Iron deficiency anemia
Iron deficiency anemia is the most common anemia worldwide, a microcytic hypochromic anemia driven by chronic blood loss, poor intake or malabsorption, or increased iron demand. A ferritin below 15 ng/mL confirms depleted iron stores, and confirmed disease in men or postmenopausal women mandates bidirectional endoscopy to find an occult gastrointestinal source before treating with oral or intravenous iron.
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What this article covers
- Overview
Definition: iron deficiency anemia (IDA) is a microcytic, hypochromic anemia from body iron stores inadequate to sustain heme synthesis, the final step of hemoglobin production.
- Epidemiology
Global burden: IDA is the leading cause of anemia globally; the World Health Organization estimates up to 60% of pregnant women worldwide have anemia, mostly from iron deficiency.
- Risk factors
Chronic blood loss: menstrual bleeding, gastrointestinal bleeding (often microscopic, from peptic ulcer disease, colonic polyps, or colorectal cancer), and other overt or occult sources.
- Pathophysiology
Depletion precedes anemia: iron stores (reflected by ferritin) fall first, followed by a fall in transport iron (serum iron, transferrin saturation), and only then does hemoglobin synthesis fail.
- Clinical features
Fatigue and exertional symptoms: fatigue, dyspnea on exertion, dizziness, decreased exercise tolerance, and irritability, often disproportionately severe relative to the degree of anemia.
- Differential diagnosis
Colorectal cancer or other GI malignancy: the most dangerous cause of occult blood loss producing IDA in a man or postmenopausal woman; requires bidirectional endoscopy to exclude.
- Diagnosis
Confirm iron deficiency with serum ferritin, the single best test: ferritin below 15 ng/mL is highly specific (99%) though only moderately sensitive (59%) and confirms the diagnosis; because ferritin…
- Management
Treat the underlying cause first: definitive management of the bleeding source found on GI evaluation (for example polypectomy, ulcer treatment), a gluten-free diet for confirmed celiac disease, or…
- Complications
Missed occult malignancy: treating presumed IDA with iron alone, without source evaluation, risks delayed diagnosis of colorectal or other GI cancer.
- Prognosis
Excellent with correction of the cause: once the source is treated and iron stores repleted, hemoglobin and red cell indices normalize.
- Prevention
Universal infant screening: hemoglobin screening for IDA in all infants at 9 to 12 months of age per CDC recommendations, with iron supplementation for exclusively breastfed infants and avoidance of…
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- Anemia of chronic disease
Anemia of chronic disease, also called anemia of inflammation, is a normocytic normochromic anemia driven by hepcidin-mediated iron sequestration and cytokine blunting of erythropoiesis in patients with chronic infection, autoimmune disease, malignancy, or kidney disease. The iron-study pattern of low serum iron, low total iron-binding capacity, and normal-to-high ferritin distinguishes it from iron deficiency, and management centers on treating the underlying disease rather than iron supplementation.
- Alpha-thalassemia
Alpha-thalassemia is an inherited microcytic anemia caused by deletions of one or more of the four alpha-globin genes, ranging from a silent carrier state to fatal hemoglobin Barts hydrops fetalis, and it is distinguished from iron deficiency by a normal or elevated RBC count, a normal RDW, and normal iron studies. Diagnosis of the trait requires excluding iron deficiency and often direct globin gene testing because hemoglobin electrophoresis is typically normal, while hemoglobin H disease shows a detectable beta-globin tetramer and HbH inclusions on supravital stain.
- Beta-thalassemia
Beta-thalassemia is an inherited hemoglobinopathy caused by point mutations that reduce or abolish beta-globin chain synthesis, producing a spectrum from asymptomatic trait to transfusion-dependent thalassemia major (Cooley anemia) with ineffective erythropoiesis, marrow expansion, and hepatosplenomegaly. Diagnosis rests on hemoglobin electrophoresis showing elevated HbA2 and HbF, and management of major disease centers on chronic transfusion paired with iron chelation, since transfusional iron overload is the leading cause of death.
- Sideroblastic anemias
Sideroblastic anemias are disorders of defective mitochondrial heme synthesis in which iron accumulates around the erythroblast nucleus, producing ring sideroblasts on marrow Prussian blue stain and, unlike iron deficiency, iron overload rather than iron depletion. Causes are hereditary, clonal (myelodysplastic syndrome with ring sideroblasts), or reversible acquired (alcohol, lead, isoniazid/B6 deficiency, copper deficiency, zinc excess, chloramphenicol), and management centers on identifying and reversing the cause, a pyridoxine trial, and treating iron overload.
- Celiac disease
Celiac disease is an immune-mediated small-intestinal enteropathy triggered by dietary gluten in genetically predisposed individuals, presenting with malabsorptive diarrhea, iron-deficiency anemia, or dermatitis herpetiformis. Diagnosis requires IgA tissue transglutaminase serology with a total IgA level while the patient still eats gluten, confirmed by duodenal biopsy showing villous atrophy, and the only treatment is a strict lifelong gluten-free diet.
- Hemochromatosis
Hemochromatosis is a disorder of iron overload, most often hereditary HFE C282Y homozygosity causing hepcidin deficiency and excess intestinal iron absorption, that deposits iron in the liver, pancreas, heart, joints, skin, and pituitary. Screening rests on fasting transferrin saturation and ferritin, confirmation on HFE genetic testing, and treatment on regular therapeutic phlebotomy to a target ferritin of 50 to 100 ng/mL.