Review
Pharmacology & Pharmacy
Donald C. Moore, Justin R. Arnall
Summary: Sutimlimab, a first-in-class complement C1s inhibitor, is an effective therapeutic option for the management of CAD-associated hemolysis. It rapidly improves hemoglobin levels and symptoms. However, safety concerns include infusion-related reactions and the risk of infections.
ANNALS OF PHARMACOTHERAPY
(2023)
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.
Article
Immunology
Ken T. Simmons, Joanne Chan, Sami Hussain, Eileen L. Rose, Kate Markham, Tony S. Byun, Sandip Panicker, Graham C. Parry, Michael Storek
Summary: The objective of this study was to characterize the complement-inhibiting activity of SAR445088, a monoclonal antibody specific for the active form of C1s. The results demonstrated that SAR445088 is a potent, selective inhibitor of the classical pathway of complement. In addition, it was found that SAR445088 has potential therapeutic effects in treating classical pathway-driven diseases.
CLINICAL IMMUNOLOGY
(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
Hematology
Ram Gelman, Fadi Kharouf, Yuval Ishay, Alexander Gural
Summary: Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are two distinct immune-mediated hematologic disorders, and while no clear association exists between them, complement activation is known to occur in both cases.
ACTA HAEMATOLOGICA
(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
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
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
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)
Article
Hematology
Alexander Roeth, Wilma Barcellini, Shirley D'Sa, Yoshitaka Miyakawa, Catherine M. Broome, Marc Michel, David J. Kuter, Bernd Jilma, Tor Henrik Anderson Tvedt, Ilene C. Weitz, Ronnie Yoo, Deepthi Jayawardene, Deepthi S. Vagge, Katarina Kralova, Frank Shafer, Marek Wardecki, Michelle Lee, Sigbjorn Berentsen
Summary: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. Sutimlimab showed sustained improvement in hemolysis, anemia, and quality of life during a 2-year treatment period. However, disease activity reoccurred after cessation of sutimlimab treatment.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
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)
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)
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
Medicine, General & Internal
Abdelwahab Jalal Eldin, Roshni Thomas, Gary Gibson, Davis Abongwa, Israa Hassan, Mpey K. Tabot Tabot, Gagan Singh, Ravi Sarma
Summary: This is a case of secondary cold agglutinin hemolytic anemia in a 23-year-old female. It highlights the importance of considering secondary cAHA in patients with cold symptoms or unexplained hemolysis.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Hematology
Bjarne Osterud, Nadezhda Latysheva, Christian Schoergenhofer, Bernd Jilma, John-Bjarne Hansen, Omri Snir
Summary: The study developed a sensitive and specific TF activity assay based on FX activation acceleration, showing high sensitivity and specificity. It can reliably quantify TF activity on cell surface, cell lysate, and isolated EVs, suitable for both laboratory and clinical research.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Letter
Hematology
Georg Gelbenegger, Ulrich Jaeger, Michael Fillitz, Shirley D'Sa, Ronwyn Cartwright, Frank Shafer, Marek Wardecki, Jennifer Wang, Christian Schoergenhofer, Bernd Jilma
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Medical Informatics
Peter Klimek, Dejan Baltic, Martin Brunner, Alexander Degelsegger-Marquez, Gerhard Garhoefer, Ghazaleh Gouya-Lechner, Arnold Herzog, Bernd Jilma, Stefan Kaehler, Veronika Mikl, Bernhard Mraz, Herwig Ostermann, Claas Roehl, Robert Scharinger, Tanja Stamm, Michael Strassnig, Christa Wirthumer-Hoche, Johannes Pleiner-Duxneuner
Summary: Despite various European initiatives, there is still a lack of cross-border consensus on the quality standards for Real-world data (RWD) in Austria. An Austrian expert group led by the Austrian Society for Pharmaceutical Medicine has developed a set of quality criteria for RWD to be used effectively in medical research.
JMIR MEDICAL INFORMATICS
(2022)
Article
Hematology
Cihan Ay, Katarina D. Kovacevic, Daniel Kraemmer, Christian Schoergenhofer, Georg Gelbenegger, Christa Firbas, Peter Quehenberger, Petra Jilma-Stohlawetz, James C. Gilbert, Shuhao Zhu, Martin Beliveau, Franz Koenig, Alfonso Iorio, Bernd Jilma, Ulla Derhaschnig, Ingrid Pabinger
Summary: This study evaluated the safety, pharmacokinetics, and pharmacodynamics of rondaptivon pegol in patients with hemophilia A. The results showed that rondaptivon pegol was well tolerated and significantly increased the levels of FVIII and VWF in patients with hemophilia A.
