Review
Hematology
Jeremy W. Jacobs, Cristina A. Figueroa Villalba, Garrett S. Booth, Jennifer S. Woo, Laura D. Stephens, Brian D. Adkins
Summary: Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia that is often overlooked and challenging to diagnose due to the complicated testing methods required. A systematic review of reported cases revealed that PCH most commonly occurs in children with a preceding viral infection, and corticosteroid use is frequent but potentially ineffective. The presence of complement and absence of IgG bound to red blood cells is the most common DAT result, although other findings were observed in a third of cases.
Review
Pharmacology & Pharmacy
Zhengrui Xiao, Irina Murakhovskaya
Summary: AIHA is a rare autoimmune disorder characterized by the destruction of red blood cells mediated by autoantibodies, presenting challenges in treatment. Traditional first-line therapies have associated adverse effects and treatment failures, with high rates of relapse. Some patients are refractory to available treatments, leading to the importance of novel therapies.
Review
Medicine, General & Internal
Aikaterini Voulgaridou, Theodosia A. Kalfa
Summary: Autoimmune hemolytic anemia (AIHA) is a rare disease in children that requires prompt diagnosis and treatment. Warm AIHA and cold agglutinin syndrome caused by cold-reactive antibodies are common types, and further evaluation is needed for cases with negative DAT results. w-AIHA in children is often secondary to underlying immune dysregulation syndromes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Sigbjorn Berentsen, Wilma Barcellini, Shirley D'Sa, Bernd Jilma
Summary: Sutimlimab, the first complement inhibitor to be extensively studied in cold agglutinin disease, has shown high response rates with low toxicity. The drug appears highly useful in severely anemic patients and in those in whom chemoimmunotherapy is contraindicated or has failed. The choice of therapy in cold agglutinin disease should be individualized.
Review
Hematology
Wilma Barcellini, Bruno Fattizzo
Summary: Warm autoimmune hemolytic anemia is a disease caused by increased destruction of red blood cells by IgG autoantibodies, with complex pathogenic mechanisms and unpredictable prognosis. Treatment options include steroids, splenectomy, immunosuppressants, and rituximab, but challenges exist in choosing and managing these therapies.
Review
Hematology
Sigbjorn Berentsen, Geir E. Tjonnfjord
Summary: Cold agglutinin disease can be treated through targeted therapies focusing on clonal B-cell lymphoproliferation and complement-mediated hemolysis. Bendamustine plus rituximab combination and sutimlimab have shown success in treating the disease. Bendamustine-rituximab is effective but slow-acting, while sutimlimab is highly efficacious and acts rapidly with low toxicity.
TRANSFUSION MEDICINE REVIEWS
(2022)
Review
Hematology
Sigbjorn Berentsen
Summary: Significant progress has been made in the treatment of CAD in recent decades, with recommendations mainly based on nonrandomized trials and personal experience due to the lack of comparative trials. Individualized treatment options tailored to patients' symptoms and disease characteristics are crucial to avoid ineffective therapies.
Review
Pathology
Angela Guenther, Anne Tierens, Agnieszka Malecka, Jan Delabie
Summary: Primary cold agglutinin disease is a type of autoimmune hemolytic anemia caused by circulating antibodies against I antigen. It has been recognized as a distinct B-cell lymphoproliferative disease and has been included in the most recent classifications of mature B-cell neoplasms.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2023)
Review
Immunology
Femke V. M. Mulder, Dorothea Evers, Masja de Haas, Marjan J. Cruijsen, Sophie J. Bernelot Moens, Wilma Barcellini, Bruno Fattizzo, Josephine M. I. Vos
Summary: This article discusses severe autoimmune hemolytic anemia (AIHA), including its definition, understanding of severity and prognosis. Though there are no validated predictors for severe disease course, certain risk factors can aid in identifying severe cases. Certain serological subtypes are associated with lower hemoglobin levels, higher transfusion need and mortality. Currently, there is no evidence-based therapeutic approach, but there are general management strategies and emerging therapeutic options. Further research and development of prediction models and new drugs are needed in the future.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pediatrics
Shrutiprajna Kar, C. G. Delhi Kumar, Rakhee Kar, Abhishekh Basavarajegowda
Summary: This study aimed to investigate the triggers, clinical profile, treatment response, and outcome of autoimmune hemolytic anemia (AIHA) in children. A total of 46 children aged 1 month to 14 years were included in the study. Secondary AIHA was more common than primary AIHA, with systemic lupus erythematosus (SLE) being the most common trigger. Primary AIHA had a better prognosis.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Review
Biotechnology & Applied Microbiology
Georg Gelbenegger, Sigbjorn Berentsen, Bernd Jilma
Summary: Cold agglutinin disease (CAD) is a difficult-to-treat autoimmune hemolytic anemia and B cell lymphoproliferative disorder. This review summarizes clinical and experimental antibody-based treatments for CAD and discusses potential future treatments for CAD.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Review
Immunology
Sigbjorn Berentsen, Bruno Fattizzo, Wilma Barcellini
Summary: Autoimmune hemolytic anemia (AIHA) is a condition characterized by increased erythrocyte turnover caused by autoimmune mechanisms. Different treatment options exist for warm-antibody AIHA and cold agglutinin disease, targeting various pathways and mechanisms involved. However, the optimal treatment for AIHA is still uncertain and further evidence-based therapies are needed, emphasizing the importance of prospective clinical trials.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Alexander Roeth, Sigbjorn Berentsen, Wilma Barcellini, Shirley D'Sa, Bernd Jilma, Marc Michel, Ilene C. Weitz, Masaki Yamaguchi, Jun-ichi Nishimura, Josephine M. Vos, Michael Storek, Nancy Wong, Parija Patel, Xiaoyu Jiang, Deepthi S. Vagge, Marek Wardecki, Frank Shafer, Michelle Lee, Catherine M. Broome
Summary: Sutimlimab, a humanized monoclonal antibody, shows potential as an important advancement in the treatment of cold agglutinin disease (CAD) by selectively inhibiting the classical complement pathway and rapidly halting hemolysis.
