fetal development 4
Infancy and childhood require increased iron, particularly in preterm or low-birthweight infants 4
Endurance athletes may experience iron deficiency due to high hepcidin levels 5

Chronic kidney disease can cause iron deficiency through reduced intake, reduced absorption, dialysis losses, and functional iron deficiency from elevated hepcidin 7
Chronic heart failure is associated with iron deficiency in 40-70% of cases due to malabsorption, malnutrition, GI blood loss, and hepcidin-mediated reduced iron mobilization 7
Chronic inflammatory disorders increase hepcidin, reducing iron absorption and mobilization 8

Multiple etiologies frequently coexist, and finding one cause should not deter further investigation, particularly in older adults 5, 1
Age and sex determine the investigation approach, with approximately one-third of men and postmenopausal women having underlying pathological GI abnormalities requiring bidirectional endoscopy 1
Functional iron deficiency occurs when inflammation prevents iron mobilization despite adequate stores, common in CKD, CHF, and IBD 8, 7