What is the appropriate workup for anemia?

Workup for Anemia

Begin the anemia workup with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies (serum ferritin and transferrin saturation), and inflammatory markers (C-reactive protein), which together provide the essential foundation for diagnosing the vast majority of anemias. 1, 2, 3

Define Anemia and Initiate Workup

Diagnostic thresholds:

• Hemoglobin < 13 g/dL in men 1, 2, 3
• Hemoglobin < 12 g/dL in non-pregnant women 1, 2, 3
• Hemoglobin < 11 g/dL in pregnant women 1, 2

For chronic kidney disease patients specifically, initiate workup when: 4

• Hemoglobin < 12 g/dL (Hct < 37%) in adult males and post-menopausal females 4
• Hemoglobin < 11 g/dL (Hct < 33%) in pre-menopausal females and pre-pubertal patients 4

Essential First-Line Laboratory Tests

Order these tests simultaneously at initial presentation: 1, 2, 3

1. Complete blood count with red cell indices - provides hemoglobin, hematocrit, MCV, MCH, MCHC, and RDW 1, 2, 3
2. Reticulocyte count - distinguishes impaired production (low/normal) from increased destruction or blood loss (elevated) 1, 2, 3
3. Iron studies panel: 1, 2, 3
   • Serum ferritin (< 30 μg/L confirms iron deficiency without inflammation) 1, 2
   • Transferrin saturation (< 15-16% supports iron deficiency) 1, 2
   • Total iron-binding capacity 3
4. C-reactive protein - identifies inflammatory states that affect ferritin interpretation 1, 3

Critical technical point: Use automated cell counters for all measurements, and in hemodialysis patients, obtain samples pre-dialysis as post-dialysis values are unreliable due to hemoconcentration 4

Algorithmic Classification by MCV

Microcytic Anemia (MCV < 80 fL)

Most common causes: 1, 2, 3

• Iron deficiency anemia (most common)
• Thalassemia trait
• Anemia of chronic disease
• Sideroblastic anemia

Diagnostic approach:

• If ferritin < 30 μg/L and transferrin saturation < 15%, diagnose iron deficiency anemia 1, 2
• If iron studies are normal, obtain hemoglobin electrophoresis to evaluate for thalassemia, particularly in patients of Mediterranean, African, or Southeast Asian descent 1
• MCH is more reliable than MCHC for detecting iron deficiency as it's less dependent on storage conditions 1

Normocytic Anemia (MCV 80-100 fL)

Most common causes: 2, 3

• Acute blood loss
• Hemolysis
• Anemia of chronic disease/inflammation
• Early iron deficiency
• Chronic kidney disease

Diagnostic approach:

• Elevated RDW with normal MCV suggests early iron deficiency or mixed nutritional deficiencies 1
• Low MCHC with normal MCV indicates hypochromia, often accompanying iron deficiency 1
• If hemolysis suspected, measure haptoglobin, LDH, and bilirubin 1
• Assess for chronic diseases and inflammatory conditions 1, 3

Macrocytic Anemia (MCV > 100 fL)

Most common causes: 1, 2, 3

• Vitamin B12 deficiency
• Folate deficiency
• Medications (methotrexate, hydroxyurea, antiretrovirals)
• Alcohol use
• Myelodysplastic syndrome

Diagnostic approach:

• Measure vitamin B12 and folate levels 1, 2
• Review medication list for causative agents 3
• Consider bone marrow evaluation if other causes excluded 3

Special Population Considerations

Chronic Kidney Disease Patients

Monitoring frequency: 2, 3

• Check hemoglobin at least every 3 months in patients with GFR < 30 mL/min/1.73 m² 2, 3
• Initiate full workup if hemoglobin drops below thresholds listed above 2, 3

Treatment sequence: 2

• Treat identified iron deficiency first 2
• If anemia persists despite iron repletion, consider erythropoietin therapy 2
• Do NOT routinely measure serum erythropoietin levels in CKD patients with normochromic, normocytic anemia—it's not clinically useful 2

High-Risk Patients Requiring Regular Monitoring

Screen regularly in: 1

• Chronic kidney disease patients 1
• Inflammatory bowel disease patients 1
• Other chronic inflammatory conditions 1

Critical Pitfalls to Avoid

Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause, as this represents a dangerous and common error. 2, 3

Watch for combined deficiencies: 2, 3

• Elderly patients and those with inflammatory bowel disease frequently have multiple concurrent deficiencies (e.g., iron plus B12) 2, 3
• Treating only one deficiency will result in persistent anemia 2, 3

Ferritin interpretation requires clinical context: 1

• Ferritin is an acute phase reactant and can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease 1
• In inflammatory states, ferritin < 100 μg/L may still indicate iron deficiency 1

High-dose folic acid supplementation can mask B12 deficiency symptoms while allowing neurologic damage to progress—always check B12 before treating with folate. 1

In adults with confirmed iron deficiency, investigate for blood loss: 1

• Gastrointestinal evaluation is warranted in adult men and postmenopausal women without obvious bleeding source 1
• Menstrual losses explain most cases in premenopausal women 1

When to Consider Bone Marrow Examination

Reserve bone marrow evaluation for: 3

• Unexplained normocytic or macrocytic anemia after initial workup 3
• Suspected myelodysplastic syndrome 3
• Pancytopenia or other cytopenias 3
• Atypical presentations not explained by standard testing 3