Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Abstract The understanding of the clinical manifestations in paroxysmal nocturnal haemoglobinuria (PNH) has made great progress. The main symptoms of this disease such as abdominal pain, renal failure or pulmonary hypertension and even the basis of the dramatic thrombophilia can be related to intravascular haemolysis and liberation of free haemoglobin resulting in NO depletion. In addition, there has been a recent great progress in elucidating the pathophysiology of clonal expansion within PNH bone marrow. In the majority of patients with haemolytic PNH, there are additional mutations within genes beyond PIG‐A and rather affecting growth and differentiation of clonal bone marrow cells. In contrast to the formerly proposed single mechanism hypotheses such as immune selection or intrinsic gain of clonal dominance, this appears to follow a pattern of a complex clonal hierarchy putatively integrating both earlier anticipated mechanisms. Treatment of PNH is mainly supportive. The only curative approach as allogeneic stem cell transplantation should only be applied to patients with complications such as secondary bone marrow aplasia or transformation into MDS or AML. Symptomatic haemolytic PNH will be treated with eculizumab, an inhibitor of the terminal complement cascade. Treatment with eculizumab can significantly prevent PNH‐related symptoms including the abnormal thrombophilia. Recently, it was demonstrated that in contrast to untreated historic PNH patients, meanwhile a n...
Source: European Journal of Haematology - Category: Hematology Authors: Tags: Review Article Source Type: research