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Target-specific anticoagulant

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https://www.readbyqxmd.com/read/29344007/four-factor-prothrombin-complex-concentrate-improves-thrombin-generation-and-prothrombin-time-in-patients-with-bleeding-complications-related-to-rivaroxaban-a-single-center-pilot-trial
#1
Bettina Schenk, Stephanie Goerke, Ronny Beer, Raimund Helbok, Dietmar Fries, Mirjam Bachler
Background: Direct oral anticoagulants (DOACs) pose a great challenge for physicians in life-threatening bleeding events. The aim of this study was to test the efficacy of reversing the DOAC rivaroxaban using four-factor PCC (prothrombin complex concentrate), a non-specific reversing agent. Methods: Patients with life-threatening bleeding events during rivaroxaban treatment were included and administered 25 U kg-1 of PCC. Blood samples were collected immediately prior to as well as after PCC treatment at predefined time intervals...
2018: Thrombosis Journal
https://www.readbyqxmd.com/read/29338293/betrixaban-a-new-oral-factor-xa-inhibitor-for-extended-venous-thromboembolism-prophylaxis-in-high-risk-hospitalized-patients
#2
Scott G Garland, Christina E DeRemer, Steven M Smith, John G Gums
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of acute medically ill patients with venous thromboembolism (VTE) risk factors. DATA SOURCES: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted using the following keywords: betrixaban, PRT054021, FXa inhibitor, novel oral anticoagulant, NOAC, direct oral anticoagulant, DOAC, and target specific oral anticoagulant, TSOAC...
January 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29336885/structural-basis-for-activity-and-specificity-of-an-anticoagulant-anti-fxia-monoclonal-antibody-and-a-reversal-agent
#3
Lauren K Ely, Marco Lolicato, Tovo David, Kate Lowe, Yun Cheol Kim, Dharmaraj Samuel, Paul Bessette, Jorge L Garcia, Thomas Mikita, Daniel L Minor, Shaun R Coughlin
Coagulation factor XIa is a candidate target for anticoagulants that better separate antithrombotic efficacy from bleeding risk. We report a co-crystal structure of the FXIa protease domain with DEF, a human monoclonal antibody that blocks FXIa function and prevents thrombosis in animal models without detectable increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and active site, while the heavy chain provides electrostatic interactions with the surface of FXIa. The structure accounts for the specificity of DEF for FXIa over its zymogen and related proteases, its active-site-dependent binding, and its ability to inhibit substrate cleavage...
January 2, 2018: Structure
https://www.readbyqxmd.com/read/29329680/correlation-of-severity-of-chronic-obstructive-pulmonary-disease-with-potential-biomarkers
#4
Seema Singh, S K Verma, Santosh Kumar, M K Ahmad, Anuradha Nischal, S K Singh, R K Dixit
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a non-specific inflammation, which involves the airways, lung parenchyma and pulmonary vessels. The inflammation causes the activation of inflammatory cells and the release of various inflammatory mediators such as interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha (TNF-a). The present study was designed to assess the serum cytokines [Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α)] levels in chronic obstructive pulmonary disease (COPD) patients and they were correlated with severity of disease by spirometric measurements...
January 9, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29316202/anticoagulant-prophylaxis-and-therapy-in-children-current-challenges-and-emerging-issues
#5
Fiona Newall, Brian Branchford, Christoph Male
This review aims to describe the unique challenges of anticoagulant prophylaxis and treatment in children, and to highlight areas for research for improving clinical outcomes of children with thromboembolic disease. The evidence presented demonstrates the challenges of advancing the evidence-base informing optimal management of thromboembolic disease in children. Recent observational studies have identified risk factors of venous thromboembolism in children, but there are few interventional studies assessing the benefit-risk of using thromboprophylaxis in risk-stratified clinical subgroups...
