keyword
https://read.qxmd.com/read/38193066/effect-of-emicizumab-neutralizing-antibodies-on-activated-partial-thromboplastin-time-based-clotting-time-test-results-in-patients-treated-with-emicizumab
#21
JOURNAL ARTICLE
Cristina Novembrino, Massimo Boscolo-Anzoletti, Eleonora Galbiati, Sho Shinohara, Flora Peyvandi
BACKGROUND: Emicizumab is a bispecific humanized monoclonal antibody that shortens the activated partial thromboplastin time (aPTT), making aPTT-based tests unreliable. OBJECTIVES: To evaluate the efficacy of a mixture of 2 anti-idiotype monoclonal antibodies (anti-emi) in neutralizing emicizumab in samples from persons with hemophilia A treated with emicizumab. METHODS: Fifty samples from persons with hemophilia A treated with emicizumab were analyzed for aPTT and factor VIII procoagulant activity; FVIII inhibitor titer was measured using Nijmegen-Bethesda assay in 50 plasma samples of additional patients (positive for FVIII inhibitor) treated with emicizumab...
November 2023: Research and Practice in Thrombosis and Haemostasis
https://read.qxmd.com/read/38193044/inhibitor-development-according-to-concentrate-in-severe-hemophilia-reporting-on-1392-previously-untreated-patients-from-europe-and-canada
#22
JOURNAL ARTICLE
Kathelijn Fischer, Riitta Lassila, Flora Peyvandi, Alexander Gatt, Rob Hollingsworth, Thierry Lambert, Radek Kaczmarek, Amanda Bettle, Nasrin Samji, Georges-Étienne Rivard, Manuel Carcao, Alfonso Iorio, Mike Makris
BACKGROUND: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant. OBJECTIVES: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B. METHODS: The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively...
November 2023: Research and Practice in Thrombosis and Haemostasis
https://read.qxmd.com/read/38147060/cost-effectiveness-analysis-of-emicizumab-prophylaxis-in-patients-with-haemophilia-a-in-india
#23
JOURNAL ARTICLE
Tulika Seth, M Joseph John, Prantar Chakrabarti, Chandrakala Shanmukhaiah, Shailendra Prasad Verma, Nita Radhakrishnan, Tuphan Kanti Dolai
INTRODUCTION: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). AIM: This study assessed the economic evaluation of emicizumab treatment for non-inhibitor severe haemophilia A (HA) patients in India. METHODS: A Markov model evaluated the cost-effectiveness of emicizumab prophylaxis compared to on-demand therapy (ODT), low-dose prophylaxis (LDP; 1565 IU/kg/year), intermediate-dose prophylaxis (IDP; 3915 IU/kg/year) and high-dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors...
December 26, 2023: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://read.qxmd.com/read/38142846/frontier1-a-partially-randomized-phase-2-study-assessing-the-safety-pharmacokinetics-and-pharmacodynamics-of-mim8-a-factor-viiia-mimetic
#24
RANDOMIZED CONTROLLED TRIAL
Steven R Lentz, Pratima Chowdary, Lidia Gil, Francisco J Lopez-Jaime, Johnny Mahlangu, Irina Matytsina, Anne Louise Nielsen, Jerzy Windyga
BACKGROUND: Mim8 (denecimig) is a factor VIII (FVIII) mimetic bispecific antibody in development for the treatment of hemophilia. Data from the phase 1 part of FRONTIER1 (EudraCT: 2019-000465-20, NCT04204408, and NN7769-4513) suggested that Mim8 was well tolerated in healthy participants and exhibited pharmacokinetic (PK) properties consistent with dose proportionality. OBJECTIVES: The partially randomized, phase 2, multiple ascending dose (MAD) part of FRONTIER1 aimed to evaluate the safety, PK, pharmacodynamics (PD), and exploratory efficacy of Mim8 in participants with hemophilia A with or without FVIII inhibitors...
April 2024: Journal of Thrombosis and Haemostasis: JTH
https://read.qxmd.com/read/38127586/emicizumab-prophylaxis-in-infants-with-hemophilia-a-haven-7-primary-analysis-of-a-phase-3b-open-label-trial
#25
JOURNAL ARTICLE
Steven W Pipe, Peter W Collins, Christophe Dhalluin, Gili Kenet, Christophe Schmitt, Muriel Buri, Victor Jiménez-Yuste, Flora Peyvandi, Guy Young, Johannes Oldenburg, Maria Elisa Mancuso, Kaan Kavakli, Anna Kiialainen, Sonia Deb, Markus Niggli, Tiffany Chang, Michaela Lehle, Karin Fijnvandraat
Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those ≤12 months of age with severe HA without factor (F)VIII inhibitors. Participants in this phase 3b trial received emicizumab 3 mg/kg maintenance dose every 2 weeks for 52 weeks, and are continuing emicizumab during the 7-year long-term follow-up...
