LAUSR

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder that affects about 1-1,5 cases per million individuals, characterized by hemolysis, peripheral blood cytopenia, bone marrow dysfunction, thrombosis, renal impairment and arterial and pulmonary hypertension. The first case of PNH was probably described in 1793 by a surgeon, Dr Charles Stewart, in the medical commentaries “Account of a singular periodical discharge of blood from the urethra”. In the following decades several cases have been reported by the most eminent physicians and scientists of the time. In 1882 Paul Strübing was the first to identify PNH as a new disease entity. Hijmans in 1911 considered the possibility that the complement system mediated the hemolysis of PNH erythrocytes and in the same year, Italian scientists Ettore Marchiafava and Nazari scrupulously described the pathogenesis of the affection. In the 1925 Enneking introduced for the first time the name “paroxysmal nocturnal hemoglobinuria”, to define this pathology. Despite the increased knowledge of this syndrome, therapies for PNH were still only experimental and symptomatic, with the use of antimicrobial agents, corticosteroids and blood transfusions. The natural history of PNH changed remarkably only in the 2007, with the introduction of Eculizumab complement blockade agent. The Ravulizumab, a long-acting C5 complement inhibitor approved on December 2018 by the U.S. food and drug Administration (FDA), and on July 2019 by the European Commission, represent a new promising instrument for PNH treatment. Second generation of anti-complement agents are currently under investigation, representing future promising instruments for the treatment of PNH.