Paroxysmal nocturnal hemoglobinuria: Where we stand

Abstract

For the last 20 years, therapy of paroxysmal nocturnal hemoglobinuria (PNH) relied-up until recently-on antibody based terminal complement inhibitionon. PNH pathophysiology-a mutational defect leading to partial or complete absence of complement-regulatory proteins on blood cells-leads to intravascular hemolysis and consequences such as thrombosis and other sequelae. A plethora of new drugs interfering with the proximal and terminal complement cascade are under recent development and the first "proof-of-pinciple" proximal complement inhibitor targeting C3 has been approved in 2021. "PNH: where we stand" will try to give a brief account on where we came from and where we stand focusing on approved therapeutic options. The associated improvements as well as potential consequences of actual and future treatments as well as their impact on the disease will continue to necessitate academic and scientific focus on improving treatment options as well as on side effects and outcomes relevant to individual patient lives and circumstances in order to develop effective, safe, and available treatment for all hemolytic PNH patients globally.Note: Due to space limitation the author mostly cites reviews and overviews, giving readers the chance to easily find continuative summaries of potentially interesting topics. He therefore does apologize

Functional Analysis of a Novel Complement C5a Receptor 1-Blocking Monoclonal Antibody

“…Whether this effect primarily occurs via inhibition of C5a generation, the formation of the terminal complement complex, or both is still unresolved. In PNH, it is most likely that C5b-9 formation is the most important mediator of this hemolytic disease [32], but in several other diseases, C5a might be the most important mediator.…”

Multisite Thrombosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria

“…Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare bone marrow disorder caused by acquired mutations in the phosphatidylinositol glycan class A gene, which lead to a partial or total loss of the cellular complement regulators CD55 and CD59. 1 In addition to complement-mediated hemolysis and cytopenia, venous and arterial thromboses at multiple and/or unusual sites are a common complication and occur in up to 44% of patients in historic PNH cohorts. 1,2 A 58-year-old woman was admitted to our emergency department with a 2-day history of rapidly progressive muscle weakness of all extremities and altered behavior (►Fig.…”

“…1 In addition to complement-mediated hemolysis and cytopenia, venous and arterial thromboses at multiple and/or unusual sites are a common complication and occur in up to 44% of patients in historic PNH cohorts. 1,2 A 58-year-old woman was admitted to our emergency department with a 2-day history of rapidly progressive muscle weakness of all extremities and altered behavior (►Fig. 1).…”

“…1,2 A 58-year-old woman was admitted to our emergency department with a 2-day history of rapidly progressive muscle weakness of all extremities and altered behavior (►Fig. 1). The patient reported severe headache and abdominal pain for about a week.…”

“…3,4 In addition, allogenic hematopoietic stem cell transplantation remains a curative option for some patients. 1 In summary, although PNH is an orphan disease, it has promising treatment options. PNH should be considered in patients with newly diagnosed thromboses, especially if located at multiple and/or unusual sites.…”