Article
Education, Scientific Disciplines
Jenny McDade Despotovic, Taylor Olmsted Kim
Summary: Cold reactive autoimmune hemolytic anemia is a rare condition caused by the production of autoantibodies against endogenous red blood cells. Treatment mainly focuses on reducing antibody production to manage the disease.
HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM
(2022)
Article
Hematology
Zhao Wang, Lijin Bo, Yan Xu, Huijuan Liu, Yuping Zhao
Summary: Our study examined serum complement levels in 146 AIHA patients, finding reduced C3 levels in AIHA patients and a tendency towards lower C4 levels in DAT-positive patients. Serum C4 levels were negatively correlated with CAT and DAT titers, and in certain patients with positive CAT and/or DAT (anti-C3d) but negative DAT (anti-IgG), C3/C4 levels were negatively correlated with indirect bilirubin levels.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2021)
Letter
Hematology
Bruno Fattizzo, Marc Michel, Anna Zaninoni, Juri A. Giannotta, Stephanie Guillet, Henrik Frederiksen, Josephine M. I. Vos, Francesca R. Mauro, Bernd Jilma, Andrea Patriarca, Francesco Zaja, Anita Hill, Sigbjorn Berentsen, Wilma Barcellini
Letter
Hematology
Wilma Barcellini, Anna Zaninoni, Juri A. Giannotta, Giuliana Merati, Marco Capecchi, Bruno Fattizzo, Elena Trombetta, Andrea Artoni
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Physiology
Benedetta Porro, Edoardo Conte, Anna Zaninoni, Paola Bianchi, Fabrizio Veglia, Simone Barbieri, Susanna Fiorelli, Sonia Eligini, Alessandro Di Minno, Saima Mushtaq, Elena Tremoli, Viviana Cavalca, Daniele Andreini
Summary: The study highlighted the association between erythrocyte morphodynamic characteristics and plaque instability in nonob CAD patients, suggesting the use of these blood cell features in identifying high-risk patients without severe coronary stenosis. Positive correlations were found between RBC rigidity, osmotic fragility, or aggregability, and HRP features in nonob CAD group, with these RBC morphodynamic features being identified as independent predictors of non-calcified plaque volume.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Immunology
Anna Zaninoni, Juri A. Giannotta, Anna Galli, Rosangela Artuso, Paola Bianchi, Luca Malcovati, Wilma Barcellini, Bruno Fattizzo
Summary: Daratumumab, a monoclonal antibody targeting CD38, has shown efficacy in multiple myeloma and is now being investigated for its potential in treating autoimmune conditions like cold agglutinin disease. The drug not only depletes plasma cells but also demonstrates immunomodulatory effects by influencing the levels of various cytokines. Research also suggests its potential in refractory autoimmune hemolytic anemia, Evans syndrome, and other autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Physiology
Elisa Fermo, Cristina Vercellati, Anna Paola Marcello, Ebru Yilmaz Keskin, Silverio Perrotta, Anna Zaninoni, Valentina Brancaleoni, Alberto Zanella, Juri A. Giannotta, Wilma Barcellini, Paola Bianchi
Summary: This study utilized a 43 genes targeted Next Generation Sequencing (t-NGS) panel to diagnose Congenital Hemolytic Anemias (CHAs), identifying new pathogenic variants and increasing diagnoses in cases with unexplained anemia. The implementation of laboratory work-up with t-NGS proved beneficial for rare and ultra-rare diseases.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Hematology
Julia Jansen, Min Qiao, Laura Hertz, Xijia Wang, Elisa Fermo, Anna Zaninoni, Raffaella Colombatti, Ingolf Bernhardt, Paola Bianchi, Lars Kaestner
Summary: In patients with Gardos channelopathy, there is an increased intracellular Ca2+ concentration. The activity of K(Ca)3.1 may lead to membrane potential flickering in red blood cells, activating the Ca(v)2.1 channel and allowing Ca2+ entry.