Review
Pharmacology & Pharmacy
Georg Gelbenegger, Bernd Jilma
Summary: This article reviews the role of platelets in thrombosis and discusses the pharmacodynamics, drug-drug interactions, and reversal strategies of antiplatelet drugs. Expert opinion suggests personalized antiplatelet therapy, including platelet function and genetic testing and the use of scores.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2022)
Letter
Hematology
Georg Gelbenegger, Ulrich Jaeger, Michael Fillitz, Christian Schoergenhofer, Christian Sillaber, Bernd Jilma
Article
Hematology
Alexander Roeth, Catherine M. Broome, Wilma Barcellini, Bernd Jilma, Quentin A. Hill, David Cella, Tor Henrik Anderson Tvedt, Masaki Yamaguchi, Michelle Lee, Frank Shafer, Marek Wardecki, Xiaoyu Jiang, Parija Patel, Florence Joly, Ilene C. Weitz
Summary: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia that leads to fatigue and reduced quality of life. In the Phase 3 CADENZA trial, treatment with the complement inhibitor sutimlimab showed rapid improvement in hemolysis, increased hemoglobin levels, and alleviated fatigue in CAD patients. Patient-reported outcomes also demonstrated significant benefits from sutimlimab treatment.
EUROPEAN JOURNAL OF HAEMATOLOGY
(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)
Article
Pharmacology & Pharmacy
Lisa Christina Horvath, Felix Bergmann, Arthur Hosmann, Stefan Greisenegger, Kerstin Kammerer, Bernd Jilma, Jolanta M. Siller-Matula, Markus Zeitlinger, Georg Gelbenegger, Anselm Jorda
Summary: This study compared the efficacy between thrombectomy alone and thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion. The results showed that although combined treatment increased successful reperfusion, it also increased the risk of overall intracranial hemorrhage. Thrombectomy alone was non-inferior to combined treatment in terms of functional independence at a 10% non-inferiority margin, but not at a 5% inferiority margin.
VASCULAR PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gloria M. M. Gager, Ceren Eyileten, Marek Postula, Anna Nowak, Aleksandra Gasecka, Bernd Jilma, Jolanta M. M. Siller-Matula
Summary: This study investigated the relationship between blood-derived microRNAs (miRNAs) and long-term all-cause mortality in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The expression of miR-223 was found to be associated with improved long-term survival in NSTE-ACS patients. This hypothesis-generating study suggests that miR-223 may be a suitable predictor for long-term all-cause mortality.
Article
Cell Biology
Matthias Weiss-Tessbach, Birgit Reiter, Elisabeth Gludovacz, Thomas Boehm, Bernd Jilma, Marlene Rager-Resch
Summary: This study aimed to investigate the preventive effects of recombinant human diamine oxidase with a mutated heparin-binding motif (rhDAO_mHBM) on histamine-induced hemodynamic effects. The results demonstrated that pretreatment with rhDAO_mHBM in guinea pigs led to lower heart rate, histamine plasma concentrations, and higher body core temperatures at the end of the histamine challenge. Furthermore, rhDAO_mHBM prevented the hemodynamic instability caused by histamine infusion. These findings suggest that rhDAO_mHBM has potential clinical applications in preventing histamine-induced hemodynamic effects.
INFLAMMATION RESEARCH
(2023)
Article
Nutrition & Dietetics
Melanie Gsoellpointner, Margarita Thanhaeuser, Fabian Eibensteiner, Robin Ristl, Bernd Jilma, Renate Fuiko, Sophia Brandstetter, Angelika Berger, Nadja Haiden
Summary: This study analyzed the intake of polyunsaturated fatty acids (PUFAs) during complementary feeding (CF) in very low birth weight (VLBW) infants and its impact on neurodevelopment. The results showed that higher intake of total PUFAs, docosahexaenoic acid (DHA), and arachidonic acid (AA) was associated with improved cognitive and motor function at 12 months of age. However, the dietary intake of AA and DHA did not meet the recommended levels, highlighting the need to increase PUFA, DHA, and AA intake during CF for better neurodevelopmental outcomes in VLBW infants.
Review
Cell Biology
Benjamin Panzer, Christoph W. Kopp, Christoph Neumayer, Renate Koppensteiner, Alicja Jozkowicz, Michael Poledniczek, Thomas Gremmel, Bernd Jilma, Patricia P. Wadowski
Summary: Toll-like receptors (TLRs) play a critical role in viral infections by inducing pro-inflammatory responses and disrupting vascular homeostasis. The injury to the vessel wall leads to pro-thrombotic processes and eventually causes micro-vessel plugging and tissue necrosis. TLRs also directly contribute to virus sensing and platelet activation. Upregulation of von Willebrand factor release and extra-cellular trap formation by TLRs further enhance thrombotic processes during inflammation. This review focuses on TLR signaling pathways in humans, which provoke pro-thrombotic responses during viral infections, particularly in individuals with cardiovascular diseases.
Review
Pharmacology & Pharmacy
Katharina A. Mayer, Klemens Budde, Bernd Jilma, Konstantin Doberer, Georg A. Boehmig
Summary: This article discusses the pathophysiology and current therapeutic strategies for antibody-mediated rejection (ABMR) in kidney transplant, as well as the ongoing clinical trials for new treatment approaches. It suggests that innovative treatment strategies for ABMR may become available within the next 5-10 years.
EXPERT OPINION ON EMERGING DRUGS
(2022)