What type of anemia is indicated by microcytic and macrocytic components with low iron and high iron binding capacity?

Mixed Anemia: Combined Iron Deficiency and Macrocytic Component

This is a mixed anemia with concurrent iron deficiency and a macrocytic process, evidenced by the markedly elevated RDW (51.9) and high MCV (101.8) despite low-normal hemoglobin, with iron studies showing borderline iron deficiency in the setting of possible inflammation. 1

Laboratory Analysis

Your labs reveal a complex picture:

• MCV 101.8 fL = Macrocytic (>98 fL) 2
• MCH 34.8 pg = Normal to high (suggests adequate hemoglobin content per cell) 1
• RDW 51.9% = Markedly elevated (indicates two distinct red cell populations) 1, 3
• Iron 77 μg/dL with TIBC 223 μg/dL = Low-normal iron with low TIBC
• Transferrin saturation 35% = Normal (calculated as iron/TIBC × 100)

Type of Anemia

This represents a mixed picture of microcytic and macrocytic anemia, where the elevated MCV masks underlying iron deficiency. 1, 3 The extremely high RDW (51.9) is the critical clue—it indicates two populations of red cells: some microcytic (from iron deficiency) and some macrocytic (from B12/folate deficiency or other causes). 1, 3

Key Diagnostic Features:

• Elevated RDW with macrocytosis = Mixed nutrient deficiencies where microcytosis from iron deficiency coexists with macrocytosis, resulting in a falsely normal or elevated MCV 1
• Low TIBC (223) = Suggests inflammation or chronic disease, as TIBC is typically elevated (>400) in pure iron deficiency 2
• Normal transferrin saturation (35%) = Argues against pure iron deficiency, where TSAT is typically <16-20% 2

Most Likely Causes

Primary Consideration: Anemia of Chronic Disease with Concurrent B12/Folate Deficiency

In the presence of inflammation (suggested by low TIBC), ferritin levels between 30-100 μg/L indicate combined true iron deficiency and anemia of chronic disease. 2 Your iron studies show:

• Normal TSAT (35%) with low-normal iron
• Low TIBC (suggests inflammation suppressing iron metabolism)
• This pattern is inconsistent with pure iron deficiency 2

Secondary Considerations:

1. Inflammatory Bowel Disease (IBD): Patients with IBD commonly have mixed nutrient deficiencies with both iron deficiency and B12/folate deficiency, presenting with mixed micro- and macrocytosis 2, 1

2. Medication-induced macrocytosis: Thiopurines (azathioprine, 6-mercaptopurine) cause macrocytosis through myelosuppressive activity, not vitamin deficiency 1

3. Pernicious anemia with iron deficiency: Can occur concurrently, particularly in autoimmune conditions, where macrocytic anemia is revealed after iron supplementation 4

4. Hypothyroidism: Can cause macrocytosis (up to 55% of cases) with concurrent iron deficiency from menorrhagia or malabsorption 5

Diagnostic Algorithm

Step 1: Check B12 and folate levels immediately 1, 3

• If normal, consider methylmalonic acid (specific for B12 deficiency) and homocysteine (elevated in both B12 and folate deficiency) 1

Step 2: Assess ferritin level 2, 6

• Without inflammation: ferritin <30 μg/L confirms iron deficiency 2
• With inflammation: ferritin up to 100 μg/L may still indicate iron deficiency 2, 1

Step 3: Evaluate for chronic inflammation 2

• Check CRP, ESR
• Screen for IBD, autoimmune conditions, chronic infections
• In inflammation: ferritin >100 μg/L with TSAT <20% = anemia of chronic disease 2

Step 4: Obtain reticulocyte count 1, 6

• Low/normal reticulocytes = ineffective erythropoiesis (nutritional deficiency or bone marrow disorder) 1
• Elevated reticulocytes = hemolysis or hemorrhage 1

Step 5: Review peripheral blood smear 3

• Look for hypersegmented neutrophils (B12/folate deficiency)
• Assess for dimorphic population (microcytes and macrocytes)
• Evaluate for schistocytes (hemolysis) 1

Step 6: Medication review 1

• Identify drugs causing macrocytosis (thiopurines, methotrexate, antiretrovirals, alcohol)

Critical Pitfalls to Avoid

• Do not assume thalassemia trait based solely on family history without checking ferritin 6—your MCV is too high for thalassemia trait

• Do not overlook B12/folate deficiency because MCV appears "only mildly elevated" 3—the iron deficiency is masking more severe macrocytosis

• Do not interpret normal TSAT as excluding iron deficiency in inflammatory states 2—inflammation alters iron parameters

• Do not neglect follow-up even if initial workup is unrevealing 1—unexplained macrocytosis requires monitoring as bone marrow disorders may develop

• Do not treat iron deficiency alone without addressing the macrocytic component 4—correcting iron deficiency may unmask severe macrocytic anemia

Treatment Approach

Address both deficiencies simultaneously after confirming diagnoses: 4

1. If B12/folate deficiency confirmed: Start replacement therapy before or concurrent with iron supplementation to prevent unmasking severe anemia 4

2. If iron deficiency in inflammatory state: Oral iron may be ineffective; consider intravenous iron 2

3. Monitor CBC closely during treatment: Expect reticulocytosis within 1-2 weeks if nutritional deficiencies are the cause 6

4. Reassess in 8-12 weeks: RDW should normalize as both cell populations correct 1, 3