Iron Deficiency Anemia Causes and Investigation

Major Causes by Category

Gastrointestinal blood loss is a leading cause of iron deficiency anemia in men and postmenopausal women, with potential sources including colorectal cancer, gastric cancer, peptic ulcer disease, and NSAID-induced mucosal damage 1, 2, 3
Menstrual blood loss is the most common cause of iron deficiency anemia in premenopausal women 2
Other bleeding sources, such as urinary tract bleeding, epistaxis, and blood donation, can also contribute to iron deficiency anemia 4, 5

Celiac disease is a cause of iron deficiency anemia, found in 3-5% of cases 1, 6
Previous gastrectomy, gastric atrophy, and chronic PPI therapy can impair iron absorption 3, 4, 5
Bacterial overgrowth, gut resection or bypass, and small bowel tumors can also contribute to iron malabsorption 4, 3

Approximately one-third of men and postmenopausal women with iron deficiency anemia have an underlying pathological abnormality, most commonly in the GI tract 1
Multiple causes may coexist in the same patient, and finding one cause should not deter further investigation 5
Serum ferritin is the most powerful test for diagnosing iron deficiency, but may be falsely normal in inflammatory conditions 2, 3
A good response to iron therapy strongly suggests iron deficiency even with equivocal iron studies 6

A detailed history and physical examination can help identify risk factors and potential causes of iron deficiency anemia 6
Confirmation of iron deficiency through serum ferritin and other iron studies is essential for diagnosis 6
Bidirectional GI endoscopy, including gastroscopy and colonoscopy, is recommended in men and postmenopausal women to investigate the GI tract 1, 2
Wireless capsule endoscopy may be considered for recurrent or refractory cases to assess the small bowel 1

Oral and mucosal signs such as angular cheilitis, atrophic glossitis, and koilonychia reflect chronic iron deficiency and aid in distinguishing Plummer‑Vinson syndrome from isolated esophageal disease. 7

Duodenal biopsies obtained during upper endoscopy should be performed to screen for celiac disease, which is identified in roughly 3–5 % of patients with iron‑deficiency anemia. 8
Serologic testing for tissue transglutaminase antibodies is recommended as a non‑invasive screen for celiac disease in this population. 8

Colonoscopy is advised to exclude lower‑gastrointestinal sources of occult bleeding (e.g., colorectal cancer, polyps) in individuals diagnosed with Plummer‑Vinson syndrome. 8
Bidirectional endoscopy (upper + lower) should be completed even after an esophageal web is identified, because concurrent pathology is present in about 1–10 % of cases. 9

Clinicians should not halt further gastrointestinal investigation after locating a single abnormality—especially in older patients—since multiple etiologies frequently coexist in iron‑deficiency anemia. 7