Chapter 5: Megaloblastic Anaemias and Other Macrocytic Anaemias

Megaloblastic Anaemias and Other Macrocytic Anaemias focuses predominantly on megaloblastic anaemias, a subset where DNA synthesis is impaired, leading to a distinct cellular morphology where the nucleus matures more slowly than the surrounding cytoplasm. This asynchrony is typically driven by deficiencies in vitamin B12 or folate, both of which are critical cofactors in the biochemical pathways that produce DNA precursors like thymidine monophosphate. Vitamin B12, or cobalamin, is acquired through animal-derived foods and requires a sophisticated absorption process involving gastric intrinsic factor and specific ileal receptors. When this process fails—often due to an autoimmune attack on gastric parietal cells that prevents intrinsic factor secretion—it results in pernicious anaemia. Folate, or pteroylglutamic acid, is found in various foods but is easily destroyed by cooking; its deficiency often stems from poor diet, malabsorption syndromes like gluten-induced enteropathy, or increased physiological demand during pregnancy. Beyond the shared clinical signs of anaemia, such as a "lemon yellow" jaundice and beefy-red glossitis, severe B12 deficiency is uniquely associated with subacute combined degeneration of the spinal cord due to defective myelin methylation. Furthermore, maternal deficiency in these vitamins is a significant risk factor for neural tube defects in developing fetuses. Diagnostic investigations rely on identifying oval macrocytes and hypersegmented neutrophils in the blood, alongside bone marrow findings of hypercellularity, lacy nuclear chromatin, and giant metamyelocytes. The chapter also differentiates these conditions from non-megaloblastic macrocytosis, which can be caused by factors like chronic alcohol consumption, liver disease, or certain cytotoxic drugs. Proper management requires accurate identification of the underlying deficiency, as treating B12-deficient patients with folate alone can mask the anaemia while allowing irreversible neurological damage to progress.