Ana Villegas-Martínez, Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, Madrid, España
Mónica Ballesteros-Andrés, Servicio de Hematología, Hospital General Universitario Gregorio Marañón, Madrid. España
Santiago Bonanad-Boix, Hospital Universitario y Politécnico La Fe, Valencia, España
F. Ataulfo González-Fernández, Servicio de Hematología, Hospital Clínico San Carlos, Madrid; 2Servicio de Hematología, Hospital General Universitario Gregorio Marañón, Madrid. España
Inés Hernández-Rodríguez, Servicio de Hematología y Hemoterapia, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain
Isidro Jarque-Ramos, Servicio de Hematología, Hospital Universitari i Politécnic La Fe, Valencia. España
Ramiro J. Núñez-Vázquez, Hospital Universitario Virgen del Rocío, Sevilla, España
Amparo Sempere-Talens, Servicio de Hematología, Hospital Universitario y Politécnico La Fe; Grupo de Investigación Hematología, IISLAFE; Valencia, España
Pedro Puerta-Alcalde, Servicio de Inmunología, Hospital Clínic de Barcelona, Barcelona. España
David Beneitez-Pastor, Servicio de Hematología y Hemoterapia, Hospital Universitari Vall d’Hebron, Barcelona, Spain
Anna Gaya-Valls, Servicio de Inmunología, Hospital Clínic de Barcelona, Barcelona. España
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.
Keywords: Paroxysmal nocturnal hemoglobinuria; Diagnosis; Treatment; Inhibitors of proximal complement; Inhibitors of terminal complement