Recent advances in the study of the molecular basis of paroxysmal nocturnal haemoglobinuria (PNH) have demonstrated that its crucial pathophysiological mechanism is the somatic mutation of the pig-A gene, with the consequent defective expression of glycosyl-phosphatidylinositol-anchored proteins on the surface of blood cells, in particular erythrocytes, which makes these cells abnormally susceptible to autologous complement activation. Even though different therapeutic approaches have been described for the treatment of PNH-associated anaemia, no definitive treatment is currently available for this disorder. We describe the more relevant of the recent insights into the pathophysiology of PNH and the effects of long-term treatment with recombinant human erythropoietin (r-HuEPO) in two patients with PNH and severe anaemia. Other aspects of these cases have been published elsewhere. In both patients, treatment with r-HuEPO was followed by a progressive increase in the concentration of haemoglobin that was then maintained with lower doses of r-HuEPO without any relevant adverse events. The clinical response to r-HuEPO was observed in spite of the fact that baseline serum erythropoietin (EPO) levels were increased and appropriate to the degree of anaemia in both patients. These results suggest that r-HuEPO may be appropriate for the long-term correction of anaemia associated with PNH, and that the response to r-HuEPO might be independent of the level of endogenous EPO, at least in patients with PNH. The hypothetical mechanism of r-HuEPO bioactivity in this particular clinical setting is discussed.
|Number of pages||7|
|Journal||Erythropoiesis: New Dimensions in the Treatment of Anaemia|
|Publication status||Published - 1998|
ASJC Scopus subject areas