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

Anemia Workup

Begin the anemia workup by simultaneously ordering a complete blood count with red cell indices, reticulocyte count, iron studies panel (ferritin, transferrin saturation, total iron-binding capacity), and C-reactive protein at initial presentation. 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
• For chronic kidney disease patients, initiate workup when hemoglobin < 12 g/dL (Hct < 37%) in adult males and post-menopausal females, and < 11 g/dL (Hct < 33%) in pre-menopausal females 1

Classification by MCV and Diagnostic Algorithm

Microcytic Anemia (MCV < 80 fL)

• Iron deficiency anemia is confirmed by serum ferritin < 30 μg/L and transferrin saturation < 15% 3
• In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency—measure CRP to assess inflammation 2
• If ferritin is 30-100 μg/L, suspect combined iron deficiency and anemia of chronic disease 2
• Anemia of chronic disease/inflammation is diagnosed when ferritin > 100 μg/L with transferrin saturation < 20% in the presence of elevated CRP 2
• If ferritin is elevated AND transferrin saturation is elevated, or when transferrin saturation is low with ferritin 20-100 μg/L, suspect genetic disorders of iron metabolism (sideroblastic anemia, IRIDA, hemochromatosis) 2
• Order hemoglobin electrophoresis if iron studies are normal to evaluate for thalassemia 2

Normocytic Anemia (MCV 80-100 fL)

• Consider acute blood loss, hemolysis, anemia of chronic disease, early iron deficiency, or chronic kidney disease 1, 2
• Use reticulocyte count to distinguish between impaired production (low reticulocyte count) and increased destruction or blood loss (elevated reticulocyte count) 2
• Check lactate dehydrogenase, haptoglobin, and bilirubin if hemolysis is suspected 4

Macrocytic Anemia (MCV > 100 fL)

• Check vitamin B12 and folate levels to identify deficiency states 1, 2
• Consider medications, alcohol use, or myelodysplastic syndrome as alternative causes 1, 2

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 3
• All adults with confirmed iron deficiency anemia require urinalysis/urine microscopy, celiac disease screening, and in appropriate cases, upper and lower GI endoscopy 2
• Men and postmenopausal women with iron deficiency anemia must undergo gastrointestinal endoscopy to identify the source 5

Vitamin B12 Deficiency (Pernicious Anemia)

• Administer 100 mcg intramuscular or deep subcutaneous cyanocobalamin 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 6
• Avoid the intravenous route as almost all vitamin will be lost in urine 6
• Administer folic acid concomitantly if needed 6

Folate Deficiency

• Treat with oral folate supplementation, but ensure B12 deficiency is excluded first to avoid masking B12 deficiency symptoms 3

Anemia of Chronic Disease/Inflammation

• Primary treatment involves addressing the underlying condition 2
• Iron supplementation, folic acid, and vitamin B12 may be needed based on specific deficiencies identified 7

Anemia in Chronic Kidney Disease

• Monitor hemoglobin at least every 3 months in patients with GFR < 30 mL/min/1.73 m² 1, 3
• Initiate full workup if hemoglobin drops below thresholds (< 12 g/dL in women, < 13 g/dL in men) 2, 3
• Treat identified iron deficiency first; if anemia persists despite iron repletion, initiate erythropoietin or analogue therapy 1, 3
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia 3

Special Population Considerations

Inflammatory Bowel Disease

• Anemia is typically multifactorial (iron deficiency from blood loss plus anemia of chronic disease) 2
• Use disease-specific ferritin thresholds: < 30 μg/L without inflammation, up to 100 μg/L with inflammation 2
• Minimum screening should include CBC, CRP, and serum ferritin at regular intervals based on disease activity 2

Elderly Patients

• Never assume anemia is "normal aging"—always investigate the underlying cause 1, 3
• Watch for combined deficiencies, such as iron and B12 deficiency, which are common in this population 1, 3

Critical Pitfalls to Avoid

• Ferritin interpretation requires clinical context, as it can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease 1
• Watch for combined nutritional deficiencies, especially in elderly patients and those with inflammatory bowel disease 1, 3
• 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 2
• For X-linked sideroblastic anemia, screen male probands' mothers, sisters, and daughters, as female carriers can develop phenotype later in life 2