Paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is a unique disorder in which many of the patient’s red cells have an abnormal susceptibility to activated complement. This results from the presence of a clone that originates from a haematopoietic stem cell bearing an acquired somatic mutation in the X-linked gene PIGA, required for the biosynthesis of the glycosylphosphatidylinositol molecule which anchors many proteins to the cell membrane, including the complement regulators CD59 and CD55. The ‘classical’ presentation is with ‘passing blood instead of urine’ (haemoglobinuria). Sometimes the patient presents with the full triad of (1) haemolytic anaemia, (2) pancytopenia, and (3) thrombosis—most commonly of intra-abdominal veins. An element of bone marrow failure is always present; and sometimes the disease may be preceded by or may evolve to bone marrow aplasia indistinguishable from acquired aplastic anaemia. Definitive diagnosis is based on demonstrating the presence of a discrete population of ‘PNH red blood cells’ by flow cytometry using anti-CD59. In most cases, especially when the patient is transfusion dependent and/or has severe signs and symptoms, there is an indication for long-term treatment with the complement inhibitor eculizumab.