What are the causes of iron deficiency anemia?

Causes of Iron Deficiency Anemia

The most common causes of iron deficiency anemia are gastrointestinal blood loss in men and postmenopausal women, and menstrual blood loss in premenopausal women. 1

Primary Causes of Iron Deficiency Anemia

Blood Loss

• Gastrointestinal blood loss

  • Colonic cancer
  • Gastric cancer
  • Peptic ulcer disease
  • Angiodysplasia
  • NSAID-induced mucosal damage
  • Inflammatory bowel disease (IBD) 2, 1
  • Cameron lesions in hiatal hernias 1
  • Hemorrhoids

• Gynecological causes

  • Menstrual blood loss (primary cause in premenopausal women) 1
  • Uterine fibroids
  • Endometriosis

• Other sources of blood loss

  • Blood donation
  • Epistaxis (nosebleeds)
  • Hematuria (renal tract pathology) 2

Impaired Iron Absorption

• Celiac disease 2, 3
• Atrophic gastritis 3
• Post-gastrectomy or gastric bypass surgery 2, 3
• Long-term proton pump inhibitor (PPI) therapy 2
• Helicobacter pylori infection

Increased Iron Requirements

• Pregnancy 3
• Infancy and early childhood
• Adolescent growth spurt
• Endurance athletes 2

Inadequate Dietary Intake

• Poor diet lacking iron-rich foods
• Vegetarian/vegan diets without proper iron supplementation
• Malnutrition

Chronic Inflammatory Conditions

• Chronic kidney disease (24-85%) 3
• Heart failure (37-61%) 3
• Cancer (18-82%) 3
• Inflammatory bowel disease (13-90%) 3

Diagnostic Approach

Iron deficiency progresses through several stages before anemia develops:

1. Depletion of iron stores
2. Iron-deficient erythropoiesis
3. Iron deficiency anemia

Laboratory findings in iron deficiency:

• In patients without inflammation: serum ferritin <30 mcg/L or transferrin saturation <16% 2
• In patients with inflammation: serum ferritin <100 mcg/L and transferrin saturation <16% 2
• If serum ferritin is between 30-100 mcg/L with low transferrin saturation, a combination of true iron deficiency and anemia of chronic disease is likely 2

Investigation of Underlying Causes

For men and postmenopausal women with IDA:

• Upper gastrointestinal endoscopy with small bowel biopsy
• Colonoscopy or CT colonography 2
• Urinalysis to check for microscopic hematuria 2

For premenopausal women:

• Gynecological assessment if menstrual blood loss is excessive
• GI investigation if menstrual blood loss does not adequately explain the degree of iron deficiency

Clinical Pearls and Pitfalls

• Important caveat: Even mild anemia should not be dismissed as insignificant, as it may indicate serious underlying disease such as gastrointestinal malignancy 2

• Common pitfall: Assuming a single cause for iron deficiency when multiple contributing factors may be present 2

• Warning sign: Iron deficiency anemia in men and postmenopausal women should always prompt investigation for gastrointestinal malignancy, even if other potential causes are identified 2, 1

• Special consideration: In patients with inflammatory conditions, standard markers of iron deficiency may be altered, making diagnosis more challenging 2

• Practical tip: Cameron lesions in hiatal hernias are frequently missed during routine endoscopy and should be specifically looked for in patients with unexplained iron deficiency anemia 1