Article
Hematology
Gloria F. Gerber, Robert A. Brodsky
Summary: This article discusses the theoretical basis and clinical studies of using C3 inhibitors in the treatment of PNH, as well as provides suggestions for treatment sequencing.
Article
Medicine, General & Internal
Peter Hillmen, Jeff Szer, Ilene Weitz, Alexander Roeth, Britta Hoechsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos de Castro, Hisakazu Nishimori, Lisa Tan, Mohamed Hamdani, Pascal Deschatelets, Cedric Francois, Federico Grossi, Temitayo Ajayi, Antonio Risitano, Regis Peffault de la Tour
Summary: The study demonstrated that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Review
Hematology
Robert A. Brodsky
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-mediated hemolytic anemia with diverse manifestations, requiring differentiated treatment approaches; terminal complement inhibition is effective for intravascular hemolysis treatment but not bone marrow failure; novel complement inhibitors under clinical development show promising prospects for future applications.
Article
Hematology
Britta Hoechsmann, Flore Sicre de Fontbrune, Jong Wook Lee, Alexander D. Kulagin, Peter Hillmen, Amanda Wilson, Jing L. Marantz, Hubert Schrezenmeier
Summary: A study evaluated the effects of eculizumab treatment in PNH patients and found that it significantly improved outcomes in terms of reducing hemolysis, MAVE rates, TEs, and transfusions.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Raymond Siu Ming Wong, Juan Ramon Navarro-Cabrera, Narcisa Sonia Comia, Yeow Tee Goh, Henry Idrobo, Daolada Kongkabpan, David Gomez-Almaguer, Mohammed Al-Adhami, Temitayo Ajayi, Paulo Alvarenga, Jessica Savage, Pascal Deschatelets, Cedric Francois, Federico Grossi, Teresita Dumagay
Summary: PNH is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan, the first C3-targeted therapy, has shown superior efficacy and safety compared to supportive care in complement inhibitor-naive patients with PNH, leading to significant stabilization of hemoglobin levels and reduction in lactate dehydrogenase levels.
Review
Hematology
David Dingli, Jaroslaw P. Maciejewski, Loree Larratt, Ronald S. Go, Britta Hoechsmann, Ke Zu, Philippe Gustovic, Alexander D. Kulagin
Summary: This study investigated the relationship between the proportion of GPI-deficient granulocytes at PNH onset and the risk for major adverse vascular events (MAVEs) and other parameters at last follow-up. It found that a higher proportion of GPI-deficient granulocytes at baseline was associated with increased risk of MAVEs, high disease activity, elevated lactate dehydrogenase (LDH) ratio, and higher rates of MAVEs and thrombotic events (TEs). Fatigue was present in most patients, while abdominal pain was more frequently reported with larger clone size. These findings suggest that baseline clone size can indicate disease burden and risk of MAVEs and TEs in PNH patients.
ANNALS OF HEMATOLOGY
(2023)
Review
Immunology
Melissa A. Colden, Sushant Kumar, Bolormaa Munkhbileg, Daria V. Babushok
Summary: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease that involves mutations in a specific gene, leading to hemolysis and abnormal clonal expansion of blood cells. The mechanisms behind this expansion are still debated, but recent advancements in research and technology offer new opportunities for understanding the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Hematology
Jens Panse
Summary: In the past 20 years, therapy for paroxysmal nocturnal hemoglobinuria (PNH) mainly relied on antibody-based terminal complement inhibition. PNH is a disease characterized by a mutation that causes the absence or deficiency of complement-regulatory proteins on blood cells, leading to intravascular hemolysis and related complications. Recently, there has been a development of new drugs targeting the proximal and terminal complement cascade, with the approval of the first proximal complement inhibitor targeting C3 in 2021. This article aims to provide an overview of the progress made in PNH treatment and discuss the approved therapeutic options, as well as the potential impact and consequences of current and future treatments on patients' lives.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Deniz Goren Sahin, Olga Meltem Akay, Muzaffer Keklik, Vahap Okan, Abdullah Karakus, Cengiz Demir, Mehmet Ali Erkurt, Kadir Ilkkilic, Rahsan Yildirim, Gulsum Akgun Cagliyan, Salih Aksu, Mehmet Hilmi Dogu, Mehmet Sinan Dal, Volkan Karakus, Ali Ihsan Gemici, Hatice Terzi, Engin Kelkitli, Serdar Sivgin, Ali Unal, Mehmet Yilmaz, Orhan Ayyildiz, Serdal Korkmaz, Bulent Eser, Fevzi Altuntas
Summary: This study aimed to collect PNH patient data from hematology centers across Turkey to identify clinical features and management. After evaluating patients from 19 different institutions, it was found that fatigue and abdominal pain were the most frequent presenting symptoms. This study provided valuable information for understanding the disease and differences between patients in Turkey and existing literature.
