What is the initial workup and treatment approach for a patient with suspected anemia?

Anemia Workup

Begin the anemia workup with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies panel (ferritin, transferrin saturation, total iron-binding capacity), and C-reactive protein—these tests ordered simultaneously provide the essential foundation for diagnosing the vast majority of anemias. 1, 2

Diagnostic Thresholds

• Anemia is defined as hemoglobin < 13 g/dL in men, < 12 g/dL in non-pregnant women, and < 11 g/dL in pregnant women 1, 2, 3
• For chronic kidney disease patients specifically, initiate workup when hemoglobin < 12 g/dL in adult males and post-menopausal females, and < 11 g/dL in pre-menopausal females 2, 3

Classification by Mean Corpuscular Volume (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 serum ferritin < 30 μg/L and transferrin saturation < 15% 1
• Critical caveat: In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency—measure CRP to assess inflammation 3
• If ferritin is 30-100 μg/L, suspect a combination of true iron deficiency and anemia of chronic disease 3
• When ferritin is elevated (> 100 μg/L) with low transferrin saturation (< 20%), consider anemia of chronic disease/inflammation 3
• If iron studies are normal, order hemoglobin electrophoresis to evaluate for thalassemia 3

Normocytic Anemia (MCV 80-100 fL):

• May be caused by acute blood loss, hemolysis, anemia of chronic disease, early iron deficiency, or chronic kidney disease 2, 3
• The reticulocyte count helps distinguish between impaired production (low reticulocyte count) and increased destruction or blood loss (elevated reticulocyte count) 3

Macrocytic Anemia (MCV > 100 fL):

• Often caused by vitamin B12 deficiency, folate deficiency, medications, alcohol use, or myelodysplastic syndrome 2, 3

Treatment Approach by Etiology

Iron Deficiency Anemia:

• Oral iron supplementation is first-line treatment, with parenteral iron reserved for patients who cannot tolerate or absorb oral preparations 1
• All adults with confirmed iron deficiency anemia require urinalysis/urine microscopy, celiac disease screening, and in appropriate cases, upper and lower GI endoscopy 3
• Men and postmenopausal women with iron deficiency anemia should be evaluated with gastrointestinal endoscopy 4

Vitamin B12 Deficiency:

• Administer intramuscular or deep subcutaneous cyanocobalamin 100 mcg 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, 5
• Avoid the intravenous route as almost all vitamin will be lost in urine 5
• Folic acid should be administered concomitantly if needed 5

Folate Deficiency:

• Treat with oral folate supplementation 1
• Critical pitfall: Exercise caution to avoid masking B12 deficiency symptoms 1

Anemia of Chronic Disease/Inflammation:

• Primary treatment involves addressing the underlying condition 3
• Diagnostic criteria include serum ferritin > 100 μg/L and transferrin saturation < 20% in the presence of inflammation 3

Special Population Considerations

Chronic Kidney Disease:

• Monitor hemoglobin at least every 3 months in patients with GFR < 30 mL/min/1.73 m² 1, 2, 3
• Initiate full workup if hemoglobin drops below thresholds 2, 3
• Treat identified iron deficiency first; if anemia persists despite iron therapy, initiate erythropoietin or analogue therapy 1, 3
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia 1

Inflammatory Bowel Disease:

• Anemia is typically multifactorial (iron deficiency from blood loss plus anemia of chronic disease) 3
• Use disease-specific ferritin thresholds: < 30 μg/L without inflammation, up to 100 μg/L with inflammation 3
• Minimum screening should include CBC, CRP, and serum ferritin at regular intervals based on disease activity 3

Critical Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause 1, 2, 3
• Watch for combined deficiencies (especially iron and B12 deficiency), particularly in elderly patients and those with inflammatory bowel disease 1, 2, 3
• Ferritin interpretation requires clinical context, as it can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease 2
• Consider genetic disorders when microcytic anemia is refractory to iron supplementation, there is a family history of anemia, or ferritin > 100 μg/L with elevated transferrin saturation 3