New Insights in Diagnosis and Therapy of Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is an acquired ultrarare disease caused by a somatic mutation of PIGA gene located at band 22 of the short arm of the X chromosome, which is unable to carry out the synthesis of glycosil-phosphatidyl-inositol. The loss of complement regulators CD55 and CD59 is associated with the lack of the protective complement regulators in RBCs that become highly susceptible to complement-mediated lysis. PNH is characterized by intravascular hemolysis, high prevalence of thrombotic events, and a variable degree of bone marrow failure. It may arise from aplastic anemia, myelodysplasia and myeloproliferative neoplasms. Recently, a new clinical variant of PNH has been reported, the so-called “ahemolytic white blood cell PNH”, which may be associated with thrombotic episodes. In 2006, the introduction of eculizumab therapy has revolutionized the treatment for PNH patients. More recently, ravulizumab, crovalimab, iptacopan, danicopan, and pegcetacoplan have been introduced in the marketplace, with short/medium-term data supporting their safety and effectiveness. However, no trial has directly compared the clinical outcomes of the new drugs, and also the inclusion criteria in the various phase 3 trials were different, making a comparison between them difficult and unsatisfactory. It is conceivable that artificial intelligence and machine learning-based scoring models may be crucial for predicting the effectiveness of the anti-complement therapy.