ANNALS OF HEMATOLOGY
(2021)
Review
Hematology
Austin G. Kulasekararaj, Ioanna Lazana
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by deficiency of GPI-linked complement regulators. Despite the introduction of C5 inhibitors, residual hemolysis still occurs, leading to anemia and transfusion dependency in some patients. The development of longer-acting and subcutaneous formulations of C5 inhibitors, as well as proximal complement inhibitors, have shown promising results in improving hemoglobin levels and reducing hemolysis. Combination treatments have also been explored. This review discusses the current therapeutic options and emerging approaches for PNH.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Austin G. Kulasekararaj, Antonio M. Risitano, Jaroslaw P. Maciejewski, Rosario Notaro, Peter Browett, Jong Wook Lee, Mingjun Huang, Michael Geffner, Robert A. Brodsky
Summary: The study showed that adding an oral complement inhibitor danicopan to PNH patients who were dependent on eculizumab led to an increase in Hgb levels, a reduction in blood transfusion requirements, and improvements in fatigue, with good tolerability.
Article
Hematology
Britta Hoechsmann, Regis Peffault de Latour, Anita Hill, Alexander Roeth, Timothy Devos, Christopher J. Patriquin, Wen-Chien Chou, Deepak Jain, Ke Zu, Chuntao Wu, Jong Wook Lee
Summary: The objective of this analysis was to identify risk factors for thromboembolic events (TE) in patients with paroxysmal nocturnal hemoglobinuria (PNH) who were not treated with C5 inhibitors. Multivariable analysis revealed that a history of TE, >= 30% GPI-negative granulocytes, and LDH ratio >= 1.5 x ULN with >= 2 high disease activity criteria are risk factors for TE in PNH patients.
ANNALS OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ioanna Lazana, Sean Apap Mangion, Selma Babiker, Joanna Large, Roochi Trikha, Mark Zuckerman, Shreyans Gandhi, Austin G. Kulasekararaj
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by hemolysis and thrombosis, with a significant impact on morbidity and mortality. This study investigated the association between respiratory virus infections and breakthrough hemolysis (BTH) in PNH patients on eculizumab treatment. The results indicate that respiratory virus infections pose a significant risk for BTH in PNH patients and highlight the need for regular screening and close monitoring of patients with respiratory symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Bruno Fattizzo, Fabio Serpenti, Juri Alessandro Giannotta, Wilma Barcellini
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease with ongoing research on its pathophysiology, diagnostics, and treatment. Advanced flow cytometry techniques have enabled detection of small PNH clones, but data interpretation remains challenging. New complement inhibitors may improve patients' quality of life and response rates, but questions regarding their use and long-term safety need further investigation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Patricia Eiko Yamakawa, Ana Rita Fonseca, Ismael Dale Cotrim Guerreiro da Silva, Matheus Vescovi Goncalves, Dirce Maria Marchioni, Antonio Augusto Ferreira Carioca, David Michonneau, Celso Arrais-Rodrigues
Summary: This study aimed to identify the dysfunctional pathways involved in the pathophysiology of PNH by comparing the metabolic profiles of PNH patients to healthy controls, as well as analyzing the metabolomic profiles before and after eculizumab treatment. The results showed significant differences in metabolomes between PNH patients and healthy controls, and eculizumab treatment appeared to improve defects in the Acyl CoA metabolism, reducing oxidative stress and inflammation.