Anemia Mechanisms

Anemia is classified by three fundamental mechanisms: decreased RBC production (hypoproliferative), increased RBC destruction (hemolytic), and blood loss (acute or chronic). The reticulocyte production index (RPI) is the key discriminator — an RPI <2 indicates hypoproliferative anemia (the marrow is failing to compensate), while RPI >2 indicates appropriate marrow response to peripheral destruction or blood loss. Hypoproliferative anemias are further subclassified by MCV: microcytic (MCV <80 fL) suggests iron deficiency, thalassemia, sideroblastic anemia, or lead poisoning (mnemonic: TAILS); normocytic (MCV 80-100 fL) suggests anemia of chronic disease, CKD, aplastic anemia, or early iron/B12 deficiency; macrocytic (MCV >100 fL) suggests B12/folate deficiency (megaloblastic) or liver disease, hypothyroidism, myelodysplasia (non-megaloblastic). Hemolytic anemias are classified as intrinsic (RBC defects: membrane disorders like spherocytosis, enzyme defects like G6PD deficiency, hemoglobinopathies like sickle cell) versus extrinsic (immune-mediated autoimmune hemolytic anemia, microangiopathic hemolytic anemia in TTP/HUS/DIC, mechanical valves, infections). The hemolysis workup reveals elevated LDH, elevated indirect bilirubin, decreased haptoglobin (consumed binding free hemoglobin), elevated reticulocyte count, and schistocytes on peripheral smear in microangiopathic processes.