Once the corrected count or production index places the patient in a branch, the MCV category from the previous chapter tells you which differential to open.
A high reticulocyte response means the marrow is working, so the anemia comes from red cells being lost or destroyed. Blood loss may be acute, as in trauma or a bleeding ulcer, or chronic and occult, as in a slowly bleeding colon lesion. Hemolysis means red cells are destroyed in the circulation, from immune causes, membrane defects such as hereditary spherocytosis, enzyme deficiencies such as G6PD deficiency, mechanical fragmentation from prosthetic valves or microangiopathy, or hemoglobinopathies. The MCV helps here: a high reticulocyte count with a normocytic or macrocytic picture fits hemolysis or acute blood loss, while a high count with microcytosis suggests a hemoglobinopathy such as thalassemia or a chronic blood loss that has depleted iron stores.
A low reticulocyte response means the marrow is not keeping up. The differential includes marrow failure from aplastic anemia, infiltration by malignancy, or fibrosis; nutritional deficiency of iron, vitamin B12, or folate; anemia of chronic disease driven by inflammation and hepcidin; and chronic kidney disease from erythropoietin deficiency. The MCV again narrows the list: low reticulocytes with microcytosis point to iron deficiency or anemia of chronic disease, low reticulocytes with macrocytosis point to B12 or folate deficiency or myelodysplasia, and low reticulocytes with normocytosis point to anemia of chronic disease, early deficiency, or marrow failure. A mixed picture, such as a patient with both iron deficiency and B12 deficiency, can produce a normal MCV while the reticulocyte count stays low.