Article
Hematology
Cristina Vercellati, Anna Zaninoni, Anna P. Marcello, Elisa Fermo, Bruno Fattizzo, Juri A. Giannotta, Paola Bianchi, Alberto Zanella, Wilma Barcellini
Summary: This study describes the clinical and hematological characteristics of 446 patients with hereditary spherocytosis diagnosed in a reference center over the past 40 years. The frequency of splenectomy has decreased over time, possibly due to an increasing awareness of the risks of thrombosis and infection after splenectomy.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Bruno Fattizzo, Marta Bortolotti, Juri Alessandro Giannotta, Anna Zaninoni, Dario Consonni, Wilma Barcellini
Summary: Thrombosis was observed in approximately 11% of AIHA patients, mainly associated with intravascular hemolysis, need for transfusions, multiple treatments, and infections. The study suggests considering primary anticoagulant prophylaxis in these cases.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Oncology
Bruno Fattizzo, Giorgia Virginia Levati, Juri Alessandro Giannotta, Giulio Cassanello, Lilla Marcella Cro, Anna Zaninoni, Marzia Barbieri, Giorgio Alberto Croci, Nicoletta Revelli, Wilma Barcellini
Summary: Low-risk myelodysplastic syndromes (LR-MDS) have diverse clinical features and outcomes. Treatment options are limited, mainly focusing on erythropoiesis-stimulating agents (ESAs) and transfusion support. The contribution of molecular lesions and autoimmune phenomena to the disease's pathogenesis and clinical course are still being investigated.
FRONTIERS IN ONCOLOGY
(2022)
Review
Chemistry, Medicinal
Marta Bortolotti, Loredana Pettine, Anna Zaninoni, Giorgio Alberto Croci, Wilma Barcellini, Bruno Fattizzo
Summary: Thrombopoietin receptor agonists (TPO-RA) are used to treat chronic immune thrombocytopenia and relapsed refractory aplastic anemia. However, their off-label use is becoming more common, especially in cases of aplasia after chemotherapy and stem cell transplant. Recent evidence suggests that TPO-RA have immunomodulating properties in addition to stimulating platelet production. In this case study, eltrombopag was effective in treating prolonged bone marrow aplasia caused by autologous stem cell transplant. The drug also had an effect on inflammatory cytokine levels and bone marrow histology. This review of literature highlights the efficacy and safety of TPO-RA after stem cell transplant and chemotherapy for hematologic conditions.
Article
Physiology
Cristina Vercellati, Anna Paola Marcello, Bruno Fattizzo, Anna Zaninoni, Agostino Seresini, Wilma Barcellini, Paola Bianchi, Elisa Fermo
Summary: In this study, we investigated the genetic basis of hereditary spherocytosis using targeted next generation sequencing, and compared the molecular results with the biochemical lesion of RBC membrane. The study revealed complex relationships between the primary molecular lesion and the final effect in the RBC membrane cytoskeleton, and further underlines the concept that there is not a unique approach to the diagnosis of HS.
FRONTIERS IN PHYSIOLOGY
(2022)
Meeting Abstract
Hematology
Bruno Fattizzo, Cristina Vercellati, Anna Marcello, Marta Bortolotti, Anna Zaninoni, Elisa Fermo, Paola Bianchi, Wilma Barcellini
Article
Immunology
Bruno Fattizzo, Francesco Versino, Anna Zaninoni, Anna Paola Maria Luisa Marcello, Cristina Vercellati, Silvia Artuso, Wilma Barcellini
Summary: This study reported the first Italian patient treated with pegcetacoplan in a named patient program for paroxysmal nocturnal hemoglobinuria (PNH). Treatment with pegcetacoplan resulted in significant improvement in the patient's condition, with good tolerability, providing a safe and effective option for PNH patients with suboptimal response to anti-C5 agents.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Anna Zaninoni, Roberta Marra, Elisa Fermo, Dario Consonni, Immacolata Andolfo, Anna Paola Marcello, Barbara Eleni Rosato, Cristina Vercellati, Wilma Barcellini, Achille Iolascon, Paola Bianchi, Roberta Russo
Summary: This study investigated iron homeostasis and dyserythropoiesis in pyruvate kinase deficiency (PKD) patients. The results showed that PKD patients had intermediate levels of sTfR, hepcidin, ERFE, and EPO between CDAII and HS. PKD patients also exhibited higher levels of sTfR and similar levels of EPO compared to CDAII, but both higher than in HS.
SCIENTIFIC REPORTS
(2023)
Letter
Hematology
Bruno Fattizzo, Alfredo Marchetti, Anna Zaninoni, Marta Lionetti, Marta Riva, Lorenzo Rizzo, Loredana Pettine, Nicole Galli, Federico Mazzon, Elisa Fermo, Akihiro Maeda, Alessio Marella, Matteo Claudio Da Via, Francesco Passamonti, Niccolo Bolli, Wilma Barcellini
AMERICAN JOURNAL OF HEMATOLOGY
(2023)