Chapter 22: Aplastic Anaemia and Bone Marrow Failure

Aplastic Anaemia and Bone Marrow Failure lesson explores the critical conditions associated with bone marrow failure and the resulting depletion of all primary blood cell lines, known as pancytopenia. It focuses primarily on aplastic anaemia, a state where the bone marrow becomes hypocellular and is largely replaced by fatty tissue, often triggered by an autoimmune strike against hematopoietic stem cells. The material distinguishes between inherited syndromes, such as Fanconi anaemia—characterized by physical deformities and faulty DNA repair mechanisms—and acquired forms stemming from toxic exposures like benzene, specific medications like chloramphenicol, or viral infections such as hepatitis. Learners will delve into the molecular basis of dyskeratosis congenita, involving telomere maintenance failures, and Shwachman-Diamond syndrome, which links ribosomal defects to pancreatic and hematological issues. Furthermore, the discussion covers Paroxysmal Nocturnal Haemoglobinuria (PNH), a unique clonal disorder where a lack of protective surface proteins (GPI-anchors) leads to complement-mediated red cell destruction and dangerous blood clots. Clinical management strategies are detailed, ranging from supportive care with filtered transfusions to definitive interventions like immunosuppressive therapy using anti-thymocyte globulin, ciclosporin, and eltrombopag, as well as the curative potential of allogeneic stem cell transplantation for younger patients. Additional rare pathologies are examined, including pure red cell aplasia, often linked to parvovirus B19 or autoimmune triggers, and congenital dyserythropoietic anaemias, providing a thorough overview of the diagnostic and therapeutic landscape in modern haematology.