Current status of diagnosis and treatment of nocturnal paroxysmal hemoglobinuria. 2024

Abstract

Paroxysmal nocturnal hemoglobinuria is a rare disease caused by clonal expansion of one or more hematopoietic progenitor cells that have acquired one or more mutations in the PIG-A gene that prevent the synthesis of GPI anchor molecules necessary for the function of certain proteins on the cell surface. It causes intravascular hemolysis mediated by uncontrolled complement activation in the absence of function of the GPI-dependent regulators CD55 at the proximal level and CD59 at the terminal level. In addition, there is a predisposition to the development of thrombosis and some degree of marrow failure. Although terminal complement inhibitors (iC5) have modified survival and quality of life, not all patients achieve transfusion independence or normal hemoglobin levels. The fundamental causes may be due to bone marrow failure, residual intravascular hemolysis or extravascular hemolysis due to C3-sensitized red blood cells as a consequence of the use of anti-iC5 inhibitors, a condition that has motivated the development of proximal pathway inhibitors. In this review, we analyze in depth the diagnosis, treatment and follow-up of paroxysmal nocturnal hemoglobinuria patients with the approved inhibitors of the terminal and proximal complement pathway, and the drugs pending approval.