What is the appropriate work‑up and initial management for a patient with mild anemia (hemoglobin (Hb) 10.5 g/dL, hematocrit (Hct) 32.4 %, mean corpuscular hemoglobin (MCH) 99 pg, red‑cell distribution width (RDW) 13 %)?

Macrocytic Anemia Work-Up and Management

This patient has macrocytic anemia (MCH 99 pg indicates elevated MCV) with mild severity (Hb 10.5 g/dL), requiring immediate investigation for vitamin B12 and folate deficiency, thyroid dysfunction, and potential gastrointestinal pathology, with the normal RDW (13%) suggesting a homogeneous macrocytic process rather than combined deficiency. 1, 2

Initial Laboratory Work-Up

Order the following tests immediately:

• Vitamin B12 and folate levels – These are first-line tests for macrocytic anemia to identify nutritional deficiencies 2, 3
• Thyroid function tests (TSH, free T4) – Hypothyroidism commonly causes macrocytic anemia 2, 3
• Reticulocyte count – Essential to assess bone marrow response and distinguish between hypoproliferative versus hemolytic causes 2, 4
• Serum ferritin and iron studies – To exclude concurrent iron deficiency, which can mask macrocytosis and is indicated by the normal RDW 5, 2
• Peripheral blood smear – Provides additional morphologic information about red cell abnormalities 3

Clinical Significance of Normal RDW

The normal RDW (13%) in this macrocytic anemia is clinically important because it suggests a homogeneous population of macrocytes rather than a mixed picture. 5, 4

• A raised RDW would suggest combined deficiency (e.g., concurrent iron and folate deficiency), but this patient's normal RDW makes a single etiology more likely 5
• This pattern is consistent with vitamin B12 deficiency, folate deficiency, or hypothyroidism as isolated causes 4, 3

Severity Classification and Urgency

This patient has mild anemia by ESMO criteria (Hb 10.0-11.9 g/dL), but the degree of anemia does not diminish the urgency of investigation. 1

• Any level of anemia warrants full investigation, as even mild anemia may indicate significant underlying pathology including gastrointestinal malignancy 1
• The British Society of Gastroenterology emphasizes that mild anemia is no less indicative of important disease than severe anemia 5

Gastrointestinal Evaluation

If vitamin B12 deficiency is confirmed, investigate for malabsorption:

• Upper GI endoscopy with small bowel biopsies should be performed to exclude celiac disease, which presents in 2-3% of patients with nutritional anemia 5
• Consider evaluation for pernicious anemia (anti-intrinsic factor antibodies, anti-parietal cell antibodies) 5
• Full GI investigation including colonoscopy may be warranted in adult men and postmenopausal women to exclude occult blood loss and malignancy, even with macrocytic morphology 5

Treatment Algorithm Based on Results

If vitamin B12 deficiency confirmed:

• Initiate replacement therapy with investigation of underlying cause (malabsorption, dietary deficiency, pernicious anemia) 2
• Repeat CBC after 2-4 weeks to assess response 2

If folate deficiency confirmed:

• Initiate folate replacement with investigation of underlying cause 2
• Always check B12 before treating isolated folate deficiency to avoid neurologic complications 3

If hypothyroidism confirmed:

• Treat underlying thyroid disorder; anemia typically resolves with thyroid hormone replacement 2, 3

If reticulocyte count is elevated:

• Evaluate for hemolysis or blood loss despite macrocytic morphology 2, 3

If reticulocyte count is low/normal:

• Consider bone marrow disorders or aplasia; hematology referral indicated 2, 3

Common Pitfalls to Avoid

• Do not assume dietary insufficiency alone explains the anemia without full GI investigation, as borderline deficient diets are common but should not be presumed as the sole cause 5
• Do not transfuse this stable patient with mild anemia in the absence of cardiac disease or symptoms; transfusion is not indicated above Hb 7-8 g/dL 1, 2
• Do not miss combined deficiencies – although RDW is normal here, always check both iron studies and vitamin levels as concurrent deficiencies can mask each other's morphologic features 5, 4

Follow-Up Strategy

• Repeat CBC after 2-4 weeks of appropriate therapy to assess hemoglobin response 2
• If no improvement after appropriate therapy, hematology referral is warranted for consideration of bone marrow evaluation or other causes 2
• Monitor for symptom development, particularly fatigue and dyspnea, which may worsen quality of life even with mild anemia 1