What is the initial workup and treatment for anemia?

Initial Workup and Treatment for Anemia

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 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 3

Essential Initial Laboratory Tests

Order these tests together at the first visit:

• Complete blood count with red cell indices (hemoglobin, MCV, MCH, MCHC) 1, 2, 3
• Absolute reticulocyte count to evaluate bone marrow response 4, 1, 3
• Serum ferritin (most useful single marker for iron deficiency) 1, 3
• Transferrin saturation (TSAT) 4, 1, 3
• C-reactive protein to assess for inflammation 1, 3
• Vitamin B12 and folate levels 4, 1, 2

Morphologic Classification and Diagnostic Approach

Microcytic Anemia (MCV < 80 fL)

• Most commonly indicates iron deficiency anemia, but also consider thalassemia, anemia of chronic disease, or sideroblastic anemia 1, 2, 5
• Confirm iron deficiency with serum ferritin < 30 μg/L (without inflammation) and transferrin saturation < 15-16% 1, 2
• MCH is more reliable than MCHC for detecting iron deficiency because it is less dependent on storage conditions 1
• Critical caveat: Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease—interpret in clinical context 1, 3
• 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, early iron deficiency, or chronic kidney disease 1, 2, 6
• A low or normal reticulocyte count indicates impaired erythropoiesis, while an elevated reticulocyte count suggests increased red cell production (hemolysis or acute blood loss) 1
• For suspected hemolysis, measure haptoglobin (decreased), LDH (elevated), and indirect bilirubin (elevated) 1, 6
• Important pitfall: MCV-guided classification can be misleading—16% of microcytic patients and 90% of macrocytic patients may have etiologies not predicted by MCV alone 7

Macrocytic Anemia (MCV > 100 fL)

• Most commonly indicates vitamin B12 or folate deficiency, but also consider medications, alcohol use, or myelodysplastic syndrome 1, 2, 3
• Measure vitamin B12 and folate levels in all macrocytic anemia cases 1, 2

Treatment Approach Based on Etiology

Iron Deficiency Anemia

• Oral iron supplementation is first-line treatment for most patients 2
• 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 4
• Reserve parenteral iron for patients who cannot tolerate or absorb oral preparations, or when rapid repletion is needed 4, 2
• Always investigate the underlying cause: gastrointestinal bleeding in adult men and postmenopausal women, menstrual losses in premenopausal women 1

Vitamin B12 Deficiency

• Treat with intramuscular or deep subcutaneous cyanocobalamin 100 mcg daily for 6-7 days 8
• If clinical improvement and reticulocyte response occur, give the same dose on alternate days for seven doses, then every 3-4 days for 2-3 weeks 8
• Maintenance therapy: 100 mcg monthly for life 2, 8
• Avoid the intravenous route as almost all vitamin will be lost in urine 8

Folate Deficiency

• Treat with oral folate supplementation 1, 2
• Critical warning: High-dose folic acid may mask vitamin B12 deficiency symptoms—always check B12 levels before treating with folate alone 1
• If B12 deficiency coexists, administer folic acid concomitantly with B12 treatment 8

Anemia of Chronic Disease

• Address the underlying inflammatory or chronic condition as primary treatment 1, 6
• Erythropoietin therapy may be considered in specific situations such as chronic kidney disease 1

Chronic Kidney Disease-Associated Anemia

• Monitor hemoglobin at least every 3 months in patients with GFR < 30 mL/min/1.73 m² 2, 3
• Treat identified iron deficiency first before considering erythropoietin therapy 2, 3
• If anemia persists despite iron repletion, initiate erythropoietin or analogue therapy 2
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia 2

Critical Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause 2, 3
• Watch for combined deficiencies (especially iron and B12 deficiency) in elderly patients and those with inflammatory bowel disease 2, 3
• Do not rely solely on MCV for classification—85% of anemic patients have MCV within normal range, and MCV-guided classification can incorrectly rule out etiologies 7
• Assess for potential sources of blood loss in all adults with iron deficiency, as it often indicates ongoing bleeding 1
• In patients without obvious blood loss, gastrointestinal evaluation may be warranted 1