December 21, 2023: Blood
https://read.qxmd.com/read/38115953/nxt007-mediated-hemostatic-potential-is-suppressed-by-activated-protein-c-catalyzed-inactivation-of-activated-factor-v
#26
JOURNAL ARTICLE
Yuto Nakajima, Kenichi Ogiwara, Keito Inaba, Takehisa Kitazawa, Keiji Nogami
BACKGROUND: Activated protein C (APC) inactivates activated factor (F) V (FVa) and FVIIIa. NXT007, an emicizumab-based engineered therapeutic bispecific antibody, enhances the coagulation potential of FVIII-deficient plasma (FVIIIdef-plasma) to near normal levels. However, little is known about the effect of APC-induced inactivation in NXT007-mediated hemostatic function. OBJECTIVES: To investigate the contribution of APC-mediated reactions to NXT007-driven hemostasis...
January 2024: Research and Practice in Thrombosis and Haemostasis
https://read.qxmd.com/read/38115777/acquired-hemophilia-a-treated-with-rituximab-in-a-62-year-old-female-with-rheumatoid-arthritis-a-case-based-review
#27
JOURNAL ARTICLE
D Mohamadzadeh, S Assar, F Farsad
Acquired hemophilia A (AHA) is a rare autoimmune disorder with unpredictable hemostasis that is caused by autoantibody formation against coagulation factor VIII. AHA can occur in the context of autoimmune inflammatory rheumatic disorders. Here we report the case of a 62-year-old female with an 11-year history of rheumatoid arthritis (RA) who presented with cutaneous and mucosal bleeding. Activated partial thromboplastin time was prolonged and not corrected by the mixing test. Factor VIII activity was decreased, and the anti-factor VIII antibody was positive...
December 19, 2023: Reumatismo
https://read.qxmd.com/read/38112996/emicizumab-mediated-hemostatic-function-assessed-by-thrombin-generation-assay-in-an-in-vitro-model-of-factor-viii-depleted-thrombophilia-plasma
#28
JOURNAL ARTICLE
Koji Yada, Kenichi Ogiwara, Naruto Shimonishi, Yuto Nakajima, Tetsuhiro Soeda, Takehisa Kitazawa, Keiji Nogami
Patients with hemophilia A (PwHA) may have concurrent deficiency of representative anticoagulant proteins, protein (P)C, PS, and antithrombin (AT), which reduces bleeding frequency. However, emicizumab-driven hemostasis in PwHA with such thrombophilic potential remains unclarified. This study investigated the influence of natural anticoagulants on emicizumab-driven coagulation in HA model plasma. Various concentrations of PS and AT were added to PS-deficient plasma and AT-deficient plasma in the presence of anti-FVIII antibody (FVIIIAb; 10BU/mL)...
December 19, 2023: International Journal of Hematology
https://read.qxmd.com/read/38074034/an-insidious-case-of-severe-acquired-factor-viii-inhibitor
#29
Falguni Patel, Kimberly Boldig, Jennifer Miatech, Pramod Reddy
Acquired hemophilia occurs when neutralizing antibodies inhibit the activity of coagulation factors, commonly occurring with factor VIII. Most cases are idiopathic; however, autoimmune diseases, certain medications, and malignancies can predispose patients to the development of these inhibitors. Moreover, the initial presentation of the disease is more often catastrophic bleeding, with ecchymosis or mucosal bleeding being less common. This case report outlines an incidental finding of a severe factor VIII inhibitor (with 0% activity) with non-catastrophic bleeding at presentation in the setting of potential lymphoma...
November 2023: Curēus
https://read.qxmd.com/read/38066923/diagnosis-and-laboratory-monitoring-of-hemophilia-a
#30
JOURNAL ARTICLE
Sean Platton, Suthesh Sivapalaratnam, Priyanka Raheja
Acquired hemophilia A (AHA) is a rare disorder in which autoantibodies against factor VIII (FVIII) lead to a bleeding phenotype that varies from life-threatening to no bleeding at all. Prolonged activated partial thromboplastin times (APTT) in patients with a bleeding phenotype should be investigated to rule out AHA and should never be ignored in a preprocedure patient. Most inhibitors in AHA are heat and time dependent, so mixing studies performed only on an immediate mix are not useful: both lupus anticoagulants and treatment with direct oral anticoagulants can coexist with AHA and confound the diagnosis...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
https://read.qxmd.com/read/38066708/efficacy-effectiveness-and-safety-of-emicizumab-prophylaxis-of-people-with-hemophilia-a-a-systematic-review-and-meta-analysis
#31
REVIEW
Roberto Lúcio Muniz, Ricardo Mesquita Camelo, Maiara Silva Araújo, Mariana Michel Barbosa, Augusto Afonso Guerra, Francisco de Assis Acurcio, Juliana Alvares-Teodoro
BACKGROUND: Emicizumab is a monoclonal antibody approved for prophylaxis against bleeds for people with hemophilia A (PwHA). A systematic review was conducted evaluating the efficacy/effectiveness and the safety of emicizumab as prophylaxis for PwHA compared to prophylaxis with factor VIII (FVIII) or bypassing agents (BPA), respectively in patients without and with inhibitors. RESEARCH DESIGN AND METHODS: Database-directed search strategies were performed in Aug/26/22 and updated in Mar/16/2023...
