How does aspirin (acetylsalicylic acid) affect iron deficiency anemia?

Impact of Aspirin on Iron Deficiency Anemia

Aspirin can worsen iron deficiency anemia through two primary mechanisms: by causing gastrointestinal blood loss and potentially through iron chelation by its metabolites, which may increase iron excretion.

Mechanisms of Aspirin's Effect on Iron Deficiency Anemia

1. Gastrointestinal Blood Loss

• Aspirin, even at low doses (75-162 mg/day), increases the risk of gastrointestinal bleeding by damaging the gastric mucosa 1
• The British Society of Gastroenterology guidelines identify NSAID use, including aspirin, as a common cause of occult gastrointestinal blood loss leading to iron deficiency anemia 1
• Major gastrointestinal bleeding rates with aspirin use are estimated at 2-4 per 1,000 middle-aged individuals and 4-12 per 1,000 older individuals over a five-year period 1

2. Iron Chelation Effect

• Recent research suggests aspirin metabolites may act as iron chelators 2
• Approximately 90% of oral aspirin is metabolized into compounds (salicyluric acid, salicylic acid, 2,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid) that have high affinity for binding iron 2
• These metabolites may increase iron excretion and alter iron balance, particularly with long-term use 2

Clinical Evidence

Risk in Elderly Populations

• The ASPREE trial found that daily low-dose aspirin (100mg) increased incident anemia in older adults (HR 1.20,95% CI 1.12-1.29) 3
• Aspirin users had greater prevalence of low ferritin levels (<45 μg/L) at 3 years compared to placebo (13% vs 9.8%) 3
• Hemoglobin concentrations declined more steeply in aspirin users by 0.6 g/L per 5 years compared to placebo 3
• This effect occurred independent of major bleeding events 3

Conflicting Evidence

• One cross-sectional study of 464 elderly subjects found that chronic low-dose aspirin use was associated with 42% less anemia, contradicting other findings 4
• This highlights the complexity of aspirin's effects on iron metabolism and the need for prospective studies

Diagnostic Considerations for Patients on Aspirin

When evaluating iron deficiency anemia in patients taking aspirin:

1. Confirm iron deficiency with serum ferritin (<12 μg/dL is diagnostic) 1, 5

   • Note that ferritin may be falsely elevated with inflammation, malignancy, or hepatic disease
   • Transferrin saturation <30% can help confirm diagnosis

2. Conduct gastrointestinal evaluation 1, 5

   • Upper GI endoscopy (reveals cause in 30-50% of patients)
   • Small bowel biopsies during endoscopy (2-3% of IDA cases have celiac disease)
   • Lower GI examination (colonoscopy) unless carcinoma or celiac disease is found
   • Note that dual pathology (lesions in both upper and lower GI tract) occurs in 10-15% of cases

Management Recommendations

1. Consider aspirin's necessity and risk-benefit ratio

   • For secondary prevention in those with established cardiovascular disease, benefits typically outweigh risks 1
   • For primary prevention, carefully weigh cardiovascular benefit against risk of anemia and bleeding 1

2. Monitor hemoglobin levels in patients on long-term aspirin therapy 3

   • Periodic monitoring of hemoglobin should be considered in older persons on aspirin

3. Iron supplementation for patients with confirmed iron deficiency 5, 6

   • Oral iron (ferrous sulfate, fumarate, or gluconate) at 100-200 mg elemental iron daily
   • Continue for 3 months after normalization of hemoglobin to replenish iron stores
   • Consider IV iron for patients with intolerance to oral iron, poor absorption, or ongoing blood loss

Special Considerations

• Elderly patients are at higher risk for aspirin-induced iron deficiency anemia 3
• Patients with other risk factors for GI bleeding (history of peptic ulcer, concurrent anticoagulant use) require closer monitoring 1
• Vegetarians or those with low dietary iron intake may be more susceptible to aspirin-induced iron deficiency 2

Common Pitfalls to Avoid

• Failing to investigate the cause of iron deficiency anemia in patients on aspirin
• Attributing anemia solely to aspirin without completing appropriate GI evaluation
• Inadequate duration of iron therapy after correcting the underlying cause
• Not considering the possibility of dual pathology (multiple causes of iron deficiency)

Remember that aspirin's effect on iron deficiency anemia is an important consideration in long-term management, particularly in elderly patients and those with other risk factors for iron deficiency.