A5008146377- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Chronic Myeloid Leukemia Treatments
- Venous Thromboembolism Diagnosis and Management
- Hemostasis and retained surgical items
- Cancer-related gene regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Heparin-Induced Thrombocytopenia and Thrombosis
- Blood disorders and treatments
- Blood groups and transfusion
- Acute Myocardial Infarction Research
- Monoclonal and Polyclonal Antibodies Research
- Hematopoietic Stem Cell Transplantation
- Intramuscular injections and effects
- Orthopaedic implants and arthroplasty
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Virus-based gene therapy research
- Systemic Lupus Erythematosus Research
- COVID-19 Clinical Research Studies
- Chronic Lymphocytic Leukemia Research
- Parvovirus B19 Infection Studies
- Sepsis Diagnosis and Treatment
University of Minnesota Medical Center
2014-2024
University of Minnesota
2013-2024
Palmetto Hematology Oncology
2001-2017
University of Minnesota Children's Hospital
2007
University Medical Center
2004-2006
Institute of Molecular Biology and Biophysics
2003-2004
Veterans Health Administration
1997
Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons severe hemophilia A. The findings of phase 3 study the efficacy and safety valoctocogene therapy evaluated after 52 weeks men A have been published previously.We conducted open-label, single-group, multicenter, trial which 134 who were receiving prophylaxis received single infusion 6×1013 genomes per kilogram body weight. primary end point...
Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection.
BackgroundBAY 94‐9027 is a B‐domain‐deleted recombinant factor VIII (rFVIII) with site‐specific attachment of poly(ethylene glycol) that has shown an extended half‐life in animal models hemophilia.ObjectivesTo assess the pharmacokinetics and safety BAY after single repeated administration subjects severe hemophilia A.Patients/MethodsThis 8‐week, prospective, multicenter, open‐label, phase I trial was conducted 14 aged 21–58 years FVIII < 1%, ≥ 150 days exposure to FVIII, no history...
Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial late/tertiary vs on-demand therapy. Prophylaxis improved function, quality life, activity pain but not joint structure by MRI. improves function must start before bleeding onset to prevent arthropathy.Background Limited exist the impact severe A pre-existing disease. Objectives To describe bleeding, health structure, health-related...
Essentials Recombinant factor VIII BAY 94-9027 conjugates in a site-specific manner with polyethylene glycol. was given to patients severe hemophilia A as prophylaxis and treat bleeds. prevented bleeds at dose intervals up every 7 days effectively treated treatment mainly well tolerated no patient developed inhibitors. Click hear Dr Tiede's perspective on half-life extended for the of SUMMARY: Background is B-domain-deleted prolonged-half-life recombinant (FVIII) that Objective Assess...
Liver sinusoidal endothelial cells are a major endogenous source of Factor VIII (FVIII), lack which causes the human congenital bleeding disorder hemophilia A. Despite extensive efforts, gene therapy using viral vectors has shown little success in clinical trials. Here we achieved cell type-specific targeting hyaluronan- and asialoorosomucoid-coated nanocapsules, generated dispersion atomization, to direct genes liver hepatocytes, respectively. To highlight therapeutic potential this...
Rare cases of COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine-induced immune (VITT). Currently, information on the characteristics persistence anti-PF4 VITT after Ad26.COV2.S vaccination is limited, available diagnostic assays fail differentiate ChAdOx1 nCoV-19-associated from similar clinical disorders, namely heparin-induced (HIT) spontaneous HIT. Here we demonstrate...
Summary Development of antibodies (Ab) that inhibit the procoagulant function factor VIII (fVIII) seriously complicates treatment hemophilia A patients. It also causes acquired hemophilia, a rare yet serious autoimmune disease. The design effective fVIII-specific tolerizing procedures will require elucidation role different CD4+ T cell subsets drive inhibitor synthesis. To examine contribution Th1 and Th2 cells in anti-fVIII Ab response, we measured concentration Th1- Th2-driven IgG...
