Initial Workup for Anemia
Order a complete blood count with red cell indices, absolute reticulocyte count, iron studies panel (serum ferritin, transferrin saturation, total iron-binding capacity), vitamin B12 and folate levels, and C-reactive protein simultaneously at initial presentation. 1, 2, 3
Essential Laboratory Tests to Order Together
The following tests should be obtained as a comprehensive panel at the first encounter:
Complete blood count (CBC) with hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, white blood cell count with differential, and platelet count 1, 2, 3
Absolute reticulocyte count to assess bone marrow response—a low count indicates impaired erythropoiesis while an elevated count suggests increased red cell production or hemolysis 1, 2, 3
Iron studies panel including serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity 1, 2, 3
Vitamin B12 and folate levels to evaluate for nutritional deficiencies 1, 2, 3
C-reactive protein (CRP) to assess for inflammation that may affect ferritin interpretation 1, 2
Interpreting Key Laboratory Values
Iron Studies Interpretation
Serum ferritin < 30 μg/L confirms iron deficiency in the absence of inflammation 1, 2
Transferrin saturation < 15-16% supports iron deficiency and is less affected by inflammation than ferritin 1, 2
Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease—always interpret in clinical context 1, 2, 3
Elevated ferritin with low TSAT suggests anemia of chronic inflammation 2
MCV-Based Classification (Use with Caution)
Microcytic anemia (MCV < 80 fL) most commonly indicates iron deficiency, but can also represent thalassemia trait, anemia of chronic disease, or sideroblastic anemia 1, 2, 3
Normocytic anemia (MCV 80-100 fL) may indicate acute blood loss, hemolysis, anemia of chronic disease, early iron deficiency, or chronic kidney disease 1, 2, 3
Macrocytic anemia (MCV > 100 fL) suggests vitamin B12 or folate deficiency, medications, alcohol use, or myelodysplastic syndrome 1, 2, 3
Critical Pitfall: Don't Rely on MCV Alone
MCV-guided classification can be misleading—in one study, 16% of microcytic patients had etiologies inconsistent with expected causes, and 90% of macrocytic patients had unexpected etiologies 4
Order the full laboratory panel regardless of MCV rather than using MCV to guide which tests to order 4
Low MCH with elevated RDW is highly suggestive of iron deficiency even when MCV remains normal, with 72% sensitivity for detecting iron deficiency 1
When to Pursue Additional Testing
Hemolysis Workup
If reticulocyte count is elevated, measure:
- Haptoglobin (decreased in hemolysis) 1
- LDH (elevated in hemolysis) 1
- Indirect bilirubin (elevated in hemolysis) 1
When to Consult Hematology
Abnormalities in two or more cell lines (bicytopenia or pancytopenia) warrant immediate hematology consultation 2
Unexplained anemia after initial workup is unrevealing 2
Consider bone marrow aspiration and biopsy when additional cytopenias are present or diagnosis remains unclear 2
Investigating Underlying Causes
In adult men and postmenopausal women with confirmed iron deficiency, investigate for gastrointestinal bleeding 1, 2
In premenopausal women, assess menstrual losses as a potential cause 1
If iron studies are normal with microcytosis, obtain hemoglobin electrophoresis to evaluate for thalassemia trait, particularly in patients of appropriate ethnic background 1
Common Pitfalls to Avoid
Never assume anemia is "normal aging" in elderly patients—always investigate the underlying cause 3
Watch for combined deficiencies (iron plus B12, especially in elderly patients and those with inflammatory bowel disease) 3
Don't order tests sequentially based on MCV—order the comprehensive panel upfront to avoid delays and missed diagnoses 4
Remember that normal MCV does not exclude iron deficiency—early iron deficiency can present with normal MCV but low MCH and elevated RDW 1