Erythrocyte Disorders
Approach to erythrocyte disorders
Classify anemia by MCV and reticulocyte response before ordering specialized tests. A low corrected reticulocyte count indicates a production problem; a high count indicates loss or destruction (bleeding, hemolysis). Confirm hemolysis with at least two of: elevated LDH, elevated indirect bilirubin, low haptoglobin, increased reticulocytes; then the direct antiglobulin test separates immune from non-immune causes.
Microcytic anemia: iron deficiency (low ferritin, high RDW, high TIBC, low saturation), thalassemia trait (normal iron studies, low RDW, target cells, basophilic stippling, high HbA2), anemia of inflammation (low iron, low TIBC, normal or high ferritin), sideroblastic anemia (ring sideroblasts on Prussian blue). Normocytic: early iron deficiency, inflammation, renal disease, aplastic anemia, marrow infiltration, hemolysis. Macrocytic: B12/folate deficiency (hypersegmented neutrophils, elevated methylmalonic acid in B12 deficiency), alcohol and liver disease, drugs, hypothyroidism, and myelodysplasia (dysplasia, not macrocytosis alone).
Membrane and enzyme defects: hereditary spherocytosis (spherocytes, increased MCHC, abnormal EMA binding or osmotic fragility, negative DAT), G6PD deficiency (bite cells, Heinz bodies; test after hemolysis resolves because reticulocytes are enzyme-rich), and paroxysmal nocturnal hemoglobinuria (flow cytometry for CD55/CD59 on red cells and CD14/CD24 on monocytes).
Trap: a normal ferritin does not exclude iron deficiency during inflammation, and a normal MCV does not exclude combined deficiencies such as iron plus B12.
Rule of thumb: Mentzer index = MCV/RBC; a value below 13 favors thalassemia trait, above 13 favors iron deficiency.