Comprehensive approach to paroxysmal nocturnal hemoglobinuria for the correct identification of patients who may benefit from switching from iC5 to iCP – expert consensus opinion

Marta Morado-Arias, Servicio de Hematología y Hemoterapia, Hospital Universitario La Paz, Madrid, España
Mónica Ballesteros-Andrés, Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, España
Alejandro Contento-Gonzalo, Servicio de Hematología, Hospital Carlos Haya, Málaga, España
Miguel Gómez-Álvarez, Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, Madrid, España
Carmen González-González, Servicio de Hematología y Hemoterapia, Hospital Universitario de Donostia, Donostia, Gipuzkoa, España
Ana P. González-Rodríguez, Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, España
Amparo Sempere-Talens, Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Valencia, España

Introduction: Paroxysmal nocturnal hemoglobinuria is a rare disease characterized by hemolytic anemia predominantly intravascular and cytopenias. Complement terminal C5 inhibitors (C5i) have significantly altered the treatment landscape. Objective: To facilitate the identification of patients with suboptimal response to C5i secondary to anemia and/or fatigue who may benefit from a therapeutic switch to proximal complement inhibitors (CPi). Material and methods: Narrative review with a collaborative methodology based on the clinical opinion of paroxysmal nocturnal hemoglobinuria experts, supported by scientific evidence. Results: First, diagnostic and treatment monitoring tests, differences between intravascular and extravascular hemolysis, and the utility of cytometric studies are detailed. A questionnaire for patients is proposed to identify the persistence of symptoms. Finally, the consequences of persistent anemia and/or chronic hemolysis are reviewed, along with recommendations for managing iron overload. Conclusions: Although C5i improves survival, treatment response is often suboptimal, which affects patients’ quality of life. This document provides tools to identify patients with clinically significant hemolysis who may benefit from an CPi.

Keywords: Paroxysmal nocturnal hemoglobinuria. Intravascular hemolysis. Extravascular hemolysis. Proximal complement inhibitors. Erythroid clone. Iron overload.