December 8, 2023: Expert Review of Hematology
https://read.qxmd.com/read/38058226/hybrid-human-porcine-factor-viii-proteins-partially-escape-the-inhibitory-effects-of-anti-factor-viii-inhibitor-alloantibodies-having-a2-or-c2-domain-specificity
#32
JOURNAL ARTICLE
Kuniyoshi Mizumachi, Yuto Nakajima, Naruto Shimonishi, Shoko Furukawa, Kenichi Ogiwara, Masahiro Takeyama, Keiji Nogami
INTRODUCTION: Porcine factor (pF)VIII has low cross-reactivity with anti-human (h)FVIII inhibitor alloantibodies. Clinical trials of pFVIII in congenital haemophilia A patients with inhibitor (PwHA-I) are in progress. Most polyclonal anti-hFVIII inhibitors recognize its A2 and/or C2 domain(s), and recombinant human-porcine hybrid (hp)FVIII proteins may escape neutralization by these inhibitors. AIM: To evaluate the ability of hpFVIII to limit the anti-FVIII activity of inhibitor alloantibodies...
December 6, 2023: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://read.qxmd.com/read/38049124/emicizumab-for-the-treatment-of-acquired-hemophilia-a-consensus-recommendations-from-the-gth-aha-working-group
#33
JOURNAL ARTICLE
Christian Pfrepper, Robert Klamroth, Johannes Oldenburg, Katharina Holstein, Hermann Eichler, Christina Hart, Patrick Moehnle, Kristina Schilling, Karolin Trautmann-Grill, Mohammed Alrifai, Cihan Ay, Wolfgang Miesbach, Paul Knoebl, Andreas Tiede
BACKGROUND:  Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Standard treatment consists of bleeding control with bypassing agents and immunosuppressive therapy. Emicizumab is a bispecific antibody that mimics the function of activated FVIII irrespective of the presence of neutralizing antibodies. Recently, the GTH-AHA-EMI study demonstrated that emicizumab prevents bleeds and allows to postpone immunosuppression, which may influence future treatment strategies...
December 4, 2023: Hämostaseologie
https://read.qxmd.com/read/37951852/non-viral-and-viral-delivery-systems-for-hemophilia-a-therapy-recent-development-and-prospects
#34
REVIEW
Ali Rajabi Zangi, Ala Amiri, Pouya Pazooki, Fatemeh Soltanmohammadi, Hamed Hamishehkar, Yousef Javadzadeh
Recent advancements have focused on enhancing factor VIII half-life and refining its delivery methods, despite the well-established knowledge that factor VIII deficiency is the main clotting protein lacking in hemophilia. Consequently, both viral and non-viral delivery systems play a crucial role in enhancing the quality of life for hemophilia patients. The utilization of viral vectors and the manipulation of non-viral vectors through targeted delivery are significant advancements in the field of cellular and molecular therapies for hemophilia...
November 11, 2023: Annals of Hematology
https://read.qxmd.com/read/37921115/safety-findings-of-dosing-gene-therapy-vectors-in-nhp-with-pre-existing-or-treatment-emergent-anti-capsid-antibodies
#35
JOURNAL ARTICLE
Sundeep Chandra, Brian R Long, Carlos Fonck, Andrew C Melton, Jeremy Arens, Jill Woloszynek, Charles A O'Neill
Replication-incompetent adeno-associated virus (AAV)-based vectors are nonpathogenic viral particles used to deliver therapeutic genes to treat multiple monogenic disorders. AAVs can elicit immune responses; thus, one challenge in AAV-based gene therapy is the presence of neutralizing antibodies against vector capsids that may prevent transduction of target cells or elicit adverse findings. We present safety findings from two 12-week studies in nonhuman primates (NHPs) with pre-existing or treatment-emergent antibodies...
