What is the initial workup for a patient presenting with anemia from a hematology standpoint?

Initial Hematologic Workup for Anemia

Order a complete blood count with red cell indices, absolute reticulocyte count, serum ferritin, transferrin saturation, and vitamin B12/folate levels simultaneously at initial presentation. 1, 2

Essential First-Line Laboratory Tests

The following tests should be obtained together as the foundation of anemia evaluation:

• Complete blood count (CBC) including hemoglobin, red cell indices (MCV, MCH, MCHC), white blood cell count with differential, and platelet count 3, 2
• Absolute reticulocyte count to assess bone marrow response and distinguish regenerative from non-regenerative anemia 3, 1
• Iron studies panel including serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity 3, 1, 2
• Vitamin B12 and folate levels to identify nutritional deficiencies 3, 1, 2
• C-reactive protein (CRP) to assess for inflammation, which affects ferritin interpretation 1, 2

Diagnostic Thresholds

Anemia is defined as:

• Hemoglobin <13 g/dL in men 1, 2, 4
• Hemoglobin <12 g/dL in non-pregnant women 1, 2, 4
• Hemoglobin <11 g/dL in pregnant women 1, 4

Classification by Mean Corpuscular Volume (MCV)

Microcytic Anemia (MCV <80 fL)

• Most common causes: Iron deficiency anemia, thalassemia trait, anemia of chronic disease, sideroblastic anemia 3, 1, 2
• Key diagnostic markers: Ferritin <30 μg/L confirms iron deficiency without inflammation; TSAT <20% indicates inadequate iron for erythropoiesis 1, 4
• Critical action: In adult men and postmenopausal women with confirmed iron deficiency, refer to gastroenterology to rule out gastrointestinal malignancy 4

Normocytic Anemia (MCV 80-100 fL)

• Most common causes: Acute blood loss, hemolysis, anemia of chronic disease, early iron deficiency, chronic kidney disease 3, 1, 2
• Reticulocyte count interpretation: Low/normal count indicates impaired erythropoiesis; elevated count (>100 × 10⁹/L) suggests hemolysis or acute bleeding 3, 4
• Essential additional test: Measure serum creatinine and calculate GFR in all patients with normocytic anemia 4

Macrocytic Anemia (MCV >100 fL)

• Most common causes: Vitamin B12 deficiency, folate deficiency, medications, alcohol use, myelodysplastic syndrome 3, 1, 2
• Diagnostic workup: TSH, vitamin B12, folate levels; consider bone marrow biopsy if unexplained 3

Critical Interpretation Points

Ferritin Interpretation Requires Clinical Context

• Ferritin is an acute-phase reactant and can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease 3, 1, 2
• In chronic kidney disease patients on hemodialysis, ferritin interpretation is particularly difficult due to chronic inflammation 3
• When ferritin is elevated (>100 μg/L) but TSAT is low (<20%), this suggests functional iron deficiency from chronic inflammation 4

Reticulocyte Count Assessment

• A low reticulocyte count indicates impaired bone marrow production, most commonly from erythropoietin deficiency in CKD patients with adequate iron stores 3
• An elevated reticulocyte count suggests appropriate bone marrow response to hemolysis or bleeding 3, 4
• The reticulocyte index (adjusted for degree of anemia) provides more accurate assessment than absolute count alone 3

Red Cell Indices Provide Early Clues

• Low MCH with elevated RDW is highly suggestive of iron deficiency, even before frank anemia develops 1
• Low MCHC suggests hypochromia, which often accompanies iron deficiency even when MCV remains normal 1
• Normal MCV with elevated RDW suggests mixed nutritional deficiencies or early iron deficiency 1

When to Evaluate Bone Marrow

Abnormalities in two or more cell lines (anemia plus leukopenia or thrombocytopenia) warrant hematology consultation and likely bone marrow evaluation 3

Common Pitfalls to Avoid

• Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause 2
• Watch for combined deficiencies (iron plus B12 deficiency), especially in elderly patients and those with inflammatory bowel disease 2
• Do not delay gastroenterology referral in patients with iron deficiency, as dual pathology (upper and lower GI bleeding) occurs in 1-10% of patients 4
• In CKD patients not on erythropoietin therapy, finding iron deficiency should prompt careful assessment for gastrointestinal bleeding 3

Special Population: Chronic Kidney Disease

For CKD patients specifically:

• Monitor hemoglobin at least every 3 months in patients with GFR <30 mL/min/1.73 m² 2
• Initiate workup when hemoglobin drops below 12 g/dL in adult males and postmenopausal females, or below 11 g/dL in premenopausal females 2
• If GFR <30 mL/min/1.73 m², consider nephrology referral for evaluation of anemia of chronic kidney disease 4