Erythrocyte Disorders and Anemias
Anemia classification and laboratory reasoning
Anemias are approached by MCV and reticulocyte response. Microcytic hypochromic causes include iron deficiency (low ferritin, high TIBC, low saturation, high RDW), thalassemia (normal or high ferritin, often normal RDW, target cells, basophilic stippling), anemia of chronic disease (low TIBC, normal or high ferritin, low saturation), and sideroblastic anemia (ring sideroblasts, lead, alcohol, B6 deficiency). Normocytic anemia with reticulocytosis suggests hemolysis or blood loss; confirm with LDH, indirect bilirubin, haptoglobin, and DAT. Hemolytic patterns include spherocytes in autoimmune hemolysis, bite cells and Heinz bodies in G6PD deficiency, schistocytes in microangiopathy, and PNH detected by CD55/CD59 flow cytometry. Macrocytic anemia divides into megaloblastic (B12/folate deficiency, hypersegmented neutrophils, pancytopenia) and nonmegaloblastic (liver disease, alcohol, hypothyroidism, reticulocytosis, MDS). Iron studies, hemoglobin electrophoresis/HPLC, osmotic fragility, EMA binding, and genetic testing resolve ambiguous cases.
Traps: ferritin is an acute-phase reactant and can look normal in iron deficiency with inflammation; TIBC falls in chronic disease. B12 deficiency causes neurologic signs, folate deficiency usually does not. Spherocytes are not specific for hereditary spherocytosis. Combined iron and B12 deficiency can normalize MCV. A high reticulocyte count can raise MCV.
Worked example: Hb 90 g/L, MCV 72 fL, RDW normal, ferritin 150 µg/L, target cells-this is thalassemia trait, not iron deficiency. Mentzer index (MCV/RBC) below 13 supports thalassemia.