Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria

Abstract

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, non-malignant hematologic disease characterized by complement-mediated hemolysis (with or without hemoglobinuria), fatigue, increased susceptibility to thrombosis, and bone marrow dysfunction. The development of complement inhibitors has transformed outcomes for patients with PNH, but patients may still experience pharmacodynamic breakthrough hemolysis (BTH), which can be caused by exposure to a complement amplifying condition (CAC), such as vaccination, infection, or surgery.

Materials and methods: A 13-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on how to classify pharmacodynamic BTH in patients with complement-inhibitor treated PNH. Physicians reviewed literature, rated the appropriateness of over 400 scenarios, and discussed the ratings at an in-person meeting.

Results: After the meeting, the panel agreed on 77% of scenarios. Here, we present the group's agreed-upon recommendations on how to manage BTH caused by a CAC, as well as provide a severity classification system for BTH and strategies to mitigate risk of BTH in special circumstances (e.g. vaccination, planned or unplanned surgery, and pregnancy).

Discussion: In general, as severity of BTH increased, experts agreed more interventions to manage the BTH were appropriate. These recommendations are based on clinical experience and opinion. Without clear data from randomized trials to guide the management of BTH, expert opinion can be useful to support patient care.

Keywords: (Need 8): Consensus; Aplastic anemia; Bone marrow failure; Coagulation disorders; Complement inhibitors; Hemolysis; Paroxysmal nocturnal hemoglobinuria; Red cell disorders.