What is the minimum work‑up for anemia?

Minimum Workup for Anemia

The minimum workup for anemia requires a complete blood count with red cell indices (including MCV and RDW), reticulocyte count, serum ferritin, transferrin saturation, and C-reactive protein—all obtained simultaneously at initial presentation. 1, 2, 3

Essential Laboratory Tests

The following tests constitute the minimum diagnostic panel and should be ordered together:

• Complete blood count (CBC) with red cell indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW) 1, 2, 3

• Reticulocyte count (absolute, not just percentage) to distinguish impaired erythropoiesis from increased red cell destruction or loss 1, 2, 4

• Serum ferritin as the single most useful marker of iron stores, with levels <30 μg/L confirming iron deficiency in the absence of inflammation 1, 2, 4

• Transferrin saturation (TSAT) with values <15-20% indicating inadequate iron availability for red cell production and being less affected by inflammation than ferritin 1, 2, 4

• C-reactive protein (CRP) to interpret ferritin values correctly, since ferritin rises as an acute-phase reactant during inflammation and can mask true iron deficiency 1, 2, 4

• Differential blood cell count to identify abnormal white cell or platelet patterns that may suggest bone marrow pathology 1

Diagnostic Thresholds

Anemia is defined by hemoglobin levels below these sex- and pregnancy-specific cutoffs:

• Men: hemoglobin <13 g/dL 2, 4, 3
• Non-pregnant women: hemoglobin <12 g/dL 2, 4, 3
• Pregnant women: hemoglobin <11 g/dL 2, 4, 3

Algorithmic Approach After Initial Testing

Once the minimum workup is complete, classify the anemia by MCV and reticulocyte response:

Microcytic Anemia (MCV <80 fL)

• If ferritin <30 μg/L or TSAT <20%, iron deficiency is confirmed and requires investigation for the source of blood loss (gastrointestinal evaluation in adult men and postmenopausal women) 1, 2, 4

• If ferritin is normal/elevated but TSAT remains low (<20%), consider anemia of chronic inflammation with functional iron deficiency 1, 2, 4

• If iron studies are normal, obtain hemoglobin electrophoresis to evaluate for thalassemia trait, particularly in patients of Mediterranean, African, or Southeast Asian descent 2

Normocytic Anemia (MCV 80-100 fL)

• If reticulocyte count is elevated, evaluate for hemolysis by measuring haptoglobin, lactate dehydrogenase (LDH), indirect bilirubin, and examining the peripheral smear for schistocytes 2, 4

• If reticulocyte count is low/normal, assess for anemia of chronic disease, early iron deficiency (check iron studies), chronic kidney disease (measure creatinine and calculate GFR), or bone marrow suppression 2, 4, 3

Macrocytic Anemia (MCV >100 fL)

• If reticulocyte count is low/normal, measure serum vitamin B12 and folate levels, review medications (thiopurines, methotrexate, anticonvulsants), and check thyroid-stimulating hormone and liver function tests 2, 3

• If reticulocyte count is elevated, evaluate for hemolysis or recent blood loss with recovery 2

Critical Pitfalls to Avoid

• Mixed deficiencies can normalize the MCV but produce an elevated RDW; for example, concurrent iron and vitamin B12 deficiency may yield a normal MCV, so always check iron studies even when MCV appears normal 2, 3

• Ferritin >30 μg/L does not exclude iron deficiency in the presence of inflammation; in inflammatory states (elevated CRP), ferritin thresholds up to 100 μg/L may be required to rule out iron deficiency 1, 2

• Low MCH with elevated RDW is highly suggestive of iron deficiency even before hemoglobin drops significantly, and this pattern warrants iron studies and treatment 2

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause, as age alone does not cause anemia 3

When to Extend the Workup

If the cause remains unclear after the minimum workup, obtain:

• Vitamin B12 and folate levels if macrocytosis is present or if there is clinical suspicion (neurologic symptoms, malabsorption history) 1, 2, 3

• Peripheral blood smear review to identify hypersegmented neutrophils (megaloblastic anemia), schistocytes (hemolysis), or abnormal cell morphology 1, 2

• Hemolysis panel (haptoglobin, LDH, indirect bilirubin, direct antiglobulin test) if reticulocyte count is elevated 2, 4

• Serum creatinine and GFR in all patients with normocytic anemia to screen for chronic kidney disease 4, 3

• Hematology referral if the diagnosis remains unclear after extended workup, if pancytopenia is present, or if bone marrow examination is needed 1, 2, 4