Acquired Aplastic Anaemia and Paroxysmal Nocturnal Haemoglobinuria

Aplastic anaemia (AA) is a rare bone marrow failure characterised by pancytopenia and a hypocellular bone marrow. Although AA is commonly acquired, idiopathic and immune mediated, late onset inherited AA secondary to DNA repair defects, telomere maintenance disorders need to be carefully excluded. AA is characterised by quantitative and qualitative defects in haemopoietic stem cells. The aberrant immune response seen in acquired AA, secondary to an unknown initiating event (viral infection or drugs), triggers expansion of auto-reactive cytotoxic CD8+ T-cells. Thus treatment modalities are either immunosuppressive therapy [antithymocyte globulin (ATG) and ciclosporin] or allogeneic haematopoietic stem cell transplant (HSCT); the latter treatment resulting not only in replacement of the haemopoietic compartment but also much of the immune system. Overall survival has improved dramatically reaching up to 80% with both treatment modalities. Long term follow-up after ATG to monitor for relapse, clonal disorders and haemolytic paroxysmal nocturnal haemoglobinuria (PNH) is essential. PNH is unique as an acquired haemolytic disorder in which the defect is intrinsic to the red cell and leads to abnormal susceptibility to activated complement. Patients have a propensity to develop thromboses that are frequently life-threatening. PNH is also associated with bone marrow failure and indeed may provide a unique insight into the pathophysiology of a variety of bone marrow failure syndromes. The development of targeted therapy, terminal complement inhibitor eculizumab, has revolutionised the treatment paradigm and altered the natural history of this debilitating disease.