A5011450008- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Platelet Disorders and Treatments
- Vitamin K Research Studies
- Hemophilia Treatment and Research
- Mast cells and histamine
- Protease and Inhibitor Mechanisms
- Blood properties and coagulation
- Antiplatelet Therapy and Cardiovascular Diseases
- Venous Thromboembolism Diagnosis and Management
- Cell Adhesion Molecules Research
- Complement system in diseases
- Erythrocyte Function and Pathophysiology
- Acute Ischemic Stroke Management
- Atrial Fibrillation Management and Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mechanical Circulatory Support Devices
- Renin-Angiotensin System Studies
- Venomous Animal Envenomation and Studies
- Peptidase Inhibition and Analysis
- Heparin-Induced Thrombocytopenia and Thrombosis
- Neurological Disorders and Treatments
- Hemostasis and retained surgical items
- Apelin-related biomedical research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Oregon Health & Science University
2015-2024
Aronora (United States)
2015-2024
University of Southern Denmark
2023
The University of Texas Health Science Center at San Antonio
2023
University of Portland
2022
Vanderbilt University
2009-2016
Bayer (United States)
2016
University Medical Center Utrecht
2009-2016
Bayer (Germany)
2016
Ionis Pharmaceuticals (United States)
2013
Background Red blood cell–derived microparticles ( RMP s) are small phospholipid vesicles shed from RBCs in units, where they accumulate during storage. Because bioactive, it could be suggested that s mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent. Study Design and Methods This study was performed to establish impact coagulation isolated units. Using calibrated automated thrombography, we investigated whether affect thrombin generation...
Objective— During coagulation, factor IX (FIX) is activated by 2 distinct mechanisms mediated the active proteases of either FVIIa or FXIa. Both coagulation factors may contribute to thrombosis; FXI, however, plays only a limited role in arrest bleeding. Therefore, therapeutic targeting FXI produce an antithrombotic effect with relatively low hemostatic risk. Approach and Results— We have reported that reducing levels antisense oligonucleotides produces activity mice, administration primates...
Objective- Factor XI (FXI) contributes to thrombotic disease while playing a limited role in normal hemostasis. We generated unique, humanized anti-FXI antibody, AB023, which blocks factor XIIa-mediated FXI activation without inhibiting by thrombin or the procoagulant function of FXIa. sought confirm antithrombotic activity AB023 baboon thrombosis model and evaluate safety, tolerability, pharmacokinetics, pharmacodynamics healthy adult subjects. Approach Results- In primate acute vascular...
Staphylococcus aureus infections can produce systemic bacteremia and inflammation in humans, which may progress to severe sepsis or septic shock, even with appropriate antibiotic treatment. Sepsis be associated disseminated intravascular coagulation consumptive coagulopathy. In some types of mouse infection models, the plasma protein factor XI (FXI) contributes pathogenesis sepsis. We hypothesize that FXI also primates, pharmacological interference will alter outcome aureus-induced lethality...
Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with mouse model sepsis induced cecal ligation and puncture (CLP) suggested that the protease factor XIa contributed disseminated intravascular coagulation (DIC) cytokine during sepsis. We investigated importance XI responses first 24 hours after CLP. Compared wild type littermates, XI-deficient (FXI-/-) mice had survival advantage CLP, smaller increases in plasma...
BackgroundThe contact factor XII (FXII) activates upon with a variety of charged surfaces. Activated FXII (FXIIa) XI, which IX, resulting in thrombin generation, platelet activation, and fibrin formation. In both vitro vivo rabbit models, components medical devices, including extracorporeal oxygenators, are known to incite formation FXII‐dependent manner. Since has no role hemostasis its inhibition is therefore likely safe antithrombotic approach, we investigated whether also reduces...
Human coagulation factor (F) XI deficiency, a defect of the contact activation system, protects against venous thrombosis, stroke, and heart attack, whereas FXII, plasma prekallikrein, or kininogen deficiencies are asymptomatic. FXI inhibition production, activated (FXIa) inhibitors, antibodies to that interfere with FXI/FXII interactions reduce experimental thrombosis inflammation. inhibitors antithrombotic in patients, FXII atheroprotective apolipoprotein E-deficient mice.Investigate...
Complement factor H (CFH) is the major inhibitor of alternative pathway complement system and structurally related to beta2-glycoprotein I, which itself known bind ligands, including coagulation XI (FXI). We observed reduced activation when FXI was inhibited in a baboon model lethal systemic inflammation, suggesting cross-talk between cascade. It unknown whether or its activated form, (FXIa), directly interacts with system. explored could interact inhibit activity CFH. found that FXIa...
Despite the ubiquitous utilization of central venous catheters in clinical practice, their use commonly provokes thromboembolism. No prophylactic strategy has shown sufficient efficacy to justify routine use. Coagulation factors FXI (factor XI) and FXII XII) represent novel targets for device-associated thrombosis, which may mitigate bleeding risk. Our objective was evaluate safety an anti-FXI mAb (monoclonal antibody), gruticibart (AB023), a prospective, single-arm study patients with...
Anticoagulation is a rational approach to the treatment of sepsis-associated consumptive coagulopathy, but its application limited because risk excessive bleeding. Factor XI (FXI) contributes substantially pathological blood coagulation (thrombosis), whereas it only modestly normal hemostasis. We found that FXI-deficient mice have reduced coagulopathy and increased survival relative FXI-expressing wild-type during cecal ligation puncture-induced acute peritonitis/sepsis. This finding...
Factor XI (FXI) promotes hemostasis and thrombosis through enhancement of thrombin generation has been shown to play a critical role in the formation occlusive thrombi arterial injury models. The aim this study was investigate mechanisms governing interactions between FXI platelets.Platelet adhesion immobilized abrogated presence low-density lipoprotein (LDL) receptor antagonist, receptor-associated protein (RAP), soluble recombinant apolipoprotein E 2 (ApoER2), or LDL-binding domain 1...