Clinical meaning
Anemia is classified by mechanism into three categories: decreased production (hypoproliferative), increased destruction (hemolytic), and blood loss. The reticulocyte production index (RPI) is the key discriminator: RPI <2 indicates inadequate marrow response (production problem), while RPI >2 indicates appropriate marrow response to peripheral red cell loss (destruction or hemorrhage). Decreased production anemias are further classified by MCV: microcytic (MCV <80 fL) includes iron deficiency, thalassemia, anemia of chronic disease, and sideroblastic anemia; normocytic (MCV 80-100 fL) includes anemia of chronic disease, renal failure (erythropoietin deficiency), aplastic anemia, and myelophthisic processes; macrocytic (MCV >100 fL) includes megaloblastic causes (B12 and folate deficiency with hypersegmented neutrophils) and non-megaloblastic causes (liver disease, hypothyroidism, myelodysplastic syndrome, medications). Hemolytic anemias are classified as intrinsic (intracorpuscular defects: membrane disorders like hereditary spherocytosis, enzyme defects like G6PD deficiency, hemoglobinopathies like sickle cell disease) versus extrinsic (extracorpuscular: autoimmune hemolysis with positive direct Coombs test, mechanical destruction/microangiopathic hemolytic anemia with schistocytes, infections like malaria). Hemolysis markers include elevated LDH, elevated indirect bilirubin, decreased haptoglobin, elevated reticulocyte count, and urinary hemosiderin. The clinician integrates CBC morphology, reticulocyte index, iron studies, B12/folate levels, hemolysis markers, peripheral smear findings, and bone marrow biopsy results to establish the specific etiology and guide targeted therapy.