What is the best course of treatment for a patient with iron deficiency anemia (IDA) and copper deficiency?

Management of Iron Deficiency Anemia with Concurrent Copper Deficiency

The best treatment approach for a patient with both iron deficiency anemia (IDA) and copper deficiency is intravenous iron replacement therapy along with oral copper supplementation, while investigating and addressing the underlying causes of both deficiencies.

Diagnostic Considerations

• Iron deficiency anemia should be diagnosed using serum ferritin, with a cut-off of 45 ng/mL recommended by the American Gastroenterological Association (AGA) 1
• Copper deficiency diagnosis requires measuring serum copper, serum ceruloplasmin, and 24-hour urine copper levels 2
• Both deficiencies can present with similar hematologic manifestations, including microcytic anemia, though copper deficiency may also cause neutropenia and leukopenia 2

Treatment Algorithm

Step 1: Address Both Deficiencies Simultaneously

• Iron replacement therapy:

  • For patients with concurrent copper deficiency, intravenous (IV) iron is preferred as first-line therapy to rapidly correct anemia 1
  • Oral iron may be less effective due to potential absorption issues that could be present with dual deficiencies 1

• Copper replacement therapy:

  • Oral copper supplementation (copper gluconate, copper sulfate, or copper chloride) for mild to moderate deficiency 2
  • IV copper replacement may be necessary in severe cases or when oral supplementation fails 3, 2

Step 2: Investigate and Address Underlying Causes

• Gastrointestinal evaluation:

  • Bidirectional endoscopy (upper endoscopy and colonoscopy) is strongly recommended to identify potential sources of blood loss or malabsorption 1
  • Small bowel biopsy during upper endoscopy to evaluate for celiac disease, which can cause both iron and copper malabsorption 1

• Common causes to investigate:

  • Gastrointestinal blood loss (most common cause of IDA in men and postmenopausal women) 1
  • Malabsorption syndromes, particularly celiac disease 1
  • Bariatric surgery history (disrupts duodenal absorption of both nutrients) 1
  • Excessive zinc supplementation (can induce copper deficiency) 3, 2
  • Inflammatory bowel disease (can cause both deficiencies) 1

Special Considerations

Celiac Disease

• If celiac disease is confirmed, a strict gluten-free diet should be implemented alongside supplementation 1
• Even with strict gluten avoidance, up to 20% of patients will remain iron deficient and may require ongoing supplementation 1

Inflammatory Bowel Disease

• For patients with IBD, IV iron has greater efficacy than oral iron in achieving hemoglobin increases (odds ratio, 1.57; 95% CI, 1.13–2.18) 1
• Treatment should include optimizing management of underlying inflammation alongside iron and copper supplementation 1

Bariatric Surgery

• Post-bariatric surgery patients often require IV iron due to anatomic considerations affecting absorption 1
• A single dose of IV iron has been shown to be more effective than oral ferrous fumarate or gluconate in these patients 1

Monitoring and Follow-up

• After initial treatment, monitor blood counts periodically (every 3-6 months initially) to detect recurrent anemia 1
• Hematological manifestations of copper deficiency are typically fully reversible with supplementation over 4-12 weeks 2
• Long-term iron replacement therapy may be appropriate when the cause of recurrent IDA is unknown or irreversible 1

Important Caveats

• Excessive zinc supplementation can block intestinal absorption of copper, so zinc intake should be evaluated and potentially adjusted 3
• Neurological manifestations of copper deficiency may only be partially reversible, emphasizing the importance of prompt diagnosis and treatment 2
• The combination of iron and copper supplementation may enhance effectiveness, as copper is required for proper iron metabolism and hemoglobin synthesis 4, 2