What is the interpretation and recommended course of action for a patient with a slightly elevated MCV (Mean Corpuscular Volume) and low MCHC (Mean Corpuscular Hemoglobin Concentration)?

Interpretation and Management of Elevated MCV with Low MCHC

This patient requires immediate evaluation for vitamin B12 and folate deficiency given the macrocytosis (MCV 100.8 fL), while the low MCHC (31.6 g/dL) indicates concurrent iron deficiency, creating a mixed picture that demands assessment of both nutritional deficiencies. 1, 2

Initial Diagnostic Workup Required

The combination of elevated MCV with low MCHC is diagnostically significant and requires specific testing:

• Measure serum vitamin B12 and folate levels immediately, as MCV exceeding 100 fL warrants nutritional assessment 1
• Obtain serum ferritin, transferrin saturation, and C-reactive protein to confirm iron deficiency and rule out inflammation 1, 2
• Review peripheral blood smear to assess red cell morphology and identify megaloblastic changes or hypochromic cells 1
• Check reticulocyte count to differentiate between decreased production versus increased destruction 1

Clinical Significance of This Pattern

This specific combination reveals important pathophysiology:

• Low MCHC specifically indicates hypochromic red blood cells with decreased hemoglobin content, reflecting iron-restricted erythropoiesis 2
• The elevated MCV suggests megaloblastic process from B12/folate deficiency, which typically produces MCV >100 fL 1
• When both abnormalities coexist, the MCV may be "normalized" into upper-normal range by the opposing effects of macrocytosis (from B12/folate deficiency) and microcytosis (from iron deficiency), making the MCV of 100.8 fL particularly revealing 3
• The normal hemoglobin (12.4 g/dL) does not exclude significant nutritional deficiencies, as combined deficiencies can mask the severity of either condition alone 4

Medication and Medical History Review

Critical questions to address immediately:

• Review all current medications for agents causing macrocytosis (hydroxyurea, azathioprine, 6-mercaptopurine, methotrexate) 1
• Assess for gastrointestinal disease, particularly inflammatory bowel disease with small bowel involvement or resection, which predisposes to both B12 and iron malabsorption 1
• Evaluate for chronic blood loss as the source of iron deficiency 2
• Screen for malabsorption syndromes including celiac disease and atrophic gastritis 1

Management Algorithm

Step 1: Confirm nutritional deficiencies

• If B12 <200 pg/mL or folate <2 ng/mL with ferritin <30 ng/L, diagnose combined deficiency 1, 2

Step 2: Initiate replacement therapy

• Begin B12 supplementation (1000 mcg IM weekly if deficient, or oral 1000-2000 mcg daily if absorption intact) 1
• Start oral iron supplementation (ferrous sulfate 325 mg daily to three times daily on empty stomach) 2
• Add folate 1 mg daily if folate deficiency confirmed 1

Step 3: Monitor response

• Recheck CBC in 4-6 weeks to assess reticulocyte response and improvement in indices 1
• Expect MCV to normalize over 2-3 months as B12/folate stores replete 1
• MCHC should improve within 6-8 weeks as iron stores rebuild 2

Critical Pitfalls to Avoid

• Do not assume normal hemoglobin excludes significant deficiency: Combined nutritional deficiencies can produce near-normal hemoglobin with abnormal indices 4, 3
• Do not rely on MCV alone to exclude iron deficiency: When macrocytosis and microcytosis coexist, MCV may appear falsely normal or only mildly elevated 3
• Do not delay B12 replacement while awaiting test results if clinical suspicion is high, as neurologic complications can become irreversible 1
• Do not overlook underlying malignancy or gastrointestinal pathology as the cause of combined deficiencies, particularly in patients over 50 years 1, 2

Special Considerations

If inflammatory bowel disease is present or suspected:

• Annual monitoring of B12 and folate is mandatory, especially with extensive small bowel disease or prior resection 1
• Macrocytosis may reflect both nutritional deficiency and thiopurine therapy if patient is on immunosuppressants 1

The RDW of 14.5% (upper normal) supports mixed deficiency, as this reflects increased variation in red cell size from two opposing processes 1, 3