What is the initial workup and management for a patient presenting with anemia?

Initial Workup and Management of Anemia

Begin with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies (serum ferritin and transferrin saturation), and inflammatory markers (CRP) as 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
• These thresholds should trigger immediate workup rather than observation 1

Morphologic Classification and Initial Testing

Microcytic Anemia (MCV < 80 fL):

• Most commonly indicates iron deficiency anemia, but also consider thalassemia, anemia of chronic disease, or sideroblastic anemia 1, 2
• Confirm iron deficiency with serum ferritin < 30 μg/L and transferrin saturation < 20% 3, 1, 4
• In the presence of inflammation (elevated CRP), ferritin cutoffs are less reliable; use transferrin saturation < 20% as the primary diagnostic criterion 3, 2
• If ferritin is 30-100 μg/L with transferrin saturation < 20%, consider functional iron deficiency or mixed picture requiring further evaluation 3

Normocytic Anemia (MCV 80-100 fL):

• Check reticulocyte count first to distinguish regenerative from non-regenerative causes 3, 2
• If reticulocytes > 100 × 10⁹/L, evaluate for hemolysis (LDH, haptoglobin, bilirubin, peripheral smear) or acute blood loss 3, 2
• If reticulocytes are low/normal, measure serum creatinine and calculate GFR to rule out chronic kidney disease 3
• Check inflammatory markers (CRP) to identify anemia of chronic disease 3

Macrocytic Anemia (MCV > 100 fL):

• Measure vitamin B12 and folate levels 1, 2
• Check TSH to rule out hypothyroidism 3
• Consider myelodysplastic syndrome if other causes excluded, particularly in elderly patients 3

Critical Evaluation Points

Iron Status Assessment:

• Serum ferritin < 30 μg/L confirms absolute iron deficiency without inflammation 3, 1, 4
• Transferrin saturation < 20% indicates inadequate iron availability for erythropoiesis 3, 1
• In patients with ferritin 30-100 μg/L and transferrin saturation < 20%, consider referral to gastroenterology to rule out malignancy as a source of chronic blood loss 3

Renal Function:

• Measure serum creatinine and calculate GFR in all patients with normocytic anemia 3
• If GFR < 30 mL/min/1.73 m², consider nephrology referral for evaluation of anemia of chronic kidney disease 3, 1

Reticulocyte Count:

• Low or normal reticulocyte count indicates impaired erythropoiesis (bone marrow problem, nutritional deficiency, chronic disease) 3, 2
• Elevated reticulocyte count suggests hemolysis or acute blood loss requiring urgent evaluation 3, 2

Initial Management Based on Etiology

Iron Deficiency Anemia:

• Oral iron supplementation (ferrous sulfate 325 mg daily or on alternate days) is first-line treatment 1, 4
• Intravenous iron is indicated for: oral iron intolerance, malabsorption (celiac disease, post-bariatric surgery), chronic inflammatory conditions (CKD, heart failure, IBD, cancer), ongoing blood loss, or second/third trimester pregnancy 1, 4
• Expect hemoglobin increase of 1-2 g/dL within one month of oral iron therapy; if not achieved, consider malabsorption, continued bleeding, or need for IV iron 5

Vitamin B12 Deficiency:

• Treat with intramuscular or deep subcutaneous cyanocobalamin, with maintenance doses given monthly for life 1

Folate Deficiency:

• Treat with oral folate supplementation 1, 2
• Critical pitfall: Always check B12 levels before treating with folate, as high-dose folic acid may mask B12 deficiency symptoms while allowing neurologic damage to progress 1, 2

Anemia of Chronic Kidney Disease:

• Monitor hemoglobin at least every three months in patients with GFR < 30 mL/min/1.73 m² 1
• Treat identified iron deficiency first 1
• If anemia persists despite iron therapy, initiate erythropoietin or analogue therapy 1
• Iron supplementation should be continued throughout erythropoietin therapy to optimize response 3

Referral Indications

Gastroenterology:

• Iron deficiency with ferritin < 30 μg/L or transferrin saturation < 20% to rule out gastrointestinal malignancy, particularly in men and postmenopausal women 3, 6
• Bidirectional endoscopy (gastroscopy and colonoscopy) is recommended for unexplained iron deficiency anemia, except in premenopausal women < 40 years without red flags 6

Nephrology:

• Abnormal creatinine or GFR suggesting chronic kidney disease 3
• Anemia with GFR < 30 mL/min/1.73 m² requiring evaluation for erythropoietin therapy 1

Hematology:

• Unexplained anemia after initial workup 3
• Suspected hemolysis, bone marrow failure, or myelodysplastic syndrome 3
• Anemia not responding to appropriate therapy 3

Critical Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the cause 1
• Watch for combined deficiencies (iron, B12, folate), especially in elderly patients and those with inflammatory bowel disease 1
• Do not rely on hemoglobin alone; red cell indices and iron studies are essential for accurate diagnosis 7
• In adults with iron deficiency, always evaluate for gastrointestinal blood loss as the most common cause 4, 5
• Measuring serum erythropoietin levels is usually not indicated in chronic kidney disease patients with normochromic, normocytic anemia 1