What is the interpretation and next steps for a patient with mild macrocytic anemia and a slightly elevated white blood cell count?

Interpretation and Next Steps for Mild Macrocytic Anemia with Leukocytosis

This patient has mild macrocytic anemia (Hgb 12.2 g/dL, MCV 96.2 fL) with mild leukocytosis (WBC 12.4), and the immediate next step is to obtain serum vitamin B12, folate, reticulocyte count, and TSH to identify the underlying cause before initiating any treatment. 1, 2

Laboratory Interpretation

Anemia Assessment:

• The hemoglobin of 12.2 g/dL represents mild anemia in an adult male (normal >13.0 g/dL) 3
• The MCV of 96.2 fL indicates borderline macrocytosis, approaching the threshold of 100 fL that defines true macrocytosis 1, 4
• This pattern suggests early megaloblastic changes or a mixed picture 3

White Blood Cell Pattern:

• The WBC count of 12.4 with absolute neutrophilia (6.65) and lymphocytosis (4.02) represents mild leukocytosis 1
• The presence of immature granulocytes (0.14) is notable and may indicate an inflammatory process or bone marrow stress 3
• This pattern is nonspecific but warrants investigation for underlying infection, inflammation, or hematologic disorder 1

Immediate Diagnostic Workup

Essential First-Line Tests:

• Serum vitamin B12 level (deficiency defined as <150 pmol/L or <203 ng/L; if borderline, obtain methylmalonic acid >271 nmol/L to confirm deficiency) 1, 2
• Serum folate and RBC folate levels (deficiency: serum folate <10 nmol/L or RBC folate <305 nmol/L) 1, 2
• Reticulocyte count to differentiate megaloblastic (low/normal count) from non-megaloblastic causes (elevated count suggests hemolysis or hemorrhage) 3, 1, 2
• TSH and free T4 to exclude hypothyroidism as a cause of macrocytosis 1, 2

Additional Recommended Tests:

• Peripheral blood smear to evaluate for neutrophil hypersegmentation (highly sensitive for megaloblastic anemia) and assess red cell morphology 5, 4
• Red cell distribution width (RDW) to detect coexisting iron deficiency, which can mask macrocytosis 3, 1
• CRP and creatinine to assess for inflammatory conditions or renal failure 1, 2
• Liver function tests given that liver disease is a common cause of nonmegaloblastic macrocytic anemia 5, 6

Differential Diagnosis Algorithm

If Reticulocyte Count is Low/Normal:

• Vitamin B12 deficiency (most common megaloblastic cause) 1, 7
• Folate deficiency 1, 7
• Hypothyroidism 1, 5
• Medications (methotrexate, azathioprine, hydroxyurea) 1, 2
• Myelodysplastic syndrome (less likely given age and presentation) 1, 6
• Chronic liver disease 5, 6
• Alcohol use disorder 5, 6

If Reticulocyte Count is Elevated:

• Hemolysis (check haptoglobin, LDH, bilirubin) 3, 1
• Recent hemorrhage 1, 5

Critical Treatment Considerations

Never initiate folate supplementation before ruling out and treating vitamin B12 deficiency, as this can precipitate subacute combined degeneration of the spinal cord—an irreversible neurological complication. 1, 2

Treatment Algorithm Based on Results:

• If B12 deficiency confirmed without neurological symptoms: Cyanocobalamin 1 mg IM three times weekly for 2 weeks, then 1 mg every 2-3 months for life 1, 2
• If B12 deficiency with neurological symptoms: Hydroxocobalamin 1 mg IM on alternate days until no further improvement, then 1 mg every 2 months 1, 2
• If folate deficiency (after excluding B12 deficiency): Oral folic acid 5 mg daily for minimum 4 months 1, 2
• If hypothyroidism: Thyroid hormone replacement 1

Monitoring Response

• Repeat complete blood count to monitor treatment response 1, 2
• An acceptable response is defined as hemoglobin increase of at least 2 g/dL within 4 weeks of treatment 1

Important Caveats

• The mild leukocytosis with immature granulocytes warrants clinical correlation—assess for fever, infection, or inflammatory conditions that may be contributing to both findings 3, 1
• In patients with inflammatory conditions, ferritin may be falsely elevated despite true iron deficiency; check transferrin saturation and RDW if inflammation is present 3, 1, 2
• A wide RDW can unmask coexisting iron deficiency when microcytosis and macrocytosis neutralize each other, resulting in a deceptively normal MCV 3, 1
• Review current medications for causative agents (azathioprine, methotrexate, hydroxyurea) 1, 2