Iron Deficiency Anemia: Symptoms and Causes
Iron deficiency anemia presents with both general anemia symptoms (breathlessness, fatigue, heart failure) and specific iron deficiency manifestations (angular stomatitis, glossitis, koilonychia, restless legs syndrome, pagophagia, blue sclerae), with the most common causes being gastrointestinal blood loss in men and postmenopausal women, and menstrual blood loss in premenopausal women. 1
Clinical Manifestations
General Anemia Symptoms
- Breathlessness, fatigue, and heart failure are the primary manifestations of anemia itself 1
- Dyspnea, lightheadedness, and exercise intolerance occur commonly, with worsening heart failure in those with pre-existing cardiac disease 2
- Patients may experience irritability, depression, and difficulty concentrating 2
Iron-Specific Symptoms
- Angular stomatitis and glossitis (inflammation of mouth corners and tongue) 1
- Koilonychia (spoon-shaped nails) 1
- Restless legs syndrome affects 32-40% of patients with iron deficiency 2
- Pagophagia (ice craving) occurs in 40-50% of cases 1, 2
- Blue sclerae (bluish discoloration of the whites of eyes) 1
Important caveat: Many patients with iron deficiency anemia are completely asymptomatic, and symptom prevalence varies with age, comorbidities, and the severity and rate of development of iron deficiency 2
Major Causes by Category
Blood Loss (Most Common)
- Gastrointestinal bleeding is the leading cause in men and postmenopausal women, including colorectal cancer, gastric cancer, peptic ulcer disease, and NSAID-induced mucosal damage 3
- Menstrual blood loss is the most common cause in premenopausal women, with approximately 38% having iron deficiency without anemia and 13% having iron-deficiency anemia 3, 2
- Other bleeding sources include urinary tract bleeding (renal cell carcinoma), chronic nosebleeds, and blood donation 1, 3
Malabsorption
- Celiac disease accounts for 3-5% of iron deficiency anemia cases and should be routinely screened serologically 1, 3
- Gastric causes include previous gastrectomy, atrophic gastritis (autoimmune or H. pylori-related), and chronic PPI therapy causing hypochlorhydria 3, 4
- Intestinal causes include bacterial overgrowth, gut resection or bypass surgery (especially bariatric procedures), and small bowel tumors 3, 2
Inadequate Intake and Increased Demand
- Dietary insufficiency from inadequate iron intake 3, 2
- Pregnancy causes physiologically increased iron requirements, with up to 84% of pregnant women in the third trimester having iron deficiency 2
- Endurance athletes commonly develop iron deficiency, possibly due to high hepcidin levels 1
Chronic Inflammatory Conditions
- Inflammatory bowel disease (13-90% prevalence of iron deficiency) 2
- Chronic kidney disease (24-85% prevalence) 2
- Heart failure (37-61% prevalence) 2
- Cancer (18-82% prevalence) 2
Critical Clinical Pearls
Approximately one-third of men and postmenopausal women with iron deficiency anemia have underlying pathological abnormalities, most commonly in the GI tract, making investigation essential. 3, 5
Key Pitfalls to Avoid
- Multiple causes frequently coexist in the same patient—finding one cause (such as menstruation or NSAID use) should not deter further GI investigation, particularly in older age groups 1, 3
- Long-term NSAID usage is a common contributing factor that must be identified and addressed 1
- Physical examination is generally unremarkable but may occasionally provide the diagnosis (e.g., hereditary hemorrhagic telangiectasia) 1
- A family history of true iron-refractory IDA is rare but suggests genetic disturbance of iron absorption pathways (TMPRSS6 mutations) 1, 4
Risk Stratification
Age, sex, hemoglobin concentration, and mean cell volume are all independent predictors of GI cancer risk in iron deficiency anemia and must be considered in holistic risk assessment. 1 The cancer risk in iron deficiency without anemia is low 1