Is it normal to have concurrent iron deficiency and vitamin B12 deficiency?

Concurrent Iron and Vitamin B12 Deficiency: Causes, Diagnosis, and Management

It is not normal to have concurrent iron deficiency and vitamin B12 deficiency, and this combination requires thorough investigation as it may indicate serious underlying pathology that could significantly impact morbidity and mortality if left untreated. 1

Prevalence and Significance

• Concurrent deficiencies of iron and vitamin B12 can occur in specific clinical scenarios and warrant comprehensive evaluation 1
• The combination is particularly common in certain conditions such as:
  • Pernicious anemia (75% of patients with pernicious anemia also develop iron deficiency) 2
  • Malabsorptive disorders affecting both nutrients 1
  • Post-bariatric surgery states 1
  • Inflammatory bowel disease 1

Pathophysiology of Concurrent Deficiencies

• Iron deficiency typically manifests as microcytic, hypochromic anemia 1
• Vitamin B12 deficiency typically causes macrocytic anemia 1
• When both occur simultaneously:
  • The MCV (mean corpuscular volume) may appear normal due to opposing effects 1
  • Red cell distribution width (RDW) is typically elevated, indicating variable red cell sizes 1
  • Diagnosis may be delayed due to "masking" of typical hematologic patterns 1

Diagnostic Approach

• Complete blood count with red cell indices (MCV, MCH, RDW) should be assessed 1
• Iron studies should include:
  • Serum ferritin (levels <15 μg/L confirm iron deficiency; <45 μg/L warrant investigation) 1
  • Transferrin saturation 1
  • Consider inflammatory markers (CRP) as inflammation can elevate ferritin 1
• Vitamin B12 assessment:
  • Serum B12 levels (levels <350 pg/mL may be significant) 3
  • Consider methylmalonic acid and homocysteine levels if B12 deficiency is suspected despite normal B12 levels 4
• Response to therapy can be diagnostic - a good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) suggests iron deficiency 1

Common Underlying Causes

• Gastrointestinal disorders:
  • Atrophic gastritis (affects both iron and B12 absorption) 2
  • Inflammatory bowel disease 1
  • Celiac disease 1
• Surgical causes:
  • Bariatric surgery (particularly procedures bypassing the duodenum and proximal jejunum) 1
  • Small bowel resection 5
• Nutritional causes:
  • Strict vegetarian/vegan diets without supplementation 5
  • General malnutrition 5
• Other causes:
  • Pernicious anemia (autoimmune gastritis leading to both B12 and iron malabsorption) 2
  • Medications affecting gastric pH or nutrient absorption 1

Management Principles

• Critical safety consideration: Always treat vitamin B12 deficiency before initiating folic acid treatment to avoid precipitating subacute combined degeneration of the spinal cord 1

• For vitamin B12 deficiency:

  • With neurological involvement: Hydroxocobalamin 1 mg IM on alternate days until no further improvement, then 1 mg IM every 2 months 1
  • Without neurological involvement: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks, then maintenance with 1 mg IM every 2-3 months lifelong 1
  • Urgent neurologist and hematologist consultation for patients with neurological symptoms 1

• For iron deficiency:

  • Oral iron supplementation may be sufficient for mild anemia (Hb >10 g/dL) 1
  • Consider intravenous iron in severe deficiency or when oral therapy is ineffective 1
  • In patients with pernicious anemia, intravenous iron appears more effective than oral supplementation 2

• Investigate underlying causes:

  • Sources of blood loss should be identified and addressed 1
  • Malabsorptive disorders should be diagnosed and treated 1
  • Consider endoscopic evaluation in appropriate clinical scenarios 1

Follow-up and Monitoring

• Monitor response to therapy with repeat complete blood counts 1
• Long-term monitoring is warranted as recurrence is common 1
• Patients with conditions predisposing to deficiencies (e.g., bariatric surgery, IBD) should have regular monitoring of iron, B12, and folate levels 1

Special Considerations

• In patients with inflammatory conditions, standard cutoffs for ferritin may miss iron deficiency (consider using higher threshold of 50 μg/L) 1
• Patients with pernicious anemia require lifelong B12 replacement and regular iron status assessment 2
• Consider potential interactions between treatments (e.g., calcium supplements or antacids may reduce iron absorption) 1