Iron Deficiency Anemia – Causes

Causes of iron deficiency. Physiological: In infants, consumption of iron stores that accumulate during gestation to support rapid growth may lead to absolute iron deficiency. In adolescence, there is continued increased iron requirements owing to rapid growth. In female adolescents, menstruation further increases the risk for iron deficiency. During pregnancy, demands for absorbed iron increase, which some cannot meet exclusively by dietary iron intake. Causes of iron deficiency during pregnancy include expansion of maternal red cell mass, and growth of the fetus and placenta. Inadequate diet: Plant-based iron (non-heme iron) is not as well absorbed as iron obtained from meat and fish (heme iron), hence the increased risk of iron deficiency in vegetarians and vegans. Malabsorption: Non-heme iron is in the form of Fe³⁺ (ferric iron). Heme iron is complexed as Fe²⁺ (ferrous iron) in hemoglobin and myoglobin. Absorption of non-heme Fe³⁺requires gastric acid-dependent reduction to Fe²⁺. Thus, factors that lead to achlorhydria may cause iron deficiency. Although iron is primarily absorbed in the duodenum, surgical procedures that involve the stomach (e.g., bariatric surgery) commonly lead to iron deficiency. Mechanisms include decreased iron intake post-operative reduction in food intake and changes in food preferences, malabsorption from hypochloridria and surgeries that involve bypassing of duodenum and proximal jejunum and blood loss from blind intestinal loops and marginal ulcers. Chronic blood loss: Chronic blood loss, especially from menstruation and gastrointestinal sources, is by far the most common cause of iron deficiency.

Two important considerations:

Iron deficiency anemia is often multifactorial, and dual pathology (for example, significant disease in both upper and lower GI tract) is found in 1%–10% of cases—this should be particularly considered in the older patient.
In males and postmenopausal women, cancer of the gastrointestinal tract is found in 8%–10% of cases.
In premenopausal women, cancer of the gastrointestinal tract is found in about 1% of cases.

Snook et al, Gut. 2021;70(11):2030-2051

Ko et al, Gastroenterology. 2020;159:1085-1094

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