What is the initial step in anemia workup and subsequent treatment?

Anemia Workup: Initial Diagnostic Approach

Begin the anemia workup with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies panel (serum ferritin, transferrin saturation, total iron-binding capacity), and C-reactive protein—all ordered simultaneously at initial presentation. 1, 2, 3

Diagnostic Thresholds

Anemia is defined by hemoglobin levels below these cutoffs: 1, 2, 3

• Men: < 13 g/dL
• Non-pregnant women: < 12 g/dL
• Pregnant women: < 11 g/dL

Essential First-Line Laboratory Tests

Order these tests together at the initial workup: 1, 2, 3

• Complete blood count with red cell indices (hemoglobin, hematocrit, MCV, MCH, MCHC, RDW)
• Absolute reticulocyte count
• Serum ferritin
• Transferrin saturation (TSAT)
• Total iron-binding capacity (TIBC)
• C-reactive protein (to assess for inflammation)

Algorithmic Classification by MCV

Microcytic Anemia (MCV < 80 fL)

Most commonly indicates iron deficiency anemia, but also consider thalassemia, anemia of chronic disease, or sideroblastic anemia. 1, 2, 3

Confirm iron deficiency with: 1, 2

• Serum ferritin < 30 μg/L (in absence of inflammation)
• Transferrin saturation < 15-16%

Critical caveat: Ferritin is an acute phase reactant and can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease—interpret in clinical context. 2, 3

If iron studies are normal, obtain hemoglobin electrophoresis to evaluate for thalassemia trait, particularly in patients of Mediterranean, African, or Southeast Asian descent. 2

Normocytic Anemia (MCV 80-100 fL)

Consider these etiologies: 2, 3

• Acute blood loss
• Hemolysis
• Anemia of chronic disease/inflammation
• Early iron deficiency (before MCV drops)
• Chronic kidney disease

For suspected hemolysis, measure haptoglobin, LDH, and indirect bilirubin. 2

For chronic kidney disease patients, initiate workup when hemoglobin drops below 12 g/dL in men and postmenopausal women, or below 11 g/dL in premenopausal women. 3

Macrocytic Anemia (MCV > 100 fL)

Measure vitamin B12 and folate levels to evaluate for nutritional deficiencies. 2, 3

Also consider: 2, 3

• Medications (methotrexate, hydroxyurea, antiretrovirals)
• Alcohol use
• Myelodysplastic syndrome
• Hypothyroidism

Reticulocyte Count Interpretation

A low or normal reticulocyte count indicates impaired erythropoiesis (bone marrow not responding appropriately), suggesting nutritional deficiencies, bone marrow disorders, or chronic disease. 2

An elevated reticulocyte count indicates increased red cell production, suggesting hemolysis or acute blood loss with appropriate marrow response. 2

Treatment Based on Etiology

Iron Deficiency Anemia

Oral iron supplementation is first-line treatment, with parenteral iron reserved for patients who cannot tolerate or absorb oral preparations, or when rapid repletion is needed. 1, 2

Critical step: In adult men and postmenopausal women with confirmed iron deficiency, investigate for gastrointestinal bleeding as the underlying cause. 2

Vitamin B12 Deficiency (Pernicious Anemia)

Administer 100 mcg cyanocobalamin by intramuscular or deep subcutaneous injection daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life. 1, 4

Avoid the intravenous route—almost all vitamin will be lost in urine. 4

Folate Deficiency

Treat with oral folate supplementation, but exercise caution as high-dose folic acid may mask B12 deficiency symptoms and allow neurologic complications to progress. 1, 2

Anemia of Chronic Disease

Address the underlying condition first—this is the primary treatment. 2, 5

For chronic kidney disease patients with TSAT ≤ 30% and ferritin ≤ 500 ng/mL, consider a 1-3 month trial of oral or intravenous iron. 2

If anemia persists despite iron repletion, consider erythropoietin therapy in specific situations such as chronic kidney disease. 1, 3

Critical Pitfalls to Avoid

Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause. 1, 3

Watch for combined deficiencies (iron plus B12, or iron plus folate), especially in elderly patients and those with inflammatory bowel disease. 1, 3

Do not measure serum erythropoietin levels in chronic kidney disease patients with normochromic, normocytic anemia—this test is usually not indicated. 1

Always assess for blood loss when iron deficiency is confirmed, as this is the most common cause in adults. 2