What is the treatment plan for a 69-year-old patient with macrocytic anemia (elevated Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH)), hypercholesterolemia (elevated Total Cholesterol), and low Blood Urea Nitrogen (BUN) levels?

Management of Macrocytic Anemia in a 69-Year-Old Patient

Immediate Diagnostic Workup Required

Your patient has macrocytic anemia (MCV 104 fL, MCH 35.2 pg, hemoglobin 14.1 g/dL) that requires immediate evaluation for vitamin B12 and folate deficiency before any treatment is initiated. 1, 2

Essential First-Line Laboratory Tests

• Serum vitamin B12 level (deficiency defined as <150 pmol/L or <203 ng/L) 2, 3
• Serum folate and RBC folate levels (deficiency: serum folate <10 nmol/L or RBC folate <305 nmol/L) 2, 3
• Reticulocyte count to differentiate between deficiency states versus hemolysis or bleeding response 1, 3
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism as a cause 2
• Methylmalonic acid if B12 level is borderline (>271 nmol/L confirms deficiency) 2

Additional Tests to Identify Coexisting Deficiencies

• Serum ferritin and transferrin saturation to identify concurrent iron deficiency, which can mask macrocytosis 1, 2, 3
• Red cell distribution width (RDW) - an elevated RDW suggests coexisting iron deficiency even when MCV is elevated 2
• Haptoglobin and LDH if reticulocytes are elevated to assess for hemolysis 1, 3

Your patient's RDW is normal (12.1%), making coexisting iron deficiency less likely, but ferritin should still be checked. 2

Treatment Algorithm Based on Etiology

If Vitamin B12 Deficiency is Confirmed

Critical: Always exclude and treat vitamin B12 deficiency BEFORE initiating folate supplementation, as folate can mask B12 depletion and allow irreversible neurological damage to progress. 1, 2, 3

For B12 Deficiency WITHOUT Neurological Symptoms:

• Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2
• Followed by maintenance: 1 mg intramuscularly every 2-3 months for life 1, 2, 4

For B12 Deficiency WITH Neurological Symptoms:

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 1, 2
• Then 1 mg intramuscularly every 2 months for life 1, 2

If Folate Deficiency is Confirmed (After Excluding B12 Deficiency)

• Oral folic acid 5 mg daily for a minimum of 4 months 1, 2, 3

If Myelodysplastic Syndrome (MDS) is Diagnosed

• Lenalidomide for patients with del(5q) cytogenetic abnormality 1, 3
• Erythropoietin therapy for patients with normal cytogenetics, <15% marrow ringed sideroblasts, and serum erythropoietin ≤500 mU/mL 3
• Add G-CSF if no response to erythropoietin alone 1, 3
• Verify iron repletion before starting erythropoietin therapy 3

Monitoring Response to Treatment

• Serial monitoring of MCV, MCH, hemoglobin, and reticulocyte count every 2-4 weeks initially 1, 3
• An increase in hemoglobin of at least 2 g/dL within 4 weeks indicates acceptable response 2
• Reticulocyte response should be observed within 1 week of appropriate vitamin replacement 4

Mandatory Hematology Referral Criteria

Refer immediately to hematology if: 1, 3

• Cause remains unclear after complete workup
• Suspicion for myelodysplastic syndrome (especially with leucopenia or thrombocytopenia)
• Hemolytic anemia is confirmed
• Pancytopenia is present
• No response to appropriate vitamin replacement after 2-3 weeks

Common Causes to Consider in This Patient

The most common causes of macrocytosis in hospitalized patients are medications, alcohol use, liver disease, and reticulocytosis, with megaloblastic anemia (B12/folate deficiency) accounting for less than 10% of cases. 5 However, MCV values >100 fL warrant investigation for vitamin deficiency regardless of prevalence. 6, 5

Medication Review

Your patient should be evaluated for medications causing macrocytosis, including: 1, 2

• Anticonvulsants
• Methotrexate
• Azathioprine or 6-mercaptopurine
• Hydroxyurea
• Sulfasalazine

Alcohol Use Assessment

Chronic alcohol use causes macrocytosis independent of nutritional deficiencies and may impair B12 absorption. 2, 6, 7

Critical Pitfalls to Avoid

• Never treat folate deficiency before excluding B12 deficiency - this can precipitate subacute combined degeneration of the spinal cord 1, 2, 3
• Do not overlook coexisting iron deficiency - mixed deficiencies require treatment of both simultaneously 3
• Do not assume normal hemoglobin excludes significant pathology - macrocytosis is not related to hemoglobin concentration and may be the only indicator of vitamin deficiency, preleukemia, or alcoholism 6

Management of Other Laboratory Abnormalities

Hypercholesterolemia (Total Cholesterol 210 mg/dL)

Your patient's LDL is 98 mg/dL (borderline), HDL is excellent at 98 mg/dL, and triglycerides are normal. The LDL/HDL ratio of 1.0 is favorable. This does not require immediate pharmacologic intervention but warrants lifestyle modification counseling.

Low BUN (6 mg/dL)

This isolated finding with normal creatinine (eGFR 94 mL/min/1.73) likely reflects adequate hydration or low protein intake and does not require specific treatment in the absence of other symptoms.