January 6, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29304529/passivating-injured-endothelium-with-kinexins-in-thrombolytic-therapy
#6
Yunn-Hwa Ma, Chao-Wei Huang, Chih-Jen Wen, Yi-Ching Lu, Shiaw-Pyng Wey, Tze-Chein Wun
Without conjunctive administration of an anticoagulant, endothelial injury-induced thrombosis is resistant to thrombolysis and prone to re-thrombosis. We hypothesized that co-delivery of recombinant tissue plasminogen activator (rtPA) with annexin V-containing anticoagulants that specifically target the injured endothelium may passivate the thrombogenic elements of the vascular injury site and enhance rtPA-induced thrombolysis. In this study, the effects of conjunctive administration of Kinexins (Kunitz inhibitor-annexin V fusion proteins) with rtPA on thrombolysis were determined in vitro and in vivo...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29251360/laboratory-characteristics-of-ischemic-stroke-patients-with-atrial-fibrillation-on-or-off-therapeutic-warfarin
#7
Raghav V Aachi, Lee A Birnbaum, Christopher H Topel, Ali Seifi, Shaheryar Hafeez, Réza Behrouz
BACKGROUND: In patients with atrial fibrillation (AF), despite adequate anticoagulation, ischemic stroke (IS) is an uncommon yet concerning occurrence. HYPOTHESIS: Specific laboratory parameters may affect the efficacy of warfarin despite therapeutic international normalized ratio (INR) in patient with AF who present with IS. METHODS: We used the database from a multicenter clinical trial to identify AF patients who presented with IS. We trichotomized the cohort into patients with therapeutic INR on warfarin, subtherapeutic INR on warfarin, and on no anticoagulants...
December 18, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/29241899/comparison-of-oral-anticoagulants-for-stroke-prevention-in-nonvalvular-atrial-fibrillation-a-multicriteria-decision-analysis
#8
REVIEW
Tommi Tervonen, Anastasia Ustyugova, Sumitra Sri Bhashyam, Gregory Y H Lip, Paolo Verdecchia, Ryan Kwan, Savion Gropper, Jutta Heinrich-Nols, Kevin Marsh
BACKGROUND: Decision on the most appropriate oral anticoagulation therapy for stroke prevention in patients with nonvalvular atrial fibrillation is difficult because multiple treatment options are available, and these vary in their clinical effects and relevant nonclinical characteristics. OBJECTIVES: To use a multicriteria decision analysis (MCDA) to compare the oral anticoagulants apixaban, dabigatran, edoxaban, rivaroxaban, and vitamin K antagonist (VKAs; specifically warfarin) in patients with nonvalvular atrial fibrillation...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29212638/reversal-strategies-for-newer-oral-anticoagulants
#9
Adam J Singer, Susan Wilson
Nonvitamin K antagonist oral anticoagulants have advantages compared with warfarin, but both types of anticoagulants come with uncertainty about how best to manage life-threatening bleeding events, urgent surgeries, and invasive procedures. Nurse practitioners and physician assistants may need to manage such emergency situations in the critical care setting. Achieving hemostasis quickly is key, and efforts to do so have relied mainly on blood products. Targeted reversal agents are in clinical development and one, idarucizumab, which reverses dabigatran anticoagulation, has been approved...
2017: AACN Advanced Critical Care
https://www.readbyqxmd.com/read/29208276/development-of-novel-ph-sensitive-thiolated-chitosan-pmla-nanoparticles-for-amoxicillin-delivery-to-treat-helicobacter-pylori
#10
Muhammad Arif, Quan-Jiang Dong, Mazhar Ali Raja, Shah Zeenat, Zhe Chi, Chen-Guang Liu
The cysteine conjugated chitosan/PMLA multifunctional nanoparticles were synthesized as targeted Nano-drug delivery system to eradicate Helicobacter pylori. Helicobacter pylori specifically express urea transport protein on its membrane to carrying urea to the cytoplasm urease to supply ammonia that protects bacteria in the acid environment of the stomach. The clinical suitability of topical antimicrobial agents is required to get rid of Helicobacter pylori inside the inflamed basal region. In this work, cysteine conjugated chitosan derivative, Cys-CS for their mucoadhesive and anticoagulant properties was designed and synthesized, for the preparation of multifunctional nanoparticles...