November 3, 2023: Toxicologic Pathology
https://read.qxmd.com/read/37920545/induction-of-long-term-tolerance-to-a-specific-antigen-using-anti-cd3-lipid-nanoparticles-following-gene-therapy
#36
JOURNAL ARTICLE
Chun-Yu Chen, Amber Vander Kooi, Alex Cavedon, Xiaohe Cai, Jonathan Hoggatt, Paolo G V Martini, Carol H Miao
Development of factor VIII (FVIII) inhibitors is a serious complication in the treatment of hemophilia A (HemA) patients. In clinical trials, anti-CD3 antibody therapy effectively modulates the immune response of allograft rejection or autoimmune diseases without eliciting major adverse effects. In this study, we delivered mRNA-encapsulated lipid nanoparticles (LNPs) encoding therapeutic anti-CD3 antibody (αCD3 LNPs) to overcome the anti-FVIII immune responses in HemA mice. It was found that αCD3 LNPs encoding the single-chain antibodies (Fc-scFv) can efficiently deplete CD3+ and CD4+ effector T cells, whereas αCD3 LNPs encoding double-chain antibodies cannot...
December 12, 2023: Molecular Therapy. Nucleic Acids
https://read.qxmd.com/read/37916312/emicizumab-the-hemophilia-a-game-changer
#37
JOURNAL ARTICLE
Pedro E Alcedo Andrade, Pier Mannuccio Mannucci, Craig M Kessler
In hemophilia, the unmet needs regarding adherence to prophylaxis and lack of effective longterm prophylaxis regimens, especially in patients with inhibitors, led to the production of emicizumab, the first non-factor medicine for subcutaneous administration in patients with severe and moderate hemophilia A with or without factor VIII inhibitors. This article describes the research steps behind the development of this game-changer medication, its success for the prophylaxis of bleeding episodes as witnessed by the results of pivotal clinical trial but also by real life use in the frame of a still expanding global market...
November 2, 2023: Haematologica
https://read.qxmd.com/read/37899190/-diagnosis-and-treatment-of-autoimmune-acquired-coagulation-factor-deficiency
#38
JOURNAL ARTICLE
Yoshiyuki Ogawa
Autoimmune coagulation factor deficiency (AiCFD) is an acquired bleeding disorder caused by immunoglobulins (autoantibodies) that target a single coagulation factor. Most of these autoantibodies are polyclones and primarily neutralizing antibodies (inhibitors) that inhibit the function of coagulation factors; however, non-neutralizing autoantibodies that enhance clearance are also present. AiCFD has been reported in nearly all coagulation factors and von Willebrand factor, and its representative disease is acquired hemophilia A, which is caused by autoantibodies against coagulation factor VIII...
2023: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://read.qxmd.com/read/37886476/a-scan-of-pleiotropic-immune-mediated-disease-genes-identifies-novel-determinants-of-baseline-fviii-inhibitor-status-in-hemophilia-a
#39
Tom Howard, Marcio Almieda, Vincent Diego, Kevin Viel, Bernadette Luu, Karin Haack, Rajalingam Raja, Afshin Ameri, Meera Chitlur, Natalia Rydz, David Lillicrap, Raymond Watts, Craig Kessler, Christopher Ramsey, Long Dinh, Benjamin Kim, Jerry Powell, Juan Peralta, Ruayda Bouls, Shirley Abraham, Yu-Min Shen, Carlos Murillo, Henry Mead, Paul Lehmann, Eli Fine, Miguel Escobar, Satish Kumar, Sarah Williams-Blangero, Carol Kasper, Laura Almasy, Shelley Cole, John Blangero, Barbara Konkle
Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene ( F8 )-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called "FVIII-inhibitors (FEIs)" and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and F8 -mutational-heterogeneity...
October 18, 2023: Research Square
https://read.qxmd.com/read/37858328/emicizumab-prophylaxis-in-patients-with-acquired-haemophilia-a-gth-aha-emi-an-open-label-single-arm-multicentre-phase-2-study
#40
MULTICENTER STUDY
Andreas Tiede, Christina Hart, Paul Knöbl, Richard Greil, Johannes Oldenburg, Ulrich J Sachs, Wolfgang Miesbach, Christian Pfrepper, Karolin Trautmann-Grill, Katharina Holstein, Jan Pilch, Patrick Möhnle, Christoph Schindler, Carmen Weigt, Dorothea Schipp, Marcus May, Christiane Dobbelstein, Fabius J Pelzer, Sonja Werwitzke, Robert Klamroth
BACKGROUND: Acquired haemophilia A is caused by neutralising autoantibodies against coagulation factor VIII, leading to severe bleeding. Standard treatment involves immunosuppressive therapy, which is associated with adverse events and mortality in the frail population of patients with acquired haemophilia A. This study investigated whether emicizumab, a factor VIIIa mimetic antibody, protects patients with acquired haemophilia A from bleeding and allows deferral of immunosuppression during the first 12 weeks after diagnosis...
November 2023: Lancet Haematology
keyword
keyword
98730
2
3
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.