What are the common causes of repeated iron deficiency anemia in different patient populations, including premenopausal women, pregnant women, and individuals with gastrointestinal disorders?

Causes of Repeated Iron Deficiency Anaemia

Repeated iron deficiency anaemia in adults most commonly results from chronic gastrointestinal blood loss (particularly from malignancy, angiodysplasia, or NSAID use in men and postmenopausal women), menstrual blood loss in premenopausal women, and malabsorption disorders—with approximately one-third of men and postmenopausal women harboring underlying GI pathology, including malignancy in a third of those cases. 1

Population-Specific Causes

Men and Postmenopausal Women

Gastrointestinal blood loss is the predominant mechanism in this population, requiring urgent investigation to exclude malignancy 1:

• Malignant lesions: Colorectal cancer and gastric cancer are the most critical diagnoses to exclude, as they frequently present with IDA in the absence of specific symptoms 1
• NSAID-induced mucosal damage: A frequently unreported cause of occult GI blood loss that patients often fail to mention because they don't consider over-the-counter medications significant 2, 3
• Angiodysplasia: Vascular ectasias that can cause persistent blood loss, particularly in elderly patients 1
• Peptic ulcer disease: Though less common with modern H. pylori treatment 1
• Inflammatory bowel disease: Crohn's disease and ulcerative colitis can present with IDA 1

Malabsorption disorders account for a significant proportion of cases 1:

• Coeliac disease: Found in 3-5% of all IDA cases and must be screened for in every patient with unexplained anaemia 2, 3, 4
• Atrophic gastritis: Reduces gastric acid secretion necessary for iron absorption 5
• H. pylori gastritis: Impairs iron absorption through reduced acid secretion 5
• Post-bariatric surgery: Approximately 25% of patients develop IDA within 2 years following Roux-en-Y gastric bypass, markedly more common in women 1

Premenopausal Women

Menstrual blood loss is the commonest cause in this population, but this should not preclude investigation when IDA is recurrent or severe 1:

• Heavy menstrual bleeding: The primary physiological cause in women of reproductive age 1
• Pregnancy: Increased iron demands during pregnancy and lactation 1
• GI pathology: Still present in a proportion of premenopausal women, particularly those over 40 years or with alarm symptoms 1, 6
• Coeliac disease: Must be screened for regardless of menstrual history 1, 2

Pregnant Women

Increased iron requirements during pregnancy create a unique vulnerability 1:

• Physiological increased demand: Expansion of maternal red cell mass and fetal/placental iron requirements 7
• Pre-existing low iron stores: Women entering pregnancy with depleted stores are at highest risk 7
• Underlying GI pathology: Should still be considered if IDA is severe or refractory to supplementation 1

Recurrent IDA After Initial Treatment

When IDA recurs despite adequate initial treatment and investigation, consider these specific causes 1:

Inadequate Investigation or Treatment

• Incomplete initial endoscopy: Failure to perform bidirectional endoscopy (both upper and lower GI) misses dual pathology in 10-15% of patients 2, 4
• Missed coeliac disease: Occurs when screening serology is not performed 2, 3, 4
• Inadequate iron repletion: Stopping iron therapy before stores are replenished (target ferritin >50 ng/mL) 4

Small Bowel Pathology

Small bowel lesions are the primary consideration when bidirectional endoscopy is negative 1:

• Small bowel angiodysplasia: Requires wireless capsule endoscopy for diagnosis 1
• Small bowel tumours: Including lymphoma and leiomyoma 1
• Crohn's disease: Isolated small bowel involvement 1

Chronic Inflammatory Conditions

Inflammatory bowel disease is a particularly important cause of recurrent IDA 1:

• Active IBD: One-third of patients with active IBD have iron deficiency 1
• Persistent intestinal inflammation: Recurrent IDA may indicate ongoing inflammatory activity even with clinical remission and normal biomarkers 1
• Impaired oral iron absorption: Systemic inflammation and small bowel involvement reduce oral iron efficacy 1

Medication-Related Causes

Anticoagulants and antiplatelet agents can unmask or exacerbate bleeding from underlying lesions 2:

• Chronic NSAID use: Including over-the-counter preparations that patients fail to report 2, 3
• Aspirin and antiplatelet therapy: Can unmask angiodysplasia 2
• Anticoagulation: Reveals previously occult vascular lesions 2

Post-Surgical States

GI surgery predisposes to recurrent IDA through multiple mechanisms 1:

• Gastric resection or bypass: Reduces acid secretion and intrinsic factor, impairing iron and B12 absorption 1
• Small bowel resection: Reduces absorptive surface area 1
• Bariatric surgery: Particularly Roux-en-Y gastric bypass, with IDA developing in approximately 25% of patients by 2 years post-operatively 1

Critical Diagnostic Pitfalls to Avoid

Do not assume a single cause explains recurrent IDA without completing comprehensive investigation 2, 4:

• Multiple coexisting etiologies: Present in 10-15% of patients, so finding one cause should not stop the investigation 2, 4
• Minor findings: Do not accept minor endoscopic findings (such as mild gastritis) as the sole explanation without completing lower GI investigation 2, 4
• Dietary deficiency assumption: Even with a positive dietary history, full GI investigation is still required in men and postmenopausal women 2
• Failure to screen for coeliac disease: Results in missed diagnoses in 3-5% of cases 2, 3, 4
• Inadequate medication history: Explicitly ask about all NSAID use, as patients frequently fail to report over-the-counter medications 2, 3

Monitoring for Recurrence

Patients with IBD and IDA require structured monitoring 1:

• Every 3 months for at least one year after correction of IDA 1
• Periodic monitoring thereafter to detect recurrence early 1
• Recurrent IDA may indicate persistent intestinal inflammation even with apparent clinical remission 1

Post-bariatric surgery patients require lifelong monitoring given their 25% risk of developing IDA 1