What is the diagnosis for a patient with an elevated MCV (Mean Corpuscular Volume) of 102 and MCH (Mean Corpuscular Hemoglobin) of 33.5?

Diagnosis: Mild Macrocytosis - Requires Systematic Evaluation for Underlying Cause

The most likely diagnosis is early vitamin B12 or folate deficiency, medication effect, or alcohol use, but this mild macrocytosis (MCV 102) with normal MCH requires a structured workup to identify the specific etiology before making a definitive diagnosis. 1

Initial Diagnostic Approach

The combination of MCV 102 and MCH 33.5 (normal) indicates macrocytosis without hypochromia, which narrows the differential diagnosis significantly. 1

Essential First-Line Tests

You must obtain the following tests immediately to establish the diagnosis: 2, 1

• Reticulocyte count - This is the single most critical test to differentiate between ineffective erythropoiesis (low/normal reticulocytes suggesting vitamin deficiency or bone marrow disorder) versus increased red cell production (elevated reticulocytes suggesting hemolysis or recent hemorrhage) 2, 1

• Serum vitamin B12 and folate levels - These are mandatory in all patients with macrocytosis, as deficiency is the most common cause even with mild MCV elevation 2, 1, 3

• Peripheral blood smear - Look specifically for oval macrocytes (suggests megaloblastic anemia) versus round macrocytes (suggests liver disease or alcohol use) 4

• Liver function tests - Liver disease commonly causes mild, uniform macrocytosis with MCV rarely exceeding 110 fL 4

Differential Diagnosis Based on MCV 102

Most Likely Causes at This MCV Level

Vitamin B12 or folate deficiency remains possible even at MCV 102, as 53% of patients with low B12/folate levels present with macrocytosis and elevated MCH before anemia develops. 5 The classic teaching that MCV must exceed 110-120 fL for megaloblastic anemia is incorrect - deficiency can present with mild macrocytosis. 5, 6

Medication-induced macrocytosis should be strongly considered, particularly if the patient takes: 1, 3

• Azathioprine or 6-mercaptopurine
• Hydroxyurea
• Methotrexate
• Antiretroviral medications

Alcohol use causes mild, uniform macrocytosis even without liver disease 4

Less Likely but Important Considerations

Reticulocytosis from hemolysis or recent hemorrhage - ruled out by obtaining reticulocyte count 1

Early myelodysplastic syndrome (MDS) - Consider this especially in elderly patients, though MDS typically presents with other cytopenias 2

Critical Pitfall to Avoid

The normal MCH (33.5) does NOT exclude concurrent iron deficiency. MCH is actually more sensitive than MCV for detecting iron deficiency, and a normal MCH in the setting of macrocytosis suggests pure macrocytosis rather than a mixed picture. 1 However, you should still check iron studies (ferritin, transferrin saturation) because:

• Mixed deficiencies can mask each other, resulting in falsely normal MCV 1
• Red cell distribution width (RDW) will be elevated if mixed deficiency exists 2, 1

If Initial Workup Shows Normal B12/Folate

Do not stop your evaluation if B12 and folate are normal. 1 You must then:

1. Check methylmalonic acid (MMA) and homocysteine - These detect tissue-level B12/folate deficiency despite normal serum levels 1, 7

   • MMA is specific for B12 deficiency with better sensitivity than serum B12 1
   • Homocysteine is elevated in both B12 and folate deficiency 1, 7

2. Review medications thoroughly - Thiopurines cause macrocytosis through myelosuppressive activity, not vitamin deficiency 1

3. Consider hematology referral if the cause remains unclear after complete workup, especially if MCV is progressively worsening 1

Monitoring Strategy

Even if no cause is identified, this patient requires ongoing monitoring because a significant percentage of patients with unexplained macrocytosis develop primary bone marrow disorders or worsening cytopenias over time. 1 Repeat CBC every 3-6 months and reassess B12/folate levels periodically, as deficiencies may develop later. 1