February 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29136827/biobarcode-assay-for-the-oral-anticoagulant-acenocoumarol
#11
Marta Broto, J Pablo Salvador, Roger Galve, M Pilar Marco
A novel approach for therapeutic drug monitoring of oral anticoagulants (OA) in clinical samples is reported, based on a NP-based biobarcode assay. The proposed strategy uses specific antibodies for acenocumarol (ACL) covalently bound to magnetic particles (pAb236-MP) and a bioconjugate competitor (hACL-BSA) linked to encoded polystyrene probes (hACL-BSA-ePSP) on a classical competitive immunochemical format. By using this scheme ACL can be detected in low nM range (LOD, 0.96 ± 0.26, N = 3, in buffer) even in complex samples such as serum or plasma (LOD 4 ± 1)...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29135251/micellar-thrombin-binding-aptamers-reversible-nanoscale-anticoagulants
#12
Alexander Roloff, Andrea S Carlini, Cassandra E Callmann, Nathan C Gianneschi
Aptamers are nucleic acid-based ligands that exhibit promising features including specific and reversible target binding and inhibition. Aptamers can function as anticoagulants if they are directed against enzymes of the coagulation cascade. However, they typically suffer from nucleolytic digestion and fast clearance from the bloodstream. We present thrombin-binding aptamer amphiphiles that self-assemble into nanoscale polymeric micelles with a densely functionalized aptamer-displaying corona. We show that these micellar aptamers retain their native secondary structure in a crowded environment and are stabilized against degradation by nucleases in human serum...
November 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29127864/assessment-of-the-quality-of-anticoagulation-management-in-patients-with-pulmonary-arterial-hypertension
#13
Tamara Roldan, Elena Villamañán, Juan J Rios, Aaron B Waxman
BACKGROUND: Studies assessing the quality of anticoagulation therapy in patients with pulmonary arterial hypertension (PAH) have not been conducted. OBJECTIVE: To assess the quality of anticoagulation management, the rate of anticoagulation-related complications in patients with PAH, and to identify risk factors for poor anticoagulation. METHODS: This observational, retrospective cohort study included patients with confirmed PAH taking a regimen of oral anticoagulants from two centers: Brigham and Women's Hospital in Boston, and Hospital Universitario La Paz in Madrid from January 2009 to August 2015...
November 2, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29100534/validation-of-a-pan-orthopox-real-time-pcr-assay-for-the-detection-and-quantification-of-viral-genomes-from-nonhuman-primate-blood
#14
Eric M Mucker, Christopher Hartmann, Donna Hering, Wendy Giles, David Miller, Robert Fisher, John Huggins
BACKGROUND: In 1980, smallpox disease was eradicated from nature and Variola virus, the etiological agent of smallpox, was confined to two laboratories, one located in Russia (Moscow) later moved to VECTOR (Novosibirsk, Siberia) and one in the United States (CDC Atlanta). Vaccinations among the general public ceased shortly after the successful eradication campaign, resulting in an increasingly immunologically susceptible population. Because of the possibility of intentional reintroduction of Variola virus and the emergence of other pathogenic poxviruses, there is a great need for the development of medical countermeasures to treat poxvirus disease...
