What is the minimum workup for a patient presenting with anemia?

Minimum Workup of Anemia

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

Essential Laboratory Tests

The following tests form the foundation for diagnosing the vast majority of anemias and should be obtained together:

• Complete blood count (CBC) with red cell indices – provides hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW) 1, 2

• Absolute reticulocyte count – distinguishes impaired erythropoiesis (low/normal count) from hemolysis or blood loss (elevated count) 3, 1, 2

• Iron studies panel – must include serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity (TIBC) to assess both iron stores and iron availability for hemoglobin synthesis 3, 1, 2

• C-reactive protein (CRP) – essential for interpreting ferritin values, since ferritin rises as an acute-phase reactant during inflammation and can mask true iron deficiency 1, 4

Diagnostic Thresholds

Anemia is defined and triggers immediate workup at these hemoglobin levels:

• Men: < 13 g/dL 1, 2, 4
• Non-pregnant women: < 12 g/dL 1, 2, 4
• Pregnant women: < 11 g/dL 1, 2, 4

Classification by MCV Guides Next Steps

After obtaining the minimum workup, classify the anemia to direct further testing:

Microcytic Anemia (MCV < 80 fL)

• Most commonly indicates iron deficiency anemia, but also consider thalassemia trait, anemia of chronic disease, or sideroblastic anemia 1, 2

• Ferritin < 30 μg/L confirms absolute iron deficiency when inflammation is absent 1, 4

• TSAT < 15-20% supports iron deficiency and is less affected by inflammation than ferritin 3, 1, 4

• If iron studies are normal, 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)

• Reticulocyte count directs the workup: elevated count suggests hemolysis or acute blood loss; low/normal count suggests chronic disease, early iron deficiency, or bone marrow disorders 1, 2, 4

• If reticulocytes are elevated (> 100 × 10⁹/L), order hemolysis panel: haptoglobin, lactate dehydrogenase (LDH), indirect bilirubin, peripheral smear for schistocytes, and direct antiglobulin (Coombs) test 1, 4

• Measure serum creatinine and calculate GFR in all patients with normocytic anemia to evaluate for chronic kidney disease 4

Macrocytic Anemia (MCV > 100 fL)

• Measure serum vitamin B12 and folate levels to confirm or exclude megaloblastic anemia 3, 1, 2

• Obtain peripheral blood smear to look for hypersegmented neutrophils (megaloblastic pattern) or oval macrocytes 1

• Check thyroid-stimulating hormone (TSH) to exclude hypothyroidism, which commonly causes normochromic, normocytic anemia that can mimic erythropoietin deficiency 3, 4

Critical Pitfalls to Avoid

• Mixed deficiencies (iron plus B12) can neutralize the MCV, yielding a normal MCV but an elevated RDW; therefore, always order iron studies even when MCV appears normal 1, 2

• Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease, which is why CRP must be measured concurrently to interpret ferritin correctly 1, 2, 4

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause, as reversible conditions like hypothyroidism or vitamin deficiencies are common 2

• Low or normal reticulocyte count in the setting of anemia indicates inadequate bone marrow response and requires investigation for nutritional deficiencies, chronic disease, or bone marrow disorders 3, 1

When to Add Targeted Tests

Beyond the minimum workup, add these tests only when clinically indicated:

• Stool guaiac test for occult blood – recommended when iron deficiency is confirmed to test for gastrointestinal bleeding 3

• Tissue transglutaminase (tTG) antibody – screen for celiac disease, as approximately 5% of patients with iron deficiency anemia have celiac disease 4

• Hemoglobin electrophoresis – if microcytic anemia persists despite normal iron studies, particularly in patients with appropriate ethnic background for hemoglobinopathies 1

• Bone marrow examination – reserved for pancytopenia, unexplained anemia after initial workup, or suspected aplastic anemia or myelodysplastic syndrome 1