Summary. Participants in an international conference on the management of haemophilia patients with inhibitors developed a jointly authored summary findings and conclusions conference. Current knowledge genetic immunologic mechanisms underlying inhibitor development was briefly summarized. Concerning purported treatment‐related risk factors, participants commented limitations available evidence need for more rigorous prospective research fully genotyped population. Other clinical...
Summary Antibodies (Ab) that inhibit factor VIII (fVIII) may develop in patients with hemophilia A and rarely individuals without congenital fVIII deficiency (acquired hemophilia). Synthesis of inhibitors requires CD4+ T cells. We investigated the proliferative response blood cells from 11 or acquired 12 healthy subjects, to recombinant human fVIII, pools overlapping synthetic peptides spanning sequences individual domains. All had responded fVIII. The intensity responses fluctuated over...
Background and Objectives Acquired red cell aplasia (RCA) is a rare disorder can be either idiopathic or associated with certain diseases, pregnancy, drugs. In exceptionally cases, it has been reported to co-exist other autoimmune cytopenias. We report high incidence of RCA hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy.Design Methods Between February 2003 July 2005, 357 were treated immunosuppressive regimens containing the...
Rare, chronic diseases such as hemophilia and other congenital coagulation disorders require coordinated delivery of services for optimal outcomes. Hemophilia Treatment Centers (HTCs) are specialized, multidisciplinary health-care centers providing team-based care to meet the physical, psychosocial, emotional needs people with (PWH) may serve a model rare disorders. Health-care purchasers, well general medical community, not appreciate breadth quality provided by HTCs. They exemplify...
Background Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with full, active life, for many in high-income countries. The direction future will determine whether exciting developments truly advance health equity all people (PWH). National Hemophilia Foundation (NHF) and American Thrombosis Hemostasis Network conducted extensive inclusive all-stakeholder consultations identify the priorities inherited bleeding...
Summary Mice genetically deficient in factor VIII (fVIII) are a model of hemophilia A. As first step to reproduce this mouse what occurs over time A patients treated with human fVIII (hfVIII), we have investigated the course and characteristics their immune response hfVIII, after multiple intravenous injections. Anti-hfVIII antibodies appeared four five They were IgG1 lesser extent IgG2, indicating that they induced by both Th2 Th1 cells. Inhibitors six CD4+ enriched splenocytes from...
Introduction In spite of the significant advances in treatment hemophilia over last 30 years, development antibodies that neutralize procoagulant activity factor VIII (factor inhibitors) remains a serious complication with products. Recent prospective studies previously untreated patients severe have reported incidence inhibitor to be approximately 20% 25%.1-11 Factor inhibitors may also develop individuals without congenital deficiency. Acquired autoimmune occurs an 0.2 1.0 per 1,000,000...
Regular prophylaxis with exogenous factor VIII (FVIII) is recommended for individuals severe haemophilia A (HA), but standardised data are scarce. Here, we report real-world from a global cohort. Participants were men ≥18 years old HA (FVIII ≤ 1 IU/dL) receiving regular FVIII. provided 6 months of retrospective and prospectively followed up to 12 months. Annualised bleeding rate (ABR) FVIII utilisation infusion rates calculated. Differences between geographic regions explored. Of 294...
Summary. The immune response to factor VIII and the development of inhibitory antibodies is a complex multi‐factorial process involving variety regulatory genes cells, several which have potential determine risk. A better understanding mechanisms involved will increase likelihood new therapeutic options for patients with hemophilia. This review summarizes genetic non‐genetic risk factors currently under evaluation, modulative effect von Willebrand on immuno‐ antigenicity. In addition, role...
Ensuring hemostasis during invasive procedures is a challenge in patients with severe hemophilia A. This analysis evaluated efficacy and safety of BAY 94-9027, an extended-half-life recombinant factor VIII (FVIII), the surgical setting.Patients participating open-label 94-9027 clinical trial who underwent major surgery were included analysis. Investigator/surgeon assessment was primary outcome. In addition, information about FVIII use, levels perioperative period, bleeding complications...