What is the treatment for low ferritin (iron) and B12 (cobalamin) levels?

Treatment of Low Ferritin and Vitamin B12

For combined low ferritin and B12 deficiency, you must treat the B12 deficiency first and immediately, before initiating iron supplementation, to prevent masking B12 deficiency and avoid irreversible neurological damage from subacute combined degeneration of the spinal cord. 1

Critical First Step: Assess for Neurological Involvement

Before initiating any treatment, evaluate the patient for neurological symptoms including:

• Unexplained sensory symptoms
• Motor deficits
• Gait disturbances 1

This assessment determines the urgency and intensity of B12 replacement therapy.

Vitamin B12 Treatment Protocol

With Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs 1
• Then continue hydroxocobalamin 1 mg IM every 2 months for life 1
• Seek urgent specialist consultation from both neurology and hematology 1

Without Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1
• Follow with maintenance therapy of 1 mg IM every 2-3 months for life 1

The FDA-approved cyanocobalamin formulation is indicated for B12 deficiency due to malabsorption, pernicious anemia, gastrointestinal pathology, and other causes of deficiency. 2 Patients with pernicious anemia require lifelong monthly injections, and failure to maintain therapy will result in return of anemia and irreversible nerve damage. 2

Iron Deficiency Treatment (Only After B12 Treatment Initiated)

Diagnostic Confirmation

• Ferritin <15 μg/L confirms iron deficiency anemia 1
• In patients with chronic inflammation, ferritin <50 μg/L may still indicate iron deficiency; consider C-reactive protein or total iron binding capacity 1
• Always exclude sources of blood loss before treating 1

Oral Iron Supplementation (First-Line)

• Prescribe 100-200 mg elemental iron daily in divided doses 3
• Recent evidence supports alternate-day dosing for better absorption and fewer side effects 3
• Co-administer with vitamin C to enhance absorption 3
• Avoid tea and coffee around dosing times as they impair absorption 3
• Continue for minimum 4 months or until iron stores replete 3

Common side effects include nausea, abdominal pain, constipation, and diarrhea. 3

Intravenous Iron (When Oral Fails or Contraindicated)

Indications for IV iron include: 1, 3

• Failure to reach therapeutic goals with oral supplementation
• Malabsorption conditions (inflammatory bowel disease with active inflammation, celiac disease)
• Need for rapid repletion
• Hemoglobin <100 g/L in IBD patients
• Previous intolerance to oral iron

For significant deficiency requiring IV treatment, administer a single dose of 1000 mg iron over 15 minutes using modern carbohydrate-based products (such as ferric carboxymaltose). 3, 4 This rapidly corrects hemoglobin levels and replenishes iron stores. 4

Critical Pitfalls to Avoid

Never Give Folic Acid Before Treating B12 Deficiency

Folic acid supplementation may correct the anemia but allows progression of irreversible neurological damage (subacute combined degeneration of the spinal cord). 1, 2 This is the most dangerous error in managing combined deficiencies.

Monitor for Masked Deficiencies

• B12 deficiency can be masked by lack of hematological abnormalities or concomitant iron deficiency causing microcytosis 5
• Inflammation can falsely elevate ferritin levels, masking true iron deficiency 1, 3
• Always check serum B12 levels even when hematological parameters appear normal 5

Special Consideration: Pernicious Anemia with Iron Deficiency

In pernicious anemia patients, iron deficiency is highly prevalent (75% in one study) due to achlorhydria impairing iron absorption. 6 These patients may require intravenous iron supplementation as oral iron is less effective due to elevated gastric pH. 6 After 3 months, only 27% normalized iron status with oral supplementation versus 88% with IV iron. 6

Monitoring During Treatment

B12 Therapy Monitoring

• Monitor serum potassium closely in first 48 hours of treatment 2
• Obtain baseline hematocrit, reticulocyte count, B12, folate, and iron levels 2
• Repeat hematocrit and reticulocytes daily from days 5-7, then frequently until normalized 2
• If reticulocytes don't increase or remain elevated, reevaluate diagnosis and check for complicating conditions 2

Iron Therapy Monitoring

• Reassess ferritin and hemoglobin at 3 months 3
• Continue treatment until iron stores fully replete 3
• In inflammatory conditions, use transferrin saturation or soluble transferrin receptor for accurate assessment 1