Can iron deficiency cause anemia?

Can Iron Deficiency Cause Anemia?

Yes, iron deficiency is a well-established and common cause of anemia worldwide, affecting over 1.2 billion individuals globally. 1, 2

Pathophysiology and Mechanism

Iron deficiency anemia develops when the body's iron balance—intake, stores, and losses—becomes insufficient to support adequate erythrocyte (red blood cell) production. 1 This occurs through a sequential process:

• Iron stores become depleted first, followed by impaired hemoglobin synthesis, and finally the development of anemia with characteristic laboratory findings. 3
• The body attempts to compensate by suppressing hepcidin (the iron hormone), which increases iron absorption in the gut and iron release from storage sites, but this adaptation eventually fails when deficiency is severe. 2

Epidemiology and Common Causes

In developed countries like the United States:

• Gastrointestinal blood loss is the most common cause in men and postmenopausal women, with approximately 62% requiring investigation for GI bleeding. 4, 5
• Menstrual blood loss remains the leading cause in premenopausal women. 4
• Other causes include malabsorption (particularly celiac disease), poor dietary intake, previous gastrectomy, and NSAID use. 4

In developing countries:

• Low intake of bioavailable iron combined with parasitic infections are the primary drivers. 6, 7
• Iron deficiency often coexists with malnutrition, vitamin A deficiency, folate deficiency, and infection. 6

Diagnostic Confirmation

Iron deficiency anemia can be definitively diagnosed through:

• Serum ferritin <30 μg/L in the absence of inflammation (93% specificity in women of childbearing age, 92% in children aged 1-5 years). 8, 4
• Serum ferritin <12 μg/L is diagnostic regardless of other factors. 8
• Therapeutic response: An increase in hemoglobin concentration >1.0 g/dL after a course of iron supplementation confirms the diagnosis retrospectively. 4, 8

Laboratory findings include:

• Low hemoglobin and hematocrit (though these are late indicators). 8, 4
• Microcytic anemia (low mean cell volume/MCV) is characteristic, though it may be absent in combined deficiencies. 4, 8
• Elevated red cell distribution width (RDW >14%) helps distinguish iron deficiency from other causes of microcytosis like thalassemia. 4, 9

Important Clinical Caveats

Anemia screening alone has become less effective for detecting iron deficiency in the United States:

• Studies show that less than 50% of children aged 1-5 years and women of childbearing age with anemia (defined as hemoglobin <5th percentile) were actually iron deficient. 4
• Multiple other causes of anemia exist, including folate or vitamin B12 deficiency, thalassemia, sickle cell disease, recent infection, and chronic inflammation. 4, 8

Inflammation complicates diagnosis:

• Ferritin acts as an acute phase reactant and may be falsely elevated during inflammation. 8
• In inflammatory conditions, ferritin <100 μg/L may still indicate iron deficiency. 9, 8

Dimorphic anemia (combined iron and B12/folate deficiency):

• Can present with normal MCV, masking the underlying dual deficiency. 9
• Elevated RDW (>14-15%) serves as the critical diagnostic clue. 9
• Both deficiencies must be treated simultaneously for complete hematologic response. 9

Treatment Principles

Oral iron supplementation is first-line therapy:

• Target dose of 50-200 mg elemental iron daily. 5
• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks if treatment is effective. 5

Intravenous iron is increasingly utilized:

• Particularly effective in functional iron deficiency, inflammatory conditions, and when oral iron causes intolerable side effects. 2, 7
• Modern preparations allow rapid normalization with single high-dose infusions. 2, 7