What is the initial workup and management for a patient with low hemoglobin (hypochromic anemia)?

Initial Workup for Low Hemoglobin (Hypochromic Anemia)

Begin with a complete blood count with red cell indices and reticulocyte count to classify the anemia by MCV and determine if it is regenerative or non-regenerative. 1, 2

Diagnostic Classification by MCV

Microcytic Anemia (MCV < 80 fL)

• Hypochromic anemia specifically suggests iron deficiency, thalassemia, or anemia of chronic inflammation. 1
• Order iron studies immediately: serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity. 1, 2
• Ferritin < 30 μg/L confirms absolute iron deficiency without inflammation. 2
• Transferrin saturation < 20% indicates inadequate iron availability for erythropoiesis. 2
• If ferritin is elevated (>100 μg/L) but TSAT is low (<20%), this suggests anemia of chronic inflammation with functional iron deficiency. 3
• Measure C-reactive protein (CRP) to identify inflammatory states. 1

Normocytic Anemia (MCV 80-100 fL)

• Check reticulocyte count first to distinguish regenerative from non-regenerative causes. 2
• If reticulocytes > 100 × 10⁹/L, evaluate for hemolysis (obtain LDH, haptoglobin, indirect bilirubin, peripheral smear) or acute blood loss. 2
• If reticulocytes are low, measure serum creatinine and calculate GFR in all patients. 2
• If GFR < 30 mL/min/1.73 m², consider nephrology referral for anemia of chronic kidney disease. 2

Macrocytic Anemia (MCV > 100 fL)

• Order vitamin B12 and folate levels. 1
• Check thyroid-stimulating hormone (TSH) to exclude hypothyroidism. 3
• Review medications (methotrexate, anticonvulsants, alcohol use). 1
• If unexplained, refer to hematology for bone marrow evaluation to exclude myelodysplastic syndrome. 1

Essential Laboratory Tests for All Patients

• Complete blood count with red cell indices (MCV, MCH, MCHC). 1
• Reticulocyte count to assess bone marrow response. 1, 2
• Iron studies: ferritin, transferrin saturation, total iron-binding capacity. 1, 2
• Serum creatinine and GFR calculation. 2
• Inflammatory markers (CRP) if anemia of chronic disease is suspected. 1

Additional Workup Based on Clinical Context

For Iron Deficiency Anemia (Ferritin < 30 μg/L or TSAT < 20%)

• Refer to gastroenterology to rule out gastrointestinal malignancy, especially in men with any degree of anemia and postmenopausal women. 3, 2
• Obtain tissue transglutaminase (tTG) antibody to screen for celiac disease, as approximately 5% of patients with iron deficiency anemia have celiac disease. 3
• If tTG is negative, duodenal biopsies are not necessary unless diarrhea or other gastrointestinal symptoms are present. 3
• Take detailed history regarding NSAID use, aspirin, dietary intake, and blood donation. 3

For Anemia with Renal Dysfunction

• If GFR < 30 mL/min/1.73 m² and hemoglobin < 12 g/dL in women or < 13 g/dL in men, complete iron workup and consider nephrology referral. 2
• Monitor hemoglobin at least every three months in patients with GFR < 30 mL/min. 1

Initial Management

Iron Deficiency Anemia

• Oral iron supplementation is first-line treatment (ferrous sulfate 1 tablet two to three times daily, do not crush or chew). 1, 4
• Intravenous iron is indicated for oral iron intolerance, malabsorption, or chronic inflammatory conditions. 1
• Ensure ferritin > 100 μg/L and TSAT > 20% before considering erythropoietin therapy if anemia persists. 3

Anemia of Chronic Disease/Inflammation

• Primary treatment involves addressing the underlying condition. 1
• Consider intravenous iron if functional iron deficiency is present (low TSAT despite elevated ferritin). 3

Referral Indications

• Immediate gastroenterology referral for men with hemoglobin < 12 g/dL and postmenopausal women with hemoglobin < 10 g/dL with iron deficiency to exclude gastrointestinal malignancy. 3, 2
• Nephrology referral if GFR < 30 mL/min/1.73 m² with anemia. 2
• Hematology referral for unexplained anemia after initial workup, suspected hemolysis, macrocytic anemia without B12/folate deficiency, or pancytopenia. 2

Critical Pitfalls to Avoid

• Do not assume anemia is a normal physiological response to aging in elderly patients; always investigate the cause. 1
• Do not miss concurrent nutritional deficiencies, such as combined iron and B12 deficiency. 1
• Do not perform empiric iron trials in men or women over age 40 without first establishing iron deficiency and investigating for gastrointestinal sources. 5
• Do not delay gastroenterology referral in patients with iron deficiency, as dual pathology (upper and lower GI bleeding sources) occurs in 1-10% of patients. 3