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

Initial Anemia Workup

Order a complete blood count with red cell indices, reticulocyte count, iron studies panel (serum ferritin, transferrin saturation, total iron-binding capacity), and C-reactive protein simultaneously at initial presentation. 1, 2, 3

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 with GFR < 30 mL/min/1.73 m², initiate workup when hemoglobin < 12 g/dL in women or < 13 g/dL in men 4, 2, 3

Essential First-Line Laboratory Tests

The initial workup must include all of the following tests ordered together: 1, 2, 3

• Complete blood count with red cell indices (hemoglobin, hematocrit, MCV, MCH, MCHC, RDW)
• Absolute reticulocyte count to evaluate bone marrow response
• Serum ferritin
• Transferrin saturation (TSAT)
• Total iron-binding capacity (TIBC)
• C-reactive protein to assess for inflammation
• Vitamin B12 and folate levels 1, 3

Morphologic Classification and Next Steps

Microcytic Anemia (MCV < 80 fL)

• Most commonly indicates iron deficiency anemia, but also consider thalassemia trait, anemia of chronic disease, or sideroblastic anemia 2, 3, 5
• Confirm iron deficiency with serum ferritin < 30 μg/L (without inflammation) and transferrin saturation < 15-16% 1, 3
• Critical caveat: Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease—interpret in clinical context 1, 2
• If iron studies are normal despite microcytic anemia, obtain hemoglobin electrophoresis to evaluate for thalassemia trait, particularly in patients of Mediterranean, African, or Southeast Asian descent 1

Normocytic Anemia (MCV 80-100 fL)

• May indicate acute blood loss, hemolysis, anemia of chronic disease/inflammation, early iron deficiency, or chronic kidney disease 2, 6
• Important pitfall: MCV-guided classification can be misleading—research shows that 16% of microcytic patients and 90% of macrocytic patients had etiologies not matching expected MCV patterns 7
• Low MCHC with normal MCV suggests hypochromia and often indicates iron deficiency even when MCV remains normal 1
• Elevated RDW with normal MCV suggests mixed nutritional deficiencies or early iron deficiency 1

Macrocytic Anemia (MCV > 100 fL)

• Often caused by vitamin B12 deficiency, folate deficiency, medications, alcohol use, or myelodysplastic syndrome 2, 3
• Measure vitamin B12 and folate levels 1, 3
• Low or normal reticulocyte count indicates impaired erythropoiesis, while elevated reticulocyte count suggests hemolysis or acute blood loss 1

Hemolysis Workup (If Suspected)

• Measure haptoglobin (decreased), LDH (elevated), and indirect bilirubin (elevated) 1, 6
• Look for jaundice, hepatosplenomegaly, and increased reticulocyte count 6

Treatment Approach Based on Etiology

Iron Deficiency Anemia

• Oral iron supplementation is first-line treatment for most patients 3
• For chronic kidney disease patients not on dialysis with TSAT ≤ 30% and ferritin ≤ 500 ng/mL, consider a 1-3 month trial of oral iron OR intravenous iron 1
• Parenteral iron should be reserved for patients who cannot tolerate or absorb oral preparations, or when rapid repletion is needed 1, 3
• Always investigate the underlying cause: gastrointestinal bleeding in adult men and postmenopausal women, menstrual losses in premenopausal women 1

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 8
• Avoid the intravenous route as almost all vitamin will be lost in urine 8

Folate Deficiency

• Treat with oral folate supplementation 3
• Critical warning: High-dose folic acid may mask B12 deficiency symptoms—always check B12 levels before treating with folate alone 1, 3

Anemia of Chronic Disease/Inflammation

• Treat by addressing the underlying condition 1
• Erythropoietin therapy may be considered in specific situations such as chronic kidney disease 1

Chronic Kidney Disease-Related Anemia

• Treat identified iron deficiency first 4, 3
• If anemia persists despite appropriate evaluation and iron therapy, initiate erythropoietin or analogue therapy 4, 3
• Monitor hemoglobin at least every 3 months in patients with GFR < 30 mL/min/1.73 m² 4, 3

Critical Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause 2, 3
• Watch for combined deficiencies (iron and B12 deficiency occurring together), especially in elderly patients and those with inflammatory bowel disease 2, 3
• Do not rely solely on MCV for classification—use the complete panel of tests simultaneously 7
• MCH is more reliable than MCHC for detecting iron deficiency because it is less dependent on storage conditions 1
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia 3