What is the initial workup and treatment for anemia?

Initial Workup and Treatment for Anemia

Begin with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies (serum ferritin, transferrin saturation, TIBC), and inflammatory markers (CRP) as your essential first-line tests. 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

Morphologic Classification by MCV

The MCV from your initial CBC directs your diagnostic pathway:

Microcytic Anemia (MCV < 80 fL)

• Most commonly indicates iron deficiency anemia, but also consider thalassemia, anemia of chronic disease, or sideroblastic anemia. 3, 1
• Confirm iron deficiency with serum ferritin < 30 μg/L (without inflammation) and transferrin saturation < 15%. 3, 1
• Look for sources of blood loss: check stool for occult blood, and in men or postmenopausal women with confirmed iron deficiency, gastrointestinal endoscopy is warranted. 3, 4

Normocytic Anemia (MCV 80-100 fL)

• The reticulocyte count is your critical next step here. 3, 2
• Low reticulocyte index (< 1.0-2.0) indicates decreased RBC production, suggesting iron deficiency, vitamin B12/folate deficiency, aplastic anemia, bone marrow dysfunction, or anemia of chronic inflammation. 3
• High reticulocyte index indicates normal/increased production, pointing to blood loss or hemolysis. 3
• For suspected hemolysis: order Coombs test, haptoglobin (low in hemolysis), indirect bilirubin (elevated), and LDH. 3, 1
• For chronic kidney disease: check GFR and erythropoietin level if GFR < 60 mL/min/1.73 m². 3

Macrocytic Anemia (MCV > 100 fL)

• Most commonly caused by vitamin B12 or folate deficiency—measure both levels directly. 3, 1
• Non-megaloblastic causes include alcoholism, myelodysplastic syndrome, and certain drugs (hydroxyurea, diphenytoin). 3

Kinetic Approach Using Reticulocyte Index

Calculate the reticulocyte index (corrected for degree of anemia):

• RI 1.0-2.0 = normal bone marrow response 3
• RI < 1.0 = production problem (iron, B12/folate deficiency, bone marrow failure) 3
• RI > 2.0 = destruction or loss problem (hemorrhage, hemolysis) 3

Treatment Based on Etiology

Iron Deficiency Anemia

• Treat the underlying cause first—address any source of blood loss. 3, 4
• Oral iron supplementation is first-line for most patients. 2, 4
• Parenteral iron is reserved for patients who cannot tolerate or absorb oral preparations. 4

Vitamin B12 Deficiency (Pernicious Anemia)

• 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. 5
• Maintenance: 100 mcg monthly for life. 5
• Avoid intravenous route as it results in urinary loss of the vitamin. 5
• Administer folic acid concomitantly if needed. 5

Folate Deficiency

• Oral folate supplementation is appropriate. 1
• Caution: High-dose folic acid may mask B12 deficiency symptoms—always check B12 levels before treating isolated folate deficiency. 1

Anemia of Chronic Disease/Inflammation

• Primary treatment is addressing the underlying condition. 2, 6
• Supplementation with iron, folic acid, and vitamin B12 may be needed based on specific deficiencies identified. 6

Anemia in Chronic Kidney Disease (GFR < 30 mL/min/1.73 m²)

• Monitor hemoglobin at least every three months. 3, 2
• Initiate workup if hemoglobin < 12 g/dL in women or < 13 g/dL in men, including complete iron studies. 3, 2
• Treat identified iron deficiency first. 3
• If anemia persists despite iron therapy, initiate erythropoietin or analogue therapy. 3
• Monitor blood pressure with each erythropoietin dose. 3

Critical Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the cause. 2
• Do not empirically treat with nutritional supplements without identifying the specific deficiency—this can mask serious underlying conditions. 7
• Watch for combined deficiencies (e.g., iron + B12), especially in elderly patients and those with inflammatory bowel disease. 2
• In cancer or chemotherapy-induced anemia, do not transfuse based solely on hemoglobin threshold—assess symptoms and comorbidities. 3
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia. 3