Chapter 11: Red Blood Cell Pathology & Anemias

A major portion of the chapter is dedicated to the classification of anemias based on Mean Corpuscular Volume (MCV), categorized into microcytic, normocytic, and macrocytic types. The discussion on microcytic anemias provides a detailed comparison between iron deficiency anemia, characterized by low ferritin and high Total Iron Binding Capacity, and the anemia of chronic disease, where iron sequestration occurs. It also thoroughly examines thalassemias, explaining the genetic deletions in alpha-thalassemia and mutations in beta-thalassemia that disrupt hemoglobin synthesis, as well as sideroblastic anemia involving ring sideroblasts. The section on normocytic anemias distinguishes between acute blood loss and hemolytic processes, further differentiating intravascular from extravascular hemolysis. Significant attention is given to the molecular basis of Sickle Cell Disease, describing the specific glutamate-to-valine substitution that leads to vaso-occlusive crises and autosplenectomy, as well as Hemoglobin C disease. Other hemolytic conditions covered include Hereditary Spherocytosis caused by membrane protein defects, Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency linked to oxidative stress and Heinz bodies, Autoimmune Hemolytic Anemia diagnosed via the Coombs test, and Paroxysmal Nocturnal Hemoglobinuria. The chapter also explores macrocytic anemias, specifically the megaloblastic types resulting from impaired DNA synthesis due to Vitamin B12 or folate deficiencies, highlighting the specific neurological consequences of B12 deficiency and the use of methylmalonic acid for differential diagnosis. Finally, the text defines polycythemia vera as a clonal myeloproliferative disorder and contrasts it with secondary polycythemia driven by erythropoietin and relative polycythemia caused by plasma volume contraction.