What is the best course of treatment for a patient with anemia, folic acid deficiency, and potential iron deficiency, given lab results of low hemoglobin, elevated UIBC, elevated TIBC, normal ferritin, low folic acid, and low normal MCV?

Treatment Approach for Anemia with Severe Folate Deficiency

This patient requires immediate folic acid supplementation at 5 mg daily for 2-3 months, with concurrent vitamin B12 supplementation to prevent unmasking B12 deficiency, and further workup to clarify the iron status given the atypical pattern of low TIBC. 1, 2

Immediate Treatment Priority: Folate Deficiency

The folic acid level of <2 ng/mL represents severe deficiency requiring urgent treatment:

• Start folic acid 5 mg orally daily for 3 months 3, 1
• The higher dose (5 mg vs 1 mg) is appropriate given the severity of deficiency and near-normal MCV (82.6), which suggests early deficiency before full macrocytosis develops 1, 2
• Alternative dosing: 5 mg daily for 2 weeks, then 5 mg weekly for 6 weeks is also acceptable 2

Critical: Concurrent B12 Supplementation Required

Never supplement folate alone without addressing B12 status—this can precipitate or worsen irreversible neurologic damage from undiagnosed B12 deficiency. 1

• Add oral cyanocobalamin 2,000 mcg daily or use a multivitamin containing at least 2.6 mcg/day of B12 1
• Alternatively, intramuscular cyanocobalamin 1,000 mcg on days 1-10, then monthly 1
• This is mandatory even without confirmed B12 deficiency, as treating folate deficiency alone can mask megaloblastic anemia while allowing neurologic damage to progress 1

Essential Diagnostic Workup

The laboratory pattern is atypical and requires clarification before definitive iron treatment:

Iron Status Assessment:

• Serum ferritin is the single most important test—ferritin 96 ng/mL with inflammation may still indicate iron deficiency, but without inflammation suggests adequate stores 3, 4
• C-reactive protein (CRP) to identify inflammation, which lowers TIBC and can falsely elevate ferritin 2
• The low TIBC (49 mg/dL) is concerning—this typically indicates chronic inflammation, liver disease, or protein malnutrition, NOT simple iron deficiency where TIBC would be elevated 2
• Transferrin saturation (TSAT) should be calculated or measured—TSAT <20% suggests functional iron deficiency 4, 2

Additional Required Tests:

• Vitamin B12 level—must be checked before aggressive folate therapy 1, 2
• Reticulocyte count—helps differentiate megaloblastic from other anemias and assesses bone marrow response 3, 4
• Complete metabolic panel—to evaluate for liver disease or protein malnutrition given the low TIBC 2

Iron Management Decision Algorithm

If ferritin <30 μg/L without inflammation:

• Confirms absolute iron deficiency 3, 4
• Start oral iron supplementation: 100 mg elemental iron daily (or every other day if not tolerated) 3

If ferritin 30-100 μg/L with inflammation (elevated CRP):

• Likely combined iron deficiency and anemia of chronic disease 3
• Consider parenteral iron if active inflammation present, as oral iron absorption is impaired 3

If ferritin >100 μg/L:

• Iron deficiency unlikely unless TSAT <16% (functional iron deficiency) 3
• Focus on treating underlying inflammation and folate deficiency 3

Given this patient's ferritin of 96 μg/L with low TIBC:

• The low TIBC suggests this is NOT typical iron deficiency anemia 2
• Investigate for chronic disease, inflammation, or malabsorption as the primary driver 2
• Hold iron supplementation until CRP and ferritin are interpreted together 2

Monitoring and Follow-up

At 4 weeks:

• Recheck complete blood count, reticulocyte count, folate, and B12 levels 3, 1
• Hemoglobin should increase ≥2 g/dL if treatment is adequate 3
• MCV should trend toward normal 2
• Reticulocyte count may initially increase (appropriate marrow response) 1

At 3 months:

• Repeat iron studies if initial workup suggested deficiency 2
• Continue monitoring hemoglobin every 3 months if deficiencies persist 2

Critical Pitfalls to Avoid

• Do not assume simple iron deficiency with low TIBC—this pattern indicates inflammation or chronic disease, not typical iron deficiency 2
• Do not give folate without B12 coverage—risk of precipitating subacute combined degeneration of the spinal cord 1
• Do not misinterpret ferritin 96 μg/L as "normal" if inflammation is present—ferritin up to 100 μg/L may still reflect iron deficiency in inflammatory states 3
• Do not overlook gastrointestinal pathology—combined folate and potential iron deficiency suggests malabsorption (celiac disease, inflammatory bowel disease) or chronic blood loss requiring investigation 2
• Do not use albumin to assess nutritional status—it is an acute phase reactant and unreliable for this purpose 3