November 3, 2017: Virology Journal
https://www.readbyqxmd.com/read/29094808/dietary-vitamin-k-and-association-with-hepatic-vitamin-k-status-in-a-yup-ik-study-population-from-southwestern-alaska
#15
Nicholas T Au, Tove Ryman, Allan E Rettie, Scarlett E Hopkins, Bert B Boyer, Jynene Black, Jacques Philip, Joseph Yracheta, Alison E Fohner, Morayma Reyes, Timothy A Thornton, Melissa A Austin, Kenneth E Thummel
SCOPE: We investigated the relationship between dietary vitamin K and plasma PIVKA-II concentration, a biomarker of hepatic vitamin K status, in a Yup'ik study population in southwestern Alaska. METHODS AND RESULTS: A total of 659 male and female, self-reported Yup'ik people, ≥ 14 years of age, were enrolled. Blood was collected for genotyping and plasma PIVKA-II biomarker analysis. A Yup'ik-specific dietary food frequency questionnaire was used to assess vitamin K intake...
November 2, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29050502/first-evidence-trap-induced-platelet-aggregation-is-reduced-in-patients-receiving-xabans
#16
Frantisek Nehaj, Juraj Sokol, Jela Ivankova, Michal Mokan, Frantisek Kovar, Jan Stasko, Marian Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in the management of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whose target specificity is activated factor X (FXa). However, it is still not fully understood if and how xabans impact platelet function. This observational study aimed to assess the in vitro platelet function in patients with atrial fibrillation receiving xabans. This was a single-center study quantifying platelet aggregation in 41 patients treated with apixaban or rivaroxaban by light transmission aggregometry...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29027516/-chronic-thromboembolic-pulmonary-hypertension-recognition-diagnosis-and-treatment
#17
D Ruigrok, P Symersky, P W G Elbers, S Kamminga, L J Meijboom, H J Bogaard
- Chronic thromboembolic pulmonary hypertension (CTEPH), characterised by pulmonary hypertension and persistent perfusion defects despite adequate anticoagulation, causes significant morbidity and mortality.- Persistent dyspnoea after acute pulmonary embolism is frequent and an indication for additional diagnostics. Only a minority of these patients develop CTEPH.- Echocardiography and perfusion scintigraphy are the cornerstone of diagnostics when suspecting CTEPH. Right-heart catheterisation and pulmonary angiography should confirm the diagnosis...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29023569/pancreatic-and-snake-venom-presynaptically-active-phospholipases-a2-inhibit-nicotinic-acetylcholine-receptors
#18
Catherine A Vulfius, Igor E Kasheverov, Elena V Kryukova, Ekaterina N Spirova, Irina V Shelukhina, Vladislav G Starkov, Tatyana V Andreeva, Grazyna Faure, Marios Zouridakis, Victor I Tsetlin, Yuri N Utkin
Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein...
2017: PloS One
https://www.readbyqxmd.com/read/28974047/heparin-mimetics-their-therapeutic-potential
#19
REVIEW
Shifaza Mohamed, Deirdre R Coombe
Heparin mimetics are synthetic and semi-synthetic compounds that are highly sulfated, structurally distinct analogues of glycosaminoglycans. These mimetics are often rationally designed to increase potency and binding selectivity towards specific proteins involved in disease manifestations. Some of the major therapeutic arenas towards which heparin mimetics are targeted include: coagulation and thrombosis, cancers, and inflammatory diseases. Although Fondaparinux, a rationally designed heparin mimetic, is now approved for prophylaxis and treatment of venous thromboembolism, the search for novel anticoagulant heparin mimetics with increased affinity and fewer side effects remains a subject of research...
October 2, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28948451/a-diagnostic-approach-to-stroke-in-young-adults
#20
REVIEW
Christopher A Stack, John W Cole
Optimal diagnosis and management of stroke in young adults benefit from a multidisciplinary team, including a vascular neurology specialist. In addition to the "standard" vascular risk factors including smoking, hypertension, diabetes, and hyperlipidemia, one needs to consider alternative etiologies including substance abuse, carotid/vertebral artery dissections, and rare genetic conditions among others. Once a young patient is determined to have had a stroke, the next question a clinician should ask is why did this patient have a stroke? A "heart to head" diagnostic approach is recommended...
September 25, 2017: Current Treatment Options in Cardiovascular Medicine
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