Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria
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...
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Taylor & Francis Group
2024-12-01
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| Series: | Hematology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16078454.2024.2329030 |
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| author | David Dingli Carlos De Castro III Jamie Koprivnikar Austin Kulasekararaj Jaroslaw Maciejewski Brian Mulherin Jens Panse Vinod Pullarkat Alexander Röth Jamile Shammo Louis Terriou Ilene Weitz Irina Yermilov Sarah Gibbs Michael Broder David Beenhouwer David Kuter |
| author_facet | David Dingli Carlos De Castro III Jamie Koprivnikar Austin Kulasekararaj Jaroslaw Maciejewski Brian Mulherin Jens Panse Vinod Pullarkat Alexander Röth Jamile Shammo Louis Terriou Ilene Weitz Irina Yermilov Sarah Gibbs Michael Broder David Beenhouwer David Kuter |
| author_sort | David Dingli |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9910639b99bf41af8dfaccc4685e89c0 |
| institution | OA Journals |
| issn | 1607-8454 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hematology |
| spelling | doaj-art-9910639b99bf41af8dfaccc4685e89c02025-08-20T01:59:09ZengTaylor & Francis GroupHematology1607-84542024-12-0129110.1080/16078454.2024.2329030Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuriaDavid Dingli0Carlos De Castro III1Jamie Koprivnikar2Austin Kulasekararaj3Jaroslaw Maciejewski4Brian Mulherin5Jens Panse6Vinod Pullarkat7Alexander Röth8Jamile Shammo9Louis Terriou10Ilene Weitz11Irina Yermilov12Sarah Gibbs13Michael Broder14David Beenhouwer15David Kuter16Mayo Clinic, Rochester, MN, USADuke University Medical Center, Duke Cancer Institute, Durham, NC, USAHackensack University Medical Center, Hackensack, NJ, USAKing’s College Hospital and King’s College London, London, EnglandCleveland Clinic, Cleveland, OH, USAHematology Oncology of Indiana, PC, American Oncology Network, Indianapolis, IN, USARWTH Aachen University Hospital, Aachen, Germany + Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, GermanyCity of Hope, Duarte, CA, USAWest German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyNorthwestern University Feinberg School of Medicine, Chicago, IL, USAUniversity Hospital of Lille, Lille, FranceKeck School of Medicine at the University of Southern California, Los Angeles, CA, USAPHAR, Beverly Hills, CA, USAPHAR, Beverly Hills, CA, USAPHAR, Beverly Hills, CA, USAPHAR, Beverly Hills, CA, USAMassachusetts General Hospital, Boston, MA, USAIntroduction: 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.https://www.tandfonline.com/doi/10.1080/16078454.2024.2329030(Need 8): ConsensusAplastic anemiaBone marrow failureCoagulation disordersComplement inhibitorsHemolysis |
| spellingShingle | David Dingli Carlos De Castro III Jamie Koprivnikar Austin Kulasekararaj Jaroslaw Maciejewski Brian Mulherin Jens Panse Vinod Pullarkat Alexander Röth Jamile Shammo Louis Terriou Ilene Weitz Irina Yermilov Sarah Gibbs Michael Broder David Beenhouwer David Kuter Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria Hematology (Need 8): Consensus Aplastic anemia Bone marrow failure Coagulation disorders Complement inhibitors Hemolysis |
| title | Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria |
| title_full | Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria |
| title_fullStr | Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria |
| title_full_unstemmed | Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria |
| title_short | Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria |
| title_sort | expert consensus on the management of pharmacodynamic breakthrough hemolysis in treated paroxysmal nocturnal hemoglobinuria |
| topic | (Need 8): Consensus Aplastic anemia Bone marrow failure Coagulation disorders Complement inhibitors Hemolysis |
| url | https://www.tandfonline.com/doi/10.1080/16078454.2024.2329030 |
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