A5075920531- Platelet Disorders and Treatments
- Heparin-Induced Thrombocytopenia and Thrombosis
- Venous Thromboembolism Diagnosis and Management
- Intramuscular injections and effects
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- Proteoglycans and glycosaminoglycans research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood properties and coagulation
- Blood Coagulation and Thrombosis Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Autoimmune Bullous Skin Diseases
- Antiplatelet Therapy and Cardiovascular Diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Blood groups and transfusion
- Systemic Lupus Erythematosus Research
- Multiple Myeloma Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Extracellular vesicles in disease
- Erythrocyte Function and Pathophysiology
- Hemophilia Treatment and Research
- Immune cells in cancer
- Sepsis Diagnosis and Treatment
- Phagocytosis and Immune Regulation
Children's Hospital of Philadelphia
2016-2025
University of Pennsylvania
2016-2025
Philadelphia University
2024
Pediatrics and Genetics
2018
Faculty (United Kingdom)
2016
California University of Pennsylvania
2013
National Institute of Rheumatic Diseases
1992-2012
Duke University Hospital
2005
Duke University
2005
Jefferson College
2005
Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenic disorder associated with a severe prothrombotic state. We investigated whether neutrophils and neutrophil extracellular traps (NETs) contribute to the development of thrombosis in HIT. Using endothelialized microfluidic system murine passive immunization model, we show that HIT induction leads increased adherence venous endothelium. In mice, endothelial enhanced immediately downstream nascent thrombi, after which...
Abstract Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) tetramer/fondaparinux complex, (2) tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) (3) monomer/RTO-Fab non-HIT anti-PF4 antibody). Fondaparinux binds ‘closed’ end tetramer stabilizes its conformation. This...
Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated role PDI and in thrombosis by generating mice with blood cells vessel wall lacking (Mx1-Cre Pdifl/fl mice) transgenic harboring that lacks a functional C-terminal motif [PDI(ss-oo) mice]. Both mouse models showed decreased fibrin deposition platelet accumulation laser-induced cremaster...
Patients with COVID-19 present a wide variety of clinical manifestations. Thromboembolic events constitute significant cause morbidity and mortality in patients infected SARS-CoV-2. Severe has been associated hyperinflammation pre-existing cardiovascular disease. Platelets are important mediators sensors inflammation directly affected by stressors. In this report, we found that platelets from severely ill, hospitalized exhibited higher basal levels activation measured P-selectin surface...
Thrombopoiesis, the process by which circulating platelets arise from megakaryocytes, remains incompletely understood. Prior studies suggest that megakaryocytes shed in pulmonary vasculature. To better understand thrombopoiesis and to develop a potential platelet transfusion strategy is not dependent upon donors, of there shortage, we examined whether infused into mice platelets. Infused led clinically relevant increases numbers. The released were normal size, displayed appropriate surface...
Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder initiated by antibodies to complexes between platelet factor 4 (PF4) and heparin. The risk of recurrent thromboembolism persists after heparin cleared activation leading release PF4 has dissipated. We asked whether antigenic polyphosphates released from activated platelets might intensify or sustain the prothrombotic phenotype HIT. forms stable, ultralarge with various sizes, including those platelets, which are recognized...
To test the adverse effects and viral safety of intravenous immunoglobulin (IVIg) use in autoimmune diseases.Fifty-six patients with various diseases who were treated one to six IVIg courses evaluated for presence following therapy screened before after treatment serum human immunodeficiency virus antibodies, hepatitis C B surface antigen.Among 56 patients, 20 (36%) had at least effect courses. These included headache, low-grade fever, chills, anemia, low-back pain, transient hypotension,...
Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy sometimes associated with thrombosis. The hallmark HIT antibodies to the heparin/platelet factor 4 (PF4) complex that cause and thrombosis through platelet activation. Despite clinical importance, molecular mechanisms late consequences immune activation are not fully understood. Here, we studied immediate delayed effects complexes formed by human PF4 HIT-like monoclonal mouse anti-human-PF4/heparin IgG (named KKO) on...