Confirmatory test by working category
Microcytic, hypoproliferative
- Leading causes: iron deficiency, thalassemia trait, anemia of chronic disease
- Confirmatory test: iron studies (serum iron, ferritin, transferrin saturation, total iron-binding capacity)
- Add hemoglobin electrophoresis when the RDW is normal and target cells are prominent, which favors thalassemia trait
Normocytic, hypoproliferative
- Leading causes: anemia of chronic disease, early iron deficiency, marrow failure
- Confirmatory test: markers of inflammation plus iron studies; add a marrow examination when cytopenias are present in more than one lineage
Macrocytic, hypoproliferative
- Leading causes: vitamin B12 deficiency, folate deficiency, hypothyroidism, medication effect
- Confirmatory test: serum B12 and folate, with methylmalonic acid when the B12 result is borderline
Reticulocytosis (loss or destruction)
- Leading causes: hemolysis, recent blood loss
- Confirmatory test: hemolysis panel — lactate dehydrogenase, haptoglobin, indirect bilirubin, direct antiglobulin test
- Add hemoglobin electrophoresis when the smear suggests a hemoglobinopathy
The test is chosen to answer the single question that the working category leaves open. In the microcytic hypoproliferative category, that question is whether body iron stores are depleted, so ferritin is the most informative single measurement because it reflects stored iron. In the macrocytic hypoproliferative category, the open question is whether B12 or folate is deficient, so those two measurements are ordered together because the two deficiencies produce overlapping smears. In the reticulocytosis branch, the open question is whether red cells are being destroyed inside the circulation or lost outside it, so the hemolysis panel is ordered as a group because no single member is sensitive enough alone. A marrow examination is reserved for the case where the category is hypoproliferative and more than one cell line is reduced, because that pattern points to a production problem at the level of the marrow rather than a single missing nutrient.
Ferritin rises as an acute-phase reactant, so a normal or high ferritin does not exclude iron deficiency when inflammation is present. In that setting, transferrin saturation and the total iron-binding capacity help separate iron deficiency from anemia of chronic disease.